A personal history of the MASTER Trial and its link to the clinical trials network of the Australian and New Zealand College of Anaesthetists.

The aim of this paper is to link the history of the Multicentre Australian Study of Epidural Anaesthesia in high risk surgery, the MASTER Trial, the first National Health and Medical Research Council (NHMRC) funded multicentre randomised clinical trial in Australia led by anaesthetist researchers, and the decision of The Australian and New Zealand College of Anaesthetists (ANZCA) to establish a clinical trials network, in 2003, to the success of contemporary researchers in Australia and New Zealand in anaesthesia and perioperative medicine.

Design of the multicenter Australian study of epidural anesthesia and analgesia in major surgery: the MASTER trial.

The Multicenter Australian Study of Epidural Anesthesia and Analgesia in Major Surgery (The MASTER Trial) was designed to evaluate the possible benefit of epidural block in improving outcome in high-risk patients. The trial began in 1995 and is scheduled to reach the planned sample size of 900 during 2001. This paper describes the trial design and presents data comparing 455 patients randomized in 21 institutions in Australia, Hong Kong, and Malaysia, with 237 patients from the same hospitals who were eligible but not randomized. Nine categories of high-risk patients were defined as entry criteria for the trial. Protocols for ethical review, informed consent, randomization, clinical anesthesia and analgesia, and perioperative management were determined following extensive consultation with anesthesiologists throughout Australia. Clinical and research information was collected in participating hospitals by research staff who may not have been blind to allocation. Decisions about the presence or absence of endpoints were made primarily by a computer algorithm, supplemented by blinded clinical experts. Without unblinding the trial, comparison of eligibility criteria and incidence of endpoints between randomized and nonrandomized patients showed only small differences. We conclude that there is no strong evidence of important demographic or clinical differences between randomized and nonrandomized patients eligible for the MASTER Trial. Thus, the trial results are likely to be broadly generalizable.

Midterm experience with the endovascular treatment of isolated iliac aneurysms.

PURPOSE: This report describes our 5-year experience with the endovascular repair of isolated iliac aneurysms and pseudoaneurysms. METHODS: Between June 1993 and July 1998, 40 isolated iliac aneurysms and pseudoaneurysms were treated with endovascular grafts in 39 patients. Thirty-seven aneurysms were treated with endovascular grafts composed of polytetrafluoroethylene grafts and balloon expandable stents, and the other three underwent repair with a polycarbonate urethane endoluminal graft. RESULTS: All the patients underwent initially successful endovascular treatment of isolated iliac aneurysms and pseudoaneurysms and were followed from 1 to 51 months (mean, 18 months). The 4-year primary patency rate was 94.5% +/- 10%. The perioperative complications included one episode of distal embolization, an episode of colonic ischemia, five episodes of kinking or compression of the endovascular graft, and one early postoperative graft thrombosis. There was only one perioperative death in a patient whose aneurysm ruptured in the operating room just before endovascular repair. The median postoperative length of hospital stay was 3.0 +/- 1.3 days in this group of patients at moderate and high risk. The long-term complications included one graft thrombosis and two endoleaks. One small endoleak was followed until the patient died of unrelated causes, and the other one led to aneurysm rupture in the only patient temporarily lost to follow-up examination. This patient successfully underwent treatment in the standard open surgical fashion. To date, all the other aneurysms have remained stable or have decreased in size during the follow-up examinations with duplex or contrast-enhanced computed tomographic scans. CONCLUSION: Endovascular repair of iliac aneurysms and pseudoaneurysms is a safe and effective technique with good midterm results in patients at standard and high risk. These grafts are particularly beneficial for patients with medical, surgical, or anatomic contraindications for open surgical repair.

Evidence-based methods to improve anaesthesia and intensive care.

This review concerns the application of the methods of clinical epidemiology to problems in anaesthesia and intensive care. It explores the quality of evidence to guide clinical decision-making and health policy provided by experimental and various non-experimental research designs. Ten recent publications in anaesthesia and intensive care are analysed to provide relevant examples.

Improving the evidence base for anaesthesia. MASTER Anaesthesia Trial Study Group.

This paper is a brief report of the symposium, "Improving the Evidence Base for Anaesthesia and Intensive Care", organized by the MASTER Anaesthesia Trial Study Group at the Annual Scientific Meeting of the Australian and New Zealand College of Anaesthetists, Newcastle, N.S.W., on Tuesday, May 5, 1998.

Rapid attainment of steady state plasma drug concentrations within precise limits.

We describe a method of rapidly obtaining a specified steady state plasma concentration of an intravenous drug within precise limits. The technique requires an initial bolus to raise the plasma concentration to the upper limit followed by a series of constant-rate infusions each of which is associated with a minimum plasma concentration equal to the lower limit. The infusion rate is stepped down when the plasma concentration returns to the upper limit. Computer simulation, based on the method, is used to generate plasma concentration-time curves with fluctuations of up to 10% about selected steady state concentrations of amrinone, esmolol, lidocaine, midazolam, propofol, and theophylline. The utility of this general approach to intravenous dosing and potential limitations of the method are discussed.

Outcome after general or regional anaesthesia in high-risk patients.

This review is a critical analysis of research design for studies of outcome comparing epidural anaesthesia and analgesia with general anaesthesia and alternative postoperative analgesia regimens. If important advances in knowledge are to be made, appropriately designed multicentre randomized controlled trials are essential. These trials must incorporate strict controls on patient entry, a comprehensive range of carefully defined and clinically significant morbidity endpoints and the previous determination of sample size through a proper analysis of statistical power.

Mivacurium or vecuronium for muscular relaxation in day-case surgery.

Anaesthetic agents for day-case surgery ideally should have a short duration of action. This study was designed to compare the efficacy and safety of mivacurium and vecuronium for healthy adults undergoing dental day-case surgery. Thirty fit healthy adult patients (ASA I or II) randomly received either mivacurium 0.15 mg kg-1 (n = 15) or vecuronium 0.1 mg kg-1 (n = 15). Anaesthesia included propofol, fentanyl, nitrous oxide and isoflurane. Maximum depression of T1 was greater in the vecuronium group (99.8%) than in the mivacurium group (98.3%). There was no difference between grade of intubation at 2 min between the two groups, although patients receiving vecuronium had a more profound block at the time of intubation than those who received mivacurium (89.2% vs. 78.9%). Recovery to 10% T1 was faster in the mivacurium group (11.2 min vs. 33.1 min). All patients in the vecuronium group received neostigmine at the termination of surgery. The neostigmine evoked recovery index in the vecuronium group (4.39 min) was less than the spontaneous recovery index in the mivacurium group (6.78 min). One patient in the mivacurium group had a low plasma cholinesterase concentration (0.43 ku L-1); recovery times however, fell within the 95% confidence intervals (CI) for the group. There was no correlation between cholinesterase levels and recovery time. Mivacurium may be the more appropriate agent for dental day-case surgery because it has a shorter duration of action and does not generally require antagonism with an anticholinesterase.

The incidence of minor sequelae following anaesthesia in children.

A survey was performed to estimate the incidence of the minor sequelae of anaesthesia in children. During an eight-month period 266 children, aged five years and over, were personally interviewed by an anaesthetist following recovery from anaesthesia. At interview the child was questioned to ascertain any morbidity suffered and record was made of the operation performed and the anaesthetic administered. Data were then evaluated, using multivariate analysis, to identify risk factors for the more common sequelae. This study revealed a higher incidence of the minor sequelae of anaesthesia in children than had previously been reported. The three most common sequelae recorded were nausea (48.1%), vomiting (35.0%), and sore throat (31.4%).

Oxygen saturation during endoscopic retrograde cholangiopancreatography: a comparison of two protocols of oxygen administration.

Patients having endoscopic retrograde cholangiopancreatography (ERCP) are generally elderly and require sedation while in the prone position. These factors may be expected to aggravate any risk of arterial hypoxia. This study evaluated two protocols of oxygen administration, one with and one without pre-oxygenation. In 25 patients in whom pre-oxygenation with 4 litres/minute for five minutes before sedation was used, followed by continuous oxygen administration, arterial oxygen saturation did not fall below 90% at any stage during the procedure. By contrast, in 25 patients who were not pre-oxygenated oxygen saturation fell below 90% in nine (36%). As expected, hypoxia occurred most frequently during the early stages of sedation and endoscope insertion. Hypoxia did not occur in association with operations such as sphincterotomy, stone extraction or stent insertion. This study confirms that arterial hypoxia is a common event during ERCP and can be completely prevented by pre-oxygenation with four litres of oxygen given intranasally for five minutes before sedation.