Ravindranath Tiruvoipati

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial

BACKGROUNDnSevere acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support.nnnMETHODSnIn this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH <7.20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827.nnnFINDINGSn766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%.nnnINTERPRETATIONnWe recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK.nnnFUNDINGnUK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.

Standards of Reporting of Randomized Controlled Trials in General Surgery: Can We Do Better?

Objective:To evaluate the quality of reporting of surgical randomized controlled trials published in surgical and general medical journals using Jadad score, allocation concealment, and adherence to CONSORT guidelines and to identify factors associated with good quality. Summary Background Data:Randomized controlled trials (RCTs) provide the best evidence about the relative effectiveness of different interventions. Improper methodology and reporting of RCTs can lead to erroneous conclusions about treatment effects, which may mislead decision-making in health care at all levels. Methods:Information was obtained on RCTs published in 6 general surgical and 4 general medical journals in the year 2003. The quality of reporting of RCTs was assessed under masked conditions using allocation concealment, Jadad score, and a CONSORT checklist devised for the purpose. Results:Of the 69 RCTs analyzed, only 37.7% had a Jadad score of ≥3, and only 13% of the trials clearly explained allocation concealment. The modified CONSORT score of surgical trials reported in medical journals was significantly higher than those reported in surgical journals (Mann-Whitney U test, P < 0.001). Overall, the modified CONSORT score was higher in studies with higher author numbers (P = 0.03), multicenter studies (P = 0.002), and studies with a declared funding source (P = 0.022). Conclusion:The overall quality of reporting of surgical RCTs was suboptimal. There is a need for improving awareness of the CONSORT statement among authors, reviewers, and editors of surgical journals and better quality control measures for trial reporting and methodology.

Efficacy of prone ventilation in adult patients with acute respiratory failure: A meta-analysis

PURPOSEnThe use of prone ventilation in acute respiratory failure has been investigated by several randomized controlled trials in the recent past. To date, there has been no systematic review or meta-analysis of these trials.nnnMATERIAL AND METHODSnSystematic literature search was performed between 1966 and July 2006 to identify randomized trials evaluating prone ventilation. Outcome measures included mortality, changes in oxygenation, incidence of pneumonia, duration of mechanical ventilation, intensive care unit (ICU) and hospital stay, cost-effectiveness, and adverse effects including pressure sores, endotracheal tube, or intravascular catheter complications.nnnRESULTSnProne ventilation was not associated with reduction in mortality, but improvement in oxygenation was statistically significant (mean difference, 21.2 mm Hg; P < .001). There was no significant difference in incidence of pneumonia, ICU stay, and endotracheal tube complications. There was a trend toward an increased incidence of pressure sores in prone ventilated patients (odds ratio = 1.95; 95% confidence interval, 0.09-4.15; P = .08). The data on other outcomes were not suitable for meta-analysis.nnnCONCLUSIONSnThe use of prone ventilation is associated with improved oxygenation. It is not associated with a reduction in mortality, pneumonia, or ICU stay and may be associated with an increased incidence of pressure sores.

Fatal thrombosis with activated factor VII in a paediatric patient on extracorporeal membrane oxygenation

Bleeding remains a potential complication for patients requiring extracorporeal life support systems. Recombinant activated factor VII (rFVIIa) is one of the drugs used in controlling bleeding. Its use is generally found to be safe. We report a paediatric patient who developed fatal thrombosis with the use of rFVIIa whilst on extracorporeal membrane oxygenation and discuss the possible factors that lead to fatal thrombosis.

Methods of data collection and analysis for the economic evaluation alongside a national, multi-centre trial in the UK: Conventional ventilation or ECMO for Severe Adult Respiratory Failure (CESAR)

BackgroundExtracorporeal Membrane Oxygenation (ECMO) is a technology used in treatment of patients with severe but potentially reversible respiratory failure. A multi-centre randomised controlled trial (CESAR) was funded in the UK to compare care including ECMO with conventional intensive care management. The protocol and funding for the CESAR trial included plans for economic data collection and analysis. Given the high cost of treatment, ECMO is considered an expensive technology for many funding systems. However, conventional treatment for severe respiratory failure is also one of the more costly forms of care in any health system.Methods/DesignThe objectives of the economic evaluation are to compare the costs of a policy of referral for ECMO with those of conventional treatment; to assess cost-effectiveness and the cost-utility at 6 months follow-up; and to assess the cost-utility over a predicted lifetime. Resources used by patients in the trial are identified. Resource use data are collected from clinical report forms and through follow up interviews with patients. Unit costs of hospital intensive care resources are based on parallel research on cost functions in UK NHS intensive care units. Other unit costs are based on published NHS tariffs. Cost effectiveness analysis uses the outcome: survival without severe disability. Cost utility analysis is based on quality adjusted life years gained based on the Euroqol EQ-5D at 6 months. Sensitivity analysis is planned to vary assumptions about transport costs and method of costing intensive care. Uncertainty will also be expressed in analysis of individual patient data. Probabilities of cost effectiveness given different funding thresholds will be estimated.DiscussionIn our view it is important to record our methods in detail and present them before publication of the results of the trial so that a record of detail not normally found in the final trial reports can be made available in the public domain.Trial RegistrationsThe CESAR trial registration number is ISRCTN47279827.

Extracorporeal membrane oxygenation with lepirudin anticoagulation for Wegener's granulomatosis with heparin- induced thrombocytopenia

Venovenous extracorporeal membrane oxygenation with lepirudin anticoagulation was successfully used for a complicated case of Wegener’s granulomatosis and heparin-induced thrombocytopenia. Interestingly, a linear correlation was found between activated partial thromboplastin time and activated clotting time during lepirudin anticoagulation.

Coronary endarterectomy in the current era.

Purpose of review The increasing incidence of diffuse coronary artery disease in the current era challenges cardiac surgeons in accomplishing their goal of complete revascularisation. Although coronary endarterectomy is used with encouraging results in most institutions, there remains some controversy in its indications, technique, and results. The purpose of this review is to highlight the important evolutions of technique in the recent past. Recent findings Despite the increased risk factors and comorbidities in patients presenting with diffuse coronary artery disease requiring coronary endarterectomy, the results of coronary endarterectomy are improving inline with the improvements in the results of conventional coronary artery bypass grafting surgery. The improving results of coronary endarterectomy in the left anterior descending artery are further clarified. The intra- and postoperative use of prostacyclin has been shown to be effective in reducing mortality and perioperative myocardial infarction. The technique of open coronary endarterectomy with on-lay patch bypass grafting has been shown to be safe and effective in reducing mortality and improving patency as compared with the closed (traction) method of coronary endarterectomy. The use of coronary endarterectomy was also found to be effective in the treatment of in-stent restenosis in the setting of diffuse coronary artery disease. The results of off-pump coronary endarterectomy are encouraging and comparable with the conventional coronary endarterectomy using cardiopulmonary bypass. Summary With the increasing incidence of diffuse coronary artery disease and improving results of coronary endarterectomy, it is vital for cardiac surgeons to have coronary endarterectomy in their armamentarium to achieve complete coronary revascularisation.

Referral pattern of neonates with severe respiratory failure for extracorporeal membrane oxygenation

Background: Extracorporeal membrane oxygenation (ECMO) remains the mainstay of management in neonates with severe but potentially reversible respiratory failure. In the UK, ECMO is available only as a supraregional service at four centres. Objective: To explore regional variations in ECMO referrals and neonatal deaths due to severe respiratory failure in England, Wales and Northern Ireland. Methods: In this retrospective study, data regarding ECMO referrals due to neonatal respiratory failure from January to December 2002 were obtained from the four UK ECMO centres and then subdivided according to the Government Office Regions. Anonymised data regarding neonatal deaths was obtained from Confidential Enquiry into Maternal and Child Health. Neonatal deaths were classified into four groups (group 1: deaths potentially avoidable by ECMO; group 2: deaths where it was unclear whether ECMO would have been of benefit; group 3: neonates not eligible for ECMO; and group 4: data inadequate to classify deaths). Results: There was significant regional variation in the rates of both ECMO referral (0.10 to 0.46 per 1000 live births; (p<0.001)) and neonatal deaths (groups 1 and 2) (0.09 to 0.32 per 1000 live births; (p<0.001)). Regions with high referral rates for ECMO tended towards having higher group 1 plus group 2 neonatal death rates (correlation coefficient u200a=u200a0.75). Conclusion: It is possible that there are significant regional variations in the uptake of ECMO and in neonatal mortality due to severe respiratory failure. A confidential prospective study may further clarify these observations and identify the factors that might lead to these variations.