Accelerated onset of vecuronium neuromuscular block with pulmonary arterial administration

The purpose of this study was to determine the onset times of vecuronium neuromuscular block administered into either the central circulation or a peripheral vein. One hundred and twenty adult patients with a pulmonary artery (PA) catheter were randomly divided into one of three groups with respect to the routes of vecuronium administration (n = 40 in each group). Anaesthesia was induced with midazolam 2.5 mg iv and fentanyl 10–50 μg · kg^{? 1} iv and maintained with intermittent doses of fentanyl 50 μg iv and nitrous oxide 60–70% in oxygen. After immobilization of the forearm in a splint, the ulnar nerve was stimulated supramaximally every 12 sec. The resulting force of the evoked thumb twitch was recorded (Myograph 2000, Biometer, Denmark). The times from the injection to the first depression of twitch response (latent onset) in patients given vecuronium 0.08 mg · kg^{? 1} into the pulmonary artery, the right atrium, and a peripheral vein on the hand were 58.0 ± 19.5, 71.5 ± 17.1, and 82.4 ± 18.0 sec (mean ± SD), respectively. The latent onset of neuromuscular block occurred sooner in patients given vecuronium into the central vein than when administered into a vein on the hand (P < 0.01). In comparing the patients given vecuronium into the central vein, the onset times to 95% twitch depression (onset) were 152.3 ± 40.7 and 168.2 ± 35.5 sec. The onset of block was found to be faster when vecuronium was administered into the pulmonary artery than into the right atrium (P < 0.01). These findings suggest that the administration of vecuronium into the pulmonary artery is one approach to accelerate neuromuscular blockade in patients with a PA catheter.     

Acceleromyography improves detection of residual neuromuscular blockade in children

Purpose

To determine whether detection of residual blockade is improved by using the accelerograph. A secondary objective was to compare acceleromyographic measurements with those obtained by electromyography.

Methods

In a prospective, randomized, double-blind investigation, 22 anaesthetized children were studied during recovery from neuromuscular blockade following 0.1 mg· kg^?1 vecuronium iv. Assessments of depth of block began 10 min after injection and were repeated at one minute intervals using electromyography (Datex, Relaxograph) in one hand, and acceleromyography (Biometer, Tofguard) in the other, to measure responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve. Monitoring was stopped when no fade was visible and TOF ratio ≥0.7. The electromyographic (EMG) and acceleromyographic (AMG) data were compared with corresponding observations of the number of twitches and TOF fade in the visible responses of the thumb, made by the attending anaesthetist. The method of Bland and Altman was used to compare differences between AMG and EMG data.

Results

During recovery from neuromuscular blockade, fade was no longer visible clinically 38.6 ± 10.4 min (mean ± SD) after the administration of vecuronium. This corresponded to TOF ratios of 0.40 ± 0.23 by AMG and 0.34 ± 0.21 by EMG. Usually, two twitches were visible before AMG detected the first twitch. The time to TOF ratio ≥0.7 by AMG and EMG was similar at 49.1 ± 10.5 and 50.9 ± 9.0 min, respectively. The bias between AMG and EMG was one minute, with limits of agreement from ?10 to nine min.

Conclusion

AMG is superior to visual assessment in detecting residual neuromuscular block and provides similar estimates of recovering block as the more cumbersome EMG.     

Monitoring orbicularis oculi predicts good intubating conditions after vecuronium in children

Purpose

The aim of the study was to compare visual estimation of onset of neuromuscular blockade at both the adductor pollicis (AP) and the orbicularis oculi (OO) in children and to determine if monitonng the OO could predict good intubating conditions during vecuronium-induced neuromuscular blockade.

Methods

Thirty ASA I–II children (1.5–9 yr) were studied. Anaesthesia was induced with 6–8 mg · kg^?1 thiopentone. The ulnar nerve at the wrist and the temporal branch of the facial nerve were stimulated every 10 sec using train of-four (TOF) stimuli. Vecuronium. 0.15 mg · kg, was administered as a bolus. The responses at both the OO and the AP were evaluated visually. Patients were randomly divided into two groups. In the AP group (n = 15), the trachea was intubated when the AP was completely blocked. In the OO group (n = 15), intubation was performed when the OO was completely blocked. Intubating conditions were scored on a scale of 1 to 4.

Results

All the patients had complete blockade at both the orbicularis oculi and the adductor pollicis. In the two groups, time from injection of vecuronium to complete neuromuscular blockade was shorter at the orbicularis oculi than at the adductor pollicis, 1.5 ± 0.5 min vs 2.3 ± 0.7 min, respectively, (P < 0.05; mean ± SD) in the AP group, 1.7 ± 0.3 min vs 2.3 ± 0.8 min, respectively, in the OO group (P < 0.05). Intubating conditions were excellent in all patients except one. where it was rated as good. They did not differ between groups.

Conclusion

Following administration of 0.15 mg · kg^?1 vecuronium in children, monitoring of the OO can detect good intubating conditions 0.7 min earlier than with monitoring of the AP.     

Early neuromuscular recovery characteristics following administration of mivacurium plus vecuronium

Purpose

This study was designed to describe the early recovery characteristics, as well as the speed of onset of neuromuscular block, after a combination of mivacurium and vecuronium.

Methods

In this controlled, randomized study, 30 consenting ASA I–III patients were assigned to three treatment groups. The “2M2V” group received twice the dose necessary to cause 95% depression of the evoked twitch response (2 × ED₉₅) of mivacurium (0.15 mg · kg^?1) plus 2 × ED₉₅ of vecuronium (0.1 mg · kg^?1); the “2V” group received 2 × ED₉₅ of vecuronium; and the “4V” group received 4 × ED₉₅ of vecuronium. Evoked neuromuscular responses of the adductor pollicis were assessed with an adductor pollicis force transducer. The time until maximum block and times to 10% and 25% recovery (T₁₀ and T₂₅) in each group were expressed as mean ± standard deviation and compared using ANOVA.

Results

Onset of block in the 2M2V group was 27% faster than in the 2V group (2.0 ± 0.6 vs. 2.7 ± 0.8 min respectively, P < 0.05) and was similar to the 4V group (1.95 ± 0.3 min, P = NS). The times until 10% recovery were similar in the 2M2V and 4V groups (59.9 ± 12 vs 68.2 ± 25 min, P = NS) and were slower than in the 2V group (37.2 ± 9 min, P < 0.05). Between T₁₀ and T₂₅, recovery after 2M2V resembled that after 2V (6.7 ± 3 vs 5.7 ± 1 min, P = NS) and was faster than after 4V (10.9 ± 7 min, P<0.05).

Conclusions

When 2 × ED₉₅ of mivacurium is added to 2 × ED₉₅ of an intermediate or long-acting relaxant, recovery after T₁₀ will proceed as if one had administered the longeracting agent alone.     

Prolonged mivacurium infusion in young and elderly adults

Purpose

This study was designed to evaluate phanmacodynamically and phamnacokinetically if the cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients.

Methods

The mechanomyogramic neuromuscular response of the adductor pollicis was recorded in 32 adults 18–59 yr. and 19 elderly (> 60 yr.) patients dunng N₂O:O₂:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 ± 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response.

Results

The mean mivacurium infusion requirement to maintain 97 ± 1 (mean ± SD)% depression of the twitch response was 6.0 ± 0.4 μg· kg^?1· min^?1 in young adults, and 4.3 ± 0.3 μg· kg^?1· min^?1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 ± 1.2 μg· kg^?1· min^?1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with tow cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients.

Conclusion

When the mivacurium infusion was titrated to maintain 95 ± 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.     

Monitoring of vecuronium-induced neuromuscular block at the sternocleidomastoid muscle in anesthetized patients

Purpose

To assess the degree of neuromuscular block acceleromyographically at the sternocleidomastoid muscle.

Methods

Eighteen adult patients scheduled for air–oxygen–sevoflurane–fentanyl and epidural anesthesia were studied. In the patients, the right accessory nerve and the sternocleidomastoid muscle were stimulated and the contraction of the sternocleidomastoid muscle was evaluated acceleromyographically. Simultaneously, the response of the adductor pollicis muscle was measured electromyographically. Supramaximal stimulating current, degree of maximum neuromuscular block after vecuronium 0.1 mg/kg, and onset of or recovery from vecuronium-induced neuromuscular block were compared between the two muscles.

Results

The supramaximal stimulating current at the sternocleidomastoid muscle was significantly higher than that at the adductor pollicis muscle (54.8 ± 7.1 vs. 33.7 ± 10.3 mA, mean ± SD, P < 0.001). The onset of neuromuscular block at the sternocleidomastoid muscle did not significantly differ from that at the adductor pollicis muscle (214 ± 117 vs. 161 ± 87 s, P = 0.131). The degree of maximum neuromuscular block at the sternocleidomastoid muscle was significantly less than that at the adductor pollicis muscle (93.6 ± 3.1 vs. 99.2 ± 2.5%, P < 0.001). During recovery from neuromuscular block, T1/control and train-of-four ratio measured at the sternocleidomastoid muscle were significantly higher than those at the adductor pollicis muscle 10–30 and 40–120 min after vecuronium, respectively (P < 0.05).

Conclusion

The sternocleidomastoid muscle is more resistant to vecuronium than the adductor pollicis muscle. Recovery from neuromuscular block is faster at the sternocleidomastoid muscle than at the adductor pollicis muscle.     

Neuromuscular monitoring: does it make a difference?

Purpose

The objective of the present prospective study was to evaluate the influence of neuromuscular monitoring. on the level of neuromuscular blockade from induction of anaesthesia until extubdtion of the trachea.

Methods

Forty-two patients aged between 18 and 73 yr undergoing a range of surgical procedures under general anaesthesia were randomly distributed into two groups of 21 patients each. In both groups a Datex NMT Monitor® was used and electromyographic responses of the the ulnar muscles to supramaximal stimulation of the ulnar nerve were recorded. In Group 1, the anaesthetist could see the movements of the stimulated hand, but not the monitor. In Group 2, the anaesthetist could see neither the stimulated hand nor the monitor. The same anaesthetist administered the neuromuscular relaxants which were succinylcholine 1.5 mg · kg^?1 for trachéal intubation and vecuronium 0.1 mg· kg^?1 for neuromuscular relaxation during surgery, followed by 1 to 2 mg maintenance injections. Possible residual curarization was evaluated in the recovery room by head lift tests and pulse oximetry.

Results

Patients in Group 1 had deeper neuromuscular block throughout surgery, despite the use of a comparable dose of vecuronium (10.1 mg for G1 vs 11.2 mg for G2). The EMG values of T₁ and train-of-four values were not different at trachéal intubation or at extubation. No patients presented signs of residual curarization in the recovery room.

Conclusion

The study demonstrates that with the same amount of vecuronium the neuromuscular relaxation was deeper with the use of a simple neuromuscular monitoring (visual evaluation of the thumb movements). Despite the deeper neuromuscular block in the monitored group, there was no residual curarization in the recovery room.     

Comparison of vecuronium with ORG 9487 and their interaction

Purpose

To compare the pharmacodynamic behaviour of vecuronium with that of ORG 9487. we measured the time-course of action of equipotent doses of ORG 9487 and vecuronium and investigated their mutual interaction when given in succession.

Methods

Sixty ASA I–II patients were anaesthetized with thiopentone, fentanyl halothane and nitrous oxide and assigned randomly to four groups. Each patient received an initial dose (ID) of either vecuronium (V) or ORG 9487 (O) followed by maintenance doses (MD_n) of either V or O (ID/MD: O/O, V/O, O/V, and V/V). The time course of action was measured mechanomyographically, determining the duration until 25% recovery of the single twitch (DUR₂₅).

Results

The onset time of an ID of ORG 9487 was shorter than that of an ID of vecuronium (96vs 203 sec. P < 0.001). The DUR₂₅ of the ID of ORG 9487 was less than half that of vecuronium (10.7 ± 2.8 vs 28.8 ± 6.1 min, P< 0.001). The DUR₂₅ of MD₁ and MD₂ of ORG 9487 were shorter than those of vecuronium (O/O: 7.3 ± 2.8 and 8.5 ± 2.4 mm. V/O: 12.7 ± 3.3 and 11.5 ± 3.5 min,vs O/V. 16.4 ± 4.5 and 20.6 ± 4.7 min: V/V: 18.8 ± 3.0 and 20.1 ± 3.8 min, respectively, P < 0.05). An ID of vecuronium prolonged the DUR₂₅ of MD₁ and MD₂ of ORG 9487 (P < 0.05)

Conclusion

ORG 9487 is a muscle relaxant with a shorter duration of action than vecuronium. Maintenance doses of ORG 9487 are also shorter acting than roughly equipotent maintenance doses of vecuronium, irrespective of which relaxant is given initially.     

Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

Purpose

To determine the characteristics of neuromuscular block produced by two and three times the 95% effective dose (ED₉₅) of doxacurium in patients undergoing coronary artery surgery with hypothermic cardiopulmonary bypass.

Methods

In a prospective non randomized study, ten patients received doxacurium 0.05 mg·kg^?1 (Group 1) and ten others received 0.075 mg · kg^?1 (Group 2) with midazolam and sufentanil. The mechanomyographic response of the adductor pollicis muscle after supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium (10% of the initial dose) was administered until sternal closure whenever the first twitch (T₁) had recovered to 25% of control.

Results

The onset time (time to maximal T₁ depression) of doxacurium was 390 ± 148 sec in Group 1 and 370 ± 74 sec in Group 2 (P = 0.71). The clinical duration of neuromuscular block (time to 25% T₁ recovery) was 165 ± 90 min in Group 1 and 258 ± 86 min in Group 2 (P = 0.03). On arrival to recovery room the mean T₁ was 57 ± 23% in Group 1 and 24 ± 21% in Group 2(P = 0.003); the mean T₄/T₁ ratio was 0.25 ± 0.15 for five patients of Group 1 with four responses to TOF stimulation and 0.10 for the only patient of Group 2 with four twitches.

Conclusion

In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED₉₅. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.     

Atropine and neuromuscular fade in the mouse phrenic nerve-diaphragm

Purpose

These studies were intended to resolve the conflict between the reasonable inference from the scientific literature that atropine might alter neuromuscular fade and the expectation from informal clinical experience that it does not.

Methods

We examined the effect of a high concentration of atropine (20 μM) on moderate neuromuscular block and fade produced by d-tubocurarine (dTC). Isometric twitch tension was measured in the mouse phrenic nerve-diaphragm preparation. In one set of experiments, the phrenic nerve was stimulated with trains of 5 pulses at 10 Hz every second. Block and fade were measured in two groups, control and with atropine (n = 6 each). In another set of experiments, the phrenic nerve was stimulated with standard train-of-four stimulation (TOF, 4 pulses at 2 Hz every 11.5 seconds). Block and fade were measured first in a control period and then in a treatment period with either saline (n = 4) or atropine (n = 4).

Results

During 10 Hz train stimulation, atropine had no significant effect on either the block of the first twitch (control: 62 ± 17; atropine: 75 ± 4) or fade (control: 55 ± 12: atropine; 57 ± 14) produced by dTC. Similarly, atropine did not differ significantly from saline in altering dTC-induced block of first twitch (saline: 92.5 ± 14; atropine 92.5 ± 9.6% control) or fade (saline 119 ± 50; atropine 102 ± 30% control) during TOF stimulation.

Conclusions

While atropine may alter ACh release under some conditions, its action is not great enough to alter either block or fade.     

Recovery of post-tetanic and train-of-four responses at the first dorsal interosseous and adductor pollicis muscles in patients receiving vecuronium

Purpose

To compare recovery of accelographical responses to post-tetanic twitch (PTT) and train-of-four (TOF) stimuli obtained at the first dorsal interosseous muscle (DI) with those at the adductor pollicis muscle (AP) after administration of vecuronium 70 μg · kg^?1.

Methods

Sixty adult patients were randomly assigned to one of four groups: PTT-DI (n = 15), PTT-AP (n = 15), TOF-DI (n = 15), or TOF-AP (n = 15) group. In PTT-DI and PTT-AP groups, responses to PTT were measured accelographically at the DI and at the AP, respectively. In TOF-DI and TOF-AP groups, responses to TOF were measured at the DI and at the AP, respectively.

Results

The T₁/T₀ (T₀ = control) was greater in the TOF-DI than in TOF-AP group throughout recovery (P < 0.05), and the T₄/T₁ was greater in the TOF-DI than in TOF-AP group during the 30–40 min after vecuronium injection (P < 0.05). Time to the return of the first response to PTT (post-tetanic count₁, PTC₁) was less in the PTT-DI than in the PTT-AP group (17.7 ± 4.2 vs 21.7 ± 5.6 min, mean ± SD, P = 0.0341). The post-tetanic count PTC (number of single twitch stimuli in response to PTT) was greater in the PTT-DI than in the PTT-AP group during the 10–30 min after vecuronium (P < 0.05). Time to the return of T₁ was less in the TOF-DI than in the TOF-AP group (23.1 ± 6.0 vs 27.6 ± 4.9 min, P = 0.0334).

Conclusion

Recovery of responses to PTT and TOF stimuli occurred earlier at the DI than at the AP.     

Evaluation of twitch responses obtained from abductor hallucis muscle as a monitor of neuromuscular blockade: Comparison with the results from adductor pollicis muscle

The twitch responses evoked from the abductor hallucis muscle (AHM) and the adductor pollicis muscle (APM) were examined simultaneously in 20 anesthetized patients following a single bolus intravenous administration of 0.04 mg·kg⁻¹ of vecuronium bromide. The mean onset time of vecuronium-induced depression of AHM twitch responses was significantly slower than that of APM twitch responses (4.9±1.5 minvs 3.7±1.2 min, mean±SD,P<0.001), and when the clinical duration times of vecuronium were compared, AHM twitch responses recovered more quickly than APM twitch responses (15.3±4.1 minvs 19.6±6.7 min,P<0.01), although there was no statistically significant difference in the spontaneous recovery time between AHM and APM (9.8±2.9 minvs 10.0±3.6 min). It is concluded that the twitch responses of AHM may be a useful monitor of neuromuscular blockade in anesthetized patients in whom setting the blockade monitor on the patient's arms is difficult, although monitoring of twitch response of AHM is less sensitive than that of APM in case of vecuronium administration.     

Oral clonidine does not alter vecuronium neuromuscular blockade in anaesthetized patients

Since clonidine, an α₂-agonist, inhibits the release of norepinephrine or acetylcholine which can decrease nondepolarizing muscle relaxant-induced neuromuscular blockade, the authors examined whether clonidine given as an oral preanaesthetic medication would alter the onset, duration or recovery of a vecuronium neuromuscular blockade in lightly anaesthetized patients. Thirty-eight patients (aged 20–73 yr) randomly received oral clonidine either approximately 5 μg · kg^?1 (n = 21) or none (n = 17), 90 min before arrival in the operating room. We measured acceleration of thumb contraction with ulnar nerve stimulation at the wrist to assess neuromuscular blockade. The onset time (the time from injection to decrease to 5% of baseline twitch height), duration (the time interval between injection and return of the first twitch to 25% of the baseline value), and recovery index (the time interval of the first twitch from 25% to 75% of the baseline value) of neuromuscular blockade from a single bolus of vecuronium 0.1 mg · kg^?1 iv were determined and compared between the clonidine-treated and control patients during lower abdominal or extremity surgery under epidural plus general anaesthesia with fentanyl and nitrous oxide in oxygen. No differences were noted between the control and clonidine groups in onset time (100 ± 6 sec (mean ± SE) vs 101 ± 6 sec), duration (44.5 ±2.7 min vs 42.9 ±2.7 min), or recovery index (21.6 ± 2.8 min vs 19.1 ± 1.9 min) of neuromuscular blockade from vecuronium, respectively. These results show that oral preanaesthetic medication of clonidine 5 μg · kg^?1 does not alter neuromuscular blockade induced with vecuronium 0.1 mg · kg^?1 in patients during combined epidural and fentanyl/nitrous oxide general anaesthesia.     

Monitoring of neuromuscular blockade in one muscle group alone may not reflect recovery of total muscle function in patients with ocular myasthenia gravis

Purpose

We report on two patients with ocular myasthenia gravis who received rocuronium, followed later by sugammadex to reverse neuromuscular blockade. Recovery was monitored simultaneously at the adductor pollicis muscle (APM) and the corrugator supercilii muscle (CSM).

Clinical features

Two patients with ocular myasthenia gravis (case 1: 74 yr-old female, 54 kg; case 2: 71 yr-old male, 72 kg) were scheduled for surgery under general anesthesia. Neuromuscular blockade was induced with rocuronium 0.3 mg·kg^?1 after placing two separate monitors at the APM and the CSM, respectively. Additional doses of rocuronium 0.1-0.2 mg·kg^?1 were given to maintain neuromuscular blockade at fewer than two twitches at the APM during surgery. Train-of-four response at the CSM did not show recovery of the twitch after its initial disappearance. At the end of surgery, sugammadex was administered. Twitch height at the APM recovered to the control value in 12 min (case 1) and 13 min (case 2) after sugammadex administration; however, twitch height at the CSM took 26 min (case 1) and 14 min (case 2) to recover to the control value.

Conclusion

After rocuronium-induced paralysis in both patients with ocular myasthenia, spontaneous recovery and sugammadex-assisted recovery were slower at the CSM than at the APM. In patients without the disorder, CSM recovery is faster than APM recovery. Thus, in ocular myasthenia gravis, neuromuscular recovery at the APM may not reflect recovery of all muscles.     

Neostigmine requirements for reversal of neuromuscular blockade following an infusion of mivacurium

Purpose

To study the efficacy of neostigmine compared with placebo for the antagonism of neuromuscular blockade at the end of a mivacunum infusion, and to determine its optimal dose.

Methods

One hundred adult patients undergoing an elective surgical procedure received a standardized anaesthetic with 20–30 mg·kg^?1 alfentanil, a propofol infusion and nitrous oxide. Muscle relaxation was maintained at 90–95% T1 depression with 0.2 mg·kg^?1 mivacunum followed by an infusion. Neuromuscular blockade was measured with an integrated evoked electromyogram in response to train-of-four (TOF) stimuli at the ulnar nerve every 20 sec. Patients were randomized into four groups. At the end of surgery, the mivacunum infusion was stopped and patients received. immediately, in a double-blind manner, neostigmine (10, 20. or 40 mg·kg^?1) or placebo according to a random number table. The Tl and TOF ratio were recorded until adequate recovery of neuromuscular function (TOF ratio > 0.70). During the reversal penod, non-invasive blood pressure and heart rate were recorded every minute. The incidence of postoperative nausea and vomiting (PONV) was recorded in the recovery room.

Results

Data from 94 patients who completed the protocol were analysed. Compared with placebo, neostigmine 10 gmg·kg did not reduce the time to TOF > 0.70 (17.0 ± 5.1 vs 14.6 ± 4.2 mm respectively). However the time was decreased with neostigmine 20μg·kg and 40 μ·?^?1 (P < 0.001), but with no difference between these last two groups (11.4 ± 3.0 and 11.4 ± 3.5 min respectively). Changes in systolic blood pressure and heart rate were not different between the four groups. Very few PONV events were observed in all groups (global incidence 7.4%).

Conclusion

Recovery of neuromuscular blockade following a mivacunum infusion is accelerated by neostigmine. A dose of neostigmine 20μ·kg^?1 appears optimal with no further reduction in recovery time obtained from a larger dose.     

Die Wechselwirkung von Rocuronium und Rauchen Der Einfluß des Rauchens auf die neuromuskuläre Übertragung nach Rocuronium

Recent studies have shown different results concerning the effects of smoking on neuromuscular blocking agents. Some reports indicate that smokers need higher doses of vecuronium, but are more sensitive to atracurium. The aim of this study was to evaluate the effects of smoking on onset and recovery time after a single 0.6 mg/kg intubating dose of rocuronium an analog of vecuronium. Methods: Following institutional approval and informed consent, 20 smokers (>10 cigarettes/day) and 20 nonsmokers were included in the study. Following oxazepam premedication and induction with fentanyl and thiopental, single-twitch stimulation of the ulnar nerve was performed every 10 s. Following stabilisation of control responses, patients received rocuronium 0.6 mg/kg for intubation. Anaesthesia was maintained with enflurane ≤0.8 vol.% (end-tidal) and 65% nitrous oxide in oxygen. Onset time and recovery to 25% and 75% of the twitch control values were recorded. Results: Onset and recovery times were not different between smokers and nonsmokers. Conclusions: The results of the present study suggest that chronic nicotine exposure does not change onset time or duration of rocuronium neuromuscular blockade. A previous study found a greater need for vecuronium in smokers and discussed stimulation of the neuromuscular junction and enhanced biotransformation due to the enzyme-inducing properties of nicotine. The differences in our results could be partly due to a longer period of refraining from smoking in our patients, leading to very low nicotine blood concentrations without the proposed receptor-stimulating effect. Another cause for different behaviour of the two analogs could be different elimination pathways. Recent investigations suggest that rocuronium may not be eliminated principally by the liver. Therefore, enhanced nicotine-induced biotransformation, as suggested for vecuronium, would not occur with rocuronium.     

Succinylcholine and vecuronium blockade of the diaphragm,laryngeal and limb muscles in the anaesthetized goat

The purpose of the study was to compare the response of the cricoarytenoideus dorsalis muscle (CD) to neuromuscular blocking drugs with those of the thyroarytenoideus (TA), diaphragm (DI) and ulnaris lateralis (UL) muscles. Evoked electromyographic response to indirect supramaximal stimulation at 1 Hz was monitored in ten adult goats under thiopentone-halothane anaesthesia. The onset time and duration of neuromuscular blockade after intravenous administration of 500 μg · kg^?1 of succinylcholine or 4 μg · kg^?1 of vecuronium were determined. Times to 100% paralysis in CD, TA, DI and UL after succinylcholine were (mean ± SD) 39 ± 11, 39 ± 11, 42 ± 8 and 57 ± 8 seconds, respectively; the corresponding times for vecuronium were 5.6 ± 2.3, 4.6 ± 1.7, 6.0 ± 1.9 and 9.6 ± 1.7 min. The order of recovery to 25% spontaneous EMG activity was TA, CD, DI and UL after succinylcholine (durations: 9.7 ± 3.6, 11.0 ± 3.0, 15.3 ± 1.3 and 22.0 ± 1.2 min, respectively) but DI, CD, TA and UL after vecuronium (durations: 31.9 ± 18.6, 35.2 ± 19.5, 47.1 ± 19.9 and 71.7 ± 16.1 minutes, respectively). Thus, as in the diaphragm and thyroarytenoideus muscles, onset time and duration of succinylcholine or vecuronium blockade were shorter in the abductor muscle of the glottis, cricoarytenoideus dorsalis, than in the limb muscle.     

The reversal of profound mivacurium-induced neuromuscular blockade

Purpose

Mivacurium is metabolized by plasma cholinesterase catalyzed ester hydrolysis. Acetylcholinesterase antagonists used in the reversal of muscle relaxation may also inhibit plasma cholinesterase and, therefore, delay the hydrolysis of mivacurium. The clinical interaction between acetylcholinesterase antagonists and mivacurium induced neuromuscular blockade was studied.

Method

Intraoperative muscle relaxation was maintained with a mivacurium infusion to achieve a constant intense block (first twitch, T¹, 2–3% of control). Patients were randomly divided into three groups. Patients in Group 1 received no anticholinesterase, in Group 2 neostigmine 0.07 mg · kg^?1, and in Group 3 edrophonium 1 mg · kg^?1. The times between termination of the mivacurium infusion (Group 1) or the administration of the anticholinesterase (Groups 2 and 3) to 25%, 50%, 75% and 95% T₁ recovery, and to 50%, 70% and 90% recovery in the ratio, T₄/T₁ (TR) were recorded.

Result

In the neostigmine Group, T₁ recovery to 25%, 50% and 75% ( 2.32 ± 1.41, 3.90 ± 1.85 and 6.88 ± 2.66 min) was accelerated compared with control (3.36 ± 1.34, 5.78 ± 2.22, and 8.58 ± 3.60, and), but recovery to 95% (18.53 ± 9.09 vs 13.29 ± 5.24 min) was delayed. Also, TR recovery to 50%, 70%, and 90% was slower (14.47 ± 8.73, 21.25 ± 11.06 and 31.37 ± 12.11 min vs 11.75 ± 3.74, 13.78 ± 4.39 and 17.86 ± 6.44 min). However, all T₁ and TR recovery times were decreased in the edrophonium group (0.88 ± 0.51, 2.00 ± 1.50, 4.97 ± 2.96, and 9.35 ± 5.24 min for T₁ and 6.86 ± 3.93, 9.05 ± 4.51 and 12.24 ± 6.66 min for TR).

Conclusion

Neostigmine reversal of intense mivacurium neuromuscular block should be avoided, as this may result in prolongation of the block.     

The effects of magnesium sulfate on neuromuscular blockade by cisatracurium during induction of anesthesia

Background

During the induction of anesthesia, patients are at risk of aspiration while awaiting full muscle relaxation. Magnesium has been shown to have synergistic effects with neuromuscular blocking drugs. We tested if magnesium, as an adjunct, increases the speed of onset of muscle relaxation, thereby decreasing the risk of aspiration.

Methods

Eighty-eight American Society of Anesthesiologists (ASA) physical status 1 or 2 patients were randomly assigned to three groups. Group Mg-0 received 100 mL of normal saline, whereas groups Mg-25 and Mg-50 received magnesium sulfate at doses of 25 and 50 mg/kg, respectively. Anesthesia was induced with thiopental 5 mg/kg and cisatracurium 0.15 mg/kg. A peripheral nerve stimulator and single-twitch test was performed on the ulnar nerve until the twitch responses to stimulation had disappeared, and the times were recorded. Then the patients were intubated and anesthesia was maintained with 100 μg/kg/min of propofol. The intensity of blockade was measured at regular time intervals with the post-tetanic count test.

Results

The mean times to muscle relaxation in groups Mg-0, Mg-25, and Mg-50 were 226, 209, and 188 s, respectively (P = 0.047). The intensity of the block increased with the dose of magnesium, and remained highest in group Mg-50 at all times measured (P < 0.05). The speed of onset and the intensity of muscle relaxation increased as higher doses of magnesium were used.

Conclusion

The increased speed of onset of muscle relaxation produced by magnesium is not substantial enough to justify its use in combination with cisatracurium in rapid sequence induction.     

Duration of succinylcholine and vecuronium blockade but not potency correlates with the ratio of endplate size to fibre size in seven muscles in the goat

Purpose

Muscles differ in their response to neuromuscular relaxants. This study investigated whether (1) the relative responses of muscles is inverted between succinylcholine (SUX) and vecuronium (VEC), and (2) differences in dose-response or duration of action are related to the morphology of fibres, endplates and acetylcholine receptors (AChR) in muscles.

Methods

In goats during thiopentone anaesthesia, the evoked EMC response to indirect train-of-four stimulation was monitored and the cumulative dose-response curves and duration of action of SUX and VEC in the diaphragm, cricoary-tenoideus dorsalis, thyroarytenoideus, transversus abdominis, rectus abdominis, soleus and gastrocnemius muscles were determined and related to their fibre composition, fibre size, endplate size, endplate to fibre size ratio, AChR number or AChR density by regression analysis.

Results

There were no differences in the ED₅₀s of SUX [range, 119 ± 11 (SE) to 159 ± 20 μg · kg^?1] or VEC [range, 2.8 ± 0.2 to 3.7 ± 0.8 μg · kg^?1] among muscles. With either drug, duration to 25% or 50% T₁ recovery was shortest at the laryngeal muscles and longest at abdominal muscles (P = 0.0001), and correlated directly with fibre size (r ≥ 0.40: P < 0.004) and inversely with the endplate to fibre size ratio (r ≥ 0.40; P < 0.008).

Conclusion

The results show that (I) the relative responses of muscles do not differ between depolarizing and non-depolarizing relaxants; (2) the duration of blockade is shorter in muscles composed of small fibres with large endplates relative to fibre size; and (3) there is no relation between fibre type composition and sensitivity to muscle relaxants.