We have investigated the effects of midazolam and diazepam on intracellular calcium (Ca2+) handling in foetal mouse ventricular myocytes using the Ca2+-sensitive fluorescent indicator, indo-1. We also investigated separately whether flumazenil or the L-type Ca2+channel agonist, Bay K8644, antagonized these myocardial depressive effects. Midazolam and diazepam decreased the Ca2+transient and beating rate in a concentration-dependent manner, and these decreases were prevented by Bay K8644. Flumazenil did not antagonize the myocardial depressive effects. In myocytes whose sarcoplasmic reticulum was inhibited by ryanodine, midazolam and diazepam had the same potent cardiodepressive effects. Midazolam and diazepam are direct cardiac depressants, which decrease the Ca2+transient and beating rate, and the L-type Ca2+channel is important in the negative inotropism and chronotropism caused by these drugs.

The relation between left ventricular end-systolic wall stress (ESWS) and the velocity of circumferential fibre shortening (Vcfs) was examined in four non-random groups with 12 patients each. In group A, preload was increased by the administration of hydro- xyethylstarch 30 mL min−1. In group B, preload was reduced by administering nitroglycerine 4.0 ± 0.8 mg h−1. A change in pulmonary capillary wedge pressure by 3 mmHg was taken to be the end point for preload manipulation. To assess a change in the relation between ESWS and Vcfs, patients in group C received adrenaline at an infusion rate of 4 g min−1. Patients in group D served as the controls. Geometric variables of ESWS and Vcfs were determined by transoesophageal echocardiography. A linear model was used to assess the relation between ESWS and Vcfs within each group by regression analysis, and analysis of covariance performed to detect significance of intragroup and intergroup differences (P < 0.005). No significant changes were found during preload intervention. With adrenaline, Vcfs increased significantly for a given ESWS. It is concluded that the relation between ESWS and Vcfs, in a multiple patient setting, is independent of modest preload changes and may have the potential to indicate inotropic effects.

The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during propofol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback controller. At 90% block the steady-state infusion of rocuronium was 0.55 ± 0.16 mg kg−1 h−1 and the corresponding concentration 1714 ± 281 ng mL−1 in patients receiving propofol. At 50% block the corresponding infusion rate was 0.27 ± 0.11 mg kg−1 h−1 and the concentration 1077 ± 244 ng mL−1, respectively. At 50% block isoflurane reduced the rate of infusion by 52% (P < 0.005) and the concentration by 59% (P < 0.001); at 90% block both the mean infusion rate and the concentration of rocuronium were reduced by 35% (P <0.005). The mean rocuronium clearance at 50% block was unaffected by the type of anaesthesia; it was 4.1 ± 1.6 and 4.9 ± 2.7 mL kg−1 min−1 in the groups receiving propofol and isoflurane anaesthesia, respectively. We conclude that isoflurane reduces the infusion requirements of rocuronium by changing the pharmacodynamic behaviour.

Fifteen patients undergoing elective thoracic surgery were studied in order to investigate the efficacy of high frequency jet ventilation of the non-dependent lung with respect to arterial oxygenation. During the study PaO2, PaCO2, arterial pressures and heart rate were recorded during ventilation of both lungs in the lateral decubitus position during one-lung ventilation and during high frequency jet ventilation of the non-dependent lung. Mean PaO2 was 28±8.75 kPa and mean PaCO2 was 5.4±0.7 kPa during control. During one-lung ventilation, PaO2 dropped to 10.8±2.57 kPa and PaCO2 rose to 6.3±0.9 kPa. With high frequency jet ventilation to the non-dependent lung, mean PaO2 increased to 25±6.75 kPa and PaCO2 decreased to 5.16±0.9 kPa respectively. Arterial pressures and heart rate remained stable during the study period. In conclusion high frequency jet ventilation of the non-dependent lung was effective in providing arterial normoxaemia and normocapnia during one-lung ventilation.

There are only limited data on sevoflurane minimum alveolar concentration (MAC) in rats. This study was designed to determine the minimum alveolar concentration value for sevoflurane in younger and older rats. Minimum alveolar concentration determination was performed in spontaneously breathing animals, 9-week-old rats (younger, n = 8) and more than 13-month-old rats (older, n = 8). Rats were instrumented with a silastic catheter in the abdominal aorta via the femoral artery to allow for arterial blood gas sampling. Subsequently, minimum alveolar concentration for sevoflurane was determined in 40 younger and 38 older rats. Minimum alveolar concentration for sevoflurane in younger rats was significantly higher than in the older rats (2.68 ± 0.19 vs. 2.29 ± 0.19, P < 0.001). Subgroup analysis indicated that minimum alveolar concentration for sevoflurane was not affected by the presence of an arterial catheter in the abdominal aorta (younger, 2.75 ± 0.08 vs. 2.67 ± 0.21; older, 2.23 ± 0.19 vs. 2.30 ± 0.18). Minimum alveolar concentration is profoundly affected by the age of the animal, but not by limited instrumentation.

In this prospective study techniques for the subcutaneous ring block of the penis and subpubic block of the penis for analgesia after circumcision were compared. Forty-five boys having circumcision as day-case patients were allocated randomly to have either a subcutaneous ring block or a subpubic penile block. The blocks were inserted after induction of anaesthesia but before surgery. Pain scores at 15, 30, 45 and 60 min post-operatively were recorded. Side effects and analgesic requirements in hospital were recorded post-operatively. Analgesia (morphine, paracetamol or diclofenac) was given depending on the pain score. One patient was withdrawn from the study. Four of the 24 boys who had subpubic penile blocks and nine of the 16 boys who had subcutaneous ring blocks were given morphine for post-operative pain (P = 0.015). The surgeons complained about oedematous tissues in three patients, all of whom had had subcutaneous ring blocks. The subpubic penile block provided significantly better analgesia than the subcutaneous ring block of the penis.

The short-term effect of intravenous (i.v.) angiotensin converting enzyme (ACE) inhibitor enalaprilat in 10 critically ill patients, being ventilated with positive end-expiratory pressure (PEEP), on sodium and water excretion was investigated. Mean arterial pressure (MAP) decreased. Heart rate and central venous pressure (CVP) did not change. Glomerular filtration rate (GFR), urine volume (V) and sodium excretion (UNaV) decreased in two patients with reduced MAP. GFR, V and UNaV increased in two patients with decreased MAP. No relation between changes in MAP and excretion was observed in six patients. ACE decreased in all patients. Plasma renin activity increased, aldosterone decreased, while atrial natriuretic peptide as well as antidiuretic hormone did not change. Enalaprilat did not facilitate sodium and water excretion during ventilation with PEEP. Decreased MAP indicates that the investigated patients were very dependent on their renin-angiotensin system to maintain systemic perfusion pressure. Base-line MAP and CVP values were no predictors of haemodynamic and excretory changes following acute ACE inhibition.

A study was conducted on 100 middle-aged to elderly patients (n=52, healthy; n=48, suffering from either diabetes, hypertension, ischaemic heart disease or combination of these diseases) undergoing cataract extraction to assess the effects of laryngoscopy and tracheal intubation, anaesthesia and surgery, eye bandaging and tracheal extubation, saline (control), magnesium sulphate 40 mg kg−1, esmolol 4.0 mg kg−1, lignocaine 1.5 mg kg−1 and glyceryl trinitrate 7.5 μg kg−1 given i.v. at induction of anaesthesia on heart rate (HR), blood pressure (BP), rate-pressure product (RPP) and pressure-rate quotient (PRQ). Anaesthesia was standardized. Haemodynamic responses and requirements for atropine, ephedrine and labetalol to maintain HR and BP during surgery were similar inhealthy and diseased patients, and in the test drug groups. Differences produced by the test drugs were evident until 5 min following intubation. Esmolol prevented rises in HR and RPP. Glyceryl trinitrate prevented a rise in BP, but was associated with tachycardia and a fall in PRQ to < 1.0. Magnesium sulphate and lignocaine did not prevent responses to laryngoscopy and tracheal intubation, and were associated with rises in RPP. Application of the eye dressing and tracheal extubation at the end of surgery each caused significant increases in HR, BP and RPP in all groups.

The aim of the study was the determination of the influence of ventilation modes on the consumption of analgesics and sedatives, duration of intubation and pulmonary gas exchange. Assist/controlled mandatory ventilation (S-CMV, 123 patients), synchronized intermittent mandatory ventilation (S-IMV, 431 patients) and biphasic positive airway pressure ventilation (BIPAP, 42 patients) were compared in a prospective, controlled, open clinical trial over an 18-month period. Five hundred and ninety-six adult patients with normal pulmonary function before surgery and uneventful course following coronary artery bypass graft surgery were studied. Patients ventilated with BIPAP had a significantly shorter mean duration of intubation (10.1h, P < 0.05) than patients treated with S-IMV (14.7 h) and S-CMV (13.2 h). In the S-CMV group, 39.9% of the patients required single or multiple doses of midazolam, but only 13.5% in the S-IMV group and 9.5% in the BIPAP group. The mean total amount of midazolam administered to these patients was significantly higher in the S-CMV group (8.8 mg) than in the S-IMV group (6.6 mg, P < 0.05) and in the BIPAP group (4.3 mg, P < 0.05). The consumption of pethidine and piritramide did not differ between S-CMV and S-IMV, but was significantly lower during BIPAP (P < 0.05). After extubation the patients’ PaCO2 was highest in the S-CMV group. We conclude that ventilatory support with BIPAP reduces the consumption of analgesics and sedatives, and the duration of intubation. The possibilty of unrestricted spontaneous breathing in all phases of the respiratory cycle is considered to be the reason. BIPAP seems to be an alternative to S-CMV and S-IMV in short-term ventilated patients.