Intubating conditions and neuromuscular block after divided dose mivacurium or single dose rocuronium

Purpose

To evaluate the tracheal intubating conditions and neuromuscular blocking charactenstics of divided dose mivacurium or single dose rocuronium.

Methods

Thirty-two patients undergoing elective surgery were studied. Anaesthesia was with propofol 2 mg · kg^?1, followed by an infusion of l50 μg · kg^?1 · min^?1. Patients were randomized to receive either mivacurium-0.15 mg · kg^?1 followed 30 sec later by 0.1 mg · kg^?1, or rocuronium-0.9 mg · kg^?1, followed 30 sec later by placebo. Tracheal intubating conditions were assessed 90 sec after the initial dose of relaxant by an anaesthetist who was unaware of patient group. The electromyographic (EMG) response of the first dorsal interosseus muscle to ulnar nerve train-of-four was measured.

Results

Successful tracheal intubation was performed in all patients after both mivacurium and rocuronium. Intubating conditions (jaw relaxation, open visible vocal cords) were judged to be good-excellent in all but one patient before insertion of the tracheal tube. However, patients receiving mivacunum were more likely to experience coughing and bucking after tracheal tube insertion (10/16 patients) than those receiving rocuronium (3/16 patients, P < 0.05). No patient in the rocuronium group experienced moderately vigorous coughing and bucking after insertion of the tracheal tube vs six patients in the mivacurium group (P < 0.05). Time to 10 and 25% recovery of neuromuscular function was faster (P < 0.05) after divided dose mivacunum (20 ± 1 and 23 ± 1 min, respectively) than after rocuronium (45 ± 5 and 57 ± 8 min, respectively).

Conclusion

The results suggest that, during conditions of the study, divided dose mivacurium is not recommended for a 90-sec tracheal intubation in patients where moderate coughing and bucking is deemed unacceptable.     

Potency and hourly maintenance requirement of combinations of mivacurium and pancuronium in adults

Purpose

To evaluate the dose-response and maintenance requirements of a combination of mivacurium and pancuronium (cMP) in clinical practice.

Methods

In a randomised, open clinical study, 70 patients, 17–50 yr of age, were anaesthetised with propofol, alfentanil and nitrous oxide in oxygen. Thirty patients received mivacurium and 20 patients received pancuronium to establish dose-response curves for these agents. Hourly maintenance requirements of mivacurium and pancuronium to maintain 90–95% neuromuscular blockade (NMB) were determined. Thereafter, 20 additional patients received cMP in incremental doses to establish a cumulative dose-response curve for cMP followed by maintenance doses of cMP NMB was recorded by adductor pollicis electromyography.

Results

The ED₉₅ values for mivacurium and pancuronium were 100 and 66μg·kg^?1, respectively; and for the cMP 2:1 (in mg:mg basis), 32 μg·kg^?1 mivacurium together with 16 μg·kg^?1 pancuronium. This cMP was 1.8 times more potent than one parent agent (P < 0.0001 ). When cMP 2:1 was used, 60% of normal maintenance requirement of pancuronium reduced the requirement of mivacurium by > 90%. If cMP 20:1 was used, then 20% of normal maintenance requirement of pancuronium reduced the requirement of mivacurium by > 70%. Neostigmine 35 μg·kKg^?1 given at T₁ 10% recovery following cMP reversed the NMB to a TOF ratio of 0.70 in 9.5 ±3.9 min.

Conclusion

These results reflect considerable synergism between mivacurium and pancuronium. The cMP is near intermediate-acting and the NMB is easily reversed with neostigmine. By using cMR it may be possible to save some pharmacological costs during maintenance of anaesthesia.     

Mivacurium in children with Duchenne muscular dystrophy

The authors retrospectively reviewed their experience with mivacurium for neuromuscular blockade in seven children with Duchenne muscular dystrophy. Mivacurium was administered to seven children ranging in age from 8.3 to 14.4 years and in weight from 29 kg to 68 kg during either posterior spinal fusion or lower extremity release. An initial bolus dose of 0.2 mg·kg^?1 was followed by a continuous infusion. Neuromuscular blockade was monitored with a standard twitch monitor and the TOF (2 Hz for 2 s). Complete suppression of all four twitches occurred in 1.5 to 2.6 min. The continuous infusion was started with the return of the first twitch and adjusted to maintain one twitch. Time to recovery of the first twitch varied from 12 to 18 min. Continuous infusion requirements varied from 3 to 20 μg·kg^?1 with an average for the case of less than 10 μg·kg^?1 min^?1 in five of the seven patients. A moderate increase in sensitivity to mivacurium in this patient population is suggested by a decrease in infusion requirements and a prolonged effect following the initial dose.     

Smoking increases the requirement for rocuronium

Purpose

To compare the potency of rocuronium in non-smokers and smokers during general anaesthesia.

Methods

In a randomized, open clinical study, 40 patients, 17–62 yr of age, were anaesthetized with propofol, alfentanil and nitrous oxide in oxygen. After obtaining individual dose-response curves for rocuronium, bolus doses of rocuronium were given to maintain neuromuscular block at 90–99% for 60 min. Evoked adductor pollicis electromyography (EMG) was used to monitor neuromuscular block.

Results

The ED₉₅ values (± SEM) for rocuronium were 460.5 ± 28.9 and 471.5 ± 22.1 μg·kg^?1 for nonsmokers and smokers, respectively (P:NS). However, doses of rocuronium to maintain 90–99% neuromuscular block (± SEM) were 620.1 ± 46.7 and 747.4 ± 56.0 μg·kg^?1·hr^?1 for non-smokers and smokers, respectively (P = 0.0504).

Conclusion

The results may indicate increased metabolism of rocuronium in smokers rather than increased requirement of rocuronium at the receptor site.     

Mivacurium infusion requirements following vecuronium: different response between adults and children

The mivacurium infusion requirements following vecuronium were evaluated in 15 adults and 15 children in an open prospective clinical study. This study was undertaken to elucidate whether potentiation of effect occurred when a mivacurium infusion was administered after vecuronium was used for the facilitation of tracheal intubation. The adult patients were anaesthetized with N₂O:O₂, propofol and fentanyl, the children with halothane (1%) N₂O:O₂ Vecuronium 100 μg · kg^?1 was administered during stimulation of the ulnar nerve with train-of-four stimuli at 0.1 Hz. The force of contraction of the adductor pollicis was recorded. Upon recovery of the twitch response from vecuronium, a mivacurium infusion was started at 4 μg · kg^?1 · min^?1, thereafter adjustments were made to maintain the first twitch of the train-of-four (T₁ at 1–10% of control. The mean (±SE) initial infusion requirements in children of mivacurium was 4.3 (0.4) μg · kg^?1 · min^?1 which increased linearly (P < 0.001) over the next 90 min to 10 μg · kg^?1 · min^?1. In adults the infusion requirement was lower than in children and remained at approximately 3 μg · kg^?1 · min^?1 over the next 75 min. At the end of the surgical procedure, the children recovered faster than the adults with no child requiring reversal. Because of prolonged recovery (>20 min), seven adults required reversal with 15–70 μg · kg^?1 neostigmine. Mivacurium infusion requirements following vecuronium are higher in children than adults. Potentiation of the effects of mivacurium were seen when vecuronium preceeded mivacurium. This potentiation of effect lasted longer in adults than in children.     

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.     

Mivacurium in infants and children

Mivacurium is the only available short-acting nondepolarizing muscle relaxant in clinical use. It is a bis-quaternary benzylisoquinolinium ester hydrolysed by plasma-cholinesterase into inactive compounds. The ED₅₀ and ED₉₅ in children are about 50 μg·kg^?1 and 90 μg·kg^?1 respectively. In infants, they have a tendency to be lower. A standard intubating dose of 0.25 mg·kg^?1 causes complete neuromuscular depression in 1.5–2 min, recovery to 5% in 6–10 min, and complete recovery in 15–20 min. The recent tendency is to use 0.3 mg·kg^?1 to obtain better intubating conditions with slight prolongation of effect. Since the recovery profile of mivacurium is independent of the dose and duration, it is most suitable for administration by continuous infusion. The infusion requirement in children is 10–16 μg·kg^?1 min^?1, which is about twice that of adults. Cutaneous flushes from histamine release are commonly seen with the larger doses of mivacurium; however, the associated hypotensive effects are minimal and counteracted by the tracheal intubation. The duration of action of mivacurium is prolonged in patients with cholinesterase deficiency. Mivacurium's neuromuscular effects can be satisfactorily antagonized by edrophonium or neostigmine.     

Target-achieved propofol concentration during on-pump cardiac surgery: a pilot dose-finding study

Purpose

Propofol concentrations that produce laboratory-based cardioprotective effects are generally greater than those produced under routine anesthesia during cardiac surgery. It is unknown whether experimental cardioprotective propofol concentrations can routinely be achieved during cardiopulmonary bypass (CPB) using continuous infusion.

Methods

Twenty-four patients scheduled for primary aortocoronary bypass grafting with CPB were allocated to receive one of three propofol infusion rates; 50, 100, or 150 μg · kg^?1 · min^?1 in an open-label pilot study. Data were described using a line of best fit to derive an experimental clinical maneuver predicted to produce a whole blood concentration of 5 μg · mL^?1 at reperfusion. A predetermined interim analysis of 30 patients who were receiving the derived maneuver in an ongoing study was used to evaluate the maneuver. Cardiac index (CI), systemic vascular resistance index (SVRI), and left ventricular stroke work index (LVSWI) were recorded.

Results

The infusion rate-concentration curve had an equation of y = 0.215e ^0.0279x , where y represents the whole blood concentration and x represents the infusion rate (r ² = 0.781). The predicted infusion rate to achieve a mean concentration of 5 μg · mL^?1 was 113 μg · kg^?1 · min^?1. The nearest practical rate is 120 μg · kg^?1 · min^?1, producing a concentration of 5.39 (1.45) μg · mL^?1. The values for CI, SVRI, and LVSWI were similar between groups at corresponding time periods.

Conclusions

An infusion rate of 120 μg · kg^?1 · min^?1 is clinically practical and capable of achieving experimental cardioprotective propofol concentrations at reperfusion.     

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.     

Neuromuscular blocking effects of rocuronium during desflurane, isoflurane, and sevoflurane anaesthesia

Purpose

To determine the magnitude of the potentiation of rocuronium by desflurane, isoflurane and sevoflurane 1.5 MAC anaesthesia.

Methods

In a prospective, randomised, study in 80 patients, the cumulative dose-effect curves for rocuronium were determined during anaesthesia with desflurane, sevoflurane and isoflurane (with N₂O 70%, 15 min steady state) or total intravenous anaesthesia (TIVA) using propofol/fentanyl. Neuromuscular block was assessed by acceleromyography (TOF-Guard®) after train-of-four (TOF) stimulation of the ulnar nerve (2Hz every 12sec, 200 μsec duration), Rocuronium was administered in increments of 100 μg·kg^?1 until first twitch (T₁) depression > 95%.

Results

Rocuronium led to more pronounced T₁ depression with desflurane or sevoflurane anaesthesia than with TIVA. The ED₅₀ and ED₉₅ were lower during desflurane (95 ± 25 and 190 ± 80 μg·kg^?1) and sevoflurane (120 ±30 and 210 ± 40 μg·kg^?1) than with TIVA (150 ± 40 and 310 ± 90 μg·kg^?1) (P < .01), while the difference was not significant for isoflurane (130 ± 40 and 250 ± 90 μg·kg^?1). Following equi-effective dosing (T₁ > 95%) the duration to 25% T₁ recovery, recovery index (25/75), and TOF_0.70 was: 13.2 ± 1.8, 12.7 ± 3.4, and 26.9 ± 5.7 min during anaesthesia with desflurane; 15.5 ± 5.0, 11.4 ± 3.8, and 31.0 ± 6.0 min with sevoflurane; 13.9 ± 4.7, 10.7 ± 3.3, and 26.3 ± 8.9 min with isoflurane; and 13.9 ± 3.9, 11.3 ± 5.7, and 27.5 ± 8,2 min with TIVA anaesthesia (P: NS).

Conclusion

Interaction of rocuronium and volatile anaesthetics resulted in augmentation of the intensity of neuromuscular block but did not result in significant effects on duration of or recovery from the block.     

Ketamine concentrations during cardiopulmonary bypass

Purpose

To describe the serum concentrations of ketamine following a clinically relevant dosing schedule during cardiopulmonary bypass (CPB).

Methods

Design: Prospective case series. Setting: Tertiarycare teaching hospital. Patients: Six patients undergoing coronary artery bypass grafting and over age 60 yr. Intervention: Following induction of anaesthesia each patient received a bolus of ketamine 2 mg· kg^?1 followed by an infusion of 50 μg· kg^?1 · min^?1 which ran continuously until two hours after bypass. Main Outcome Measures: Ketamine serum concentrations were measured at five minutes after bolus, immediately following aortic cannulation, 10 and 20 min on CPB, termination of CPB, termination of the drug infusion and three and six hours after infusion termination.

Results

At the time of aortic cannulation, ketamine concentrations were 3.11 ± 0.81μg · ml^?1, these levels decreased by one third with the initiation of CPB. By the end of CPB the concentrations had returned to levels roughly equivalent to those observed at the time of aortic cannulation. Following cessation of the infusion, ketamine concentration declined in a log-linear fashion with a half-life averaging 2.12 hr. (range 1.38–3.09 hr).

Conclusions

This dosage regimen maintained general anaesthetic concentrations of ketamine throughout the operative period. These levels should result in brain tissue concentrations in excess of those previously shown to be neuroprotective in animals. Thus we conclude that this infusion regimen would be reasonable to use in order to assess the potential neuroprotective effects of ketamine in humans undergoing CPB.     

40 Hz Auditory steady-state response and EEG spectral edge frequency during sufentanil anaesthesia

Purpose

The auditory steady-state evoked response (ASSR) is an evoked potential which provides a sensitive measure of the effects of general anaesthetics on the brain. We used pharmacokinetic-pharmacodynamic (PK-PD) modelling to compare the effects of sufentanil on the amplitude of the ASSR with its effect on spectral edge frequency (SEF) of the electroencephalogram.

Methods

Nine patients scheduled for elective cardiac surgery participated. Midazolam (70 μg·kg^?1 im) was given 60 min before entering the operating room. Anaesthesia was induced with 5 μg·kg^?1 sufentanil at a rate of 0.83 μg·kg^?1·min^?1. The ASSR, SEF and plasma sufentanil concentrations were measured for 30 min ater induction of anaesthesia before surgery. The half-life between the central and effect site compartments (t_1/2K_eo), the 50% inhibitory concentration (IC₅₀) and the slope factor (gamma) were computed.

Results

The amplitude of the ASSR increased during the first three minutes of infusion of sufentanil by up to 40%. This was followed by a rapid decrease between the fourth and fifth minutes to 16% of baseline. The SEF decreased progressively during the first five minutes of infusion to 18% of baseline. Both measures subsequently showed modest recovery. The parameters gamma, IC₅₀ and t_1/2K_eofor ASSR were (mean ±SD) 6,0 ±3.7, 2.1 ±1,2 ng·ml^?1 and 7.3 ±2.4 min. For SEF the values were 5.9 ±5.2, 1.4 ±0.7 ng·ml^?1 (P < 0.05 compared with ASSR) and 6.8 ±2,4 min.

Conclusion

The sensitivity of ASSR to sufentanil is less than that of the SEF.     

Heart rate changes in cardiac transplant patients and in the denervated cat heart after edrophonium

Purpose

The effect of edrophonium on heart rate in cardiac transplant patients and in an animal model of acute cardiac denervation were studied, to evaluate the functional state of the peripheral parasympathetic pathway fol lowing cardiac denervation.

Methods

Edrophonium was studied in patients with normally innervated hearts (controls) and m cardiac trans plants. Edrophonium was also studied in vagotomized. beta-blocked cats. In Group I animals, the vagus nerve was not stimulated. In Groups 2 & 3 the right vagus nerve was electrically stimulated to produce approximately 20% and 40% reductions in baseline heart rate, respectively.

Results

Maximum heart rate reduction in transplants (7.3 ± 0.8 beats·min^?1 with 0.6 ± 0.08 mg·kg^?1) was less than in controls (13.3 ± 1.6 beatsmm with 0.4 + 0.05 mg·kg^?1, P < 0.01). In Group I animals heart rate decreased maximally by 20.9 ± 2.5 beats·min^?1 with 9.0 ± 1.9 mg·kg^?1. In Groups 2 and 3, with doses < 15 mg·kg^?1, reduc tions m heart rate were greater than in Group I and maximual reductions were obtained with lower doses (Group 2: maximum reduction by 20.3 ± 2.8 beats·min^?1 with 1.3 ± 0.1 mg·kg^?1: Group 3: 22.6 ± 4.0 beats·min^?1 with 0.8±0.2 mg·kg^?1, P < 0.001) Doses > 1.5 mg·kg^?1 in Groups 2 and 3 produced increases in heart rate.

Conclusion

Edrophonium produced bradycardia in cardiac transplants suggesting spontaneous release of acetylcholinee from parasympathetic postganglionic neurons m the transplanted heart. The magnitude of the brady cardia was less in transplant than in control patients. Findings from animal studies suggest that the reduction in transplants can be attributed to diminution or absence of tonic cardiac parasympathetic drive. At high doses, edrophonium may interfere with parasympathetic neuron activation.     

Esmolol versus ketamine-remifentanil combination for early postoperative analgesia after laparoscopic cholecystectomy: a randomized controlled trial

Purpose

Controversy surrounds the optimal technique to moderate pain after laparoscopic cholecystectomy (LC). Opioid analgesics, sympatholytic drugs, and adjuvants, such as ketamine, have all been used. We compared esmolol with a combination of remifentanil plus ketamine in patients undergoing LC to determine the impact of these drugs on morphine requirements and pain control.

Methods

Sixty American Society of Anesthesiologists physical status I-II patients undergoing LC and anesthetized with sevoflurane were randomized to one of two groups. Group E patients received a bolus of esmolol 0.5?mg·kg^?1 iv at induction followed by an infusion of 5-15???g·kg^?1·min^?1, and Group R-K patients received a bolus of ketamine 0.5?mg·kg^?1 iv and remifentanil 0.5???g·kg^?1 iv at induction followed by a remifentanil infusion titrated over a range of 0.1-0.5???g·kg^?1·min^?1. All patients received paracetamol, dexketoprofen, and levobupivacaine via infiltration of laparoscopic port sites. After surgery, a predetermined bolus of morphine was administered according to a verbal numerical rating scale (VNRS) for pain intensity. The primary outcome of interest was postoperative morphine requirement.

Results

Median consumption of morphine was higher in Group R-K than in Group E (5?mg [4-6] vs 0?mg [0-2], respectively; P?<?0.001). In the postanesthesia care unit, patients in Group R-K had higher pain scores than patients in Group E (difference in maximum VNRS, -11; 95% confidence interval (CI), -19 to -3). The concentration of sevoflurane to maintain a bispectral index~40 was higher in Group E than in Group R-K (between-group difference 0.3%; 95% CI, 0.15 to 0.40). The incidence of postoperative nausea and vomiting was similar between the two groups.

Conclusion

Intraoperative esmolol infusion reduces morphine requirements and provides more effective analgesia compared with a combination of remifentanil-ketamine given by infusion in patients undergoing LC.     

Latex anaphylaxis during tissue expander insertion in a healthy child

Purpose

To report intraoperative latex anaphylaxis that occurred in an otherwise healthy child. Although latex anaphylaxis is seen in patients with myelodysplasia, genitourinary anomalies, sensitised healthcare workers, and patients with frequent exposure to latex, it has not been described in otherwise healthy children.

Clinical features

A nine-year-old girl developed intraoperative latex anaphylaxis manifested by increased airway pressure, expiratory wheezing, a decrease in oxygen saturation, severe hypotension and urticaria. The patient was treated with 5 μg·kg^?1 epinephrine iv and 5 mg·kg^?1 hydrocortisone iv. She required an epinephrine infusion of 0.4 μg·kg^?1 ·min^?1 and prolonged ICU admission. Her only previous latex exposure was during plastic surgical procedures. Latex allergy was confirmed weeks later using the prick method allergy testing.

Conclusion

Latex anaphylaxis can occur in otherwise healthy children whose only latex exposure occurred during a previous operation, including plastic surgery.     

Antagonism of atracurium-induced block in obese patients

Purpose

To investigate the relationship between total body weight (TBW) or body mass index (BMI) and atracurium reversal time.

Methods

The study population comprised 25 patients with TBW < 80 kg and 25 patients with TBW ≥80 kg anaesthetised with midazolam, thiopentone, fentanyl, nitrous oxide and halothane. Neuromuscular block was induced with 0.5 mg· kg^?1 atracurium and maintained with doses of 0.15 mg· kg^?1. Neuromuscular transmission was recorded using train-of-four (TOF) nerve stimulation and mechanomyography. Neostigmine, 0.07 mg· kg^?1, was administered when the first twitch in TOF had recovered to 10% of control. Reversal time was defined as: time from administration of neostigmine until TOF ratio recovered to 0.70.

Results

There was no difference in reversal time between patients with TBW < 80 kg (7.2 ± 2.6 min, mean ± SD), and patients with TBW ≥80 kg (6.9 ± 3.6 min). When patients were grouped according to BMI there was no difference in reversal time between groups with low BMI (6.9 ± 2.6 min) or high BMI (7.1 ± 3.6 min). There was, furthermore, no difference in reversal time between the 15 patients in the study population with the smallest TBW or BMI and the 15 patients with the greatest TBW or BMI. There was no correlation between TBW or BMI and reversal time.

Conclusion

When atracurium-induced neuromuscular block is antagonised with 0.07 mg· kg^?1 neostigmine, TBW or BMI have no influence on reversal time.     

Inhibition of cerebral metabolic and circulatory responses to nitrous oxide by 6-hydroxydopamine in dogs

Purpose

To determine whether cerebral metabolic and circulatory consequences of N₂O result from activation of the sympathoadrenal system. The effects of pretreatment with intracistemal injection of 6-OHDA, which produces chemical sympathectomy, were studied in dogs.

Method

Seven days before measurement dogs were pretreated with intracisternal injection of either saline vehicle (sham-group) or 100 μg· kg^?1 6-hydroxydopamine (6-OHDA group). Cerebral blood flow (CBF) was measured using an electromagnetic flow-meter probe and cerebral metabolic rate for oxygen (CMRO₂) was calculated as the product of CBF and arterial-sagittal sinus blood oxygen content difference [C(a-v)O₂].

Results

In the sham group, N₂O (60%) increased CMRO₂ from 6.11 ± 0.21 ml· 100 g^?1· min^?1 to 7.10 ± 0.39 ml· 100g^?1· min^?1 and CBF from 63 ± 5 ml· 100 g^?1 · min^?1 to 173 ± 26 ml· 100 g^?1· min^?1. In the 6-OHDA group, CMRO₂ did not change during N₂O exposure, whereas CBF increased from 61 ± 3 ml· 100 g^?1· min^?1 to 135 ±19 ml· 100 g^?1· min^?1 but less then in the sham group. The 6-OHDA group displayed a reduction in cortical noradrenaline (NA) concentration from 263.2 ± 35.6 ng·g^?1 to 102.7 ± 16.5 ng· g^?1. Cortical dopamine (DA) concentration was not affected by 6-OHDA administration.

Conclusion

These results suggest that most of the increase in CMRO₂ and, at least a part of, the increase in CBF during N₂O exposure in the sham-group are related to sympathoadrenal-stimulating effects of N₂O.     

Preoperative ketorolac increases bleeding after tonsillectomy in children

Purpose

To compare the incidence of vomiting following codeine or ketorolac for tonsillectomy in children.

Methods

We had planned to enrol 240 patients, aged 2–12 yr undergoing elective tonsillectomy into a randomized, single-blind study in University Children’s Hospital. The study was terminated, after 64 patients because interim analysis of the data by a blinded non-study scientist concluded that the patients were at undue risk of excessive perioperative bleeding. After induction of anaesthesia by inhalation with N₂O/halothane or with propofol 2.5?3.5 mg· kg^?1 iv, the children were administered 150 μg· kg^?1 ondansetron and 50 μg · kg^?1 midazolam. Maintenance of anaesthesia was with N₂O and halothane in O₂. Subjects were administered either 1.5 mg · kg^?1 codeine im or 1 mg· kg^?1 ketorolac iv before the commencement of surgery. Intraoperative blood loss was measured with a Baxter Medi-Vac® Universal Critical Measurement Unit. Postoperative management of vomiting and pain was standardized. Vomiting was recorded for 24 hr after anaesthesia. Data were compared with ANOVA, Chi-Square analysis and Fisher Exact Test.

Results

Thirty-five subjects received ketorolac. Demographic data were similar. The incidence of vomiting during the postoperative period was 31% in the codeine-group and 40% in the ketorolac-group. Intraoperative blood losses was 1.3 ± 0.8 ml · kg^?1 after codeine and 2.2 ± 1.9 ml · kg^?1 after ketorolac (mean ± SD) P < 0.05. Five ketorolac-treated patients had bleeding which led to unscheduled admission to hospital, P < 0.05, Exact Test.

Conclusion

Preoperative ketorolac increases perioperative bleeding among children undergoing tonsillectomy without beneficial effects.     

Onset of vecuronium neuromuscular blockade at the hand with an arterio-venous shunt

Purpose

To evaluate the onset of vecuronium neuromuscular blockade in the hand with an arteno-venous shunt for haemodialysis.

Methods

In 15 adult patients receiving haemodialysis for renal failure the onset of vecuronium-induced neuromuscular blockade after 0.08 mg·kg^?1 vecuroniumiv was measured. Using train-of-four mechanomyographic monitoring, the force of contraction of the adductor pollicis of both hands with and without arteno-venous shunt was measured simultaneously.

Results

The times from the injection to the first depression of twitch response (latent onset) and 95% twitch depression (onset) in the hand with and without arteno-venous shunt were114.7 ± 33.4 and 218.7 ± 59.9 and 117.3 ± 34.3 and 208.7 ± 60.9 sec respectively. No difference in the onset of vecuronium neuromuscular blockade in the hand an arterio-venous shunt was demonstrated.

Conclusion

The presence of an artenovenous fistula does not modify the onset on neuromuscular blockade. Either arm can be used to monitor onset of neuromuscular blockade in chronic renal failure patients with an arterio-venous shunt in the hand for haemodialysis     

Bradycardia produced by pyridostigmine and physostigmine

Purpose

The bradycardia produced by pyridostigmine and physostigmine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sensitivity to block by cholinergic receptor antagonists.

Methods

Cats were anaesthetised, vagotomised and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M₁ receptors were blocked with hexamethonium and pirenzepine, respectively. M₂ receptors were blocked with gallamine, pancuronium and AFDX-116.

Results

With pyridostigmine and physostigmine, the dose-response relationship for the decrease in heart rate (ED₅₀ 1.05 ± 0.25 and 0.198 ± 0.03 mg·kg^?1, respectively) was shifted to the right of that for the inhibition of cholinesterase activity (ED₅₀ 0.094 ± 0.03 and 0.032 ± 0.01 mg·kg^?1, respectively). The decrease in cholinesterase activity reached a plateau at a cumulative dose of 0.56 ± 0.08 and 0.32 ± 0.08 mg·kg^?1, respectively. In contrast, there did not appear to be a plateau in the bradycardic effect. The bradycardia produced by pyndostigmine and physostigmine was blocked by hexamethonium (ED₅₀ 10 ± 1.3 and 15.3 ± 2.4 mg·kg^?1, respectively), pirenzepine (ED₅₀ 68 ± 16 and 138 ± 32 μg·kg^?1. respectively), gallamine (56 ± 11 and 67 ± 17 μg·kg^?1, respectively ), pancuronium (32 ± 10 and 30 ± 4 μg·kg^?1, respectively), and AFDX-116 (31 ± 4 and 28 ± 4 μg·kg^?1, respectively).

Conclusion

The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not dearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscannic M₁ and a high sensitivity to muscarinic M₂ receptor antagonists.