Unsuccessful lumbar puncture in a paediatric patient with achondroplasia.

We present a case of an unsuccessful lumbar puncture performed on an anaesthetised 17-year-old girl with achondroplasia who was diagnosed with and being treated for acute lymphoblastic leukaemia. Magnetic resonance imaging (MRI) subsequently showed spinal stenosis and no observable cerebrospinal fluid around the nerve roots at the levels of the lumbar pedicles and discs. A recommendation is made to obtain MRI scans before proceeding with lumbar puncture and/or spinal anaesthesia in this patient group to ensure that the anatomical features of the insertion site are favourable to a successful outcome.

Pharmacodynamics and intubating conditions of cisatracurium in children during halothane and opioid anesthesia.

STUDY OBJECTIVES: To determine the pharmacodynamics and intubating conditions of cisatracurium 0.2 mg/kg in children aged 2 to 12 years. DESIGN: Open-label, randomized study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 42 ASA physical status I and II patients, 24 to 155 months of age. INTERVENTIONS: Patients were assigned to one of two groups: halothane anesthesia (G1) and opioid anesthesia (G2). Subsequently, each group was divided into two age subgroups: 24-59 months and 60-155 months. All patients were premedicated with midazolam intranasal 0.1 to 0.2 mg/kg. In G1, anesthesia was induced with halothane up to 3% and N(2)O/O(2) (60-70/30-40%). Halothane was reduced to 0.05). CONCLUSIONS: Cisatracurium 0.2 mg/kg offered acceptable intubating conditions at 90 seconds in 98% of pediatric patients, regardless of the anesthesia-based technique. Longer clinical duration in the halothane group in younger children may be due to age-related potentiation or to the small number of patients enrolled in the younger subgroup.

Neuromuscular effects of rapacuronium in pediatric patients during nitrous oxide-halothane anesthesia: comparison with mivacurium.

PURPOSE: To describe neuromuscular effects of rapacuronium in pediatric patients during N2O-halothane anesthesia and compare them with mivacurium in children. METHODS: 103 pediatric patients, seven days -12 yr, received rapacuronium or mivacurium during N2O-halothane anesthesia. Onset and recovery of block were measured using EMG (Datex). Block was compared between groups based on drug treatment and age. Children < two years received 1 or 2 mg x kg(-1) rapacuronium: 2-12 yr received either 2 mg x kg(-1) or 3 mg x kg(-1) rapacuronium, or 0.2 mg x kg(-1) mivacurium. RESULTS: There were no differences in onset (1.7+/-1.8 min) or maximum block (T1 2.4+/-8%) among neonates, infants, and toddlers after either dose of rapacuronium. There was no difference between 1 and 2 mg x kg(-1) of rapacuronium block at 60 sec. Train-of-four ratio (T4/T1) >0.7 occurred later after 2 mg x kg(-1) than 1 mg x kg(-1) in these patients (P<0.05). There was no difference in T25 among neonates, infants and toddlers for 1 mg x kg(-1) or 2 mg x kg(-1) doses. Rapacuronium, 3 mg x kg(-1), produced maximum block 1.5 min earlier than did mivacurium, 0.2 mg x kg(-1) (P<0.001). There was no difference in block at 60 sec, maximum block or time to maximum block between 2 and 3 mg x kg(-1) rapacuronium for children > two years of age. Maximum block occurred 1.0+/-0.5 min after 2 or 3 mg x kg(-1) when T1 was 0.2+/-1.1% of baseline. T25 and T4/T1 >0.7 occurred 10 to 11 min later after this dose of rapacuronium than after mivacurium. CONCLUSION: Rapacuronium produces block earlier than mivacurium. Recovery from rapacuronium block is dose related and slower than that following mivacurium during halothane anesthesia.

Influence of the priming technique on pharmacodynamics and intubating conditions of cisatracurium.

STUDY OBJECTIVES: To determine the effects of the priming technique on the intubating conditions and pharmacodynamics of different doses of cisatracurium. DESIGN: Open-label, randomized study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 60 ASA physical status I, II, and III female patients. INTERVENTIONS: Patients were randomly assigned to one of four groups. Patients from Groups 1, 2, and 3 received 0.01 mg/kg cisatracurium as a priming dose, and patients from Group 4 received placebo. Four minutes later, patients from Groups 1, 2, 3, and 4 received the following intubating doses of cisatracurium: 0.09 mg/kg, 0.14 mg/kg, 0.19 mg/kg, and 0.2 mg/kg, respectively. Anesthesia was induced with thiopental sodium, sufentanil, droperidol, and nitrous oxide (N2O; 6 L/min) in oxygen (O2; 4 L/min) and maintained with isoflurane up to 0.7%, N2O in O2, and sufentanil. Mechanomyography assessed the neuromuscular function of the adductor pollicis with train-of-four supramaximal impulses. The trachea was intubated when the amplitude of the first twitch decreased to 10% to 15% of control. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among the groups regarding the demographic data, the value of the first twitch at 60 seconds, the time to 90% block, and the onset time. Clinical duration of cisatracurium was significantly different between Group 3 and Groups 1 and 2, whereas Group 4 differed significantly from Group 1. Intubating conditions did not differ significantly among the groups. CONCLUSION: When primed, cisatracurium 0.09 mg/kg and 0.14 mg/kg produced an onset time comparable with that of 0.2 mg/kg and allowed an earlier spontaneous recovery (p < 0.05). In this study, there was no benefit in priming cisatracurium 0.19 mg/kg.

Transdermal fentanyl in postoperative pain.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the safety and effectiveness of a transdermal fentanyl delivery system for the relief of pain following abdominal surgery. METHODS: In a nonblinded, noncrossover, placebo-controlled study, 40 ASA I and II patients of both sexes, 18-69 years of age, who were scheduled for abdominal surgery under general anesthesia, were randomly divided into two groups of 20 patients each. Patients in group I received a transdermal patch containing 0.16 mg/cm2 of fentanyl, which was applied to the skin over the subclavian area 60 minutes before the induction of anesthesia. For body weight less than 60 kg, a 30 cm2 patch was applied, and for weight greater than 60 kg, a 40 cm2 patch was used. A second group of 20 patients received placebo patches of identical size. Approximately 20 to 30 minutes before the expected end of surgery, 60 mg ketorolac was administered intramuscularly. Patients were observed for 36 hours after placement of the patch. If patients reported their pain at rest as 5 or greater at rest on a 0-10 visual analog scale, they were given 30-mg increments of ketorolac 5 to 7 hours apart. If this regimen did not relieve their pain, they received 1,300 mg acetaminophen between two ketorolac doses. If despite this, they still had pain 30 minutes afterward, intravenous morphine was given, and the patients were excluded from further study. The patch was removed in four patients in the fentanyl group and seven in the placebo group for various reasons, which included, inadequate pain relief requiring additional analgesia postoperatively and more than 1 microgram/kg of sufentanil given intraoperatively or immediately prior to the end of surgery. During the 36-hour observation period, 30 doses of 30 mg ketorolac and 14 doses of 1.3 g acetaminophen were given to 13 patients in the placebo group and 18 doses of ketorolac and 8 doses of acetaminophen were administered to 16 in the fentanyl group. RESULTS: The differences in postoperative analgesic requirements were significant. Plasma fentanyl concentrations at 12 and 24 hours after the application of the fentanyl patch were 0.98 +/- 0.14 ng/mL and 1.22 +/- 0.17 ng/mL, respectively. At 8, 16, 24, and 36 hours after application of the patch, the pain relief, assessed by a VAS at rest and with movement, was similar in the two groups. In the fentanyl and control groups, 12 and 5 patients, respectively, experienced nausea, and 2 and 3 patients, respectively, vomited. CONCLUSIONS: Similar postoperative analgesia was achieved with less parenteral analgesics in patients who received transdermal fentanyl preoperatively than in control patients. Fentanyl, 50-75 micrograms/h, administered in a transdermal delivery system, did not depress respiratory rate or hemoglobin oxygen saturation. Although the exact role of continuously administered opioids in managing acute postoperative pain has yet to be clearly defined, it is concluded that if properly used, this new transdermal device can be effective in providing a background of analgesia, which may assist in the management of acute postoperative pain as well as some chronic pain states.

The effect of age on the pharmacokinetics of the opioid antagonist nalmefene.

1. The disposition of nalmefene was evaluated in young and elderly normal healthy volunteers. Subjects received either a single 1 mg (n = 18 young; n = 11 elderly) or 2 mg (n = 8 young; n = 15 elderly) intravenous bolus dose of nalmefene. 2. Following the administration of nalmefene, the initial plasma concentrations were significantly higher in elderly vs young subjects. The higher concentrations were the result of the 30 to 40% smaller central compartment apparent volume of distribution that was observed in the elderly subjects as compared with the young volunteers (2.8 +/- 1.1 vs 3.9 +/- 1.11 kg-1 for 1 mg dose). The elderly volunteers also had a significantly shorter distributional half-life (t1/2 lambda 1) than young volunteers (0.7 +/- 0.7 vs 1.3 +/- 0.8 h for 1 mg dose). No significant differences between groups were observed for the elimination half-life, clearance or steady-state apparent volume of distribution. 3. Although transiently higher nalmefene plasma concentrations were observed in the elderly immediately following drug administration, there was no association between this observation and adverse events. We conclude that no dosage alteration is warranted in elderly patients.

Facilitation of rapid-sequence intubation with large-dose vecuronium with or without priming.

STUDY OBJECTIVES: To determine the effect of priming on the intubation and onset times of vecuronium 0.3 mg/kg. DESIGN: Randomized, unblinded study. SETTING: Operating rooms and postanesthetic recovery unit of a university-affiliated general hospital. PATIENTS: Thirty female ASA physical status I and II patients scheduled for intraperitoneal surgery divided into two groups of 15 each. INTERVENTIONS: Anesthesia was induced and maintained with sufentanil, droperidol, thiopental sodium, and nitrous oxide in oxygen. Patients in Group 1 were given vecuronium 0.015 mg/kg 4 minutes before induction and vecuronium 0.285 mg/kg 1 minute after induction. Patients in Group 2 received a single 0.3 mg/kg dose of vecuronium 1 minute after thiopental sodium. The ulnar nerve was stimulated every 10 seconds with train-of-four supramaximal impulses of 0.2 millisecond duration at 2 Hz. The compound electromyogram (EMG) of the adductor pollicis was continuously recorded. The trachea was intubated when the amplitude of the EMG decreased to 15% to 25% of control. At the end of surgery, residual neuromuscular block was reversed with edrophonium 0.75 mg/kg. MEASUREMENTS AND MAIN RESULTS: All patients in Group 1 could be intubated in 80 seconds or less, and the longest onset time was 120 seconds. In Group 2, the longest intubation time was 140 seconds, and the longest onset time was 200 seconds. Clinical durations in both groups were unpredictable, ranging from 47 to 185 minutes in Group 1 and from 63 to 160 minutes in Group 2. Ten of the 30 patients required an additional 0.5 mg/kg of edrophonium for antagonism of the residual neuromuscular block. There were no significant changes in heart rate or blood pressure attributable to vecuronium. CONCLUSIONS: Seventy-five percent to 85% neuromuscular block of the adductor pollicis, required for atraumatic tracheal intubation, developed in 80 seconds or less when vecuronium 0.3 mg/kg was administered in divided doses and in 140 seconds or less when it was injected as a single bolus dose. Clinical duration of vecuronium 0.3 mg/kg is long and unpredictable, and reversal of residual neuromuscular block may require larger doses of anticholinesterases. It is recommended that an intubating dose of vecuronium 0.3 mg/kg be used only in patients undergoing long surgical procedures that require prolonged postanesthetic mechanical ventilation.

Antagonism of fentanyl-induced respiratory depression with nalmefene.

We determined the ability of a new opioid antagonist, naimefene, to prevent fentanyl-induced respiratory depression in 8 healthy male volunteers. Ventilation and pulmonary function were measured with the respiratory inductive plethysmograph (RIP), which is non-invasive and requires no connection to the airway. Each volunteer was tested two times on different days. During the first session, each volunteer was monitored for one hour of baseline measurement followed by 4 hourly injections of fentanyl (1 microgram/kg) administered in an open-label manner. In the second session, the subjects were monitored for one hour after 1 mg of intravenous nalmefene was administered. Intravenous fentanyl or identical placebo were then given in a double-blind manner as in the first session. Progressive and profound respiratory depression occurred with fentanyl administration alone. In the absence of nalmefene, fentanyl converted normal breathing pattern to an irregular breathing pattern. When the subjects were treated with nalmefene prior to fentanyl administration, all of these changes were almost completely prevented. Pulmonary variables which reflected this difference between the fentanyl-alone group and the nalmefene-pretreated groups included frequency (p less than 0.001), tidal volume (p less than 0.001), percent rib cage contribution to tidal volume (p less than 0.001) and expiratory time (p less than 0.001). This study showed that nalmefene is an effective long-acting opioid antagonist, and that RIP accurately measures changes in respiration caused by opioid administration.

Species variation in the site and mechanism of the neuromuscular effects of diadonium in rodents.

The unusually wide, 80-fold species variation observed by others (1,2) in the neuromuscular (NM) potency of diadonium, a nondepolarizing muscle relaxant (MR), between cat and man suggested that the site and mechanism of its NM effect may vary in different species. To obtain information on this question, the NM potency of diadonium and the reversibility of its NM effect by neostigmine and/or 4-aminopyridine (4AP) was investigated on the in vitro phrenic nerve--hemidiaphragm preparations of rats, mice and guinea pigs. The concentration of diadonium that caused 90% NM block (IC90) was much greater in guinea pigs, 1.74 +/- 0.02 and 1.28 +/- 0.01 mu, when the preparations were stimulated with single stimuli at 0.1 Hz or with 0.1 s trains of 50 Hz tetani every 10 s, respectively, than in rats (IC90 = 62.4 +/- 0.89 and 52.1 +/- 1.00 microM) or mice (IC90 = 51.9 +/- 0.98 and 44.4 +/- 0.22 microM). In guinea pigs, the NM blocking effect of diadonium could be antagonized by neostigmine. This indicates that in this species the NM blocking effect of diadonium is primarily caused by inhibition of the interaction of acetylcholine (ACh), released by the nerve impulse, with the cholinergic receptors (cholinoceptors) of the postjunctional membrane (p.j.m.). By contrast, in rats and mice diadonium was not antagonized by neostigmine but was reversed by 4-aminopyridine. This suggests that in these species, in contrast to other nondepolarizing MR, diadonium does not inhibit NM transmission postsynaptically, but by inhibiting the positive nicotinic feedback mechanism of mobilization of ACh from reserve depots to release sites, causes a presynaptic NM block.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of temperature and calcium concentration on the myoneural effect of antibiotics.

To obtain information on the sites and mechanisms of the myoneural effect of aminoglycoside and polypeptide type antibiotics, the influence of neomycin, streptomycin, gentamicin and polymyxin B on the depression of the force of contraction (P) of the rat phrenic nerve-hemidiaphragm preparation was investigated at 37 degrees C, 27 degrees C or 17 degrees C and also at 37 degrees C in electrolyte solutions containing 2.5, 1.25 or 0.625 mM CaCl2. Decreasing the temperature or the CaCl2 concentration ((CaCl2)o) of the bath significantly (p less than 0.001) decreased P. The depressant effect of aminoglycosides on P (about 50% of control at 17 degrees C) was increased more with lower temperatures than that of polymyxin B (about 20%). The effect of lowering the (CaCl2)o on the depression of P (about 90% of control at the lowest (CaCl2)o) was about the same with the 4 antibiotics. The development of the maximal effect and the recovery of P after washout was slower with polymyxin B than with the 3 aminoglycosides. 4-Aminopyridine antagonized the depression of P caused by polymyxin B less than that caused by aminoglycosides. The findings suggest that aminoglycosides depress myoneural activity primarily by inhibiting stimulated release of ACh. Polymyxin B also inhibits ACh release, but inhibition of the contraction of myofibrils contributes more significantly to its myoneural effects than with aminoglycosides. It is conceivable that blocking of the ionophores of the postjunctional membrane also contributes to the myoneural effects of polymyxin B.

The influence of temperature and calcium concentration on the myoneural effect of antibiotics.

To obtain information on the sites and mechanisms of the myoneural effect of aminoglycoside and polypeptide type antibiotics, the influence of neomycin, streptomycin, gentamicin and polymyxin B on the depression of the force of contraction (P) of the rat phrenic nerve-hemidiaphragm preparation was investigated at 37 degrees C, 27 degrees C or 17 degrees C and also at 37 degrees C in electrolyte solutions containing 2.5, 1.25 or 0.625 mM CaCl2. Decreasing the temperature or the CaCl2 concentration ((CaCl2)o) of the bath significantly (p less than 0.001) decreased P. The depressant effect of aminoglycosides on P (about 50

of control at 17 degrees C) was increased more with lower temperatures than that of polymyxin B (about 20

). The effect of lowering the (CaCl2)o on the depression of P (about 90

of control at the lowest (CaCl2)o) was about the same with the 4 antibiotics. The development of the maximal effect and the recovery of P after washout was slower with polymyxin B than with the 3 aminoglycosides. 4-Aminopyridine antagonized the depression of P caused by polymyxin B less than that caused by aminoglycosides. The findings suggest that aminoglycosides depress myoneural activity primarily by inhibiting stimulated release of ACh. Polymyxin B also inhibits ACh release, but inhibition of the contraction of myofibrils contributes more significantly to its myoneural effects than with aminoglycosides. It is conceivable that blocking of the ionophores of the postjunctional membrane also contributes to the myoneural effects of polymyxin B.

The influence of temperature and calcium concentration on the myonneural effect of antibiotics

Para obtener información acerca del sitio y mecanismo de ácción del efecto de los antibióticos del tipo glucósidos y polipéptidos en al unión mioneural, se examinó la influencia de la neomicina, estreptomicina, gentamicina y polimixina B sobre la fuerza de contracción (P) en la preparación del hemidiafragma de rata a 37-, 27-, y 17-C, y a una temperatura de 37-C en soluciones electrolíticas conteniendo 2.5, 1.25 y 0,625 mM de cloruro cálcico (CaCl2). Al disminuir la temperatura y la concentración del CaCl2 en el baño disminuye P de una manera significativa (p < 0.001). El efecto depresivo de P de los aminoglucósidos fue aumentado más por la disminución de la temperatura que por el efecto de la polimixina B. El efecto de la disminución de CaCl2 sobre P (arededor del 90% de depresión en al concentración mínima de CaCl2) fue el mismo con los cuatro antibióticos. La aparición del efecto máximo y la recuperación de P después del lavado de la preparación fue más lenta con polimixina B que con los 3 aminoglucósidos. El agregado de 4-aminopiridina antagoniza menos la depresión de P causada por la polimixina B que la causada por los aminoglucósidos. Los resultados sugieren que los aminoglucósidos deprimen la actividad mioneural primariamente inhibiendo la descarga post-estimulación de acetilcolina (ACh). Polimixina B también inhibe la descarga de ACH, pero la inhibición de la contracción de las miofibrillas contribuye de una manera más significativa a su efecto mioneural que en el caso de los aminoglucósidos. Es concebible que el bloqueo de ionóforos en la membrana postsináptica contribuya al efecto mioneural de la polimixina B (AU)

The influence of temperature and calcium concentration on the myonneural effect of antibiotics

Para obtener información acerca del sitio y mecanismo de ácción del efecto de los antibióticos del tipo glucósidos y polipéptidos en al unión mioneural, se examinó la influencia de la neomicina, estreptomicina, gentamicina y polimixina B sobre la fuerza de contracción (P) en la preparación del hemidiafragma de rata a 37-, 27-, y 17-C, y a una temperatura de 37-C en soluciones electrolíticas conteniendo 2.5, 1.25 y 0,625 mM de cloruro cálcico (CaCl2). Al disminuir la temperatura y la concentración del CaCl2 en el baño disminuye P de una manera significativa (p < 0.001). El efecto depresivo de P de los aminoglucósidos fue aumentado más por la disminución de la temperatura que por el efecto de la polimixina B. El efecto de la disminución de CaCl2 sobre P (arededor del 90% de depresión en al concentración mínima de CaCl2) fue el mismo con los cuatro antibióticos. La aparición del efecto máximo y la recuperación de P después del lavado de la preparación fue más lenta con polimixina B que con los 3 aminoglucósidos. El agregado de 4-aminopiridina antagoniza menos la depresión de P causada por la polimixina B que la causada por los aminoglucósidos. Los resultados sugieren que los aminoglucósidos deprimen la actividad mioneural primariamente inhibiendo la descarga post-estimulación de acetilcolina (ACh). Polimixina B también inhibe la descarga de ACH, pero la inhibición de la contracción de las miofibrillas contribuye de una manera más significativa a su efecto mioneural que en el caso de los aminoglucósidos. Es concebible que el bloqueo de ionóforos en la membrana postsináptica contribuya al efecto mioneural de la polimixina B

Potentiation of neuromuscular blocking agents by calcium channel blockers in rats.

The effect of calcium channel blockers (Ca-antagonists) on the potency and reversibility of muscle relaxants (MR) was investigated in the in vitro phrenic nerve-hemidiaphragm and in vivo sciatic nerve-tibialis anterior preparation of rats. To increase the relevance of the experimental findings to the clinical situation, the [Ca++] and [Mg++] in vitro were the same as in the plasma of rats and humans and the stimulation parameters used in vitro and in vivo were similar to those that elicit voluntary movements of the muscles used. Both verapamil and nifedipine significantly decreased the I50 and I90 of d-tubocurarine (d-Tc), pancuronium, vecuronium, and atracurium in vitro and those of the first three MR in vivo (P less than 0.001). In vitro, the depression of the force of contraction of the diaphragm (P) caused by all the Ca-antagonist-MR combinations could be reversed only partially by washout, neostigmine, or 4-aminopyridine. In vivo, because of limitations imposed by their cardiovascular depressant effect, the muscles were exposed to lower concentrations of Ca-antagonists for shorter periods. Under these circumstances the decrease of P caused by all Ca-antagonist-MR combinations recovered spontaneously close to control levels. This study indicates that acute administration of verapamil during anesthesia may increase MR potency, but it is unlikely that spontaneous recovery or reversibility of the residual neuromuscular (NM) block at the end of anesthesia will be significantly affected. However, long-term administration of Ca-antagonists may make difficult the reversal of the residual NM block.

The effect of verapamil and EGTA on the rat phrenic nerve-hemidiaphragm preparation.

Relatively high concentrations of verapamil or EGTA [ethylene glycol-bis (beta-aminoethyl ether) N, N, N',N'-tetra acetic acid] inhibit contraction (P) of the rat phrenic nerve-hemidiaphragm preparation elicited by direct or indirect stimulation. The inhibitory effect of verapamil is greater (P less than 0.002) with direct (I50 = 26.3 +/- 1.7 microM) than indirect = I50 = 37.6 +/- 1.9 microM) stimulation. For EGTA the reverse is true: I50 is 1320 +/- 80 microM with direct and 1100 +/- 60 microM with indirect stimulation. The greater than 90% verapamil-induced depression of P can only be partially reversed by washout. Increasing the [Ca2+] or the addition of 4-aminopyridine (4AP) has insignificant antagonist effect. Except for the antagonism by 4AP during direct stimulation, the EGTA-induced depression of P is better antagonized by washout, increase of the [Ca2+], or the addition of 4AP than that caused by verapamil. Neostigmine did not antagonize the depression of P caused by either verapamil or EGTA. The findings presented indicate that the primary site of action of verapamil is postjunctional and that of EGTA is prejunctional.

Neuromuscular drug interactions of clinical importance.

The addition of marginally effective concentrations of d-tubocurarine (d-Tc), neomycin, or polymyxin B to the organ bath of rat phrenic nerve-hemidiaphragm preparations significantly (p < 0.05 to 0.001) increased the neuromuscular (NM) blocking effect of lidocaine. When both d-Tc and neomycin or polymyxin B were added the increase of the NM effect of lidocaine was even greater (p < 0.001). Washout re-established NM transmission. The NM block produced by combinations of d-Tc, neomycin, or polymyxin and lidocaine could be reversed partially by Ca2+ or neostigmine, and completely by 4-aminopyridine. The block caused by d-Tc and lidocaine was partially antagonized by neostigmine or 4-aminopyridine., The neomycin-lidocaine or the polymyxin B-lidocaine block, however, was not antagonized by thse compounds. The concentrations of d-Tc, antibiotics, and lidocaine that caused significant block in this in vitro preparation may be present at the NM junction of patients, who in the perioperative period had received combinations of therapeutic doses of d-Tc, neomycin, other aminoglycosides, or polymyxin B and lidocaine. This may cause impairment of spontaneous respiration requiring assisted ventilation.

Mutual potentiation of the neuromuscular effects of antibiotics and relaxants.

The interaction of d-tubocurarine, pancuronium, or succinylcholine with neomycin, streptomycin, or polymyxin B was investigated using a rat phrenic nerve-hemidiaphragm preparation. All neuromuscular blocking agents (relaxants) mutually potentiated the neuromuscular blocking action of one another; combinations of ineffective concentrations of relaxants and antibiotics caused an 82 to 98% neuromuscular block. This extensive potentiation of the neuromuscular effects of relaxants by antibiotics can be attributed to the fact that antibiotics not only have a curare-like stabilizing effect on the postjunctional membrane, but also decrease presynaptic acetylcholine release. Neostigmine (0.25 microgram/ml) only partially antagonized the neuromuscular block caused by the various drug combinations. In contrast, 4 microgram/ml of 4-aminopyridine returned the twitch tension, depressed by combined administration of relaxants and antibiotics, to or above control values except in the case of neuromuscular block caused by the combinations of succinylcholine and polymyxin B.