Download Recurarization in the recovery room following the use of magnesium

Recurarization in the recovery room
References
1 Cheek TG, Gutsche BB. Maternal physiologic alterations
during pregnancy. In: Shnider SM, Levinson G, eds.
Anesthesia for Obstetrics. United States: Williams and Wilkins,
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2 Mannucci PM, Tuddenham EG. The hemophiliasÐfrom royal
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4 Cahill MR, Colvin BT. Haemophilia. Postgrad Med J 1997; 73:
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British Journal of Anaesthesia 91 (3): 435±8 (2003)
DOI: 10.1093/bja/aeg179
Recurarization in the recovery room following the use of
magnesium sulphate
W. J. Fawcett* and J. P. Stone
Department of Anaesthesia, Royal Surrey County Hospital, Egerton Road, Guildford, Surrey GU2 7XX, UK
*Corresponding author. E-mail: [email protected]
A 67-yr-old man weighing 104 kg, with a history of hypertension, underwent laparoscopic
cholecystectomy. His preoperative serum potassium was 3.4 mmol litre±1. The patient received
cisatracurium 14 mg, which was antagonized with neostigmine 2.5 mg and glycoprolate 0.5 mg
at the end of the procedure. A repeat dose of neostigmine 2.5 mg and glycoprolate 0.5 mg was
required 5 min later, as the neuromuscular block was incompletely antagonized. He was transferred to the recovery room about 10 min after the end of surgery, having had recovery of
neuromuscular function demonstrated with no fade on peripheral nerve stimulation at 50 Hz
for 5 s. Five minutes later he developed rapid atrial ®brillation, which was treated over 5 min
with magnesium sulphate 2 G i.v.. Within the next 3 min, the patient developed marked neuro-
Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2003
Fawcett and Stone
muscular weakness of a non-depolarizing pattern leading to respiratory arrest. This necessitated re-intubation of the trachea and arti®cial ventilation for 20 min, until there was spontaneous recovery of neuromuscular function demonstrated by peripheral nerve stimulation.
Administration of magnesium appears to have caused recurarization in this patient. The dose of
magnesium alone would not be expected to cause muscle weakness. Potentiation of neuromuscular blocking drugs by magnesium is well recognized, and we recommend its use is avoided
for at least 30 min after reversal of neuromuscular block.
Br J Anaesth 2003; 91: 435±8
Keywords: anaesthesia; complications, morbidity; neuromuscular block, cisatracurium;
pharmacology, magnesium
Accepted for publication: May 9, 2003
The use of parenteral magnesium has increased over the last
few years, particularly in obstetrics, in surgery for
phaeochromocytoma, and in the management of patients
with tetanus.1 Magnesium also has a role in cardiology,1
especially in the treatment of arrhythmias including atrial
®brillation.2
The depressant effects of magnesium at the neuromuscular junction were ®rst described in the 1950s,3 when it was
shown to cause a reduction in pre-junctional acetylcholine
release, with consequent potentiation of non-depolarizing
neuromuscular blocking drugs.4 5 These effects necessitate
neuromuscular monitoring when magnesium and neuromuscular blocking drugs are given together. The following
case report illustrates that even when magnesium is
administered after neuromuscular function has recovered
postoperatively, if the patient has recently received
neuromuscular blocking drugs, then synergism between
the two agents may lead to recurarization.
Case report
A 67-yr-old man was to undergo for laparoscopic
cholecystectomy. He had a history of hypertension, which
was well controlled (arterial pressure 140/85 mm Hg). He
had no prior cardiovascular symptoms and a good exercise
tolerance. He was obese, weighing 104 kg, with a height of
1.81 m (body mass index of 31.5 kg m±2), and had a hiatus
hernia. His medication at the time of surgery was enalapril
and lansoprazole. He had undergone several uneventful
anaesthetics in the past. There was no recorded dif®culty
with tracheal intubation. Physical examination was unremarkable. The resting ECG showed sinus rhythm with a rate
of 80 beats min±1, with a normal QRS axis. There were
voltage criteria for left ventricular hypertrophy, and some
lateral lead ST depression. His serum potassium was 3.4
mmol litre±1, with the rest of his biochemistry within normal
limits.
Following pre-oxygenation, anaesthesia was induced
with propofol 200 mg, alfentanil 1 mg, granisetron 1 mg,
and cisatracurium 14 mg. Cricoid pressure was applied until
the trachea was intubated, and the patient's lungs were
ventilated with nitrous oxide 67%, oxygen 33%, and
iso¯urane to an end-tidal concentration of 1%. A total of
morphine 10 mg of was administered during the operation.
Anaesthesia and surgery were uneventful apart from a fall in
the patient's oxygen saturation to 91% after pneumoperitoneum, requiring an increase in FIO2 to 50%. Iso¯urane
was increased to an end-tidal concentration of 1.3%.
Oxygen saturation remained at 94±96% thereafter. He
remained in sinus rhythm throughout, and his arterial
pressure remained within normal limits.
At the end of surgery, 40 min later, neuromuscular block
was antagonized with glycopyrrolate 0.5 mg and neostigmine 2.5 mg. A few minutes after this, some tracheal tug
was noted. Peripheral nerve stimulation showed a trainof-four (TOF) count of four twitches at 2 Hz, but with
obvious fade at 50 Hz for 5 s. A repeat dose of glycopyrrolate 0.5 mg and neostigmine 2.5 mg was administered.
Five minutes later there was no demonstrable fade at 50 Hz
and the patient's respiratory pattern was normal. The
trachea was extubated and the patient transferred to the
recovery room.
On arrival in the recovery room he had an oxygen
saturation of 94%, a heart rate of 100 min±1 and an
arterial pressure of 160/90 mm Hg. He remained stable
for about 5 min, when his heart rate suddenly became
irregular and increased to 170 beats min±1, with an
arterial pressure of 194/110 mm Hg. He received oxygen
60%. ECG con®rmed rapid atrial ®brillation. The patient
was treated with an i.v. bolus of magnesium sulphate 2G
i.v. over 5 min, and the ventricular response rate slowed
over the next minute to 120 beats min±1 and an arterial
pressure of 154/88 mm Hg. However, 3 min later the
patient's respirations became shallow, and he became
agitated before respirations ceased and his oxygen
saturation fell to 80%. Cricoid pressure was re-applied
and his trachea re-intubated, following which he was
given midazolam 5 mg. The urgency of the situation did
not permit administration of anaesthetic agents before reintubation. Peripheral nerve stimulation detected only the
436
Recurarization in the recovery room
®rst twitch of the TOF, and marked fade on stimulation at
50 Hz. The patient's lungs were ventilated with oxygen
and the patient was sedated with boluses of propofol 30±
50 mg every 5 min. No further neostigmine or
glycopyrrolate was administered and after 20 min,
neuromuscular monitoring demonstrated four twitches
and no fade on tetanic stimulation. At this point, his
heart rate was 100 beats min±1 in atrial ®brillation and
arterial pressure 130/77 mm Hg. Spontaneous ventilation
resumed shortly after and his trachea was extubated. He
remained in recovery for a further 2 h. He was discharged
back to the ward in atrial ®brillation at a rate of 100
beats min±1, having received digoxin 500 mg i.v., with
potassium chloride 40 mmol i.v. in progress. His oxygen
saturation was 94% on air and a 12 lead ECG showed no
changes other than atrial ®brillation.
He was discharged the next day on a maintenance dose of
digoxin. There were no new changes on his ECG. On direct
questioning, he admitted to having had palpitations several
times in the preceding 3 months, lasting for up to 1 h at a
time. He was later seen by a cardiologist, who commenced
the patient on warfarin and arranged an echocardiograph.
Discussion
A patient is described in whom late recurarization occurred
following the use of magnesium sulphate for treatment of
atrial ®brillation. It is highly likely that magnesium caused
the recurarization.
Reversal of neuromuscular block was initially inadequate, demonstrated by tracheal tug and fade with
peripheral nerve stimulation. Various factors may have
contributed to this: the ®rst dose of glycopyrrolate and
neostigmine was probably administered in the presence of
considerable neuromuscular block, as a large initial dose of
cisatracurium was antagonized within 40 min. In addition,
the patient had hypokalaemia, which potentiates neuromuscular block. However, adequate return of neuromuscular
function was demonstrated before leaving the operating
theatre.
Magnesium has a well-documented effect at the
neuromuscular junction, where it inhibits pre-junctional
acetylcholine release with consequent potentiation of nondepolarizing neuromuscular blocking drugs.3±5 Following
antagonism of residual neuromuscular block by neostigmine, adequate neuromuscular function was con®rmed by
the ability of the patient to sustain tetanus at 50 Hz for 5
s. This correlates well with other clinical tests, such as
sustained headlift, which indicate return of normal
neuromuscular function, in particular respiratory function
and airway protection.6 Although magnesium alone may
cause muscle weakness if administered in large doses,1
this would be unlikely with the modest dose used in this
patient (2G).
Following the administration of magnesium sulphate,
the patient redeveloped a non-depolarizing block that
took 20 min to resolve spontaneously. We attribute this to
a reduction in acetylcholine release at the neuromuscular
junction, which under usual circumstances would have
had no demonstrable effect. However, in a patient in
whom there is still non-depolarizing neuromuscular
blocking drug present at the neuromuscular junction,
and hence acetylcholine receptor occupancy, even a
relatively small dose of magnesium was enough to
cause weakness.
Recurarization is a well-documented phenomenon, and
was particularly common with the older neuromuscular
blocking drugs such as pancuronium, d-tubocurarine, and
gallamine. In 1979, Viby-Mogensen demonstrated an incidence of residual curarization of 42% in the recovery room.7
Later studies con®rmed his ®ndings, with an incidence of
between 20 and 50% with these drugs.8±11 This problem is
less common as the advent of atracurium and vecuronium,
possibly as a result of other factors such as improved
neuromuscular monitoring and awareness of the problem,
with an incidence of residual recurarization of 0±12%.8±12
Indeed, an editorial questioned whether or not we need to
antagonize residual neuromuscular block.13 We think it is
unlikely that recurarization was spontaneous as the dose of
cisatracurium was given 50 min earlier, and the drug
undergoes organ independent biotransformation. Moreover,
the onset of recurarization was rapid, dramatic, and closely
related to administration of magnesium sulphate.
Use of magnesium sulphate to treat atrial ®brillation
merits discussion. There were several therapeutic options
including cardioversion. The authors' familiarity with the
drug was a key reason for its use, as it is useful for the
termination of many arrhythmias including atrial ®brillation,2 particularly if hypokalaemia exists.1 Moreover the
drug's vasodilator and sympatholytic properties are useful
in a patient with hypertension and presumed ischaemic heart
disease. Other treatment options were amiodarone, b
blockade, or digoxin. Cardioversion was not used because
the urgency of the situation did not warrant it, and there is a
small risk of an embolic event if there is mural thrombus
present.
The use of glycopyrrolate and neostigmine is standard to
reverse neuromuscular block, and yet it is not without risk.
Nausea and vomiting, bronchospasm, and anastomotic
dehiscence are all potential problems of neostigmine,13 as
is tachycardia with glycopyrrolate. In this patient, it is
possible that glycopyrrolate caused a tachycardia, which
then predisposed to the onset of atrial ®brillation, in an
individual who may have had episodes of atrial ®brillation
in the past. However, glycopyrrolate is associated with
greater heart rate stability than atropine.
There is now increased understanding and use of
magnesium as a therapeutic agent. The potentiation of
neuromuscular blocking drugs by magnesium is well
recognized, but it must be remembered that a signi®cant
amount of neuromuscular blocking drug may still be present
at the neuromuscular junction after apparently normal
437
Nagdyman et al.
muscle tone has returned, and even at this stage muscle
weakness may recur. In future, we would avoid the use of
magnesium sulphate for at least 30 min after reversal of
residual neuromuscular block, to minimize the risk of this
recurring.
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Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2003