Comparison of the haemodynamic effects of pipecuronium and pancuronium during fentanyl anaesthesia.

Haemodynamic variables were measured following administration of pipecuronium 70 micrograms.kg-1 and pancuronium 90 micrograms.kg-1 (approximately equivalent to 1.5 x ED95) in patients anaesthetised with fentanyl 50 micrograms.kg-1 and scheduled to undergo coronary artery bypass grafting. There were significant increases in heart rate (22%), mean arterial pressure (10%), cardiac index (16%), and the rate pressure product (35%) following administration of pancuronium. The absolute values of these parameters were, however, within acceptable clinical limits. Administration of pipecuronium produced minimal and insignificant changes in these parameters. Other measured or derived indices showed only small changes with both agents and these were generally insignificant. There were no incidences of significant bradycardia following pipecuronium administration. The results from the present study suggest that pipecuronium would have advantages for use in patients with significant cardiovascular disease.

Propofol sedation after open heart surgery. A clinical and pharmacokinetic study.

One hundred adult patients who required mechanical ventilation after open heart surgery for coronary revascularisation were studied. All received a standard premedication and a high dose opioid anaesthetic. On arrival in the intensive care unit they were allocated randomly to receive either propofol or midazolam to maintain sedation within a predetermined range. Patients who received propofol underwent extubation of the trachea, using standard criteria, after a mean time (log-transformed) of 7.6 minutes after sedation for approximately 17 hours. The corresponding time was 125 minutes in those given midazolam. There were significantly higher morphine requirements during sedation, and higher arterial carbon dioxide tensions 30 minutes after extubation of the trachea, in patients who received midazolam. Pharmacokinetic analysis in 20 patients showed that the elimination half-life of propofol was prolonged (470 minutes) and clearance was reduced (1.14 litres/minute) compared with subjects who had not undergone cardiopulmonary bypass. The rapid clinical recovery was reflected in a rapid redistribution half-life (13.4 minutes), but this was also longer than the redistribution time of 2-4 minutes in other patients.

A pharmacokinetic study of midazolam in paediatric patients undergoing cardiac surgery.

Midazolam 0.3 mg kg-1 was given as a single dose to three groups of children undergoing cardiac surgery to determine its pharmacokinetic profile in this situation. The first group, undergoing closed heart surgery, received the midazolam during the operation. The other groups underwent cardiopulmonary bypass (CPB) with and without complete circulatory arrest. Mean clearance was 512 ml kg-1 h-1 and mean elimination half-lives were 3.3 h following CPB, with a tendency to a higher clearance in those children who had not undergone bypass. In a subsequent part of the study, 10 children received an infusion of midazolam 0.05 mg kg-1 h-1, in combination with intermittent doses of morphine, in the postoperative period. Mean plasma midazolam concentrations consistent with adequate sedation were 80-100 ng ml-1 during the infusion. One child who had not undergone CPB had very low plasma concentrations of midazolam with the same rate of infusion, consistent with the tendency for higher clearance in this group in the bolus pharmacokinetic study.

Comparison of sufentanil-oxygen and fentanyl-oxygen anaesthesia for coronary artery bypass grafting.

Haemodynamic variables were compared in 40 adults undergoing coronary artery bypass grafting during anaesthesia induced with either sufentanil 5 micrograms kg-1 or fentanyl 25 micrograms kg-1 in combination with pancuronium 0.1 mg kg-1. Further doses of sufentanil 2.5 micrograms kg-1 or fentanyl 12.5 micrograms kg-1 were given before skin incision and again before sternotomy. All patients were receiving beta-adrenoceptor blocking therapy. Satisfactory induction of anaesthesia was produced with both drugs and opioid supplementation prevented any marked haemodynamic response to skin incision and to sternotomy. Following induction of anaesthesia, sufentanil produced the greater decrease in mean arterial pressure and left ventricular stroke work index which continued throughout the study. This suggests that, in the doses used in this study, sufentanil is preferable to fentanyl in patients with coronary artery disease.

Midazolam sedation following open heart surgery.

Midazolam given as hourly intermittent injections was compared with the same dose given by infusion for postoperative sedation in patients after cardiopulmonary bypass. A stable concentration was rapidly attained with the infusion whereas 6-8 h was required to attain stable plasma (trough) concentrations in the intermittent injection group. Plasma concentrations decreased rapidly to low values within 6 h of discontinuation of therapy. High plasma concentrations and a long (16 h) half-life were noted in one patient who may be a slow metabolizer of the drug.

Haemodynamic effects of vecuronium, pancuronium and atracurium in patients with coronary artery disease.

Thirty patients with ischaemic heart disease scheduled for coronary artery bypass grafting were randomly allocated to three equal groups. Following morphine, hyoscine and pentobarbitone premedication, anaesthesia was induced with diazepam 0.3 mg kg-1. Five minutes later neuromuscular blockade was induced with pancuronium 0.1 mg kg-1, vecuronium 0.1 mg-1 or atracurium 0.5 mg kg-1, followed after 6 min by fentanyl 25 micrograms kg-1. Pancuronium and atracurium caused significant increases in heart rate, while vecuronium induced little change. Systemic vascular resistance decreased significantly from 1515 dyn s cm-5 to 1200 dyn s cm-5 following atracurium. Cardiac index was increased transiently in the atracurium group, but a more sustained increase was observed following pancuronium. Nine patients in the atracurium group showed skin flushing and one developed skin weals.

Pharmacokinetics of diazepam and midazolam when used for sedation following cardiopulmonary bypass.

The water-soluble benzodiazepine, midazolam, was compared with diazepam for postoperative sedation in patients following cardiopulmonary bypass. Midazolam in repeated doses produced a stable plasma concentration within 4 h, showed no tendency to cumulation and was cleared rapidly following discontinuation. Similar doses of diazepam given with the same frequency produced plasma concentrations which were still increasing at the time of discontinuation and which were still greater than their baseline values 24 h later.

Haemodynamic changes during induction of anaesthesia with midazolam and diazepam (Valium) in patients undergoing coronary artery bypass surgery.

Midazolam 0.3 mg/kg and diazepam 0.5 mg/kg were used for induction of anaesthesia in two groups of 10 patients each undergoing coronary artery bypass surgery. Haemodynamic variables were measured during induction of anaesthesia, after pancuronium and following tracheal intubation. Haemodynamic indices were derived from these measurements using standard formulae. The induction of anaesthesia with midazolam produced a slight but significant increase in heart rate. There was a significant fall in systemic arterial pressure and pulmonary artery pressure following both drugs. Despite the fall in systemic arterial pressure, the cardiac index was maintained in patients who received midazolam. The cardio-stimulatory effect of laryngoscopy and tracheal intubation was not prevented by either of the benzodiazepines and morphine in the dosage used. Midazolam is a suitable alternative to diazepam as part of an intravenous induction regimen in patients with ischaemic heart disease.

Interaction of an antimutator gene with DNA repair pathways in Escherichia coli K-12.

A mutation in the purB gene of E. coli K-12, isolated and partially characterized by Geiger and Speyer (1977), confers a temperature sensitive requirement for adenine and an antimutator phenotype at 30 degrees C. Several hypotheses about the mechanism of action of this mutation, named mud for mutation defective, were tested in the present work. The mud mutation has no effect upon the induction of the SOS response, so the antimutator phenotype is unlikely to be due to repression of mutagenic repair. Mud cells are resistant to the cytotoxic and mutagenic effects of alkylating agents such as MNNG, but this resistance is not due simply to derepression of the adaptive response. DNA isolated from mud cells is not undermethylated relative to DNA from purB+ cells, so the antimutator phenotype of mud cannot be due to reduced hotspot base-substitution mutation at methylated cytosine residues. Nor is there a longer lag in post-replicative DNA methylation, which indicates that there is no enhancement of mismatch repair resulting from an extended time window for strand discrimination. Measurement of nucleotide pool levels demonstrated an elevation of dCTP in mud cells and a reduction of all other nucleoside triphosphates.

Kinetics of methylation in Escherichia coli K-12.

Newly synthesized DNA is undermethylated in E. coli K-12. The amount of N6-methyl deoxyadenylic acid in labeled DNA varied from 0.3 mol% of total adenine for a 2-min pulse to 1.7 mol% for DNA that was labeled for more than two generations.

Continuous intravenous anaesthesia with Althesin for resection of tracheal stenosis.

The anaesthetic management of patients undergoing tracheal resection for tracheal stenosis and the advantage of the maintenance of spontaneous respiration without intubation of the distal tracheal segment is discussed. The case reports of two such patients using a continuous intravenous infusion of Althesin with maintenance of spontaneous respiration are presented. The technique expedited the surgical reanastomosis due to lack of instrumentation in the surgical field. While some mild respiratory depression as evidenced by carbon dioxide retention did occur, the technique is worthy of consideration for the procedure.

Diazepam and flunitrazepam as induction agents for cardiac surgical operations.

Diazepam and flunitrazepam were compared in equipotent doses as induction agents for premedicated patients having cardiac surgery. Both drugs caused a significant fall in arterial blood pressure, a rise in Paco2 and a fall in Pao2. There was no significant difference between the two drugs in onset time of anaesthesia, cardiovascular or respiratory depression, or quality of induction. There was also no significant difference from induction with thiopentone in these respects. Diazepam, over a 0.2 to 0.6 mg/kg range of doses showed no difference in toxicity, although induction was clinically smoother with the higher dose.

The premedication of cardiac surgical patients. A clinical comparison of four regimes.

One of four groups of patients was not premedicated; the others received diazepam 10 mg by mouth, diazepam 20 mg by mouth or a combination of pentobarbitone orally and morphine and hyoscine intramuscularly. The cardiovascular and respiratory parameters were studied before and after the premedication and any changes in sedation, apprehension and reaction to pain were noted. The ease of induction of anaesthesia in the four groups was compared. Most of the patients who received the pentobarbitone, morphine and hyoscine combination came to theatre calm, sedated and often asleep. They showed no significant cardiovascular or respiratory depression and the induction of anaesthesia was more satisfactory than in the other groups. Two of the patients who were not premedicated became very agitated in the ward and the remainder of the patients in this group were apprehensive in the anaesthetic room and during induction. The effects of diazepam in the two doses studied were intermediate between those who received the pentobarbitone, morphine and hyoscine and those who were not premedicated.

A clinical comparison of AH8165 and pancuronium as muscle relaxants in patients undergoing cardiac surgery.

The non-depolarizing muscle relaxant AH8165 has been compared at two doses (0.5 and 1.0 mg/kg) with pancuronium (0.1 mg/kg) during induction of anaesthesia for patients having major cardiac surgery. After barbiturate-opiate premedication and thiopentone induction, administration of pancuronium was followed by no significant alteration in heart rate or arterial pressure. Both doses of AH8165 werr followed by significant tachycardia, and the higher dose by arterial hypotension. The lower dose of AH8165 was unsatisfactory for tracheal intubation, but the AH8165 1 mg/kg gave intubating conditions similar to those with pancuronium 0.1 mg/kg.