Succinylcholine apnoea: Attempted reversal with ...

536 Succinylcholine
apnoea:
David R. Bevan Ma MRCPFFARCS, Attempted
Francois Donati PHD MD reversal with
anticholinesterases

Anttcholinesterases were administered in an attempt to The use of anticholinesterases to antagonize pro-
antagonize prolonged neuromuscular blockadefollowing longed neuromuscular blockade (NMB) after suc-
the administration of succinylcholine in a patient later cinylcholine administration to patients with atypical
found to be homozygousfor atypical plasma cholinester- plasma cholinesterase has had variable success.
use. Edrophonium 10 rag, given 74 min after succmyl- Vickers~ concluded that anticholinesterase agents
choline, when train-of-four stimulation was characteris- prolonged the block in succinylcholine-sensitive
tic ofphase H block, produced partial antagonism which individuals and that electromyographic responses,
was not sustained Repeated doses of edrophonium to at least using tetanic stimulation, may not identify
70 mg and neostigmine to 2.5 mg dM not antagonize or the change from phase I to phase II block. Savarese
augment the block. Spontaneous respiration recom- et al. 2 using train-of-four stimulation, studied four
menced 200 min after succinylchotine administration. It patients with prolonged succinylcholine apnoea.
is concluded that ant&holinesteruses are only partially After surgery all arnved in the recovery room with a
effective in restoring neuromuscularfunctwn in succinyl- train-of-four ratio (T4/T1) of less than 0.5, charac-
choline apnoea despite muscle twitch activity typical of teristic of phase II block but this was reversed
phase 11block. successfully with anticholinesterase in only three.
More recently, Viby-Mogeosen3 has recommended
Key words the combination of human cholinestcrase and a
NEUROMUSCULARRELAXANTS:succinylcholine; eholinesterase inhibitor to accelerate recovery from
COMPLICATIONS:apnoea; ANTAGONISTS, such a block.
NEUROMUSCULARRELAXANTS:neostigmine,
Recently, we were able to record the progress of
edr0ph0nium.
the lIMB in a patient who was given succinylcho-

line and who was later shown to be homozygous
for atypical plasma cholinesterase. Attempts were
made to restore neuromuscular function with anti-
cholinesterases when the appearances of the block
were ~ypical of phase II, T4/T1 <0.5.

From the Departments of Anaesthesia, Royal Victoria Case report
Hospital & McGill University, Montreal, Quebec. A 40-year-old woman, 157 cm tall and weighing
51 kg was scheduled for laparotomy for chronic
Address correspotu~ence to: Dr. David R. Bevan, lower abdominal pain. Her past medical history
Department of Anaesthesia, Royal Victoria Hospital, included a cholecystectomy at age 26 and an
687 Pine Avenue West, Montreal, Qua., H3A 1At. abdominal hysterectomy three years later. Both
operations were performed under general anaes-
thesia, the details of which were unavailable. The
patient denied problems associated with anaesthesia
in the postoperative period. However, her husband

CAN ANAESTHSOC I 1983/ 30:5 1pp536-539

Bevan and Donati: SUCCINYLCHOLINE APNOEA REVERSAL 537

nGURE Train-of-fourrecordingof neuromuscularactivityfollowingattemptedantagonismwith

atropineand edrophonium(ATR-ED)or atropineand neostigmine(ATR-NEO)of prolonged
NMB in a patienthomozygousfor atypicalplasmacholinesterase.Time is shownon the x-axisand
force of contractionon the y-axis. See text for details.

admitted later that recovery after the cholecystec- normal. Laboratory data showed a haemoglobin of
tomy seemed to be prolonged. 128 g/l, and normal plasma electrolytes, urea and
creatinine. Serum calcium, bilirubin, albumen,
At the present admission the patient was other- total protein, glutamic-oxaloacetic transaminase,
wise healthy. She denied allergies or family prob- glutamic-pyruvic transaminase, lactic dehydroge-
lems associated with anaesthesia. Examination of nase and alkaline phosphatase were all normal.
the cardiovascular and respiratory system was

538 C A N A D I A N A N A E S T H E T I S T S ' S O C I E T Y J O U R N A L

One hour before anaesthesia, she was given 2.5 mg, had no effect on neuromuscular activity:
morphine 7.5 mg and atropine 0.4 mg intramuscu- the block was neither antagonized nor augmented.
larly. On arrival in the operating room blood Ninety minutes after the administration of succinyl-
pressure was measured, electrocardiogram was choline (T1 = 100 per cent, T4/T1 = 0.33), the
recorded, an intravenous infusion was commenced ventilator was disconnected and the patient made
in the right arm and stimulating needles were attempts at spontaneous respiration. However, this
inserted subcutaneously over the left ulnar nerve for was associated with a gradual increase in end-tidal
neuromuscular monitoring. The left hand and fore- CO2 to 60 mmHg, when positive pressure ventila-
arm were immobilized in a plaster cast and the tion was reinstated. At the end of surgery, the
thumb was connected to a force displacement patient was transferred to the recovery room where
transducer (Grass FT 10) so that the response of the ventilation and neuromuscular monitoring were
continued. Gradual recovery of neuromuscular
adductorpollicis to ulnar nerve stimulation could be function ensued and spontaneous respiration re-
commenced at 200 min (T 1 = 90 per cet~t, T4/T 1 =
recorded on a Grass Polygraph pen-and-ink re- 0.7). Five hours after administration of succinyl-
corder. The hand and forearm were covered with choline some train-of-four fade was still present
gauze pads so that the skin temperature of the thumb (T4/TI = 0.8). There were no further postoperative
was maintained above 33~C. complications. Blood was taken, 24 hours later, for
plasma cholinesterase assay which was characteris-
Anaesthesia was induced with thiopentone, 275 tic of the homozygous atypical gene:
mg, and maintained with 70 per cent nitrous oxide
in oxygen with isoflurane, 0.5-1 per cent, given total activity 24.4 U (normal 43-69)
initially via a facemask and a Mapleson A circuit dibucaine inhibition 29% (normal 78-85)
during spontaneous ventilation. Ulnar nerve stimu- fluoride inhibition 24% (normal 57-64)
lation was commenced, after induction of anaes- chloride inhibition 52% (normal 11-20)
thesia, with trains-of-four square wave impulses of
0.2 msec duration and 2 Hz frequency every 12 sec Later testing of the patient's two children showed
using a Grass $48 stimulator and SIU5 isolation them to be a typical heterozygotes.
unit. Control twitch measurements were made after
a stable baseline had been obtained. Then, succinyl- Discussion
choline 60 mg was given which was followed by Fade in the response of the adductor pollicis to
paralysis within 1 min (Figure). The trachea was train-of-four stimulation of the ulnar nerve is
intubated and the patient was ventilated throughout characteristic of non-depolarizing or phase II NMB,
surgery to normocapnia as assessed by end-tidal When present it predicts that anticholinesterases
carbon dioxide tension measured with a Hewlett- will antagonize the non-depolarizing block of
Packard HP capnograph. curare-like drugs4 or the phase II block of succinyl-
choline.5 By these criteria the NMB in the present
The subsequent course of the NMB is shown in patient at 74 min (TI depression of 58 per cent,
the Figure. There was total absence of response to T4/T1 of <0.1) suggested that the block should be
nerve stimulation until nearly 60 min after admin- antagonized with anticholinesterases, Indeed, the
istration of succinylcholine. This was followed by degree of fade to train-of-four stimulation was
slow recovery of first twitch tension (TI) with greater than that reported for the same degree of T 1
considerable train-of-four fade. At 74 rain, when depression with non-depolarizing NMB. 6 Edro-
T1 was about 40 per cent control and the train-of- phonium was chosen first because, when used to
four ratio was less than 0.1, the twitch response was antagonize pancuronium, it produced better restora-
typical of phase II block. Thus, an anticholinester- tion of T4/T1 fade for the same degree of T1
ase, edrophonium 10 mg, was given with atropine. depression than did neostigmine.7
This was followed by rapid, partial reversal of the
NMB so that 90 sec after its administration TI was In practice, these hypotheses could not be sup-
120 per cent of control and T4/TI was 0.43. This ported. Although edrophonium lOmg was fol-
antagonism was not sustained. Two minutes later, lowed by partial reversal of NMB, this was neither
T1 had decreased slightly to 106 per cent and T~-/T1
to 0.37. Further doses of anticholinesterases, edro-
phonium to a total of 70 mg and neostigmine to

Bevan and Donati: SUCC1NYLCHOL1NEAPNOEAREVERSAL 539

sustained nor improved by subsequent administra- 4 Ali HH, Savarese JJ. Monitoring of neuromuscular
tion of either edrophonium or neostigmine, The function. Anesthesiology 1976; 45: 216-49.
degree of recovery of neuromuscular function was
inadequate for spontaneous respiration. 5 Lee C. Dose relationships of phase 1I, tachyphylaxis
and train-of-four fade in suxamethonium-indueed
Viby-Mogensen3 suggested that in patients with neuromuscular block in man. Br J Anaesth 1975; 47:
prolonged response to succinylcholine, depolariz- 841-5.
ing NMB persisted because of the presence of
suceinylcholine in the palsma, Edrophonium was 6 Williams NE, Webb SN, Calvey TN. Differential
said to be effective in antagonizing the non- effects of myoneural blocking drugs on neuro-
depolarizing component of the block but may muscular transmission. Br J Anaesth 1980; 52:
potentiate any residual depolarizing component, 1111-5.
Human cholinesterase was recommended for the
reversal of depolarizing NMB. This explanation 7 Donati F, Ferguson A, Bevan DR. Twitch de-
does not account for the observations made in our pression and train-of-four ratio after antagonism of
patient because she showed the train-of-fourfade of pancuronium with edrophonium, neostigmine or
non-depolarizing block and the block was never pyridostigmine. Anesth Analg 1983; 62:314-6.
augmented after either antieholinesterase. Thus, the
NMB had the appearances only of a non-depolariz- 8 Baraka A. Suxamethonium-neostigmine interac-
ing block which could not be antagonized with tion in patients with normal or atypical cholinester-
anticholinesterase. Irrespective of the exact mecha- use. Br J Anaesth 1977; 49: 479-84.
nism of action, the diagnosis of phase II block by
assessment of train-of-four fade does not guarantee 9 Baraka A, WakidN, MansourR, Haddad W.
successful antagonism by anticholinesterases in Effect of neostigmine and pyridostigmine on the
patients homozygous for atypical cholinesterase. plasma cholinestemse activity. Br J Anaesth 1981;
53: 849-51,
It is possible that repeated doses of antieholines-
terases delayed recovery from NMB in our patient 10 Donati F, Bevan DR. Effect of enflurane and fen-
by decreasing the already low plasma cholinesterase tanyl on the clinical characteristics of long-term
activity,a'9 This possibility must be weighed against succinylcholine infusion. Can Anaesth $ne 1 1982;
the favourable response of some succinylcholine- 29: 59-64.
sensitive patients to anticholinesterases, t~ This
report also suggests that if edrophonium produces 11 Miller RD, Stevens WC. Antagonism of suceinyl-
an initial antagonism of NMB followed by its choline paralysis in a patient with atypical pseudo-
intensification, then no further anticholinesterase cholinesterase, Anesthesiology 1972; 36:511-3.
should be given. We agree with Viby-Mogensen
that the NMB will last until plasma concentrations R6sum~
of succinylcholine decrease to sub-paralytic levels On a tent~, d l'aide d'anticholinestdrasiques, de produire
either by redistribution and excretion or by metabo- l'antagonisrae d'un bloc neuromusculaire prolong~
lism induced with exogenous cholinesterase. caus~ par l'adrainistration de 1.2 rag'kg -j de succinyl-
choline chez une patiente qui s'est av~rde ~.tre horaozy.
References gate pour la cholinestdrase plasmatique atypique. On a
1 Viekers MDA, The mismanagement of snxa- donn~ 10 rag d' ~drophoniura 74 minutes aprds l' adrainis.
methonium apnoea. Br J Anaesth 1963; 35: 260-8. tration de succinytcholine lorsque le train de quatre
2 Savarese JJ, Ali HH, Murphy JD, Padget C, Lee stimulations (train-of-four) possgdait tes caract~risti-
C-M, Ponitz J, Train-of-four nerve stimulation ques d' un bloc de phase H. IIen a rdsultd un antagonisrae
in the management of prolonged neuromuscular partiel et non soutenu. Le bloc neurorausculaire est
block following succinylcholine. Anesthesiology demeur~, inchang~ d ta suite de r adrainistration r~p~t~e
1975; 42: 106-11. d'ddrophoniura, jusqu'd une dose totale de 70 rag, et
3 Viby-MogensenJ. Succinylcholine neuromuscular 2.5 rag de n~ostigraine. La patiente s'est raise d respirer
blockade in subjects homozygous for atypical plasma spontan~raent 200 minutes aprds la dose de succinylcho-
cholinesterase. Anesthesiology t981; 55: 429-34. line. On en conclut que les anticholinestdrasiques ne sont
que partielleraent efficaces dans te traiteraent d'une
apn~e prolong~e due d la succinylcholine et ce, en ddpit
des contractions stirautdes caractdristiques d"un btoc de
phase II.