The non-stimulant cardioselective beta adrenocepter antagonist atenolol has been studied in volunteers in order to define its pharmacokinetic characteristics. Atenolol (100 and 200 mg orally) is rapidly absorbed, reductions in heart rate and systolic pressure being observed in 30 min. The effect persists for up to 8 h. Over 85% of an intravenous dose is excreted in urine within 24 h but only 50% of an oral dose. The bioavailability of approximately 50% is due to reduced absorption. Peak blood levels are observed at 2-4 h and the half life of atenolol given orally is 5-6 h. Atenolol reduces the cardiac response to standing and head-up tilt. It does not reduce circulating levels of renin but slightly impairs the renin response to tilt. Atenolol both orally and intravenously reduces supine diastolic pressure about four hours after administration, the effect persisting for up to 24 h.

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Avoidance of increasing afterload is important during anaesthesia for cardiac surgery. We studied the haemodynamic consequence of deliberate vasodilation during sternotomy in nine patients (mean age 57 -+ 12 years, mean left ventricular ejection fraction 0.51 +-0.09) undergoing valvular replacement. Nicergoline, a new ergol derivative, produces vasodilation (alpha blocking effect), bradycardia (central effect) and has no effect on myocardial metabolism) It was given as a continuous infusion, started after induction, at a rate of 0.8 mg. kg-t/hour.This group was compared to a control group of 12 patients (mean age 60 +-13 years; mean left ventricular ejection fraction 0.51 -+ 0.1) undergoing valvular replacement (seven patients) coronary artery bypass graft (four patients) or aneurysmectomy (one patient). Premedication was pentobarbitone sodium 60-120 mg PR., with intramuscular promethazine I mg. kg -I and meperidine 1 rag. kg -I. Anaesthesia was neurolepanalgesia with droperidol 100 mg and fentanyl 2 mg in 500 ml D5W infused during 15 minutes of induction at 5 mg. kg-t/hr and then maintained at 2 mg. kg-I/hr during sternotomy. Flunitrazepam 0.25 to 0.5 mg and paneuroniurn bromide 0.08 mg-kg -l were given at induction. Measurements were made before and after stcrnotomy in the two groups of patients.In the control group, sternotomy did result in an increased rate-pressure product (p < 0.01), while cardiac index and systemic vascular resistance remained unchanged. In the nieergoline group, increase in rate pressure product was not significant. Cardiac index increased significantly (p < 0.05) as systemic vascular resistance decreased; volume needed to maintain adequate filling pressure was higher in this group (p < 0.05) as was the weight gain during operation (p < 0.05) and postoperative bleeding. This may be related to nicergoline platelet anti-aggregation properties.Our study suggests that deliberate vasodilation such as produced with nicergoline may yield to increased vasoplegia, bleeding and weight gain during operation despite decrease in MVO2 and aftedoad. Intravenous nitroglycerin (NG) is used in coronary patients during anaesthesia to reduce blood pressure (BP) and rate-pressure-product (RPP). It is given orally or intravenously to awake patients for angina. Does the awake patient with cerebration and an active autonomic system react to NG differently than an anaesthetized patient?We studied seven patients having coronary grafts, both awake, sedated and, later, after sternotomy with hypertension. With a radial needle and two thermodiluuon catheters (pulmonary artery and coronary sinus) we determined total coronary sinus flow (CSF), cardiac index (CI), vascular resistance (SVR), total coronary sinus flow (CSF), myocardian oxygen consumption (MVO2) and lactate extraction. Studies were done before and after NG 100 ug/min with mean doses of 1.04 mg given in 10.6 minutes awake and 1.2 mg given in 8.2 minutes after sternotomy.These male patients had a mean age of 57.4 years and mean surface area of 1.95 m 2. Mean...

During thoraco-abdominal aortic aneurysmectomy, the aorta is replaced from the left subclavian artery to the aortic bifurcation. We wished to describe the haemodynamic events occurring during clamping and unclamping of the thoracic aorta and the metabolic changes associated with the interruption of organ perfusion beyond the left subclavian artery. MethodsWe studied I I patients (58-77 years) undergoing thoracoabdominal aortic aneurysm resection without the use of cardiopulmonary bypass. All patients had normal left ventricular systolic function. No patient had angina.Diazepam, fentanyl, pancuronium, air/O2 anaesthesia was used, An arterial line, a Swan-Ganz catheter and a left double lumen endobronchial tube were inserted. The left lung was collapsed to facilitate surgical exposure. Immediately prior to the application of the thoracic aortic cross-clamp, sodium nitroprusside was infused in an attempt to eliminate excessive hypertension at the time of cross-clamp. This was continued for the duration of the cross-clamp (mean 72 minutes) to maintain systolic arterial pressures between 150-200 mmHg. An IV infusion of five per cent sodium bicarbonate was given to achieve a serum b/carbonate of 30-35 nunol.L-~ prior to unclamping of the aorta. ResultsHaemodynamic results (Table I) Cross-clamping of the thoracic aorta produced an immediate increase in mean arterial blood pressure (MAP). This reverted hack to preclamp levels with removal of the clamp, Mean pulmonary artery pressure (MPAP) increased significantly with clamp application and this increase persisted after removal of the clamp. There was no significant change in either systemic vascular resistance (SVR) or pulmonary vascular resistance (PVR). Cardiac indices (CI) were not affected by clamp application but increased significantly after clamp removal. Both the central venous (CVP) and pulmonary capillary wedge pressures (PCWP) increased with clamp application and these changes persisted after clamp removal.Metabolic results (Table 11) An average of 791 mmol of sodium bicarbonate (range 240-1545 mmol) was infused during the time of crossclamp. Unclamping of the aorta with re-establishment of circulation to liver, gut, and kidneys produced an acid wash out, resulting in a highly significant drop in pH (p < 0.001) and plasma bicarbonate. PCO2 rose significantly Catecholamine release may influence the haemodynamic response to anaesthetic induction with narcotics in patients with coronary disease. 1 Previous studies have yielded conflicting results regarding serum catecholamine responses to narcotic anaesthesia.~-4 We have noted unexplained, potentially deleterious, increases in heart rate (HR) and arterial pressure (AP) in occasional patients during induction with high-dose fentanyl. 5 Therefore we tested the hypothesis that catecholamine release accompanies anaesthetic induction with potent narcotics. MethodsInstitutional approval was obtained and all patients gave informed consent. Thirty-three patients with preoperative left ventricular ejection fraction >0.50...

G. Smedstad rat), FRCPCSince the days of Queen Victoria, the very act of providing pain relief for childbirth has been controversial. Although nobody today questions the efficacy and validity of modern obstetric analgesia and anaesthesia, there are those who query the need for the routine use of epidural analgesia in normal obstetrics, and there are anaesthetists who would rather not be involved in obstetrics. The objections to chloroform and ether were based on religious rather than medical tenets. These days women object to technological intrusions in the birthing process, and practitioners worry about medical complications and legal repercussions should anything go wrong.Modern obstetric anaesthesia is sophisticated. Our understanding of the pharmacological action of the drugs we use and the physiological changes that result when pain is relieved has increased in the last few years. This overview will try to examine some of the most common of these controversies. The test doseThe use, efficacy and validity of the epidural test dose continues to be controversial. The ideal test dose should differentiate between correct placement of an epidural needle or catheter, and an intravascular or intrathecal placement or injection. Thus, the test dose needs to fulfil two separate criteria: (1) contain a marker to identify intravascular injection without causing systemic toxicity; (2) provide a reliable, easily detected and safe, sensory and/or motor block if injected into the subarachnoid space. There is no perfect agent for this purpose. The marker for intravascular injection is usually epinephrine. Moore I reported thar the addition of 15/~g of epinephrine to local anaesthetic solutions resulted in a 30-beat increase in heart rate after 20 seconds when the drugs were injected intravenously in premedicated surgical patients. The validRy of this study, when applied to women in labour, has been criticized by many authors, most notably Cartwright. 2 During a contraction, the heart rate increases some 20-30 per cent, so the timing of the injection in relation to the contraction is, therefore, crucial. The heart rate must be monitored continuously by an ECG and closely observed to pick up a sustained increase unrelated to labour itself. Even so, Cartwright showed that, statistically, if one relied upon heart rate increase alone to determine intravaseular placement of the epidural catheter, there would be a false positive test in 12 per cent of patients. If the catheter was removed in all these patients it would be replaced unnecessarily in 12 out of 13 cases. Quite apart from its unreliability, the use of epinephrine as a marker is controversial. Twenty micrograms of IV epinephrine has been shown to decrease uterine blood flow in experimental models. In healthy mothers and babies the addition of epinephrine to the local anaesthetic for epidural analgesia has not been shown to be detrimental, but doubt still remains whether the use of this drug is safe where placental blood flow is compromised, in pre-eclamptic patients, or ...