ACCCN's Critical Care Nursing

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TABLE 19.13 Treatment of DKA and HHNS 344-346

Issue Treatment considerations
Dehydration and ● Intravenous fluid is initially given to restore intravascular volume. Isotonic fluid such as normal saline or a colloid
sodium loss solution may be used. Solutions containing sodium are used in order to replace sodium lost as a result of the osmotic
diuresis.
● Assessment of volume status is undertaken using basic clinical assessment, such as heart rate, blood pressure, urine
output (allowing for the possibility of continuing osmotically-driven diuresis), or invasive haemodynamic monitoring.
● Hypotonic solutions are added after the initial fluid resuscitation to correct the total body water deficit.
● Adequate resuscitation and rehydration reduces the effect of the counterregulatory hormones.
Insulin therapy ● A soluble insulin is usually administered via continuous infusion to allow rapid titration of dose.
● Blood glucose levels and blood chemistry should be regularly monitored.
● Care is taken to prevent too rapid a change in blood sugar level, as this will cause a rapid reduction in the
extracellular fluid osmolarity. This rapid reduction would result in fluid shift from the extracellular space to the
intracellular space, which may result in cerebral oedema.
● There is a risk of hypoglycaemia resulting from insulin therapy. Sympathetic activation accompanies a low blood
glucose level and results in sweating, tremor, tachycardia and anxiety. Reduced blood glucose levels also cause
global CNS depression and result in depression of the level of consciousness and possibly fitting. Severe
hypoglycaemia with a blood glucose level <2 mmol/L is a medical emergency and is treated with administration of
50 mL 50% glucose.
Electrolytes ● Intravenous potassium replacement will be required.
● Plasma potassium levels will fall rapidly as a result of commencement of insulin therapy and to a lesser extent with
rehydration. Insulin causes the lowering of plasma potassium by mediating the re-entry of potassium into the
intracellular compartment.
● Phosphate and magnesium replacement may be required.
DKA = diabetic ketoacidosis; HHNS = hyperglycaemic hyperosmolar non-ketotic state.



replacement, correction of acidosis (in DKA), monitoring outcomes in this group of patients. EN is the preferred
for and prevention of complications hypoglycaemia, method of nutritional support in the critically ill, although
hypokalaemia, hyperglycaemia, and fluid volume over- ensuring adequate delivery of nutrients can be challeng-
load, and patient teaching and support. 341,350,351 Assess- ing. The availability of enteral feeding guidelines is useful
ment of blood glucose levels is essential. Effectiveness of for some aspects of clinical practice although there
treatment is usually assessed by resolution of the acidosis remains little evidence to inform many of the issues, such
and the control of hyperglycaemia. Regular testing of as measurement of gastric residual volume, that concern
arterial blood gases, blood sugar and electrolytes (espe- nurses. When nutritional goals are difficult to achieve, PN
cially potassium) is vital until the blood sugar has stabi- may be used to supplement EN. Less frequently, critically
lised and the ketosis and acidosis resolves. 344 Considering ill patients may require TPN as their sole nutritional
that fewer patients are now admitted to ICU with DKA support therapy.
and HHNS, understanding the management of these
patients is vital and protocols have been developed to Critically ill patients, particularly those who have respira-
guide practice. 350,351 tory failure requiring mechanical ventilation for >48
hours and those with coagulopathy, are at increased risk
Blood ketones (beta-hydroxybutyrate) can now easily be for developing stress-related mucosal disease. Recognis-
measured using blood from a fingerprick with a bedside ing risk factors and implementing prophylactic pharma-
handheld monitor. It has been suggested that blood cotherapy is required to reduce the incidence of clinically
ketone monitoring allows for insulin titration with refer- important bleeding.
ence to ketones in addition to usual blood sugar monitor-
ing. 352 An outline of the collaborative treatment of DKA Liver dysfunction causing hepatocellular injury and death
and HHNS is presented in Table 19.13.
can occur due to direct injury or cellular stress. This can
be mediated via several avenues, such as metabolic dis-
SUMMARY turbances, ischaemia, inflammatory processes, or reactive
oxygen metabolites from drug and alcohol ingestion.
During episodes of critical illness, metabolic function can Acute failure can be acute or chronic. In Australia and
become compromised and the normal processes respon- New Zealand, high rates of hepatitis B and C predispose
sible for digestion, endocrine and liver function deterio- individuals to chronic liver dysfunction that can lead to
rate. Specifically, the gastrointestinal system can become acute hepatic decompensation. Whilst acute liver failure
hypoperfused and normal physiological processes respon- is uncommon, patients who present are often critically
sible for digestion, absorption, immunity and protection ill. In addition, liver failure causes major disturbances in
become compromised. Critical illness increases the meta- other body systems often resulting in coagulopathy, cere-
bolic demand and nutritional support that meets this bral oedema (hepatic encephalopathy), sepsis, renal
increased demand has been shown to improve clinical failure and metabolic derangement. Therapy is usually

Gastrointestinal, Liver and Nutritional Alterations 529

directed at multi-organ support as extracorporeal liver stress, it is also associated with poor wound healing and
support therapies have not sufficiently developed to higher rates of infection after surgery in diabetic patients;
sustain liver function during the acute phase. higher risk of death after myocardial infarction in dia-
Liver transplantation remains the definitive treatment betic and non-diabetic patients; and poor outcomes after
option for acute and chronic liver failure patients when stroke. The use of intensive control of blood glucose has
supportive multi-organ therapy is not sustainable. been shown to improve both mortality and morbidity
Preexisting hepatic dysfunction and liver transplantation outcomes in select groups of patients but also presents a
surgery can lead to a high risk of haemorrhage and challenge for nursing practice where episodes of hypogly-
coagulopathy post-operatively. Careful haematological caemia occur.
management is required to control postoperative bleed- DKA and HHNS are seen in a small proportion of criti-
ing. Clinicians must ensure that patients receive appro- cally ill patients and the treatment revolves around cor-
priate haemodynamic management for hyperdynamic rection of intravascular volume, rectifying electrolyte
states and that measures to avoid rises in ICP are abnormalities and, in DKA, insulin therapy to stop keto-
implemented. genesis. Nursing management of the patient with hyper-
During episodes of critical illness, hyperglycaemia and glycaemic states should focus on frequent assessment of
increased insulin resistance can occur. Although hypergly- volume status, monitoring electrolyte concentrations and
caemia has been seen as a beneficial adaptive response to assessment of blood glucose levels.





Case study

The patient in her mid-twenties was admitted to ICU in the late ventilator. However, later in the afternoon plans for extubation
afternoon (day 1) after a respiratory arrest post tonic clonic seizure. were cancelled and enteral feeds recommenced because the
Her initial CT scan and chest X-ray showed no acute changes. She patient developed respiratory distress. Her oxygen saturation
had a medical history of severe seizures every three months associ- decreased to 77%, respiratory rate increased to 40–50 breaths
ated with her congenital disease, characterised by hypotonia and per minute and she had a left-sided wheeze. The chest X-ray
mild-to-severe generalised muscle weakness. She was intubated demonstrated fluid overload which was treated with salbutamol
and placed on a mechanical ventilator on her arrival to ICU because nebulisers and frusemide. Pressure support and positive end-
she suffered a seizure shortly after her arrival. expiratory pressure (PEEP) were also increased. She was given
remifentanyl and clonidine because she was restless and agitated.
The initial medical plan was to control her seizures, optimise her
respiratory function and extubate as early as possible. Early enteral A septic screen for her fever revealed Gram-positive cocci growing
feeding, preferably with in 24 hours, is standard treatment in the in her sputum and Gram-negative bacilli in urine, which were
ICU and enteral tube feeds were commenced within 30 minutes of treated with antibiotics.
her ICU admission. Confirmation of tube placement was made by On day 4 she was again fasted from 0600 hours and extubated at
X-ray on insertion of the enteral tube; that was done daily and 1135 hours. She required Guedel and nasopharyngeal airways for
whenever tube position may have changed. The Salem sump naso- secretion clearance post extubation. Because her respiratory status
gastric tube was aspirated four-hourly, as per unit protocol. Enteral was borderline and she may have required re-intubation,
tubes were secured to the face by adhesive surgical tape which re-commencement of enteral feeds was delayed after extubation.
were changed daily and whenever necessary. This unplanned prolonged interruption continued until the late
morning of day 5 (28 hours from the commencement of fasting).
On day 2 the feeds were stopped for anti-epileptic medication
(phenytoin), administered via the nasogastric tube. Sedation was She was discharged to the ward on day 6 and enteral feeding was
also stopped in anticipation of early extubation. Weaning was not continued on the ward. She had one interruption of 3 hours to her
tolerated and the planned extubation cancelled. There was no feeding on the day of discharge from ICU. This was for reposition-
adjustment to the volume of feed administered as a result of the ing of the nasogastric tube because of poor taping technique.
interruptions to feeding for medication and weaning. Ideally, Interruptions to enteral feeding in the ICU are common. Reasons
enteral feed volumes should be adjusted to account for the for stopping feeds include weaning from mechanical ventilation,
planned interruption for medication, providing that the adjusted gastric intolerance, procedures and medication administration by
hourly volumes are tolerated by the patient. The acceptable time the enteral route. For this patient, expedited extubation was the
that patients can be underfed with no adverse consequences is goal of management and the most common reason for stopping
unknown.
the feeds. While some interruptions to feeding are inevitable, it is
Feeds were stopped for three hours from 0600 h on day 3 for important to keep them to a minimum to facilitate patients in
enterally-administered medication. Late in the morning they were achieving their target feed volumes and to minimise handling of
stopped again as part of the plan to wean her from the mechanical the enteral feed delivery system.

530 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



Research vignette
Juve-Udina M-E, Valls-Miro C, Carreno-Granero A, Maria-Estalella G, to critical care nursing there are omissions and discrepancies in
Monterde-Prat D et al. To return or to discard? Randomised trial on both the conduct of the study and the analysis that undermine the
gastric residual volume management. Intensive Critical Care Nursing credibility of the findings.
2009; 25 (5): 258–67.
The value for maintaining GRV within safe limits, i.e. below
Abstract 5 mL/kg was cited by Horn and colleagues in their secondary
355
Objectives analysis of intermittent versus continuous feeding in a paediatric
355
The study aimed to determine the effect of returning or discarding ICU. Horn and colleagues used the value recommended by
the gastric residual volume (GRV) on gastric emptying delays and Taylor and Baker (the primary reference) in their paper published
356
feeding, electrolyte balance and patient outcomes among critically on paediatric enteral nutrition. There was no information on how
ill patients. Gastric emptying delay (GED) was defined as the dif- this value was derived and it may not be appropriate for adults.
ficulty in maintaining GRV within safe limits, i.e. below 5 ml/kg. The GED was categorised into three groups but the rationale for
The GED was categorised as light GED (151–250 mL/6 hours), mod- using these categories was not provided. Other important out-
erate GED (251–350 mL/6 hours) or severe GED (>350 mL/ comes of interest are not well defined. For example testing glucose
6 hours). 353 values in pulmonary secretions is not an acceptable method to
define pulmonary aspiration. The report does not explicitly define
Methods the ‘discard’ group.
The prospective, randomised clinical trial was conducted in a single
medical-surgical intensive care unit (ICU) of a public university hos- In conducting the study, randomisation procedures are explained
pital. Patients admitted to the ICU for longer than 48 hours, aged but it is unclear who controlled allocation of patients to the return
18 or older, who had haemodynamic monitoring and were fed or discard group, thereby opening the study to selection bias if the
enterally or parenterally were recruited to the study over one year. allocation was inconsistent. The study is unblinded as expected but
Participants were excluded if connected to an intermittent gastric mention of why it was not possible to blind should be included in
aspiration system. Computer-generated randomisation was used the report. All patients were accounted for but ‘intention to treat’
to randomise participants to the return (intervention) or discard principles were not used. The type of ICU, but not its location, is
(control) group. The estimated sample size (59 participants in each reported as mixed medical-surgical (general) ICU which are the
group) was informed by sample size calculations. The study most common ICUs in Australia. The selection criteria were listed
finished for a participant if: (1) there was no need for further GRV and recruitment was described as continuous over a year. It is
monitoring, (2) occurrence of adverse event associated with the revealed later in the paper that recruitment did not occur for 2
procedure (pulmonary aspiration or cardio-respiratory arrest months over summer although no reason for not recruiting during
during or immediately after the procedure), (3) faecal aspirates, (4) this period was provided. This may have been an important omis-
major protocol error or (5) death. Gastric residual volumes were sion as acknowledged by the authors.
checked every 6 hours and an algorithm was used to guide man- An algorithm was used to guide management of GRV but it is
agement of GRV. Data were collected by the investigators or by the unclear and two standard volumes were prescribed for enteral
trained registered nurses from the ICU and included the incidence feeds. While feeding was administered continuously the algorithm
of (1) blocked NGT; (2) pulmonary aspiration episodes; (3) intoler- indicates different administration and cessation times which are
ance episodes (nausea, vomiting, diarrhoea and abdominal disten- quite confusing.
sion); (4) enteral feeding delays; (5) hyperkalaemia episodes; (6)
hyperglycaemia episodes and (7) discomfort episodes, identified The data collected on factors that may be potentially affected by
by significant changes in vital signs and also from the Ramsay seda- the return or discard of GRV were impressive. The lack of signifi-
tion score. 354 cance between groups is disappointing but not unexpected. Even
though sample size calculations were performed, the estimates for
Results and Conclusion
No significant differences were found in participant demographics the effect size may not be realistic and subgroup analysis was not
or outcome measures between the groups. The exceptions were decided a priori.
participants in the intervention group had a lower incidence and While the limitations of the study were discussed, important issues
severity of delayed gastric emptying episodes (P = 0.001) and more such as conduct of the study in a single centre, use of subgroup
episodes of hyperglycaemia. The investigators concluded that analyses and not using intention to treat analysis were omitted. A
returning gastric aspirates improved GRV management without major limitation in our opinion was to include patients who
increasing the risk for potential complications. received parenteral nutrition. It would be more informative to
study only those patients receiving enteral feeding in a sufficiently
Critique large sample using a strict standardised feeding regimen to assess
Gastric residual volume (GRV) is routinely measured in many ICUs the effect of administering enteral nutrition and the effect of GED.
to monitor gastric tolerance to enteral feeding and abdominal Patients who receive parenteral nutrition are likely to have impaired
decompression and drainage for patients not fed enterally. This gut function and their inclusion only confuses the results. Perform-
study compared two methods of managing gastric aspirate after it ing some statistical modelling may have enhanced understanding
was removed from the stomach, i.e. return or discard. Gastric aspi- of the outcomes of the study.
rates were returned in the ‘intervention’ group if the GRV was not
greater than 250 mL, if so then the return volume was limited to There is a wide variation in the management of GRV and little avail-
250 mL. Whilst using a robust study design in an area of relevance able evidence to guide practice. The volume of GRV considered
357

Gastrointestinal, Liver and Nutritional Alterations 531



Research vignette, Continued
excessive and the ideal frequency of checking GRV have not been and risk of contamination but exposes staff to splash injury; these
established. Similarly, whether to return or discard gastric aspirate events were not measured. While this study provides some infor-
is controversial. The argument to support return of aspirates to mation about GED, high quality research is needed to answer some
maintain electrolyte and fluid balance was not shown in this study. of these difficult questions. There is not enough evidence from this
Discarding aspirates minimises handling of feed delivery systems study to guide or change practice.






Learning activities
1. How do changes to the gastrointestinal system in critical illness these strategies over other pharmacological agents to prevent
influence your patient’s ability to achieve their energy–protein the development of stress-related mucosal disease.
goals? 6. Consider why acute liver dysfunction/failure causes serious
2. With reference to the case study, what factors may contribute systemic sequelae, such as coagulopathy and hepatic enceph-
to malnutrition and how might you address these in your clini- alopathy, and why liver function can be restored following the
cal practice? insult.
3. After reviewing the case study, what interruptions to enteral 7. Identify the current practice for glycaemia control in the unit
feeding were necessary and what could have been avoided? you work in or have access to. If tight glycaemia control is used,
What impact might repeated interruptions have on patient identify the practices that have been instituted to minimise the
outcomes? incidence and severity of hypoglycaemia. If tight glycaemia
4. Review your patients’ notes and calculate what their total daily control is not used, identify what protocol is used and what BSL
caloric intake should be. Once you have obtained this figure, threshold is used. Describe the rationale that supports the
compare the prescribed intake to the actual intake. If patients practice you identify.
have not received their total daily caloric intake, consider what 8. Compare and contrast the physiological changes that occur in
factors may have contributed to this and how these might be DKA and HHNS. How do these differences influence the man-
overcome in future. agement strategy for restoring normoglycaemia?
5. Identify what types of stress ulcer prophylaxis are used in your
clinical area. Discuss with your colleagues the advantage of


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Management of Shock 20







Margherita Murgo
Gavin Leslie




While the cause of shock may be multifactorial, treatment
Learning objectives focuses on optimising tissue perfusion and oxygen de-
livery. Shock is often classified according to the primary
After reading this chapter you should be able to: underlying mechanism: a disruption of intravascular
● describe the clinical manifestations of shock blood volume, impaired vasomotor tone or altered
5
● distinguish between the various shock states cardiac contractility. The shock syndrome is one of the
● describe general principles of shock management most pervasive manifestations of critical illness present
● identify appropriate monitoring for a patient with shock in intensive care patients.
● review and evaluate care for a patient with a specific shock Early detection and management of shock to reverse
6
type pathological processes improves patient outcomes.
Although the traditional hallmark of shock is hypoten-
sion (SBP <90 mmHg) this can be a late or misleading
sign and is considered a medical emergency. It is there-
7
fore critical that other signs and symptoms are identified
Key words early by frequent observations to detect a patient’s dete-
riorating state and respond before irreversible shock
8
anaphylactic shock ensues. No one vital sign is adequate in determining the
6
cardiogenic shock level or extent of shock nor is there a specific laboratory
distributive shock test which diagnoses the shock syndrome.
hypovolaemic shock This chapter provides an overview of the pathophysiology
neurogenic shock of shock, the commonly described categories and associ-
obstructive shock ated pathologies, along with appropriate monitoring and
sepsis interventions for managing a patient in shock.
septic shock
severe sepsis PATHOPHYSIOLOGY
systemic inflammatory response syndrome
Traditionally, shock is classified by aetiology: hypovolae-
mic, cardiogenic and distributive. 3,4,9 Each has a specific
mechanism of action that leads to altered tissue perfusion
INTRODUCTION and oxygen and nutrient uptake at the cellular level (see
Table 20.1). In practice, it is common to find overlap
between different shock types (e.g. in sepsis there may
It is a bad symptom when the head, hands, and feet are cold, also be hypovolaemia and/or myocardial dysfunction).
while the belly and sides are hot, but it is a very good symptom
when the whole body is equally hot Shock occurs when there is an inability of the body to
The Book of prognostics by Hippocrates, 400 BC 1 meet metabolic demands of the tissues; hypoperfusion
(decreased blood flow to the tissues) results in cellular
Shock is an altered physiological state that affects the
functioning of every cell and organ system in the body. It dysfunction, as there is homeostatic imbalance between
4,10
is a complex syndrome reflecting changing blood flow to nutrient supply and demand, and adaptive responses
body tissues with accompanying cellular dysfunction and can no longer accommodate circulatory changes. These
eventual organ failure. Shock presents as a result of adaptive responses are moderated via numerous ‘sensors’
2,3
impaired nutrient delivery to the tissue: throughout the thorax and large vessels in particular,
which detect subtle changes in pressure (baroreceptors)
● when compensatory mechanisms can no longer or biochemical changes (chemoreceptors). These recep-
respond to decreases in tissue perfusion 4 tors feed back to the hypothalamus which regulates
● nutrient uptake is impaired at the cellular level. through the pituitary gland (for the release of a number 539

540 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

tissues while other areas receive more blood flow than
TABLE 20.1 Shock types 5 needed, 4,7,10,13,14 is often referred to as distributive shock,
and is typical of the shock types that affect vasomotor
Shock type Main characteristic tone (e.g. septic, neurogenic and anaphylactic shock).
This maldistribution may leave some organ systems isch-
Hypovolaemic a reduction in circulating blood volume
through haemorrhage or dehydration aemic for long periods leading to persistent organ dys-
6
or plasma fluid loss function and failure. There is also evidence supporting
the presence of cytopathic hypoxia as a result of excessive
Cardiogenic pump failure (impaired cardiac
contractility) usually as result of nitric oxide and tumour necrosis factor-alpha (TNFα)
myocardial infarction production (cellular proinflammatory mediators), where
● obstructive a sub category of cardiogenic shock there is impaired mitochondrial (the powerhouse of the
shock characterised by blockage of cell) oxygen utilisation which leads to depleted stores of
circulation to the tissues by impedance adenosine tri-phosphate (ATP) 4,11,13,15,16 and interferes
of outflow or filling in the heart (e.g. 16
due to cardiac tamponade or with electron transport and metabolism (see Chapter
pulmonary emboli) 19). Nitric oxide is associated with vascular relaxation
and is a major contributor to alterations in microvascu-
Distributive shock a maldistribution of circulation from 17
sepsis, anaphylaxis or neurogenic injury lature and capillary leak in sepsis.
Organ systems have varying responses in shock and are
not measured directly. Often surrogate markers of global
of hormones such as antidiuretic hormone [ADH] and hypoperfusion are used to indicate the severity of
adrenocorticoid trophic hormone [ACTH] to target organs shock. 18–19 Lactate and acid–base disturbances, such as an
such as the kidney) and the cortex of the adrenal gland increase in strong ion gap, have been suggested as early
to respond and counter the developing effects of shock. markers of mitochondrial dysfunction and cellular hypo-
Concurrently direct feedback stimulates the sympathetic perfusion. 8,20 These ‘surrogate’ biochemical markers of
nervous system to act on blood vessel tone, particularly hypoperfusion (pH, serum lactate and standard base
the arterioles, and also target organs such as the adrenal excess) assess acidaemia and provide some insight into
gland and kidney to respond via the release of endoge- the degree of shock present. Lactate, a strong anion with
21
nous catecholamines (adrenaline and noradrenaline), normal production of 1500–4500 mmol/day, is a product
mineral and glucocorticoids (aldosterone, cortisol), and of carbohydrate metabolism. Increased levels are present
the renin–angiotensin–aldosterone system (RAAS). RAAS in tissue hypoxia, hypermetabolism, decreased lactate
activation results in synthesis of angiotensin II, a power- clearance, inhibition of pyruvate dehydrogenase and acti-
ful vasoconstrictor that further potentiates the reduction vation of inflammatory cells; all characteristics of devel-
in peripheral blood vessel capacity. oping shock (see Table 20.2). Increased lactate production
Collectively, these responses form a sympatho– is a warning sign of impending organ failure, as it is
endocrine–adrenal–axis that moderates the systemic indicative of anaerobic metabolism. Blood lactate levels
response to shock. The axis maintains circulation to the have been directly linked to deteriorating patient out-
vital organ system and combines with the inflammatory comes in shock. 21,22
response to limit local and systemic tissue damage and As the shock state deteriorates and the body fails to com-
ultimately confer a survival advantage. Combined pensate, organ systems begin to fail. This is complicated
responses include profound vasoconstriction, oligo- by a systemic inflammatory response (SIRS) which can
anuria (fluid retention), redirection of blood flow to vital be a direct cause of the shock state (see section on Dis-
organs, hyperglycaemia, immunomodulation and proco- tributive shock) or develop as a consequence of protracted
agulation. This universal response to impending shock shock. This results in ‘capillary leak’ or increased micro-
is particularly effective in compensating for loss of vascular permeability which leads to interstitial oedema
circulating blood volume, but may be counterproductive as a consequence of alterations to tissue endothelium.
when pump failure occurs or ‘uncoupled’ in distributive Many immune mediators including circulating cytokines,
shock states. oxygen free-radicals and activated neutrophils alter the
As adaptive responses fail, cardiac output becomes insuf- structure of the endothelial cells, creating space to allow
ficient to provide adequate organ perfusion despite larger intravascular molecules to cross into the extravas-
23
increasing tissue oxygen consumption (see Chapters 9 cular space, with proteins and water moving from the
24
and 10). When oxygen is ‘supply dependent’, oxygen intravascular space into the interstitium. This response
delivery is decreased and, to compensate, increased mechanism improves the supply of nutrient-rich fluid to
extraction occurs to enable continued tissue consump- the site of local injury, however, systemically, fluid shifts
tion. However, when oxygen delivery falls below a critical lead to hypovolaemia, impaired organ function and
threshold, and extraction demand rises above the avail- development of acute organ injury such as acute lung
24
able blood oxygen levels, this compensation mechanism injury (ALI) and acute kidney injury (AKI). This devel-
fails and oxygen debt results. 6,11,12 oping organ injury is the precedent to organ failure (more
fully described in Chapter 21).
Hypoperfusion may also exist despite a relatively normal
cardiac output, and may not be immediately evident The next sections describe the general assessment and
6
clinically. This maldistribution of bloodflow to some management of shock, different classifications of shock

Management of Shock 541

shock. Therapy is targeted to maintain oxygen delivery
TABLE 20.2 Lactate production 9 (DO 2 ) to vital organs to prevent ischaemia and cell
death. 25,26 Ideally, organ systems and tissues should be
25
Lactate production monitored individually, however global measures such
as perfusion pressure, cardiac output (CO) and DO 2 ,
Product of carbohydrate Glucose, glycolysis; pyruvate,
metabolism (1400– lactate are commonly used as surrogates to assist in treatment
19
4500 mmol/day) decision making. Patient assessment and haemody-
namic monitoring, including calculation of CO, are
Rise in lactate levels
used to differentiate shock states and assess progress
Tissue hypoxia Hypodynamic shock in relation to treatment. 26–28 CO is seen by many clini-
Organ ischaemia cians as an important assessment of shocked patients
Hypermetabolism Increased aerobic glycolysis as it is a major determinant of DO 2 . 25,26 Critically ill
Increased protein catabolism patients are frequently assessed clinically, although
Haematological malignancies cardiac output estimations from physical examination
Decreased clearance of lactate Liver failure are generally unreliable and patient status may change
29
Shock quickly. Therefore invasive techniques are most com-
monly used in critical care to measure CO (see also
Inhibition of pyruvate Thiamine deficiency
dehydrogenase Endotoxin Chapter 9).
Activation of inflammatory cells
Phagocytosis Wounds (e.g. trauma/burns) NON-INVASIVE ASSESSMENT
Liver
Gastrointestinal Perfusion status is determined clinically using gross organ
Lungs (e.g. ARDS) function such as mental status, urine output and periph-
6
Major source in sepsis eral warmth and colour. Basic physical assessment of
cardiovascular, central nervous system and renal function
Phagocytes Lungs are essential when assessing a patient at risk of shock.
Wounds Subtle changes in urine output, heart rate and capillary
Liver: neutrophil sequestration
increased, glucose uptake refill are all signs of physiological compensation in
increased response to altered tissue perfusion associated with shock.
Gut: prone to hypoxia, Regular tracking of these vital signs and trend monitoring
phagocytes through careful documentation can alert clinicians to
impending deterioration in the shock state. Level of con-
sciousness may deteriorate; an early sign may be anxiety,
and specific management principles to avoid, or at least and progress to restlessness, agitation or coma. Other
limit, tissue injury and the eventual progression to organ assessment findings include cool, clammy skin, postural
3
failure. hypotension, tachycardia and decreased urine output.
The reliability of these measures is questionable, particu-
PATIENT ASSESSMENT larly where multiple assessments by different clinicians
are performed; in the ICU continuous ECG monitoring
Critically ill patients often exhibit signs of tissue hypoxia and invasive monitoring techniques are employed to
25
as a result of cardiovascular disturbances. Table 20.3 assist in the objective assessment of changes in cardiovas-
provides an overview of the physiological changes in cular state.




TABLE 20.3 Physiological changes in shock 37
Physiological change
Shock Systemic vascular Pulmonary capillary Pulmonary vascular
classification Cardiac output resistance Capillary circulation pressure resistance
Hypovolaemic ↓ ↑ ↓ ↓ ↑
Cardiogenic ↓ ↑ ↓ ↑ ↑
Distributive:
● septic ↑ ↓ ↓ ↓ ↑
● anaphylactic ↓ ↓ ↓ ↓ ↓
● neurogenic ↓/= ↓ ↓ ↓ ↑
Obstructive ↓ ↓ ↓ ↑ ↑
↑ increase; ↓ decrease; = no change.

542 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

Although CO estimations based on physical assessment
findings are unreliable, physical examination using an BOX 20.1 VIP acronym 37
estimation of vascular resistance has shown reasonable
30
accuracy. Clinical assessment may determine CO using ● Ventilation, including airway, added oxygen and
the rearranged equation of systemic vascular resistance ventilation
(SVR = MAP − CVP/CO) where vascular resistance is mea- ● Infusion of appropriate volume expanders
30
sured through peripheral skin temperature changes. A ● Improved heart Pumping with drug therapy such as antiar-
reliable and accurate non-invasive clinical assessment rhythmics, inotropes, diuretics, and vasodilators.
technique of estimating cardiac output would be clini-
27
cally useful allowing assessment of patients without
invasive monitoring, or used to verify accuracy from inva-
sive devices. While a number of non-invasive cardiac activities using the acronym VIP (see Box 20.1). It is also
37
output measuring devices are available, further research suggested that giving critically ill patients a daily
and refinement is required before widespread application ‘FASTHUG’ improves the quality of care for patients in
is considered in critical care. 31 ICU. Specific management of patients with shock are
38
discussed separately below depending on the cause.
INVASIVE ASSESSMENT
Continuous assessment of heart rate and blood pressure
by an intra-arterial catheter also enables circulatory access
for frequent blood sampling to assess serum lactate levels,
electrolytes and blood gas estimation including pH level. Practice tip
The indicator dilution method using a thermal (thermo- Fast hug mnemonic: 38
dilution) signal (cold or hot) is the customary clinical Feeding (prevent malnutrition, promote adequate caloric
26
standard for measuring CO in ICU. This is usually intake)
achieved by placement of a pulmonary artery catheter Analgesia (reduce pain, improve physical and psychological
(PAC), or a central line in conjunction with a thermistor- wellbeing)
tipped arterial cannula (transpulmonary aortic thermo- Sedation (titrate to the 3Cs – calm, cooperative, comfortable)
dilution). Other invasive techniques measure CO Thromboembolic prophylaxis (prevent DVT)
continuously using pulse contour or arterial pressure Head of bed elevated (up to 45° to reduce reflux and VAP)
analysis and ultrasound doppler methods use an oesoph- Ulcer prophylaxis (to prevent stress ulceration)
ageal probe. All methods have degrees of invasiveness, Glycaemic control (to maintain normal blood glucose levels)
can be time-consuming to yield measurements of accept-
able accuracy , may be expensive and are not without
32
risk of complications. 27,33 The PAC is a controversial
assessment tool 26,28,33 due to the risk associated with the
invasive line versus benefits for the measurement of CO . HYPOVOLAEMIC SHOCK
34
This has led to increased interest in less or non-invasive
measures of CO. Hypovolaemia is a common primary cause of shock and
also a factor in other shock states. Insufficient circulating
A further invasive assessment approach is the continuous blood volume is the underlying mechanism, leading to
estimation of mixed venous oxygen saturation using a decreased cardiac output and altered perfusion. 39,40 Death
light-emitting sensor in a PAC. As tissue oxygen delivery related to haemorrhage is most likely in the first few
fails to meet demand and oxygen extraction rises, the hours after injury. The most obvious cause is direct
40
residual oxygen content of blood returning to the lungs injury to vessels leading to haemorrhage, but there are
will fall; in effect a surrogate indicator of failure to meet more insidious causes such as dehydration from
body tissue oxygen demand. This technology was used prolonged vomiting or diarrhoea, sepsis and burns.
41
35
in the landmark study by Rivers and colleagues. to Hypovolaemic shock is classified as mild, moderate or
monitor early deterioration of septic shock patients pre- severe, depending on the amount of volume loss
senting to the ED in need of resuscitation and was part (see Table 20.4). As the shock state worsens, associated
3
of a goal-directed approach to managing patients. This compensatory mechanisms will be more pronounced,
single-centre US study has been the subject of much inter- and hypovolaemic shock may deteriorate to Multi Organ
est for its claimed improvement in patient outcome, with Dysfunction Syndrome (MODS) if poor oxygen delivery
this goal-directed approach being assessed in a major is prolonged (see Chapter 21).
39
multicentre study in an effort to verify its findings within
an international context and varying approach to critical CLINICAL MANIFESTATIONS
care delivery. 36
Symptoms of haemorrhage may not be present until
more than 15–30% of blood volume is lost, and will
MANAGEMENT PRINCIPLES deteriorate as the shock state worsens. 3,41 Estimating
Managing a patient in shock focuses on treating the blood or plasma loss is difficult and dilutional effects of
underlying cause, and restoration and optimisation of resuscitation fluids may be evident when assessing hae-
41
perfusion and oxygen delivery; this includes relevant moglobin and hematocrit. As the body compensates for

Management of Shock 543



TABLE 20.4 Signs and symptoms of hypovolaemic shock 3

Parameter Mild (15–30% loss) Moderate (30–40%) Severe (>40%)
Blood pressure No change Lowered Hypotensive
Pulse (beats/min) ≥100 beats/min ≥120 beats/min ≥140 beats/min
Respirations >20/min >30/min >40/min
Neurological Normal to slightly anxious Mildly anxious to confused Confused, lethargic
Urine output >30 mL per hour 20–30 mL per hour 5–15, negligible
Capillary refill Normal Reduced >4 sec Reduced >4 sec



the reduced circulating volume, widespread vasoconstric-
tion occurs in most body systems apart from the heart
and CNS; SVR rises markedly in an attempt to retain a Hypothermia
viable circulatory system (this accounts for many of the Temp <35°C
signs and symptoms associated with circulatory compen-
sation). However, as tissues are starved of oxygen and Acidosis Coagulopathy
INR >1.5
pH <7.2
nutrients over a prolonged ischaemic time, local media- SBE >-6 PT >18 secs
tors are released as part of the inflammatory responses, Lactate >4 mmol/L APTT >45 secs
leading to organ microvasculature vasodilation and capil- lonised Ca <1.1 mmol/L Fibrinogen <1.0 g/L
Platelets <50
laries re-open to maintain oxygen delivery and reduce
41
hypoxia. This is a hallmark of developing MODS.
Physiological
derangements
NURSING PRACTICE with massive
Clinical management of hypovolaemia centres on mini- transfusion
mising fluid loss and rapid restoration of circulating
41
blood volume once the airway and breathing are secure.
More than one large-bore intravenous cannulae are FIGURE 20.1 Physiological derangements of massive blood transfusion.
usually inserted and lost circulating volume is replaced
by colloids, isotonic crystalloids or blood products to
achieve haemodynamic endpoints (e.g. MAP >65 mmHg). Current initiatives of the agency include development
Body heat can be lost rapidly due to blood loss, the rapid and promulgation of evidence based guidelines for both
infusion of room temperature fluids and exposure in the massive transfusion and intensive care.
pre-hospital setting or during repeated physical examina-
tion. It is therefore important to institute measures to Fluid resuscitation
maintain patient temperature >35°C to avoid coagulopa- Fluid resuscitation is a first-line treatment for hypovolae-
thies and loss of thermoregulation. The aim is to ame- mic shock; providing fluid volume increases preload and
42
liorate the lethal triad of anaemia, coagulopathy and therefore cardiac output (Starling’s law) and organ perfu-
hypothermia. 40–42 sion. A related principle is that the fluid infused should
Debate surrounds early surgical intervention prior to reflect fluid loss, e.g. plasma replacement in burns, fresh
aggressive fluid resuscitation. The premise is that allow- blood in massive haemorrhage. Giving a ‘fluid challenge’
40
ing a lower perfusion pressure prior to achieving haemo- is not always appropriate; the determining factors will be
stasis with controlled or no fluid infusion results in assessment of volume responsiveness, and whether the
less blood loss, due to the compensatory mechanisms infusion will not be deleterious, causing overload, fluid
6
40
described above. Use of medications such as Factor IVa shifts and perpetuating inflammatory responses. The
and EPO also remains controversial in the setting of criti- fluid type, volume, rate and targeted endpoints is docu-
41
42
cal haemorrhage. Guidelines for ‘massive transfusion’ mented; often this is structured as a bolus dose in
currently being finalised by the National Blood Authority volume/kg to achieve a measured haemodynamic vari-
(NBA) do not recommend use of Factor IVa beyond able. When massive transfusion is required, attention
licensed indications, although there may be an indication should be given to product selection and hence a proto-
when conventional therapy has failed to secure haemo- col can be employed.
stasis following massive blood loss and transfusion of
blood products. The current debate also includes dosage Independent Practice
and thromboembolic complications associated with Critical care nurses must be efficient and practised at
42
its use. The NBA is a statutory agency established in initial patient assessment to establish the degree of
2003 to improve and enhance the management of the compensation occurring in a hypovolaemic patient.
Australian blood banks and plasma product sector. Figure 20.1 highlights clinical manifestations of

544 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E


• Trauma
• Surgery
Major haemorrhage • Post partum haemorrhage
• GI bleed
• Ruptured aortic aneurysm



• Mild (750mL)
Blood loss • Moderate (750-1500mL)
• Severe (1500+)


• Massive transfusion
protocol (including dose,
Massive timing, ratio of
transfusion RBC’s:FFP:Platelets and
required
when to consider
factor Vlla)



FIGURE 20.2 Indications for massive transfusion.


haemorrhage. Careful consideration of a patient’s clinical severe hypovolaemia is suspected then blood is often
picture will establish a hierarchy and priority of needs. used to improve oxygen-carrying capacity. Further dilu-
Most hospitals have some level of track and trigger tion of blood by volume expanders increases hypoxia
response that escalates care to appropriate levels (e.g. (otherwise known as isovolaemic anaemia) and red cells
MET calling criteria), however nurses are in a position to are usually needed. Use of isotonic saline as a volume
establish first line management such as intravenous expander is common, although resuscitation with large
access where this is a required skill. There are also many volumes of saline solutions can be associated with hyper-
examples of protocols and guidelines for nurses to initi- chloraemic acidosis. Blood and blood components are
40
ate fluid resuscitation where a patient has indications of usually considered necessary where patients exhibit signs
inadequate circulating blood volume; e.g. a fluid bolus up of moderate to severe haemorrhage (see Figure 20.2).
to 20 mL/kg of colloidor 30–40 mL/kg crystalloid may be There is no perfect resuscitation fluid, and selection is
recommended (depending on organisational guidelines). guided by patient condition and the type of fluid lost.
There are a number of factors to consider when admin-
Collaborative Management istering blood products in massive volume. Massive trans-
Selection of the appropriate fluid indications for surgical fusion is defined as replacement of a patient’s total blood
management and ‘permissive hypotension’ (deliberate volume in less than 24 hours (approximately 10 units of
48
limiting or minimising resuscitation until after adequate red cells); 47,48 although the literature is inconsistent. A
surgical control of haemorrhage). 40,42 will be assessed number of complications are evident (e.g. transfusion
3
by the multidisciplinary team. Goal-directed therapy reactions, coagulopathies, hypothermia, sepsis) and is
48
includes prevention of tissue hypoxia, typically through associated with high mortality. Patients receiving
rigorous fluid resuscitation with either crystalloids or col- massive blood transfusions require careful monitoring
loids to achieve specific haemodynamic endpoints (e.g. a for signs of metabolic derangements, hypothermia, citrate
CVP of 8–12 mmHg, MAP >70 mmHg, urine output toxicity, hyperkalaemia and coagulopathies (due to deple-
>0.5 mL/kg/h). Vasopressor and inotrope therapy may be tion of clotting factors). Dilution and clotting factor con-
then added to maintain adequate perfusion pressure; sumption cause microvascular bleeding, often manifesting
noradrenaline is the vasopressor of choice because of as oozing from multiple sites even after surgical correc-
vasoconstrictor effects. 43 tion. 47,48 Massive transfusion of stored blood with high
oxygen affinity adversely affects oxygen delivery to the
Preload management tissues. It is therefore preferable to transfuse blood cells
The colloid versus crystalloid fluid resuscitation debate that are less than 1 week old; 2,3-diphosphoglycerate
(use of albumin-based solutions or colloids) continues levels rise rapidly after transfusion, and normal oxygen
despite findings from the SAFE study conducted in Aus- affinity is usually restored within a few hours of
47
tralasia; crystalloids (isotonic saline based solutions) transfusion.
were as effective as colloids for fluid resuscitation. 44–46 The Each unit of blood contains approximately 3 g of citrate,
scientific rationale for using colloids over crystalloids is which binds to ionised calcium. A healthy adult liver
to preserve plasma oncotic pressure so as to retain intra- metabolises 3 g of citrate every 5 minutes. If blood is
vascular fluid and minimise oedema. Colloids may also transfused rapidly or the liver is impaired, citrate toxicity
20
attenuate the inflammatory response. If moderate to and hypocalcaemia may develop. The patient should

Management of Shock 545

therefore be monitored for signs of tetany, hypotension guidelines has been developed and the massive transfu-
47
and electrocardiographic evidence of hypocalcaemia. As sion guideline is complete and will be followed by a
stored blood ages, plasma potassium levels rise (possibly number of other specialised guidelines. All guidelines
to over 30 mmol/L). Hypokalaemia may be more will be available to download from the National Blood
common as red cells begin active metabolism and intra- Authority website as they are completed (see Online
cellular uptake of potassium restarts with transfusion. 47 resources).
Acid–base disturbances may also be evident due to the
stored blood lactic acid levels and the citric acid. Citrate CARDIOGENIC SHOCK
metabolises to bicarbonate, and a profound metabolic
alkalosis may result from massive blood transfusion. As Cardiogenic shock manifests as circulatory failure
49
hypothermia causes reduced citrate and lactic acid meta- from cardiac dysfunction, and is reflected in a low
2
bolism, an increase in the affinity of haemoglobin to cardiac output (CI <2.1 L/min/m ), hypotension (SBP
oxygen, platelet dysfunction and an increased tendency <90 mmHg) and severe pulmonary congestion, high
47
for cardiac dysrhythmias, the patient and the blood central vascular filling pressures (CVP; PAOP
50
transfused should be warmed to avoid complications. >18 mmHg). Additional invasive parameters are: intra-
2
thoracic blood volume index >850 mL/m ; global end-
2
Leucocyte depletion occurs during donation in Australia diastolic volume >700 mL/m ; and extravascular lung
and decreases up-regulation of the inflammatory immune volume index >10 mL/kg. 51,52 Cardiogenic shock is com-
response associated with transfusion. Current clinical monly associated with AMI and manifests when 40% or
practice guidelines for the administration of blood prod- more of the left ventricle is ischaemic. It is also related to
ucts and red cells to stable adult patients are listed in mechanical disorders (e.g. acute cardiac valvular dysfunc-
Tables 20.5 and 20.6. A new structure with multiple tion or septal defects), deteriorating cardiomyopathies or





TABLE 20.5 Clinical practice guidelines for red blood cell and platelet administration
Appropriate Use of Blood Components
For Stable Adults & Children >4 months (corrected) age
Adapted from NHMRC/ASBT guidelines (www.anzsbt.org.au)
Haemoglobin is NOT the sole deciding factor for transfusion – consider other patient factors e.g. signs of hypoxia and ongoing blood loss.
Red Cells
Hb Considerations
<70 g/L Transfusion is often clinically useful unless early Hb recovery is expected. A threshold of <60 g/L may be
appropriate for children.
70–100 g/L Likely to be appropriate during surgery with major blood loss or if there are signs or symptoms of
impaired oxygen transport.
>80 g/L May be appropriate to control anaemia-related symptoms in a patient on a chronic transfusion regimen
or during marrow suppressive therapy.
>100 g/L Not likely to be appropriate unless there are specific indications
WHAT DOSE?
Red Cells (mL) = 0.4 × wt (kg) × (desired – actual) Hb (g/L)
Platelets
Use of platelets is likely to be appropriate as prophylaxis for:
Indication Considerations
9
9
Bone Marrow Failure At a platelet count of <10 × 10 /L in the absence of risk factors and <20 × 10 /L in the presence of risk
factors (e.g. fever, antibiotics, evidence of haemostatic failure)
Surgery/Invasive To maintain platelet count at >40 × 10 /L. For surgical procedures with high risk of bleeding (e.g. ocular
9
9
or neurosurgery) it may be procedure appropriate to maintain at 100 × 10 /L
Platelet Function Disorders May be appropriate in inherited or acquired disorders, depending on clinical features and setting. In this
situation, platelet count is not a reliable indicator
Use of platelets is likely to be appropriate as therapy for:
Bleeding Any patient in whom thrombocytopenia is considered a major contributory factor.
Massive Bleeding/Transfusion Confined to patients with thrombocytopenia and/or functional abnormalities who have significant
bleeding. Often with platelet count <50 × 10 /L (<100 × 10 /L with diffuse microvascular bleeding).
9
9

546 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 20.6 Adverse reactions to blood products

Symptom Possible diagnosis Investigation Action
Fever >1°C over baseline or Bacterial contamination Blood and Bag cultures Stop transfusion Supportive care IV antibiotics
>38°C Chills, rigors Febrile Non-Haemolytic Exclude other causes Anti-pyretics
Use leucodeplete products
Rash, hives, wheeze, Allergy Nil Slow transfusion Antihistamine
dyspnoea, hypotension Anaphylaxis Patient IgA level ABC resuscitation
Anti-IgA antibodies Adrenaline and steroid IgA deficient or
washed cells in future
Chills, hypotension, back ABO incompatibility Check ABO type DAT IAT Stop transfusion
pain, haemoglobinuria, Emergency (code or MET) call
ooze from IV sites Haemolysis EUC, Coag, Hb Haemolysis Tests Maintain BP and renal function
Bacterial contamination Blood and Bag cultures IV antibiotics if sepsis possible
Dyspnoea, productive TRALI* occurs within 6 HLA granulocyte antibody tests Stop transfusion, supportive care Notify ARCBS
cough, pink frothy hours of transfusion
sputum, pulmonary
oedema, hypotension
with TRALI
*TRALI – Transfusion related acute lung injury.



congestive cardiac failure, 53,54 trauma and obstruction or to reduce pain, improve coronary perfusion and reduce
inhibition of left ventricular ejection (referred to as oxygen demand. Treatment of the underlying cause is
obstructive shock e.g. pulmonary emboli, dissecting again critical; this may include surgery to repair obstruc-
aneurysm, tamponade) 37,53 (see Chapter 10). Myocardial tion to flow or percutaneous resolution of a coronary
depression from non-cardiac causes such as sepsis, acido- artery blockage.
sis, myocardial depressant factor, hypocalcaemia or drug
55
impact may be so severe as to present as cardiogenic
shock. CLINICAL MANIFESTATIONS
The clinical features of cardiogenic shock are reflective of
Incidence has been estimated at 3% of patients present- congestive cardiac failure, although with greater
56
ing with AMI, and mortality remains high (50–80%), severity: 50,51,58
given death from AMI overall is 7%. This is despite
treatment advances including emergency revascularisa- ● low cardiac output and hypotension
tion. 57,58 Wider distribution of interventional cardiac ● poor peripheral perfusion: pale, cool, clammy
revascularisation services has likely improved outcome peripheries
for patients who present early in the course of their ● oliguria
acute disease. ● altered mentation, restlessness and anxiety
● tachycardia and arrhythmias
Clinical signs include poor peripheral perfusion, tachy- ● pulmonary congestion with widespread inspiratory
cardia and other signs of organ dysfunction such as con- crackles and hypoxaemia (perhaps with frank pulmo-
fusion, agitation, oliguria, cool extremities, dyspnoea, nary oedema)
49
many of which are present in hypovolaemic shock. ● dyspnoea and tachypnoea
Compensatory mechanisms are conflicting for a patient ● respiratory alkalosis (hyperventilation) or acidosis
with cardiogenic shock, as cardiac workload is increased (respiratory fatigue)
on an already-failing heart yet cardiac muscle oxygen ● lactic acidosis
delivery may be compromised. A careful but rapid ● distended neck veins, elevated jugular venous
54
assessment of the clinical history is helpful in differentiat- pressure.
ing the precipitant cause of this shock.
Features consistent with the cause of the cardiogenic
Managing patients with heart failure as a result of cardio- shock may also be present, including chest pain and ST
genic shock can be challenging and is often undertaken segment changes, murmurs, features of pericardial tam-
simultaneously with preparation for definitive treatment. ponade and arrhythmias.
Maintaining perfusion is difficult, as compensatory
mechanisms usually cause further harm to the heart. In the absence of invasive monitoring, the profile of
While judicious administration of fluid is considered hypotension, peripheral hypoperfusion, and severe pul-
in terms of optimising remaining cardiac function monary and venous congestion are evident although this
(Starling’s Principle), administration of pharmacological ‘classic’ profile is not universal. On initial examination,
agents that reduce cardiac workload and improve func- 30% of patients with shock of left ventricular aetiology
tion is paramount: dobutamine for inotropic and had no pulmonary congestion and 9% had no
afterload-reducing effects via vasodilation; and morphine hypoperfusion. 59

Management of Shock 547


Systolic dysfunction
stroke volume, ejection fraction





Blood pressure Cardiac output




Sympathoadrenal activation
(compensation)




Heart rate Inotropy Systemic
vascular resistance



Myocardial oxygen demands
(± ischaemia)



Congestion
left ventricular end-diastolic volume and pressure
left atrial pressue
global end-diastolic volume index
pulmonary capillary wedge pressure
pulmonary artery pressure
extravascular lung water index
intrathoracic blood volume index
right ventricular systolic/diastolic pressure
right atrial pressure

FIGURE 20.3 Sequence of haemodynamic changes in cardiogenic shock ( ↑ = increase, ↓ = decrease).



Based on the underlying pathology of an acute left ven- (cardiac index <2.2 L/min/m ). 62–64 While use of a PAC is
2
tricular myocardial infarction, the structural or contractile a well-described measure of severity in cardiogenic shock
abnormality impairs systolic performance resulting in (as with hypovolaemic shock), evidence of improved
incomplete left ventricular emptying. This results in patient outcome is unclear. 28,65
50
subsequent progressive congestion of first the left atrium,
then the pulmonary circulation, right ventricle, right Once oxygen consumption falls below tissue needs,
atrium and finally the venous circulation. 50,60,61 When resulting anaerobic metabolism causes lactate generation
50,62
invasive haemodynamic monitoring is available, sequence and the subsequent lactic acidosis. Progressive tissue
of changes exist as illustrated in Figure 20.3. ischaemia and injury ensues, along with worsening meta-
bolic acidosis unless oxygen delivery can be restored.
A patient with cardiogenic shock is also assessed and Myocardial contractile performance further worsens
monitored for their oxygen delivery and tissue oxygen when myocardial ischaemia develops or when existing
requirements (oxygen consumption). Systemic DO 2 falls ischaemia or infarction is worsened, and a vicious cycle
in proportion to a declining cardiac output, and is further of ischaemia and dysfunction ensues. 62
worsened as hypoxaemia develops due to pulmonary Compensatory responses effective in lessening severity of
oedema. Initially, VO 2 may be sustained by an increase hypovolaemic shock are initially advantageous, but may
62
in tissue oxygen extraction ratio (O 2ER). Normally 25% ultimately be counterproductive when cardiogenic shock
of delivered oxygen is extracted by tissues, but as delivery is due to myocardial infarction:
falls, tissues extract proportionally more oxygen to meet
metabolic needs. Oxygen consumption can therefore be ● Tachycardia offsets low stroke volume but increases
sustained until the severity of oxygen delivery deficit myocardial oxygen consumption and decreases dia-
exceeds the ability to increase extraction. Maximal extrac- stolic duration, reducing coronary perfusion time.
tion is approximately 50%, and consumption falters ● Vasoconstriction limits the severity of hypotension
when oxygen delivery falls to around 500–600 mL/min but increases resistance to left ventricular emptying

548 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

and may contribute to worsening of the cardiac output, ● implementing measures to reduce patient anxiety,
in particular when cardiogenic shock is due to con- including communication, explanation and analgesic
tractile dysfunction. and sedative medications (avoiding those that are
● An increase in cardiac workload to overcome the rise cardio-depressive) where appropriate
in systemic afterload increases myocardial oxygen ● ensuring that visiting practices are appropriate for
demand, but cannot be met due to coronary artery the patient (which may require facilitating lengthy
occlusion. visits by a loved one, limiting visiting time, or being
● Developing pulmonary congestion is no longer con- selective with the visitors who remain with the
tained within the pulmonary capillary and moves into patient).
the alveolar capillary space, creating pulmonary
oedema, further impeding oxygen delivery to the Collaborative Management
circulation. Typical treatment regimens require preload reduction,
augmentation of contractility with intravenous inotropes
NURSING PRACTICE and afterload manipulation. These aspects are under-
Treatment of cardiogenic shock includes haemodynamic taken concurrently due to the potential severity of cardio-
genic shock. Endotracheal intubation with mechanical
management, respiratory and cardiovascular support, ventilation is implemented if necessary (the need for
biochemical stabilisation and reversal or correction of the mechanical ventilation is associated with an increase in
underlying cause. This complex presentation requires a mortality) (see Chapter 15).
67
coordinated approach to the multiple aspects of care of
a patient with cardiogenic shock. Preload management
Preload reduction relieves pulmonary congestion, reduces
Independent Practice myocardial workload and improves contractility, which is
A rapid response to impending deterioration associated in part impaired by overstretched ventricles. Careful
with cardiogenic shock includes repeated assessment and assessment of patient fluid status is necessary prior to
measures to optimise oxygen supply and demand. either the administration of small aliquots of fluid to
enhance deteriorating myocardial function or enhanced
Assessment diuresis to reduce circulating blood volume. Any fluid
offloading is balanced against the risk of excessive blood
Frequent, thorough assessment of the patient’s status is volume depletion and depression of cardiac output and
essential, focusing on: blood pressure. Desired endpoints of therapy are a
68
1. identification of patients at risk of clinical reduction in right atrial, pulmonary artery, and pulmo-
deterioration; nary artery wedge pressures, or in intrathoracic blood
2. assessment of the severity of shock and identifica- volume, global end-diastolic volume and extravascular
tion of organ or system dysfunction; lung water, depending on available monitoring equip-
3. assessment of the impact of treatment; and ment. Measures to reduce preload include:
4. identification of complications of treatment. ● sitting a patient up with their legs either hanging over
Assessment follows a systematic approach and is con- the side of the bed or in a dependent position
68
ducted as often as indicated by the patient’s condition, ● IV diuretics (frusemide) given usually as intermittent
centring on the cardiovascular system, as well as related boluses or if necessary as a continuous infusion
systems that cardiac function influences, including respi- ● venodilation (glyceryl trinitrate infusions at 10–
69
ratory, renal, neurological and integumentary. 200 µg/min titrated to blood pressure)
● continuous haemofiltration (might be considered to
rapidly reduce circulating volume)
Optimising oxygen supply and demand ● continuous positive airway pressure (indicated for
As cardiogenic shock is associated with an imbalance of pulmonary relief, with the additional benefit of reduc-
oxygen supply and demand throughout the body, mea- ing venous return).
sures to optimise this balance by increasing oxygen Additional measures to reduce pulmonary hypertension
supply and decreasing demand are essential. Strategies to may be employed. Morphine is useful to lessen the
increase oxygen supply include: anxiety and oxygen demands during cardiogenic shock,

● positioning the patient upright to promote optimum and may offer additional benefits by reducing pulmonary
68
ventilation by reducing venous return and lessening artery pressure and pulmonary oedema. Other treat-
pulmonary oedema (but may contribute to worsening ment options include correction of hypercapnoea if
hypotension) present, and nitric oxide by inhalation.
● administering oxygen, continuous positive airway
pressure (CPAP) and bi-level positive airway pressure Inotropic therapy
(BiPAP) support as required. 66 Intravenous positive inotropes promote myocardial con-
tractility to improve cardiac output and blood pressure.
Strategies to reduce oxygen demand include:
Currently available inotropes are not uniform in their
● limiting physical activity beneficial effect on cardiac output and blood pressure

Management of Shock 549



TABLE 20.7 Inotrope drug actions and characteristics 70-73

Drug Action Dose range Physiological effect Nursing considerations
dobutamine Synthetic adrenergic agonist 100–2000 µg/min Inotropy CVC administration
β 1 -agonist Vasodilation Arrhythmia risk
β 2 -agonist ↑↑Cardiac output Excess dilation may cause
↑Blood pressure hypotension
↑Heart rate
dopamine Dopaminergic ‘Inotropic’ dose Mainly inotropic CVC administration
β 1 -agonist 5–10 µg/kg/min ↑Blood pressure Tachycardia
α-agonist (at higher doses) ‘High’ dose ↑Cardiac output Arrhythmia risk
10–20 µg/kg/min Inotrope Risk peripheral vascular
Vasoconstriction dominates compromise
↑↑Blood pressure
levosimendan Calcium sensitiser Loading: 6–12 µg/kg over Inotropy Tachycardia
10 min Vasodilation Arrhythmia risk
Infusion 0.05–0.2 µg/kg/min ↑↑Cardiac output Risk hypokalaemia
(maximum 24–48 hours’ use) Risk Q-T prolongation
Excess dilation may cause
hypotension
Half-life 5 days
adrenaline Sympathomimetic 1–20 µg/min or higher Potent inotrope and Tachycardia common
α-agonist constrictor Arrhythmia risk
β 1 -agonist ↑Cardiac output Risk peripheral vascular
β 2 -agonist ↑↑Blood pressure compromise
↑↑Heart rate Myocardial work
milrinone Phosphodiesterase inhibitor Loading: 50–75 µg/kg Inotropy Vasodilation may be
Infusion: 0.375–0.75 µg/kg/min Potent vasodilator marked
↑↑Cardiac output Observe for hypotension
↓Blood pressure
noradrenaline Sympathomimetic 1–20 µg/min or higher Potent inotrope and Reflex bradycardias
α-agonist constrictor Arrhythmia risk
β 1 -agonist ↑↑Blood pressure Risk peripheral vascular
little effect on β 2 -receptors ↑coronary artery blood flow compromise
vasopressin vascular (V-1) receptors 0.1–0.4 µg/min Inotropy Check liver function
renal (V-2) receptors ↑SVR
↑vasoconstrictor
↑ = increase; ↓ = decrease.



because of additional vasoactive actions (either vasodila- myocardial pumping and an increased cardiac output.
tion or constriction) (see Table 20.7). Selection of an ino- The effect on blood pressure is variable, as the opposing
tropic agent is therefore partly based on inotropic potency actions of increased contractility and vasodilation are not
as well as the desired effect on vascular resistance: uniform in potency, and occur with differing effects
between patients. Inodilators are generally selected when
● vasodilation in addition to inotropy (inodilator effect) a patient has an elevated afterload and low cardiac
favours cardiac output, but may compromise blood output. By reducing afterload, left ventricular emptying
70
pressure 70 is favoured with a reduction in cardiac contractility,
● vasoconstriction in addition to inotropy (inoconstric- reducing myocardial oxygen demand. Inodilators are
tor effect) improves blood pressure, but may at times therefore preferred in ischaemic cardiogenic shock. 71–73
compromise left ventricular emptying and cardiac
output. In contrast, inoconstrictors constrict the vasculature,
resulting in increased preload and afterload while also
70
All inotropes present a paradox in the treatment of car- increasing myocardial contractility. These increases, par-
diogenic shock, as they have the potential to raise heart ticularly in afterload, generally result in a raised blood
rate, increase myocardial oxygen demands, and increase pressure, but the impact on cardiac output is less predict-
the frequency of arrhythmias to a greater or lesser extent. able. An increase in cardiac output is often seen with
Monitoring is used to identify heart rate, rhythm and the these agents, but the increase in afterload may become
development of ST segment or T wave changes. limiting to left ventricular emptying when there is signifi-
cant contractile impairment. Inoconstrictors are therefore
The vasodilation seen with inodilator agents may reduce generally selected when the afterload and resultant blood
both preload and afterload, leading to more effective pressure are more severely compromised than the cardiac

550 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

output. Vasoconstriction also further increases myocar- Respiratory support
dial work and myocardial oxygen demand, and may Varying degrees of pulmonary oedema accompany car-
worsen ischaemia. 74
diogenic shock, causing hypoxaemia due to intrapulmo-
Dobutamine has traditionally been the inodilator of nary shunt, decreased compliance and increased work
75
choice, although accumulating evidence for levosimen- of breathing (WOB). Hyperventilation with respiratory
dan, a calcium-sensitising agent, suggests improved out- alkalosis may initially compensate for hypoxaemia and
comes. 71,73 However, the slow onset of action time of lactic acidosis, but fatigue during this increased WOB
levosimendan (hours) makes it a less suitable drug for may cause patient progression to hypoventilation and
acute resuscitation; other inotropes are therefore cur- respiratory acidosis. Oxygen is administered for hypox-
rently used initially and if required, levosimendan is then aemia, but responses may be limited as the primary gas
introduced. The long half-life (>5 days) of levosimendan exchange defect is an intrapulmonary shunt. Non-
confers a lasting impact on contractility after cessation of invasive ventilatory approaches may be sufficient, but a
the infusion. Milrinone is also an effective inodilator, wary eye for the need to intubate and mechanically ven-
70
but excessive vasodilation may contribute to significant tilate should be maintained in the acute phase of treat-
hypotension; in practice a concurrent vasoconstrictor ment. CPAP at conventional levels of 5–15 cmH 2 O is
(e.g. noradrenaline) may be administered. Close manage- well established as a support for the spontaneously
79
ment of intravascular fluid volume is critical when using breathing patient with pulmonary oedema. CPAP
these agents. improves hypoxaemia, lessens WOB, reduces left ven-
tricular afterload and provides additional benefit by
Dopamine and adrenaline are the major agents in the impeding venous return, an effect that may lessen pul-
inoconstrictor class, and are more effective at raising monary congestion. These benefits are weighed against
blood pressure than inodilators. Both agents also increase the potential for hypotension.
cardiac output, but when there is significant impairment
of contractility the increase in afterload may cause cardiac If hypoventilation and dyspnoea continue despite the use
output to suffer. Importantly, inoconstrictors increase of CPAP, non-invasive bi-level positive airway pressure
myocardial work and oxygen demands, raise heart rate, (BiPAP) is considered. Additional pressure support is
and increase the risk of tachyarrhythmias; these impacts applied during inspiration, above existing CPAP, improv-
are stronger with adrenaline than for dopamine. ing inspiratory efficiency, with increased tidal volume and
less work of breathing. 66,80 Endotracheal intubation and
Afterload control ventilation should be undertaken when neither CPAP nor
Specific management of afterload, independent of BiPAP result in improvement, or when the patient con-
contractility, is sometimes necessary, although caution is tinues to deteriorate or tire. Many clinicians prefer to
needed as the maintenance of blood pressure often intubate and ventilate early, even in the absence of a
provides little scope for further afterload reduction. Arte- specific respiratory need, to decrease the cardiovascular
riodilators such as sodium nitroprusside reduce afterload demands of the greater ventilatory effort. However this
and increase cardiac output, although with limitations approach is controversial as mechanical ventilation is
81
due to hypotension. The introduction of oral angiotensin- associated with poorer patient outcomes and disturbs
76
converting enzyme (ACE) inhibitors as soon as possible cardiovascular balance as it exerts changes to intratho-
after stabilisation of the patient with infarct-related car- racic pressures, particularly at inspiratory initiation.
diogenic shock is strongly recommended. 77,78 Ventilation strategies largely reflect those for other com-
pliance disorders (e.g. ARDS), and are described in more
Adjunctive therapies detail in Chapter 15. Initially, full mechanical ventilation
A range of adjunctive therapies are available for refractory with little or no contribution from the patient is appro-
shock, when first-line treatments are not effective, and priate to correct arterial blood gases and lessen the
can include insertion of an intraaortic balloon pump, cardiovascular demands of the ventilatory burden. Sub-
initiation of mechanical ventilation and correction of sequent reduction of ventilatory support, as the patient’s
metabolic disturbances. These strategies are discussed respiratory ability improves, follows conventional
below in relation to cardiogenic shock. processes.
Intra-aortic balloon pumping Biochemical normalisation
Frequent biochemistry measurement is necessary to
Low cardiac output, pulmonary congestion, reduced detect and monitor the following aspects of care:
MAP, and myocardial ischaemia from cardiogenic shock
may all be improved by the introduction of intra-aortic ● arterial blood gases to identify the adequacy of venti-
balloon pump (IABP) therapy (see Chapter 12). Balloon lation and oxygenation and the presence of metabolic
inflation during diastole raises MAP and promotes coro- acidosis
nary and systemic blood flow, while balloon deflation in ● lactic acid measurement to assess the level of shock
advance of systole reduces afterload. This afterload reduc- and changes in patient response to treatment
tion improves cardiac output and reduces left ventricular ● hypokalaemia or hypomagnesaemia due to aggressive
systolic pressure, lessening the oxygen demands of the diuretic use
ischaemic ventricle by reducing the necessary contractile ● hyperkalaemia due to severe acidosis, especially in the
force of the left ventricle. presence of renal failure

Management of Shock 551

● hyperglycaemia due to the stress response to acute
illness, and in response to sympathomimetic TABLE 20.8 PIRO acronym 85
administration
● bicarbonate levels decline due to pH buffering, but Predisposition Factors that dispose certain patient groups
replacement therapy is not routinely undertaken to be more susceptible to infection and
unless the arterial pH is life-threatening organ dysfunction, including genetic
● urea and creatinine to detect the onset of acute renal predisposition, age, and comorbidities
like alcohol use and diabetes.
failure due to renal hypoperfusion.
Infection Type of infecting organism. How is it
Haemofiltration-based therapies (as slow continuous diagnosed? How severe is the infection?
ultrafiltration, continuous veno-venous haemofiltration Is it local or general? What is the site of
or haemodialysis) are used for fluid and electrolyte infection and the related outcomes?
control when renal function suffers or as acute method Hospital/ICU or community-acquired?
for unloading fluid from the circulation (see Chapter 18). Response Stratify severity, using biomarkers (e.g. IL-6
or procalcitonin) to gauge severity of the
inflammatory/immune responses, and to
DISTRIBUTIVE SHOCK STATES predict how patients will respond and
potential outcomes. Also assess ABGs,
Distributive shock states result in impaired oxygen and lactate levels, WBC, temperature, C
nutrient delivery to the tissues as a result of failure of the reactive protein.
vascular system (the blood distribution system). While Organ dysfunction Describe using either physiological levels
there may be additional factors (e.g. infection) beyond or level of intervention. Use scoring
simple failure to provide sufficient perfusion to the capil- systems to quantify level (mild,
moderate, severe) and predict outcomes.
lary bed due to widespread vascular dilation, the common
factor for all underlying causes of distributive shock is
widespread failure of the vasculature. The most common
categories of distributive shock are associated with sys-
temic inflammatory response syndrome, anaphylaxis and the critical care literature, and led to a worldwide cam-
neurogenic shock. paign in 2002 to reduce the mortality from sepsis.

SEPSIS AND SEPTIC SHOCK The Surviving Sepsis Campaign
Systemic Inflammatory Response Syndrome (SIRS) was a The Surviving Sepsis campaign is an international collab-
term developed to describe the clinical manifestations of orative formed after the Barcelona Declaration in 2002 to
many processes characterised by systemic inflammation reduce the mortality of sepsis by 25% over a 5-year period,
82
including sepsis, burns, pancreatitis and trauma. This by increasing awareness and developing treatment guide-
definition was however limited and problematic as it lines for severe sepsis and shock, including a comprehen-
89,90
described general signs and was non-specific. 83,84 Despite sive list of graded recommendations.
84
a revision in 2001, SIRS was viewed as a valid descriptor Various recommendations were combined to form ‘care
but not useful for clinical diagnosis in that form. It was bundles’ (‘a group of interventions related to a disease
however noted that the use of the SIRS definition in sepsis process that, when executed together, result in better out-
to aid in early identification was important. Signs and comes than when implemented individually’) 91, p.5 and
symptoms were subsequently added to SIRS in response promulgated through professional organisations (e.g.
to infection (sepsis): hyperglycaemia, altered mentation, Institute of Healthcare Improvement [IHI]). Bundles have
generalised oedema, as well as a number of inflamma- been introduced to change processes of care and as
tory, haemodynamic, organ dysfunction and tissue per- quality or benchmarking measures (see Chapter 3).
fusion variables. A staging system (PIRO) was also Although the first version of the sepsis guidelines was
introduced to profile the processes in septic patients supported by ANZICS, the subsequent and much
85
88
(see Table 20.8). expanded version was not, as many of the recommenda-
tions were based on research involving non-ICU and/or
Severe sepsis and septic shock is a leading cause of admis-
sion to ICU and has an associated high mortality. The non-sepsis patients. Further research and evaluation is
terms ‘severe sepsis’ and ‘septic shock’ were defined and needed as mortality benefits of ‘care bundles’ may be a
then refined during international consensus meetings result of increased clinician awareness rather than the
92
that also described SIRS 82,84 (see Table 20.9 and Chapter impact of treatment changes.
21). The incidence of severe sepsis in Australia and New An example of a refuted bundle relates to tight glycaemic
Zealand was 11.8% of ICU admissions, with median ICU control. The recommendation in the surviving sepsis
and hospital stays of 6 days and 18 days respectively, and guidelines supported tight glycaemic control and origi-
corresponding mortality rates of 32% at 28 days and an nated from research where the glycaemic control practice
86
93
in-hospital mortality of 40%. A Victorian epidemiologi- differed from Australia and New Zealand. The NICE-
87
cal study reflected similar results. More recent Australian SUGAR study subsequently concluded that measures
data shows mortality remaining relatively high but in to maintain blood glucose level of ≤10 mmol/L
decline. 36,88 The consequence of this high mortality increased mortality particularly in relation to severe
focused attention on sepsis and its associated sequelae in hypoglycaemia. A recent meta analysis of 26 ICU related
94

552 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



TABLE 20.9 Sepsis, severe sepsis and MODS definitions 82,84

Term Definition
Infection ● Characterised by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host
tissue by those organisms.
● Bacteraemia: the presence of viable bacteria in the blood.
SIRS ● A non-specific syndrome that results from a wide variety of severe clinical insults; present with two or more of the
following:
● temperature >38°C or <36°C
● heart rate >90 beats/min
● respiratory rate >20 breaths/minute or PaCO 2 <32 mmHg
3
● WBC count >12 000/mm or >10% immature (band) forms.
● Other signs include: altered mental status, positive fluid balance or significant oedema, hyperglycaemia in the absence of
diabetes, raised procalcitonin and/or C reactive protein, hypotension, hypoxaemia, acute oliguria, raised serum creatinine,
coagulation abnormalities, ileus, thrombocytopenia, hyperbilirubinaemia, hyperlactaemia, decreased capillary refill/
mottling.
Sepsis ● Systemic inflammatory response to infection. Manifestations of sepsis are the same as defined for SIRS. Determine if
symptoms are a result of a direct systemic response to an infectious process and represent an acute alteration from
baseline in the absence of other known causes for the abnormalities.
Severe sepsis ● Sepsis associated with organ dysfunction, hypoperfusion or hypotension. Hypoperfusion abnormalities and perfusion
abnormalities may include but are not limited to lactic acidosis, oliguria or acute alteration in mental status.
Septic shock ● A subset of severe sepsis; sepsis-induced hypotension (a systolic blood pressure <90 mmHg or a reduction of ≥40 mmHg
from baseline) in the absence of other causes, despite adequate fluid resuscitation, and perfusion abnormalities (e.g. lactic
acidosis, oliguria, acute alteration in mental status). Patients receiving vasopressor or inotropic agents may not be
hypotensive by the time they manifest hypoperfusion abnormalities or organ dysfunction, but are still considered to have
septic shock.
● Acute circulatory failure with persistent arterial hypotension unexplained by other causes and despite adequate fluid
resuscitation (see also sepsis-induced hypotension).
MODS ● Presence of altered organ function in an acutely ill patient where homeostasis cannot be maintained without intervention.
MODS = multiple organ dysfunction syndrome; SIRS = systemic inflammatory response syndrome.



‘tight glycaemic control’ studies, suggested that the prac- CLINICAL MANIFESTATIONS
tice could increase risk to ICU patients. The more prag-
95
matic approach of maintaining blood glucose levels close Septic shock results when infectious agents or infection-
to normal without inducing hypoglycaemia and other induced mediators in the blood stream produce haemo-
metabolic imbalances is therefore appropriate. The dynamic compromise. Primarily a form of distributive
96
guideline was subsequently modified in 2009 to include shock, it is characterised by ineffective tissue oxygen
findings from NICE-SUGAR. 97 delivery and extraction associated with inappropriate
peripheral vasodilation, despite preserved or increased
98
cardiac output. Hypovolaemia is also associated with
septic shock due to the characteristic increased vasodilata-
tion. This presents a clinical picture of a warm, pink and
Practice tip apparently well-perfused patient in early stages of septic
shock with an elevated cardiac output, in contrast to that
Types of sepsis bundles 137 seen in hypovolaemic or cardiogenic shock patients.
Resuscitation bundle: Unchecked, cellular dysfunction in the presence of a
1. Measure lactate. failing compensatory process leads to cellular membrane
2. Culture prior to administration of antimicrobials. damage, loss of ion gradients, leakage of lysosomal
3. Administer empirical antimicrobials as soon as possible. enzymes, proteolysis due to activation of cellular prote-
4. Volume-load as appropriate. ases and reductions in cellular energy stores which may
5. Use vasopressors for persisting hypotension. result in cell death. Once enough cells from vital organs
6. Maintain directed goals of therapy. have reached this stage, shock becomes irreversible and
death can occur despite eradication of the underlying
Sepsis management bundle: septic focus. About half of the patients who succumb to
1. Use low-dose corticosteroids for septic shock if septic shock die of failure of multiple organs. 98
appropriate.
2. Give drotrecogin alfa if appropriate. The effect of sepsis and septic shock on the cardiovascular
3. Maintain glycaemic control. system is profound; the haemodynamic hallmark is gen-
4. Use protective ventilation strategies. eralised arterial vasodilation with an associated decrease
in systemic vascular resistance. Arterial vasodilation is

Management of Shock 553

mediated in part by cytokines that upregulate the expres- Initial Management: Diagnosis, Source
sion of inducible nitric oxide synthase in the vasculature. Control and Antimicrobial Therapy
Vascular response to the vasodilatory effect of nitric oxide Identifying and removing the source of infection and
and the activation of ATP-sensitive potassium channels treating the infection with appropriate antimicrobial
combine to cause closure of the voltage-gated calcium therapy are the mainstays of therapy for a patient with
channels in the cell membrane. As the vasoconstrictor sepsis. Australian data indicate that in the ICU setting the
effect of noradrenaline and angiotensin II depend on most prevalent site of primary infection is pulmonary,
open calcium channels, lack of response to these pressor followed by abdominal, together accounting for 70% of
hormones that are central to compensatory mechanisms cases. Similar epidemiology is reported in international
86
in shock can occur with the inevitable failure of delivery sepsis studies. 104,105 In 2005, ICU pneumonia practices
of oxygen to the functional mitochondria resulting in were studied in 14 ICUs and demonstrated a ventilator
99
lactic acidosis in patients with sepsis. With high circulat- associated pneumonia (VAP) incidence of 28%. A
106
ing levels of endogenous vasoactive hormones during further cohort study comparing Australian and Danish
sepsis, downregulation of their receptors occurs.
hospitals noted a lower incidence of VAP with a concomi-
tant increase in broad spectrum antibiotics prescribed
NURSING PRACTICE AND COLLABORATIVE based on clinical signs and multiresistant organisms at
MANAGEMENT the Australian site. 107
As with other forms of shock, initial management includes To provide patients with appropriate antimicrobial treat-
not only acting to correct physiological deterioration by ment for targeting the infecting organism, obtaining
initiating fluid management and frequent observation appropriate samples prior to instigating antimicrobial
and assessment, but also addressing the underlying cause therapy is the clinical standard, although any prescribed
of sepsis through source (of infection) control. treatment should not be delayed as time to antibiotic
108
administration is important in severe sepsis. In one
Initial Management: Fluid Resuscitation large retrospective study, every additional hour to effec-
Measuring surrogate markers of preload as an indicator tive antimicrobial initiation in the first 6 hours after onset
of volume status is a contentious issue, as CVP as a of hypotension was associated with >7% decrease in sur-
108,109
measure of preload is not a good marker of volume vival. Optimising dosage to achieve a therapeutic
responsiveness. 32,100 While CVP was used in sepsis trials concentration is also important. Current practice is to
of early goal-directed therapy (EGDT) protocols 35,101–103 continuously infuse glycopeptides to maintain a serum
and is an often documented endpoint of resuscitation, concentration above the minimum inhibitory concentra-
EGDT has been widely discussed and criticised in the tion and therefore kill microbes more effectively. More
literature. Australian data indicates that the incidence of recently there has been evidence that β-lactams should
110
patients meeting the criteria and mortality is lower than also be infused. Recently a paradigm shift has been
36
the treatment group in the original EGDT trial. This is suggested in relation to antimicrobial therapy; to get it
currently the focus of a large trial by the ANZICS Clinical right the first time with high doses, while limiting the
Trials Group (ARISE). 36 duration of therapy and the potential to increase
resistance. 111
Fluid resuscitation with crystalloid or colloid has long
been controversial in the critical care literature. The land- Where a patient is able to respond appropriately during
mark Saline versus Albumin Fluid Evaluation (SAFE) history and physical assessment, timelines of the infective
44
study demonstrated that in the adult intensive care process should be documented. Sites considered as infec-
patient population, albumin can be considered safe, tive sources include decubitus ulcers, invasive lines,
without demonstrating any clear advantage over saline. drains, wounds, sinuses, ears, teeth, throat, chest, blood,
In the study conducted in 14 Australian and 2 New lungs, back, abdomen, perianal, genital/urinary tract,
Zealand ICUs, 6997 patients were randomised to receive bones and joints. More invasive sampling may include
either saline (n = 3500) or albumin (n = 3497). No sig- bronchioalveolar lavage, CSF, pleural fluid, abdominal
nificant differences were noted between the two treat- collections or biopsy of other sites as clinically appropri-
ment groups for 28-day all-cause mortality, days in ate. X-rays, CT Scans and surgical consultation will also
intensive care, days in hospital, days on mechanical ven- be a priority.
44
tilation and days of renal replacement therapy. The Sur- Minimum continuous monitoring includes ECG, blood
viving Sepsis Campaign guidelines do not advocate one pressure, pulse oximetry and other measures to assess
89
preferred resuscitation fluid. Irrespective of fluid selec- preload and volume responsiveness, along with regular
tion, the disruption of the vascular bed in early septic assessment of lactate, oxygenation and markers of inflam-
shock through widespread vasodilatation results in mation and coagulation.
increased capillary permeability and rapidly developing
interstitial oedema. Large amounts of fluid can be admin-
istered without seemingly improving oxygen delivery Ongoing Collaborative Management:
whilst adding to developing generalised oedema which Drug Therapy
further impairs cellular delivery of oxygen and nutrients. A range of drug therapies aimed at supporting and ame-
Fluid resuscitation alone is therefore of limited value in liorating the signs and symptoms of septic shock are
septic shock and other measures must be considered. available and whilst inotropes in particular provide an

554 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

important adjunct in managing the acute shock phase, Drotrecogin alfa-activated (rhu), a recombinant form
other drug therapies remain controversial. of activated protein C, was developed using DNA
recombinant technology as a treatment for sepsis. Previ-
Inotropes and vasopressors ous drug trials had targeted particular aspects of the host
response to sepsis but had not yielded positive results.
A goal of maintaining MAP greater than 65 mmHg is Preclinical studies devised dose-dependent reductions in
common, with inotropes and vasopressors commenced the markers of fibrinolysis (D-dimer) and inflammation
when fluid resuscitation is considered adequate. Ad mini- (Interleukin 6) leading to a Phase III clinical trial which
stration of these drugs requires continuous blood pres- resulted in drotrecogin alfa-activated rhu being the first
sure monitoring and enables effective titration to meet drug approved for the treatment of severe sepsis. The
the treatment goal. Australian practice preferences published phase III trial was a large multi-centre, double-
noradrenaline (for its specific alpha-receptor effects) and blind randomised controlled trial (PROWESS); this
113
adrenaline as the vasopressors of choice. Dobutamine landmark study was the first drug trial to demonstrate a
(2.5–10 mcg/kg) is often added to support patients positive result in the treatment of severe sepsis. PROWESS
with myocardial dysfunction to increase myocardial was conducted in 11 countries with the hypothesis that
90
contractility and oxygen delivery to the tissues. Refrac- administration of drotrecogin alfa at 24 mcg/kg/min for
tory hypotension, resistant to vasopressors, has been 96 hours would reduce 28-day all-cause mortality in
linked to downregulation of receptors. Vasopressin (0.4– patients with severe sepsis, with an acceptable safety
0.6 units/hour) has been shown to reduce the require- profile.
ments of other vasopressor agents.
Controversy followed publication of the PROWESS
Administration of arginine vasopressin in vasodilatory paper and licensing of drotrecogin alfa. A further study,
shock may help maintain blood pressure despite the ADDRESS, mandated by the Food and Drug Administra-
relative ineffectiveness of other vasopressor hormones. tion in the USA to investigate the effect of the drug on
99
Specifically, arginine vasopressin may inactivate the KATP patients with a low risk of death, was stopped prema-
channels and thereby lessen vascular resistance to nor- turely due to futility and an increased risk of significant
adrenaline and angiotensin II. It also decreases the bleeding. Studies on children were also stopped due to
synthesis of nitric oxide (as a result of a decrease in the unacceptable risk profile. An open label trial,
the expression of nitric oxide synthase) as well as cyclic ENHANCE, was then conducted to replicate the results
114
guanosine monophosphate (cGMP) signalling by nitric of PROWESS; the Australian data indicated that depend-
99
oxide. The sites of major arterial vasodilation in sepsis ing on the selection criteria used, up to 8% of patients
– the splanchnic circulation, the muscles and the skin may be eligible for treatment with drotrecogin alfa (acti-
– are vascular beds that contain abundant arginine vated). Evidence for use remains equivocal. Use is cur-
115
vasopressin receptors. In sepsis, vasopressin stores are rently rare and where used in severe sepsis, preparation
quickly depleted. Administration of exogenous arginine and administration requires additional education and
vasopressin (0.04–0.06 units/min) can raise blood pres- continual assessment and specific attention to signs of
sure by 25–50 mmHg by returning plasma concentra- bleeding including cerebral haemorrhage.
tions of antidiuretic hormones to their earlier high
levels. 99
Other adjuncts
Steroids Adequate nutritional support to offset high caloric and
protein demands is relevant with enteral feeding pre-
The use of steroid therapy in severe sepsis remains con- ferred. Translocation of gut bacteria due to splanchnic
troversial. At times, steroid replacement therapy may be hypoperfusion and increased permeability is a factor in
used when patients display resistance to increasing doses secondary septic insults and stress ulceration. Equally
116
of adrenergic agonists, i.e. adrenal insufficiency. Some important to patient-specific measures is institution of
research indicates that patients with septic shock that are diligent infection control practices in ICU. For more
117
unable to increase cortisol levels in response to a chal- information on organ support refer to the relevant chap-
lenge may benefit from administration of low-dose cor- ters in Section II and Chapter 21.
ticosteroids (see Chapters 19 and 21 for further
112
information).
ANAPHYLAXIS
Recombinant human activated protein C Anaphylaxis is the most severe, potentially life-threatening
118–121
Activated protein C is a plasma protease produced in form of an allergic reaction, usually as a type I hyper-
response to thrombin formulation. Actions of activated sensitivity classification (IgE-mediated hypersensitiv-
121
120
protein C include: ity). Anaphylaxis appears rare, although data are
sporadic in the literature; 0.01–0.02% of the general pop-
121
● decreased inflammation through reduced levels of ulation is affected. Anaphylaxis appears more common
TNFα and NFKβ in Western countries, but this may be related to more
122
● decreased thrombin production leading to thorough reporting mechanisms. The prevalence of
anticoagulation allergy with anaphylaxis has been documented as high as
● profibrinolytic action through modulation of fibrino- 7% in one Australian study of children, with insect stings,
lysis inhibitors. oral medications or food the most often cited causes.

Management of Shock 555

However, in this study, less than 1% of the population be considered when there are two or more organ systems
actually suffered an anaphylactic reaction manifesting involved. 125
with generalised multisystem allergic reaction, including Of note is the high mortality in patients with asthma and
evidence of airway involvement, rashes, GIT and cardio- those on beta-blocker or ACE inhibitor medications; 119,126
vascular dysfunction. 123
these medications may limit the effectiveness of adrena-
This allergic response is via a host mast-cell reaction line therapy. Age and preexisting lung disease are the
mediated by immunoglobulin E (IgE), and an antibody most important factors in relation to severity; older
118
produced in response to the allergen that is attached to people and those with asthma or airways disease have a
basophils (mast cells). Once sensitised to an allergen, higher risk of a life-threatening reaction. 124
subsequent exposure may lead to an anaphylactic reac-
tion in affected individuals. The mechanism is that sub- NURSING PRACTICE AND COLLABORATIVE
sequent exposure leads to mast-cell–allergen complexes CARE: INITIAL MANAGEMENT
and the release of histamine. 124 Reactions to an allergen Diagnosis of an anaphylactic reaction requires an appro-
cannot be predicted in anaphylaxis, with a subsequent priate assessment and history, including acute onset,
119
exposure leading to an amplified or lesser response. history of allergic reaction and initial measures instituted
There can be an initial reaction, which subsides with to support airway, breathing and circulation (ABC).
treatment over about 24 hours, but often described is a Removal of the causative agent (if possible) and early
second or rebound reaction up to 8–10 hours after initial treatment (within 30 minutes of exposure to an allergen)
exposure to an allergen. 118,122
results in improved outcomes. ABC measures are impor-
CLINICAL MANIFESTATIONS tant considering the rapid impact of circulating mediators
and potential decline in respiratory and cardiovascular
Exposure to an allergen causes release of histamine and function. Securing the airway is vital as most anaphylactic
other mediators, with subsequent vasodilation and related deaths are due to asphyxiation. Adrenaline is
121
increased microvascular permeability – a distributive recommended as first-line drug treatment 119,121,122,124 often
form of shock. Histamine acts, and is metabolised, rapidly as an IM injection.
while other mediators have a sustained effect. The
121
antigen–antibody reaction may directly damage vascular NURSING PRACTICE AND COLLABORATIVE
walls, while release of vasoactive mediators such as his- CARE: AIRWAY MANAGEMENT
tamine, serotonin, bradykinins and prostaglandins trigger
a systemic response, resulting in vasodilation and Early elective intubation is recommended for patients
increased capillary permeability, with widespread loss of with airway oedema, stridor, or any oropharyngeal swell-
fluid into the interstitial space and hypovolaemia. Blood ing. Patients with airway swelling and/or angiooedema
pressure and cardiac output/index may fall with a com- are at high risk for rapid deterioration and respiratory
125
pensatory rise in heart rate. Severe bronchospasm may compromise. Late presentation to hospital or delayed
also occur from mediator-induced bronchial oedema and intubation when airway swelling is present may mean
pulmonary smooth muscle contraction. Abdominal that intubation and other emergency airway procedures
9
pain is thought to be due to the inflammation of Peyer’s may be extremely difficult. Multiple attempts at intuba-
patches (clusters of lymphatic tissue containing tion increase laryngeal oedema or cause trauma to the
B-lymphocytes, located in the mucosa and submucosa of airway. Early recognition of the potentially difficult airway
the small intestine). 124 A list of signs and symptoms for allows planning for alternative airway management by
125
anaphylaxis appears in Table 20.10. Anaphylaxis should experts in difficult airways.
NURSING PRACTICE AND COLLABORATIVE
CARE: ADJUNCTIVE SUPPORT
Adjunctive drugs include H 2 -antagonists, antihistamines,
corticosteroids and other beta 2 -agonists for airway symp-
TABLE 20.10 Clinical manifestations of toms. The H 2 -antagonists are competitive antagonists of
anaphylaxis 119,122,123 histamine at the parietal cell H 2 receptor. Blocking both
H 1 and H 2 receptors is an advantage with urticaria
System Clinical manifestations present. Corticosteroids may be beneficial for persistent
Nervous Syncope, dizziness, weakness, seizures, anxiety bronchospasm, asthma and severe cutaneous reactions
Respiratory Stridor, wheeze, cough, pharyngeal/laryngeal but not in acute management. Glucagon and noradrena-
oedema, dyspnoea, bronchospasm, line may be required for patients on beta-blockers who
tachypnoea, cyanosis, use of accessory may have resistant severe hypotension and bradycar-
muscles dia. 127 Glucagon exerts positive inotropic and chrono-
Cardiovascular Tachycardia, hypotension, arrhythmias tropic effects, independently of catecholamines, while
atropine may reverse bradycardia. Vasopressin is also
Abdominal Nausea, vomiting, cramps, pain, diarrhoea 121
suggested where shock is refractory to adrenaline.
Other Flushed skin, pruritus, urticaria, angiooedema, Given that a second reaction may occur after the initial
erythema, rash, lacrimation, conjunctival allergic response, monitoring should continue for up
injection, warmth, itching 121
to 48 hours.

556 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

PREVENTATIVE CARE NURSING PRACTICE AND COLLABORATIVE
Individuals with known allergies are taught avoidance of MANAGEMENT
allergens, and the use of emergency kits with adrenaline The extent of injury, whether complete (no sensory or
for IM injection. 120,124 Desensitisation therapy may reduce motor function) or incomplete (some sensory or motor
severity of symptoms. function), determines clinical medical management. Pri-
ority focuses on airway, breathing and circulation.
NEUROGENIC/SPINAL SHOCK After neck and torso stabilisation, a patient is placed in a

Neurogenic shock is a form of distributive shock caused position that supports spinal precautions (neutral neck
by loss of vasomotor (sympathetic) tone from disruption positioning) with the spinal boards removed within 20
to or inhibition of neural output. Characteristics include minutes if possible. Caution for spinal instability remains
SBP <90–100 mmHg and a HR <80 bpm without other despite medical imaging clearance, due to the potential
obvious causes. 128 Note that the HR is within otherwise for spinal ligament damage. The patient is positioned
accepted normal limits. Most often it is described as a supine, with their legs in alignment with the torso. Eleva-
triad of hypotension, bradycardia and hypothermia. The tion of the head may cause pooling of blood in the lower
130
primary cause is a spinal cord injury above T6, secondary limbs, exacerbating hypotension, and makes the patient
to disruption of sympathetic outflow from T1–L2 and to sensitive to sudden position changes.
unopposed vagal tone, leading to decreased vascular Loss of sympathetic outflow requires close cardiac and
resistance and associated vascular dilation. 129 It may also haemodynamic monitoring for bradycardia and hypoten-
develop after anaesthesia, particularly spinal, cerebral sion. Symptomatic bradycardia is treated and may require
medullary ischaemia or when there is spinal cord com- cardiac pacing if unresponsive to atropine. Therapies
plete or partial injury above the midthoracic region (tho- include fluid resuscitation with the addition of inotropes
racic outflow tract). if necessary to improve vasomotor tone to increase
Spinal shock is a subclass of neurogenic shock, with a preload and maintain a MAP >80–85 mmHg 129 to restore
transient physiological (rather than anatomical) reflex spinal cord perfusion and to prevent secondary neuronal
131
depression of cord function below the level of injury and hypoperfusion. A higher (supranormal) MAP may be
associated loss of sensorimotor functions. Incidence has targeted to improve recovery and prevent secondary inju-
131
been reported at 14% of patients presenting to the ED ries. Volume expansion with colloids and crystalloids
within 2 hours of injury and predominantly affects or blood products will vary depending on patient situa-
patients with cervical damage. 128 Spinal shock can also tion, however subgroup analysis in the SAFE trial indi-
occur with a spinal cord laceration or contusion, and is cated that colloids and hypotonic solutions may not be
44
associated with varying degrees of motor and sensory the best options.
deficit (see also Chapters 17 and 23). Trauma is fre- Respiratory function is closely monitored to prevent or
quently the reason for primary injury and simultaneous minimise atelectasis, pneumonia and secretion reten-
131
injuries may also be responsible for haemodynamic com- tion. The level of injury is indicative of the potential for
promise. 128 Haemorrhagic shock in combination with respiratory muscle weakness (see Table 20.11). The dia-
neurogenic shock has a poor outcome. phragm is innervated by the phrenic nerve (originating at
C3–C5); any injury above C3 leads to complete respira-
CLINICAL MANIFESTATIONS tory muscle paralysis and patients will require ventilatory
131
support. Incomplete injuries between C3 and C5 may
Inhibited sympathetic outflow results in dominance of
the parasympathetic nervous system, with a reduction in also require ventilation initially but subsequently recover
systemic vascular resistance and lowered blood pressure. some respiratory function.
Preload to the right heart is reduced, which lowers stroke Hypothermia may be present, resulting from dilated
volume and subsequent cardiac output/index. The usual peripheral blood vessels allowing radiant loss of heat. A
response to reduction in cardiac output (a raised heart patient is monitored for core temperature changes, and
rate) does not occur due to the parasympathetic nervous external warming devices may be required.
system and blockage of sympathetic compensatory
responses, and the patient may be bradycardic and hypo-
tensive, 129 with their skin warm and dry.
TABLE 20.11 Respiratory muscle innervation by
In spinal shock there may be an initial rise in blood pres- cord level
sure due to release of catecholamines, followed by hypo-
tension. 129 Flaccid paralysis, including that of the bladder Cord level innervation Accessory muscle
and bowel, is observed and sustained priapism may
develop. Symptoms may last hours to days, until the C3–C5 (mostly C4) Diaphragm
reflex arcs below the level of injury begin to regain func- C6 Serratus anterior
tion. This is a result of damage to the spinal cord, and Latissimus dorsi
results in pale, cold skin above the site of injury, and Pectoralis
warm, pink skin below the site of injury. Anhidrosis T1–11 Intercostals
(absence of sweating) may be present. Heart rate may be
slow, requiring intervention. T6–L1 Abdominals

Management of Shock 557

Paralytic ileus is a concern in the acute phase of injuries feature a complex interaction of generic compensatory
above T5, where disruption of integrative innervation mechanisms which attempt to sustain perfusion and
132
pathways leads to unmodulated colonic functioning particularly oxygen delivery to the vital organ systems
and peristaltic hypomotility. Ileus may lead to respiratory of the body. These protective responses are particularly
compromise and should be managed. The patient should strong in supporting cerebral perfusion and combine
remain ‘nil by mouth’ and treatment includes gastric responses from the SNS, endocrine and adrenal/renal
decompression, adequate IV hydration and electrolyte systems. As shock develops cellular dysfunction occurs
balance. Drug therapy with prokinetics, probiotics, aperi- in response to the release of a large collection of
ents and IV neostigmine or lignocaine has been reported systemic and local inflammatory mediators which
to be useful. in evitably overwhelm cell function and lead to diffuse
organ injury if shock continues unabated. The clas-
Pressure care is attended every second hour and where
Jordan frames are used, slats are removed between use. sification system described here differentiates shock
The patient is susceptible to deep venous thrombosis into categories including hypovolaemic, cardiogenic
(DVT), so sequential calf compression devices and other and distributive; classification is dependent on aetio-
prophylaxis are initiated early with D-dimers monitored logy. Clear assessment is required to distinguish the
regularly. type of shock aids in appropriate treatment decisions,
targeting the cause and managing associated symptoms.
SUMMARY Critical care nurses are in a position to provide clear
assessment and first-line emergency management of
Shock is a generic term describing a syndrome and the various shock states. Collaborative integrated care
pervasive set of potentially life-threatening symptoms. is important to provide the patient with the best pos-
The pathophysiological changes associated with shock sible outcome.



Case study

Locally and internationally, there are many reports that demon- The ED was very busy and no further observations were recorded
strate systematic hospital challenges for in-patients that develop until 0100h when her blood pressure was noted to be 82/60. The
shock. Identified issues include failure to recognise or respond to ED workflow was interrupted by the arrival of multiple patients
deteriorating patients, inadequate or delayed treatment, unstable from a nearby traffic accident that diverted nursing and medical
patient transfers and a lack of clinical supervision. This has led to staff to the resuscitation bays.
the implementation of track and trigger systems and development Only two further sets of observations were documented over the
of various standards and performance indicators aimed at improv- next four hours and recorded as 82/60 and then SBP 60. A further
ing patient care. The following case study highlights some of these fluid bolus of 500 mL of normal saline was administered. The
issues.
medical registrar was notified at 0540h by the team leader. After
examination, antibiotics were prescribed and an indwelling
An independent 80-year-old female, Ellen, presented to the emer- catheter inserted. There was no residual volume. Ellen was
gency department (ED) at 2200 h. The ED was very busy and short- then seen by the ICU registrar at 0620h. Central and arterial lines
staffed. Ellen was prescribed antibiotics for a urinary tract infection were inserted and it was recommended that the patient be trans-
(UTI) 10 days ago but stopped taking them 6 days ago because of ferred to ICU.
thrush. She started to feel very sick this evening and called an
ambulance. Relevant medical history includes hypertension and a Unfortunately, prior to transfer, Ellen died. The case was investigated
recent diagnosis of chronic renal failure which is currently being through a root cause analysis process as it was allocated the
investigated. On arrival, the triage nurse recorded Ellen’s blood highest severity code. Recommended system improvements
pressure at 104/37. An initial fluid bolus of 500 mL of normal saline included processes to improve early recognition of deterioration
was administered by the receiving ED nurse as per the local policy. and sepsis.



Research vignette

Harrison GA, Jacques T, McLaws ML, Kilborn G. Combinations of criteria could be wasteful of resources. This study searched a large
early signs of critical illness predict in-hospital death- the SOCCER database to explore the association of combinations of recordings
study (signs of critical conditions and emergency responses). of early signs (ES), or early with late signs (LS) with in-hospital
Resuscitation 2006; 71(3): 327–34. death.
Abstract Methods
Background A cross-sectional survey was undertaken of 3046 non-do not
Medical emergency team (MET) call criteria are late signs of a dete- attempt resuscitation adult admissions in 5 hospitals without MET
riorating clinical condition. Some early signs predict in-hospital over 14 days. The medical records were reviewed for recordings of
death but have a high prevalence so their use as single sign call 26 ES and 21 LS and in-hospital death. Combinations of ES with or

558 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



Research vignette, Continued
without LS were examined as predictors of death. Global modified could be expensive in terms of demand with limited benefit, at
early warning scores (GMEWS) were calculated. least in reduction in mortality. So whilst this study further indenti-
fies both early and late signs of deterioration that will allow for
Results
ES with LS, plus LS only, had higher odds ratios than ES alone. Four more refined calling criteria, it does fail to deliver the definitive set
combinations of ES were strongly associated with death: cardiovas- of calling criteria for clinical emergency response systems. Weak-
cular plus respiratory with decrease in urinary output, cardiovascu- nesses include the retrospective nature of the review and the reli-
lar plus respiratory with a decrease in consciousness, respiratory ance on charted records. The original sample is now over 10 years
with decrease in urinary output, and cardiovascular plus respira- old and care practices may have moved on since then. It does
134
tory. In other combinations, recordings of SpO 2 90–95%, systolic acknowledge the MERIT study, the only large-scale prospective
blood pressure 80–100 mmHg or decrease in urinary output in turn assessment of the MET system in Australia but does not discuss in
occurring with one or more disturbed blood gas variable were detail why this research failed to show a difference where a MET
associated with death. Compared with admissions whose GMEWS system was in place.
were 0–2, admissions with GMEWS 5–15 were 27.1 times more Of note, parameters in the cardiovascular category most consis-
likely to die while those with GMEWS 3–4 were 6.5 times more tently feature in the combination of signs closely associated with
likely. clinical deterioration. This emphasises both the value and the
Conclusions importance of these measures in defining clinical deterioration in
The results support the inclusion of early signs of a deteriorating patients, and provides a strong message for all clinicians working
clinical condition in sets of call criteria. in acute care as to the risks of ignoring these signs or failing to fully
assess patients on a regular basis. Many other signs not listed spe-
Critique cifically as cardiovascular are not mutually exclusive, with changes
It has long been recognised that vital signs falling out of ‘normal in mentation, urine output and blood pH inextricably linked to
ranges’ are associated with adverse events for patients. This large perfusion of specific organ systems and tissues as a whole. It is also
scale study reviewed the case notes of 3160 patients from five NSW clear that as the patient in shock deteriorates, the chances of suc-
hospitals in late 2000 for early and late physiological signs of clini- cessful intervention and recovery are reduced.
cal deterioration. It is considered a landmark Australian study given The SOCCER study continues to support the value of close, fre-
the magnitude of the review and the rigorous application of cat- quent clinical observation and the linking of signs and symptoms
egories to define patient deterioration. Twenty-six early signs and within the patient’s overall physiologic system that provides the
symptoms and 21 late signs and symptoms were defined prior to astute clinician with numerous indicators of the health or other-
the review that was initially carried out by two ICU trained nurses wise of the cardiovascular system and the impending shock syn-
and then verified by two of the investigators. The participant hos- drome. It also supports less-experienced clinicians in seeking help
pitals were chosen for their representativeness of ‘typical’ acute to interpret the patient’s clinical state and gaining support to avoid
case mix and excluded those with do not resuscitate orders, under deterioration to the point where late signs become an all-too-
14 years of age, day only admissions, non admitted ED patients, obvious message of imminent patient mortality.
deaths in O.R. prior to ward transfer, ICU patients (whilst in ICU) and
specific specialties such as palliative care or psychiatry. The care- Although there are more signs included in the SOCCER study than
133
fully selected sites for investigation and exclusion criteria all con- would be available on a standard bedside observation chart,
tributed to ensuring the findings were both representative and research such as this has led to initiatives to standardise observa-
generalisable to the broader Australian and international context. tion charts and highlight appropriate calling criteria and escalation
procedures. Standardisation in this way supports organisations to
Early signs of deterioration included, but were not limited to, SBP
80–100 mmHg, heart rate 40–49 or 121–140 b/min, respiratory rate provide equitable service to patients. In NSW there has been state-
135
5–9 or 31–40 b/min, SPO 2 90–95%, altered mentation, GCS 9–11 or wide implementation of the ‘Between the Flags’ program which
fall >2, urine output <200 mL in 8 hrs, amongst others. Likewise, includes a colour-coded chart, escalation procedure and indepth
late signs include cardiac arrest, SBP <80 mmHg, GCS ≤8, PaO 2 <50 online training modules. This program enables clinicians to respond
mmHg, pH <7.2, along with others. An ‘other’ category was appropriately and communicate effectively when patients deterio-
included. rate. The Australian Commission on Safety and Quality in Health-
care has also developed a program to support organisations in
Not surprisingly, early signs, when combined with late signs, were increasing structures for hospital patients to receive comprehen-
136
more strongly predictive than early signs alone of risk of death. sive care regardless of location and time of day. These are impor-
Having noted this, many of the early signs listed did not result in tant initiatives to combat avoidable in-hospital complications and
death so any system of response based on the early signs alone deaths.




Learning activities
The following reflective questions prompt analysis of the systems areas for improvement. After reading the case study consider the
in place where you work, to reinforce appropriate care and identify following questions:

Management of Shock 559



Learning activities, Continued
1. What assessments are important to obtain appropriate infor- Reflect on a case of a patient with shock that you have been
mation for a patient presenting with signs of hypoperfusion? involved in, and consider the following:
2. What systems are in place where you work to ensure adequate 5. What elements of care or ‘care bundles’ were effective in man-
processes are in place to assess patients presenting in shock? aging symptoms of shock?
3. How could the patient in the case study have been managed 6. What processes would you use in future to syste-
differently? matically assess, manage and evaluate care of a patient in
4. What are the clinical escalation processes in the facilities you shock?
have worked in?



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21 Multiple Organ Dysfunction

Syndrome




Melanie Greenwood
Alison Juers



also affects physiological systems such as the haemato-
Learning objectives logical, immune and endocrine systems. MODS therefore
more accurately describes altered organ function in a
After reading this chapter, you should be able to: critically ill patient who requires medical and nursing
● define the common terminology related to multiple organ interventions to achieve homeostasis. 4
dysfunction syndrome MODS is associated with widespread endothelial and
● describe the related pathophysiology of multiple organ parenchymal cell injury because of hypoxic hypoxia,
dysfunction syndrome direct cytotoxicity, apoptosis, immunosuppression and
● identify the clinical manifestations of multiple organ coagulopathy. Four clinical stages describe a patient with
4
dysfunction syndrome developing MODS: 5
● identify patients at risk of developing multiple organ 1. increasing volume requirements and mild respira-
dysfunction, including predictors of mortality tory alkalosis, accompanied by oliguria, hypergly-
● initiate appropriate monitoring, care planning and caemia and increased insulin requirements
evaluation strategies for the patient with multiple organ 2. tachypnoea, hypocapnia and hypoxaemia, with
dysfunction in relation to the current evidence base moderate liver dysfunction and possible haemato-
● discuss treatment strategies that promote homeostasis in logical abnormalities
the patient with multiple organ dysfunction syndrome 3. developing shock with azotaemia, acid–base
disturbances and significant coagulation
abnormalities
4. vasopressor dependence with oliguria or anuria,
ischaemic colitis and lactic acidosis.
Key words
Cellular damage in various organs in patients who
cytokines/mediators develop MODS begins with the onset of local injury that
multiple organ dysfunction syndrome is then compounded by activation of the innate immune
system. This includes a combination of pattern recogni-
multiple organ failure tion, receptor activation and release of mediators at the
sepsis microcellular level, leading to episodes of hypotension or
apoptosis hypoxaemia and secondary infections. The primary
4,5
inflammation therapeutic goal for nursing and medical staff is prompt,
procoagulation definitive control of the source of infection or pro-
inflammation and early recognition of preexisting factors
6
that may lead to subsequent organ damage away from the
initial site of injury. This preemptive therapy is instituted
INTRODUCTION to maintain adequate tissue perfusion and prevent the
onset of MODS. Recognition and response to early signs
The term multiple organ dysfunction syndrome (MODS) of clinical deterioration are therefore important to mini-
was established by an expert consensus conference in mise further organ dysfunction.
1992 to describe a continuum of physiologic derange-
ments and subsequent dynamic alterations in organ func- This chapter initially describes the pathophysiology of
1,2
tion that may occur during a critical illness. Previous inflammatory and infective conditions that may lead to
terminologies in the literature were confusing. For multiple organ dysfunction. System responses and spe-
example, multiple organ failure (MOF) was a term com- cific organ dysfunction are discussed, expanding on dia-
monly used, but somewhat misleading as normal physio- logue in previous chapters, particularly Chapters 19 and
logic function can, in most cases, be restored in survivors 20. Assessment of the severity of MODS and nursing
of a critical illness who have temporary organ dysfunc- considerations in the treatment of the MODS patient is
3,4
562 tion. Although the syndrome affects many organs, it presented.

Multiple Organ Dysfunction Syndrome 563

PATHOPHYSIOLOGY breakdown of cellular components into apoptic bodies.
This normally orderly process is deranged in critical
The syndrome of multiple organ dysfunction is most illness, leading to tissue or organ bed injury and MODS.
closely related to an outcome of sepsis, which was Proinflammatory cytokines released in sepsis may delay
described in Chapter 20. MODS is a state characterised apoptosis in activated macrophages and neutrophils, but
by aberrant cellular responses involving multiple organ in other tissues, such as gut endothelium, accelerated
systems and sequential processes. The pathogenesis of apoptosis occurs. 8
MODS is complex, simultaneously involving every cell
type, neuro-hormonal axis and organ system. 7 In contrast, necrosis is a form of cell death characterised
by cellular swelling and loss of membrane integrity as a
In brief, hypoxic hypoxia results from altered metabolic result of hypoxia or trauma. Necrosis has been termed
regulation of tissue oxygen delivery which contributes to ‘cellular energy crisis’, and is unregulated resulting in
10
further organ dysfunction. Microcirculatory injury as a loss of membrane sodium/potassium/ATP-ase pumps.
result of lytic enzymes, and vasoactive substances (nitric This loss leads to cell swelling, rupture and spillage of
oxide, endothelial growth factor), is compounded by the intracellular contents into surrounding regions creating
inability of erythrocytes to navigate the septic microcir- collateral damage. Necrosis therefore can involve signifi-
10
culation. Mitochondrial electron transport is affected by cant amounts of tissue and organ bed damage. Apoptosis
endotoxins in sepsis, nitric oxide and TNF-alpha, leading differs from necrosis in that it does not seem to involve
to disordered energy metabolism (see Figure 21.1). This the recruitment of inflammatory cells or mediators to
causes cytopathic or histotoxic anoxia (the inability to complete its task. Activation of an enzyme cascade sys-
8
use oxygen, even when available). This context of tematically cleaves proteins, including the cell’s nuclear
7,8
impaired oxygen utilisation rather than delivery results DNA, with the end-result being death of the cell. This
from diminished mitochondrial production of cellular requires energy from mitrochondria and if not available
energy (ATP), despite normal or even supranormal intra- necrosis of the cell occurs. Apoptosis and necrosis are
9
cellular PO 2 levels. Cytopathic hypoxia appears resistant processes that if is therefore important to understand in
to resuscitation measures, and this may ultimately worsen relation to future MODS research.
already-existing organ dysfunction. During sepsis or isch-
aemia, mitochondria respond by facilitating cell death Increased concentrations of cell-free plasma DNA are
rather than the restoration of homeostasis. 7 present in various clinical conditions such as stroke, myo-
cardial infarction and trauma, a likely result of acceler-
Apoptosis is normal physiological programmed cell ated cell death. Maximum plasma DNA concentrations
death and is the main mechanism to eliminate dysfunc- correlated significantly with APACHE II scores and
10
tional cells. Apoptosis involves chromatin condensa- maximum SOFA scores (described later in this chapter),
tion, membrane blebbing, cell shrinkage and subsequent with cell-free plasma DNA concentrations higher in


Reduced delivery of
oxygen and glucose

Anaerobic metabolism Protein synthesis
Lactate ATP production Lipolysis
pH Cell function

+
+
Na /K pump
+
Intracellular Ca ++ K + Na and H O
2
Denaturing of protein
Cell membrane leakiness Cellular swelling


Lysis and rupture
of organelles


Cell lysis/death

Protein synthesis
Lipolysis
Cell function
FIGURE 21.1 Pathophysiology of cellular dysfunction.
97

564 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E


Coagulation Activated protein C
Endothelium cascade Activated protein C

Tissue Factor
Factor VIlla
IL-6 PAI-1
IL-1 Inactivation
TNF-
Monocyte Factor Va Inactivation
Inhibition Protein C Inactivation Suppressed
Activated
fibrinolysis
THROMBIN TAFI
Neutrophil Fibrin
Inhibition IL-6 Reduction

Tissue factor of rolling Activated Fibrin clot
protein C
Inflammatory response Thrombotic response Fibrinolytic response
FIGURE 21.2 Tissue factor pathway (Courtesy Eli to Infection to Infection to Infection
Lilly and Company).



hospital non-survivors than in survivors. Using regression and fail, and the body is no longer able to maintain
analysis, maximum plasma DNA was an independent homeostasis (see Figure 21.2).
16
predictor of hospital mortality. 11
Initially, proinflammatory mediators are released locally
Other cellular organelles may also exhibit pathological to fight foreign antigens and promote wound healing.
reactions in MODS. In ischaemia/reperfusion, endoplas- Antiinflammatory mediators are also released to down-
14
mic reticulum loses its ability to process proteins which regulate the initial response to the insult. If the local
7
induces the expression of heat shock proteins, affecting defence system is overwhelmed, inflammatory mediators
transcription of proteins necessary for organ specific func- appear in the systemic circulation and recruit additional
tions. For example, liver cell metabolism, renal cell func- leucocytes to the area of damage. A whole-body stress
7
tion or cardiac cell contractility may be affected. This response ensues, further compounding the situation.
has led to the controversial concept of a mode of hiberna- If proinflammatory mediators and antiinflammatory
tion of cells at the expense of survival of the whole response is imbalanced, the patient may develop systemic
organism. 7 inflammatory response syndrome (SIRS) and subsequent
15
immunological dissonance of organ dysfunction. 2,15,16
Cellular communication is also altered in MODS. Cells
normally communicate through highly interactive bidi- Regardless of the trigger event, lymphocytes (T cells, B
rectional networks. The endothelium acts as a communi- cells, natural killer cells) and macrophages are activated
cation interface between cells, organs and systems and is by cytokines (cellular signalling agents) to commence the
involved in orchestration of systemic responses, includ- inflammatory or anti-inflammatory response. A number
ing haemodynamic regulation, inflammation and coagu- of Interleukins (IL) have been identified as key cytokines
lation; oxygen and nutrient delivery; oxidative stress and in proinflammatory (e.g. IL-1, IL-6; and similar to tumour
sensing of psychological stress and neuroendocrine alter- necrosis factor alpha [TNFα] actions) or antiinflamma-
ations. In critical illness, endothelia release molecules tory (e.g. IL-10, IL-6, IL-4) responses. The inflammatory
7
that trigger the immune and neuroendocrine systems to response results in clinical signs of hypoperfusion, culmi-
produce a generalised inflammatory response. The com- nating in shock.
7
bination of the pathophysiological processes involved Intracellular transcription factors, in particular nuclear
with the development of MODS, compensatory mecha- factor kappa B (NFκB), are important in innate and adap-
nisms and the effect on target organs and systems is now tive immunity, 17,18 as they regulate the transcription of
discussed. genes involved in the inflammatory and acute stress
SYSTEMIC RESPONSE response, leading to expression of TNFα, interleukins and
18,19
NFκB therefore plays an important role
tissue factor.
After an overwhelming incident such as trauma, sepsis or in response pathways in critical states including hypoxia,
18,20,21
non-infectious inflammation, a complex range of inter- ischaemia, haemorrhage, sepsis, shock and MODS.
related reactions occurs that result in a cascade of The inflammatory cascade activates a number of prosta-
responses. The complex host-response generated involves glandins and leucotrienes that also have pro- and anti-
the inflammatory immune systems, hormonal activation inflammatory effects. Thromboxane A2 plays a role in the
and metabolic derangements, resulting in multiple organ acute phase, in part due to stimulation of platelet aggre-
system involvement. 12,13 These host-responses are initially gation, leading to microvascular thrombosis and tissue
15
adaptive to maintain nutrient perfusion to the tissues, injury; it may also play a role in pulmonary broncho-
however eventually organ systems become dysfunctional constriction and myocardial depression.

Multiple Organ Dysfunction Syndrome 565

The specific pathophysiological concepts of inflamma- including circulating cytokines, oxygen free-radicals and
tion, oedema and infection are discussed below. activated neutrophils, alter the structure of endothelial
cells, enabling larger molecules (proteins, water) to cross
INFLAMMATION into the extravascular space. 23,28 This response mechanism
improves supply of nutrient-rich fluid to the site of injury,
Inflammation is part of innate immunity, a generic
response to injury, and is normally an excellent mecha- but if this becomes systemic, fluid shifts can lead to hypo-
nism to localise injury and promote healing. 22,23 The basis volaemia, third-spacing (interstitial oedema) or affect
23
of this immune response is recognition and an immedi- other organs (e.g. acute lung injury, ALI).
ate response to an invading pathogen without necessarily
24
having previous exposure to the pathogen. Neutrophils, INFECTION AND IMMUNE RESPONSES
macrophages, natural killer cells, dendrites, coagulation
and complement are the principal active components of Infection exists when there is one of the following: posi-
29
the innate host response. 23 tive culture, serology, presence of polymorphonuclear
leucocytes in a normally sterile body fluid except blood,
The classic signs of inflammation are: and clinical focus of infection such as perforated viscus
or pneumonia. In sepsis, the most common sites of infec-
● pain
● oedema tion are the lungs (34–54%), intra-abdominal organs
30,31
● erythema and heat (from vasodilation) (15–28%) and urinary tract (5–10%). 29 The incidence
● leucocyte accumulation and capillary leak. 22,23 of bloodstream infections is 30–40%, although one-
third of cases with septic shock have negative blood
Nitric oxide and prostaglandins (e.g. prostacyclin), are cultures; one reason suggested for this is antibiotic
32
the primary mediators of vasodilation and inflammation administration prior to sample collection. The type of
23
at the injury site. Injured endothelium produces mole- infecting organism has also changed over time, with
cules that attract leucocytes and facilitate movement to Gram-positive bacteria predominant, accounting for at
the tissues. White blood cells accumulate by margination least one-third of pathogens in septic shock; Gram-
(adhesion to endothelium during the early stages of negative, fungal, viruses and parasitic organisms are also
inflammation) and neutrophils accumulate at the injury involved. The increasing incidence of resistant organ-
29
site, where rolling and adherence to binding molecules isms, partially as a result of the indiscriminate use of
on the endothelium occurs with eventual movement antibiotics, is an ongoing concern.
23
across the endothelium into the tissues. Different blood
components therefore escape the intravascular space and The immune response to infection has both non-specific
occupy the interstitial space where they play the main and specific actions, with inflammation and coagulation
role in successive phases of the inflammatory response. responses intricately linked in sepsis pathophysio-
23,24,33,34
The endothelium therefore plays a bidirectional mediat- logy. Tissue injury and the production of inflam-
ing role between blood flow and the interstitial space matory mediators lead to:
where inflammation mainly takes place. Macrophages, ● coagulation via the expression of tissue factor and
25
neutrophils and monocytes are responsible for phagocy- factor VIIa complex (tissue factor pathway; the primary
tosis and the production of toxic free radicals to kill cascade for initiation of coagulation; previously
24
invading pathogens. The complement system, a collec- termed the ‘extrinsic’ pathway) 28,33-35
tion of 30 proteins circulating in the blood, is also acti- ● coagulation amplification via factors Xa and Va,
vated, with plasma and membrane proteins acting as leading to massive thrombin formation and fibrin
adjuncts to inflammatory and immune processes. When clots (common coagulation pathway). 28,33
26
activated by inflammation and microbial invasion, these
processes facilitate lysis (cellular destruction) and phago- Note that blood cell injury or platelet contact with endo-
cytosis (ingestion) of foreign material. 23,26 thelial collagen initiates the contact activation pathway
(previously termed the ‘intrinsic’ coagulation pathway). 33
Dysfunction of organ systems often persists after the
initial inflammatory response diminishes; this is largely
unexplained, although dysoxia (abnormal tissue oxygen PROCOAGULATION
metabolism and utilisation) has been implicated. 22,27 Tissue factor is a procoagulant glycoprotein-signalling
36
Hypoxia induces release of IL-6, the main cytokine that receptor, expressed when tissue is damaged or cytokines
initiates the acute phase response. After reperfusion of are released from macrophages or the endothelium
ischaemic tissues, tissue and neutrophil activation forms (see Figure 21.3). Prothrombin is formed, leading to
reactive oxygen species (e.g. hydrogen peroxide) as a thrombin and fibrin generation from activated platelets.
byproduct. These strong oxidants damage other mole- Resulting clots are stabilised by factor XIII and thrombin-
23
cules and cell structures that they form, resulting in activatable fibrinolysis inhibitor (TAFI). 33,36 Fibrinolysis
water and sodium infiltrate and cellular oedema. is a homeostatic process that dissolves clots via the
plasminogen–tissue plasminogen activator (tPA)–plas-
OEDEMA min pathway (involving antithrombin, activated protein
37
Oedema occurs as a consequence of alterations to tissue C [APC] and tissue factor pathway inhibitor). APC:
endothelium, with increased microvascular permeability ● reduces inflammation by decreasing TNF and NFκB
(‘capillary leak’). As noted earlier, many mediators, production

566 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E







Infection
(Bacterial, Inflammation Endothelial
viral, fungal, Coagulation Dysfunction Hypoperfusion Acute
Organ
or parasitic and Ischaemia Dysfunction
infection/ Fibrinolysis Microvascular
endotoxin) Thrombosis



FIGURE 21.3 Progression of SIRS-Sepsis-Shock-
MODS (Courtesy Eli Lilly and Company).




TABLE 21.1 Actions of the stress response 38

Response stage Neurohormonal response Actions
Alarm reaction Hypothalamus ● Impulses to sympathetic nervous system and adrenal medulla
Noradrenaline/adrenaline ● α-Adrenergic receptors: vasoconstriction or arterial wall smooth muscle
and viscera; rise in heart rate and contractility
● Increased hepatic glucose production
● β 2 -Adrenergic receptors: vasodilation to lungs and skeletal muscles
Resistance reaction Anterior pituitary/ ● Secretes adrenocorticotrophic hormone (ACTH)
corticotrophin-releasing factor
Anterior pituitary/thyroid-stimulating ● Stimulates T3 and T4 production, increasing use of glucose for adenosine
hormone (TSH) triphosphate (ATP) production
Human growth hormone (hGH) ● Increase in protein synthesis
● Increased mobilisation of fatty acids from adipose tissue for energy use
● Decreased rate of glucose utilisation
● Excessive secretion may result in ketosis and insulin resistance
ACTH ● Cortisol secretion by adrenal cortex
Kidney/renin release ● Angiotensin–aldosterone secretion
Angiotensin II ● Intense vasoconstriction of arterioles, renal retention of sodium and water,
with increased total peripheral resistance and arterial blood pressure
Aldosterone ● Sodium reabsorption and water retention with an increase in intravascular
volume, cardiac output and blood pressure
Exhaustion ● Progressive loss of homeostasis
● Cellular dysfunction



● reduces thrombin production when activated via sympathetic–adrenal–medullary axis, results in ongoing
thrombin–thrombomodulin complexes (anticoagu- production of glucocorticoid hormones and catechol-
17
lant action) amines. This response interferes with the regulation of
● inhibits thrombin-activatable fibrinolysis inhibitor cytokine-producing immune cells, leading to immune
and plasminogen activator inhibitor-1 (profibrino- dysfunction. Other compensatory mechanisms are insti-
lytic action). 33,34 gated in an attempt to maintain supply and perfusion to
organs. 15
APC is consumed in severe sepsis, and thrombomodulin
is unable to activate protein C, 33,34,37 promoting a pro- These homeostatic mechanisms are activated through
inflammatory, prothrombotic state. 34 positive or negative feedback systems to counteract stress.
When stress is extreme or prolonged, these normal
ENDOCRINE RESPONSE homeostatic mechanisms may be insufficient and a
Physiological changes are triggered as a normal patient may respond through a sequence of physiological
response to a stressor. In a critically ill patient, however, changes called the stress response. The stress response
chronic activation of the stress response, including occurs in three stages: the alarm reaction, the resistance
the hypothalamic–pituitary–adrenal axis and the reaction and exhaustion (see Table 21.1). 38

Multiple Organ Dysfunction Syndrome 567

38
The alarm reaction (flight-or-fight response) is initiated
when stress is detected, increasing the amount of glucose TABLE 21.2 Acute organ dysfunction 46,98
and oxygen available to the brain, skeletal muscle and
heart. Two-thirds of total blood volume is also redistrib- Organ system Clinical parameters
38
uted to support central circulation. A rise in glucose
production and the breakdown of glycogen in skeletal Cardiovascular Patient requires vasopressor support (systolic
BP <90 mmHg) or MAP <70 mmHg for 1
muscle increases circulating glucose levels, providing an hour despite fluid bolus
immediate energy source. The long-lasting second stage
is a resistance reaction, involving hypothalamic, pituitary Respiratory Patient requires mechanical ventilation: P/F
ratio <250, PEEP >7.5 cmH 2 O
38
and adrenal hormone release. Response exhaustion
occurs when these physiological changes can no longer Renal Low urine output <0.5 mL/kg/h; raised
maintain homeostasis. creatinine >50% from baseline or requiring
acute dialysis
3
Haematological Low platelet count (<1 000 000/mm ) or APTT/
COMPENSATORY MECHANISMS PTT > upper limit of normal
Internal equilibrium (homeostasis) is maintained by the Metabolic Low pH with increased lactate (pH <7.3 and
nervous and endocrine systems, and these work symbio- plasma lactate > upper limit of normal)
tically with other compensatory mechanisms, such as Hepatic Liver enzymes >2 × upper limit of normal
endothelial cells, to maintain cellular perfusion. The
nervous system responds rapidly to maintain homeosta- CNS Altered level of consciousness/reduced
Glasgow Coma Scale score
sis by sending impulses to organs to activate neurohor-
monal responses (see Chapters 16 and 20). Endothelins Gastrointestinal Translocation of bacteria, possible elevated
(ET-1, ET-2, ET-3) are potent vasoconstrictors produced pancreatic enzymes and cholecystitis
20
by endothelial cells that regulate arterial pressure. The
endocrine system works in a slow and sustained manner
by secreting hormones, which travel via the blood to ORGAN DYSFUNCTION
end-organs.
Organ dysfunction is a common clinical presentation in
An initial acute-adaptive response is activated when an ICU. Patients with dysfunction in the respiratory, cardio-
insult or stress occurs. For example, the body senses a vascular, hepatic or metabolic systems were 50% more
disruption of blood flow through baroreceptor and che- likely to require ICU treatment and had a higher mortal-
moreceptor reflex actions: baroreceptors located in the ity than patients not requiring intensive care. Timely
41
13
carotid sinus detect changes in arterial pressure; chemo- identification of organ dysfunction is therefore critical, as
receptors co-located with the baroreceptors detect O 2 , early intervention reduces damage and improves recovery
+
CO 2 and H concentration. When alterations are sensed, in organ systems. As each organ fails, the average risk of
the cardiovascular centre in the brain adjusts autonomic death rises by 11–23%, with up to 75% of patients in
outflow accordingly. In a patient with decreased tissue sepsis clinical trials having at least two failing organs.
38
42
perfusion, there is increased peripheral vasoconstriction, The organ system that most commonly fails is the pul-
contractility and heart rate. Blood flow is shunted to the monary system, followed by the cardiovascular, renal and
vital organs (brain, heart, lungs), and away from less vital haematological systems. Organ and systems dysfunc-
43
areas (e.g. gastrointestinal and reproductive organs). tion are a result of hypoperfusion, inflammation, cellular
39
Important hormonal regulators of blood flow are also dysfunction and oedema. Dysfunction of the cardiovas-
activated from decreased blood flow to the kidneys, cular (Chapters 10 and 12), respiratory (Chapters 14 and
including adrenocorticotrophic hormone (ACTH), and 15), renal (Chapter 18), and hepatic and gastrointestinal
the renin–angiotensin–aldosterone system (see Chapter systems (Chapter 19) have been previously addressed.
18). Adrenal medullary hormones, adrenaline and nor- This next section addresses the haematological, endo-
adrenaline, vasopressin (antidiuretic hormone) and atrial crine and metabolic systems. Neurological dysfunction is
natriuretic peptide also regulate blood flow to maintain also common in the patient with MODS and comple-
adequate circulation and tissue oxygenation. 13,38,39 ments previous discussions in Chapter 17.
Arterial pressure is a major determinant of tissue perfu-
20
sion as it forces blood through the regional vasculature. HAEMATOLOGICAL DYSFUNCTION
Hypotension (systolic blood pressure <90 mmHg or Systemic inflammatory response syndrome (SIRS) and
mean arterial pressure [MAP] <70 mmHg) results from disseminated intravascular coagulation (DIC) have
either low systemic vascular resistance or a low cardiac pivotal and synergistic roles in the development of
20
44
output. Glomerular filtration falls, leading to reduced MODS. The coagulopathy present in MODS results
urine output; low cerebral blood flow results in an altered from deficiencies of coagulation system proteins (e.g.
8
level of consciousness; and other manifestations reflect protein C, antithrombin 3 and tissue factor inhibitors).
low-flow states in other organ systems. To maintain Inflammatory mediators initiate direct injury to the vas-
oxygen supply, respirations and heart rate increase to cular endothelium, releasing tissue factor, triggering the
40
meet organ oxygenation demands. Organ dysfunction extrinsic coagulation cascade and accelerating thrombin
8
ensues if balance is not sufficiently restabilised production. Coagulation factors are activated as a result
(see Table 21.2). of endothelial damage with binding of factor XII to the

568 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

subendothelial surface, activation of factors XI, XII, X, such as in purpura fulminans or ischaemia in the extremi-
8
VIII, calcium and phospholipid. The final pathway is ties. 47,48 Administration of APC in its role as inhibitor of
production of thrombin which converts soluble fibrino- the coagulation cascade is controversial. A Cochrane
gen to fibrin. Fibrin and aggregated platelets form intra- review of four studies involving 4911 participants (4434
vascular clots. adults and 477 paediatric patients) identified no reduc-
tion in risk of death (28-day mortality) in adult partici-
Inflammatory cytokines also initiate coagulation though
activation of tissue factor (TF), a principal activator of pants with severe sepsis, but was associated with a higher
coagulation. Endotoxins increase the activity of inhibi- risk of bleeding. Effectiveness was not associated with the
49
tors of clot breakdown (fibrinolysis). Levels of protein C degree of severity of sepsis. Studies continue into this
and endogenous activated protein C are decreased in area of clinical practice.
sepsis; this inhibits coagulation cofactors Va and VIIa and
acts as an antithrombotic in the microvasculature. 8 Endocrine Dysfunctions
Numerous endocrine derangements are noted in critically
Microvascular thrombosis that leads to MODS results ill patients, including abnormalities in thyroid, adreno-
from two major syndromes: thrombotic microangiopathy cortical, pancreas, growth and sex hormones. A high thy-
(TMA) and disseminated intravascular coagulation (DIC). rotropin (TSH) level is a significant independent predictor
TMA is characterised by formation of microvascular plate- of non-survival in critically ill patients, while subclinical
50
let aggregates and occasionally fibrin formation. Typically hypothyroidism has significant negative effects on cardiac
there is history of injury to the microvascular endothe- function and haemodynamic instability. 50,58
lium (e.g. thrombotic thrombocytopenic purpura, hae-
molytic uremic syndrome, haemolytic anaemia, elevated Adrenal Insufficiency
liver enzymes and low platelet syndromes of pregnancy
44
or antiphospholipid antibody syndrome). TMA usually Adrenal insufficiency is present in approximately 30% of
32,43,51,52
presents with normal coagulation profiles such as pro- patients with sepsis or septic shock, and is associ-
thrombin times and partial thromboplastin time. 44 ated with chronic adrenal insufficiency and recent physio-
50
logical stress, or in new-onset adrenal insufficiency. This
Disseminated intravascular coagulation results from adrenal insufficiency can be caused by sepsis, surgery,
widespread activation of tissue factor-dependent coagula- bleeding and head trauma. Adrenal insufficiency as a
tion, insufficient control of coagulation and plasminogen- cause of shock should be considered in any patient with
mediated attenuation of fibrinolysis. This leads to hypotension with no signs of infection, cardiovascular
44
formation of fibrin clots, consumption of platelets and disease or hypovolaemia. Incidence ranges from 0–95%,
53
coagulation proteins, occlusion of the microvasculature, partly because there is no standard definition for adrenal
and resultant reductions in cellular tissue oxygen deliv- insufficiency.
44
ery. DIC is most commonly a result of trauma or sepsis
and is an exaggerated response to normal coagulation Eosinophilia (>3% of total white blood count) is reported
aimed at limiting infection, exsanguination and promot- as a marker of adrenal insufficiency. Methods to diagnose
ing wound healing. 44 acute adrenal insufficiency include: (1) a single random
cortisol level check, or a change in cortisol level after
3
Thrombocytopenia (a platelet count of <80,000/mm or endogenous adrenocorticotrophic hormone (ACTH) is
a decrease of ≥50% over the preceding three days) signi- administered; or (2) a short corticotrophin stimulation
45
fies haematological failure, with leucocytopenia/cytosis, test with administration of high-dose ACTH. A change in
46
markers of coagulation and DIC also present. Treatment cortisol level (≤9 µg/dL) is considered relative adrenal
is supportive and aimed at removing the triggering insults. insufficiency. It is however argued that patients with
Clinical biomarkers include a simultaneous rise in pro- severe sepsis may have appropriate cortisol levels, but not
34
thrombin time, APTT and thrombocytopenia. A patient the reserve function to respond to the stimulation test. 31
may exhibit bleeding from puncture sites (e.g. invasive
vascular access), mucous membranes including bowel, or Steroid Therapy
upper gastrointestinal tract. Bruising or other subcutane- As septic shock is a major complication of infectious
ous petechiae may be evident. The skin should be pro- processes, the relationship between the immune, coagu-
tected from trauma. 54
lation and neuroendocrine systems has been explored.
Primary therapy is directed at the cause of the insult, with The role of corticosteroids in the treatment of septic
SIRS, ischaemia, uraemia, hepatotoxins and sources shock has led to a number of trials that suggested some
of infection, injury or necrosis managed concurrently. survival benefit for low-dose corticosteroid therapy. More
Aggressive resuscitation includes crystalloid or colloid research is required, however, because of conflicting find-
administration, replacement of blood components and ings from individual studies.
clotting factors using packed cells, platelets, cryoprecipi- Therapy with corticosteroids at a physiological dose,
tate and fresh frozen plasma. Endpoints for haemoglo- rather than a high dose, followed observations that
bin, platelets and coagulation levels have not been agreed patients with septic shock who had a reduced response
upon and replacement is therefore individualised. 47
to corticotropin were more likely to have increased mor-
The role of heparin or fractionated heparin is controver- tality, and that pressor response to noradrenaline may be
55
sial in the presence of sepsis, particularly in those with improved by the administration of hydrocortisone. A
overt thromboembolism or extensive fibrin deposition, trial exploring steroid use in sepsis demonstrated reduced

Multiple Organ Dysfunction Syndrome 569

vasopressor requirements and early lower mortality, but Hypocalcaemia
52
no difference in 1-year survival. A multicentre trial dem- Hypocalcaemia is common in patients with SIRS, and
47
onstrated that hydrocortisone administration did not affects myocardial contractility and neuromuscular func-
improve survival in patients with septic shock. Shock tions. The link between neuromuscular changes such as
reversal was shorter in patients who received hydrocorti- polyneuropathy or polymyopathy and critical illness has
sone, but there were more episodes of infection including not been established beyond early investigations into
56
new sepsis and septic shock. Although the largest trial corticosteroid use, neuromuscular blocking medication
of corticosteroids in patients with septic shock, the study administration and prolonged mechanical ventilation. 61
was not adequately powered to detect a clinically impor-
tant treatment and so findings are to be interpreted with
55
caution. It is therefore appropriate to reserve corticoste- NEUROLOGICAL DYSFUNCTION
roids for patients with septic shock whose blood pressure Recent evidence has highlighted that multiple organ dys-
is poorly responsive to fluid resuscitation and high dose function can result from severe traumatic brain injury
57
vasopressor therapy. Long-term treatment with cortico- (TBI) or subarachnoid haemorrhage (SAH) (see Chapter
steroids may result in an inadequate response of the 17). Cardiovascular and respiratory dysfunction contrib-
adrenal axis to subsequent stress such as infection, surgery ute to mortality in approximately two-thirds of all deaths
62
or trauma, with resulting onset or worsening of shock. following severe TBI. In non-traumatic SAH the inci-
Other studies using corticosteroids for adrenal insuf- dence and importance of life-threatening conditions
ficiency in critically ill patients demonstrated lower from non-neurological physiology has been identified,
mortality. e.g. 8 including lethal arrhythmias, myocardial ischaemia and
dysfunction and neurogenic pulmonary oedema. The
62
Corticosteroid administration is associated with hyper- cause of cardiovascular and respiratory organ dysfunction
glycaemia and may affect patient outcomes, necessitating following these acute severe neurological events is associ-
insulin therapy to normalise blood glucose levels. A ated with dysfunction of the sympathetic nervous system.
recent multicentre trial (Corticosteroids and Intensive Beta blockers may modulate the sympathetic storm
Insulin Therapy for Septic Shock [COIITS]), demon- resulting from severe neurological injury. 62
54
strated that intensive insulin therapy did not improve
in-hospital mortality for patients treated with hydrocor- Critically ill patients may develop a syndrome of neuro-
tisone and oral fludrocortisones for septic shock. muscular dysfunction characterised by generalised muscle
weakness and an inability to wean successfully from
Glycaemia Control mechanical ventilation. Critical illness neuromyopathy
syndromes (CINM) or ICU-Acquired Weakness (ICU-
Hyperglycaemia is common in critically ill patients as a AW) has been associated with risk factors including
result of stress-induced insulin resistance and accelerated hypergylcaemia, SIRS, sepsis, MODS, renal replacement
glucose production, and excessive circulating levels of therapy, glucocorticoids, neuromuscular blocking agents
glucagon, growth hormone, sympathomimetics and glu- and catecholamine administration. The risk of CINM/
63
cocorticoids (see Chapter 19). An increased caloric intake ICU-AW is nearly 50% in patients with sepsis, MODS or
from parenteral or enteral nutrition will also increase protracted ventilation, with short-term survival uncer-
63
glucose levels. Hyperglycaemia has undesirable effects tain. Glycaemic control may be a potential strategy for
such as fluid imbalance, immune dysfunction, promoting decreasing CINM/ICU-AW risk. 63
inflammation, abnormalities in granulocyte adherence,
31
chemotaxis, phagocytosis and intracellular killing. Survivors of sepsis-induced multiple organ dysfunction
Resulting associations between hyperglycaemia and may also suffer long-term cognitive impairment, includ-
adverse clinical outcomes have been reported in many ing alterations in memory, attention, concentration and/
64
observational studies. Potential benefits of exogenous or global loss of cognitive function. The participation
insulin administration include normalising immune of the brain during sepsis is poorly understood; septic
functional, improving oxygen delivery to ischaemic areas encephalopathy is the more common neurological dys-
of myocardium, tissue repair and preventing transfusion, function, accounting for up to 70% of brain dysfunc-
64
31
dialysis and critical illness polyneuropathy. Intensive tions. Chapter 4 described the physical, psychological
insulin therapy has also been suggested to improve mor- and cognitive sequelae for survivors of a critical illness
bidity, reducing the risk of sepsis, excessive inflammation during their recovery.
and multiple organ failure, transfusion requirements and
dependence on mechanical ventilation. 59 MULTIORGAN DYSFUNCTION
The Normoglycaemia in Intensive Care Evaluation and MODS contributes to significant morbidity and use of
Survival Using Glucose Algorithm Regulation Study intensive care resources worldwide. Patients with MODS
(NICE-SUGAR) examined tight glycaemic control with have an increased ICU length of stay when compared to
65
60
insulin during critical illness. Maintaining blood glucose high-risk patients without multiple organ involvement.
at less than 10 mmol/L resulted in 10% reduction in The epidemiology of MODS is changing however, with
90-day mortality compared to a tighter glycaemic control studies in post-injury organ failure indicating a reduction
60
target (4.5–6.0 mmol/L). Lower target blood sugar in incidence, disease severity, duration and mortality. 65,66
levels are therefore not recommended for managing gly- Mortality ten years ago was estimated at 40–60%, rising
caemia in critical ill patients. with subsequent organ dysfunction. 42,67,68 More recent

570 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

data in post-injury MODS indicates a reduction in mor- variations of SOFA-based models have emerged in the
tality rates to 14–27%. 65,66 This decrease in mortality is literature, such as single SOFA scores calculated at admis-
occurring despite increasing patient acuity and may reflect sion or at a set time after admission, sequential SOFA
improvements in the delivery of critical care. 6 scores (mean SOFA score), dynamic SOFA scores and
scores of separate SOFA components. 69,70 SOFA scores at
admission are comparable with severity of illness models
SCORING SYSTEMS such as APACHE or SAPS for predicting mortality. SOFA
70
Organ dysfunction can be a consequence of a primary scoring has the advantage of ease of use, as the clinical
insult or a secondary insult due to circulating mediators and laboratory data required are those that are routinely
(e.g. the patient with ALI from pneumonia that also has available. As such, the use of dynamic SOFA scoring as a
renal dysfunction or failure as a consequence). This is means of monitoring patient response to treatments is
69,71
sometimes quantified by scoring systems, traditionally being explored.
used for predicting mortality but increasingly being
explored as clinical management tools. 69-71 These systems OTHER FACTORS
are continually being tested and modified, to assess organ Biomarkers such as lactate and strong ion gap (SIG) are
dysfunction severity and prognosis in an effort to identify also being studied as indicators of occult hypoperfusion
patients who will benefit most from timely clinical inter- and severity of organ dysfunction. Blood lactate levels are
71
vention. Scoring systems such as APACHE (acute physio- associated with SOFA scores, particularly in the early
logy and chronic health evaluation), SAPS (simplified stage of ICU admission, supporting early resuscitation as
acute physiology score) and MPM (mortality probability a management strategy to prevent organ dysfunction.
models) account for information relating to a 24-hour Serial lactate scores may therefore be appropriate to
cycle of patient data (commonly in the first 24 hours of guiding optimal oxygen delivery in early resuscitation,
admission), but do not account for the dynamic nature with hyperlactataemia a sign of impending organ dys-
of many of the factors that affect clinical outcomes. function. Prospective, well-controlled studies are however
needed to confirm the role of lactate and SIG in MODS
Specific instruments designed to assess organ dysfunction 74-76
or failure include the sepsis-related/sequential organ management.
failure assessment (SOFA) score, the multiple organ Variations in the human DNA sequences can affect the
dysfunction score and the logistic organ dysfunction way a person responds to disease. Researchers have
system. 70,72 Traditionally SOFA uses the worst values for studied the gene code for PAI-1 which is a key element
six commonly measured clinical parameters within a in the inhibition of fibrinolysis and is active during acute
24-hour period: PaO 2 /FiO 2 (P/F ratio), an index that may inflammation (the gene most studied is found at the
77
be used to characterise acute respiratory distress syn- 4G/5G insertion/deletion loci), finding that different
73
drome; platelet count, bilirubin level, blood pressure, aspects bind as either a repressor (5G) or activator (4G)
Glasgow Coma Scale score, and urine output or creati- protein. For example, the 4G allele (position on the gene)
nine concentration. As the number of dysfunctional of the 4G/5G gene sequence variation has been associ-
organ systems increases, there is a rise in mortality as ated with increased susceptibility to community acquired
measured by SOFA scores (see Table 21.3). Many pneumonia and increased mortality in cases of severe



TABLE 21.3 Sequential Organ Failure Assessment (SOFA) score 69,99

SOFA score 0 1 2 3 4
Respiration >400 ≤400 ≤300 ≤200 a ≤100 a
PaO 2 /FiO 2
Coagulation platelets >150 ≤150 ≤100 ≤50 ≤20
3
× 10 /mm 3
Liver <1.2 mg/dL 1.2–1.9 2.0–5.9 6.0–11.9 >12.0
Bilirubin >32 µmol/L 20–32 33–101 102–204 >204
Cardiovascular MAP >70 mmHg MAP <70 mmHg Dopamine ≤5 or Dopamine >5 or Dopamine >15 or
hypotension Dobutamine adrenaline ≤0.1 or adrenaline >0.1 or
(any dose) b noradrenaline ≤0.1 b noradrenaline >0.1 b
CNS 15 13–14 10–12 6–9 <6
Glascow Coma Scale
Renal creatinine or <1.2 mg/dL 1.2–1.9 2–3.4 3.5–4.9 >5.0
urine output <110 µmol/L 110–170 171–299 300–440 >440
or or
<500 mL/day <200 mL/day
a with respiratory support
b adrenergic agents administered for at least 1 hour (doses in µg/kg per min)

Multiple Organ Dysfunction Syndrome 571

pneumonia. It has also been reported to affect the risk of which components of EGDT are effective is lacking. Trials
developing severe outcomes and higher mortality in currently underway to address this issue include the
77
meningococcal sepsis and trauma. Among critically ill ProCESS (Protocolized Care for Early Septic Shock) and
83
patients with severe sepsis due to pneumonia, carriers of ARISE study. See Chapter 20 for further discussion of
the PAI-1 4G/5G genotypes have higher risk for MODS resuscitation in septic shock.
77
and septic shock. In future, identification of genetic
factors may assist selection of appropriate therapy for the Early Treatment of Infection
patient at risk. Timely treatment of infection appears important in the
prevention and management of MODS, with early anti-
NURSING PRACTICE microbial therapy in septic shock recommended in the
Improvement in patient survival with MODS is thought SSG. The CATSS (Cooperative Antimicrobial Therapy of
to be due to improved shock management, awareness of Septic Shock) Database Research Group identified that:
secondary insults, improved critical care management ● inappropriate initial antimicrobial therapy was associ-
and a better understanding of the risk factors associated ated with a five-fold decrease in survival to hospital
with MODS. Current prevention and management strate- discharge 84
gies therefore focus on efficient shock resuscitation, ● the incidence of early acute kidney injury (AKI)
timely treatment of infection, exclusion of secondary increased with delays in antimicrobial therapy from
inflammatory insults and organ support. 65
the onset of hypotension. 85
Effective Shock Resuscitation Other single centre studies also supported the SSG recom-
A number of interventions have been recommended to mendation of antimicrobial therapy within the first hour
86
reduce mortality for patients with MODS due to sepsis. of diagnosing severe sepsis. As early antimicrobial
The surviving sepsis guidelines (SSG) are based on clini- administration may be difficult to achieve given compet-
cal evidence graded according to the quality of evidence ing patient management priorities (e.g. airway manage-
76
available, although there is controversy and dissent ment, volume resuscitation, vasopressor administration),
regarding some recommendations, particularly Early systems must be developed to promote early administra-
86
Goal Directed Therapy (EGDT) (see Table 21.4) (see tion. Nurses are in a pivotal position to ensure these
Chapter 20 for further discussion). guidelines or processes are developed, implemented and
evaluated.
The multicentre, prospective, observational ARISE study
(Australasian resuscitation in sepsis evaluation) assessed
the resuscitation practices and outcomes in patients pre-
senting to EDs with sepsis with hypoperfusion or septic
shock. Overall in-hospital mortality of 23% was compa- Practice tip
rable to inhospital mortality reported in studies of early Tips for promoting early antimicrobial administration in severe
EGDT. The study confirmed that protocolised ScvO 2 - sepsis/septic shock: 86,89
directed EGDT is not routinely practised in Australia or ● Ensure high priority in severe sepsis/septic shock
New Zealand, and recommended that EGDT not be algorithms
adopted in Australia and New Zealand without further ● Do not delay antimicrobial administration if difficulty sam-
multicentre randomised controlled trials. While some pling blood cultures
78
evidence of the benefits of EGDT from a quality improve- ● Ensure adequate supply of antimicrobials in ED and ICU
79
ment perspective are emerging, these benefits may be that fit local colonisation patterns
due to increased awareness of sepsis management rather ● Utilise appropriate antibiotics that can be given via IV push
80
than EGDT. In addition, the complex invasive technolo- vs longer infusion
gies which underpin EGDT are not practical in resource- ● Emphasise education of staff on the significance of early
81
limited low- and middle-income countries. Early administration of initial antimicrobial
resuscitation in severe sepsis does appear to improve ● Consider other potential barriers to early antimicrobial
82
patient outcomes, however, the evidence in relation to administration in your facility


TABLE 21.4 EGDT in severe sepsis: initial targets 76
Combination antibiotic therapy may offer a survival
Item Target benefit in septic shock, but may be deleterious to patients
87
with a low mortality risk. Certainly antibiotic overuse
CVP 8–12 mmHg and misuse is of concern given the emergence of antibi-
12–15 mmHg in mechanically ventilated patient or otic resistance. Other factors that can lead to antibiotic
88
patient with decreased ventricular compliance
failure in the critically ill include increased volume of
MAP ≥65 mmHg distribution secondary to expanded extracellular volume,
Urine output ≥0.5 mL/kg/hr transient increased drug clearance due to elevated cardiac
output (early sepsis) and increased free-drug levels sec-
ScvO 2 / SvO 2 ≥70%/≥65%
ondary to reduced serum albumin. Maximum antibiotic

572 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E

dosage levels are therefore recommended in life-
threatening infections, as inadequate antibiotic penetra- BOX 21.1 Surviving Sepsis campaign
tion can occur due to impaired vascularity of infected
tissue (inhibits delivery of antibiotic), antibiotic anta- The Surviving Sepsis campaign is an international collaborative
gonism (uncommon but possible with combination formed in 2003 to reduce the mortality of sepsis. Guidelines for
therapy) and coexisting unrecognised bacterial infec- the management of severe sepsis and shock were updated in
89
tion. Nursing assessment of patient response to antibi- 2008 and offer a comprehensive list of graded recommenda-
76
otic therapy (resolution or exacerbation of signs of sepsis) tions to care for these patients. Many of the recommendations
and surveillance for sites of unrecognised infection is for practice have implications for critical care nurses and the
therefore important. multidisciplinary team (see Online resources). The third edition
is due for release in 2012.
Exclusion of Secondary Insults and
Organ Support
Prevention of secondary inflammatory insults and organ and evaluation. The complex care required to nurse the
support includes a broad range of interventions including MODS patient is highlighted in the clinical case study.
90
use of massive transfusion protocols, recognition of
abdominal compartment syndrome via urine catheter SUMMARY
65
76
manometry, lung protective ventilation, early nutri- Multiple organ dysfunction is a common presentation to
60
tional support, 91,92 glycaemic control, haemodynamic critical care units across Australasia. Critical care nurses
76
support using vasopressors and intropes, renal replace- require high-level knowledge of pathophysiology and
76
ment therapy, nitric oxide therapy and extracorporeal early recognition of failure of individual organs and the
membrane oxygenation (ECMO). Routine evidence- antecedents to the development of organ failure. The
based measures are also essential, including hygiene, pathophysiological consequence of systemic inflamma-
bowel management, pressure area, mouth and eye tory response and sepsis requires understanding of indi-
care and other processes of care (e.g. FAST-HUG; see vidual organ function and responses to stressors so that
Chapter 20).
preemptive strategies can be initiated to prevent further
Awareness of the latest evidence that underpins manage- organ failure and support individual organs. Patients
ment of these complex patients is important, including with MODS are complex patients to manage, requiring
emerging therapies such as the use of statins 93,94 and ACE- highly-skilled nursing care that involves vigilant assess-
95
inhibitors (see Research vignette). Also note that the third ment, planning of intervention priorities, monitoring
edition of the SSG is due for release in 2012 (see Box and ongoing treatment evaluation. Well-developed time
96
21.1). There is a surprising dearth of literature specifi- management skills are required to include all routine
cally addressing the complex nursing care required by a cares and required treatment. Balancing care priorities
MODS patient. These patients require highly-skilled begins on patient presentation as highlighted by the
nurses who are able to balance competing priorities via importance of initial resuscitation and early antimicro-
ongoing patient assessment, care planning, monitoring bial therapy.



Case study

Mr Wyland, aged 43, was brought in by ambulance to the Emer- 0.9% was administered during resuscitation, and then a further
gency Department (ED). He was hypoxic, cyanotic, tachypnoeic, 500 mL of 4% albumin stat. Mr Wyland was subsequently reviewed
clammy and tachycardic with a history of severe COPD/asthma (no by an intensive care consultant for ventilation difficulties second-
domiciliary oxygen, ex-smoker 25 pack years). His wife had been ary to bronchospasm. He was placed on permissive hypercapnia
unwell with an upper respiratory tract infection in the past week. ventilation via SIMV volume-control with a VT 450 mL, peak flow
He had been administered oxygen at 15 L/min via a non-rebreather rate of 80 L/min, RR 8 bpm and 0 cm PEEP (to maximise expiratory
mask and nebulised ventolin twice in transit, with no clinical time and reduce gas trapping – I : E ratio 1 : 11). He was ordered
improvement. combination IV antibiotics (ticarcillin clavulanate and gentamicin)
and nasogastric oseltamivir (Tamiflu) which were administered 3.5
On initial assessment he was noted to be in extremis: Temperature
39.5°C, HR 135 bpm, BP 165/96 mmHg, SpO 2 88%, minimal air hours post-ED presentation. An adrenaline infusion was com-
entry bilaterally and very distressed. He was administered ventolin menced to improve his bronchospasm and hypotension that was
and atrovent nebulisers, IV MgSO 4 20 mmols, a ventolin IV infusion unresponsive to prior fluid challenges. His ventilation continued to
was commenced and hydrocortisone 100 mg was administered. be problematic and he was transferred to ICU after 6 hours in ED.
BiPAP was initiated, but poorly tolerated. During preparation for
intubation and mechanical ventilation, Mr Wyland went into respi- On admission to ICU he was in severe respiratory acidosis (ETCO 2
ratory, then cardiac, arrest (PEA). = 96). Sedation and drug paralysis infusions were commenced
(midazolam and vecuronium) and permissive hypercapnia ventila-
Four cycles of CPR were completed with stat doses of IV adrenaline tion continued with an increase in VT to 550 mL (Pplat 25 cmH 2O;
1 mg × 4 prior to ROSC after 11 minutes. One litre of normal saline I : E ratio 1 : 8.9). A ketamine infusion was added (to improve

Multiple Organ Dysfunction Syndrome 573



Case study, Continued
bronchospasm) and regular steroids ordered (exacerbation COPD/ via infusions. He was coagulopathic, his lactate level had risen and
asthma). The adrenaline infusion continued (MAP 70 mmHg) and his abdomen was still distended.
maintenance fluids commenced (CVP 14 mmHg). A noradrenaline
infusion was added after 2 hours of admission to maintain MAP > For days 4 and 5 in ICU, Mr Wyland continued to be in septic shock
65 mmHg and weaned within 4 hours of commencement. He was and intravenous vasopressin was added. A CAT scan was per-
actively cooled to 33.5°C for 24 hours (to improve outcome post formed to exclude hypoxic brain injury. Some right ventricular dila-
arrest). tion was noted on TOE, however his left ventricular function had
normalised. While clinical concern was raised about the possibility
New infiltrates were noted on chest X-rays (possible pulmonary of an ischaemic gut (offensive stools), he was not considered an
oedema, aspiration or left ventricular dysfunction). Intravenous operative candidate. His antibiotics were changed on day 5
frusemide was administered and a transoesophageal echo (TOE) (meropenem and vancomycin) to cover secondary infection.
revealed an ejection fraction of 25–30%. A bronchoscopy was
performed to exclude obstruction. Nasogastric feeding was On day 6 in ICU Mr Wyland showed some signs of improvement.
commenced. His bronchospasm was resolving. Inotrope requirements were
decreasing and vasopressin and noradrenaline infusions were
On the evening of day 1 in ICU Mr Wyland’s blood glucose levels weaned. Candida was isolated on endotracheal aspirates on day 7
(BGLs) were unstable and an insulin infusion was commenced to of ICU stay (nystatin commenced) and Mr Wyland remained intoler-
maintain glycaemia at 4–10 mmol/L. His abdomen was distended, ant to enteral feeding. A further prokinetic (erythromycin) was
bowel sounds were quiet and enteral feeding was ceased due to added. He remained fully ventilated with improving oxygenation,
high aspirates. Intravenous metoclopramide was commenced CRRT continued and his lactate levels were decreasing.
(prokinetic).
By day 8 in ICU Mr Wyland’s lung mechanics were improving and
By day 2 in ICU Mr Wyland developed renal dysfunction (creatinine
141 µmol/L). By the evening he was anuric and CRRT was com- IV salbutamol, ketamine and sedation were weaned. His ICU stay
menced (CVVHDF). His BP was increasingly labile and a noradrena- was further complicated by intermittent bowel obstructions and
line infusion was recommenced. He was now febrile despite being lower GI bleeding (requiring massive transfusion) secondary to
on CRRT. Enteral feeding was recommenced and feeds were being ischaemia during his initial cardiac arrest. This was managed con-
absorbed. servatively and nutrition maintained via a combination of TPN and
enteral feeding when tolerated. He had a tracheostomy tube
Microbiology results available on day 3 revealed a pneumococcal inserted on day 11 and commenced T-piece trials by day 16. He
lung infection and human metapneumovirus on nasopharyngeal also suffered from critical illness polymyoneuropathy which was
aspirate, therefore oseltamivir was ceased and antibiotics changed diagnosed on the basis of continued weakness post-cessation of
according to sensitivities. Mr Wyland was becoming increasingly sedation. He had established good urine output by day 25 in ICU
unstable haemodynamically (septic shock, LV dysfunction) requir- and was discharged from ICU on day 40 for further pulmonary and
ing 12 mcg/min of adrenaline and 15 mcg/min of noradrenaline physical rehabilitation.






Research vignette

Schmidt H, Hoyer D, Rauchhaus M, Prondzinsky R, Hennen R, Schlitt Methods
A et al. ACE-inhibitor therapy and survival among patients with 178 score-defined consecutive patients were enrolled. Inclusion
multiorgan dysfunction syndrome (MODS) of cardiac and non- criteria was an APACHE II score ≥20 at admission to the ICU.
cardiac origin. International Journal of Cardiology 2010; 140(3): Patients were evaluated for ACEI therapy and followed for 28, 180
296–303. and 365 days. HRV was calculated according to international
standards.
Abstract Results
Background 68 patients received an ACEI during their ICU stay whereas 110 did
The multiple organ dysfunction syndrome (MODS) is the sequen- not. The 28-day mortality was 55% (no ACEI treatment) vs 22%
tial failure of organ systems after a trigger event (e.g. cardiogenic (ACEI treatment, p < 0.0001) and the 1-year mortality accounted for
shock) with a high mortality. ACE-inhibitors (ACEI) are known to 75% (no ACEI) vs 50% (ACEI), p < 0.0001. There was no significant
ameliorate depressed autonomic dysfunction (heart rate variability survival difference between early and later application of ACEI
– HRV) to improve endothelial function and to decrease blood (after day 4), both application modes were characterised by an
pressure. Modifications of these targets reduce major adverse improved survival. MODS patients with ACEI treatment at admis-
cardiovascular events (patients with arterial hypertension, coro- sion had a better preserved HRV.
nary artery disease and chronic heart failure). Our study aimed Conclusions
to characterise potential benefits of ACEI therapy in MODS Our results may suggest that MODS patients with ACEI treatment
patients. may have lower short-and longer-term mortality. HRV was less

574 P R I N C I P L E S A N D P R A C T I C E O F C R I T I C A L C A R E



Research vignette, Continued
attenuated when patients received ACEI therapy at admission. therapy including recorded duration of administration (pretreat-
Consequently, effectiveness of ACEI therapy should be validated in ment, duration of treatment and discontinuation) was retrieved
a prospective trial. from a database, along with medication list, 28-day, 180-day,
Critique 365-day mortality and severity of illness score. Heart rate variability
The researchers set the background to the work by drawing atten- was obtained from 24-hour continuous Holter ECG recordings.
tion to two factors associated with MODS: autonomic dysfunction Patient population showed similar age, APACHE II and SOFA scores;
and the immune response that leads to vascular and cellular organ 20 female/68 male patients received ACEI and 38 female/110 male
dysfunction. The authors describe how inflammatory mediators without ACEI.
activate sensory pathways which stimulate a cholinergic antiin- The authors suggest that the mechanisms behind mortality reduc-
flammatory reaction to prevent leakage of proinflammatory medi- tion in the MODS patient receiving ACEI therapy appear multifac-
ators into the circulation. They put forward the concept that this eted. ACEI may affect inflammatory reactions through modulation
antiinflammatory vagal pathway might be suppressed in sepsis of the renin–angiotensin–aldosterone system which has not only
and MODS and strategies to modulate both systems may have vasoconstrictive actions but also pro-inflammatory properties. In a
prognostic implications. MODS patient autonomic function is blunted. Modulation of the
renin–angiotensin–aldosterone system with ACEI therapy increases
Further, the authors reiterate the association between patients autonomic control of heart rate and reduction in adrenergic activ-
receiving statin therapy and reduced inflammation and subse- ity. This means that cardiovascular reflexes are optimised and there
quent rate of severe sepsis, ICU admission and mortality in patients is a decrease in myocardial oxygen demand. MODS patients on
admitted to hospital with acute bacterial infection. This is further ACEI had an improved parasympathetic modulation of heart rate
reported as improved outcome in MODS patients receiving statin compared to those not receiving ACEI.
therapy versus those that did not, attributed to improved endothe-
lial function, reduced inflammation and improved autonomic func- The study results suggested that MODS patients receiving ACEI
tion. Recent work in the area of statin therapy has been reported therapy may have significantly reduced 28-day, 180-day and
demonstrating that chronic statin therapy was associated with 365-day mortality compared to those not receiving ACEIs. There
decreased mortality in postoperative patients who had major did not appear to be a difference in one-year mortality comparing
94
adverse outcomes such as MODS. This paper therefore sets the early and later ACEI administration. Patients receiving ACEI treat-
scene to present a strong argument to support the research aims ment had less attenuated HRV, probably by preventing a reduction
of investigating whether ACEI is associated with reduced mortality in vagal tone and therefore modulating the inflammatory response.
in MODS; whether a potential reduction in mortality is seen only The study was well designed, although data were retrospectively
in cardiogenic triggered MODS; and whether the time of ACEI analysed using a small population of MODS patients. Despite this
application has impact on outcome. The hypothesis was that ACEI limitation, it is a significant study in relation to mortality outcomes
therapy could be advantageous for MODS patients despite its for patients with MODS that should encourage future prospective
blood-pressure-lowering features.
trials. Along with earlier work on statin therapy, ACEI treatment
An independent observer conducted a retrospective analysis of strategies may provide additional mortality benefits that translate
mortality for 178 MODS patients with or without ACEI therapy. ACEI into improved health care outcomes for critically ill patients.






Learning activities

1. Review the coagulation cascade and inflammatory and 5. Think of a patient with MODS who you have recently cared for.
immune functions of the body. Reflect on the important elements of your nursing care that
2. Review the role of the adrenal gland and its relationship to allowed you to effectively manage this patient. Consider what
adrenal insufficiency in the patient with MODS. aspects of your care you would like to change when you next
3. Develop a care plan for Mr Wyland (discussed in the case study) care for a complex MODS patient.
for his ICU stay. Ensure that you include routine cares as well 6. Review the pharmacology, therapeutic actions and interac-
as care specifically targeted at organ support. Discuss your tions of statins and ACEI. Using the evidence based literature,
plan with an experienced colleague. consider their application in patients with MODS.
4. List some of the important assessment findings that influenced
the care of Mr Wyland during his stay in ICU, e.g. increasing
bronchospasm, unstable BGLs, quiet bowel sounds.

Multiple Organ Dysfunction Syndrome 575

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