Adverse reaction to neuromuscular blockers: frequency, investigation, and epidemiology.

A survey is presented of neuromuscular drug involvement in 390 clinically severe anaphylactoid reactions (grades II-IV reported to a Sheffield laboratory from 1988 to the end of 1992 from hospitals throughout the UK. Despite advances in patient monitoring and newer drugs, the reporting frequency and individual drug involvement were remarkably similar to those of a previous report from the laboratory in 1988. The highly immunogenic drug suxamethonium still predominated (48% of reports), but there was now much reduced use of the similarly immunogenic drug, alcuronium. The incidence of reactions to vecuronium and atracurium remained similar (12% and 18% reports, respectively) and acceptable to the anaesthetist. However, in choosing drugs for individual patients, the anaesthetist may wish to note that vecuronium reactors mainly showed bronchospasm, and atracurium reactors hypotension. By a systematic laboratory investigation, based on measurement of plasma tryptase and urinary methylhistamine, reaction mechanisms were assessed in 53 reactions. Despite their overall clinical similarity, analysis revealed that only one reaction in three was likely to be due to IgE-mediated anaphylaxis (Type 1). Not only was suxamethonium the most frequently reported drug, but in this study 11 reactions were identified as Type 1 response: no allergic reactions were identified for either vecuronium or atracurium, although single cases were identified for alcuronium, gallamine, and tubocurarine, with two unidentified. The remaining reactions were judged to be non-immune, although most involved mast cell degranulation. These reactions were no less hazardous than Type 1 reactions (one death), and two deaths were recorded. The importance of laboratory investigation as a feature of postreaction care is emphasized.

Atracurio mas alcuronio en anestesia / Atracurio and alcuronio in anesthesia

Con el presente trabajo se busca demostrar los beneficios del ejemplo alternado en un mismo paciente de dos relajantes musculares no despolarizantes, en este caso atracurio y alcuronio, obteniendose condiciones optimas mas o menos rapidas de intubacion endo-traqueal, adecuada relajacion quirurgica, sin la necesidad de revertir a estos relajantes al finalizar el acto quirurgico. Disminuyendo de esta forma la dosis total de ambos relajantes, probabilidad de depresion respiratoria por relajacion residual post anestesica.

Bradycardia and vecuronium: comparison with alcuronium during cholecystectomy.

We have compared the incidence of bradycardia in two groups of patients undergoing cholecystectomy. Twenty consecutive patients were allocated randomly to receive either vecuronium (n = 8) or alcuronium (n = 12) as part of a standard anaesthetic technique. Bradycardia was defined as a heart rate less than 50 beat min-1. Five episodes of bradycardia occurred with vecuronium and none with alcuronium (P less than 0.01).

Persistence of allergy to anaesthetic drugs.

Intradermal testing and RIA testing for specific IgE antibodies to neuromuscular blocking drugs (NMBDs) were performed in patients referred to an Anaesthetic Allergy Clinic. Six patients were initially investigated four to 29 years after clinical anaphylaxis during anaesthesia and two of these patients and sixteen others were investigated by intradermal testing on two occasions at least four years apart. Seven patients had RIA tests for NMBD-specific IgE antibodies on two occasions at the time of skin testing. In all but two patients the evidence for drug-specific antibodies persisted 4-29 years after the reactions. In one patient all tests became negative and in another the skin test became negative but the positive RIA persisted. Evidence of antibodies to NMBDs persisted in 21 of 22 patients who had had anaphylactic reactions to these drugs during anaesthesia. In the absence of evidence of allergy diminishing with time in the majority of patients it would seem wise to avoid drugs responsible for reactions for the rest of the patient's life.

Evaluation of a new reactive solid phase for radioimmunoassay of serum specific IgE against muscle relaxant drugs.

Until now, immunoassays for detection of anti-muscle relaxant IgE in serum have been performed with the drug coupled to epoxy-activated Sepharose or to RAST papers dics. In the present work we have used a quaternary ammonium-Sepharose in which the quaternary ammonium reactive group (choline chloride) was directly coupled to Sepharose via an ether linkage. 50 microliters of the quaternary ammonium solid phase (QAS) was incubated with 50 microliters of serum for 3 h, washed, incubated 18 h with 125I-anti-IgE and washed again. The results were expressed as the percentage of 125I-anti-IgE absorbed onto the solid phase. The results were at 1.3 +/- 0.5% for 20 control sera, with an upper normal limit estimated to 2.3%. The within-run reproducibility ranged from 3.2% to 10.0%. The results were significantly correlated with those obtained with either alcuronium-epoxy-Sepharose, choline-epoxy-Sepharose, the RAST-alcuronium or with the RAST-succinyl choline (respectively, r = 0.66, r = 0.80, r = 0.81, r = 0.40 and r = 0.85). The values obtained with the sera of 83 patients ranged from 0.3 to 38.5%. The sensitivity was estimated at 87.9%, 66.7% and 40.7% with the QAS-RIA, the RAST-succinyl choline and the RAST-alcuronium, respectively. The inhibition of adsorption of specific IgE onto the gel ranged from 13.0 to 90.6% in presence of 130 nmol of soluble muscle relaxants. In 83.3% of 30 cases, the highest inhibition was obtained with the muscle relaxant which was clinically incriminated.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylactic anaesthetic reactions. The value of paper radioallergosorbent tests for IgE antibodies to muscle relaxants and thiopentone.

The three currently available paper radioallergosorbent tests ('suxamethonium', alcuronium and thiopentone) were evaluated. 'Suxamethonium' radioallergosorbent test (which employs choline conjugated to paper discs) proved to be reliable in the detection of allergy to neuromuscular blockers, which were confirmed as the most common cause of anaphylactic reaction during general anaesthesia. Thiopentone radioallergosorbent test may also be useful, and is recommended in conjunction with 'suxamethonium' radioallergosorbent test in the preliminary investigation of reactions. Patients with positive 'suxamethonium' radioallergosorbent test usually require further testing, including alcuronium radioallergosorbent test, skin testing with a wide range of drug concentrations or leucocyte histamine release test.

[Atracurium--increased duration of its effect following alcuronium]. / Atracurium--Verlängerte Wirkdauer nach Alcuronium.

The duration of action of a supplementary dose of Atracurium 0.125 mg/kg after an initial dose of Atracurium 0.5 mg/kg respectively Alcuronium 0.25 mg/kg was investigated in 2 groups of 7 patients each. The average duration of action of Atracurium after Alcuronium (44.62 +/- 9.95 min) was 1.75 times longer than that of Atracurium after Atracurium (25.49 +/- 4.08 min). The difference is statistically significant (p = 0.05). For the clinical application of a combination of Atracurium with Alcuronium, 2 conclusions which might appear contradictory can be considered: 1. the pretreatment with Alcuronium can enhance intentionally the duration of action of Atracurium and spare total dosage of muscle relaxants at the same time. Prompt antagonism of muscle blockade of Atracurium remains unchanged according to our experience. 2. the pretreatment with Alcuronium may be dangerous whenever Atracurium is administered close to the end of the operation because of the possibility of prolonged postoperative muscle relaxation.

The use of tacrine (THA) and succinylcholine compared with alcuronium during laparoscopy.

Either tacrine (THA) with succinylcholine or alcuronium was used on a randomized basis for laparoscopic procedures in twenty young females. The technique using THA with succinylcholine was found to be more suitable and predictable for this procedure and gave a smoother anaesthetic course, brighter recovery and minimal postoperative complications.

[Anesthesia and hepatic porphyria]. / Anesthésie et porphyries hépatiques.

Three of the acute hepatic porphyrias, acute intermittent porphyria, variegata porphyria and hereditary coproporphyria, are characterized by an idiosyncratic reaction to many common drugs; the resulting excessive excretion of porphyrin precursors is responsible for episodes of acute neurological dysfunction. This review aimed to focus the attention of the anaesthesiologist on the porphyrinogenic properties of all the drugs used in anaesthesia and intensive care. An outline of the chemistry of porphyrins and the enzymatic pathways were recalled, so as to place the acute porphyrias in their proper perspective. There follows a reminder of the clinical aspect of acute porphyric crises. The part played by drugs is then assessed from clinical and laboratory data concerning their porphyrinogenicity. Those drugs for which there is conflicting evidence regarding their safe use in porphyric patients are discussed: propofol, ketamine, benzodiazepines, etomidate, local anaesthetics. Recommendations supported by clinical and experimental data are given, especially the results obtained with the chick embryo liver model. Treatment of the acute crisis is provided, with particular emphasis on the use of haematin. The anaesthetic management of hepatic porphyric patients is described. Those drugs which are well-known porphyrinogenic compounds in the chick embryo liver must be excluded from use for anaesthesia in the porphyric patients, even if they have been observed to be innocuous in rare cases of asymptomatic patients. Finally, recommendations for anaesthesia in symptomatic cutanea porphyria are given.

Adverse reactions to atracurium and alcuronium. A prospective surveillance study.

A multicentre prospective surveillance study was undertaken to compare the incidence and severity of adverse reactions attributed to atracurium and alcuronium. Clinical manifestations were used by the anaesthetist to diagnose an adverse reaction (a cutaneous reaction, a greater than 20% change in arterial pressure or heart rate, and bronchospasm). Of the 1956 patients receiving atracurium, 10.1% had adverse reactions compared with 17.9% of the 1425 patients receiving alcuronium (P less than 0.001). There were no longterm sequelae. The atracurium group had a markedly lower incidence of hypotension (3.4% v. 13.7%; P less than 0.0001), but a higher incidence of cutaneous reactions (4.6% v. 2.3%; P less than 0.005) which were not associated with other adverse reactions. There was a low incidence of bronchospasm in both groups (0.2% v. 0.1%).

Anaphylaxis to muscle relaxants: cross-sensitivity studied by radioimmunoassays compared to intradermal tests in 34 cases.

Thirty-four patients (31 female and three male patients) with a previous anaphylactoid shock to muscle relaxants were investigated. The seric antimyorelaxant IgE was detected by radioimmunoassay (RIA), and the results were compared to intradermal test (IDR) reactions to dilutions of the commercial drugs. The RIA was carried out with a Sepharose-myorelaxant solid phase and anti-IgE 125I-labeled IgG. The results corresponded to the percentage of labeled anti-IgE bound on the solid phase. The RIA with Sepharose-alcuronium and Sepharose-choline was estimated positive from determination with normal sera (n = 12) when bound IgE was greater than 1.0% and 1.5%, respectively. The RIA and IDR were positive in 43.5% and 75%, respectively, of the cases, with a concordance of 66%. One test at least was positive in 79.4% of the cases. No correlation was found between IgE seric levels and the RIA nor between the cutaneous sensitivity and the RIA. Cross-reactivity with Sepharose-choline and Sepharose-alcuronium was observed in 50%, and it was demonstrated by IDR in only 34.2%. The RIA demonstrated the specificity of IgE to quaternary ammonium compounds as myorelaxant drugs. The positive IDR revealed the bridging of mast cell-bound specific IgE, depending on structural conditions, such as the flexibility of the molecules or the variable specificity of the antibodies, restricted to quaternary ammonium ions or enlarged to a broader part of the incriminated molecules.

Profound reversible myocardial depression after anaphylaxis.

Profound myocardial depression developed in 2 patients after severe anaphylactic reactions following the induction of anaesthesia in 1 case and a bee-sting in the other. Neither patient had pre-existent cardiac disease. In both patients haemodynamic assessment, radionuclide ventriculography, and two-dimensional echocardiography confirmed the clinical impression of profound systolic myocardial dysfunction. Haemodynamic stability was attained by intra-aortic balloon counterpulsation, which was probably life-saving in both cases. Cardiac function improved rapidly although some contractile depression persisted for several days. At follow-up both patients had normal cardiac function with no evidence of underlying heart disease.

Allergy to suxamethonium: persisting abnormalities in skin tests, specific IgE antibodies and leucocyte histamine release.

Twenty-one patients, who had previously experienced an anaphylactic reaction to suxamethonium during general anaesthesia, were selected for this study. Initially, skin tests with muscle relaxants were carried out in the twenty-one patients, detection of specific anti-choline IgE in nineteen, and leucocyte histamine release in seventeen. These three tests were then repeated between 1 year and 4 years after the initial evaluation. In the majority of patients, sensitization to the muscle relaxants persisted for more than 1 year after the anaphylactic reaction. Only three patients out of twenty-one (4%) had negative skin tests when retested 1-4 years later. A reduction in leucocyte histamine release was noticed in one of the seventeen retested patients (6%). Modifications of anti-choline IgE were observed in five of nineteen patients (26%). The persistence of sensitization to suxamethonium may result from repeated stimulation by occasional contacts with quaternary ammonium compounds. This study demonstrates the reliability of skin tests, leucocyte histamine release and detection of anti-choline IgE to diagnose allergic reactions to suxamethonium, even when they are performed a long time after the initial anaphylactic reaction.

Prolonged paralysis following an infusion of alcuronium in a patient with renal dysfunction.

The case is described of a patient who underwent artificial ventilation in an intensive therapy unit and received an infusion of alcuronium 10 mg/hour for more than 4 days, in the presence of significant renal (and later, some degree of hepatic) impairment. Prolonged and profound neuromuscular block persisted despite haemodialysis (5 hours on each of 3 days) followed by 72 hours of continuous haemofiltration; it appeared to resolve only after plasma exchange (4 litres). The total of persistent block, for 9 days after the infusion had been stopped, is thought to be the longest period ever reported after administration of alcuronium. Neuromuscular block was monitored throughout this period using the train-of-four twitch technique. The potentiating effects of concurrent aminoglycoside therapy and hepatic dysfunction on the degree of paralysis are discussed.

Anaphylactoid reaction to alcuronium.

A 67-year-old woman suffered cardiovascular collapse during induction of anaesthesia. This was later shown to be anaphylactic in origin; the causative agent was alcuronium. In vitro testing showed a highly specific sensitivity to alcuronium with minimal cross-reactivity. Future anaesthesia with decreased risk was thereby assured. The clinical nature of this reaction and a review of the literature implicate the cardiovascular system as the principal target in this type of reaction to alcuronium and suggest that the heart is directly involved.