Ketamine potentiates nondepolarizing neuromuscular relaxants in a primate

Ketamine has many neuromuscular effects in vitro. Its neuromuscular effects in vivo have been controversial and inconsistent. To systematically examine its neuromuscular effects over a wide dose range and its interaction with all popular nondepolarizing neuromuscular relaxants, the effects of ketamine 2, 5, and 10 mg/kg IV were studied on a continuous but incomplete (50%) neuromuscular block preestablished by an IV infusion of d-tubocurarine, atracurium, vecuronium, and pancuronium. Indirectly stimulated adductor pollicis muscle response of monkeys anesthetized with 0.5-1.0% halothane in oxygen were quantified. Ketamine in the absence of a neuromuscular relaxant had no effect on the thumb twitch. In a dose-dependent manner, ketamine significantly enhanced the 50% depression of the thumb twitch preestablished by a constant IV infusion of each of the four muscle relaxants studied. Ketamine 2 mg/kg potentiated the neuromuscular relaxants in the following order of magnitude: vecuronium greater than atracurium greater than d-tubocurarine greater than pancuronium. However, with a 10 mg/kg dose of ketamine, pancuronium became as potentiated as was vecuronium, i.e., pancuronium = vecuronium greater than atracurium greater than d-tubocurarine. It is concluded that in the primate, ketamine potentiates all nondepolarizing muscle relaxants in a dose-dependent manner.     

Anaphylaxis to muscle relaxants. Predictive value of intradermal tests and study of crossed anaphylaxis

37 patients were studied, all of whom presented with anaphylaxis to a muscle relaxant. The diagnosis was made after simultaneous intradermal testing (IDT), human basophil degranulation tests (HBDT) and Prausnitz-Küstner tests (PK) of passive cutaneous anaphylaxis. Three tests were positive in 6 patients, both IDT and PK in 9, and both IDT and HBDT in 8. In 14 patients, the IDT, repeated twice, were positive both times. A search for crossed anaphylaxis to the other muscle relaxants was carried out in all the patients during a second series of tests, a few months to years after the first one. The drugs tested, at dilutions of the pharmaceutical preparation of 10(-3) or more, were: suxamethonium, gallamine, alcuronium, pancuronium, vecuronium, d-tubocurarine. The reliability of IDT in the diagnosis of anaphylaxis is discussed in terms of the small reactive concentration, the producibility of the tests, the one HBDT that did become positive later, and in one case the occurrence of shock by crossed anaphylaxis. Skin reactivity seemed to remain constant with time, so allowing the use of IDT as a diagnostic tool, in cases of old anaphylactoid shocks, occurring during general anaesthetics. The frequency of crossed anaphylaxis was assessed to be about 84%. The sensitivity to one or other drugs varied with each patient. Pancuronium and vecuronium appeared to be the least likely drugs to cause crossed anaphylaxis. The predictive use of these tests is discussed. It is also suggested that muscle relaxants with only one quaternary ammonium group should be used, this chemical characteristic probably reducing the risks of sensitization.     

Prevention of succinylcholine myalgias: a meta-analysis

Meta-analysis is a term used to describe statistical methods for evaluating a series of research reports; this analysis transcends the limitations that may be inherent in each of the individual studies summarized. Forty-five research reports of clinical trials for the prevention of myalgias after succinylcholine were assembled. Four classes of preventive drugs (nondepolarizing muscle relaxants, benzodiazepines, succinylcholine in "self-taming" doses, and local anesthetics) were reported in detail sufficient to allow for inclusion in a meta-analysis of clinical efficacy. Each study was summarized by determining the difference in the incidence of myalgias on the first postoperative day between treatment and control groups. A random-effects variance components approach was used. Seven meta-analyses were performed (atracurium, d-tubocurarine, gallamine, pancuronium, diazepam, succinylcholine in self-taming doses, and lidocaine). For each meta-analysis there was statistically significant heterogeneity among studies. Atracurium, d-tubocurarine, gallamine, pancuronium, diazepam, and lidocaine all significantly decreased the frequency of myalgias by about 30%. Succinylcholine in self-taming doses alone was not efficacious.     

Pancuronium,vecuronium, and d-tubocurarine inhibit and succinylcholine stimulates choline acetyltransferase activity

The effects of the nondepolarizing muscle relaxants (NDMR), pancuronium, vecuronium, and d-tubocurarine and a depolarizing muscle relaxant, succinylcholine, were studied on choline acetyltransferase (ChAT) activity. A radiochemical assay was used in the determination of ChAT activity using purified placental enzyme. Pancuronium at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 3, 10, 15, 40 and 85 per cent, respectively; vecuronium at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 5, 10, 26 and 57 per cent, respectively; d-tubocurarine at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 0, 4, 12.5 and 29 per cent, respectively; whereas succinylcholine at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M activated ChAT activity by 8, 10, 1, and 2 per cent, respectively. Even though our present data demonstrated a significant dose-dependent inhibitory effect on ChAT activity by pancuronium, vecuronium and d-tubocurarine, it is unlikely that this inhibitory effect will contribute to the mechanism of action of NDMR. Our data, however, may suggest an additional mechanism for the phenomena of tetanic and train-of-four fades that are seen following the administration of nondepolarizing muscle relaxants.     

The non-depolarizing myorelaxants in orotracheal intubation. A clinical comparison

The present study was designed to compare the rapidity of onset of neuromuscular blockade after administration of 5 different neuromuscular relaxants (succinylcholine, d-tubocurarine, pancuronium, atracurium and vecuronium) in 75 patients, randomly allocated in 5 treatment groups. The facilitation for endotracheal intubation was evaluated using a clinical score. The for onset relaxation was shorter when using succinylcholine. Among non-depolarizing relaxants an adequate facilitation for endotracheal intubation was observed, two minutes after administration of atracurium and vecuronium, while endotracheal intubation was difficult when using d-tubocuranine and pancuronium.     

Five Non-Depolarizing Muscle Relaxants in Precurarization

Five different non-depolarizing muscle relaxants and a control solution of saline were studied as precurarization agents. Two hundred and twenty-two surgical patients (ASA I-II) were allocated in a double-blind fashion to one of the following groups: d-tubocurarine 0.05 mg/kg, alcuronium 0.03 mg/kg, pancuronium 0.01 mg/kg, gallamine 0.25 mg/kg, ORG NC-45 (vecuronium) 0.01 mg/kg and saline solution 0.005 ml/kg. Pretreatment was performed 4 min before administering a 1.5 mg/kg bolus of succinylcholine (SCh). Fasciculations, intubation conditions, duration of neuromuscular blockade after SCh, serum potassium changes and postoperative myalgias (in 60 patients) were recorded. All the drugs studied prevented fasciculations significantly (P less than 0.05) more than in the control group. d-Tubocurarine and alcuronium were superior to the others in this respect. Intubation conditions were best in the control and pancuronium groups, but there was no significant difference between the pancuronium and d-tubocurarine or between the d-tubocurarine and alcuronium groups. Pancuronium pretreatment prolonged the SCh block significantly, whereas other agents shortened the duration of the SCh block. The antagonism of the SCh block apparently also affected intubation conditions, although intubation remained satisfactory. A statistically significant rise in serum potassium level was measured only in the control and pancuronium groups. In the control and pancuronium groups, four patients out of 10 had postoperative myalgias, whereas in the other groups only one or none out of 10 had them (0/10 vs. 4/10; 0.10 greater than P greater than 0.05). In conclusion, d-tubocurarine and alcuronium seem to have advantages over pancuronium, ORG NC-45 and gallamine for precurarization.     

Pretreatment with d-tubocurarine, vecuronium, and pancuronium attenuates succinylcholine-induced increases in plasma norepinephrine concentrations in humans.

We studied in patients the effect of d-tubocurarine, which has sympathetic ganglion blocking action, on succinylcholine-induced increases in plasma levels of catecholamines, and compared it with the effects of vecuronium and pancuronium, which have little sympathetic ganglion blocking action. Thirty-two patients were divided into five groups: seven were given 3 mL saline; seven received 1 mg/kg succinylcholine; and six, seven, and five patients were given 0.08 mg/kg d-tubocurarine, 0.01 mg/kg vecuronium, and 0.01 mg/kg pancuronium, respectively, all of which were injected 5 min before 1 mg/kg succinylcholine. Succinylcholine alone significantly increased plasma norepinephrine concentrations, systolic blood pressure, and heart rate from 187 +/- 39 pg/mL (mean +/- SEM), 93 +/- 2 mm Hg, and 77 +/- 4 beats/min to 429 +/- 61 pg/mL, 120 +/- 7 mm Hg, and 102 +/- 6 beats/min, respectively, with onset of fasciculations. Pretreatment with d-tubocurarine, vecuronium, and pancuronium significantly and equally attenuated both the fasciculations and the cardiovascular responses to succinylcholine. These results suggest that the sympathetic ganglion blocking action of neuromuscular relaxants when given before succinylcholine is not an important factor in attenuation of succinylcholine-induced increases in plasma levels of catecholamines.     

The value of prick tests in the detection of anaphylaxis caused by muscle relaxants

Intradermal tests (IDR) are a sure diagnostic procedure for confirming the IgE origin of anaphylactoid accidents due to muscle relaxant drugs. Because carrying these out and interpreting them correctly is difficult, epidermal prick-tests (PT) could be used if they proved as sure as IDR. To ascertain this, IDR and PT were carried out in 38 patients who had a shock after being given a muscle relaxant 6 months to 5 years previously; for these tests, increasing concentrations of five muscle relaxants were used (suxamethonium, gallamine, alcuronium, pancuronium and vecuronium). The PT were also carried out with the five same pure and diluted muscle relaxants in a group of 147 volunteer controls. For the 38 patients, PT and IDR were always positive for the same drugs, but at different concentrations, the epiderm seeming less sensitive than the derm (with a ratio of 1 to 100). In the control group, all the tests were negative, even with the pure drug. PT with muscle relaxants were sensitive, specific of anaphylaxis, and permanent. Easy to carry out, easily interpreted, they could be useful as tests for predicting latent sensitisation in risk patients requiring muscle relaxants. But all muscle relaxants must be tested, and not just the one the anaesthetist is likely to use.     

Facilitation of rapid endotracheal intubations with divided doses of nondepolarizing neuromuscular blocking drugs

The authors sought to determine whether prior administration of a small, subparalyzing dose of nondepolarizing muscle relaxant would shorten the onset time of an intubating dose of muscle relaxant. Initially, in 60 anesthetized patients, twitch response of adductor pollicis to ulnar nerve stimulation was studied after a small dose of pancuronium 0.015 mg . kg-1, metocurine 0.03 mg . kg-1, or d-tubocurarine 0.04 mg . kg-1, followed 3 min later by pancuronium 0.08 mg . kg-1 or atracurium 0.4 mg . kg-1 administered iv. After 60 s, the minimum neuromuscular block, in all patients was 79.0 +/- 5.0%. A 95% depression or twitch tension occurred between 59.1 +/- 5.3 and 86.1 +/- 5.9 s. In another 60 patients, intubating conditions under similar regimen were studied, except the small dose of muscle relaxant was given immediately prior to induction of anesthesia. At the end of 60 s, good to excellent intubating conditions were present in 100% of the patients following the second dose of pancuronium and in 83% of the patients following atracurium. In 17% of the patients, after atracurium intubating conditions were fair. When nondepolarizing neuromuscular blocking drugs are administered in divided doses, neuromuscular blockade adequate for endotracheal intubation is achieved in less than 90 s. This facilitates rapid endotracheal intubation in a time comparable to using succinylcholine, without undesirable effects of the depolarizing neuromuscular blocking drugs.     

Train-of-four fade of non depolarizing muscle relaxants: an insight into the mechanism of precurarization

This study was carried out to assess the prejunctional effect of non depolarizing muscle relaxants during the onset of neuromuscular blockade using the train-of-four ratio (TR). The prejunctional effect was compared with previous results concerning the ability of the relaxants to prevent suxamethonium-induced fasciculations. Fifty-three adult patients were relaxed with small incremental doses of either alcuronium (0.03 mg.kg-1), atracurium (0.04 mg.kg-1), pancuronium (0.01 mg.kg-1), d-tubocurarine (0.05 mg.kg-1) or vecuronium (0.01 mg.kg-1) during anaesthesia with thiopentone, fentanyl and nitrous oxide in oxygen. The muscle relaxant was given after recovery from an initial suxamethonium blockade needed for tracheal intubation. The evoked integrated EMG response to supramaximal train-of-four (2 Hz) stimulation was recorded every 20 s. TR % was calculated at different first twitch (T1) levels during the onset of neuromuscular blockade. Significant changes occurred at the 100% and 90% T1 levels, alcuronium having the lowest mean TR values. Atracurium, pancuronium and vecuronium gave similar TR values. Results with d-tubocurarine placed it between alcuronium and the others. These train-of-four ratio results were compared with the ability of non depolarizing muscle relaxants to prevent fasciculations. In conclusion, the stronger the train-of-four fade, the greater was the ability of the relaxant to prevent suxamethonium-induced fasciculations. This supports the theory that the blockade of prejunctional cholinergic receptors is the mechanism of action of precurarization.     

Iontophoretic study of speed of action of various muscle relaxants.

The speed of action of nondepolarizing muscle relaxants is inversely related to potency. The hypothesis that this effect occurs at the end plate was tested in a frog (Rana pipiens) cutaneous pectoris muscle preparation. Brief acetylcholine pulses (10-100 ms) were applied iontophoretically from a central barrel of a triple-barrelled microelectrode located near an end plate. Long pulses (10-200 s) of muscle relaxant (gallamine, rocuronium, d-tubocurarine, atracurium, vecuronium, pancuronium, and doxacurium) were applied from one of two other barrels. The responses were a voltage change at the end plate, measured with an intracellular electrode. To evaluate potency, intracellular voltage changes following iontophoretic acetylcholine pulses were measured after application of various concentrations of muscle relaxants. The following were the equilibrium dissociation constants, which represent concentration of relaxant for 50% inhibition of response (mean plus or minus standard deviation): gallamine, 4.56 +/- 0.44 microM (n = 5); rocuronium, 0.71 +/- 0.09 microM (n = 6); d-tubocurarine, 0.59 +/- 0.07 microM (n = 4); atracurium, 0.31 +/- 0.03 microM (n = 4); vecuronium, 0.23 +/- 0.02 microM (n = 5); pancuronium, 0.18 +/- 0.03 microM (n = 3); doxacurium, 0.11 +/- 0.03 microM (n = 5). Both onset and offset of effect of muscle relaxant proceeded with an exponential time course.(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe anaphylactic reactions after administration of rocuronium

The authors report four cases of severe anaphylactic reactions (grade III or IV) to rocuronium bromide. In three of them, it was the first contact with a muscle relaxant. In three patients the reaction was mediated by IgE anti-bodies. A cross-reactivity with other muscle relaxants was existing in two cases (suxamethonium, vecuronium and atracurium in one patient, suxamethonium, vecuronium and pancuronium in the other.     

Radioimmunoassay method for the detection of IgE antibodies specific to alcuronium

A radio-immunoassay (RIA) was used to screen for specific IgE to myorelaxants. Alcuronium was coupled to epoxy-activated Sepharose. Sixteen patients with anaphylaxis to alcuronium (n = 2), gallamine (n = 2) or suxamethonium (n = 12) were studied. The diagnosis was established by intradermal tests (ID), passive cutaneous anaphylaxis tests and human basophil degranulation tests. The amount of non specific label retained by Sepharose-ethanolamine (with sera of patients) and Sepharose-alcuronium (with sera of 11 control subjects) was estimated. The RIA was positive 10/16 (8/14 patients having reacted to a muscle relaxant other than alcuronium). The RIA seemed to be useful in the diagnosis of anaphylaxis to muscle relaxants. Drug-reactive antibodies were specific of the quaternary ammonium radical, which was the common allergenic determinant of all molecules of muscle relaxants. This test accounted for in vitro cross-reactivity, but had no predictive value for the clinical risk of crossed-anaphylaxis. This risk was best assessed by ID; it was positive in three cases. Although it was not possible to compare ID and RIA, the interpretation of which was different, both tests should be recommended for the detection of sensitivity to muscle relaxants.     

Effects of succinylcholine on the pharmacodynamics of pipecuronium and pancuronium.

To study the effects of succinylcholine on subsequent pharmacodynamics of nondepolarizing muscle relaxants, a comparative pharmacodynamic study was carried out in patients having balanced anesthesia (thiopental, fentanyl, nitrous oxide/oxygen) in whom equipotent doses of pipecuronium (80 micrograms/kg) and pancuronium (100 micrograms/kg) were given with or without prior administration of succinylcholine (1 mg/kg). Fifty-two patients were randomly assigned to one of the following four groups: 1, pancuronium (100 micrograms/kg); 2, pipecuronium (80 micrograms/kg); 3, succinylcholine (1 mg/kg) plus pancuronium (100 micrograms/kg); and 4, succinylcholine (1 mg/kg) plus pipecuronium (80 micrograms/kg). In groups 3 and 4, the nondepolarizing relaxant was given after succinylcholine when the twitch height recovered to 75% of its control value. For maintenance of neuromuscular blockade, additional increments of pancuronium (20 micrograms/kg) or pipecuronium (15 micrograms/kg) were given. Neuromuscular function was monitored throughout induction, maintenance, spontaneous recovery, and pharmacologic reversal of the neuromuscular block. Mean onset times for pancuronium (group 1) and pipecuronium (group 2) given without succinylcholine were (mean +/- SEM) 2.5 +/- 0.3 and 2.8 +/- 0.2 min, respectively. Mean onset times (times to maximum twitch depression) of the two drugs given after succinylcholine (groups 3 and 4) were significantly shorter (1.4 +/- 0.4 and 1.6 +/- 0.1 min, respectively). Clinical durations (i.e., until 25% twitch recovery of pancuronium and pipecuronium) were not significantly different among the four groups, varying from 81.1 +/- 5.4 (group 4) to 107.0 +/- 17.0 (group 2) min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of magnesium and calcium on muscle contractility and neuromuscular blockade produced by muscle relaxants and aminoglycoside]

The muscle contractility and neuromuscular blockade of muscle relaxants are influenced by the electrolytes, especially magnesium ion(Mg2+) and calcium ion(Ca2+), in the extracellular fluid. The present study was designed to evaluate the effects of Mg2+ and Ca2+ on muscle contractility and on the blocking properties of d-tubocurarine, succinylcholine and aminoglycoside antibiotics, tobramycin in vitro, using rats' phrenic nerve-hemidiaphragm preparations. Mg2+ inhibited the twitch tensions in a concentration dependent manner. A low concentration of Ca2+ decreased the twitch tensions, but a high concentration of Ca2+ had no effect on them. Mg2+ potentiated the block produced by d-tubocurarine, succinylcholine and tobramycin depending on the concentration of Mg2+, and good regression lines were obtained. Ca2+, however, antagonized the neuromuscular blockade of the three drugs at any level of Mg2+ concentration. From these findings, it should be noticed that special care must be taken to prevent a profound neuromuscular blockade due to the drug interaction of each drug when a muscle relaxant or an aminoglycoside antibiotics is administered to a patient suffering from hypermagnesemia and/or hypocalcemia.     

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.     

Neuromuscular Relaxants as Antagonists for M sub 2 and M sub 3 Muscarinic Receptors

Background: Neuromuscular relaxants such as pancuronium bind to M sub 2 and M3 muscarinic receptors as antagonists. Blockade of muscarinic receptors in atria of the M2 subtype mediates tachycardia. In the lung, blockade of M2 receptors on parasympathetic nerves potentiates vagally induced whereas blockade of M sub 3 receptors on bronchial smooth muscle inhibits bronchospasm. The current study was designed to quantify the affinity of a series of neuromuscular relaxants for the M2 and M3 muscarinic receptors, which were individually stably transfected in Chinese hamster ovary cell lines.

Methods: Competitive radioligand binding assays determined the relative binding affinities of the neuromuscular relaxants pancuronium, succinylcholine, mivacurium, doxacurium, atracurium, rocuronium, gallamine, and pipecuronium for the muscarinic receptor in the presence of a muscarinic receptor antagonist (sup 3 H-QNB) in membranes prepared from cells individually expressing either the M2 or M3 muscarinic receptor.

Results: All muscle relaxants evaluated displaced3 H-QNB from muscarinic receptors. The relative order of potency for the M2 muscarinic receptor (highest to lowest) was pancuronium, gallamine, rocuronium, atracurium, pipecuronium, doxacurium, mivacurium, and succinylcholine. The relative order of potency for the M3 muscarinic receptor (highest to lowest) was pancuronium, atracurium, pipecuronium, rocuronium, mivacurium, gallamine, succinylcholine, and doxacurium.     

Acute and chronic changes in intra- and extracellular potassium and responses to neuromuscular blocking agents

The effects of acutely induced metabolic and respiratory alkalosis with reduction of serum potassium concentration as well as chronic total body potassium depletion induced by furosemide treatment were evaluated and correlated with alteration of neuromuscular blockade induced by d-tubocurarine, pancuronium, and succinylcholine in 12 mongrel dogs. Acute respiratory and metabolic alkalosis significantly reduced serum potassium by about 26%, while chronic furosemide treatment (1 mg/kg IV daily for 14 +/- 4 days) significantly reduced both serum potassium concentration (4.16 +/- 0.31 to 3.27 +/- 0.14 mEq/L) and skeletal muscle potassium content (80.9 +/- 5.6 to 58.7 +/- 4.1 mEq/kg). Succinylcholine neuromuscular blockages was essentially unchanged by acute respiratory or metabolic alkalosis or by chronic furosemide treatment, except for more rapid onset of blockade when 0.1 mg/kg succinylcholine was administered during metabolic alkalosis. Acute respiratory alkalosis shortened the duration of neuromuscular blockade induced by d-tubocurarine and pancuronium while acute metabolic alkalosis shortened the duration of pancuronium only and had no effect on d-tubocurarine. Chronic furosemide treatment had no effect on either d-tubocurarine or pancuronium neuromuscular blockage. Potassium concentration gradients between the intracellular and the extracellular compartments may be more important than cellular potassium depletion per se in affecting responses to neuromuscular blocking agents such as succinylcholine, d-tubocurarine, or pancuronium. Serum alkalemia and hypokalemia antagonize the duration of the neuromuscular blocking action of d-tubocurarine and pancuronium but not that of succinylcholine.     

Méthode radio-immunologique de détection des IgE spécifiques à l'alcuronium

A radio-immunoassay (RIA) was used to screen for specific IgE to myorelaxants. Alcuronium was coupled to epoxyactivated Sepharose. Sixteen patients with anaphylaxis to alcuronium (n=2), gallamine (n=2) or suxamethonium (n=12) were studied. The diagnosis was established by intradermal tests (ID), passive cutaneous anaphylaxis tests and human basophil degranulation tests. The amount of non specific label retained by Sepharose-ethanolamine (with sera of patients) and Sepharose-alcuronium (with sera of 11 control subjects) was estimated. The RIA was positive 10/16 (8/14 patients having reacted to a muscle relaxant other than alcuronium). The RIA seemed to be useful in the diagnosis of anaphylaxis to muscle relaxants. Drug-reactive antibodies were specific of the quaternary ammonium radical, which was the common allergenic determinant of all molecules of muscle relaxants. This test accounted for in vitro cross-reactivity, but had no predictive value for the clinical risk of crossed-anaphylaxis. This risk was best assessed by ID; it was positive in three cases. Although it was not possible to compare ID and RIA, the interpretation of which was different, both tests should be recommended for the detection of sensitivity to muscle relaxants.     

Nitroglycerin and the neuromuscular blockade produced by gallamine, succinylcholine, d-tubocurarine, and pancuronium

The finding in cats of prolonged pancuronium neuromuscular blockade in conjunction with intravenous infusion of nitroglycerin was previously reported by this laboratory. To expand on this finding the present study compared the effects of nitroglycerin on neuromuscular blockade produced by gallamine, d-tubocurarine, succinylcholine, and pancuronium, and further characterized the nitroglycerin-pancuronium interaction. The results indicate that of the relaxants studied only pancuronium neuromuscular blockade is prolonged, and that the prolongation is not due to altered plasma elimination of pancuronium. In vitro pancuronium blockade was not affected by nitroglycerin, suggesting the involvement of a metabolite in the block prolongation response. Reversibility of the prolonged pancuronium block by neostigmine is not influenced by nitroglycerin.