Weal and flare responses to intradermal rocuronium and cisatracurium in humans{dagger}

Thirty volunteers underwent intradermal skin testing with increasingconcentrations of rocuronium and cisatracurium to evaluate wealand flare responses, and whether either agent would cause mastcell degranulation and sensitization upon re-exposure. We foundthat intradermal injection of rocuronium and cisatracurium atconcentrations >10^–4 M resulted in positive weal (>8 mm)responses, and positive flare responses at >10^–4 and>10^–5 M respectively. Only cisatracurium caused mildto moderate mast cell degranulation, and neither drug causedsignificant in vitro histamine release from whole blood collectedfrom study subjects 4 weeks after skin testing. Skin testingwith rocuronium and cisatracurium should be performed at concentrations<10^–4 and <10^–5 M respectively to avoid false-positiveresponses. The ability of these agents to produce positive wealand flare responses at relatively low concentrations may explainthe high incidence of potential reactions reported. Br J Anaesth 2000; 85: 844–9     

Prolonged residual paralysis after a single intubating dose of rocuronium

It is often argued that neuromuscular monitoring is unnecessarywhen only one dose of an intermediate-acting neuromuscular blockingagent is given. This case report documents that it may takemore than 3.5 h before it is possible to antagonize a blockcaused by a normal dose of rocuronium (0.6 mg kg^–1). Possiblecauses of the extremely prolonged duration of action are discussed,as is the importance of quantitative neuromuscular monitoring.     

Screening for mast cell tryptase and serum IgE antibodies in 18 patients with anaphylactic shock during general anaesthesia

BACKGROUND: In the perioperative setting multiple agents can cause anaphylaxis. Often the reactions are dramatic, and due to their lifethreatening potential it is crucial that the responsible agent is identified in order to avoid future adverse reactions. The aim of the present study was to measure the concentration of serum mast cell tryptase (MCT), to investigate the prevalence of serum IgE antibodies against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex and to perform skin prick tests (SPTs) in 18 patients experiencing an anaphylactic reaction during induction of general anaesthesia. METHODS: Serum samples from 18 patients with an anaphylactic reaction during general anaesthesia were analyzed for MCT and specific IgE against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex. Skin prick tests were performed in 11 out of 18 patients. RESULTS: Ten patients had elevated MCT levels and specific IgE against ammonium ion, morphine and (with the exception of patient nos 3, 9 and 10) suxamethonium. Seven of these patients had positive SPTs to suxamethonium. One of the patients tested positive to latex in addition to suxamethonium. Two patients showed elevated MCT, while specific IgE against the drugs tested was not detected. Three patients tested positive to ammonium ion, morphine and suxamethonium, but negative to MCT. Three patients tested negative to both MCT and specific IgE. CONCLUSIONS: Fifteen out of 18 sera tested positive for MCT and/or specific IgE against neuromuscular blocking drugs (NMBDs). Ten of the 18 patients experienced an IgE-mediated anaphylactic reaction to NMBDs during anaesthesia, verified by detection of specific IgE and elevated levels of MCT.     

Anaphylactoid reactions during anaesthesia

Sixty one patients who had suffered intra-operative anaphylactoid reactions were studied. Intradermal testing identified the causative agent in 84% of cases and, in 75% of these, muscle relaxants were responsible. Predisposing factors in patients sensitive to muscle relaxants were: female sex, previous allergy and atopy. The incidence of previous exposure was considerably higher than that reported in the literature. Pancuronium is suggested to be the least likely currently available agent to provoke a major anaphylactoid reaction.     

Remifentanil and propofol without muscle relaxants or with different doses of rocuronium for tracheal intubation in outpatient anaesthesia

BACKGROUND: The use of muscle relaxants in outpatient anaesthesia is controversial; some authors recommend an induction regimen including propofol and opioids without muscle relaxants. This study evaluated the requirements for rocuronium after remifentanil/propofol. METHODS: We examined in four groups of ASA I-II patients (n= 30 for each) the intubating conditions three minutes after induction of anaesthesia with remifentanil 0.5 microg kg(-1) min(-1), propofol 2 mg kg(-1) without muscle relaxants or with different doses of rocuronium (0.6 mg kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1)) applying the criteria proposed by the Copenhagen Consensus Conference. In the second part of the study the time course of neuromuscular block was determined by electromyography using train-of-four (TOF) stimulation. To this end, another 60 ASA I-II patients were randomly assigned to receive remifentanil 0.5 microg kg(-1) min(-1), propofol 2 mg kg(-1) and either rocuronium 0.6 mg kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1), or 0.3 mg kg(-1) followed by neostigmine 40 microg kg(-1) and atropine 20 microg kg(-1) at a T1 recovery of 10% (n=15 for each). RESULTS: Intubating conditions were good or excellent in 30 patients after rocuronium 0.6 mg kg(-1) and in 18 patients when rocuronium was omitted (P<0.01). After 0.45 mg kg(-1) and 0.3 mg kg(-1) rocuronium the numbers were 29 and 30 patients, respectively. Reducing rocuronium from 0.6 mg kg(-1) to 0.45 mg kg(-1) or 0.3 mg kg(-1) increased the onset time from 136 (35) s to 199 (34) s and 249 (52) s (mean (SD)), (P<0.01); the clinical duration decreased from 38 (10) min to 24 (8) min and 16 (5) min, respectively (P<0.01); and the duration to a TOF-ratio of 0.8 decreased from 60 (11) min to 45 (9) min and 34 (7) min (P<0.01). After rocuronium 0.3 mg kg(-1) this time interval further decreased to 22 (3) min when neostigmine was given at a T1 of 10% (P<0.01 compared with spontaneous recovery after rocuronium 0.3 mg kg(-1)). CONCLUSION: After remifentanil/propofol intubation conditions were poor in 40% of patients without muscle relaxants; adding reduced doses of rocuronium to this regimen improved the intubation conditions significantly. In addition, reducing the initial dose of rocuronium markedly shortened its time course of action.     

Complete heart block during anaesthesia in a patient with sarcoidosis

An apparently fit young man with sarcoidosis developed complete heart block during an emergency mastoidectomy. A temporary transvenous pacemaker was inserted, but permanent pacing was required in the postoperative period. The clinical and pathological features of cardiac sarcoidosis are described; complete heart block is the commonest presentation of cardiac involvement. The role of anaesthesia as the precipitating factor in this case is discussed.     

Use of cisatracurium during fast-track cardiac surgery

We prospectively studied spontaneous recovery from cisatracurium-inducedneuromuscular block in 18 patients scheduled for cardiac surgery,and its suitability for fast-track cardiac surgery. Neuromuscularblock was induced by an i.v. bolus (range 0.15–0.3 mgkg^–1) and maintained by a continuous infusion (range 1.1–3.2µg kg^–1 min^–1) of cisatracurium until sternalclosure. In the intensive care unit (ICU), spontaneous recoverywas evaluated by the train-of-four (TOF) ratio measured at theadductor pollicis muscle. The ICU medical staff were unawareof the TOF ratios until sedation was stopped. At that time,if the TOF ratio was less than 0.9, sedation was recommenced.On arrival in ICU, all patients had residual paralysis. Themean time to reaching a TOF ratio of at least 0.9 was 102 min(range 74–144 min) after discontinuation of the cisatracuriuminfusion. Fifteen patients (83%) were successfully extubatedduring the first 8 h after stopping the cisatracurium infusion.Only one patient showed residual paralysis when sedation wasdiscontinued. These results support the use of cisatracuriumas a suitable neuromuscular blocking agent for fast-track cardiacsurgery. Br J Anaesth 2001; 86: 130–2     

Comparison of a new neuromuscular transmission monitor compressomyograph with mechanomyograph

BACKGROUND: We developed a new neuromuscular transmission monitor, the compressomyograph (CMG, European patent number: EP 06018557.6, US patent number: US 60/824.541). This is the first preliminary report comparing neuromuscular block monitored by CMG and the Relaxometer mechanomyograph (MMG). METHODS: The two monitors were randomly allocated to the left or right hands of 16 patients. T1, first twitch of the train-of-four (TOF) expressed as percentage of control response, and the TOF ratio (T4:t1) were used to evaluate the neuromuscular block produced by rocuronium 0.6 mg kg(-1). RESULTS: The CMG monitor exhibited no pre-relaxation reverse fade (T4>T1) or T1 exceeding 100%. There was no significant difference in mean (SD) onset time, Dur(25) (time to T1 25% recovery), or Dur(0.9) (time to 0.9 TOF ratio recovery) measured by the CMG [2.4 (0.9), 22.6 (4.1), 43.1 (10.3) min, respectively] compared with MMG [2.1 (0.9), 22.9 (3.3), 43.3 (10.0) min, respectively]. According to Bland and Altman analysis, the bias (upper and lower limits of agreement) for T1% was -0.3% (+13.4% and -13.8%) and for TOF ratio was -0.009 (+0.068 and -0.085). CMG showed 100% sensitivity and 75% specificity in indicating full relaxation for tracheal intubation, and 80% sensitivity with 86% specificity in predicting MMG 0.9 TOF ratio. CONCLUSIONS: The CMG could be a reliable clinical monitor in the daily anaesthesia practice that does not require time to set up or rigid support of the arm.     

The new neuromuscular blocking agents: do they offer any advantages?

Br J Anaesth 2001; 87: 912–25     

Rapacuronium recovery characteristics and infusion requirements during inhalation versus propofol-based anaesthesia

We examined the effect of four maintenance anaesthetics on theneuromuscular blocking activity and spontaneous recovery characteristicsafter a short-term infusion of rapacuronium. Eighty ASA I–IIIadult patients undergoing elective surgery were studied at fourcentres. Anaesthesia was induced with propofol 1.5–2.5 mg kg^–1and fentanyl 1–2 µg kg^–1, followedby a bolus of rapacuronium 1.5 mg kg^–1. Thepatients were randomized to receive either desflurane (2–4%end-tidal, ET), sevoflurane (0.75–1.5% ET), isoflurane(0.4–0.8% ET), or a propofol infusion (75–150 µg kg^–1 min^–1)for maintenance of anaesthesia in combination with nitrous oxide(60–70%) in oxygen. When the first twitch (T₁) of a train-of-fourstimulus (using the TOF Guard^® accelerometer) returned to5%, an infusion of rapacuronium was started at 3 mg kg^–1 h^–1and adjusted to maintain T₁/T₀ at 10%. The duration of infusionlasted between 45 and 60 min, and the average infusionrates of rapacuronium were similar in all groups, ranging from1.6 to 2.5 mg kg^–1 h^–1. There wereno significant differences among the groups in the times forT₁/T₀ to return to 25%, 75% or 90%, or for T₄/T₁ to return to70% and 80% upon discontinuation of the infusion. When potentinhalation anaesthetics are used in clinically relevant concentrationsfor maintenance of anaesthesia, the neuromuscular recovery profileof rapacuronium administered as a variable-rate infusion forup to 1 h is similar to that found with a propofol-basedanaesthetic technique. Br J Anaesth 2000; 85: 302–5     

Neostigmine-induced reversal of vecuronium in normal weight, overweight and obese female patients

Background. The purpose of this study was to compare neostigmine-inducedreversal of vecuronium in normal weight, overweight and obesefemale patients. Methods. In total, 15 each of normal weight (18.5BMI<25),overweight (25BMI<30) and obese (BMI30) patients were enrolled.Anaesthesia was induced and maintained with fentanyl, propofoland nitrous oxide. Neuromuscular block was induced with vecuronium0.1 mg kg^–1 on the basis of the patient's real body weight(RBW) and was monitored using acceleromyographic train-of-four(TOF) of the adductor pollicis. All patients received neostigmine0.04 mg kg^–1 combined with atropine 0.02 mg kg^–1at 25% recovery of the first twitch (T1) of TOF and were allowedto recover to a TOF ratio of 0.9. Results. The time from administration of vecuronium to spontaneousrecovery of T1 to 25% of control was significantly longer inthe obese [mean (SD, range); 68.4 (16.3, 39.8–110.8) min]and the overweight groups [49.3 (6.2, 39.8–60.8) min]as compared with the normal weight group [41.0 (9.0, 27.5–59.5)min]. The times for facilitated recovery with neostigmine toa TOF ratio of 0.7 did not differ among groups. However, therecovery to a TOF ratio of 0.9 in the obese [25.9 (6.7, 13.5–41.0)min] and the overweight groups [14.6 (7.7, 3.3–28.5) min]were significantly longer than that in the normal weight group[6.9 (2.0, 3.0–10.7) min]. Conclusions. Early reversal after neostigmine is prompt; however,recovery to a TOF ratio of 0.9 is slow in overweight and obesepatients when vecuronium is dosed on the basis of the patient'sRBW.     

Rocuronium in infants, children and adults during balanced anaesthesia

We studied 20 infants, 20 children and 20 adults during balanced anaesthesia to compare the neuromuscular blocking effects of rocuronium in these age groups. Neuromuscular function was recorded by adductor pollicis emg and a cumulative log-probit dose-response curve of rocuronium was established. Thereafter, full spontaneous recovery of the neuromuscular function was recorded. Onset time of the first dose of rocuronium was shorter in children than in infants or adults. The potency of rocuronium was greatest in infants and least in children; the ED₅₀ doses (mean ± SD) being 149 ± 36 μg˙kg^?1 in infants, 205 ± 52 μg˙kg^?1 in children and 169 ± 47 μg˙kg^?1 in adults (P<0.05 between infants and children) and the ED₉₅ doses being 251 ± 73 μg˙kg^?1, 409 ± 71 μg˙kg^?1 and 350 ± 77 μg˙kg^?1, respectively (P<0.05 between all groups). The emg recovery following an average 94.5 ± 4.8% neuromuscular blockade established by rocuronium was roughly similar in all study groups. Thus, one ED₉₅ dose of rocuronium, unlike vecuronium, acts as an intermediate-acting agent in all age groups.     

Neuromuscular effects of rocuronium in children during halothane anaesthesia

Rocuronium bromide, a nondepolarizing muscle relaxant has been shown to have a short onset and intermediate duration of action in adults and young children. We evaluated onset time, intubating conditions, as well as duration of action of rocuronium in children ages four to 12 years during nitrous oxide-halothane anaesthesia. Following a stable recording of train-of-four (TOF) impulses at the ulnar nerve, patients were given rocuronium 600 μg˙kg^?1 intravenously. We found that the time to 90% and 100% neuromuscular (N-M) block of the (TOF) was 51 ± 18 s and 66 ± 32 s respectively. Intubation was achieved at 94 ± 31 s and rated as good or excellent in all cases. Time to recovery of N-M transmission to 25%, 75% and 90% of control was 29 ± 8 min, 42 ± 14 min and 46 ± 16 min respectively. Heart rate increased ～12 BPM after drug injection, while the blood pressure remained unchanged. From our data we conclude that, as in other age groups, rocuronium has a rapid onset, intermediate duration of action in children 4–12 years of age, and appears devoid of significant side effects.     

Onset and duration of mivacurium-induced neuromuscular block in patients with Duchenne muscular dystrophy

Background. To determine the response to mivacurium, we prospectivelystudied onset time and complete spontaneous recovery from mivacurium-inducedneuromuscular block in patients with Duchenne muscular dystrophy(DMD). Methods. Twelve boys with DMD, age 5–14 yr, seven of themwheelchair-bound, ASA II–III, and 12 age- and sex-matchedcontrols (ASA I) were enrolled in the study. Anaesthesia wasinduced with fentanyl 2–3 µg kg^–1 and propofol3–4 mg kg^–1 titrated to effect, and maintained bycontinuous i.v. infusion of propofol 8–12 mg kg^–1and remifentanil as required. The lungs were ventilated withoxygen in air. Neuromuscular transmission was assessed by acceleromyographyusing train-of-four (TOF) stimulation every 15 s. After baselinereadings, a single dose of mivacurium 0.2 mg kg^–1 wasgiven. The following variables were recorded: (i) lag time;(ii) onset time; (iii) peak effect; (iv) recovery of first twitchfrom the TOF response to 10, 25 and 90% (T₁₀, T₂₅, T₉₀) relativeto baseline; (v) recovery index (time between 25 and 75% recoveryof first twitch); and (vi) recovery time (time between 25% recoveryof first twitch and recovery of TOF ratio to 90%). For comparisonbetween the groups the Mann–Whitney U-test was applied. Results. There were no differences between the groups in lagtime, onset time and peak effect. However, all recorded recoveryindices were significantly (P<0.05) prolonged in the DMDgroup. The median (range) for time points T₁₀, T₂₅ and T₉₀ inthe DMD and control group was 12.0 (8–16) vs 8.4 (5–15)min, 14.1 (9–20) vs 10.5 (7–17) min and 26.9 (15–40)vs 15.9 (12–23) min, respectively. The recovery indexand recovery time were similarly prolonged in the DMD group. Conclusions. These results support the assumption that mivacurium-inducedneuromuscular block is prolonged in patients with DMD. This study was presented at the Annual Meeting of the AmericanSociety of Anaesthesiologists, Las Vegas, October 2004. These authors contributed equally to this work.     

Spontaneous remission of left bundle branch block during anaesthesia

Routine pre-operative evaluation of a 58-year-old man scheduled for repair of an inguinal hernia, disclosed a blood pressure of 200/100 mmHg. This decreased to 150/100 mmHg after a period of rest. An electrocardiogram taken as a result of this chance finding showed left bundle branch block. There were no other cardiovascular symptoms or signs. Soon after induction of general anaesthesia, the conduction defect disappeared. The return to sinus rhythm was sudden and sustained and was not related to changes in heart rate or blood pressure. One month later, his electrocardiograph remained normal.     

Effect of an intubation dose of rocuronium on Spectral Entropy and Bispectral Index responses to laryngoscopy during propofol anaesthesia

Background. The spectral entropy of the electroencephalogramhas been proposed to monitor the depth of anaesthesia. StateEntropy (SE) reflects the level of hypnosis. Response Entropy(RE), computed from electroencephalogram and facial muscle activity,reflects the response to nociceptive stimulation. We evaluatedthe effect of rocuronium on Bispectral Index^TM (BIS) and entropyresponses to laryngoscopy. Methods. A total of 25 patients were anaesthetized with propofolusing a target-controlled infusion. At steady state, they randomlyreceived 0.6 mg kg^–1 rocuronium (R) or saline (S). After3 min, a 20 s laryngoscopy was applied. BIS, RE and SE wererecorded continuously and averaged over 1 min during baseline,at steady state, 2 min after R or S administration (R/S+2) and0, 1, 2 and 3 min after laryngoscopy (L0, L1, L2, L3). Results. At R/S+2, the RE–SE gradient was higher in GroupS than in Group R. Laryngoscopy provoked an increase in BIS,RE and SE. Comparing R/S+2 and L0 values in Groups R and S,BIS increased from 43 (6) to 49 (8) and 42 (9) to 51 (15), SEincreased from 43 (7) to 50 (8) and 41 (10) to 55 (12), andRE increased from 46 (8) to 54 (9) and 47 (12) to 66 (15), respectively.BIS and SE did not differ between groups. At L0, RE and RE–SEwere higher in Group S [66 (15) and 11 (4), respectively] thanin Group R [54 (9) and 4 (2), respectively]. Conclusions. Rocuronium alters the RE–SE gradient andthe RE and RE–SE responses to laryngoscopy. Muscle relaxationmay confound interpretation of entropy monitoring.     

Acute motor axonal polyneuropathy after a cisatracurium infusion and concomitant corticosteroid therapy

A 40-yr-old male was admitted to the intensive care unit followingblunt chest trauma. He had multiple rib fractures, bilateralpneumothoraces, and acute respiratory failure requiring mechanicalventilation. Sedation was achieved with midazolam and morphine,and later with propofol. The patient was paralysed with a continuousinfusion of cisatracurium 1.42–5.75 µg kg^–1min^–1. Methylprednisolone 125 mg i.v. every 12 h was alsostarted. After discontinuation of the cisatracurium infusion7 days later, the patient manifested a flaccid quadriplegiawith absence of deep-tendon reflexes. No sensory deficits wereobserved. Electromyography (EMG), repetitive nerve stimulationtesting, and single fibre EMG (SFEMG) were performed at regularintervals after stopping cisatracurium. Clinical symptoms andelectrophysiological examinations supported the diagnosis ofacute motor axonal polyneuropathy related to concomitant administrationof cisatracurium and corticosteroid therapy. Br J Anaesth 2004; 92: 289–93     

Infusion of amino acid enriched solution hastens recovery from neuromuscular block caused by vecuronium

We investigated the effect of an amino acid infusion on neuromuscularblock produced by vecuronium, and on rectal temperature andsurface temperature over the adductor pollicis muscle. Sixtyadult patients undergoing general anaesthesia were randomlydivided into four groups of 15 patients each: amino acid (AA)-post-tetaniccount (PTC); AA-train-of-four (TOF); control (C)-PTC; or C-TOFgroup. In the AA-PTC and AA-TOF groups, after a bolus of vecuronium0.1 mg kg^–1, a continuous infusion of an 18 amino acidenriched solution (AMIPAREN^®) was started at a rate of 166kJ h^–1. In the C-PTC and C-TOF groups, normal saline wasadministered. Time from vecuronium to the return of the PTCin the AA-PTC group was significantly shorter than in the C-PTCgroup (mean (SD), 13.3 (4.5) versus 18.0 (5.6) min, P<0.05).Times to return of T1, T2, T3, and T4 (first, second, third,and fourth twitch of TOF) in the AA-TOF group were significantlyshorter than in the C-TOF group (21.1 (4.5) versus 28.0 (8.2)min for T1, P<0.05). PTC in the AA-PTC group was significantlygreater than in the C-PTC group; 25–35 min after administrationof vecuronium (P<0.05). T1/T0 and T4/T1 in the AA-TOF groupwere significantly higher than in the C-TOF group, 40–120and 50–120 min after vecuronium respectively (P<0.05).Rectal temperature and surface temperature over the adductorpollicis muscle in the AA-PTC and AA-TOF groups were significantlyhigher than in the control groups 50–120 and 100–120min after vecuronium respectively (P<0.05). Infusion of aminoacid enriched solution hastens recovery from neuromuscular block. Br J Anaesth 2001; 86: 814–21