Duminda N. Wijeysundera

Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications:: A meta-analysis☆

PURPOSEnTo investigate the effects of alpha(2)-adrenergic agonists on perioperative mortality and cardiovascular complications in adults undergoing surgery.nnnMETHODSnMEDLINE (1966 to May 2002), EMBASE (1980 to May 2002), the Cochrane Clinical Trials Register, the Science Citation Index, and bibliographies of included articles were searched without language restriction. Randomized trials comparing preoperative, intraoperative, or postoperative (first 48 hours) administration of clonidine, dexmedetomidine, or mivazerol with controls were included. Studies had to report any of the following outcomes: mortality, myocardial infarction, ischemia, or supraventricular tachyarrhythmia. Treatment effects were calculated using the fixed-effects model. Heterogeneity was assessed using the Q test.nnnRESULTSnTwenty-three trials comprising 3395 patients were included. Overall, alpha(2)-adrenergic agonists reduced mortality (relative risk [RR] = 0.64; 95% confidence interval [CI]: 0.42 to 0.99; P = 0.05) and ischemia (RR = 0.76; 95% CI: 0.63 to 0.91; P = 0.003) significantly. They also reduced mortality (RR = 0.47; 95% CI: 0.25 to 0.90; P = 0.02) and myocardial infarction (RR = 0.66; 95% CI: 0.46 to 0.94; P = 0.02) during vascular surgery. During cardiac surgery, alpha(2)-adrenergic agonists reduced ischemia (RR = 0.71; 95% CI: 0.54 to 0.92; P = 0.01) and were associated with trends toward lower mortality (RR = 0.49; 95% CI: 0.12 to 1.98; P = 0.3) and a reduced risk of myocardial infarction (RR = 0.83; 95% CI: 0.35 to 1.96; P = 0.7).nnnCONCLUSIONnAlpha-2 adrenergic agonists reduce mortality and myocardial infarction following vascular surgery. During cardiac surgery, they reduce ischemia and may also have effects on mortality and myocardial infarction. Large randomized trials are needed to evaluate these agents during cardiac and vascular surgery.

Risk Associated With Preoperative Anemia in Cardiac Surgery A Multicenter Cohort Study

Background— Preoperative anemia is an important risk factor for perioperative red blood cell transfusions, which are associated with postoperative morbidity and mortality. Whether preoperative anemia also is an independent risk factor for adverse outcomes after cardiac surgery, however, has not been fully elucidated. Methods and Results— In this multicenter cohort study, data were collected on 3500 consecutive patients who underwent cardiac surgery during 2004 at 7 academic hospitals. The prevalence of preoperative anemia, defined as hemoglobin <12.5 g/dL, and its unadjusted and adjusted relationships with the composite outcome of in-hospital death, stroke, or acute kidney injury were obtained. The overall prevalence of preoperative anemia was 26%, with values ranging from 22% to 30% at the participating hospitals. After the exclusion of patients who had severe preoperative anemia (hemoglobin <9.5 g/dL) or preoperative kidney failure and those who underwent emergency surgery, the composite outcome was observed in 7.5% of patients (247 of 3286). The unadjusted odds ratio for the composite outcome in anemic versus nonanemic patients was 3.6 (95% confidence interval, 2.7 to 4.7). The risk-adjusted odds ratios, obtained by multivariable logistic regression and propensity-score matching to control for important confounders (including comorbidities, institution, surgical factors, and blood transfusion), were 2.0 (95% confidence interval, 1.4 to 2.8) and 1.8 (95% confidence interval, 1.2 to 2.7), respectively. Conclusions— Preoperative anemia is independently associated with adverse outcomes after cardiac surgery. Future studies should determine whether therapies aimed at treating preoperative anemia would improve the outcomes of patients undergoing cardiac surgery.

Platelet transfusions are not associated with increased morbidity or mortality in cardiac surgery.

PurposeTo determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery.MethodsIn this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis.ResultsOf the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets -1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events.ConclusionsTransfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.RésuméObjectifDéterminer la relation indépendante entre la transfusion de plaquettes réduites en leucocytes et les événements indésirables en cardiochirurgie.MéthodeDans une étude par observation, la cueillette prospective des données initiales et périopératoires détaillées a été faite pour des patients successivement opérés en cardiochirurgie dans un seul établissement entre 1999 et 2004. Les associations indépendantes entre transfusion plaquettaire et résultat clinique (syndrome de bas débit, infarctus du myocarde, accident vasculaire, insuffisance rénale, septicémie et mort) ont été déterminées par une analyse multivariée de régression logistique et une analyse cas-témoins du score de propension.RésultatsDes 11 459 patients analysés, 2 174 (19 %) ont reçu des plaquettes réduites en leucocytes -1 408 ont eu 5 U, 471 ont eu 10 U, 140 ont eu 15 U et 155 ont eu 20 unités ou plus. Tous les taux ďévénements indésirables mesurés étaient plus élevés chez ceux qui avaient reçu des plaquettes, mais ni éanalyse de régression logistique ni éanalyse du score de propension n’ont montré ďassociation entre la transfusion de plaquettes et éun des événements indésirables.ConclusionEn cardiochirurgie, la transfusion de plaquettes réduites en leucocytes n’est pas associée à des complications cliniques quand ďimportants facteurs de confusion sont corrigés.Objectif nDeterminer la relation independante entre la transfusion de plaquettes reduites en leucocytes et les evenements indesirables en cardiochirurgie.

Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery

BACKGROUNDnThe surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may thereby prevent cardiac complications.nnnOBJECTIVESnThis review assessed the efficacy and safety of preoperative (within 24 hours), intraoperative, and postoperative (first 48 hours) alpha-2 adrenergic agonists for preventing mortality and cardiac complications after surgery performed under either general or neuraxial anaesthesia, or both.nnnSEARCH STRATEGYnWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August week 4 2008), EMBASE (1980 to week 36 2008), the Science Citation Index, and reference lists of articles.nnnSELECTION CRITERIAnWe included randomized controlled trials that compared alpha-2 adrenergic agonists (clonidine, dexmedetomidine, or mivazerol) against placebo or non-alpha-2 adrenergic agonists. Included studies had to report on mortality, myocardial infarction, myocardial ischaemia, or supraventricular tachyarrhythmia.nnnDATA COLLECTION AND ANALYSISnThree authors independently assessed trial quality and extracted data. Two authors independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials.nnnMAIN RESULTSnWe included 31 studies (4578 participants). Study quality was generally inadequate, with only six studies clearly reporting methods for blinding and allocation concealment. Overall, alpha-2 adrenergic agonists reduced mortality (relative risk (RR) 0.66; 95% CI 0.44 to 0.98; P = 0.04) and myocardial ischaemia (RR 0.68; 95% CI 0.57 to 0.81; P < 0.0001). However, their effects appeared to vary with the surgical procedure. The most encouraging data pertained to vascular surgery, where they reduced mortality (RR 0.47; 95% CI 0.25 to 0.90; P = 0.02), cardiac mortality (RR 0.36; 95% CI 0.16 to 0.79; P = 0.01), and myocardial infarction (RR 0.66; 95% CI 0.46 to 0.94; P = 0.02). With regard to adverse effects, alpha-2 adrenergic agonists significantly increased perioperative hypotension (RR 1.32; 95% CI 1.07 to 1.62; P = 0.009) and bradycardia (RR 1.66; 95% CI 1.14 to 2.41; P = 0.008).nnnAUTHORS CONCLUSIONSnOur study provides encouraging evidence that alpha-2 adrenergic agonists may reduce cardiac risk, especially during vascular surgery. Nonetheless, these data remain insufficient to make firm conclusions about their efficacy and safety. A large randomized trial of alpha-2 adrenergic agonists is therefore warranted. Additionally, future research must determine which specific alpha-2 adrenergic agonist should be used, and whether it is safe to combine them with other perioperative interventions (for example beta-adrenergic blockade).

Selective β1-antagonism with bisoprolol is associated with fewer postoperative strokes than atenolol or metoprolol: a single-center cohort study of 44,092 consecutive patients.

Background:Perioperative metoprolol increases postoperative stroke. Animal studies indicate that the mechanism may be related to attenuated &bgr;2-adrenoreceptor-mediated cerebral vasodilatation. The authors therefore conducted a cohort to study whether the highly &bgr;1-specific &bgr;-blocker (bisoprolol) was associated with a reduced risk of postoperative stroke compared with less selective &bgr;-blockers (metoprolol or atenolol). Methods:The authors conducted a single-center study on 44,092 consecutive patients with age 50 yr or more having noncardiac, nonneurologic surgery. The primary outcome was stroke within 7 days of surgery. The secondary outcome was a composite of all-cause mortality, postoperative myocardial injury, and stroke. A propensity score-matched cohort was created to assess the independent association between bisoprolol and less &bgr;1-selective agents metoprolol or atenolol. A secondary analysis using logistic regression, based on previously identified confounders, also compared selective &bgr;1-antagonism. Results:Twenty-four percent (10,756) of patients were exposed to in-hospital &bgr;-blockers. A total of 88 patients (0.2%) suffered a stroke within 7 days of surgery. The matched cohort consisted of 2,462 patients, and the pairs were well matched for all variables. Bisoprolol was associated with fewer postoperative strokes than the less selective agents (odds ratio = 0.20; 95% CI, 0.04–0.91). Multivariable risk-adjustment in the &bgr;-blockers-exposed patients comparing bisoprolol with the less selective agents was associated with a similarly reduced stroke rate. Conclusions:The use of metoprolol and atenolol is associated with increased risks of postoperative stroke, compared with bisoprolol. These findings warrant confirmation in a pragmatic randomized trial.

Association of echocardiography before major elective non-cardiac surgery with postoperative survival and length of hospital stay: population based cohort study

Objective To determine the association of resting echocardiography before elective intermediate to high risk non-cardiac surgery with survival and length of hospital stay. Design Population based retrospective cohort study. Setting Acute care hospitals in Ontario, Canada, between 1 April 1999 and 31 March 2008. Participants Patients aged over 40 years who had elective intermediate to high risk non-cardiac surgery. Intervention Resting echocardiography within 6 months before surgery. Main outcome measures Postoperative survival (30 days and 1 year) and length of hospital stay; postoperative surgical site infection as an outcome for which no association with echocardiography would be expected. Results Of the 264u2009823 patients in the entire cohort, 15.1% (n=40u2009084) had echocardiography. After use of propensity score methods to assemble a matched cohort (n=70u2009996) that reduced differences between patients who had or had not had echocardiography, echocardiography was associated with increases in 30 day mortality (relative risk 1.14, 95% confidence interval 1.02 to 1.27), 1 year mortality (1.07, 1.01 to 1.12), and length of hospital stay but no difference in surgical site infections (1.03, 0.98 to 1.06). The association with mortality was influenced (P=0.02) by whether patients had had stress testing or had risk factors for cardiac complications. No association existed between echocardiography and mortality among patients who had stress testing (relative risk 1.01, 0.92 to 1.11) or among patients at high risk who had not had stress testing (1.00, 0.87 to 1.13). However, echocardiography was associated with mortality in patients at low risk (relative risk 1.44, 1.14 to 1.82) and intermediate risk (1.10, 1.02 to 1.18) who had not had stress testing. Conclusions Preoperative echocardiography was not associated with improved survival or shorter hospital stay after major non-cardiac surgery. These findings highlight the need for further research to guide better use of this common preoperative test.

Determinants of complications with recombinant factor VIIa for refractory blood loss in cardiac surgery

PurposeRecombinant factor VIIa (rFVIIa) is being used for refractory, excessive blood loss (EBL) after cardiac surgery, but its safety for this indication is not known.MethodsThe unadjusted and risk-adjusted adverse event (AE) rates were compared between 114 consecutive cardiac surgical patients who received rFVIIa for refractory EBL and 541 concurrent patients who developed EBL but did not receive rFVIIa. Similarly, timing of rFVIIa therapy was assessed by dichotomizing rFVIIa patients based on median number of red blood cell (RBC) units received before therapy. The measured AE was a composite of death, stroke, renal failure, myocardial infarction, and major vein thrombosis. For risk adjustment, logistic regression models for this outcome were constructed using known predictors of AEs.ResultsThe median RBC units transfused before rFVIIa therapy was eight. The AE rates in the untreated, early (≤ 8 U), and late (> 8 U) treated patients were 24% (129/541), 30% (20/66), and 60% (29/48). The risk-adjustment model included total RBC units, pump time, weaning difficulty, gender, weight, and age. The unadjusted and adjusted AE odds ratios (OR) in the treatedvs untreated groups were 2.41 [confidence interval (CI) 1.58 -3.67;P < 0.0001 ] and 1.04 (CI 0.60 — 1.81 ;P = 0.9). In the rFVIIa group, the adjusted AE OR was lower in the early treated group (OR 0.41; CI 0.18 — 0.92;P = 0.03).ConclusionIn cardiac surgical patients with refractory hemorrhage, rFVIIa therapy is not associated with increased risk of AEs, and early treatment may be associated with better outcomes.RésuméObjectifLe facteur VIIa recombinant (rFVIIa) est utilisé pour traiter les pertes sanguines excessives (PSE) réfractaires après une opération cardiaque sans qu’on en connaisse l’innocuité.MéthodeLes taux d’événements indésirables (EI) non ajustés et ajustés en fonction des risques ont été comparés entre 114 patients consécutifs de cardiochirurgie ayant reçu le rFVIIa pour des PSE et 541 patients consécutifs qui ont eu des PSE mais pas de rFVIIa. De même, la programmation du traitement au rFVIIa a été étudiée par une division dichotomique des patients, recevant le rFVIIa, fondée sur le nombre médian d’unités de culots globulaires (CG) reçues avant le traitement. Les EI étaient la mort, l’accident vasculaire, l’insuffisance rénale, l’infarctus du myocarde et la thrombose veineuse majeure. Des modèles de régression logistique ont été construits pour ajuster le risque en utilisant les prédicteurs connus d’EI.RésultatsLa médiane des unités de CG transfusées avant le traitement au rFVIIa a été de huit. Les taux d’EI chez les patients non traités, traités tôt (≤ 8 U) et tard (> 8 U) ont été de 24 % (129/541), 30 % (20/66) et 60 % (29/48). Le modèle d’ajustement du risque comprenait le nombre total d’unités de CG, le temps de perfusion, les difficultés de sevrage, le sexe, le poids et l’âge. Les risques relatifs (RR) d’EI non ajustés et ajustés chez les patients traités vs non traités ont été de 2,41 [intervalle de confiance (IC) de 1,58 -3,67 ;P< 0,0001] et 1,04 (IC 0,60-1,81 ;P = 0,9). Dans le groupe rFVIIa, le RR d’EI ajusté a été plus bas chez les patients traités tôt (RR 0,41 ; IC 0,18 — 0,92 ; P = 0,03).ConclusionChez les patients de cardiochirurgie victimes d’hémorragie réfractaire, le traitement au rFVIIa n’est pas associé

Opioids Prescribed After Low-Risk Surgical Procedures in the United States, 2004-2012.

Adverse events related to opioid analgesics are common.1,2 Although opioids represent a component of pain treatment regimens following low-risk surgery,3,4 few data exist regarding patterns of postoperative opioid prescribing over time. We assessed trends in the amount of hydrocodone/acetaminophen and oxycodone/acetaminophen prescribed, 2 opioids commonly used for postoperative pain management.

Cardiac surgery-associated acute kidney injury

Acute kidney injury develops in up to 30% of patients who undergo cardiac surgery, with up to 3% of patients requiring dialysis. The requirement for dialysis after cardiac surgery is associated with an increased risk of infection, prolonged stay in critical care units and long-term need for dialysis. The development of acute kidney injury is independently associated with substantial short- and long-term morbidity and mortality. Its pathogenesis involves multiple pathways. Haemodynamic, inflammatory, metabolic and nephrotoxic factors are involved and overlap each other leading to kidney injury. Clinical studies have identified predictors for cardiac surgery-associated acute kidney injury that can be used effectively to determine the risk for acute kidney injury in patients undergoing cardiac surgery. High-risk patients can be targeted for renal protective strategies. Nonetheless, there is little compelling evidence from randomized trials supporting specific interventions to protect or prevent acute kidney injury in cardiac surgery patients. Several strategies have shown some promise, including less invasive procedures in those at greatest risk, natriuretic peptide, fenoldopam, preoperative hydration, preoperative optimization of anaemia and postoperative early use of renal replacement therapy. The efficacy of larger-scale trials remains to be confirmed.

La transfusion de plaquettes n’est pas associée à une hausse de la morbidité ou de la mortalité en cardiochirurgie

PurposeTo determine the independent relationship between leukoreduced platelet transfusions and adverse events in cardiac surgery.MethodsIn this observational study, detailed baseline and perioperative data were prospectively collected on consecutive patients who underwent cardiac surgery at a single institution from 1999 to 2004. The independent associations of platelet transfusion with clinical outcomes (low output syndrome, myocardial infarction, stroke, renal failure, sepsis, and death) were determined by multivariable logistic regression analysis and propensity score case-control analysis.ResultsOf the 11,459 patients analyzed, 2,174 (19%) received (leukoreduced) platelets -1,408 received 5 U, 471 received 10 U, 140 received 15 U, and 155 received 20 or more units. Although all measured adverse event rates were higher in those who received platelets, in neither the logistic regression analyses nor the propensity score analyses was there any association between platelet transfusion and any of the adverse events.ConclusionsTransfusion of leukoreduced platelets in cardiac surgery is not associated with adverse clinical outcomes when adjustments are made for important confounders.RésuméObjectifDéterminer la relation indépendante entre la transfusion de plaquettes réduites en leucocytes et les événements indésirables en cardiochirurgie.MéthodeDans une étude par observation, la cueillette prospective des données initiales et périopératoires détaillées a été faite pour des patients successivement opérés en cardiochirurgie dans un seul établissement entre 1999 et 2004. Les associations indépendantes entre transfusion plaquettaire et résultat clinique (syndrome de bas débit, infarctus du myocarde, accident vasculaire, insuffisance rénale, septicémie et mort) ont été déterminées par une analyse multivariée de régression logistique et une analyse cas-témoins du score de propension.RésultatsDes 11 459 patients analysés, 2 174 (19 %) ont reçu des plaquettes réduites en leucocytes -1 408 ont eu 5 U, 471 ont eu 10 U, 140 ont eu 15 U et 155 ont eu 20 unités ou plus. Tous les taux ďévénements indésirables mesurés étaient plus élevés chez ceux qui avaient reçu des plaquettes, mais ni éanalyse de régression logistique ni éanalyse du score de propension n’ont montré ďassociation entre la transfusion de plaquettes et éun des événements indésirables.ConclusionEn cardiochirurgie, la transfusion de plaquettes réduites en leucocytes n’est pas associée à des complications cliniques quand ďimportants facteurs de confusion sont corrigés.Objectif nDeterminer la relation independante entre la transfusion de plaquettes reduites en leucocytes et les evenements indesirables en cardiochirurgie.