Fentanyl Vecuronium

A 65-year-old man undergoing elective sternal debridement and rewiring was given a prophylactic infusion of vancomycin 1 g preoperatively. Anesthesia was induced with thiopental, suxamethonium, and fentanyl, and maintained with fentanyl, vecuronium, and isoflurane. A few minutes after wound irrigation with bacitracin (about 25U/ml), his blood pressure fell precipitously, necessitating intravenous fluids and adrenaline. His face and arms were flushed. Afterwards, he reported having had a rash several years before after the use of an over-the-counter ointment composed of polymyxin B, bacitracin, and neomycin. 

A 77-year-old man is admitted to the hospital for a coronary artery bypass. He has been treated with a (3-blocker (Tenormin 100 mg per day), which he took every morning. He is induced with propofol 1 mg/kg, fentanyl 5 jjig/kg and vecuronium 8 mg for muscle relaxation. After 3 minutes a decreasing heart rate becomes a worry for the anesthesiologist. The heart rate continues to fall until it reaches 38 BPM. At this point the patient s blood pressure is 80/60 and the anesthesiologist gives atropine 0.4 mg and ephedrine 10 mg. This treatment results in a stable patient. What effects were most likely produced by the anesthesia procedure Could this have been avoided ... 

Answer This feature of bradycardia is typical of patients who take (3-blockers, which should be continued so they result ultimately in better anesthetic management. The drugs given could have been modified (i.e., etomidate instead of propofol, which does not raise or may cause a slower heart rate). The potent opioids in the fentanyl family all cause vagal transmitted bradycardia. The muscle relaxant vecuronium (norcuron) has no effect on heart rate and could have been replaced by pancuronium, which has a vagolytic effect and will counter bradycardia in the usual induction bolus doses. 

In 113 patients undergoing general anesthesia, intravenous midazolam 15 mg slowed recovery of the twitch height after vecuronium and atracurium compared with diazepam. The recovery index was not altered (162). However, in another study in 20 patients, midazolam 0.3 mg/kg did not affect the duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation produced by suxamethonium 1 mg/kg, nor the duration of blockade and adequacy of relaxation for tracheal intubation produced by pancuronium 0.025 mg/kg in incremental doses until 99% depression of muscle-twitch tension was obtained (161). Furthermore, in 60 patients undergoing maintenance anesthesia randomly assigned to one of six regimens (etomidate, fentanyl, midazolam, propofol, thiopental plus nitrous oxide, or isoflurane plus nitrous oxide), midazolam did not alter rocuronium dosage requirements (165). 

Etomidate is the indnction agent of choice in atopic patients, in whom etomidate, fentanyl, and vecuronium comprise the safest combination of drugs for general anesthesia. However, non-allergic anaphylactic (anaphylactoid) reactions have been observed, even with this combination (23,24), and it can even be life-threatening one patient also had a myocardial infarction (24). 

Symptoms suggestive of severe sensorimotor neuropathy developed in a 40-year-old woman 15 days after admission for a severe exacerbation of asthma (7). During this time she was given isoflurane 0.5-3% in oxygen, vecuronium bromide 4-6 mg/hour, and fentanyl 100 micrograms/hour. The neuropathy resolved spontaneously over the next 3 months. 

McCoy EP, Maddineni VR, Elliott P, Mirakhur RK, Carson IW, Cooper RA. Haemodynamic effects of rocuronium during fentanyl anaesthesia comparison with vecuronium. Can J Anaesth 1993 40(8) 703-8. 

The expected cardiovascular stability of vecuronium has been confirmed in man (2,21-23). Even doses as large as 0.28 mg/kg in patients undergoing coronary artery bypass grafting produced negligible effects (24). Bradycardia is the only cardiovascular adverse effect reported, and this is seen in association with opioids such as fentanyl (25) and sufentanil (SEDA-11, 125) (26) or other drugs that are themselves capable of producing bradycardia. The lack of vagolytic and sympathomimetic activity of vecuronium... 

Salmenpera M, Peltola K, Takkunen O, Heinonen J. Cardiovascular effects of pancuronium and vecuronium during high-dose fentanyl anesthesia. Anesth Analg 1983 62(12) 1059-64. 

The inhalational anaesthetics increase the effects of the neuromuscular blockers to differing extents, but nitrous oxide appears not to interact significantly. Ketamine has been reported to potentiate the effects of atracurium. Propofol does not appear to interact with mivacurium or vecuronium. Xenon is reported not to interact with mivacurium or rocuronium, and has less effect than sevoflurane on vecuronium neuromuscular blockade. Bradycardia has been seen in patients given vecuronium with eto-midate or thiopental. Propofol can cause serious bradycardia if it is given with suxamethonium (succinylcholine) without adequate antimuscarinic premedication, and asystole has been seen when fentanyl, propofol and suxamethonium were given sequentially. 

The dosage of the neuromuscular blocker may need to be adjusted according to the anaesthetic in use. For example, the dosage of atracurium can be reduced by 25 to 30% if, instead of balanced anaesthesia (with thiopental, fentanyl and nitrous oxide/oxygen)," enflurane is used, and by up to 50% if isoflurane or desflurane are used. Another study recommended reduced doses of neuromuscular blockers such as atracurium and tubocurarine in children undergoing anaesthesia with enflurane or isoflurane. In one study, enflurane and isoflurane reduced the vecuronium infusion rate requirements by as much as 70%, when compared with fentanyl anaesthesia. Another study demonstrated that although halothane and isoflurane could both increase the neuromuscular potency of vecuronium, only isoflurane prolonged the recovery from neuromuscular blockade. ... 

Bradycardia occurring during anaesthetic induction with vecuronium and etomidate, or to a iesser extent thiopental, has also been reported, particularly in patients also receiving fentanyl, see also Neuromuscular blockers + Opioids , p.l30. 

Inoue K, El-Banayo A, Stolarski L, Reichelt W. Vecuronium induced bradycardia following induction of anaesthesia with etomidate or thiopentone, with or widiout fentanyl. BrJ AnaesOi (1988) 60,10-17. 

In a study of 16 surgical patients, 8 took oral clonidine 4 to 5.5 micrograms/kg 90 minutes before their operation. Anaesthesia was induced by thiamylal, and maintained with nitrous oxide/isoflurane/oxygen supplemented by fentanyl. Clonidine increased the duration of neuromuscular blockade following the use of vecuronium by 26.4%, when compared with the patients not taking clonidine. ... 

A woman experienced hypertension and tachycardia when she was given pancuronium after induction of anaesthesia with morphine and nitrous oxide/oxygen. Bradycardia has been reported with vecuronium and alfentanil, fentanyl, or sufentanii, sometimes in patients receiving beta blockers and/or calcium channei blockers. 

Noninterfering alfentanil, aprotinin, atropine, bupivacaine, chlorpromazine, dalteparin, dexamethasone, diazepam, dopamine, droperidol, etomidate, fentanyl, furosemide, gallamine, haloperidol, midazolam, morphine, neostigmine, nitroglycerin, nitroprusside, oxytocin, pancuronium, pentobarbital, phenylephrine, phenytoin, pipecuronium, piperacillin, promethazine, propofol, ranitidine, succinylcholine, sufentanil, terbutaline, thiopental, vecuronium, verapamil... 

A literature review on human medicine identified numerous drugs that were inadvertently injected epidurally, and these included thiopental, methohexital, vecuronium, midazolam with fentanyl, morphine with dextrose, ephedrine, cefazolin, gentamicin, amoxicillin... 

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