A comparison of antagonism of rocuronium-induced neuromuscular blockade during sevoflurane and isoflurane anaesthesia.

Volatile anaesthetic agents potentiate neuromuscular blocking agents and retard their rate of reversal. We hypothesised that there was a difference in the rate of reversal of rocuronium-induced neuromuscular blockade based on the selection of inhalation agent. Thirty-eight patients undergoing elective surgical procedures received either sevoflurane or isoflurane, by random allocation. Neuromuscular blockade was induced using rocuronium 0.6 mg.kg-1 followed by continuous intravenous infusion to maintain 90% suppression of the single twitch response. Upon completion of surgery, the rocuronium infusion was discontinued, neostigmine 50 microg.kg-1 and glycopyrrolate 10 microg.kg-1 were administered. Times from reversal to T1 = 25, 50 and 60% and train-of-four ratio = 0.6 were recorded. The mean (SD) times to train-of-four ratio = 0.6 in the isoflurane and sevoflurane groups were 327 (132) and 351 (127) s, respectively. The mean (SD) times to single twitch response T1 = 25, 50 and 60% in the isoflurane group were 81 (33), 161 (59) and 245 (84) s, respectively, and in the sevoflurane group were 95 (35), 203 (88) and 252 (127) s, respectively. It is concluded that reversal of rocuronium-induced neuromuscular blockade is similar during isoflurane and sevoflurane anaesthesia.

Changes in plasma catecholamine concentrations and haemodynamic effects of rocuronium and vecuronium in elderly patients.

Rocuronium administration may cause tachycardia and an increase in cardiac index. Pancuronium, another steroidal non-depolarizing muscle relaxant, augments release of, and blocks re-uptake of catecholamines at adrenergic nerve endings. This study compared the haemodynamic effects of, and changes in catecholamine concentrations following administration of vecuronium (0.12 mg kg-1) or rocuronium (0.9 mg kg-1) to elderly patients. Thirty patients, 65 years or older, not receiving beta-blockers, were studied. During thiopentone, fentanyl, nitrous oxide anaesthesia, either rocuronium (0.9 mg kg-1) or vecuronium (0.12 mg kg-1) was administered, according to random allocation. In all 30 patients, blood pressure and heart rate were measured before induction of anaesthesia, immediately and 1 min after induction, 1 and 2 min after muscle relaxant administration, and immediately, 1 and 2 min after tracheal intubation. In the latter 20 patients, samples for plasma catecholamine estimation were obtained prior to, and 1 min after muscle relaxant administration and 1 min after tracheal intubation. Blood pressure and heart rate were similar in the two groups throughout the study. Plasma noradrenaline concentrations were similar in the vecuronium and rocuronium groups prior to muscle relaxant administration (589(SD240) and 444(SD213) pg mL-1, respectively), 1 min after muscle relaxant administration (602(SD220) and 520(SD392) pg mL-1, respectively) and 1 min after tracheal intubation (597(SD351) and 440(SD181) pg mL, respectively). There was no significant change in either plasma noradrenaline or adrenaline concentrations in either group following muscle relaxant administration or tracheal intubation. The use of rocuronium (0.9 mg kg-1) in elderly patients does not result in a clinically significant change in heart rate, blood pressure or plasma catecholamine concentration.

Administration of magnesium sulphate before rocuronium: effects on speed of onset and duration of neuromuscular block.

The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium-induced neuromuscular block but did not increase speed of onset.

Buprenorphine disposition in patients with renal impairment: single and continuous dosing, with special reference to metabolites.

The disposition of buprenorphine has been studied in two patient groups to assess the influence of impaired renal function on the metabolism of buprenorphine and two of its metabolites, buprenorphine-3-glucuronide (B3G) and norbuprenorphine (NorB). A single i.v. dose of 0.3 mg was given to 15 patients (nine with dialysis-dependent renal failure) undergoing lower abdominal or peripheral body surface surgery. Blood was sampled up to 24 h. Concentrations of buprenorphine, B3G and NorB were assayed by a differential radioimmunoassay technique. There were no differences in buprenorphine kinetics between anaesthetized healthy patients and those with renal impairment: mean elimination half-lives 398 and 239 min; clearance 651 and 988 ml min-1; apparent volume of distribution at steady state 313 and 201 litre, respectively. Both metabolites were undetectable following the single i.v. dose. In a second group of 20 patients (eight with renal impairment), buprenorphine was administered by continuous infusion for provision of analgesia and control of ventilation in the ITU (median infusion rate 161 micrograms h-1 (range 36-230 micrograms h-1) for a median duration of 30 h (2-565 h). Buprenorphine clearance in patients with normal and impaired renal function was similar (934 and 1102 ml min-1, respectively), as were dose-corrected plasma concentrations of buprenorphine. In patients with renal failure, plasma concentrations of NorB were increased by a median of four times, and B3G concentrations by a median of 15 times.

Anaesthesia for major craniofacial surgery: a report of 23 cases in children under four years of age.

The problems of anaesthetising infants and small children for major craniofacial surgery are discussed. A series of 23 patients is presented to illustrate the practical difficulties.

Carbon dioxide clearance during high frequency jet ventilation. Effect of deadspace in a lung model.

The effects of the volume and length of deadspace on the clearance of carbon dioxide from a lung model have been investigated during high frequency jet ventilation (HFJV) at 1, 3 and 5 Hz. At 1 Hz, increasing the volume of the deadspace without changing the length caused a reduction in the clearance of carbon dioxide. At 5 Hz, an increase in the length of deadspace decreased carbon dioxide clearance, whilst an increase in volume had no effect. Since the delivered tidal volume was less than the volume of the morphological deadspace at this frequency, the elimination of carbon dioxide must have been accomplished by mechanisms which are not considered important at normal tidal volumes and frequencies. Furthermore, the clearance of carbon dioxide at 5 Hz was very inefficient compared with that at 1 Hz. It is concluded that, during HFJV, carbon dioxide is cleared most efficiently when the frequency is low enough for the delivered tidal volume to be greater than the volume of the morphological deadspace.

Disposition of propofol in patients undergoing surgery. A comparison in men and women.

The disposition kinetics of propofol have been determined in 12 patients (six female) receiving propofol 2.5 mg kg-1 for induction of anaesthesia, which was maintained with 67% nitrous oxide in oxygen and 1-1.5% halothane. Peripheral blood samples were collected at selected times up to 8 h after the injection of the drug, and whole blood propofol concentrations determined by HPLC with fluorescence detection. Drug concentration-time data were analysed by the non-linear regression program ELSFIT. This showed the data to be describable by a tri-exponential equation, corresponding to a three-compartment model. There were no differences in the derived kinetic indices for the male and female patients, with the exception of a greater Vdss:V gamma ratio in the males. The terminal half-life in the male patients was 262 min (SEM 44), and in the female patients 309 min (60). Vdss was 329 litre (67) and 313 litre (69) in male and female patients, respectively. The clearance in both groups was 1.8 litre min-1. Seven out of 12 patients showed significant secondary peaks in blood propofol concentration associated with recovery from anaesthesia.

Transdermal hyoscine and postoperative nausea and vomiting.

Forty-two patients, undergoing major gynaecological surgery, were randomly allocated to have a patch applied to the skin behind one ear, containing either hyoscine or placebo. They were followed up at 24-hour intervals for 3 days postoperatively and divided into matched pairs for statistical analysis. There was a significant (p less than 0.01) reduction in nausea and vomiting in the first 24 hours postoperatively, but no difference thereafter. There was an increased incidence of visual disturbance in the hyoscine group at 48 hours, but no other differences in the side effects studied at any other time. However, despite receiving hyoscine there was still a high incidence (68%) of severe nausea and vomiting.

Use of an emulsion of ICI 35868 (propofol) for the induction and maintenance of anaesthesia.

2,6-Diisopropyl phenol in a fat emulsion formulation (propofol) has been used to supplement 67% nitrous oxide in oxygen anaesthesia in 20 patients premedicated with morphine 0.15 mg kg-1 and atropine 0.6 mg, and undergoing body surface surgery. Following an induction dose of propofol 2.5 mg kg-1, the mean maintenance dose was 73.4 micrograms kg-1 min-1. When compared with 10 patients receiving Althesin to supplement nitrous oxide in oxygen in a similar manner, recovery was considerably faster following propofol. The only major side-effect associated with the use of propofol was pain on injection in nine out of 20 patients. When the patients receiving propofol were compared with a second control group (n = 11) in whom anaesthesia was induced with thiopentone 4 mg kg-1 and maintained with 1% halothane and nitrous oxide in oxygen, the former group showed a significant (P less than 0.01) decrease in the plasma cortisol concentration 30 min after the induction of anaesthesia. However, by 3 h after induction, the cortisol concentration in both groups was not significantly different from the baseline (preinduction) value. The mechanism of this decrease is not known. Investigation of the influence of the fat emulsion on blood coagulation and fibrinolysis revealed no differences when compared with patients receiving Althesin.

Haematological and biochemical changes during anaesthesia with propofol ('Diprivan').

The influence of an emulsion formulation of 2,6-diisopropylphenol (propofol) on blood coagulation and fibrinolysis, and on the neuroendocrine responses to surgery has been investigated in 12 patients who received incremental doses of propofol to supplement 67% nitrous oxide in oxygen as anaesthesia for body surface surgery. The effects were compared with those in 10 patients who received Althesin to supplement nitrous oxide in oxygen in a similar manner. When pre-operative values were compared with data obtained after 30 min surgery, no significant effects on coagulation or fibrinolytic indices were found in either group. Both groups, however, showed a significant fall in haemoglobin concentration 30 min after induction of anaesthesia (P less than 0.05); and a fall in haematrocrit value was observed in those patients who received propofol (P less than 0.05). No changes in total white cell counts or platelet counts were observed. Both groups of patients showed a significant rise in blood glucose 30 min after induction of anaesthesia (P less than 0.001). After 3 h values were not significantly different from preoperative levels. The mean plasma cortisol levels fell in both groups 30 min after induction of anaesthesia, but returned to control values by 3 h. The mechanism causing this decrease is not known.

Pharmacokinetics of propofol ('Diprivan') as an induction agent.

The disposition kinetics of propofol have been determined in 12 patients (6 female) receiving 2.5 mg/kg for induction of anaesthesia which was maintained using 1.5% halothane and 67% nitrous oxide in oxygen. Patients were premedicated with oral diazepam 10 mg and were undergoing body surface surgery. Peripheral venous samples were collected up to 8 h after injection of the drug. Whole blood propofol concentrations were determined by high pressure liquid chromatography using fluorescence detection. Data analysis indicates a 3 compartment model, with a terminal half-life of 286 (s.e.m. +/- 36) min, clearance of 1803 +/- 125 ml/min, and volume of distribution of 755 +/- 109 litres. These values are significantly different from those reported previously by Adam et al., (1983) for the Cremophor formulation of the drug. Seven of the patients showed significant secondary peaks of the blood concentration associated with recovery from anaesthesia.

Propofol ('Diprivan') as a supplement to nitrous oxide-oxygen for the maintenance of anaesthesia.

Incremental doses of propofol (10-20 mg) have been used to supplement nitrous oxide in oxygen anaesthesia for patients undergoing body surface surgery. After premedication with morphine 0.15 mg/kg, anaesthesia was successfully induced in 21 patients with 2.5 mg/kg propofol. One patient with labile hypertension suffered a pronounced cardiovascular response to the induction of anaesthesia, but without operative sequelae. The mean maintenance rate of propofol was 73.4 micrograms/kg/min. When compared with 10 patients receiving incremental doses of Althesin, recovery to giving correct date of birth was significantly faster in patients receiving propofol (P less than 0.01); when compared with 11 patients receiving an induction of thiopentone 5 mg/kg and nitrous oxide/oxygen/halothane, more patients receiving propofol had recovered to giving correct date of birth by 10 min after the end of anaesthesia (P less than 0.001). However, use of propofol was associated with pain on injection in 9 out of 20 patients, and apnoea of greater than 30 s in 8 patients.

Epidural analgesia and previous Caesarean section.

A series in which six cases of ruptured uterus occurred following previous lower segment Caesarean section, out of a total of 222 'trials of scar', is presented, and the literature reviewed in an attempt to clarify the term 'relative contra-indication' as applied to this clinical circumstance. The symptoms and signs of ruptured uterus likely to be blocked by an epidural, i.e. maternal tachycardia, scar tenderness and continuous lower abdominal pain, have been shown to be either unreliable (tachycardia and tenderness) or frequently not to occur at all (pain). When pain does occur it is not necessarily masked by an epidural. It is concluded that previous lower segment Caesarean section is not a contraindication to epidural analgesia in a subsequent labour provided certain conditions are fulfilled.

Unilateral pulmonary oedema and Pseudomonas pneumonia.

A case presented clinically as unilateral pulmonary oedema; this was subsequently revealed to be due to unilateral Pseudomonas pneumonia.