Risk factors for sensorineural hearing loss in survivors with severe congenital diaphragmatic hernia.

Recent improvements in perinatal management have improved the prognosis in patients with severe congenital diaphragmatic hernia (CDH). However, in surviving patients with severe CDH, hearing loss has sometimes been reported to occur during the follow-up period. Although some of the risk factors for developing sensorineural hearing loss (SNHL) have been reported in CDH, no definitive risk factors have yet been reported. We, therefore, investigated the risk factors regarding postnatal management in patients with severe CDH. In 16 surviving patients with severe CDH, which had all been detected antenatally, and whose lung-to-thoracic ratio was less than 0.2, four patients demonstrated late onset SNHL, which occurred between 1.5 and 5 years of age. The risk factors for SNHL regarding the postnatal treatment for CDH were analyzed between the four patients with SNHL and the remaining 12 patients without SNHL, regarding such factors as the use of ototoxic drugs, neuromuscular blocking agents, high-frequency oscillation (HFO), and inhaled nitric oxide, the duration of hypocapnia, hypoxia, severe acidosis, severe alkalosis, and mechanical ventilation. In addition, the types of neuromuscular blocking agents were also analyzed, including the administration of pancuronium bromide (PB) and vecuronium bromide (VB). The patients with SNHL were found to have a significantly higher risk than the patients without SNHL regarding the duration of loop diuretics usage and the duration of usage of both mechanical ventilation and HFO. Furthermore, all four patients with SNHL used PB. In contrast, none of the five patients using VB developed SNHL The duration and cumulative dose of PB used in the patients with severe CDH showed a significant correlation to the occurrence of SNHL. Although this study was retrospective, based on our data, the prolonged use of PB, in addition to the duration of treatment by loop diuretics, mechanical ventilation, and HFO usage, might, thus, be suggested to be a possible risk factor for late onset SNHL in patients with severe CDH.

Neuroparalysis and ventilatory support in severe tetanus.

In severe form of tetanus, even with maximum dose of muscle relaxants, spasms and apnoeic spells may persist and that may be life-threatening. The aim of this study was to assess the effect of neuroparalysing the patients and then providing ventilatory support in bringing about their recovery. Forty-nine adult patients of severe tetanus (Ablett's grade IIIA--6 patients and Ablett's grade IIIB--43 patients) were studied during the period from April, 1993 to February, 1996. Mean period of onset ie, period from trismus to first spasm, in these patients was 24 hours. Patients were neuroparalysed with a bolus dose of 2-4 mg of pancuronium followed by a continuous infusion of 1-2 mg/hour and simultaneously supported with mechanical ventilation until spasms subsided. Fourteen patients (28.6%) survived and rest died. Mean duration of ventilatory support on survived patients was 14.4 days. The commonest complication encountered during ventilatory support was respiratory tract infection observed in 36 patients (73.5%). Commonest cause of death was autonomic imbalance encountered in 15 patients (30.6%). Treatment of choice in severe tetanus should be neuroparalytic ventilatory support. With use of new generation ventilators and better intensive care facility, death in severe tetanus is likely to be very less.

Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure.

AIM: To determine relationships between ototoxic drugs and 4-y sensorineural hearing loss (SNHL) in near-term and term survivors of severe neonatal respiratory failure. METHODS: All 81 survivors of the Canadian arm of the Neonatal Inhaled Nitric Oxide Study (mortality 32, loss to follow-up 9) received loop diuretics, aminoglycosides, and neuromuscular blockers (NMB), and 50 received vancomycin as neonates. Prospective, longitudinal secondary outcome using audiological tests diagnosed late-onset, progressive SNHL in 43 (53%); not flat (sloping) in 29, flat (severe to profound) in 14. Risk for SNHL was determined. RESULTS: A combination of duration of diuretic use of >14 d and average NMB dose of >0.96 mg/kg/d contributed to SNHL among survivors (odds ratio 5.2; 95% CI 1.6, 16.7). Markers of illness severity did not contribute. Dosage or duration of aminoglycosides use did not relate to SNHL. Cumulative dosages and duration of use of diuretics; NMB; use of vancomycin; and overlap of diuretics with NMB, aminoglycosides, and vancomycin individually linked to SNHL (p<0.001). CONCLUSION: Overuse of loop diuretics and/or NMB contributes to SNHL after neonatal respiratory failure; markers of illness severity or the appropriate administration of aminoglycosides do not.

Interaction between mivacurium and pancuronium: impact of the order of administration.

INTRODUCTION: Potentiation of mivacurium by low-dose pancuronium is mostly due to an inhibition of plasma butyryl cholinesterase (BchE) resulting in a decreased rate of hydrolysis of mivacurium. Nevertheless, an interaction at the receptor site could not be ruled out. By changing the order of the muscle relaxant injections, we may lessen the pharmacokinetic interaction and assess the impact at the acetylcholine receptor level. METHODS: Twenty patients scheduled for general anesthesia with propofol and fentanyl, and isoflurane were randomized into two groups receiving, mivacurium 100 microg kg-1 followed by pancuronium 15 microg kg-1 (group 1) or pancuronium 15 microg kg-1 followed by mivacurium 100 microg kg-1 (group 2). BchE before and after injection of each relaxant was measured. Neuromuscular block was assessed with a force transducer at the adductor pollicis measuring the elicited twitch to ulnar nerve stimulation. RESULTS: The neuromuscular block was greater when pancuronium was administered before mivacurium (100% versus 96+/-3%; P<0.05). Times to recovery of the elicited twitch response to 25% and 75% of control value were increased by 100% (P<0.05). After pancuronium, decreases in BchE of 11% and 14% in groups 1 and 2 were observed, respectively. CONCLUSION: Interaction between mivacurium and low dose pancuronium is significant only when mivacurium is injected after pancuronium.

Effects of priming with pancuronium or rocuronium on intubation with rocuronium in children.

Rocuronium is a non-depolarizing neuromuscular blocking agent which has a rapid onset and intermediate duration of action. The goal of this study was to compare the neuromuscular blocking actions of rocuronium with and without a priming dose of pancuronium or rocuronium in children. Thirty patients were randomly allocated into 3 groups. Ten patients received a single dose of 0.6 mg/kg rocuronium (Group I). The others received either 0.015 mg/kg pancuronium (Group II) or 0.06 mg/kg rocuronium (Group III) 3 minutes before an intubating dose of 0.54 mg/kg rocuronium was given. Neuromuscular blockade was measured via accelerographic response to single stimulations (1 Hz) of the ulnar nerve until maximal twitch depression was reached followed by train-of-four (TOF) stimuli (2 Hz) at 15 second intervals for the remainder of recovery. Groups were compared with regard to onset time, duration and recovery indices. The onset time and duration of block did not differ significantly between groups. However, the time to recovery in group II (24.5 +/- 9.9 min) was significantly prolonged compared to that in group I (12.7 +/- 3.1 min) or group III (12.7 +/- 3.9 min). We concluded that the use of rocuronium with a preceding dose of either pancuronium or rocuronium provided no advantage for intubation in children.

Effects of priming with pancuronium or rocuronium on intubation with rocuronium in children

Rocuronium is a non-depolarizing neuromuscular blocking agent which has a rapid onset and intermediate duration of action. The goal of this study was to compare the neuromuscular blocking actions of rocuronium with and without a priming dose of pancuronium or rocuronium in children. Thirty patients were randomly allocated into 3 groups. Ten patients received a single dose of 0.6 mg/kg rocuronium (Group I). The others received either 0.015 mg/kg pancuronium (Group II) or 0.06 mg/kg rocuronium (Group III) 3 minutes before an intubating dose of 0.54 mg/kg rocuronium was given. Neuromuscular blockade was measured via accelerographic response to single stimulations (1 Hz) of the ulnar nerve until maximal twitch depression was reached followed by train-of-four (TOF) stimuli (2 Hz) at 15 second intervals for the remainder of recovery. Groups were compared with regard to onset time, duration and recovery indices. The onset time and duration of block did not differ significantly between groups. However, the time to recovery in group II (24.5 +/- 9.9 min) was significantly prolonged compared to that in group I (12.7 +/- 3.1 min) or group III (12.7 +/- 3.9 min). We concluded that the use of rocuronium with a preceding dose of either pancuronium or rocuronium provided no advantage for intubation in children.

A quantitative study of the pancuronium antagonism at the motor endplate in human organophosphorus intoxication.

Nine patients with organophosphorus (OP) intoxication developing neuromuscular transmission defects were given pancuronium 1, 2, or 4 mg intravenously (IV). Thirteen patient controls with hypoxic encephalopathy received similar dosages. The responses were monitored electrophysiologically using single and repetitive nerve stimulation (20 and 50 Hz). In OP patients, pancuronium did not alter the amplitude of the single CMAP, whereas its repetitive discharges were reduced. Severe neuromuscular blocks were reversed only partially by pancuronium 4 mg. In less severe blocks, 1 and 2 mg resulted in marked improvement. In the patient controls, pancuronium 4 mg induced a severe neuromuscular block but not with 1 and 2 mg. Pancuronium dosages necessary to reverse severe OP-induced neuromuscular blockade produce a neuromuscular block when AChE activity is normal. Low dosages have little effect on normal neuromuscular transmission, but improve the block to a mild degree and may be useful as part of treatment in OP intoxications.

Double-blind, randomized, multicenter study of doxacurium vs. pancuronium in intensive care unit patients who require neuromuscular-blocking agents.

OBJECTIVE: To compare the neuromuscular-blocking and hemodynamic effects of doxacurium vs. pancuronium administered by intermittent bolus to intensive care unit (ICU) patients who required neuromuscular block to facilitate mechanical ventilation for > or = 24 hrs. DESIGN: A multicenter, prospective, double-blind, randomized study comparing doxacurium, a new benzylisoquinolone neuromuscular-blocking agent, with pancuronium. SETTING: ICUs of three tertiary care hospitals. PATIENTS: Forty critically ill patients (29 male, 11 female) with an average age of 52.5 yrs (range 19 to 80). INTERVENTIONS: With approval of our Institutional Review Boards and after obtaining informed consent, 40 critically ill patients were entered into the study. Histories and the results of physical examinations were recorded, laboratory data were collected, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated during the 8 hrs before the start of the study medication. Patients received either doxacurium (initial dose of 0.04 mg/kg) or pancuronium (initial dose of 0.07 mg/kg) by bolus injection with continuous measurement of vital signs every minute for 15 mins. We measured the degree of neuromuscular blockade using a peripheral-nerve stimulator to measure the Train-of-Four count. Patients were rebolused (doxacurium dose of 0.025 mg/kg, pancuronium dose of 0.05 mg/kg) based on clinical criteria, which were substantiated by measurement of the Train-of-Four count. The neuromuscular-blocking drugs were stopped when the patient no longer required paralysis or after 5 days of therapy, whichever came first. Group comparisons were made using repeated measures analysis of variance, Fisher's exact test, and two sample t-tests, when appropriate. Spearman's rank-correction coefficients were calculated to assess the relationship of onset time and recovery time with all baseline laboratory values and the APACHE II scores. A p < .05 was used to establish statistical significance. MEASUREMENTS AND MAIN RESULTS: There were no differences between the two groups with respect to age, gender, or APACHE II scores. There were no differences between groups in terms of adverse experiences, nor with respect to time of onset of block, number of doses, or the duration of neuromuscular blockade (2.6 vs. 2.2 days for doxacurium vs. pancuronium, respectively). There was a statistically significant increase in heart rate after the initial dose of pancuronium (120 +/- 23 vs. 109 +/- 22 beats/min postinjection vs. preinjection, respectively; p < .05) without any differences noted after doxacurium (107 +/- 21 vs. 109 +/- 21 beats/min, respectively). Furthermore, once neuromuscular block was discontinued, the pancuronium group had a more prolonged and variable recovery time (279 +/- 229 mins) compared with the doxacurium group (138 +/- 46 mins, p < .05). CONCLUSIONS: In critically ill patients requiring neuromuscular block for > 24 hrs, doxacurium was well tolerated without evidence of tachycardia and with a relatively prompt recovery profile.

Pancuronium attenuates associated hemodynamic and transcutaneous oxygen tension changes during nursery procedures.

Intermittent increases in blood pressure (BP) associated with motor activity have been implicated in the pathogenesis of intraventricular hemorrhage in premature infants. Inhibition of motor activity by pancuronium administration has also been shown to stabilize cerebral blood flow velocity (CBFV) and BP patterns. The purpose of this study was to determine whether administration of pancuronium to ill premature infants would attenuate changes in BP and transcutaneous oxygen tension (TcPO2) and the variability of CBFV pattern associated with common nursery procedures. Fourteen premature infants in the study were given a single dose of pancuronium bromide at a dose of 0.1 mg/kg intravenously. BP and TcPO2 changes were monitored during nursery procedures, that is, during radial artery blood gas sampling and a head ultrasonographic/Doppler procedure, before and during pancuronium therapy. During arterial blood gas sampling, mean percent increase in BP was significantly greater (32% +/- 21%) before pancuronium administration compared with 21% +/- 13% during pancuronium use (p < 0.05). Mean percent changes in TcPO2 were -30% +/- 21% and 5.8% +/- 7.2% before and during pancuronium use, respectively (p < 0.05). Similar significant changes in BP and TcPO2 were observed with a head ultrasonographic/Doppler procedure. Coefficients of variation of systolic and mean CBFV also decreased significantly during pancuronium therapy. We observed short-term benefits with pancuronium use on vascular dynamics and oxygenation during nursery procedures. Further studies are needed to evaluate the use of pancuronium in preterm babies supported by mechanical ventilation during the first few days of life for possible prevention of intraventricular hemorrhage, the pathophysiologic mechanism of which may be related to hemodynamic and biochemical derangement.

Plasma beta-endorphin concentrations and analgesia-muscle relaxation in the newborn infant supported by mechanical ventilation.

We evaluated the effects of pancuronium and opiates on plasma beta-endorphin concentrations in 25 infants supported by mechanical ventilation. Infants receiving opiate were randomly assigned to receive either fentanyl or morphine. There was no change in beta-endorphin concentrations after administration of pancuronium, whereas both fentanyl and morphine reduced beta-endorphin concentrations by approximately 60%.

[Status asthmaticus. Acute myopathy induced by cortisone and neuropathy during resuscitation]. / Etat de mal asthmatique. Myopathie aiguë cortisonique et neuropathie de réanimation.

A female patient treated by mechanical ventilation with high doses of pancuronium and methylprednisolone for status asthmaticus presented with acute total areflexic and severe amyotrophic tetraplegia; she died after multiple organ failure. Muscle biopsy confirmed the clinical diagnosis of "acute corticosteroid myopathy", precipitated by a corticosteroid "disuse hypersensitivity" after pancuronium. The electromyogram showed a critical illness polyneuropathy, secondary to multiple organ failure. Nerve biopsy was normal. The respective parts played by corticosteroids, curare-like derivatives and intensive care in the genesis of unexplained difficulty in weaning from the ventilator are discussed.

[Rhabdomyolysis in severe acute asthma]. / Rhabdomyolyse au cours d'un asthme aigu grave.

A case is reported of a 74-year-old man who developed rhabdomyolysis during treatment for status asthmaticus. This patient had a history of asthma. He was admitted after a cardiac arrest during a severe asthma attack. Continuous muscle relaxation (4 mg.h-1 of pancuronium for 10 days; total dose 960 mg) was required to carry out mechanical ventilation. Bronchodilators and high doses of steroids (300 mg.day-1 of methylprednisolone for 10 days) were also given. After the administration of muscle relaxant had been discontinued, the patient displayed a severe, predominantly proximal, quadriplegia as well as a raised blood creatinine kinase concentration. The urine was brown coloured over a 24 h period. Rhabdomyolysis was confirmed by muscle biopsy. The patient recovered over a period of one month. This case is discussed in the light of some other similar reports in the literature. It seems that the combination of muscle relaxant with high doses of steroids is to be incriminated.

Effect of morphine and pancuronium on the stress response in ventilated preterm infants.

Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.

Rapid-sequence intubation of head trauma patients: prevention of fasciculations with pancuronium versus minidose succinylcholine.

INTRODUCTION: Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration. Standard rapid-sequence intubation requires a nondepolarizing blocking agent before succinylcholine administration. HYPOTHESIS: Prevention of fasciculations during rapid-sequence intubation of head trauma patients can be accomplished as safely and effectively with minidose succinylcholine as with a defasciculating dose of pancuronium. DESIGN: A prospective, randomized, double-blind study. SETTING: An inner-city county trauma center with 70,000 patient visits per year. PARTICIPANTS: Sequential adult head trauma patients requiring rapid-sequence intubation who had no contraindications to succinylcholine or pancuronium. INTERVENTIONS: Each head trauma patient requiring rapid-sequence intubation who met the inclusion criteria received standard rapid-sequence intubation maneuvers and lidocaine (1 mg/kg) IV. Patients were randomized to receive either minidose succinylcholine (0.1 mg/kg) or pancuronium (0.03 mg/kg) IV one minute prior to the full paralytic dose of succinylcholine (1.5 mg/kg) IV. Fasciculations were recorded using a graded visual scale. RESULTS: Of 46 patients, eight of 19 (42%) in the pancuronium group and six of 27 (22%) in the succinylcholine group experienced fasciculations. No statistically significant difference in fasciculations was detected between the two groups using chi 2 analysis. Complete relaxation of the cords was present in all but two patients, one in each group. No patient in either group experienced emesis or significant dysrhythmias. CONCLUSION: Pretreatment with minidose succinylcholine causes no greater incidence of fasciculations than pancuronium in rapid-sequence intubation of head trauma patients in an ED setting. Thus succinylcholine may be used as the sole paralytic agent in rapid-sequence intubation of head trauma patients.

Holistic care of the patient receiving pancuronium bromide.

Pancuronium bromide therapy can be devastating to patient and family alike. However, with an understanding of the effects of drug administration, and following the holistic care considerations, the critical care nurse can provide a successful outcome for the patient.

Pancuronium improves the neuromuscular transmission defect of human organophosphate intoxication.

Two patients with acute severe organophosphate intoxication showed (1) single evoked compound muscle action potentials (CMAP) with repetitive discharges and (2) prominent decremental responses of CMAP with 20 and 50 Hz supramaximal nerve stimulation. Following the intravenous injection of single small doses of pancuronium, marked improvement in these abnormalities occurred and persisted for several hours. We postulate that the physiologic improvement following low-dose pancuronium results from blockade of acetylcholine receptors, especially those located on the terminal axon responsible for antidromic backfiring.

Comparative clinical evaluation of chandonium iodide and pancuronium bromide as muscle relaxant.

Chandonium iodide, a synthetic non-depolarising neuromuscular blocking agent and pancuronium bromide were clinically compared as muscle relaxants in 62 patients undergoing elective surgery. Anaesthesia was induced by thiopentone sodium and maintained by oxygen and nitrous oxide. Assessment of efficacy of both the muscle relaxants was graded taking into consideration intubating condition and muscular relaxation during surgery. Tolerability was assessed by noting the changes in heart rate, blood pressure and biochemical estimations. Efficacy of chandonium iodide in the dose of 0.15 to 0.18 mg/kg was comparable to that of 0.08 to 0.1 mg/kg of pancuronium bromide. Both the drugs were well tolerated.

[Patients with severe tetanus treated in the department of infectious diseases in 1986-1988]. / Chorzy na tezec o przebiegu ciezkim leczeni w klinice chorób zakaznych w latach 1986-1988.

The results of treatment of patients with tetanus having severe clinical course observed in Department of Infectious Diseases in Cracow 1986-1988 have been presented. The documentation of 30 patients with tetanus undergoing intensive therapy has been analysed. The mean age of patients was 64 years. In 26 patients the controlled respiration has been used. These patients have been treated moreover by muscular relaxants such as Pavulon or rarely the tubocurarine derivatives. Among patients treated 16 deaths were noted and 14 cases were recovered.

Side effects and changes in pulmonary function after fixed dose precurarization with alcuronium, pancuronium or vecuronium.

On hundred and sixty premedicated patients undergoing surgery were assessed for changes in pulmonary function and signs of partial neuromuscular blockade following precurarization with a fixed dose of alcuronium 2 mg, pancuronium 1 mg or vecuronium 1 mg, and the efficacy of the drugs in the prevention of suxamethonium-associated side effects was compared. In this respect, no differences were observed between the three drugs. Pretreatment with alcuronium and pancuronium was followed by small decreases in pulmonary function. Statistically significant changes were seen only when vecuronium 1 mg was used as the fixed-dose precurarization agent.

Pancuronium rapid induction sequence.

Succinylcholine is traditionally used as the muscle relaxant of choice for rapid induction sequence intubation. There are, however, many absolute and relative contraindications for the use of succinylcholine necessitating the need for an alternative muscle relaxant. This study was undertaken to evaluate the effectiveness of pancuronium bromide for muscle relaxation in the rapid induction sequence in comparison to succinylcholine. A double-blind study was undertaken in 90 patients divided into two groups: One group was intubated at 60 seconds and the other at 90 seconds. Each group was divided into four subgroups by random selection and received of the following regimens: (a) succinylcholine, 1.5 mg/kg preceded by 3 mg of d-tubocurarine; (b) pancuronium bromide, 0.1 mg/kg; (c) pancuronium bromide, 0.125 mg/kg; and (d) pancuronium bromide, 0.15 mg/kg as relaxants in rapid sequence intubation. A rapid sequence intubation was performed with each intubation by a staff member or experienced house officer. Pre- and postinduction blood pressure and heart rate were taken. Postinduction blood gases were taken. The times to completion of intubation were recorded. Cord position, ease of intubation and overall relaxation were evaluated. The results indicate that in experienced hands pancuronium bromide in a dose of 0.1-0.15 mg/kg is as an effective muscle relaxant for rapid induction sequence intubation as is succinylcholine. It is an acceptable alternative when succinylcholine is contraindicated. Intubating conditions are best 90 seconds after the administration of pancuronium bromide.