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C. Williams and M.

Leuwer

12 Neuromuscular blocking
agents and skeletal
muscle relaxants

DEPOLARIZING Suxamethonium-induced neuromuscular


paralysis has been reported in a patient
NEUROMUSCULAR
with previously undiagnosed butyryl-
BLOCKING AGENTS cholinesterase deciency [3A].
Suxamethonium (succinylcholine) A 54-year-old-woman due to undergo surgical
[SED-15, 2489; SEDA-32, 273; SEDA-33, drainage of a groin abscess was given intra-
venous propofol 200 mg and suxamethonium
299; SEDA-34, 221] 160 mg (1 mg/kg) and 50 minutes later showed
no evidence of spontaneous recovery of respi-
Immunologic Cardiac arrest shortly after ration. She was successfully weaned from the
anesthetic induction for thyroidectomy in ventilator and extubated 11 hours later. Her
a patient with decompensated thyrotoxico- butyrylcholinesterase activity was 552 IU/l
sis taking amiodarone was attributed to (reference range 26736592). Her dibucaine
number was 61% (reference range 8288).
suxamethonium; raised plasma tryptase
concentrations conrmed an anaphylactic Drugdrug interactions Carbamates Carba-
reaction (Kounis syndrome) [1A]. mates can bind to butyrylcholinesterase and
inhibit the elimination of suxamethonium.
Susceptibility factors Genetic The clinical In a severely depressed patient who received
signicance of genetic variants (K and A) of electroconvulsive therapy prolonged apnea
the butyrylcholinesterase gene after ECT resulted after administration of suxametho-
has been studied in 13 patients with suspected nium [4A]. The team treating the patient had
prolonged duration of action of suxametho- not been told that the patient had attempted
nium, 11 of whom had mutations, mostly of suicide by taking an organophosphate based
the K variant [2c]. In affected patients the insecticide.
duration of apnea was 515 minutes, com-
pared with 35 minutes in the published liter- HMG co-enzyme A inhibitors (statins) The
ature, and there was severe distress during the hypothesis that suxamethonium increases
recovery phase in two cases. The authors plasma concentrations of myoglobin, potas-
recommended objective neuromuscular mon- sium, and creatine kinase more in patients
itoring during the rst episode of ECT. who take statins than in those who do not
and that suxamethonium-induced post-
operative muscle pain is aggravated in
Side Effects of Drugs, Annual 35
J.K. Aronson (Editor)
statin users has been tested in 38 patients
ISSN: 0378-6080 who had taken statins for at least 3 months
http://dx.doi.org/10.1016/B978-0-444-62635-6.00012-7 and 32 patients who had never used statins
# 2014 Elsevier B.V. All rights reserved. [5C]. After induction of general anesthesia

243
244 Chapter 12 C. Williams and M. Leuwer

with suxamethonium 1.5 mg/kg for intuba- at 24 hours after induction of anesthesia was
tion, fasciculations were recorded; blood not affected.
samples were obtained before induction
and 5 and 20 minutes and 24 hours after
administration of suxamethonium; the
patients were questioned about myalgia 2
and 24 hours after surgery. Fasciculations NON-DEPOLARIZING
were more intense and at 20 minutes myo-
globin was slightly higher in statin users NEUROMUSCULAR
than in non-users. However, plasma potas- BLOCKING AGENTS [SED-15,
sium concentration and creatine kinase 2489; SEDA-32, 274; SEDA-33, 301;
activity were similar in the two groups, as SEDA-34, 222]
was muscle pain. These results suggest that
the effect of suxamethonium given to Rocuronium [SED-15, 3073; SEDA-32,
patients taking statins is small and probably
274; SEDA-33, 301; SEDA-34, 222]
of limited clinical consequence.
Systematic reviews Because of its fast onset
Management of adverse drug reactions of action, rocuronium is a potential alterna-
Suxamethonium can cause increased intra- tive to suxamethonium for rapid-sequence
ocular pressure and may be harmful in intubation in patients at increased risk of
patients with penetrating eye injuries. The aspiration. A systematic review of trials com-
use of dexmedetomidine in preventing the paring intubating conditions with either
rise in intraocular pressure associated with rocuronium or suxamethonium at 60 seconds
the use of suxamethonium and endotracheal following administration of drug included 37
intubation has been studied in 66 patients, trials, all of which were randomized con-
who underwent non-ophthalmic surgery in a trolled trials; 19 were deemed to be ade-
randomized placebo-controlled comparison quately concealed, and concealment was
of dexmedetomidine 0.4 and 0.6 micro- unclear in the other 18 [9M]. The data were
grams/kg given over a period of 10 minutes pooled using a random-effects model, and
before induction [6C]. Dexmedetomidine the results were reported as relative risks with
caused a fall in intraocular pressure. The pres- 95% condence intervals (RR 0.88; 95%
sure then increased after suxamethonium CI 0.82, 0.97). The authors concluded that
injection and endotracheal intubation, but suxamethonium remains the drug of choice
never exceeded the baseline value in those for rapid sequence induction in emergency
who had been given dexmedetomidine. The departments, unless there is a contraindica-
induction agent used in this study was sodium tion. However, the ability of sugammadex to
thiopental; in a randomized study propofol reverse deep neuromuscular blockade of
lowered intraocular pressure more than thio- rocuronium may alter the benet to harm bal-
pental, as did supplementary small doses of ance compared with suxamethonium.
each agent before induction [7C].
The effect of remifentanil on Immunologic The occurrence of IgE anti-
suxamethonium-induced muscle fascicula- bodies in hypersensitivity reactions to rocuro-
tions has been studied in 40 patients [8c]. nium has been studied in serum samples
Double-blind intravenous pre-treatment with from 48 patients with anaphylactic reactions
either remifentanil 1.5 micrograms/kg or intra- during anesthesia, using a rocuronium human
venous saline followed by induction with pro- serum albumin (rocHSA) conjugate coupled
pofol and suxamethonium 1 mg/kg showed to a solid phase and a radioallergosorbent
that remifentanil pretreatment reduced the test [10E]. Intradermal skin tests were per-
intensity of muscle fasciculations caused by formed with rocuronium, vecuronium, and
suxamethonium and reduced the mean maxi- suxamethonium. The effects of patients
mum amplitude of muscle action potential. serum IgE on histamine release were investi-
However, postoperative myalgia, measured gated in vitro in sensitized basophils from
Neuromuscular blocking agents and skeletal muscle relaxants Chapter 12 245

healthy blood donors. IgE to rocuronium was desaturation to 85% She was give more adrena-
found in 23 of 48 serum samples with NMBA line and a further dose of sugammadex 400 mg,
bringing the total to 16 mg/kg. Again her arterial
allergy, although only two of these were able pressure rose to 140/65 mm Hg but this time it sta-
to sensitize basophils to release histamine in bilized, the heart rate fell to 90/minute, and the
response to rocHSA. IgE responsiveness in bronchospasm relaxed. She later had positive
the basophil tests was only observed with con- screening tests with rocuronium, mivacurium,
jugated rocHSA and not with unconjugated and vecuronium, but not suxamethonium, pan-
curonium, atracurium, or cisatracurium.
rocuronium or the other drugs evaluated.
However, unconjugated rocuronium inhib- The second case suggests, not surprisingly,
ited histamine release induced by rocHSA. that it is important to give a dose of sugam-
There was a poor correlation between skin- madex sufcient to reverse the effects of
test reactivity to rocuronium and IgE to rocuronium.
rocuronium. In contrast, there was a striking Sugammadex has a high binding afnity
correlation between IgE to rocuronium and and specicity for rocuronium and other
skin-test reactivity to suxamethonium. aminosteroid neuromuscular blocking drugs
and sequesters them as an inclusion complex.
The extent to which it competes with IgE anti-
bodies, free and cell bound, for rocuronium
is not known [23R]. Little is known about
Management of rocuronium- how sugammadex interacts with mast cells;
induced anaphylaxis with experiments in rats suggest that it may inhibit
sugammadex mobilization and morphological changes
induced by administration of rocuronium in
Following a proposal that sugammadex pancreatic mast cells [24E]
might be used to treat rocuronium-induced Objections to the use of sugammadex in
anaphylactic reactions [11r], and despite the- the management of rocuronium-induced
oretical objections [12r], there have been anaphylaxis have appeared. In vitro evi-
several reports of its successful use in clinical dence from experiments in basophil cells
practice [13A20A]. The following are illus- from three patients with rocuronium allergy
trative cases. and positive skin tests suggested that sugam-
madex could prevent in vitro basophil acti-
A severe anaphylactic reaction 2 minutes after
an injection of rocuronium 50 mg failed to vation by rocuronium if applied in advance
respond to 18 minutes of treatment with oxy- but not stop it if applied after initiation of
gen, adrenaline, Ringers lactate, and hydroxy- the reaction [25E].
ethylamidone, and because of persistent In a cutaneous model of anaphylaxis in
cardiocirculatory failure and bronchospasm a rocuronium-sensitized patients, sugamma-
bolus of 2000 mg (18 mg/kg) of sugammadex
was injected [21A]. There was rapid correction dex was not effective in attenuating the type
of arterial hypotension and bronchoconstriction, 1 hypersensitivity reaction after it was trig-
starting within a few seconds. Subsequent prick gered by rocuronium, although the patients
tests were positive to rocuronium and vecuronium were anergic to sugammadex-bound rocuro-
and negative to propofol, sufentanil, mivacurium,
atracurium, cisatracurium, and suxamethonium. nium [26c]. The authors suggested that this
A 44-year-old woman had an anaphylactic shows that sugammadex can bind an aller-
reaction to rocuronium 80 mg. Her arterial gen and exclude it from interacting with the
pressure fell to 50/28 mmHg, with a heart rate immune system. However, they did not
of 130/minute, and an increased ination pres- believe that there is evidence that sugamma-
sure [22A]. She was given oxygen 100%, a
rapid infusion of 500 ml of crystalloid, and dex should be used for the treatment of
intravenous adrenaline 0.1 mg. She was then rocuronium-induced anaphylaxis.
given sugammadex 1200 mg (12 mg/kg) and It has been suggested that before sugamma-
immediately her arterial pressure increased to dex can be recommended for reversal of
180/90 mmHg, the heart rate fell to 95/minute,
and a maculopapular rash appeared. Shortly rocuronium-induced anaphylaxis, it should be
afterwards the hypotension and tachycardia discovered whether the allergenic substituted
recurred, together with bronchospasm and ammonium groups at each end of the
246 Chapter 12 C. Williams and M. Leuwer

rocuronium molecule in the inclusion complex reviewed; diazepam, baclofen, and tizanidine
with sugammadex are masked within the cavity are the most commonly prescribed drugs,
or are left exposed, in which case they could and dantrolene sodium, intrathecal baclofen
interact with rocuronium IgE antibodies [27R]. and local inltration of botulin toxin are also
A reasonable current strategy in patients used [34r].
who have anaphylactic reactions would be to
use standard therapy to start with but to use
sugammadex if there is a poor or no response
[28R]. Baclofen [SED-15, 408; SEDA-32, 276;
SEDA-33, 302; SEDA-34, 224]

The GABAB receptor is dened pharmaco-


Sugammadex [SEDA-32, 275; logically by its insensitivity to the GABAA
SEDA-33, 301; SEDA-34, 222] antagonist bicuculline and its sensitivity to the
GABA analogue baclofen. The G protein-
Cardiovascular Hypotension is a rare adverse linked GABAB receptor couples to adenylyl
reaction to sugammadex [29C] but another cyclase, voltage-gated calcium channels, and
case has been reported in a 33-year old inwardly-rectifying potassium channels.
woman who was given sugammadex 50 mg GABAB receptor agonism has been proposed
after induction of anesthesia; her blood pres- as a method of treating gastroesophageal
sure fell to 50/30 mmHg and she recovered reux disease. There has therefore been a
after being given etilephrin and phenyl- signicant effort to develop a peripherally-
ephrine [30A]. The authors speculated that restricted GABAB receptor agonist that does
pretreatment with propofol and fentanyl not have the nervous system adverse reactions
enhances the risk of hypotension due to that are observed with baclofen. The in vivo
sugammadex. and in vitro pharmacology of peripherally-
restricted GABAB receptor agonists and
Immunologic Allergic reactions have been the preclinical and clinical development of
reported in three patients within 4 minutes lesogaberan (3-amino-2-uoropropyl phos-
of a bolus of sugammadex 100 mg immedi- phinic acid), a potent and predominately
ately before extubation; skin testing was peripherally-restricted GABAB receptor ago-
positive in two [31A]. nist, have been reviewed [35RH].
Anaphylactic reactions have also been Preclinical studies have conrmed that
reported [32A]. baclofen blocks dopamine release in the
reward-responsive ventral striatum and
A t 17-year-old man developed a severe aller- medial prefrontal cortex, and consequently
gic reaction to a low dose of intravenous sugam- blocks drug motivated behavior [36E].
madex (200 mg, 3.2 mg/kg) 1 minute after However, its mechanism of action in
administration [33A]. He developed intense ery-
thema over the front of the thorax, severe lip and humans is unknown. Continuous arterial
palpebral edema, and bilateral wheeze. He had a spin-labeled (CASL) perfusion fMRI has
positive skin prick test to sugammadex. been used to examine the effects of baclo-
fen on blood ow in the human brain in
21 subjects (all smokers, 12 women), who
were randomized to either baclofen
80 mg/day (n 10) or placebo (n 11).
SKELETAL MUSCLE A 5-minute quantitative perfusion fMRI
RELAXANTS resting baseline scan was acquired before
dosing and after 21 days. Baclofen reduced
Systematic reviews The pathophysiology and cerebral blood ow in the ventral striatum
epidemiology of spasticity, its pharmacology, and medial prefrontal cortex and increased
and the efcacy and unwanted effects of dif- it in the lateral prefrontal cortex, which is
ferent drugs used to treat it have been involved in suppressing previously rewarded
Neuromuscular blocking agents and skeletal muscle relaxants Chapter 12 247

behavior. Cerebral blood ow in the insula and ketamine 20 mg for chemotherapy-


was blunted by baclofen. There were no dif- induced peripheral neuropathy, there were
ferences between the groups in adverse reac- no systemic adverse reactions [42c].
tions or cigarettes smoked per day. The Both baclofen and clonidine can improve
authors concluded that baclofens modulatory the response of symptoms to spinal cord
actions on regions involved in motivated stimulation. In a double-blind, randomized,
behavior in humans are reected in the resting placebo-controlled study in 10 patients with
state and provide insights into the mechanism neuropathic pain and insufcient pain relief
underlying its ability to block drug-motivated from spinal cord stimulation alone [43c], cloni-
behavior and its putative effectiveness as an dine, baclofen, and saline were given intra-
anti-craving or anti-relapse agent in humans. thecally by bolus injections in combination
with spinal cord stimulation. In the two
Observational studies In a retrospective patients with clonidine pumps combined ther-
analysis of 25 wheelchair-assisted adults with apy produced pain reductions of 45% and
cerebral palsy who were receiving intrathecal 55% over 15 months. The corresponding
baclofen there were complications in eight effects with baclofen were 82% and 32% after
and transient interruption of the treatment 7 months.
or surgical removal of the intrathecal pump
was necessary in four [37c]. Metabolism In 10 patients aged 2551 years
In a prospective single-arm open 7-week and body mass index 3141 kg/m2, who
study in 20 smokers taking baclofen and were given baclofen 15 mg/day increasing
bupropion SR, and having brief counselling to 30 mg/day in 10 days, and continuing
for smoking cessation, there were no serious for 12 weeks there were small but statisti-
adverse reactions [38c]. The most commonly cally signicant reductions in both body
reported adverse reactions were fatigue weight and waist circumference [44c]. There
(n 8), disturbance in attention (n 8), dry were no signicant changes in blood pres-
mouth (n 7), and insomnia (n 7). With sure or glucose and lipid metabolism.
combination therapy there was one dropout Serum leptin concentrations, which possibly
not attributed to the medication and three reect the amount of fat stores, were also
subjects required dosage reductions because signicantly reduced.
of adverse reactions.
Drug withdrawal Baclofen withdrawal is
In a retrospective audit of baclofen in the
associated with complications such as respi-
management of alcohol dependency in
ratory failure, refractory seizures, delirium,
21 patients with psychiatric co-morbidity
and labile blood pressure [45A]. The various
adverse reactions that occurred at low doses
treatment options include benzodiazepines,
included tiredness and sedation; one patient
propofol, skeletal muscle relaxants, and
taking 120 mg/day developed severe revers-
tizanidine. Delirium, extrapyramidal symp-
ible back pain, and one taking up to 275 mg/
toms, and autonomic dysfunction occurred
day developed somnolence, dizziness, and
in a 59-year-old man after abrupt with-
incontinence [39c]. The use of baclofen in the
drawal of baclofen and tizanidine and
treatment of alcohol dependence has been
resolved within 24 hours of reintroduction
reviewed [40R].
of baclofen [46A].
Placebo-controlled studies In a double- Susceptibility factors Renal disease
blind, randomized, placebo-controlled study Baclofen-induced encephalopathy has been
of baclofen 30 mg/day over 12 weeks in 80 reported in a patient with pre-end-stage
subjects with alcohol dependence, only two renal disease [47A]. A literature review of
individuals withdrew because of adverse 21 case reports involving 41 patients (23
events [41c]. men) showed that about two-thirds were
In a double-blind, placebo-controlled trial elderly and two-thirds were on dialysis.
of a topical poloxamer-based organogel con- Manifestations of baclofen toxicity usually
taining baclofen 10 mg, amitriptyline 40 mg, started 23 days after the start of treatment,
248 Chapter 12 C. Williams and M. Leuwer

although periods as long as 16 weeks have Cyclobenzaprine [SED-15, 1023;


been reported. The daily dose of baclofen SEDA-33, 305; SEDA-34, 227]
was 560 (mean 20) mg. Hemodialysis was
the most common treatment used for drug Placebo controlled studies In a double-
elimination. Recovery time ranged from blind, randomized, placebo-controlled study
2 hours in patients who received hemodial- of low-dose bedtime cyclobenzaprine 14 mg
ysis to 8 days with conservative treatment. in patients with bromyalgia restorative sleep
was improved [57c].

Drug formulations The pharmacokinetic


prole of an extended-release formulation of
Botulinum toxins [SED-15, 551; cyclobenzaprine, which delivers a sustained
SEDA-32, 276; SEDA-33, 304; plasma cyclobenzaprine concentration over
SEDA-34, 226] 24 hours, allowing once-daily dosing, has
been compared with that of immediate-
Uses The uses of botulinum toxin in pain release cyclobenzaprine 10 mg tds [58c]. The
management [48R], upper limb hypertonicity extended-release formulation produced a
in adults [49R], facial rejuvenation [50R], single daily peak in cyclobenzaprine concen-
neurogenic detrusor overactivity [51R], and tration compared with three peaks for the
cervical dystonia [52R] have been reviewed. immediate-release formulation, but the
systemic exposures were comparable. Sys-
Observational studies In a 24-month, ran- temic exposure to cyclobenzaprine in the
domized, single-blind trial of botulinum extended-release formulation was increased
toxin A in 10 children aged 314 years by food and in elderly subjects. Steady-state
with CharcotMarieTooth disease type 1A was achieved by day 7.
(OMIM 118220) one leg was treated with
intramuscular botulinum toxin A at 6-month
intervals in the tibialis posterior and peroneus
longus muscles; this did not affect the progres- Dantrolene sodium [SED-15, 1048;
sion of pes cavus [53c]. SEDA-33, 305; SEDA-34, 227]
In 133 patients with adductor spasmodic
dysphonia who were treated with laryngeal The pharmacology and pharmacokinetics
injections of botulinum toxin 51% had of dantrolene have been reviewed [59R].
some breathlessness, and dysphagia to liq-
uids was reported after 14% of treatments Observational studies Complications asso-
[54c]. The authors considered that an indi- ciated with the use of dantrolene in malig-
vidualized dosage regimen helps minimize nant hyperthermia have been reported in
adverse reactions and maximize function an analysis of data submitted to the North
and quality of life. American Malignant Hyperthermia Regis-
In a retrospective review of 22 children try [60C]. Reports of adverse metabolic
with Hirschsprungs disease treated with and musculoskeletal reactions to anesthesia
intrasphincteric injections of botulinum (AMRA) were analysed for differences
toxin there were no short-term or long- between subjects with and without compli-
term complications [55r]. cations attributed to dantrolene. In the full
dataset of 368 subjects, the most frequent
Sensory systems In a retrospective review complications associated with dantrolene
of 46 patients treated with injections of bot- were muscle weakness (22%), phlebitis
ulinum toxin in the palpebral lobe of the (9%), gastrointestinal upsets (4.1%), and
lacrimal gland for symptomatic epiphora respiratory failure (3.8%). There was a
due to lacrimal obstruction or gustatory 29% increase in the risk of any complica-
tearing, there was temporary ptosis in tion when the total dose of dantrolene was
11% of the patients [56A]. doubled, a 144% increase in risk when uid
Neuromuscular blocking agents and skeletal muscle relaxants Chapter 12 249

administration was part of the treatment, including tardive dyskinesia and tics associ-
an 83% reduction in risk in patients under- ated with Tourettes syndrome, has been
going neurosurgery, and a 74% reduction reviewed [62R]. Dose-limiting adverse
in risk in patients undergoing oral surgery. events consist mainly of sedation, parkin-
In a subset of 349 patients, omitting those sonism, akathisia, and depression, and usu-
with complications that were judged likely ally rapidly abate on dosage reduction.
to have been due to pre-existing disease
or the event of malignant hyperthermia, Placebo-controlled studies In a 12-week,
the most frequent complications associated double-blind, placebo-controlled trial in
with dantrolene were muscle weakness patients with Huntingtons disease, oral
(56%), phlebitis (9.2%), and gastrointestinal tetrabenazine (up to 100 mg/day; n 54)
upsets (4.3%); there was a 25% increase in was signicantly more efcacious than
risk of any complication when the total placebo (n 30) in improving chorea
dose of dantrolene was doubled, a 572% [63C]. Treatment-emergent adverse events
increase in risk in patients undergoing in those who took tetrabenazine mainly
obstetric or gynecological surgery, and a occurred during the dose-titration phase
56% reduction in risk if furosemide was and most of the events were mild to moder-
given; there was no effect of uid adminis- ate and were manageable with dosage
tration or other types of surgery. The adjustments or drug withdrawal.
authors concluded that complications after
dantrolene are common but rarely life- Systematic reviews In a systematic review
threatening. Unidentied factors in the sur- of three small prospective studies, eight
gical environment are associated with other trials, one case series, and eight case
changes in the risks of complications. Fluid reports of the use of tetrabenazine in the
administration, as part of the treatment of treatment of tardive dyskinesia, limiting
malignant hyperthermia, has an important adverse reactions included depression,
association with the risk of complications parkinsonism, and somnolence [64M].
after dantrolene administration and should
be monitored closely.

Respiratory High-dose oral dantrolene can


cause severe respiratory insufciency and Tizanidine [SED-15, 3436; SEDA-32,
may present difculties in the differential 278; SEDA-33, 307; SEDA-34, 227]
diagnosis of respiratory failure in patients
with high cervical spinal injuries [61A]. Cardiovascular In patch-clamp experiments
using HERG- or KCNQ1+KCNE1-
A 60-year-old man in the rehabilitation phase transfected cells, tizanidine 0.1100 mmol/l
after cervical spine injury developed general- inhibited the rapid IKr component of the
ized weakness and deteriorating respiratory
function, requiring ventilation. He had bilat- delayed rectier potassium current with an
eral basal lung collapse and a raised dia- IC50 above 100 mmol/l, prolonged repolari-
phragm and was taking high-dose oral zation in perfused guinea-pig hearts at a
dantrolene. Withdrawal of dantrolene resulted concentration of 1 mmol/l, and prolonged
in a dramatic recovery of respiratory function
within 2 days. the QTc interval in intact guinea-pigs
[65E]. Prolongation of the QT interval by
tizanidine in humans [66A] may therefore
be due to inhibition of IKr channels.

Tetrabenazine [SEDA-32, 277; Drugdrug interactions Lisinopril Hypo-


SEDA-33, 305; SEDA-34, 227] tension and bradycardia associated with
concomitant tizanidine and lisinopril ther-
The use of tetrabenazine in chorea and apy has been reported [67A]. Tizanidine is
other hyperkinetic movement disorders, a centrally acting a2 agonist and can cause
250 Chapter 12 C. Williams and M. Leuwer

bradycardia and hypotension by reducing concentration was raised at 168 mmol/l, the
sympathetic outow. blood urea nitrogen concentration was
7.5 mmol/l, the serum potassium concentration
An 85-year-old man developed profound 5.5 mmol/l, and the serum sodium concentra-
weakness, a blood pressure of 60/32 mmHg, tion of 128 mmol/l. Tizanidine, lisinopril,
and a heart rate of 37/minute after taking theophylline, omeprazole, and simvastatin were
three doses of tizanidine for 2 days in addition withheld, and he was given intravenous uids.
to chlorpromazine, citalopram, nasteride, Within 24 hours his blood pressure and heart
lidocaine patches, lisinopril, metformin, prami- rate had improved, as had the previously abnor-
pexole, omeprazole, simvastatin, theophylline, mal laboratory test values. Tizanidine was with-
diclofenac topical gel, hydrocodone + paracet- drawn, and all of his other preadmission
amol, and ondansetron. His serum creatinine medications were restarted at discharge.

References

[1] Muller V, Morell E, Le Marec C, [8] Ja Yun Mi, Hee Kim Yoon, Kwon
Pasquier P, Rousseau JM. Arrt cardiaque Go Young, Eun Shin Ji, Gun Ryu Choon,
linduction dun patient en thyrotoxicose. Kim Won, Jong Paik Nam, Ku Han Moon,
Avez-vous pens a lanaphylaxie? [Cardiac Hwan Do Sang, Suk Jung Woo. Remifenta-
arrest at induction of a patient with thyro- nil attenuates muscle fasciculations by
toxicosis. Have you thought of anaphy- succinylcholine. Yonsei Med J 2010; 51(4):
laxis?] Ann Fr Anesth Reanim 2010; 29 5859.
(6): 48890. [9] Seupaul RA, Jones JH. Does succinylcho-
[2] Mollerup HM, Gtke MR. Butyrylcholines- line maximize intubating conditions better
terase gene mutations in patients with pro- than rocuronium for rapid sequence
longed apnoea after succinylcholine for intubation? Ann Emerg Med 2011; 57(3):
electroconvulsive therapy. Acta Anaesthe- 3012.
siol Scand 2011; 55(1): 826. [10] Aalberse RC, Kleine Budde I, Mulder M,
[3] Kaufman SE, Donnell RW, Aiken DC, Stapel SO, Paulij W, Leynadier F,
Magee C. Prolonger neuromuscular paraly- Hollmann MW. Differentiating the cellular
sis following rapid-sequence intubation with and humoral components of neuromuscular
succinylcholine. Ann Pharmacother 2011; blocking agent-induced anaphylactic reac-
45(4): e21. tions in patients undergoing anaesthesia.
[4] Waghmare A, Kumar CN, Thirthalli J. Br J Anaesth 2011; 106(5): 66574.
Suxamethonium induced prolonged apnea [11] Jones PM, Turkstra TP. Mitigation of
in a patient receiving electroconvulsive ther- rocuronium-induced anaphylaxis by sugam-
apy. Gen Hosp Psychiatry 2010; 32(4): 447. madex: the great unknown. Anaesthesia
[5] Turan A, Mentoza ML, Gupta S, You J, 2010; 65(1): 8990.
Gottlieb A, Chu W, Saager L, Sessler DI. [12] Harper NJN. A reply. Anaesthesia 2011
Consequences of succinylcholine adminis- Jun; 65(1): 90.
tration to patients using statins. Anesthesi- [13] McDonnell NJ, Pavy TJ, Green LK,
ology 2011; 115(1): 2835. Platt PR. Sugammadex in the management
[6] Pal CK, Ray M, Sen A, Hajra B, of rocuronium-induced anaphylaxis. Br J
Mukherjee D, Ghanta AK. Changes in intra- Anaesth 2011; 106(2): 199201.
ocular pressure following administration of [14] Wordsworth HI, Raja Y, Harrison S. Sugam-
suxamethonium and endotracheal intubation: madex and rocuronium-induced anaphylaxis.
inuence of dexmedetomidine premedica- Br J Anaesth 2011; 106(6): 9112.
tion. Indian J Anaesth 2011; 55(6): 5737. [15] Funnell AE, Grifths J, Hodzovic I. A fur-
[7] Mirakhur RK, Elliott P, Shepherd WFI, ther case of rocuronium-induced anaphy-
Archer DB. Anaesthesia 1988; 43(Suppl): laxis treated with sugammadex. Br J
547. Anaesth 2011; 107(2): 2756.
Neuromuscular blocking agents and skeletal muscle relaxants Chapter 12 251

[16] Kawano T, Tamura T, Hamaguchi M, Yalcin A, Turan A. Effect of sugammadex


Yatabe T, Yamashita K, Yokoyama M. on rocuronium induced changes in pancreatic
Successful management of rocuronium- mast cells. Toxicol Ind Health 2013; Apr 3.
induced anaphylactic reactions with sugam- [Epub ahead of print].
madex: a case report. J Clin Anesth 2012; [25] Leysen J, Bridts CH, De Clerck LS, Ebo DG.
24(1): 624. Rocuronium-induced anaphylaxis is probably
[17] Motamed C, Baguenard P, Bourgain JL. not mitigated by sugammadex: evidence from
Possible mitigation of rocuronium-induced an in vitro experiment. Anaesthesia 2011; 66
anaphylaxis after administration of sugam- (6): 5267.
madex. J Anaesthesiol Clin Pharmacol [26] Clarke RC, Sadleir PH, Platt PR. The role
2012; 28(1): 1278. of sugammadex in the development and
[18] Badaoui R, Popov I, Dupont H. Un nouveau modication of an allergic response to
cas de choc anaphylactique induit par le rocuronium: evidence from a cutaneous
rocuronium ameliore par le sugammadex. model. Anaesthesia 2012; 67(3): 26673.
[A case of rocuronium-induced anaphylactic [27] Baldo BA, McDonnell NJ, Pham NH. The
shock, improved by sugammadex.] Can J cyclodextrin sugammadex and anaphylaxis
Anaesth 2012; 59(9): 90910. to rocuronium: is rocuronium still potentially
[19] Barbosa FT, da Cunha RM. Case of ana- allergenic in the inclusion complex form?
phylaxis induced by rocuronium treated Mini Rev Med Chem 2012; 12(8): 70112.
with sugammadex. Rev Bras Anestesiol [28] Abad Gurumeta A, Gutirrez Garca R.
2012; 62(4): 53842. Sugammadex, la ltima bala frente al
[20] Silva-Obregn JA, Gamero-Donis D, shock analctico por rocuronio? [Sugam-
Romo-Gonzales JE, Benito-Puncel C, Bor- madex: the last shot for anaphylactic shock
rallo-Prez JM, Marian-Crespo C. Ana- due to rocuronium?] Rev Esp Anestesiol
laxia tras la administracin de rocuronio. Reanim 2012; 59(4): 1779.
Potencial uso off-label de sugammadex. [29] Sorgenfrei IF, Norrild K, Larsen PB,
[Rocuronium-induced anaphylaxis. Poten- Stensballe J, Ostergaard D, Prins ME,
tial off-label use of sugammadex.] Med Viby-Mogensen J. Reversal of
Intensiva 2013; Jan 30. rocuronium-induced neuromuscular block
[21] Raft J, Leclercq M, Longrois D, by the selective relaxant binding agent
Meistelman C. Rcupration hmodynami- sugammadex: a dose-nding and safety
que et ventilatoire rapide aprs injection de study. Anesthesiology 2006; 104: 66774.
sugammadex lors dun choc anaphylactique [30] Kokki M, Ali M, Turunen M, Kokki H.
au rocuronium, rfractaire au traitement con- Suspected unexpected adverse effect of
ventionnel. [Fast recovery of haemodynamic sugammadex: hypotension. Eur J Clin
and ventilatory functions after sugammadex Pharmacol 2012; 68(5): 899900.
bolus following rocuronium-induced anaphy- [31] Godai K, Hasegawa-Moriyama M,
lactic shock refractory to conventional treat- Kuniyoshi T, Kakoi T, Ikoma K, Isowaki S,
ment.] Ann Fr Anesth Reanim 2012; 31(2): Matsunaga A, Kanmura Y. Three cases of
15861. suspected sugammadex-induced hypersensi-
[22] Barthel F, Stojeba N, Lyons G, tivity reactions. Br J Anaesth 2012; 109(2):
Biermann C, Diemunsch P. Sugammadex 2168.
in rocuronium anaphylaxis: dose matters. [32] Motoyama Y, Izuta S, Maekawa N,
Br J Anaesth 2012; 109(4): 6467. Chuma R. Case of anaphylactic reaction
[23] Baldo BA, McDonnell NJ, Pham NH. caused by sugammadex. Masui 2012; 61(7):
Drug-specic cyclodextrins with emphasis 7468.
on sugammadex, the neuromuscular [33] Menndez-Ozcoidi L, Ortiz-Gmez JR,
blocker rocuronium and perioperative ana- Olaguibel-Ribero JM, Salvador-Bravo MJ.
phylaxis: implications for drug allergy. Clin Allergy to low dose sugammadex. Anaes-
Exp Allergy 2011; 41(12): 166378. thesia 2011; 66(3): 2179.
[24] Kalkan Y, Tumkaya L, Bostan H, Tomak Y, [34] Lapeyre E, Kuks JBM, Meijler WJ. Spastic-
Altuner D, Yilmaz A, Erdivanli B, Bedir R, ity: revisiting the role and the individual
252 Chapter 12 C. Williams and M. Leuwer

value of several pharmacological treatments. clonidine and baclofen enhance the pain-
NeuroRehabilitation 2010; 27(2): 193200. relieving effect of spinal cord stimulation:
[35] Lehmann A, Jensen JM, Boeckxstaens GE. a comparative placebo-controlled, random-
GABAB receptor agonism as a novel thera- ized trial. Neurosurgery 2010; 67(1): 17381.
peutic modality in the treatment of gastro- [44] Arima H, Oiso Y. Positive effect of baclo-
esophageal reux disease. Adv Pharmacol fen on body weight reduction in obese sub-
2010; 57(C): 287313. jects: a pilot study. Intern Med 2010; 49(19):
[36] Franklin TR, Wang Z, Sciortino N, 20437.
Harper D, Li Y, Hakun J, Kildea S, [45] Ross JC, Cook AM, Stewart GL, Fahy BG.
Kampman K, Ehrman R, Detre JA, Acute intrathecal baclofen withdrawal: a
OBrien CP, Childress AR. Modulation of brief review of treatment options. Neurocrit
resting brain cerebral blood ow by the Care 2011; 14(1): 1038.
GABAB agonist, baclofen: a longitudinal [46] Karol DE, Muzyk AJ, Preudhomme XA. A
perfusion fMRI study. Drug Alcohol case of delirium, motor disturbances, and
Depend 2011; 117(2): 17683. autonomic dysfunction due to baclofen and
[37] Tasseel Ponche S, Ferrapie AL, Chenet A, tizanidine withdrawal: a review of the litera-
Menei P, Gambart G, Menegalli Bogeli D, ture. Gen Hosp Psychiatry 2011; 33(1): 84e1-2.
Perrouin Verbe B, Gay S, Richard I. Intra- [47] El-Husseini A, Sabucedo A, Lamarche J,
thecal baclofen in cerebral palsy. A retrospec- Courville C, Peguero A. Baclofen toxicity
tive study of 25 wheelchair-assisted adults. in patients with advanced nephropathy:
Ann Phys Rehabil Med 2010; 53(8): 48998. proposal for new labeling. Am J Nephrol
[38] White WD, Crockford DN, Currie SR, 2011; 34(6): 4915.
Patten S, El-Guebaly N. A prospective [48] Sim WS. Application of botulinum toxin in
single-arm open-label study of baclofen pain management. Korean J Pain 2011; 24
and bupropion SR combination therapy (1): 16.
for smoking cessation. Addict Disorders [49] Sheean G, Lannin NA, Turner-Stokes L,
Treat 2011; 10(3): 1014. Rawicki B, Snow BJ. Botulinum toxin
[39] Dore GM, Lo K, Juckes L, Bezyan S, Latt N. assessment, intervention and after-care for
Clinical experience with baclofen in the man- upper limb hypertonicity in adults. Interna-
agement of alcohol-dependent patients with tional consensus statement. Eur J Neurol
psychiatric comorbidity: a selected case series. 2010; 17(s2): 7493.
Alcohol Alcohol 2011; 46(6): 71420. [50] Carruthers J, Carruthers A. Botulinum toxin
[40] Addolorato G, Leggio L. Safety and ef- in facial rejuvenation: an update. Obstet
cacy of baclofen in the treatment of Gynecol Clin North Am 2010; 37(4): 57182.
alcohol-dependent patients. Curr Pharm [51] Smaldone MC, Ristau BT, Leng WW. Bot-
Des 2010; 16(19): 21137. ulinum toxin therapy for neurogenic detru-
[41] Garbutt JC, Kampov-Polevoy AB, sor overactivity. Urol Clin North Am
Gallop R, Kalka-Juhl L, Flannery BA. Ef- 2010; 37(4): 56780.
cacy and safety of baclofen for alcohol [52] Kamm C, Benecke R. Botulinum toxin
dependence: a randomized, double-blind, therapy for cervical dystonia: review of the
placebo-controlled trial. Alcohol Clin Exp clinical evidence and ongoing studies. Clin
Res 2010; 34(11): 184957. Invest 2011; 1(6): 891900.
[42] Barton D, Wos EJ, Qin R, Mattar BI, [53] Burns J, Scheinberg A, Ryan MM,
Green NB, Lanier KS, Bearden JD Rose KJ, Ouvrier RA. Randomized trial
3rd, Kugler JW, Hoff KL, Reddy PS, of botulinum toxin to prevent pes cavus
Rowland KM Jr, Riepl M, Christensen B, progression in pediatric CharcotMarie
Loprinzi CL. A double-blind, placebo- Tooth disease type 1A. Muscle Nerve
controlled trial of a topical treatment for 2010; 42(2): 2627.
chemotherapy-induced peripheral neuropa- [54] Novakovic D, Waters HH, DElia JB,
thy: NCCTG trial N06CA. Support Care Blitzer A. Botulinum toxin treatment of
Cancer 2011; 19(6): 83341. adductor spasmodic dysphonia: longitudinal
[43] Schechtmann G, Lind G, Winter J, functional outcomes. Laryngoscope 2011;
Meyerson BA, Linderoth B. Intrathecal 121(3): 60612.
Neuromuscular blocking agents and skeletal muscle relaxants Chapter 12 253

[55] Patrus B, Nasr A, Langer JC, Gerstle JT. hyperthermia association of the United
Intrasphincteric botulinum toxin decreases States. Anaesth Analg 2011; 112(5): 111523.
the rate of hospitalization for postoperative [61] Javed M, Bogdanov A. Oral dantrolene
obstructive symptoms in children with and severe respiratory failure in a patient
Hirschsprung disease. J Pediatr Surg 2011; with chronic spinal cord injury. Anaesthesia
46(1): 1847. 2010; 65(8): 8556.
[56] Wojno TH. Results of lacrimal gland botuli- [62] Jankovic J, Clarence-Smith K. Tetrabena-
num toxin injection for epiphora in lacrimal zine for the treatment of chorea and other
obstruction and gustatory tearing. Ophthal hyperkinetic movement disorders. Expert
Plast Reconstr Surg 2011; 27(2): 11921. Rev Neurother 2011; 11(11): 150923.
[57] Moldofsky H, Harris HW, Tad [63] Scott LJ. Tetrabenazine: for chorea associ-
Archambault W, Kwong T, Lederman S. ated with Huntingtons disease. CNS Drugs
Effects of bedtime very low dose cycloben- 2011; 25(12): 107385.
zaprine on symptoms and sleep physiology [64] Leung JG, Breden EL. Tetrabenazine for
in patients with bromyalgia syndrome: a the treatment of tardive dyskinesia. Ann
double-blind randomized placebo-controlled Pharmacother 2011; 45(4): 52531Erratum:
study. J Rheumatol 2011; 38(12): 265363. 2011; 45(5): 690.
[58] Darwish M, Hellriegel ET. Pharmaco- [65] Kaddar N, Vigneault P, Pilote S, Patoine D,
kinetic prole of once-daily cyclobenzapr- Simard C, Drolet B. Tizanidine (Zanaex): a
ine extended-release. Opin Drug Metab muscle relaxant that may prolong the QT
Toxicol 2010; 6(11): 142536. interval by blocking IKr. J Cardiovasc
[59] Inan S, Wei H. The cytoprotective effects of Pharmacol Ther 2012; 17(1): 1029.
dantrolene: a ryanodine receptor antago- [66] Del Rosario ME, Weachter R, Flaker GC.
nist. Anesth Analg 2010; 111(6): 140010. Drug-induced QT prolongation and sudden
[60] Brandom BW, Larach MG, Chen MSA, death. Mo Med 2010; 107(1): 538.
Young MC. Complications associated with [67] Publow SW, Branam DL. Hypotension and
the administration of dantrolene 19872006: bradycardia associated with concomitant
a report from the North American malignant tizanidine and lisinopril therapy. Am J
hyperthermia registry of the malignant Health-Syst Pharm 2010; 67(19): 160610.