Recovery Of Twitch Height Research Articles

A Comparative study of efficacy of high dose versus low dose of suxamethonium for endotracheal intubation

As use of suxamethonium is associated with a large number of undesirable and serious side effects, including cardiac arrhythmias and malignant hyperthermia. These undesirable effects have prompted anesthesiologists to restrict use of suxamethonium. The low dose of the drug is expected to have lower side effects without compromising its neuromuscular blocking properties as the dose dependent side effects have been known for long, so the present study carried out to compare the efficacy of high dose (1.5mg/Kg) of suxamethonium to that of low dose (0.5mg/Kg) assessed by intubation condition with neuromuscular blockade. We prospectively randomized and compared the intubating conditions with neuromuscular monitoring in 100 patients undergoing elective abdominal, gynaecological and limb surgery in CMS-TH and found duration of apnoea and time taken for recovery of twitch height was significantly shorter. Without compromising the quality of neuromuscular blockade. Suxamethonium or Succinylcholine can be used in lower doses (0.5 mg/kg) in elective cases without airway compromise to achieve intubation. Journal of College of Medical Sciences-Nepal,2011,Vol-7,No-4, 53-57 DOI: http://dx.doi.org/10.3126/jcmsn.v7i4.6812

Optimal Dose of Rocuronium for Rapid Tracheal Intubation under Sevoflurane Anesthesia

Background: There are situations in anesthesia in which it may be desirable to achieve rapid tracheal intubation. Rapid tracheal intubation with rocuronium has been studied using a probability-based approach. But these studies used intravenous anesthetics for anesthetic induction. Therefore, we aimed to predict doses of rocuronium giving 90% and 95% probabilities of intubation within 60 seconds and to estimate their action durations using sevoflurane for anesthetic induction. Methods: Anesthesia was induced in sixty patients with sevoflurane. Patients received randomly rocuronium, 0.0, 0.3, 0.6, 0.9 or 1.2 mg/kg (n = 12/dose). Laryngoscopy began 40 seconds later, aiming for intubation at 60 seconds, and conditions were graded as either perfect, acceptable or unacceptable, with the first two conditions being taken as successful intubation. Duration of action was accepted as time until a twitch height recovery of 15%. The dose versus the fraction of patients showing successful intubation was analyzed by logistic regression. Doses giving 90% and 95% ( and ) probabilities of successful intubation were calculated. Results: Of the 12 patients in each group (0.0, 0.3, 0.6, 0.9 or 1.2 mg/kg), intubation was successful in 4, 10, 12, 12 and 12 patients, respectively. The and doses were determined to be 0.34 and 0.43 mg/kg, respectively. Conclusions: After induction with sevoflurane, rocuronium at 0.43 mg/kg, gives a 95% probability of successful intubaton at 60 seconds.

Effects of Lidocaine, Verapamil and Their Mixture on Neuromuscular Blockade

Background: Lidocaine, verapamil or a lidocaine-verapamil mixture was effectively applied for blunting extubation during recovery from anesthesia. However, these drugs can enhance neuromuscular blockade and cardiovascular depression. We investigated the neuromuscular and the cardiovascular effect of lidocaine, verapamil or a lidocaine-verapamil mixture before extubation in the recovery from anesthesia. Methods: We studied ninety nine healthy adult patients (ASA class I or II), excluding the patients with cardiovascular diseases and with factors affecting neuromuscular function. Induction of anesthesia was performed with thiopental sodium 5 mg/kg and fentanyl 0.1 mg, and maintained with O2-N2O (50%)-enflurane (2%). Supramaximal single twitch stimuli (0.1 Hz) were applied to the ulnar nerve and the twitch response of the adductor pollicis was recorded by the Gould TA 240 recorder via a 2 kg Load Cell Strain Gauge modification. After stabilization of the twitch response, mivacurium (0.16 mg/kg) or vecuronium (0.1 mg/kg) was administered intravenously and endotracheal intubation was performed. Twitch heights were spontaneously recovered without a reversal agent from the neuromuscular blockade as a spontaneous group. Pyridostigmine 10 mg and glycopyrrolate 0.2 mg were administered intravenously around the time of 10% recovery of baseline twitch height as a reversal recovery group. At the time of 100% recovery of twitch height, train of four (TOF) stimuli was applied and then lidocaine, verapamil or a lidocaine-verapamil mixture was administered intravenously in both groups. Maximum depression of twitch height and the TOF ratio at this point, recovery index (RI) measured, and mean arterial pressure and pulse rates were measured before and at 2, 5, 10, 20 and 30 min. after the lidocaine-verapamil mixture administration. Results: Twitch heights were depressed slightly after lidocaine, verapamil or a lidocaine-verapamil mixture administration; however, there were no significant differences to compare with the control. TOF

NEUROMUSCULAR BLOCKADE AND INTUBATION CONDITIONS OF THE SINGLE BOLUS DOSE (2xED90) OF ROCURONIUM BROMIDE

Rocuronium bromide (2xED90), a new non depolarising neuromuscular blocking drug with rapid onset, intermediate duration of action and cardiostability was studied in open randomised trial in 30 patients. Neuromuscular block was monitored using a Train of Four stimulus by stimulator electrodes placed on the ulnar never close to the wrist. Intubation conditions were assessed subjectively by scoring the jaw relaxation, vocal cord and the response to intubation with same technique of anaesthesia. Clinical recovery (Dur25) of neuromuscular blockade was monitored. Haemodynamic changes were recorded. Intubation conditions were clinically acceptable in 99.6% of patients, (excellent 73%; good 26.6%) at 90s. Time to onset (Lag time) of neuromuscular block was 22.5 ± 12.6 sec and average time for the onset of block (maximum effect) was 90.9 ±10.6 sec. The duration of clinical muscular relaxation (25% recovery of twitch height) was 22.4 ± 8.30 min. Stability of cardiocirculatory system was seen.

This Month in ANESTHESIOLOGY

This Month in ANESTHESIOLOGY

Differential effects of vecuronium on the thumb and great toe as measured by accelography and electromyography

We evaluated possible differential effects of vecuronium on the thumb and great toe using two types of neuromuscular transmission monitor. Train-of-four stimuli were simultaneously applied to the ulnar nerve and tibial nerves using cutaneous electrodes. The responses were quantified with accelographs (thumb and left great toe) and an electromyograph (right great toe). Twenty ASA 1 or 2 patients received, by random allocation, one of two types of anaesthesia: neuroleptanaesthesia or sevoflurane-based anaesthesia. With both techniques, the shortest time to maximum block after vecuronium 0.1 mg.kg-1 occurred in the thumb as measured by accelography. The average (SD) values with neuroleptanaesthesia were: 173(23) s for thumb using accelography; 220(16) s for great toe using accelography; 205(44) s for great toe using electromyography. The average (SD) value(s) with sevoflurane-based anaesthesia were: 137(15) for thumb using accelography; 179(21) for great toe using accelography; 153(23) for great toe using electromyography. The differences between the thumb and great toe were statistically significant during both types of anaesthesia when measured with the accelograph (p < 0.01). The time from completion of maximal block to 25% recovery of twitch height in the thumb was significantly longer than that of the great toe as measured by accelography during both types of anaesthesia (p < 0.05). In contrast, there were no statistically significant differences between time to maximum block and 25% recovery of twitch height of the thumb as measured by accelography compared to the values measured for the great toe using electromyography during either anaesthetic technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Is recovery of neuromuscular transmission complete after the use of neostigmine to antagonize block produced by rocuronium, vecuronium, atracurium and pancuronium?

To test if recovery of neuromuscular transmission is complete after the use of neostigmine under standardized conditions, we have measured adductor pollicis mechanical activity in response to 0.1 Hz (twitch height), train-of-four (TOF) and 100 Hz (RF 100 Hz) ulnar nerve stimulations. We studied 56 adult anaesthetized (thiopentone, fentanyl, nitrous oxide in oxygen) patients, allocated randomly to one of four groups (n = 14) to receive rocuronium (group Roc), vecuronium (group Vec), atracurium (group Atr) or pancuronium (group Pan). Recovery of neuromuscular transmission was studied for 15 min after neostigmine 40 micrograms kg-1 was given at 25% recovery of twitch height. Fifteen minutes after antagonism, the TOF ratio was 0.91 (SEM 0.01), 0.88 (0.02) and 0.92 (0.01) (ns), and RF 100 Hz was 0.78 (0.01), 0.79 (0.02) and 0.78 (0.01) (ns) respectively, in patients in groups Roc, Vec and Atr, respectively. In patients in group Pan, TOF ratio and RF 100 Hz were only 0.76 (0.01) and 0.33 (0.04) respectively (P < 0.01, one-way analysis of variance, Duncan's multiple classification range tests). In contrast with pancuronium, antagonism of rocuronium-, vecuronium- and atracurium-induced neuromuscular blocks produced a similar high degree of recovery of neuromuscular transmission.

Repeated Doses of Rocuronium Bromide Administered to Cirrhotic and Control Patients Receiving Isoflurane

Steroid muscle relaxants often display pharmacodynamic changes in patients with cirrhosis because of alterations in elimination processes. Rocuronium is a new steroid muscle relaxant possibly eliminated through the liver. This study was designed to compare rocuronium pharmacodynamics and pharmacokinetics in cirrhotic and healthy patients. Rocuronium was administered to 26 cirrhotic patients and 24 control subjects anesthetized with isoflurane for an elective procedure. Patients were randomly allocated to received an initial dose of rocuronium: 120, 180, 250, or 300 micrograms.kg-1. Dose-response curves were established, and ED50 was calculated. Preselected maintenance doses (75, 150, or 225 micrograms.kg-1) were administered at 25% recovery of twitch height to compare clinical duration of action. At the end of the procedure, relaxation was reversed in half of the patients, and the time course of recovery was compared in the two groups. Blood samples drawn during the procedure and after the last maintenance dose allowed pharmacokinetic analysis in six cirrhotic patients and six control subjects. ED50 of the initial dose was 144 micrograms.kg-1 in cirrhotic patients and 60 micrograms.kg-1 in control subjects, related to a higher initial volume of distribution (cirrhotic 78.5 +/- 31.7 ml.kg-1, control 29.8 +/- 17.3 ml.kg-1). Time from complementary dose to 25% recovery was longer in cirrhotic patients (41.0 +/- 20.7 min vs 30.2 +/- 9.7 min), but time course of action during maintenance was not statistically different in the two groups. In cirrhotic patients receiving five maintenance doses or more, prolongation of the duration of action with successive maintenance doses could be statistically demonstrated. Spontaneous recovery was delayed in cirrhotic patients, because of impaired elimination processes: greater volume of distribution at steady-state (264 +/- 92 vs. 151 +/- 59 ml.kg-1); trend toward a lower clearance (189 +/- 60 vs. 296 +/- 169 ml.min-1). Rocuronium pharmacodynamics are moderately altered by cirrhosis, possible because of pharmacokinetic alterations. Individual variability in response to rocuronium is great, and dosage should be carefully titrated to that required.

The clinical neuromuscular pharmacology of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia.

Atracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate-duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures. Ninety-nine ASA physical status 1 or 2 patients undergoing elective surgical procedures under nitrous oxide/opioid/barbiturate anesthesia were studied. The neuromuscular blocking effect of 51W89 was assessed after administration of bolus doses from 0.015 to 0.4 mg/kg, as well as during and after continuous infusions from 11 to 249 min in length. The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.048 mg/kg. At 0.10 mg/kg, maximum block developed within 5.2 +/- 0.3 min, and recovery to 95% twitch height occurred 64.4 +/- 3.9 min after injection. At 0.4 mg/kg, onset was 1.9 +/- 0.1 min, and 95% recovery developed within 121.0 +/- 5.9 min. Comparative recovery indexes from 5% to 95% or from 25% to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.4 mg/kg (means ranged from 29.6 to 32.3 min and from 12.6 to 14.3 min, respectively). The average infusion rate necessary to maintain approximately 95% twitch suppression was 1.35 micrograms/kg/min. Recovery indexes from infusions were 5-95% 33.2 +/- 1.8 min and 25-75% 15.0 +/- 0.6 min, not differing significantly from recovery indexes from single bolus doses. Twenty-five patients received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at twitch height recovery of between 6% and 21%. Antagonism to 95% control twitch height developed within 6.8 +/- 0.3 min, and the neostigmine-accelerated 25-75% recovery index was 2.8 +/- 0.2 min. 51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate-duration neuromuscular blocking pharmacodynamics.

Differential effects of vecuronium on the thumb and great toe as measured by accelography and electromyography

We evaluated possible differential effects of vecuronium on the thumb and great toe using two types of neuromuscular transmission monitor. Train-of-four stimuli were simultaneously applied to the ulnar nerve and tibial nerves using cutaneous electrodes. The responses were quantified with accelographs (thumb and left great toe) and an electromyograph (right great toe). Twenty ASA 1 or 2 patients received, by random allocation, one of two types of anaesthesia: neuroleptanaesthesia or sevoflurane-based anaesthesia. With both techniques, the shortest time to maximum block after vecuronium 0.1 mg.kg-1 occurred in the thumb as measured by accelography. The average (SD) values with neuroleptanaesthesia were: 173(23) s for thumb using accelography; 220(16) s for great toe using accelography; 205(44) s for great toe using electromyography. The average (SD) value(s) with sevoflurane-based anaesthesia were: 137(15) for thumb using accelography; 179(21) for great toe using accelography; 153(23) for great toe using electromyography. The differences between the thumb and great toe were statistically significant during both types of anaesthesia when measured with the accelograph (p < 0.01). The time from completion of maximal block to 25% recovery of twitch height in the thumb was significantly longer than that of the great toe as measured by accelography during both types of anaesthesia (p < 0.05). In contrast, there were no statistically significant differences between time to maximum block and 25% recovery of twitch height of the thumb as measured by accelography compared to the values measured for the great toe using electromyography during either anaesthetic technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular effects of vecuronium and neostigmine in Montreal and Paris.

The potency of vecuronium was reported to be greater in Montréal than in Paris. This study was designed to determine whether there were differences in onset, duration, and reversibility with neostigmine between both centres. Twenty ASA I or II adults (ten men, ten women), aged 18-65 yr were studied in each of the two cities, during a standard thiopentone-fentanyl-nitrous oxide (60-70%) - isoflurane 0.5% end-tidal anaesthetic. Train-of-four stimulation was applied every 20 sec to the ulnar nerve at the wrist and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 0.1 mg.kg-1, was given as a bolus, and neostigmine, 0.04 mg.kg-1, was administered, with atropine 0.02 mg.kg-1, at 25% first twitch height recovery. Onset time to maximum blockade was (mean +/- SD) 3.9 +/- 1.3 min in Paris vs 4.5 +/- 1.3 min in Montréal (NS). Duration from injection to 25% first twitch recovery was shorter (28.5 +/- 6.8 min) in Paris than in Montréal (39.1 +/- 7.3 min) (P < 0.0001). Time from injection of neostigmine to a train-of-four ratio of 70% was not different in Paris (6.3 +/- 2.2 min) from Montréal (5.6 +/- 1.9 min). It is concluded that the duration of an "intubating" dose of vecuronium is longer in Montréal, but, when given at 25% first twitch recovery, neostigmine has the same efficacy in Montréal as in Paris.

Differential effects of vecuronium on the thumb and the big toe muscles evaluated by acceleration measurement.

To clarify the differential effects of vecuronium on the thumb and on the big toe, train-of-four (TOF) stimuli were applied to the ulnar nerve at the wrist and the tibial nerve at the ankle in anesthetized patients using two acceleration transducers. Ten adult patients, aged 21-55 years, were studied. Anesthesia was induced by an intravenous injection of thiopental, and vecuronium 0.1 mg·kg-1 was used for paralysis. Anesthesia was maintained with nitrous oxide (66%)-oxygen-sevoflurane (1 MAC). The duration of time to the maximal twitch depression on the thumb and the big toe was 136.5±32.5 s and 183.0±40.1 s (P<0.05), respectively. The time to 25% recovery of the twitch height on the thumb and the big toe was 48.1±17.3 min and 39.1±11.6 min, respectively; the time to 50% recovery of twitch height on the thumb and the big toe was 54.1±16.1 min and 40.0±9.2 min (P<0.05), respectively. When paralysis was reversed at 25% of TOF ratio on the thumb, the value of the TOF ratio on the big toe was 58.5±18.2% (P<0.01).

TETANIC FADE DURING RECOVERY FROM VECURONIUM BLOCK: COMPARISON OF SYSTEMIC AND ISOLATED FOREARM ADMINISTRATION

We have compared the degree of tetanic fade relative to twitch depression occurring after isolated forearm block with vecuronium and that after systemic i.v. injection. Fifteen patients received either vecuronium 0.3 mg into an isolated forearm or vecuronium 0.05 mg kg-1 systemically. Adductor pollicis mechanomyography was used to monitor recovery of twitch height at 0.2 Hz. At 25, 50, 75 and 100% recovery of twitch height, a 5-s, 50-Hz tetanus was administered and tetanic fade ratio measured. There was significantly less tetanic fade in the isolated forearm group (P < 0.01; unpaired ttest) at 25, 50 and 75% twitch height. This suggests that twitch depression and tetanic fade are independently mediated effects of vecuronium.

Neuromuscular and hemodynamic effects of mivacurium and succinylcholine in adult patients during nitrous oxide-propofol-fentanyl anesthesia.

The neuromuscular and hem+odynamic effects of mivacurium 0.15 mg/kg and succinylcholine 1 mg/kg were compared in 26 adult patients (ASA I and II) during nitrous oxide-oxygen-propofol-fentanyl anesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the hypothenar muscle resulting from supramaximal train-of-four stimuli applied to the ulnar nerve. Time to onset of over 95% block and duration to 25% recovery of control twitch after injection of mivacurium were significantly longer than for succinylcholine (201 +/- 37.6 vs 54 +/- 5.2 sec and 13.0 +/- 2.2 vs 8.4 +/- 2.1 min; mean +/- SD). Onset of mivacurium with priming technique was shortened (125 +/- 20.7 sec), but was also slower than that of succinylcholine. Although the recovery index during spontaneous recovery was significantly longer for mivacurium than for succinylcholine (6.9 +/- 1.3 vs 5.1 +/- 0.9 min), antagonism with neostigmine at 25% recovery of twitch height sufficiently facilitated the recovery index of mivacurium (4.5 +/- 1.0 min) to a level similar to that of succinylcholine with no statistical difference. The hemodynamic effects of mivacurium were few as compared to those of succinylcholine. In conclusion, mivacurium is considered to have additional advantages for short procedures when succinylcholine is undesirable.

Reaction to succinylcholine in two patients segregating for the plasma cholinesterase allele Ek.

Recently, several new alleles have been identified at plasma cholinesterase locus E1. We have had the opportunity for the first time to monitor the response to succinylcholine in two patients with the newly discovered genotype Ea1Ek1. The duration of action and type of neuromuscular block following succinylcholine 1.0 and 1.5 mg kg-1 i.v., respectively, were evaluated using train-of-four nerve stimulation and a Myograph 2000. One patient was anaesthetized with halothane, and the other was given a modified neurolept anaesthesia. Time to first response to nerve stimulation was 15 and 16 min, and time to 50% twitch height recovery was 19 and 20 min, respectively in the two patients. Both showed a depolarizing block. One of the patients received three bolus doses of succinylcholine 1 mg kg-1. This patient gradually developed a phase II block, which was easily reversed by edrophonium. The results indicate that patients with genotype Ea1Ek1 are slightly more sensitive to succinylcholine than are genotypically normal patients (Eu1Eu1) and patients heterozygous for the normal and the atypical gene (Eu1Ea1).

Influence of plasma cholinesterase activity on recovery from mivacurium-induced neuromuscular blockade in phenotypically normal patients.

The significance of plasma cholinesterase (pChe) activity for the duration of action of mivacurium in phenotypically normal patients was evaluated in 35 patients during neurolept anaesthesia. The response to train-of-four nerve stimulation was recorded using a Myograph 2000. Ten patients with normal pChe (Group I) and five patients with decreased pChe activity (Group 2) were given a small test dose of mivacurium 0.03 mg kg-1. Mivacurium 0.1 mg kg-1 was administered following spontaneous recovery from the first dose. The mean suppression of the height of the first (T1) of the train-of-four responses following mivacurium 0.03 mg kg-1 patients with normal and decreased enzyme activity was 40% and 56%, respectively, and the mean T1 suppression after mivacurium 0.1 mg kg-1 was 100% in both groups. The times to different levels of twitch height recovery following the 0.1 mg kg-1 dose did not differ between the two groups of patients. Another 20 patients with normal or decreased pChe activity (Group 3) were given mivacurium 0.2 mg kg-1. In this group the time to maximum block was 1.4 min (1.0-4.0) mean (range) and the time to reappearance of the T1 response was 15.0 min (7.4-22.7) (range). An inverse relationship was found between the patients' pChe activity and the time to first response. It is concluded that mivacurium is short-acting in patients with normal pChe phenotype and normal to low-normal pChe activity. No patient with very low pChe activity was included in the study. A prolonged response to mivacurium may, however, be expected in these patients.

COMPARISON OF INTUBATING CONDITIONS AFTER ADMINISTRATION OF ORG 9426 (ROCURONIUM) AND SUXAMETHONIUM

We have assessed intubating conditions after administration of Org 9426 (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1 in similar groups of patients. The influence of prior suxamethonium administration on the potency of Org 9426 was studied also by constructing a dose-response curve. Intubating conditions after Org 9426 were found to be clinically acceptable (good or excellent) in 95% of patients at 60 s and in all patients at 90 s and in all patients at both times after suxamethonium. The average time for the onset of block following Org 9426 at this dose was 89 s (which is shorter than with any of the currently available non-depolarizing neuromuscular blocking drugs); the duration of clinical relaxation (25% recovery of twitch height) 30 min. Prior administration of suxamethonium did not appear to influence the potency of Org 9426.

Pretreatment with pancuronium before suxamethonium administration in patients heterozygous for the usual and the atypical plasma cholinesterase gene

The object of this study was to investigate whether pretreatment with pancuronium before i.v. injection of suxamethonium could cause prolonged neuromuscular blockade in patients heterozygous for the usual and the atypical plasma cholinesterase gene (E1uE1a). Forty-three patients, 23 with genotype E1uE1a and 20 with normal genotype (E1uE1u), were pretreated with pancuronium 0.01 mg.kg-1 followed by suxamethonium 1.5 mg.kg-1, and received either neurolept anaesthesia or halothane anaesthesia. Seven patients (E1uE1a) were given suxamethonium 1.5 mg.kg-1 without pretreatment. The duration and type of neuromuscular block were evaluated using train-of-four (TOF) nerve stimulation. Type of anaesthesia did not significantly influence the results. The duration of block following pretreatment was significantly longer in heterozygous patients than in normal patients. Time to 90% twitch height recovery was 10.7 +/- 1.2 min (mean +/- s.d.) in genotypically normal patients, and 18.0 +/- 4.2 min in patients with genotype E1uE1a. Pretreatment with pancuronium caused a significantly slower recovery of the TOF ratio (phase II block). Thus, a TOF ratio of 0.7 was always reached within 13 min in genotypically normal patients. In genotypically abnormal patients, the same TOF ratio was reached within 20 min in all but three patients. In these three patients time to 90% twitch height recovery was prolonged (18-31 min), and TOF ratio did not return to normal, but stabilized at about 0.35, 0.50, and 0.65, respectively. Injection of edrophonium restored normal neuromuscular function in 10 min. It is concluded that in patients heterozygous for the usual and the atypical gene, pretreatment with pancuronium in combination with an increased dose of suxamethonium may cause a phase II block and thus a prolonged neuromuscular block.

The pharmacodynamics and pharmacokinetics of Org 9426, a new non-depolarizing neuromuscular blocking agent, in patients anaesthetized with nitrous oxide, halothane and fentanyl

The pharmacodynamics and pharmacokinetics of a new non-depolarizing neuromuscular blocking agent, Org 9426, were investigated. Ten patients undergoing elective head and neck surgery and anaesthetized with nitrous oxide, halothane and fentanyl, received a bolus dose of Org 9426 (1 mg.kg-1, 3 x ED90). The isometric contractions of the adductor pollicis muscle following ulnar nerve stimulation (0.1 Hz and intermittent TOF) were measured. Blood and urine were sampled over 8 and 24 hr, respectively. Concentrations of Org 9426 and its possible metabolites in plasma and urine were determined using HPLC. Pharmacokinetic variables were calculated by iterative linear least square regression analysis. Intubation conditions were excellent one minute after administration at a neuromuscular block of 88 (13)% (Mean (CV]. Onset time until maximum block, duration until 25% recovery of twitch height, and recovery from 25 until 75% of twitch height were 1.7 (32), 53 (19) and 20 (37) min, respectively. The TOF reached a ratio of 0.7 after 87 (19) min. Half lives were 1.8 (33), 19 (34), 131 (62) min, respectively, in a three exponential decay; distribution volume at steady-state and plasma clearance were 0.264 (56) L.kg-1 and 4.0 (21) ml.kg-1.min-1, respectively. Plasma concentration at 25% recovery of the twitch height was 1.0 mg.L-1. Within 24 h, 33 (37)% of Org 9426 was excreted unchanged in the urine. Metabolites were absent both in plasma and urine. We conclude that the difference in potency between Org 9426 and vecuronium is similar to the difference between their effective concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of bambuterol on plasma cholinesterase activity and suxamethonium‐induced neuromuscular blockade in subjects heterozygous for abnormal plasma cholinesterase

Bambuterol is a new bronchodilator which is also a reversible inhibitor of plasma cholinesterase. In patients with normal plasma cholinesterase genotype, bambuterol prolongs suxamethonium-induced neuromuscular blockade. In the present study, we investigated the interaction of bambuterol and suxamethonium in nine patients heterozygous for abnormal plasma cholinesterase during anaesthesia with fentanyl, thiopentone, halothane and nitrous oxide in oxygen. The patients (seven E1uE1a and two E1uE1s) were given 20 mg of bambuterol orally 2 h before anaesthesia. Suxamethonium 1 mg.kg-1 was given for tracheal intubation. The neuromuscular function was monitored using train-of-four (TOF) stimulation of the ulnar nerve and a force displacement transducer. Plasma cholinesterase activity decreased in all patients following bambuterol (P less than 0.001). In patients with genotype E1uE1a, median time to 90% recovery of twitch height and TOF ratio greater than or equal to 0.7 (37.5 min) was prolonged compared to 28 E1uE1a patients not treated with bambuterol (14.0 min) (P less than 0.001). Four of these patients developed a phase II block apparently not correlated to plasma cholinesterase activity. In the E1uE1s; patients, full recovery was seen after 22.0 and 31.4 min, respectively. It is concluded that in patients heterozygous for abnormal plasma cholinesterase, bambuterol 20 mg taken 2 h before anaesthesia causes a 2-3 times prolongation of the neuromuscular blockade following suxamethonium 1 mg.kg-1 and in some patients a phase II block.