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PubMedDate not supplied

Prolonged neuromuscular blockade following vecuronium infusion.

Administration of vecuronium by infusion is an increasingly common technique, both in the operating room and in the intensive care unit (ICU), for patients requiring prolonged neuromuscular blockade and mechanical ventilation. The major advantage of vecuronium over older neuromuscular blocking agents is its rapid excretion and intermediate duration of action. Prior to the current case report, the longest reported continuous paralysis after the cessation of a vecuronium infusion was 90 hours. A case of an 81-year-old patient with renal failure and subclinical chronic cirrhosis of the liver, who remained paralyzed for 13 days following a vecuronium infusion, is described. Intensive monitoring of neuromuscular function is recommended whenever muscle relaxants are administered by continuous infusion.

Aged↗
PubMed1996

Recovery from mivacurium-induced neuromuscular blockade is not affected by anticonvulsant therapy.

Long-term chronic anticonvulsant therapy produces a resistance to the effects of all nondepolarizing neuromuscular blocking agents studied to date. Since the metabolism of mivacurium is unique among the nondepolarizing neuromuscular blocking agents, the effect of anticonvulsants on its recovery parameters was examined. Forty-five patients were separated into three groups based on the number of chronic anticonvulsant medications the subjects were taking: subjects in group 1, the control group, took no anticonvulsant medication; group 2 subjects took one medication; and group 3 subjects took two medications. Mivacurium, 0.15 mg/kg i.v., was administered after induction of general anesthesia with thiopental sodium, 4-6 mg/kg, and fentanyl 2-4 micrograms/kg i.v. Maintenance anesthesia consisted of N2O in O2. 0.2-0.3% end-tidal isoflurane, and a fentanyl infusion. The evoked compound electromyograph (ECEMG) of the adductor pollicis-brevis muscle was measured for time of onset, T-1 (time at which ECEMG signal reaches 5, 25, 50, and 75% of baseline), TR (TOF ratio), and recovery index. T-1 at 25% was 18.2 +/- 1.8, 20.7 +/- 1.9, and 21.5 +/- 1.4 min for groups 1, 2, and 3, respectively, with TR at 25% being 23.7 +/- 2.3, 26.9 +/- 2.4, and 27.3 +/- 2.3 min. No significant differences were noted in neuromuscular recovery between groups at any time point. These results fail to demonstrate the resistance to the nondepolarizing neuromuscular blockade of mivacurium that has been observed with other nondepolarizing agents.

Adolescent↗
PubMed1985

Comparison between glycopyrrolate and atropine in a mixture with neostigmine for reversal of neuromuscular blockade. Studies in patients following open heart surgery.

Atropine and glycopyrrolate were compared in a mixture with neostigmine for reversal of neuromuscular blockade in patients undergoing open heart surgery. In patients not receiving beta-blocking drugs, glycopyrrolate was shown to possess advantages over atropine in terms of a lower initial increase in heart rate, better protection against the muscarinic effects of neostigmine, and smaller increases in rate-pressure product. The concomitant administration of beta-adrenergic blocking therapy significantly attenuated the effect of reversal on heart rate and the differences between atropine and glycopyrrolate were not significant. There was no difference in the incidence of arrhythmias between patients who received beta-blocking drugs and those who did not.

Adrenergic beta-Antagonists↗
PubMed1991

Potentiation of atracurium neuromuscular blockade by enflurane: time-course of effect.

This study was designed to determine the time required for potentiation of atracurium neuromuscular blockade after the introduction of enflurane. Ten ASA physical status I and II adults anesthetized with thiopental, nitrous oxide, and alfentanil were given 0.4 mg/kg atracurium besylate. The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation of the ulnar nerve was recorded. When the first twitch (T1) of the train-of-four recovered to 10% of control, an atracurium infusion was started and adjusted to keep the level of blockade constant. After 15 min of stable blockade, 1.6%-1.7% end-tidal enflurane was started and maintained for up to 2 h. Venous blood samples were drawn and plasma atracurium concentrations were measured 15 min before and 0, 5, 10, 15, 30, 45, 60, 90, and 120 min after the introduction of enflurane. Atracurium plasma concentrations were 730 +/- 127 (SEM) ng/mL at time 0. During the first 30 min, no significant decrease in plasma levels occurred; but at 45 min, concentrations were only 67% +/- 8% of their initial value (P less than 0.01) and 48% +/- 2% at 120 min (P less than 0.01). This suggests that the interaction between enflurane and atracurium is time-dependent. Clinically, the interaction between atracurium and enflurane is negligible during procedures of less than 45 min.

Adult↗
PubMed2001

Rocuronium-induced neuromuscular blockade is affected by chronic phenytoin therapy.

Patients receiving chronic anticonvulsant therapy have been reported to show resistance to certain nondepolarizing neuromuscular blockers. In this study, the effects of chronic phenytoin therapy on the onset, duration, and recovery of rocuronium action was assessed. Thirty-six patients scheduled for various neurosurgical procedures were studied: 18 receiving chronic phenytoin therapy (Group I) and 18 controls (Group II). Rocuronium 0.6 mg/kg (2 x DE95) was administered after induction of general anesthesia with 4-6 mg/kg thiopental sodium and 3-5 microg/kg intravenous (IV) fentanyl. Maintenance anesthesia consisted of N2O in O2, 0.5% end-tidal isoflurane, and a fentanyl infusion. Neuromuscular block was monitored with acceleromyography of the adductor pollicis-brevis muscle by using a TOF-GUARD Biometer monitor (Biometer International A/S, Odense, Denmark). According to the amplitude of the first response of train-of-four, neither the lag time nor the onset time differed between the two groups. However, the recovery index was significantly shorter in patients chronically treated with phenytoin (mean recovery index: control group, 8.3 +/- 1.7 minutes; phenytoin group, 6.7 +/- 2.3 minutes; P < .05). In addition, the times of recovery to 10%, 25%, 75%, and 90% of the baseline response were also significantly shorter in the phenytoin group than in the control group. We conclude that the duration of action of rocuronium and the recovery index were affected by chronic phenytoin therapy.

Adult↗
PubMed1990

Relationship between train-of-four ratio and first-twitch depression during neuromuscular blockade: a pharmacokinetic/dynamic explanation.

Fade, as measured by train-of-four, lags behind twitch depression during the initial phase of nondepolarizing neuromuscular blockade, i.e., the ratio of the fourth to first twitch height in a train (T4/T1) is greater at the onset of the block than during spontaneous recovery for the same level of first twitch depression. We believe that these data can be explained by picturing the muscle as having localized regions that respond much more slowly than the rest, leading to a delay in drug effect in that area, especially when the drug concentration rises rapidly as during bolus administration. This was modeled by computer as a muscle of 15 compartments distributed in a log-normal fashion according to equilibration rate. Experimental data consisting of the time course of first twitch and train-of-four ratio were fitted by nonlinear regression to the model. A good fit was obtained with a median equilibration time t1/2 of 3.3 min and a standard deviation of 2.1. The difference between train-of-four during onset and regression of block at the same level of first twitch depression was reproduced.

Computer Simulation↗
PubMed1996

Optimum time for neostigmine reversal of atracurium-induced neuromuscular blockade.

PURPOSE: The aim of the study was to determine the optimum time for administration of neostigmine during recovery from atracurium-induced neuromuscular blockade. METHODS: The study comprised 103 patients anaesthetised with midazolam, fentanyl, thiopentone, halothane, and nitrous oxide. Relaxation was induced with atracurium 0.5 mg. kg-1 and maintained with supplements of 0.15 mg. kg-1. The ulnar nerve was stimulated with train-of-four (TOF) and double burst stimulation (DBS). Evoked MMG responses were recorded. Patients were randomized to spontaneous recovery (n = 20) or to assisted recovery by neostigmine (0.07 mg.kg-1) at varying intervals (6-50 min) from the last atracurium dose (n = 83). RESULTS: The reversal time (time from administration of neostigmine to TOF ratio 0.7) was always < 13 min, when T1 (first twitch in TOF) was detectable or when D1 (first twitch in DBS) was > 5%. Total assisted recovery time (time from last supplemental atracurium dose to TOF ratio 0.7) increased with increasing T1 and D1 twitch heights (P < 0.05). The curve fitted to the scattergram with total assisted recovery time vs time from last atracurium supplement to neostigmine administration decreased to reach a minimum after which it increased to approach the line of identity. The minimum of the curve (total assisted recovery time 30.7 min) was reached when neostigmine was given 18.6 min after last atracurium supplement. At this time the T1 and D1 twitch height averaged 4 and 8% respectively. If prolongation of the minimum total recovery time of 2.5% is accepted, neostigmine can be given at T1 and D1 twitch height values of 0 to 8% and 4 to 15%, respectively. CONCLUSION: The optimum time for neostigmine administration, taking both the reversal time and total recovery time into consideration, is when 0 < T1 < 8% or when 5 < D1 < 15%. Giving neostigmine at more profound degrees of blockade prolongs reversal time, while giving neostigmine later in the recovery phase prolongs total recovery time.

Adolescent↗
PubMed1986

Recovery of spontaneous breathing following neuromuscular blockade with atracurium.

Atracurium 0.3 mg kg-1 was given to two groups of patients to compare the recovery of spontaneous breathing with that of peripheral neuromuscular function. Anaesthesia was maintained in one group (n = 6) with an infusion of etomidate (mean flow rate 24 micrograms kg-1 min-1) and in the other group (n = 5) with 0.5% halothane. From the time of discontinuing ventilation, about 5 min after the reappearance of the tetanic response, spontaneous breathing returned in an average time of 135 s (range 18-300) in the patients given etomidate and in 68 s (range 0-123) in the patients who received halothane (ns). The duration of action of atracurium was not significantly prolonged by halothane, probably because of the low concentration used. Adequate recovery of respiratory muscle function occurred within 30 min of administration of atracurium at a time when there was less than 25% recovery of the tetanic response of the adductor pollicis muscle. It was concluded that recovery of the muscles of respiration from neuromuscular blockade by atracurium occurred more rapidly than recovery of the muscles of the hand, but an adequate tidal volume in the absence of other clinical signs should not be regarded as a reliable indicator of complete return of neuromuscular function.

Adult↗
PubMed1983

The effect of bis-pyridinium oximes on neuromuscular blockade induced by highly toxic organophosphates in rat.

Two bispyridinium oximes, BDB-27 and HGG-12, were tested in vivo for their ability to restore neuromuscular function in rats poisoned by 1.3 LD50 of sarin, soman, tabun and XV, using isolated phrenic nerve-diaphragm preparation. Their effectiveness was evaluated in comparison with the two most potent oximes in this respect, HI-6 and TMB-4. It was found that BDB-27 was equal or superior to HI-6 in sarin, soman and XV and to TMB-4 in tabun poisoned animals. Recovery of function after HGG-12 was equal to HI-6 only in soman poisoning, but much less pronounced against neuromuscular blockade induced by the other three anticholinesterases. The results point at the equal effectiveness of BDB-27 in functional recovery in poisoning by all four toxic agents tested, so far not encountered by any other oxime.

Animals↗
PubMed1995

Optimum time for neostigmine administration to antagonize vecuronium-induced neuromuscular blockade.

We followed the recovery time course in 46 patients antagonized by neostigmine (0.036 mg kg-1) at different levels of vecuronium-induced neuromuscular blockade ranging from post-tetanic count 1 to train-of-four ratio 0.4 and in 15 patients during spontaneous recovery. Non-linear regression curve fit analyses showed that the optimal time for neostigmine administration was when the first twitch in the train of four (T1) was between 1% and 10%. Visual analyses of the scattergram in which the level of block, when neostigmine was given, was plotted against total recovery time (the time elapsed from administration of the last dose of vecuronium to train-of-four ratio 0.7) gave the same result. The reduction in total recovery time achieved by neostigmine was 32.6 min (SE diff. 6.0 min). To achieve the optimum effect, neostigmine must therefore be given 32.6 min plus the required time for peak effect of neostigmine (5.3-7.1 min), i.e. 37.9-39.7 min, before train-of-four ratio 0.7 is reached. During spontaneous recovery this corresponds to a T1 between 1% and 15%.

Adult↗
PubMedDate not supplied

Prolonged neuromuscular blockade for relaxation in two pediatric intensive care patients.

Newer neuromuscular blocking drugs provide optimum blockade and can facilitate ventilation, yet if they are discontinued, they allow predictable reversal. This article documents the use of these drugs in the treatment of two pediatric intensive care unit patients who had different physiologic problems and pharmacologic needs and who were ventilator dependent for a prolonged period. In each case, neuromuscular blockade significantly facilitated ventilation and allowed time for treatment of the underlying pathology without deleterious pharmacologic side effects resulting in a favorable outcome for both patients. The article discusses some of the unique pharmacologic properties of these drugs and the rationale for their use.

Adolescent↗
PubMed1988

Fade profiles during spontaneous offset of neuromuscular blockade: vecuronium and gallamine compared.

The characteristics of the train-of-four (TOF) response have been studied electromyographically during the onset and the spontaneous offset of neuromuscular blockade induced with vecuronium or gallamine. During the onset of blockade, at 75% depression of initial twitch height, gallamine was associated with significantly more TOF fade than vecuronium. Both agents were associated with significantly less fade during onset than during spontaneous offset. When the two neuromuscular blocking drugs were compared during spontaneous offset they showed a similar degree of fade during early offset (up to 50% recovery of initial twitch height). However, during late spontaneous offset, when the initial twitch height had recovered to 75% of control values, vecuronium was associated with more fade than gallamine.

Adult↗
PubMed2003

Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969.

BACKGROUND: The purpose of this study was to determine the changes in the plasma concentration of rocuronium and the reversal of its neuromuscular blockade after the intravenous infusion of Org 25969, the novel neuromuscular block-reversal agent, in anesthetized guinea pigs. METHODS: Rocuronium was infused for 1 h at a rate of 12-19 nmol.kg-1.min-1 to produce a steady-state 90% neuromuscular block. After 30 min, a concomitant infusion of either the reversal agent Org 25969 at a rate of 50 nmol.kg-1.min-1 or an infusion of an equivalent volume of saline was started. The time course of plasma concentrations of rocuronium was determined by use of liquid chromatography-mass spectrometry/mass spectrometry. RESULTS: In both treatment groups, a steady-state plasma concentration of rocuronium was obtained after 30 min. In the saline-treated group, the plasma concentration of rocuronium and depth of block remained constant. In the Org 25969 group, neuromuscular block was reversed while the rocuronium infusion was ongoing. Simultaneously, an increase in the total plasma concentration of rocuronium (free and complexed) was observed, even though the infusion rate of rocuronium was not changed. Compared with the saline-treated group, a small increase in the postmortem bladder concentration of rocuronium was detected. CONCLUSIONS: The authors propose that the capture of rocuronium by Org 25969 causes the rapid reversal of neuromuscular block. The reversal can be explained by the rapid transfer of free rocuronium from the effect compartment (neuromuscular junction) to the central compartment, in which it is bound to Org 25969. This explains the increase in total plasma concentration of rocuronium (free and bound to Org 25969).

Androstanols↗
PubMed1995

Effect of plasma anticonvulsant level on pipecuronium-induced neuromuscular blockade: preliminary results.

Patients receiving anticonvulsants are resistant to nondepolarizing muscle relaxants (NDMR). This study examines the effect of plasma anticonvulsant levels on pipecuronium-induced neuromuscular blockade. Twenty adult patients scheduled for neurosurgery were assigned to one of two groups. Group 0 (G0) consisted of 10 patients not on anticonvulsant therapy; group 1 (G1) included 10 patients treated either with phenytoin or carbamazepine. G1 patients were further divided into G1u (n = 4) and G1w (n = 6) subgroups, according to the plasma anticonvulsant level measured the day before surgery--under (G1u) or within (G1w) the therapeutic range. Neuromuscular transmission was monitored with a Biometer International A/S Accelograph. Anesthesia was induced and maintained using propofol and sufentanil. After calibration of the accelograph, a bolus of pipecuronium 0.08 mg/kg was given IV. The time from pipecuronium injection to the peak reduction of T1 was taken as the onset time. The time in min from pipecuronium injection to recovery of T1% (first accelograph response/baseline response) x 100 and TR% (fourth accelograph response/first accelograph response) x 100 were recorded at 25, 50, and 75% of baseline. The recovery index (RI) was taken as the time from 25 to 75% of baseline. The recovery index (RI) was taken as the time from 25 to 75% recovery of the baseline response. The onset time was not different in G0 (203 +/- 60.4 s), G1 (230.5 +/- 79.3 s), and G1u (181.8 +/- 60.4 s) but prolonged in G1w (279.2 +/- 67.7 s).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Intravenous pancuronium bromide for fetal neuromuscular blockade during intrauterine transfusion for red-cell alloimmunization.

Intravenous pancuronium bromide was administered into the umbilical cord by funipuncture to effect temporary fetal paralysis. Neuromuscular blockade was achieved in 12 fetuses undergoing a total of 34 intrauterine procedures for the treatment of severe red-cell alloimmunization. The same initial dose of 0.2 mg/kg fetal weight estimated by ultrasound was used in all cases, but anemic fetuses did not resume movement for prolonged periods. A relationship among fetal hematocrit, adjusted dose, and duration of paralysis was described by the equation: Duration (hours) = 5.24 + 10.30 adjusted dose (mg/kg) - 0.16 hematocrit (%) (R2 = 0.49; P less than .001). Intravenous pancuronium was found to be a safe and effective method for cessation of fetal movement during intrauterine procedures.

Blood Transfusion, Intrauterine↗