Dose-response relationships for edrophonium and neostigmine antagonism of atracurium and cisatracurium- induced neuromuscular block

PURPOSE: To study the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by atracurium and cisatracurium. METHODS: One hundred and twenty eight, ASA group 1 or 2 adults were given either 0.5 mg x kg(-1) atracurium or 0.1 mg x kg(-1) cisatracurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. The neuromuscular block was measured by an acceleration-responsive transducer. Responses were defined in terms of percent depression in the first twitch (T1) and train-of-four (TOF) response. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg x kg(-1)) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg x kg(-1)) was administered by random allocation. Neuromuscular function in another sixteen subjects was allowed to recover spontaneously. RESULTS: At five minutes, unlike edrophonium, neostigmine was equally effective against atracurium and cisatracurium with respect to T1 recovery. The neostigmine T1-ED50 was 10.3 +/- 1.06 (SEM) microg x kg(-1) after atracurium and 11.2 +/- 1.06) microg x kg(-1) after cisatracurium. The edrophonium ED50 was 157 +/- 1.07 microg x kg(-1) with atracurium and 47.4 +/- 1.07 microg x kg(-1) with cisatracurium, giving a neostigmine:edrophonium potency ratios of 15.2 +/- 1.7 and 4.2 +/- 0.41 (P < 0.001) for atracurium and cisatracurium, respectively. At 10 min neostigmine was 13 +/- 1.4 times as potent as edrophonium for achieving 50% TOF recovery after atracurium paralysis. After cisatracurium the potency ratio was 11.8 +/- 1.3 (NS). CONCLUSIONS: Although there were differences at five minutes, neostigmine:edrophonium potency ratios at 10 min, were similar in both relaxants studied.     

Neostigmine and edrophonium as antagonists of atracurium and pancuronium

Edrophonium 0.5 mg/kg or neostigmine 0.04 mg/kg were administered to two groups of 30 patients each for antagonism of atracurium- or pancuronium-induced neuromuscular block at 25% single twitch recovery. Neuromuscular block was studied using both single twitch and train-of-four (TOF) nerve stimulation. The times to 100% single twitch recovery were significantly more rapid for patients receiving edrophonium (P less than 0.01) in both groups (atracurium and pancuronium); the TOF ratios were similar for atracurium, but for pancuronium they were greater after neostigmine than after edrophonium, and only at 25 min were these ratios similar. It is concluded that edrophonium in a dose of 0.5 mg/kg antagonizes neuromuscular blockade induced by atracurium, as does neostigmine in a dose of 0.04 mg/kg, but the former does not consistently antagonize neuromuscular blockade induced by pancuronium even at 25% of single twitch recovery.     

Intubating conditions using cisatracurium after induction of anaesthesia with thiopentone

We studied tracheal intubation conditions produced by the muscle relaxant, cisatracurium, following induction of anaesthesia with fentanyl (2 μgkg⁻¹) and thiopentone (6 mgkg⁻¹). Sixty patients were randomly assigned to receive cisatracurium in a single bolus dose of either 0.15 or 0.20 mgkg⁻¹. Tracheal intubation was commenced 120 s after injection of the relaxant. The mean (SD) time taken to achieve intubation was significantly shorter in the 0.20 mgkg⁻¹ group (137 (16) s) than the 0.15 mgkg⁻¹ group (149 (12) s; p < 0.05). The intubating conditions were better after the larger dose. Our results suggest that when anaesthesia is induced using thiopentone, a dose of 0.20 mgkg⁻¹ of cisatracurium is recommended to ensure satisfactory intubating conditions.     

Recovery of post-tetanic count and train-of-four responses at the great toe and thumb

We have studied the recovery of post-tetanic count and train-of-four responses at the great toe and thumb accelerographically after the administration of vecuronium 0.2 mgkg⁻¹. Sixty adult patients scheduled for anaesthesia with nitrous oxide and isoflurane were studied. The times to the return of the first post-tetanic twitch were comparable at the great toe and thumb (mean (SD) times: 30.0 (6.5) min and 35.0 (8.5) min, respectively). Recovery of post-tetanic count followed similar time courses at the great toe and thumb. Also, time to the return of the first twitch of the train-of-four did not differ significantly at the great toe and thumb (47.5 (9.6) min vs. 49.7 (10.5) min). Similarly, time to the return of the second, third and fourth twitches of the train-of-four did not significantly differ at the great toe and the thumb. However, the value of the first twitch of the train-of-four, expressed as a proportion of control twitch, was significantly higher than that at the thumb between 50 min and 110 min after the vecuronium injection, and the train-of-four ratio at the great toe was significantly higher than that at the thumb between 60 min and 100 min after the vecuronium injection.     

A portable self-learning fuzzy logic control system for muscle relaxation

We have assessed the practicality and performance of the Vital Signs Paragraph neuromuscular blockade monitor as part of a 'self-learning' fuzzy logic control feedback system used to administer atracurium to a required depth of neuromuscular blockade. Fifteen patients undergoing surgery expected to last longer than 90 min entered the study. A Vital Signs Paragraph was used to measure the degree of neuromuscular blockade and control it such that the first twitch of the train-of-four was kept at 10% of its baseline value. The controller instructed a Graseby Medical 3400 infusion pump to administer an atracurium infusion to maintain this level of blockade. Five patients (33%) were withdrawn from the study due to inadequate piezo-electric sensor function. In the remaining 10 patients, the system achieved stable control of neuromuscular blockade with a mean (range) error for the first twitch of the train-of-four of −0.45 (−1.06 to 0.13)%. The mean atracurium infusion rate ranged from 0.13 to 0.67 mg.kg⁻¹.h⁻¹. These results compare reasonably well with previous results using the Datex Relaxograph, whilst the system itself was portable and easy to use. However, the reliability of the system was limited due to variability in the sensitivity of piezoelectric sensors.     

Neuromuscular interaction of sevoflurane — cisatracurium in a myasthenic patient

PURPOSE: To describe the influence of sevoflurane anesthesia on cisatracurium neuromuscular block in a myasthenic patient undergoing thymectomy. CLINICAL FEATURES: A myasthenic patient (Osserman IIB) was managed for one year before surgery with 60 mg pyridostigmine qid, 50 mg immuran tid and 30 mg prednisone therapy. Pyridostigmine was interrupted three months before surgery, and five sessions of plasmapheresis were done within 13 days before surgery. The neuromuscular response was monitored by Datex electromyographic response to train-of-four stimulation of the ulnar nerve. Sevoflurane 4% decreased the T1/C ratio by 20%. Administration of 0.025 mg x kg(-1) cisatracurium, during sevoflurane anesthesia, was followed by complete neuromuscular block for 45 min. Discontinuation of sevoflurane resulted, after 10 min, in recovery of the T which reached T1/C ratio of 50% after 30 min. CONCLUSION: The marked sensitivity of this myasthenic patient to 0.5 x ED95 of cisatracurium can be attributed to potentiation of cisatracurium neuromuscular block by sevoflurane, as evidenced by the reappearance of the first twitch of the train-of-four response 10 min after sevoflurane was discontinued.     

Neuromuscular interaction between cisatracurium and mivacurium, atracurium, vecuronium or rocuronium administered in combination

We compared the dose–response relationships of cisatracurium, mivacurium, atracurium, vecuronium and rocuronium and examined the interactions of cisatracurium with mivacurium, atracurium, vecuronium and rocuronium in humans by isobolographic and fractional analyses. We studied 180 adult patients during nitrous oxide–fentanyl–propofol anaesthesia. Neuromuscular block was monitored using mechanomyography to detect the twitch response of the ulnar nerve at the wrist. The dose–response curves were determined by probit analysis. The calculated ED₅₀ values and their 95% confidence intervals were 40.9 (38.1–43.7), 49.8 (47.0–52.6), 187.2 (175.1–199.3), 36.6 (34.7–38.5) and 136.4 (129.2–143.6) μg.kg⁻¹ for cisatracurium, mivacurium, atracurium, vecuronium and rocuronium, respectively. Corresponding ED₉₅ values were 57.6 (53.5–61.7), 91.8 (88.1–95.5), 253.1 (238.9–267.3), 52.9 (49.1–56.7) and 288.7 (276.2–301.2) μg.kg⁻¹, respectively. The interaction between cisatracurium and mivacurium, vecuronium or rocuronium was found to be synergistic, but the interaction between cisatracurium and atracurium was found to be additive. Synergy between cisatracurium and vecuronium or rocuronium was greater than between cisatracurium and mivacurium.     

Cisatracurium during halothane and balanced anaesthesia in children

Cisatracurium, 51W89, is one of the ten stereoisomers of Tracrium^® which, unlike atracurium, has been reported to have a lack of histamine mediated cardiovascular effects at doses as high as 8×ED₉₅ in adults. We compared the time-course of neuromuscular effects of 80 μg·kg⁻¹ or 100 μg·kg⁻¹ cisatracurium during N₂O-O₂-halothane or N₂O-O₂-opioid anaesthesia, respectively, in 32 children 2–12 years old. Neuromuscular function was monitored by evoked adductor pollicis EMG. Even-numbered patients ( n =16) were allowed to obtain full spontaneous recovery of neuromuscular function and odd-numbered patients ( n =16) received neostigmine 45 μg·kg⁻¹ together with glycopyrrolate at the time of 25% EMG recovery. Data are expressed as median with 10th to 90th percentile range. Cisatracurium had an onset time (time from administration to maximal effect) of 2.2 (1.7–3.8) or 2.3 (1.8–4.9) min, a clinical duration (time to 25% EMG recovery) of 34 (22–40) or 27 (24–33) min, and a spontaneous 25–75% recovery time (time from 25 to 75% EMG recovery) of 11 (9–13) or 11 (7–12) min during halothane or balanced anaesthesia, respectively (NS). Train-of-four ratio recovered to 0.70 in 2.5 (1.8–3.0) or 3.2 (2.1–4.3) min following neostigmine during halothane or balanced anaesthesia, respectively (NS). Changes in blood pressure or heart rate following cisatracurium were negligible. We regard cisatracurium as a safe and promising intermediate duration muscle relaxant the effects of which can easily be reversed with neostigmine.     

ANTAGONISM OF INTENSE ATRACURIUM-INDUCED NEUROMUSCULAR BLOCK IN CHILDREN

Antagonism of intense neuromuscular block induced by atracurium0.5 mg kg^–1 was attempted in four groups of six childrenusing one of two doses of neostigmine (0.05 mg kg^–1 and0.1 mg kg^–1) or of edrophonium (0.5 mg kg^–1 and1.0 mg kg^–1) when the first twitch of the post-tetaniccount (PTC1) was 10% of control. For comparison with normalpractice, a fifth group received neostigmine 0.05 mg kg^–1when the first twitch of the train-of-four was 10% of control.Total recovery time from PTC1 10% to a train-of-four ratio of0.8 was not reduced by early administration of the anticholinesterases,compared with conventional administration of neostigmine atT1 10%. However, recovery from intense block was faster afterneostigmine than edrophonium (P < 0.01). Doubling the dosesof the anticholinesterases did not reduce the recovery timeand had the effect of increasing variability. We conclude thatthere is no clinical advantage in attempting to antagonize intenseneuromuscular block in children using normal or increased dosesof neostigmine or edrophonium.     

Dose-response relationships for edrophonium and neostigmine as antagonists of atracurium and vecuronium neuromuscular blockade

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.     

EFFECT OF DOXAPRAM ON THE RATE OF RECOVERY FROM ATRACURIUM AND VECURONIUM NEUROMUSCULAR BLOCK

We have studied the effect of doxapram on the rates of spontaneousand neostigmine-induced recovery from neuromuscular block withatracurium and vecuronium, by measurement of the time to recoveryof Tl (first twitch in the train-of-four) from 25 to 75% ofcontrol (recovery index, RI). After each neuromuscular blockingdrug, Rl was measured without administering either doxapramor neostigmine (control group), or after administration of doxapram1 mg kg–1, neostigmine 50 µg kg–1 or a combinationof doxapram and neostigmine, in groups of 10 patients. Rl wassignificantly longer after vecuronium in the presence of doxapramcompared with control (20.1 min vs 14.6 min). There was no significantdifference in the Rl after atracurium in the presence of doxapramcompared with control (12.5 min vs 11.8 min) or when neostigminewas administered with or without doxapram (2.4 min vs 2.4 min,respectively after vecuronium; 3.3 min vs 2.9 min, respectively,after atracurium).     

Comparison of caudal block using bupivacaine and ketamine with ilioinguinal nerve block for orchidopexy in children

Forty boys weighing less than 25 kg undergoing unilateral orchidopexy were randomly allocated to receive one of two analgesic regimens. Group C received a caudal epidural block with 0.25% bupivacaine 1 mlkg⁻¹ and preservative-free ketamine 0.5 mgkg⁻¹; Group L received an ilioinguinal nerve block with 0.25% bupivacaine 0.5 mlkg⁻¹ and infiltration of the wound with 0.25% bupivacaine 0.5 mlkg⁻¹. All subjects received diclofenac sodium 1–2 mgkg⁻¹ as a rectal suppository. Postoperative pain was assessed by means of a modified Objective Pain Score and analgesia was administered if this exceeded a value of 4. The median duration of analgesia was 10 h (range 2.6 to > 24 h) in Group C and 2.9 h (range 0.7 to > 24 h) in Group L (p < 0.05). There were no differences between groups in the incidence of motor block, urinary retention, postoperative vomiting or postoperative sedation. Subjects in Group L required significantly more doses of postoperative analgesia than those in Group C (p < 0.05).     

Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade

The effect of epidurally administered bupivacaine on duration, intensity and reversal characteristics of atracurium-induced neuromuscular blockade was studied in 30 healthy patients anaesthetized with thiopentone, fentanyl, midazolam and nitrous oxide. Fifteen patients received, in addition, epidural anaesthesia with bupivacaine. The remaining patients served as controls. The ulnar nerve was stimulated at the wrist and the evoked twitch response from the adductor pollicis was measured with a force displacement transducer. Neuromuscular blockade was induced with atracurium 0.5 mg i.v. and maintained with repeated doses of atracurium 0.15 mg/kg whenever the twitch height had recovered to 15% of the initial twitch height. After operation, the neuromuscular blockade was reversed with neostigmine when the twitch height had recovered to 15%. In the epidural group the clinical duration of neuromuscular blockade, time until first response to train-of-four (TOF) and reversal time were all significantly prolonged (P less than 0.05). Post-tetanic count (PTC) after 20 min was also significantly lower in the epidural group (P less than 0.05). It is therefore concluded that epidurally administered bupivacaine prolongs atracurium-induced neuromuscular blockade. The clinical implication of the modest prolongation is, however, limited.     

Time to peak effect of neostigmine at antagonism of atracurium- or vecuronium-induced neuromuscular block

Study Objective: (1) To determine the time to peak effect of neostigmine (time to peak antagonism) during atracurium- or vecuronium-induced neuromuscular block; and (2) to determine the effect on time to peak effect of neostigmine during atracurium-induced neuromuscular block, when the dose of neostigmine is increased from 35 μg/kg to 70 μg/kg.

Design: Prospective, randomized clinical study.

Setting: Gynecologic operating room suite at a university hospital.

Patients: 45 ASA I and II women admitted for gynecologic laparotomy.

Interventions: Anesthesia was performed with thiopental sodium, fentanyl, halothane, nitrous oxide, and atracurium or vecuronium. Train-of-four (TOF) stimulation and mechanomyography were used to monitor neuromuscular transmission. Neostigmine was administered while a constant degree of neuromuscular block was maintained at a twitch height at a point between 4% and 11% of the control twitch height, using a continuous infusion of atracurium or vecuronium. The patients were randomized to three groups, with 15 patients in each group. Group 1 received atracurium block antagonized with neostigmine 35 μg/kg; group 2 received vecuronium block antagonized with neostigmine 35 μg/kg; and group 3 received atracurium block antagonized with neostigmine 70 μg/kg.

Measurements and Main Results: The degree of neuromuscular block at antagonism was similar in the three groups. Time to peak effect (mean ± SD) on TOF ratio was significantly longer in Group 1 (9.7 ± 3.0 minutes) versus Group 2 (6.6 ± 1.4 minutes; (p < 0.05). The time to peak effect on TOF ratio during atracurium-induced block was reduced from 9.7 ± 3.0 minutes to 6.3 ± 2.0 minutes when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg (p < 0.05). The peak effect on TOF ratio was significantly greater in Group 3 compared with Group 1 (p < 0.05), while it was similar in groups 1 and 2.

Conclusion: The time to peak effect of neostigmine 35 μg/kg is about 6 to 10 minutes when antagonizing a constant degree of atracurium- or vecuronium-induced neuromuscular block at a twitch height at a point between 4% and 11%. Even though the time to peak effect was longer with atracurium than with vecuronium, clinically significant differences between the antagonizing effect of atracurium versus vecuronium block were not demonstrated. The time to peak effect during atracurium-induced block decreased when the dose of neostigmine was increased from 35 μg/kg to 70 μg/kg.     

The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

Comparison of the effects of neostigmine and edrophonium on the duration of action of suxamethonium

Rapid sequence induction of anaesthesia necessitating the use of suxamethonium may occasionally be needed soon after antagonism of neuromuscular block with anticholinesterase agents. The onset and duration of action of 1 mg kg^-1 of suxamethonium was recorded in groups of 10 patients each, 5 or 10 min after the administration of edrophonium 1 mg kg^-1 or neostigmine 40 μg kg^-1 given for the antagonism of atracurium-induced neuromuscular block. Plasma cholinesterase activity was measured before, and 5 and 10 min after the administration of the anticholinesterases. A further 10 patients received suxamethonium 1 mg kg^-1 without prior atracurium or anticholinesterase administration to serve as controls. The onset of action of suxamethonium was significantly prolonged when administered 5 min after both anticholinesterases, compared to the control group ( P <0.01). Recovery of suxamethonium block was delayed significantly after neostigmine, compared to both the edrophonium and the control groups ( P <0.05–0.001). Plasma cholinesterase activity was significantly reduced with the use of neostigmine but not with edrophonium ( P <0.001).     

A comparison of acceleromyography and mechanomyography for determination of the dose–response curve of rocuronium in children

In order to compare an acceleromyograph (TOF-Guard^TM) with a mechanomyograph (Grass FT03), the dose–response relationship of rocuronium was simultaneously determined in both arms of 15 children aged 3–11 years during anaesthesia with thiopentone, alfentanil and nitrous oxide. Three subgroups of five children received rocuronium 120, 180 or 240 μg.kg⁻¹ randomly. The effective doses to produce 50% and 95% depression of the first twitch of the train-of-four determined by acceleromyography were 206 and 337 μg.kg⁻¹, respectively, while these values determined by mechanomyography were 151 and 331 μg.kg⁻¹, respectively. The dose–response curve obtained by acceleromyography was steeper and shifted to the right compared with that obtained by mechanomyography (p < 0.0001). The difference between the effective dose producing 50% twitch depression determined by the two devices was highly significant (p < 0.0001). In 13 out of 15 children, the acceleromyograph control train-of-four ratio was significantly greater than unity. Although there was a good correlation ( r  = 0.85) between simultaneous pairs of measurements of neuromuscular block, the acceleromyograph exhibited a bias of −25% relative to the mechanomyograph with wide limits of agreement (−62 to +12%). We conclude that acceleromyographic and mechanomyographic measurements should not be used interchangeably when determining the potency of muscle relaxants.     

Desflurane potentiates atracurium in humans: A comparative study with isoflurane

Study Objective: (1) To evaluate the neuromuscular effects of desflurane and its interactions with atracurium and (2) to compare desflurane and isoflurane in these effects.

Design: Sequential entry of informed and consenting patients randomly assigned to receive desfurane (n = 25) or isofurane (n = 25).

Setting: Operating suite of a county-university medical center.

Patients: Fifty adults, ASA physical status I, undergoing elective orthopedic surgery.

Interventions: Following establishment of steady desfurane or isofurane anesthesia, at 1.25 minimum alveolar concentration (MAC) exhaled for 15 minutes, a randomly predetermined dose of atracurium (0.05, 0.1, or 0.15 mg/kg) was injected intravenously (IV). At the end of surgery, neostigmine 0.04 mglkg IV was given to reverse the residual block. The neuromuscular effects of desfurane or isofurane alone, and the dose-response relationship, time course, and reversibility of the neuromuscular effects of atracurium with either anesthetic, were examined in detail and compared using electromyographic quantification of the response of the first dorsal interosseous muscle to train-of-four (TOF) stimulation of the ulnar nerve.

Measurements and Main Results: TOF fade and depression of the first response (T₁) of the TOF were measured in response to desfurane or isofurane, atracurium, and neostigmine. Desf urane caused more TOF fade than isofurane prior to atracurium administration. The TOF ratios were 0.91 ± 0.02 and 0.98 ± 0.01, respectively (p < 0.05). For other measured neuromuscular parameters, atracurium-induced depression tended to be greater in the presence of desfurane than in the presence of isofurane, but none of the measured differences reached the statistical significance level of p < 0.05. The ED₅₀, ED₉₅, and 25–75% recovery index of atracurium were 0.038 mg/kg (95% confidence level; range 0.030 to 0.047 mg/kg), 0.11 mg/kg (0.095 to 0.14 mg/kg), and 31 ± 4 minutes (means ± SEM) with desfurane anesthesia, versus 0.043 mg/kg (0.035 to 0.052 mg/kg), 0.13 mg/kg (0.11 to 0.16 mg/kg), and 23 ± 4 minutes with isofurane anesthesia (p = 0.1-0.2). Continuation of either anesthetic at 1.25 MAC prevented complete recovery of neuromuscular functions spontaneously or following neostigmine 0.04 mg/kg.

Conclusion: In ASA physical status I adults, 9% desfurane has neuromuscular effects equal to or slightly in excess of those of 1.6% isofurane.     

Neuromuscular blocking effects and train-of-four fade with cisatracurium: comparison with other nondepolarising relaxants

Neuromuscular blocking drugs exhibit different degrees of fade in response to train-of-four stimulation believed to represent their relative prejunctional effects. The present study was designed to compare the train-of-four fade after cisatracurium and compare this with other commonly used muscle relaxants. Train-of-four fade during onset and recovery of block were recorded after administration of cisatracurium 0.05 or 0.1 mg.kg-1, atracurium 0.5 mg.kg-1, vecuronium 0.08 mg.kg-1, mivacurium 0.15 mg.kg-1 or rocuronium 0.6 mg.kg-1 to patients anaesthetised with fentanyl, nitrous oxide and a propofol infusion. Neuromuscular monitoring was by stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle. The onset and recovery of block were also measured. Train-of-four fade during onset of block was greater with the lower dose of cisatracurium compared with the higher dose of cisatracurium and all other relaxants. Train-of-four fade during recovery was similar. The median times (and ranges) for the onset of maximum block were 3.4 (2.1-5.6), 1.5 (1.2-2.3), 2.1 (1.2-2.6), 2.0 (1.5-2.7) and 1.0 (0.7-1.3) min for cisatracurium 0.1 mg.kg-1 and atracurium, mivacurium, vecuronium and rocuronium, respectively. The median times (and ranges) for the recovery of T1 to 25% of control and to a train-of-four ratio of 0.8 were 41 (21-50) and 65 (40-78); 43 (37-54) and 69 (58-79); 15 (11-20) and 25 (19-30); 31 (23-46) and 60 (45-117); and 33 (18-57) and 50 (28-76) min following cisatracurium, 0.1 mg.kg-1, atracurium, mivacurium, vecuronium and recuronium, respectively.     

A comparison of the effects of tramadol and morphine on gastric emptying in man

In a previous study using an electrical bioimpedance technique and the paracetamol absorption test, we demonstrated that 0.09 mgkg⁻¹ of morphine delayed gastric emptying in healthy human volunteers. The aim of this study was to investigate whether analgesic doses of tramadol would cause a delay in gastric emptying similar to conventional opioids. Using the same volunteers and techniques as in our previous study, placebo or tramadol (1 mgkg⁻¹) was given in a randomised, double-blinded, cross-over placebo-controlled study. Gastric emptying was measured concurrently by a noninvasive epigastric bioimpedance technique and by the paracetamol absorption test. After the ingestion of 500 ml of deionised water plus paracetamol 1.5 g, the mean (SEM) time taken for gastric volume to decrease to 50% ( t _0.5) was recorded. No difference in gastric emptying rates ( t _0.5) between placebo, 7.7 (1 min), and tramadol, 9.5 (2 min), was noted. In our previous study, morphine prolonged t _0.5 to 21 (3) min (p < 0.03). The maximum concentration and area under the curve of serum paracetamol concentrations following morphine were significantly different from placebo (p < 0.05) and tramadol (p < 0.05). We conclude that tramadol at a dose of 1 mgkg⁻¹ does not delay gastric emptying in humans.