Endothelins and the lung.

Since endothelins were discovered by Yanasigawa in 1988 it has been recognised that they may have an important role in lung pathophysiology. Despite their biological importance as vasoconstrictors the physiological role of endothelin has not yet been defined within the lungs. This review explores their role in acute and chronic disease. During acute inflammation and ischaemia-reperfusion injury cytokines may induce release of endothelin. This is important in the realm of acute lung injury and during surgical procedures such as cardiopulmonary operations including lung resections and transplantation. Complications of surgery including primary organ failure resulting in poor gas exchange as well as increased pulmonary vascular resistance have been linked to the presence of excessive endothelin. Endothelin may have an important role in transplantation biology. The complex process leading to successful lung transplantation includes optimising the donor with brain death, harvesting the lungs, managing acute and chronic rejection, and protecting the vital organs from toxic effects of immunosuppressants. During chronic disease processes, the mitotic action of endothelin may be important in vascular and airway remodelling by means of smooth muscle cell proliferation. We also explore recent advances in drug development, animal models and future directions for research.

Anaesthetic assessment and management of cardiac patients for non-cardiac surgery. Part I: Assessment.

Cardiac disease is known to increase the risk of non-cardiac surgery to patients who suffer from it. Clinical and investigation data may be used to identify those at increased risk. Attempts have been made to integrate these risk factors into systems that can quantify risk in terms of increased morbidity and mortality. In this article we discuss the various aspects of cardiac illness that are known to increase risk for patients and then look at the different scoring systems that have been produced. We consider the type and urgency of surgery and finish by providing an approach to risk assessment for non-cardiac surgery.

Anaesthetic assessment and management of cardiac patients for non-cardiac surgery. Part 2: Management.

In an earlier article in this journal (June 1999) we discussed the risk that the presence of cardiac disease poses to patients undergoing non-cardiac surgery. We outlined factors in the patient's medical history, examination findings and the value of various tests in arriving at an overall assessment of risk for any given patient. In this article we concentrate on the management of these patients as they undergo surgery itself. We shall consider what measures may usefully be employed in order to minimise the risk of an adverse cardiac event occurring in the perioperative period.

Antiseptic-impregnated central venous catheters reduce the incidence of bacterial colonization and associated infection in immunocompromised transplant patients.

The incidence of bacterial colonization of central venous catheters using a standard polyurethane catheter was compared with that using an antiseptic (silver sulphadiazine and chlorhexidine) impregnated catheter in a group of patients with thoracic organ transplantation. Colonization was reduced from 25 of 35 standard catheters to 10 of 44 study catheters (P < 0.002), a 68% reduction. Similarly, the incidence of concomitant infection, by the same organism at another site was reduced from 10 of 35 standard catheters to 4 of 44 study catheters (P < 0.03), a 63% reduction.

Inhaled nitric oxide for right ventricular dysfunction following cardiac transplantation.

A 55-year-old man developed postoperative hypotension following orthotopic cardiac transplantation, unresponsive to support with inotropes and counterpulsation. Acute right ventricular failure was confirmed by transoesophageal echocardiography, and the introduction of inhaled nitric oxide resulted in immediate improvement. A beneficial effect persisted for 11 days, with hospital discharge two months postoperatively.

Intraoperative transoesophageal echocardiography for implantation of a pulsatile left ventricular assist device.

We describe the insertion of a permanent implantable left ventricular assist device and intraoperative transoesophageal echocardiography in this instance. We also review the literature on the use of intraoperative transoesophageal echocardiography.

Clinical applications of crossed immunoelectrophoresis to the study of complement activation.

The purpose of our study was to set up a reliable method for the measurement of complement activation by adapting the method of crossed immunoelectrophoresis. We utilised anti C3 antiserum and barbitone buffer, containing sufficient EDTA to prevent in vitro activation of complement. We studied 44 patients undergoing open heart surgery, with cardiopulmonary bypass (CPB) by the analysis of plasma samples taken during the operation, and also samples of plasma and dialysate effluent from patients with end stage renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD). Measurements were also carried out on stored blood, aged serum and serum treated with varying doses of lipopolysaccharide (LPS). Complement activation occurs in 95% of patients during CPB with levels ranging from less than 4.5% to 11.3% of total C3, but there was no detectable activation in any pre-bypass sample. Negligible complement activation occurs in the plasma of CAPD patients, but the dialysate effluent gave results from undetectable levels to 31.7%, in the absence of clinical peritonitis. Variable in vitro complement activation occurs in aged serum, but it was not detectable in stored blood. Serum treated with LPS showed levels of activation directly proportional to the dose of LPS and measurable at a level of 0.1 microgram/ml of serum. The method had a coefficient of variation of 4.5%, and provides a reliable way of measuring complement activation in clinical situations such as cardiopulmonary bypass and peritoneal dialysis.

A comparison of diazepam and midazolam as sedatives for minor oral surgery.

Diazepam in propylene glycol (Valium, Roche) and midazolam (Hypnovel, Roche) were compared as sedatives in 40 patients undergoing minor oral surgery. Twenty patients received each drug. The cardiovascular effects, the acceptability of the drugs to patients and dentists and the incidence of anterograde amnesia and adverse venous sequelae were investigated. Serum benzodiazepine levels were measured and recovery studied by six psychomotor tests repeated over five hours. Both drugs provided safe and acceptable sedation. More amnesia was reported in the midazolam group and more adverse venous sequelae by the diazepam patients. The recovery tests showed that the time taken to return to pre-sedation scores varied with the tests used and there was no significant evidence of the midazolam group recovering more quickly. In particular, significant impairment of delayed memory recall persisted in both groups throughout the investigation period.

Lorazepam in open-heart surgery--plasma concentrations before, during and after bypass following different dose regimens.

Thirty-six patients (29 males and 7 females) undergoing open-heart surgery received one of three different dose regimens of lorazepam. All received a weight-related oral dose (2 mg, 3 mg or 4 mg) pre-operatively for night sedation. Twenty-four patients had an additional weight-related dose (2 mg, 3 mg or 4 mg intravenously) either as part of the induction (12 patients) or just prior to connection of the heat-lung machine (12 patients). Plasma concentrations of lorazepam were measured 20 minutes after induction, immediately before bypass, 30 and 60 on bypass and 30 minutes after bypass. Only when additional intravenous lorazepam was given prior to connection to the heart-lung machine were plasma lorazepam concentrations obtained compatible with complete amnesia.

Complement activation during cardiopulmonary bypass: quantitative study of effects of methylprednisolone and pulsatile flow.

Forty four patients undergoing open heart surgery were divided into three groups. Group 1 (17 patients) underwent routine anaesthesia and surgery; group 2 (17 patients) received two doses of methylprednisolone (30 mg/kg), one during induction of anaesthesia and the other immediately before induction of cardiopulmonary bypass; and group 3 (10 patients) received pulsatile flow while undergoing pulsatile perfusion by the heart-lung machine. A modification of the previously described technique was used to detect and measure complement activation in plasma before and during the bypass period using crossed immunoelectrophoresis. About 45% of all patients showed measurable complement activation (greater than 4.5%) during cardiopulmonary bypass and the mean activation in this group was 6.4%. There was no significant difference between the three groups in complement activation. In group 2, however, women showed significantly more complement activation than men (p less than 0.05). It is suggested that neither corticosteroids nor pulsatile flow affect complement activation, but caution should be exercised in women receiving methylprednisolone.

Quinine overdose. Prevention of visual damage by stellate ganglion block.

A case of quinine poisoning is described. Stellate ganglion block was performed immediately on the basis of the clinical history of visual disturbance without waiting for physical signs to develop. There was no residual field defect despite the presence of toxic levels of the drug. It is suggested that stellate ganglion block may prevent development of visual field defects.

Catecholamine and cortisol responses to sufentanil-O2 and alfentanil-O2 anaesthesia during coronary artery surgery.

The effects of alfentanil-O2 and sufentanil-O2 anaesthesia on plasma catecholamines and cortisol were investigated in 32 patients undergoing coronary artery bypass grafting operations. After lorazepam-atropine premedication and pancuronium pretreatment, alfentanil was given to 16 patients at a rate of 3 mg.min-1 and sufentanil was given to 16 patients at 300 micrograms.min-1 until the patients were unconscious; at this time they were given succinylcholine and were intubated. After intubation an amount of alfentanil or sufentanil equal to the dose producing unconsciousness was infused over the next 30 min, at which time the operation began. Additional alfentanil or sufentanil were given whenever systolic arterial blood pressure increased more than 15 per cent of preanaesthetic values. Arterial blood samples were obtained for epinephrine, norepinephrine and cortisol assay and cardiovascular dynamics were recorded prior to anaesthetic induction, 5 min after tracheal intubation, immediately prior to and five min after incision, ten min after maximal sternal spread, just prior to beginning and after 30 and 60 min of bypass and at the end of operation. Cardiovascular dynamics were little changed throughout anaesthesia and operation. Plasma epinephrine and norepinephrine were not significantly changed until bypass. During bypass both hormones became increased and remained increased at the end of operation. Plasma cortisol decreased after incision and remained decreased until the end of operation. These data indicate that alfentanil-O2 and sufentanil-O2 anaesthesia produce similar changes in plasma catecholamines and cortisol as does fentanyl-O2 anaesthesia and hormonal effects are, therefore, not an explanation for any advantages the newer narcotics may have over fentanyl.