Davy Cheng

Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis

BACKGROUND The magnitude of risk of death related to surgery and anaesthesia is not well understood. We aimed to assess whether the risk of perioperative and anaesthetic-related mortality has decreased over the past five decades and whether rates of decline have been comparable in developed and developing countries. METHODS We did a systematic review to identify all studies published up to February, 2011, in any language, with a sample size of over 3000 that reported perioperative mortality across a mixed surgical population who had undergone general anaesthesia. Using standard forms, two authors independently identified studies for inclusion and extracted information on rates of anaesthetic-related mortality, perioperative mortality, cardiac arrest, American Society of Anesthesiologists (ASA) physical status, geographic location, human development index (HDI), and year. The primary outcome was anaesthetic sole mortality. Secondary outcomes were anaesthetic contributory mortality, total perioperative mortality, and cardiac arrest. Meta-regression was done to ascertain weighted event rates for the outcomes. FINDINGS 87 studies met the inclusion criteria, within which there were more than 21·4 million anaesthetic administrations given to patients undergoing general anaesthesia for surgery. Mortality solely attributable to anaesthesia declined over time, from 357 per million (95% CI 324-394) before the 1970s to 52 per million (42-64) in the 1970s-80s, and 34 per million (29-39) in the 1990s-2000s (p<0·00001). Total perioperative mortality decreased over time, from 10,603 per million (95% CI 10,423-10,784) before the 1970s, to 4533 per million (4405-4664) in the 1970s-80s, and 1176 per million (1148-1205) in the 1990s-2000s (p<0·0001). Meta-regression showed a significant relation between risk of perioperative and anaesthetic-related mortality and HDI (all p<0·00001). Baseline risk status of patients who presented for surgery as shown by the ASA score increased over the decades (p<0·0001). INTERPRETATION Despite increasing patient baseline risk, perioperative mortality has declined significantly over the past 50 years, with the greatest decline in developed countries. Global priority should be given to reducing total perioperative and anaesthetic-related mortality by evidence-based best practice in developing countries. FUNDING University of Western Ontario.

Simultaneous integrated coronary artery revascularization with long-term angiographic follow-up

OBJECTIVE Traditionally integrated coronary artery revascularization has been described as a 2-stage procedure. We evaluated the safety and feasibility of 1-stage, simultaneous, hybrid, robotically assisted coronary artery bypass grafting surgery and percutaneous coronary intervention. METHODS Fifty-eight patients underwent simultaneous, integrated coronary artery revascularization in an operating theater equipped with angiographic equipment. Forty-five patients were men. The mean age was 59 years. All internal thoracic arteries were harvested with robotic assistance. All anastomoses were manually constructed through a small anterior non-rib-spreading incision without cardiopulmonary bypass on the beating heart. Immediately after and within the same operative suite, both angiographic confirmation of graft patency and percutaneous coronary intervention were performed. In 52 patients therapeutic anticoagulation was achieved with the direct thrombin inhibitor bivalirudin. RESULTS There were no deaths or wound infections. There was 1 perioperative myocardial infarction. One patient had a stroke, and 3 patients required re-exploration for bleeding. The median lengths of intensive care and hospital stay were 1 and 4 days, respectively. All patients were alive and symptom free at follow-up (mean, 20.2 months; range, 1.1-40.8 months). Long-term angiographic follow-up in 54 patients showed 49 (91%) patent grafts (mean, 9.0 months; range, 4.3-40.8 months). There were 7 in-stent restenoses and 2 occluded stents. CONCLUSION For multivessel coronary artery disease, simultaneous integrated coronary artery revascularization with bivalirudin is safe and feasible. This approach enables complete multivessel revascularization with decreased surgical trauma and postoperative morbidity. Further studies are necessary to better determine patient selection and long-term outcomes.

NSAID-analgesia, pain control and morbidity in cardiothoracic surgery

ObjectiveWhile narcotics remain the backbone of perioperative analgesia, the adjunctive role of other analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs), is being recognized increasingly. This meta-analysis sought to determine whether adjunctive NSAIDs improve postoperative analgesia and reduce cumulative narcotic requirements.MethodsA comprehensive search was undertaken to identify all randomized trials, in cardiothoracic patients, of NSAIDs plus narcotics vs narcotics without NSAIDs. Medline, Cochrane Library, EMBASE, and abstract databases were searched up to September 2005. The primary outcome was visual analogue scale (VAS) pain score. Secondary outcomes included 24-hr cumulative morphine-equivalents, rescue medications required, mortality, myocardial infarction, atrial fibrillation, stroke, renal failure, hospital readmissions, and in-hospital costs.ResultsTwenty randomized trials involving 1,065 patients were included. A significant reduction in 24-hr VAS pain score was found in patients receiving NSAIDs [weighted mean difference (WMD) -0.91 points, 95% confidence interval (CI) -1.48 to -0.34 points]. In addition, patients required significantly less morphine-equivalents in the first 24 hr (WMD -7.67 mg, 95% CI -8.97 to -6.38 mg). No significant difference was found with respect to mortality [odds ratio (OR) 0.19, 95% CI 0.01 to 4.22], myocardial infarction (OR 0.71, 95% CI 0.09 to 5.71), renal dysfunction (OR 0.95, 95% CI 0.37 to 2.46), or gastrointestinal bleeding (OR 0.96, 95% CI 0.13 to 7.09).ConclusionIn patients less than 70 yr of age undergoing cardiothoracic surgery, the adjunctive use of NSAIDs with narcotic analgesia reduces 24-hr VAS pain score and narcotic requirements.RésuméObjectifLes narcotiques demeurent le pivot de ľanalgésie périopératoire, mais le rôle complémentaire ďautres analgésiques, dont les anti-inflammatoires non stéroidiens (AINS), est de plus en plus reconnu. La présente méta-analyse veut déterminer si les AINS ďappoint améliorent ľanalgésie postopératoire et réduisent les besoins cumulatifs de narcotiques.MéthodeNous avons recensé toutes les études randomisées sur des narcotiques, complétés ou non par des AINS, réalisées auprs de patients de cardiochirurgie thoracique. Les bases Medline, Cochrane Library, EMBASE et les résumés parus jusqu’à septembre 2005 ont été explorés. Le principal paramtre recherché était le score de douleur à ľéchelle visuelle analogique (EVA). Les paramtres secondaires étaient la consommation cumulative, sur 24 h, ďanalgésiques en équivalents-morphine, les besoins de médicaments ďappoint, la mortalité, la présence ďinfarctus du myocarde, la fibrillation auriculaire, ľaccident vasculaire, ľinsuffisance rénale, la réadmission hospitalire et le coût de ľhospitalisation.RésultatsVingt études randomisées regroupant 1 065 patients ont été retenues. Une réduction significative des scores de douleur, sur 24 h, a été trouvée chez ceux qui recevaient des AINS [différence moyenne pondérée (DMP) -0,91 points, intervalle de confiance de 95 % (IC) -1,48 à -0,34 points]. De plus, les patients ont demandé sensiblement moins ďéquivalents-morphine au cours des 24 premires heures (DMP -7,67 mg, IC de 95 % -8,97 à -6,38 mg). Il n’y avait aucune différence significative quant à la mortalité [risque relatif (RR) de 0,19, IC de 95 % 0,01 à 4,22], à ľinfarctus du myocarde (RR 0,71, IC de 95 % 0,09 à 5,71), à ľinsuffisance rénale (RR 0,5, IC de 95 % 0,37 à 2,46) ou au saignement gastrointestinal (RR 0,96, IC de 95 % 0,13 à 7,09).ConclusionChez les patients de moins de 70 ans qui subissent une opération cardiothoracique, ľusage ďAINS ďappoint avec ľanalgésie aux narcotiques réduit la douleur et les besoins de narcotiques sur 24 h.

N-acetylcysteine in Cardiac Surgery: Do the Benefits Outweigh the Risks? A Meta-Analytic Reappraisal

OBJECTIVE N-acetylcysteine (NAC) reduces proinflammatory cytokines, oxygen free-radical production, and ameliorates ischemia reperfusion injury; therefore, it may theoretically reduce postoperative complications in cardiac surgery. The aim of this study was to determine, through systematic review and meta-analysis of all relevant randomized trials, whether NAC reduces mortality, morbidity, or resource utilization in cardiac surgery. DESIGN Meta-analysis. SETTING University hospitals. PARTICIPANTS A total of 1,407 patients from 15 randomized studies were included in the analysis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS All randomized trials searched up to May 2009 comparing the use of NAC versus placebo during cardiac surgery in any language and reporting at least 1 predefined outcome were included. The random effect model was used to calculate odds ratios (ORs, 95% confidence intervals [CIs]) and weighted mean differences (WMD, 95% CI) for dichotomous and continuous variables, respectively. During cardiac surgery, the use of NAC did not significantly decrease acute renal failure requiring renal replacement therapy (OR = 1.05; 95% CI, 0.52-2.11; p = 0.90), new atrial fibrillation (OR = 0.67; 95% CI, 0.37-1.22; p = 0.19), or mortality (OR = 0.81; 95% CI, 0.39-1.68; p = 0.57). There were no differences in the incidence of incremental increase in serum creatinine concentration greater than 25% above baseline (OR = 0.86; 95% CI, 0.66-1.12; p = 0.26), acute myocardial infarction (OR = 0.69; 95% CI, 0.29-1.61, p =0.39), stroke (OR = 0.78; 95% CI, 0.30-2.03; p = 0.61), red blood cell transfusion requirement (OR = 0.77; 95% CI, 0.45-1.31; p = 0.33), re-exploration (OR = 1.33; 95% CI, 0.70-2.26; p = 0.29), or postoperative drainage (WMD = 33 mL; 95% CI,-125 to 191 mL; p = 0.69) between NAC and placebo. CONCLUSION Current evidence shows that the perioperative use of NAC has no proven benefit or risk on clinically important outcomes in patients undergoing cardiac surgery.

Perioperative coagulation management and blood conservation in cardiac surgery: a Canadian Survey.

OBJECTIVE To determine which strategies are currently used for (anti)coagulation management and blood conservation during cardiac surgery in Canada. DESIGN Institutional survey. SETTING University hospital. PARTICIPANTS All sites performing cardiac surgery in Canada. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The response rate was 85%. Anticoagulation with heparin is monitored routinely through the activated coagulation time (ACT). Less than 10% of centers use heparin concentrations (Hepcon HMS, Medtronic), thromboelastography, or other point-of-care tests perioperatively. Eighty percent of centers routinely use tranexamic acid as the primary antifibrinolytic agent; however aprotinin until recently, was used more commonly for patients at increased risk for bleeding. Retrograde autologous prime is commonly used (62%); however, cell savers are uncommon for routine patients undergoing cardiac surgery (29%). Although most hospitals use a hematocrit of 20% to 21% for transfusing red blood cells, more than 50% of intensive care units do not have written guidelines for the administration of protamine, fresh frozen plasma, platelets, or factor VIIa. At least one third of centers do not audit their transfusion practices regularly. CONCLUSIONS The majority of Canadian institutions do not use point-of-care tests other than ACT. Most institutions do not have algorithms for management of bleeding following cardiac surgery and at least 30% do not monitor their transfusion practice perioperatively. Cardiac surgery patients in Canada may benefit from a standardized approach to blood conservation in the perioperative period.

Stress-induced cardiomyopathy in the perioperative setting

In their report in this issue of the Journal, Suk et al. describe the case of a 37-year-old female who developed anaphylaxis in response to cefotiam administration during a laparoscopic surgical procedure. A prolonged period of profound hypotension was followed by appropriate resuscitative maneuvers, but the patient subsequently developed a cardiomyopathy requiring ongoing medical treatment. The authors highlight a rather unusual presentation of Tako-Tsubo cardiomyopathy which occurred in the perioperative setting. Increasingly, we are recognizing that Tako-Tsubo cardiomyopathy, also commonly referred to as stress-induced cardiomyopathy, transient cardiomyopathy, or apical ballooning syndrome, is a condition which may be more frequent in the perioperative setting than commonly appreciated. What is unusual about this case and somewhat unsettling is the observation that antibiotic-induced anaphylaxis or the treatment of anaphylaxis could, in turn, be associated with a potentially life-threatening cardiomyopathy. Interestingly, the pathophysiology of this cardiomyopathy may be similar to that of other disease entities that may be associated with acute cardiac dysfunction, including subarachnoid hemorrhage. Based on the underlying etiology, stress-induced cardiomyopathy can be divided into two categories. The first category is related to emotional distress, leading to catecholamine surges and resulting in cardiac dysfunction. The second category is related to physical-pathological distress secondary to disease entities, including pneumonia, severe acute asthma, or anaphylaxis, where catecholamine surges are secondary to the underlying disease process, which secondarily induces this unique cardiomyopathy. For both categories of stress-induced cardiomyopathy, there is an associated release of large quantities of epinephrine and norepinephrine, which are thought to be the primary mediators of the cardiomyopathy. The catecholamines temporarily disrupt the cardiac microvasculature resulting in myocardial dysfunction. In their report, Suk et al. infer that excess catecholamine surges may have occurred, either in response to the primary anaphylactic event or secondarily to the administration of exogenous epinephrine and norepinephrine given to treat the acute event. The original report of stress-induced cardiomyopathy originates from Japan in 1991. The authors reported on five cases from a series of 415 patients who presented with symptoms of acute myocardial infarction (AMI). Two of these patients had evidence of vasospasm at the time of angiography; two others developed vasospasm in response to the injection of ergonovine as a provocative test. There are numerous other reports in the literature of ambulatory patients presenting with stress-induced cardiomyopathy. The most comprehensive of these reports is from a systematic review of published case series. From the published series, it is inferred that up to 2% of patients presenting with AMI have a stress-induced cardiomyopathy, and furthermore, 27% of the presentations are secondary to emotional stress only, with 38% of patients having some type of physical stressor. The underlying causes in the remainder of cases were unreported. The associated mortality is reported to be 1.1%. While many case reports have documented an emotional trigger prior to the onset of symptoms, the few perioperative case reports have typically described events occurring intraoperatively under general anesthesia. D. Bainbridge, MD (&) D. Cheng, MD Department of Anesthesia & Perioperative Medicine, London Health Sciences Center-University Hospital & St. Joseph’s Health Care, University of Western Ontario, 339 Windermere Road, London, ON N6A 5A5, Canada e-mail: daniel.bainbridge@lhsc.on.ca

Role of the anesthesiologist in the wider governance of healthcare and health economics

PurposeHealthcare resources will always be limited, and as a result, difficult decisions must be made about how to allocate limited resources across unlimited demands in order to maximize health gains per resource expended. Governments and hospitals now in severe financial deficits recognize that reengagement of physicians is central to their ability to contain the runaway healthcare costs. Health economic analysis provides tools and techniques to assess which investments in healthcare provide good value for money vs which options should be forgone. Robust decision-making in healthcare requires objective consideration of evidence in order to balance clinical and economic benefits vs risks.Principal findingsSurveys of the literature reveal very few economic analyses related to anesthesia and perioperative medicine despite increasing recognition of the need. Now is an opportune time for anesthesiologists to become familiar with the tools and methodologies of health economics in order to facilitate and lead robust decision-making in quality-based procedures. For most technologies used in anesthesia and perioperative medicine, the responsibility to determine cost-effectiveness falls to those tasked with the governance and stewardship of limited resources for unlimited demands using best evidence plus economics at the local, regional, and national levels. Applicable cost-effectiveness, cost-utility, and cost-benefits in health economics are reviewed in this article with clinical examples in anesthesia.ConclusionsAnesthesiologists can make a difference in the wider governance of healthcare and health economics if we advance our knowledge and skills beyond the technical to address the “other” dimensions of decision-making – most notably, the economic aspects in a value-based healthcare system.RésuméObjectifLes ressources en soins de santé seront toujours limitées, c’est pourquoi des décisions difficiles doivent être prises quant à l’allocation de ressources limitées pour des demandes illimitées, afin d’optimiser les gains en santé par ressource dépensée. Les gouvernements et les hôpitaux, aujourd’hui en déficit financier grave, reconnaissent qu’une implication nouvelle des médecins est cruciale pour pouvoir restreindre des coûts des soins de santé incontrôlables. L’analyse de l’économie de la santé fournit des outils et des techniques permettant d’évaluer la rentabilité des investissements dans les soins de santé, et de déterminer lesquels devraient être abandonnés. Pour prendre des décisions éclairées en soins de santé, il faut considérer de façon objective les données probantes afin de soupeser les avantages cliniques et économiques eu égard aux risques.Constatations principalesLes recherches dans la littérature révèlent qu’il existe très peu d’analyses économiques liées à l’anesthésie et à la médecine périopératoire et ce, malgré la prise de conscience croissante de ce besoin. Le moment est opportun pour que les anesthésiologistes se familiarisent avec les outils et méthodologies de l’économie de la santé afin de faciliter et de mener des prises de décision robustes dans des interventions fondées sur la qualité. La responsabilité de déterminer la rentabilité de la plupart des technologies utilisées en anesthésie et en médecine périopératoire incombe aux personnes dont la tâche est la gouvernance et l’intendance de ressources limitées pour des demandes illimitées en se fondant sur les meilleures données probantes et l’économie aux niveaux local, régional et national. Les rapports coût-efficacité, coût-utilité et coût-avantage en économie de la santé sont passés en revue dans cet article, avec des exemples cliniques d’anesthésie à l’appui.ConclusionLes anesthésiologistes peuvent faire une différence dans la gouvernance élargie des soins de santé et de l’économie de la santé, si nous faisons progresser nos connaissances et nos compétences au-delà de leur dimension technique pour aborder les ‘autres’ dimensions pertinentes à la prise de décision – et tout particulièrement les aspects économiques d’un système de soins de santé fondé sur la valeur.

Evidence-based practice and health technology assessment: a call for anesthesiologists to engage in knowledge translation.

How often have senior leaders in your hospital asked you to cut drug and equipment costs? Can we justifiably afford depth of anesthesia monitoring equipment for each operating room? Based on the benefits and risks, is the routine use of inhaled nitric oxide properly justified in patients who experience difficulty in weaning from cardiopulmonary bypass? Healthcare in North America is clearly at a crux. On the one hand, there is the pressing need to do all that we can to justify the increasing costs and efforts expended to implement new drugs, technologies, and techniques into practice. On the other hand, we need to respect that we cannot (and should not) ‘‘do it all’’, especially if the new techniques or technologies will achieve only marginal benefits at best and at greater risk and cost compared with the existing status quo. There is a limit in terms of available resources: money, space, human resources, time, and effort. Evidence-based health technology assessment (EBHTA) is not necessarily a means for cost-cutting, since the best available evidence may suggest that the newest most expensive option is truly the best option, and that the payback is worth the incremental costs required. Thus, EB-HTA provides guidance to ensure that resources are not wasted and that every dollar expended improves value for money. Evidence-based medicine (EBM) is formally defined as the ‘‘conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients’’. To practice EBM, all relevant highquality evidence should be sought, even when it does not say what we want it to say. Evidence-based medicine provides tools for filtering and interpreting clinical evidence so that we are less prone to being duped by biased or misleading information that can be cleverly cloaked as scientific evidence. For example, we can use pre-filtered evidence or apply the tips set out by the users’ guides to the medical literature to improve our objectivity in determining:

Minimally invasive direct coronary artery bypass and off-pump coronary artery bypass surgery: anesthetic considerations.

Many new surgical technologies are being developed, with the overall aim of improving outcomes. One common feature of many new technologies is that they offer a safer approach than previous techniques; one of the greatest forces for change over the last 30 years is risk reduction. Cardiac surgery risk has been effectively undercut by percutaneous-based procedures, which have offered dramatic reductions in risk--at least in the short term. Beating heart techniques, whether minimally invasive direct coronary artery bypass (MIDCAB), off-pump coronary artery bypass surgery (OPCAB), or in other forms, such as percutaneous valve replacement, are likely to dramatically increase over the next decade. What role OPCAB and MIDCAB techniques will play in this new era is anyones guess.

Can we develop a Canadian Perioperative Anesthesiology Clinical Trials Group

In Canada, research in the field of anesthesiology has been restricted mainly to the domains of basic science and applied physiology. Despite being of valuable scientific relevance and importance, most of this research evaluates physiologic outcomes or surrogate clinical outcomes rather than clinically significant outcomes that could change the way in which we practice. While many medical specialties have appreciated the importance of evaluating outcomes, such as mortality, quality of life, length of stay or efficiency of care, anesthesiology has lagged behind. One of the main reasons Canadian anesthesiology has been slow to embrace outcome studies is the delayed development of a collaborative network of anesthesia investigators to advance multicentre clinical research projects. Clinical research is at a turning point and is rapidly evolving, not only in Canada but worldwide. We strongly believe that Canadian anesthesiologists are capable of markedly improving their research capacity by fostering collaborative outcome-driven research. We further believe that such research can and will change clinical practice. In order to attain this goal, we have initiated a collaborative research network, the Perioperative Anesthesiology Clinical Trials (PACT) group. The PACT group is a collaborative group of Canadian academic anesthesiologists with an interest in the design, implementation, conduct, and publication of multicentre clinical trials in anesthesiology and perioperative medicine. The aim of the PACT initiative is to help anesthesiology clinician investigators 1) to identify and investigate clinically relevant questions in anesthesiology and perioperative medicine; 2) to build research programs that answer their research questions; 3) to structure and conduct quality research with sound methodology; 4) to facilitate collaboration amongst various investigators across Canada so as to conduct multicentre research; 5) to acquire peer-reviewed funding from granting agencies; and finally 6) to execute and publish their results in high-impact peer-reviewed journals. The primary focus of the PACT initiative is to generate knowledge in perioperative anesthesia by providing a forum for the development and implementation of multicentre clinical trials that are designed to answer research questions. It is anticipated that the forum will have a fundamental impact on the practice of anesthesiology and perioperative medicine. In addition, the PACT group will provide mentoring to new investigators as a collaborative network and will facilitate the dissemination of research knowledge, best practices, and standardization of practice parameters, thereby informing the practice of anesthesiology and ensuring its continued advancement as a profession. R. Hall, MD S. Beattie, MD D. Cheng, MD P. Choi, MD A. Y. Denault, MD D. Mazer, MD W. A. C. Mutch, MD A. F. Turgeon, MD H. Yang, MD Perioperative Anesthesiology Clinical Trials Group Steering Committee, Halifax, NS, Canada