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Prolonged neuromuscular blockade with pancuronium in the presence of acute renal failure: a case report.

Prolongation of neuromuscular block following pancuronium administration to anephric patients has been reported. A patient is described whose postoperative course after resection of gangrenous bowel was complicated by acute renal failure and prolonged neuromuscular blockade. A large intraoperative dose of pancuronium was administered without monitoring neuromuscular transmission with a peripheral nerve stimulator. The course was further complicated by administration of gentamicin, an antibiotic known to potentiate neuromuscular blocking drugs. Complete return of neuromuscular transmission occurred 60 hours after administration of last dose of pancuronium and subsequent to peritoneal dialysis. After rapid distribution from plasma, pancuronium, like curare, is eliminated by the renal pathway. The absence of renal excretion considerably increases the duration of action of curare when given in high doses. It has been suggested that doses of pancuronium greater than 3.6 mg/sq m or multiple doses would result in prolonged neuromuscular block in patients without renal function. The case reported illustrates the importance of monitoring neuromuscular transmission during administration of pancuronium in the presence of renal insufficiency to avoid this complication.

Acute Kidney Injury↗

Antagonism of non-depolarising neuromuscular blockade by aminopyridines in cats.

The antagonism of pipecuronium- and vecuronium-induced neuromuscular blockade by 4-aminopyridine (4AP), 3,4-diaminopyridine (3,4AP) and 3-[(dimethylamino)-carbonyl] amino-4-aminopyridine (LF14) were studied in anaesthetized cats during constant infusion of the relaxants. Aminopyridines were administered cumulatively at steady state 90% block level. The ED50 values of 4AP, 3,4AP and LF14 were 243, 106 and 254 micrograms kg-1 in pipecuronium, and 232, 195 and 235 micrograms kg-1 in vecuronium blockade. It has been assumed that in cats the anticurare effect of aminopyridines is mainly a result of K+ channel blockade on motor nerve terminals which enhances the evoked release of acetylcholine.

4-Aminopyridine↗

Prolonged neuromuscular blockade in two critically ill patients treated with atracurium.

Recent literature suggests that the risk of prolonged neuromuscular blockade associated with atracurium compared with other nondepolarizing neuromuscular blocking agents may be minimal. Two patients experienced prolonged weakness associated with the administration of atracurium. Both received atracurium 0.5-0.7 mg/kg/hour in combination with methylprednisolone 500-600 mg/day. Electromyographic results and creatine kinase levels were suggestive of muscular weakness in both patients. Despite high-dose corticosteroid therapy, the electromyographic evidence supporting prolonged weakness did not suggest typical corticosteroid myopathy. Although some clinicians advocate routine administration of atracurium in critically ill patients due to the relative lack of reports of prolonged weakness, this may be premature. Although there are fewer reports of atracurium-associated prolonged weakness compared with pancuronium and vecuronium, the patients we describe suggest that it may occur.

Aged↗

Betamethasone-induced resistance to neuromuscular blockade: a comparison of atracurium and vecuronium in vitro.

Steroids induce resistance to neuromuscular blocking drugs. Betamethasone-induced resistance to vecuronium has been demonstrated in vitro, and a presynaptic site of interaction has been suggested. This study investigated whether atracurium is similarly affected. Rat phrenic nerve-hemidiaphragm preparations were bathed in a physiologic solution, and one-half were exposed to betamethasone (1 mumol/L). Dose responses were recorded for atracurium (8-13 mumol/L) and vecuronium (2-12 mumol/L) for control and betamethasone-treated preparations. In comparison to control, the betamethasone groups had significantly less depression of muscle contraction force at all concentrations of atracurium (P = 0.0004) and vecuronium (P = 0.002). The calculated ED50 (50% depression of muscle contraction force, expressed as mean +/- SEM) for atracurium was 8.83 +/- 0.62 mumol/L for controls and 11.19 +/- 0.54 mumol/L for betamethasone-treated preparations. The calculated ED50 for vecuronium was 4.72 +/- 0.41 mumol/L for controls and 6.84 +/- 0.66 mumol/L for betamethasone-treated preparations. Betamethasone therefore increased the ED50 for atracurium by 27% and vecuronium by 45%; however, the magnitudes of these differences were not significant (P = 0.74) between the neuromuscular blocking agents. These results indicate that betamethasone-induced resistance to nondepolarizing neuromuscular blockade affects both atracurium and vecuronium to similar degrees in vitro.

Animals↗

Paramedic-administered neuromuscular blockade improves prehospital intubation success in severely head-injured patients.

BACKGROUND: The purpose of this study was to evaluate the effect of paramedic-administered neuromuscular blocking agents as part of a rapid-sequence intubation (RSI) protocol on successful intubation of severely head-injured patients in a large, urban prehospital system. METHODS: Adult head-injured patients were prospectively enrolled over 1 year using these inclusion criteria: Glasgow Coma Scale (GCS) score of 3 to 8, transport time > 10 minutes, and inability to intubate without RSI. Midazolam and succinylcholine were administered before laryngoscopy; rocuronium was given after tube placement was confirmed using capnometry, syringe aspiration, and pulse oximetry. The Combitube was used as a salvage airway device. All adult trauma victims with a GCS score of 3 to 8 were identified during the first 12 months of the study as the trial cohort and from the preceding 12 months as the control cohort. The trial and control cohorts were compared with regard to demographic data, mechanism of injury, initial vital signs, and GCS scores. The primary outcome measure was intubation success, defined as insertion of either an endotracheal tube or a Combitube, with patients stratified by GCS score. RESULTS: The trial cohort (n = 249) and control cohort (n = 189) were similar with regard to demographic data, mechanism of injury, and initial vital signs and GCS scores. Intubation success rates increased significantly during the trial period for all patients and when stratified into GCS score of 3 and GCS score of 4 to 8. The percentage of patients intubated without neuromuscular blocking agents actually increased during the trial period. Although the number of intubations by helicopter flight crews decreased during the trial, the overall use of aeromedical resources did not change. CONCLUSION: Paramedic-administered neuromuscular blockade as part of an RSI protocol improves intubation success in a large, urban prehospital system.

Adolescent↗

Dose-response relationships for edrophonium and neostigmine as antagonists of atracurium and vecuronium neuromuscular blockade.

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.

Atracurium↗

Implementing neuromuscular blockade monitoring in a surgical intensive care unit.

Long-term infusions of neuromuscular blocking agents are being used with increasing frequency in critical care areas to paralyze patients for optimal ventilatory support or to reduce patient energy demands. Prolonged weakness with no sensory disturbance has been reported in some patients. The complex nature of the critically ill patient makes the pharmacokinetics of neuromuscular blocking agents unpredictable. Monitoring neuromuscular blockade with a peripheral nerve stimulator and administering the appropriate dose may minimize the complications of its use. The CNS can be the change agent to assist the nursing staff in incorporating recent technological innovations and research findings in nursing clinical practice. The rational model of change serves as a guide when little resistance is anticipated or when change is perceived as rational.

Drug Monitoring↗

Edrophonium antagonism of pancuronium-induced neuromuscular blockade in man: a reappraisal.

The ability of edrophonium to reverse the nondepolarizing neuromuscular blockade produced by pancuronium was studied in 40 adult patients during light nitrous oxide--enflurane anesthesia. Antagonism of paralysis was attempted when the train-of-four fade ratio had spontaneous recovered in various extents. Edrophonium was administered in incremental doses intravenously either until the fade ratio increased to 0.70 or more or until the total dose of drug amounted to 0.5 mg/kg. All patients who had spontaneous recovery of train-of-four fade ratios to at least 0.10 had adequate reversal with edrophonium. When the train-of-four count was three or fewer visible twitches, the response to endrophonium was unpredictable. No evidence of recurarization was seen.

Edrophonium↗

Edrophonium priming for antagonism of atracurium neuromuscular blockade.

Edrophonium administered in divided doses has been reported to accelerate antagonism of neuromuscular blockade, i.e., a "priming" effect. Since measured onset times can be affected by the type of stimulation used, this effect was studied using both train-of-four (TOF) and single twitch (ST) stimulation. During thiopentone-nitrous oxide-enflurane anaesthesia 20 adults were given atracurium 0.5 mg.kg-1. Both ulnar nerves were stimulated with TOF every 12 sec until one per cent recovery of first twitch (T1). At this time, ST stimulation was applied to one arm, selected at random. When the mean value of T1 and ST reached ten per cent of control, edrophonium, 1 mg.kg-1, preceded by atropine was given either as a single dose, or in two doses consisting of 0.2 mg.kg-1 followed by 0.8 mg.kg-1 three minutes later. No statistically significant differences were observed between T1 and ST for the next ten minutes, whether edrophonium had been given in single or divided doses. Giving edrophonium in divided doses did not improve recovery significantly, measured with either T1, ST or train-of-four ratio (T4/T1). Five minutes after the first administration of edrophonium, T1 was (mean +/- SEM) 86 +/- 3 and 86 +/- 2 per cent control in the single and divided dose groups respectively. Corresponding values for ST were 89 +/- 1 and 89 +/- 2 per cent (NS), and for TOF, 49 +/- 3 and 57 +/- 3 per cent (NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antagonism of neuromuscular blockade but not muscle relaxation affects depth of anaesthesia.

BACKGROUND: Conflicting effects of neuromuscular blocking drugs and anticholinesterases on depth of anaesthesia have been reported. Therefore we evaluated the effect of atracurium and neostigmine on bispectral index (BIS) and middle-latency auditory evoked potentials (AAI). METHODS: We studied 40 patients (ASA I-II) aged 18-69 yr. General anaesthesia consisted of propofol and remifentanil by target-controlled infusion and neuromuscular function was monitored by electromyography. When BIS reached stable values, patients were randomly assigned to one of two groups. Group 1 received atracurium 0.4 mg kg(-1) and, 5 min later, the same volume of NaCl 0.9%; group 2 received saline first and then atracurium. When the first twitch of a train of four reached 10% of control intensity, patients were again randomized: one group (N) received neostigmine 0.04 mg kg(-1) and glycopyrrolate 0.01 mg kg(-1), and the control group (G) received only glycopyrrolate. RESULTS: Injection of atracurium or NaCl 0.9% had no effect on BIS or AAI. After neostigmine-glycopyrrolate, BIS and AAI increased significantly (mean maximal change of BIS 7.1 [SD 7.5], P<0.001; mean maximal change of AAI 9.7 [10.5], P<0.001). When glycopyrrolate was injected alone BIS and AAI also increased (mean maximal change of BIS 2.2 [3.4], P=0.008; mean maximal change of AAI 3.5 [5.7], P=0.012), but this increase was significantly less than in group N (P=0.012 for BIS; P=0.027 for AAI). CONCLUSION: These data suggest that neostigmine alters the state of propofol-remifentanil anaesthesia and may enhance recovery.

Adult↗

Motion of the diaphragm in patients with chronic obstructive pulmonary disease while spontaneously breathing versus during positive pressure breathing after anesthesia and neuromuscular blockade.

BACKGROUND: Diaphragmatic excursion during spontaneous ventilation (SV) in normal supine volunteers is greatest in the dependent regions (bottom). During positive pressure ventilation (PPV) after anesthesia and neuromuscular blockade and depending on tidal volume, the nondependent region (top) undergoes the greatest excursion, or the diaphragm moves uniformly. The purpose of this study was to compare diaphragmatic excursion (during SV and PPV) in patients with chronic obstructive pulmonary disease (COPD) with patients having normal pulmonary function. METHODS: Twelve COPD patients and 12 normal control subjects were compared. Cross-table diaphragmatic fluoroscopy was performed while patients breathed spontaneously. After anesthetic induction and pharmacologic paralysis and during PPV, diaphragmatic fluoroscopy was repeated. For analytic purposes, the diaphragm was divided into three segments: top, middle, and bottom. Percentage of excursion of each segment during SV and PPV in normal subjects was compared with the percentage of excursion of each segment in patients with COPD. RESULTS: There was no significant difference in the pattern of regional diaphragmatic excursion (as a percentage of total excursion)-top, middle, bottom-when comparing COPD patients with control subjects during SV and PPV. In the control subjects, regional diaphragmatic excursion was 16 +/- (5), 33 +/- (5), 51 +/- (4) during SV and 49 +/- (13), 32 +/- (6), 19 +/- (9) during PPV. In COPD patients, regional diaphragmatic excursion was 18 +/- (7), 34 +/- (5), 49 +/- (7) during SV and 47 +/- (10), 32 +/- (6), 21 +/- (9) during PPV. CONCLUSION: Regional diaphragmatic excursion in patients with COPD during SV and PPV is similar to that in persons with normal pulmonary function.

Aged↗

Comparison of pancuronium and vecuronium for fetal neuromuscular blockade during invasive procedures.

Neuromuscular blocking agents, used to arrest fetal motion for invasive intrauterine procedures, may cause temporary fetal heart rate changes. After 21 invasive procedures using either pancuronium bromide or vecuronium bromide, post-procedure fetal heart rate tracings were retrospectively compared. Pancuronium was associated with an increased fetal heart rate and decreased beat-to-beat variability for 2.5 hours after its use, whereas vecuronium caused no fetal heart rate changes. Vecuronium bromide offers advantages over pancuronium, because the decreased effect on the fetal heart allows better assessment of fetal well-being immediately following invasive intrauterine procedures.

Anemia↗

Pharmacoeconomic issues of sedation, analgesia, and neuromuscular blockade in critical care.

Neuromuscular blocking agents (NMBAs) are commonly prescribed as adjunct therapy for many critically ill patients. Controversy exists regarding the appropriate long-term use of these agents, particularly since there are severe potential clinical consequences. The expanded use of NMBAs has had a significant effect on the cost of ICU care. One should determine whether or not NMBAs are being used as adjunct therapy, or as a replacement for optimal sedation and/or analgesia. This article reviews some of the indicative economic issues surrounding the use of sedatives, analgesics, and NMBAs in the critical care arena. Understanding the pharmacokinetic and pharmacodynamic differences of these agents can aid in drug selection and route of administration. Appropriate drug selection can influence the pharmacoeconomics of these agents in the ICU.

Analgesia↗

The effect of midazolam pre-medication on rocuronium-induced neuromuscular blockade.

We investigated the effect of midazolam pre-medication on rocuronium-induced neuromuscular blockade during sevoflurane anaesthesia. Twenty-two patients scheduled for elective surgery were randomly divided to receive either no pre-medication (control group) or pre-medication with 0.1 mg/kg midazolam intramuscularly (midazolam group). Anaesthesia was induced with fentanyl and propofol, and maintained with sevoflurane and nitrous oxide in oxygen. Neuromuscular responses were monitored using acceleromyography. The onset and clinical duration of action, time to recovery of first twitch of train-of-four (TOF) response to 75% of control, recovery index and time for TOF recovery to 25% and 50% were recorded. Patient-related data were similar in both groups. The parameters recorded were not significantly different between the groups. Midazolam pre-medication does not influence the time-course of action of rocuronium during sevoflurane anaesthesia.

Adjuvants, Anesthesia↗

Neuromuscular blockade with magnesium sulfate and nifedipine.

A patient who received tocolysis with nifedipine developed neuromuscular blockade after 500 mg of magnesium sulfate was administered. This reaction demonstrates that nifedipine can seriously potentiate the toxicity of magnesium. Caution should be exercised when these two tocolytics are combined.

Adult↗

Accurate monitoring of neuromuscular blockade using a peripheral nerve stimulator--a review.

For normal anaesthetic practice, monitoring of neuromuscular blockade is best performed by stimulation of the ulnar nerve at the wrist with a peripheral nerve stimulator and evaluation of the response of the thumb. Determination of the initial threshold for stimulation in the awake patient to allow estimation of the current required for supramaximal stimulation is an important set-up procedure to improve accuracy. The degree of paralysis of specific muscle groups such as the diaphragm can be inferred from their sensitivity to neuromuscular blocking agents relative to adductor pollicis. Monitoring with different stimulation patterns allows a wide spectrum of muscle paralyses to be evaluated.

Electric Stimulation↗

The influence of halothane and enflurane on the reversibility of an Org NC45 neuromuscular blockade in cats.

The pharmacodynamics of neostigmine 20 micrograms kg-1 reversing a constant neuromuscular blockade from continuous infusion of Org NC 45 was studied in 17 cats. Six cats received only intravenous thiopental anaesthesia, another five received a 1 MAC (0.73%) inhalational concentration of halothane, and the remaining six cats received 1 MAC (1.68%) enflurane. In the enflurane group statistically significantly less Org NC 45 was needed to maintain the blockade (p less than 0.05). There was no difference in the degree of reversal or in the time course of the neostigmine activity between the 3 groups (p greater than 0.05). Only the duration of action of neostigmine was prolonged under halothane anaesthesia.

Animals↗