Indian Journal of Fundamental and Applied Life Sciences ISSN: 2231-6345 (Online)

An Online International Journal Available at http://www.cibtech.org/jls.htm 2013 Vol. 3 (2) April-June, pp. 211-213/Avasthi and Tripathi

Research Article

211

ANAPHYLAXIS FOLLOWING INJECTION ATRACURIUM BESYLATE:

AN UNCOMMON BUT LIFE THREATENING COMPLICATION

*Awasthi S. and Tripathi R.K. Department of Anesthesiology, Era’s Lucknow Medical College & Hospital, Lucknow

*Author for Correspondence

ABSTRACT In the perioperative setting multiple agents can cause anaphylaxis. The reactions are often unpredictable

and remain a major cause of concern for anesthesiologist owing to their life threatening potential.

Anaphylactic reactions due to neuromuscular blocking agents (NMBA) is estimated to be the most common cause among other agents, leading to serious adverse reaction(cardiovascular collapse and

bronchospasm being the most frequent). In our study we present a case of anaphylaxis following injection

atracurium leading to severe hypotension, tachycardia, rashes and angioedema.Possible causes,

therapeutic approach and a brief review of literature has been discussed.

Key Words: Anaphylaxis, Neuromuscular blocking agents (NMBAs), Atracurium.

INTRODUCTION

An anaphylactic reaction is a rare, but severe anesthetic complication. Immediate hypersensitivity

reactions to anaesthetic and associated agents used during the perioperative (Hepner et al., 2003) period have been reported with increasing frequency. Most reactions are of immunologic origin (IgE mediated,

anaphylaxis) or related to direct stimulation of histamine release (anaphylactoid reactions) (Mertes et al.,

204)

Anaphylaxis remains the most serious adverse reaction due to NMBAs. The tetrahydroisoquinolinium class of neuromuscular blocking agents, in general, is associated with histamine release upon rapid

administration of a bolus intravenous injection (Savarese et al., 1995).

Atracurium besylate, a nondepolarizing intermediate duration, skeletal neuromuscular blocking agent of tetrahydroisoquinolinium class is well tolerated and produces few adverse reactions during extensive

clinical trials, most of them suggestive of histamine release. Most commonly, the histamine release

following administration of these agents is associated with observable cutaneous flushing, hypotension and a consequent reflex tachycardia. Because these effects are so transient, there is no reason to

administer adjunctive therapy to ameliorate either cutaneous or cardiovascular effects. But there have

been reported cases of severe anaphylactic reactions following injection atracurium leading to life

threatening complications.

CASES

A 38 YR old female patient weighing 65 kg, admitted for cholelithiasis was posted for laparoscopic cholecystectomy under general anesthesia. All preoperative investigations including liver function tests

were within normal limit and patient had no significant finding in preanesthetic examination (PAE).

After usual fasting guidelines, patient was taken to operation theatre, intravenous line was secured. All

standard monitors were connected (including pulse oximetry (SpO2, non invasive blood pressure (NIBP), ECG, ETCO2) and baseline parameters were recorded (pulse 84/min, BP 110/70 mmHg and SpO2 99%)

The patient was pre-medicated with iv midazolam 2 mg, glycopyrollate 0.2mg, ondansetrone 4mg,

fentanyl 100 ug. Induction was carried out with inj propofol (2mg/kg), followed by intubation with succinyl choline (1.5 mg/kg) using 7.5 mm cuffed disposable endotracheal tube(ETT).Infusion propofol

started(100ug/kg/min) with N2O:O2 (60:40).

Indian Journal of Fundamental and Applied Life Sciences ISSN: 2231-6345 (Online)

An Online International Journal Available at http://www.cibtech.org/jls.htm 2013 Vol. 3 (2) April-June, pp. 211-213/Avasthi and Tripathi

Research Article

212

After the patient recovered from succinylcholine induced neuromuscular blockade, atracurium was administered as 0.5mg/kg bolus dose for subsequent neuromuscular blockade. Soon after the injection

patient had nonpalpable radial artery pulse, with recordable NIBP 60/48mmg with rashes over both hands

and swelling over lips (suggestive of angioedema).On auscultation patient had bilateral decreased air entry. Immediately N2O was stopped, patient ventilated with 100% oxygen. Inj hydrocortisone 100mg i.v,

inj dexamethasone 8mg, inj Avil 44.5mg i.v ,inj mephentine 6mg given. Simultaneously i.v fluid (colloid)

pushed via 18G i.v cannula and another i.v line secured. Still the patient had non palpable radial artery,

PR 160/min, B.P 60/50 mmHg, SpO2 98%.After that inj adrenaline 0.1mg i.v administered and fast intravenous fluid continued via two 18 G iv cannula. Patient’s pulse started improving with PR 120/min,

BP 100/60mmHg, and SpO2 99%), rashes over hands and swelling over lips started dissipating.ECG,

SpO2, end tidal carbon di-oxide (ETCO2) remained normal throughout. Arterial blood gas (ABG )sample was sent , ABG report suggested no abnormal finding (pH 7.35,pCO2 45 mmHg,pO2 141 mmHg,HCO3-

19.1 mmol/l,anion gap 18.9 mmol/l,Na+ 133 mmol/l,K+3.5 mmol/l,Ca+ 0.43 mmol/l,Cl+

95mmol/l.).Considering the normal ABG report, urine output and stable vital parameters, reversal with neostigmine (3mg) and glycopyrollate (0.6mg) was planned after the patient had spontaneous effort of

breathing. Patient was extubated after return of protective reflexes. Extubation and recovery were

uneventful, the patient maintained vital parameters (P.R 90/min, B.P 110/70 mmHg) oxygen saturation at

98% without oxygen and 100% with oxygen. She was shifted to postoperative room and kept on oxygen mask and monitored for vital parameters and output. No untoward event occurred thereafter.For

confirmatory testing patient’s blood sample was sent for serum tryptase assay 30 min after the episode

,which was found to be elevated .Prick test performed on the forearm with 1:10 dilution of atracurium showed wheal measuring 3 mm.Patient was called after 6 weeks for intradermal skin testing with 10

-3

atracurium which resulted in wheal of 8 mm with surrounding flare .Patient was issued red card stating

allergic to atracurium and adviced to have an intradermal skin testing for cross reactivity of neuromuscular blocking agents before next planned surgery

DISCUSSION

Atracurium is one of the most common drugs used now days in operation theatre and ICU for neuromuscular block owing to its advantages over other blocking agents. It is contraindicated in patients

known to have a hypersensitivity to it.

Although atracurium is a less potent histamine releaser than d-tubocurarine / metcurine,the possibility of substantial histamine release in sensitive individuals or in patients in whom substantial histamine release

would be especially hazardous (e.g., patients with significant cardiovascular disease)must be considered.

Allergic reactions (anaphylactic or anaphylactoid responses) are among the most frequently reported

adverse reaction which, in rare instances, are severe (e.g., bronchospasm (Siler et al., 1993), laryngospasm and cardiac arrest).

Mertes and colleagues (Mertes et al., 2008) found that neuromuscular blocking agents are the leading

drugs responsible for immediate hypersensitivity reactions during anaesthesia, with the incidence estimated to be between 1 in 3000 to 1 in 110,000 general anaesthetics.

Moneret –Vautrin DA and others (Moneret-Vautrin et al., 2010) reported cardiovascular collapse and

bronchospasm are more frequent in IgE dependent reactions, leading cause being neuromuscular blocking agents.

Mertes PM and others (Mertes et al., 2002) estimated the incidence of anaphylaxis between 1 in 10000

and 1 in 20000 anaesthesia and NMBAs represent the most frequently involved substance administered in

perioperative period which can produce life threatening immune mediated hypersensitivity reactions. Lafforgue E and others (Lafforgue et al., 2005) reported successful extracorporeal resuscitation of a

probable perioperative anaphylactic shock due to atracurium.

Indian Journal of Fundamental and Applied Life Sciences ISSN: 2231-6345 (Online)

An Online International Journal Available at http://www.cibtech.org/jls.htm 2013 Vol. 3 (2) April-June, pp. 211-213/Avasthi and Tripathi

Research Article

213

Soetens FM and colleagues (Soetens et al., 2003) found skin testing to be a reliable tool to investigate suspected anaphylactic reactions during general anaesthesia and to guide the future use of neuromuscular

blocking drugs. Adilah Miraj and colleagues (Miraj et al., 2010) reported profound bradycardia followed by cardiac arrest soon after the administration of injection atracurium.

Thus any suspected hypersensitivity reaction during anaesthesia must be extensively investigated to

confirm the nature of the reaction, to identify the responsible drug, to study cross-reactivity in cases of

anaphylaxis to NMBAs and to provide recommendations for future anesthetic procedures. Our patient had no previous surgical intervention, so known existence of allergy to atracurium is ruled

out. Although during PAE she did not give any history of allergy to any drug, but post recovery she gave

history of allergic tendency (cutaneous flushing and rashes) to some analgesics (documents unavailable) . Considering the above incidence one should be cautious enough following injection atracurium especially

in patients with history of allergic tendency or anaphylaxis to rule out an uncommon but life threatening

complication which can be fatal if not managed properly within time.

REFERENCES

Hepner D L and Castells M C (2003). Anaphylaxis During the perioperative period: Anesthesia and

Analgesia 97(5) 1381-1395. Mertes PM and Laxenaire MC (2004). Allergy and anaphylaxis in anaesthesia.Minerva Anestesiologica

70(5) 285-91.

Savarese JJ and Wastila WB (1995). The future of the benzylisoquinolinium relaxants. Acta Anaesthesiologica Scandinavica 106 Suppl: 91-93 PMID 8533554.

Siler JN, Mager JG Jr and Wyche MQ (1993). Jr. Atracurium: hypotension, tachycardia and

bronchospasm.Minerva Anesthesiologica 59 (3) 133-135 PMID 8515854.

Mertes PM, Aimone-Gastin I, Gueant-rodriguez RM, Mouton-Faivre C, Audibert G, O’Brien J et

al. (2008). Hypersensitivity reaction to neuromuscular blocking agents. Current Pharmaceutical Design

14(27) 2809-25.

Moneret-Vautrin DA and Mertes PM (2010). Anaphylaxis to general anesthetics. Chemical Immunology and Allergy 95 180-9.

Mertes PM and Laxenaire MC (2002). Allergic reactions occurring during anaesthesia. European

Journal of Anaesthesiology 19(4) 240-62. Lafforgue E, Sleth JC, Pluskwa F and Saizy C (2005). Successful extracorporeal resuscitation of a

probable perioperative anaphylactic shock due to atracurium. Annales Francaises d'Anesthesie et de

Reanimation 24(5) 551-5.

Soetens FM, Smolders FJ, Meeuwis HC, Van der Aa PH, De Vel MA, Vanhoof MJ and Soetens MA (2003). Intradermal skin testing in the investigation of suspected anaphylactic reactions during

anaesthesia-a retrospective survey. Acta Anaesthesiologica Belgica 54(1) 59-63.

Miraj A, Foand A and Seth B (2010). Cardiac arrest following an anaphylactic reaction to atracurium.