Myocardial Injury After Noncardiac Surgery in Major General Surgical Patients a Prospective Observational Cohort Study.

OBJECTIVE: The objective of this study was to determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in major general surgery patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in major general surgical patients have not been described. METHODS: This was an international prospective cohort study of a representative sample of 22,552 noncardiac surgery patients 45 years or older, of whom 4490 underwent major general surgery in 24 centers in 13 countries. All patients had fifth-generation plasma high-sensitivity troponin T (hsTnT) concentrations measured during the first 3 postoperative days. MINS was defined as a hsTnT of 20-65 ng/L and absolute change >5 ng/L or hsTnT ≥65 ng/L secondary to ischemia. The objectives of the present study were to determine (1) whether MINS is prognostically important in major general surgical patients, (2) the clinical characteristics of major general surgical patients with and without MINS, (3) the 30-day outcomes for major general surgical patients with and without MINS, and (4) the proportion of MINS that would have gone undetected without routine postoperative monitoring. RESULTS: The incidence of MINS in the major general surgical patients was 16.3% (95% CI, 15.3-17.4%). Thirty-day all-cause mortality in the major general surgical cohort was 6.8% (95% CI, 5.1%-8.9%) in patients with MINS compared with 1.2% (95% CI, 0.9%-1.6%) in patients without MINS ( P <0.01). MINS was independently associated with 30-day mortality in major general surgical patients (adjusted odds ratio 4.7, 95% CI, 3.0-7.4). The 30-day mortality was higher both among MINS patients with no ischemic features (ie, no ischemic symptoms or electrocardiogram findings) (5.4%, 95% CI, 3.7%-7.7%) and among patients with 1 or more clinical ischemic features (10.6%, 95% CI, 6.7%-15.8%). The proportion of major general surgical patients who had MINS without ischemic symptoms was 89.9% (95% CI, 87.5-92.0). CONCLUSIONS: Approximately 1 in 6 patients experienced MINS after major general surgery. MINS was independently associated with a nearly 5-fold increase in 30-day mortality. The vast majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Perioperative ischaemic brain injury and plasma neurofilament light: a secondary analysis of two prospective cohort studies.

BACKGROUND: Ischaemic brain infarction can occur without acute neurological symptoms (covert strokes) or with symptoms (overt strokes), both associated with poor health outcomes. We conducted a pilot study of the incidence of preoperative and postoperative (intraoperative or postoperative) covert strokes, and explored the relationship of postoperative ischaemic brain injury to blood levels of neurofilament light, a biomarker of neuronal damage. METHODS: We analysed 101 preoperative (within 2 weeks of surgery) and 58 postoperative research MRIs on postoperative days 2-9 from two prospective cohorts collected at the University of Wisconsin (NCT01980511 and NCT03124303). Participants were aged >65 yr and undergoing non-intracranial, non-carotid surgery. RESULTS: Preoperative covert stroke was identified in 2/101 participants (2%; Bayesian 95% confidence interval [CI], 0.2-5.4). This rate was statistically different from the postoperative ischaemic brain injury rate of 7/58 (12%, 4.9-21.3%; P=0.01) based on postoperative imaging. However, in a smaller group of participants with paired imaging (n=30), we did not identify the same effect (P=0.67). Patients with postoperative brain injury had elevated peak neurofilament light levels (median [inter-quartile range], 2.34 [2.24-2.64] log10 pg ml-1) compared with those without (1.86 [1.48-2.21] log10 pg ml-1; P=0.025). Delirium severity scores were higher in those with postoperative brain injury (19 [17-21]) compared with those without (7 [4-12]; P=0.01). CONCLUSION: Although limited by a small sample size, these data suggest that preoperative covert stroke occurs more commonly than previously anticipated. Plasma neurofilament light is a potential screening biomarker for postoperative ischaemic brain injury.

Determinants of tobacco smoking abstinence one year after major noncardiac surgery: a secondary analysis of the VISION study.

BACKGROUND: Tobacco smoking is a leading preventable cause of death and increases perioperative risk. Determinants of smoking abstinence after noncardiac surgery and the association between smoking and 1-yr vascular outcomes are not fully elucidated. METHODS: We did a prospective cohort study of 40 004 patients, aged ≥45 yr, enrolled between August 2007 and November 2013, and followed for 1 yr after surgery. Patients were categorised as never smokers, ex-smokers (quit >4 weeks preoperatively), and current smokers (smoking ≤4 weeks preoperatively). Primary outcome was abstinence at 1 yr. Secondary outcome was a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 yr. RESULTS: Of 4658 current smokers, 1838 (39.5%) were abstinent 1 yr after surgery. Median (inter-quartile range) time to resumption was 7 (3-23) days post-surgery. Perioperatively, 7.2% of current smokers obtained smoking cessation pharmacotherapy. Older age (adjusted risk ratio [aRR] 1.21; 95% confidence interval [CI]: 1.12-1.32); having recent coronary artery disease (aRR 1.41; 95% CI: 1.29-1.55); cancer (aRR 1.37; 95% CI: 1.18-1.59); and undergoing major vascular (aRR 1.20; 95% CI: 1.02-1.41), urgent/emergent (aRR 1.14; 95% CI: 1.05-1.23), or thoracic (aRR 1.41; 95% CI: 1.26-1.56) surgeries increased abstinence. One-year abstinence was less likely when patients stopped smoking 0-1 day (aRR 0.53; 95% CI: 0.43-0.66) and 2-14 days (aRR 0.76; 95% CI: 0.71-0.82) before surgery compared with >14 days before surgery. Current smokers (adjusted hazard ratio [aHR] 1.14; 95% CI: 1.01-1.29) and ex-smokers (aHR 1.11; 95% CI: 1.03-1.21) had higher risk of the 1-yr vascular outcome compared with never smokers. CONCLUSIONS: Long-term tobacco abstinence is more likely after major surgery in those with serious medical comorbidities. Interventions to prevent smoking resumption after surgery remain a priority. Clinical trial registration NCT00512109.

Sex differences in outcomes after coronary artery bypass grafting: a pooled analysis of individual patient data.

AIMS: Data suggest that women have worse outcomes than men after coronary artery bypass grafting (CABG), but results have been inconsistent across studies. Due to the large differences in baseline characteristics between sexes, suboptimal risk adjustment due to low-quality data may be the reason for the observed differences. To overcome this limitation, we undertook a systematic review and pooled analysis of high-quality individual patient data from large CABG trials to compare the adjusted outcomes of women and men. METHODS AND RESULTS: The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events, MACCE). The secondary outcome was all-cause mortality. Multivariable mixed-effect Cox regression was used. Four trials involving 13 193 patients (10 479 males; 2714 females) were included. Over 5 years of follow-up, women had a significantly higher risk of MACCE [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.21; P = 0.004] but similar mortality (adjusted HR 1.03, 95% CI 0.94-1.14; P = 0.51) compared to men. Women had higher incidence of MI (adjusted HR 1.30, 95% CI 1.11-1.52) and repeat revascularization (adjusted HR 1.22, 95% CI 1.04-1.43) but not stroke (adjusted HR 1.17, 95% CI 0.90-1.52). The difference in MACCE between sexes was not significant in patients 75 years and older. The use of off-pump surgery and multiple arterial grafting did not modify the difference between sexes. CONCLUSIONS: Women have worse outcomes than men in the first 5 years after CABG. This difference is not significant in patients aged over 75 years and is not affected by the surgical technique.

Association between postoperative haemoglobin concentrations and composite of non-fatal myocardial infarction and all-cause mortality in noncardiac surgical patients: post hoc analysis of the POISE-2 trial.

BACKGROUND: Myocardial infarction is the most common postoperative major vascular complication. Perioperative anaemia may contribute to cardiac supply-demand mismatch, and therefore myocardial injury. We therefore tested the hypothesis that the lowest in-hospital postoperative haemoglobin concentration is associated with a composite of non-fatal myocardial infarction and all-cause mortality within the first 30 days after noncardiac surgery. METHODS: We conducted a retrospective analysis of patients enrolled in the PeriOperative Ischemic Evaluation-2 (POISE-2) trial. We assessed the association between the lowest postoperative haemoglobin concentration during the initial hospitalisation and a composite of non-fatal myocardial infarction (Third Universal Definition) and all-cause mortality within 30 postoperative days, using a multivariable logistic regression model. RESULTS: We analysed 7227 patients from POISE-2, of whom 7.8% developed myocardial infarction; 1.5% died within 30 days. The composite primary outcome of non-fatal myocardial infarction and all-cause mortality occurred in 8.9% patients overall, ranging from 16% in patients with postoperative haemoglobin concentrations <88 g L-1 to 4.1% in patients with postoperative haemoglobin >113 g L-1. After adjusting for baseline factors, in patients with a lowest postoperative haemoglobin concentration <110 g L-1, each 10 g L-1 reduction in the lowest postoperative haemoglobin concentration was associated with a 1.46 (95% confidence interval: 1.37-1.56; P<0.001) fold increase in the odds of the composite outcome. In contrast, there was no significant relationship amongst patients with lowest postoperative haemoglobin concentration >110 g L-1. CONCLUSIONS: Postoperative anaemia may be a modifiable risk factor for non-fatal myocardial infarction and all-cause mortality.

Association between postoperative haemoglobin and myocardial injury after noncardiac surgery: a retrospective cohort analysis.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common, mostly silent, and a strong predictor of postoperative mortality. MINS appears to result from myocardial supply-demand mismatch. Recent data support restrictive perioperative transfusion strategies that can result in low postoperative haemoglobin concentrations. Whether low postoperative haemoglobin is associated with myocardial injury remains unknown. We therefore tested the hypothesis that anaemia is associated with an increased risk of myocardial injury in adults having noncardiac surgery. METHODS: We conducted a retrospective analysis of adults ≥45 yr old who had routine postoperative troponin T (TnT) monitoring after noncardiac surgery at the Cleverland Clinic (including those enrolled in the PeriOperative ISchemic Evaluation-2 Trial [POISE-2], the Safety of Addition of Nitrous Oxide to General Anaesthesia in At-risk Patients Having Major Non-cardiac Surgery [ENIGMA-II], Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study [VISION], and Anaesthetic Depth and Complications After Major Surgery [BALANCED] trial). Patients with baseline increase in TnT and non-ischaemic aetiologies for TnT increase were excluded. The association between postoperative haemoglobin concentration during the 3 initial postoperative days and the incidence of MINS (fourth-generation TnT ≥0.03 ng ml-1 judged as attributable to ischaemia) was assessed using a time-varying covariate Cox proportional hazards survival analysis. RESULTS: Among 6141 patients, 4480 were analysed. The incidence of MINS was 155/4480 (3.5%), ranging from 0/345 (0%) among patients whose lowest postoperative haemoglobin exceeded 13 g dl-1 to 52/611 (8.5%) in patients whose minimum postoperative haemoglobin was <8 g dl-1. The confounder-adjusted hazard ratio [95% confidence interval] for having MINS was 1.29 [1.16-1.42] for every 1 g dl-1 decrease in postoperative haemoglobin in a time-varying covariate analysis. Similar associations were identified in sensitivity analyses. CONCLUSION: Lower postoperative haemoglobin values are associated with MINS. Whether this association is modifiable by prevention or treatment of anaemia remains to be determined.

Preoperative prediction of Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study.

BACKGROUND: Diagnostic criteria for Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS) have been defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or is judged to be the direct cause of death. Preoperative prediction guides for BIMS can facilitate informed consent and planning of perioperative care. METHODS: In a prospective cohort study of 16 079 participants aged ≥45 yr having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011, 17.3% (2782) experienced BIMS. An electronic risk calculator for BIMS was developed and internally validated by logistic regression with bootstrapping, and further simplified to a risk index. Decision curve analysis assessed the potential utility of each prediction guide compared with a strategy of identifying risk of BIMS based on preoperative haemoglobin <120 g L-1. RESULTS: With information about the type of surgery, preoperative haemoglobin, age, sex, functional status, kidney function, history of high-risk coronary artery disease, and active cancer, the risk calculator accurately predicted BIMS (bias-corrected C-statistic, 0.84; 95% confidence interval, 0.837-0.852). A simplified index based on preoperative haemoglobin <120 g L-1, open surgery, and high-risk surgery also predicted BIMS, but less accurately (C-statistic, 0.787; 95% confidence interval, 0.779-0.796). Both prediction guides could improve decision making compared with knowledge of haemoglobin <120 g L-1 alone. CONCLUSIONS: BIMS, defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or that is judged to be the direct cause of death, can be predicted by a simple risk index before surgery. CLINICAL TRIAL REGISTRATION: NCT00512109.

Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study establishing diagnostic criteria and prognostic importance.

BACKGROUND: We aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. METHODS: This was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. RESULTS: Of 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin <70 g L-1, transfusion of ≥1 unit of red blood cells, or that was judged to be the cause of death. Bleeding independently associated with mortality after noncardiac surgery occurred in 17.3% of patients (2782). Death occurred in 5.8% of patients with BIMS (161/2782), 1.3% (39/3028) who met bleeding screening criteria but not BIMS criteria, and 1.1% (115/10 269) without bleeding. BIMS was associated with mortality (adjusted hazard ratio: 1.87; 95% confidence interval: 1.42-2.47). We estimated the proportion of 30-day postoperative deaths potentially attributable to BIMS to be 20.1-31.9%. CONCLUSIONS: Bleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, blood transfusion, or that is judged to be the cause of death, is common and may account for a quarter of deaths after noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT00512109.

Prospective observational study of postoperative infection and outcomes after noncardiac surgery: analysis of prospective data from the VISION cohort.

BACKGROUND: Infection is a frequent cause of postoperative morbidity and mortality. The incidence, risk factors, and outcomes for postoperative infections remain poorly characterised. METHODS: This is a secondary analysis of a prospective international cohort study of patients aged ≥45 yr who had noncardiac surgery (VISION), including data describing infection within 30 days after surgery. The primary outcome was postoperative infection. The secondary outcome was 30 day mortality. We used univariable and multivariable logistic regression to identify baseline risk factors for infection. Results are presented as n (%) or odds ratio (OR) with 95% confidence intervals. Some denominators vary according to rates of missing data. RESULTS: Among 39 996 surgical patients, 3905 (9.8%) experienced 5152 postoperative infections and 715 (1.8%) died. The most frequent infection was surgical site infection (1555/3905 [39.8%]). Infection was most strongly associated with general surgery (OR: 3.74 [3.11-4.49]; P<0.01) and open surgical technique (OR: 2.03 [1.82-2.27]; P<0.01); 30 day mortality was greater amongst patients who experienced infection (262/3905 [6.7%] vs 453/36 091 patients who did not [1.3%]; OR: 3.47 [2.84-4.22]; P<0.01). Mortality was highest amongst patients with CNS infections (OR: 14.72 [4.41-49.12]; P<0.01). CONCLUSIONS: Infection is a common and important complication of noncardiac surgery, which is associated with high mortality. Further research is needed to identify more effective measures to prevent infections after surgery.

A Prospective International Multicentre Cohort Study of Intraoperative Heart Rate and Systolic Blood Pressure and Myocardial Injury After Noncardiac Surgery: Results of the VISION Study.

BACKGROUND: The association between intraoperative cardiovascular changes and perioperative myocardial injury has chiefly focused on hypotension during noncardiac surgery. However, the relative influence of blood pressure and heart rate (HR) remains unclear. We investigated both individual and codependent relationships among intraoperative HR, systolic blood pressure (SBP), and myocardial injury after noncardiac surgery (MINS). METHODS: Secondary analysis of the Vascular Events in Noncardiac Surgery Cohort Evaluation (VISION) study, a prospective international cohort study of noncardiac surgical patients. Multivariable logistic regression analysis tested for associations between intraoperative HR and/or SBP and MINS, defined by an elevated serum troponin T adjudicated as due to an ischemic etiology, within 30 days after surgery. Predefined thresholds for intraoperative HR and SBP were: maximum HR >100 beats or minimum HR <55 beats per minute (bpm); maximum SBP >160 mm Hg or minimum SBP <100 mm Hg. Secondary outcomes were myocardial infarction and mortality within 30 days after surgery. RESULTS: After excluding missing data, 1197 of 15,109 patients (7.9%) sustained MINS, 454 of 16,031 (2.8%) sustained myocardial infarction, and 315 of 16,061 patients (2.0%) died within 30 days after surgery. Maximum intraoperative HR >100 bpm was associated with MINS (odds ratio [OR], 1.27 [1.07-1.50]; P < .01), myocardial infarction (OR, 1.34 [1.05-1.70]; P = .02), and mortality (OR, 2.65 [2.06-3.41]; P < .01). Minimum SBP <100 mm Hg was associated with MINS (OR, 1.21 [1.05-1.39]; P = .01) and mortality (OR, 1.81 [1.39-2.37]; P < .01), but not myocardial infarction (OR, 1.21 [0.98-1.49]; P = .07). Maximum SBP >160 mm Hg was associated with MINS (OR, 1.16 [1.01-1.34]; P = .04) and myocardial infarction (OR, 1.34 [1.09-1.64]; P = .01) but, paradoxically, reduced mortality (OR, 0.76 [0.58-0.99]; P = .04). Minimum HR <55 bpm was associated with reduced MINS (OR, 0.70 [0.59-0.82]; P < .01), myocardial infarction (OR, 0.75 [0.58-0.97]; P = .03), and mortality (OR, 0.58 [0.41-0.81]; P < .01). Minimum SBP <100 mm Hg with maximum HR >100 bpm was more strongly associated with MINS (OR, 1.42 [1.15-1.76]; P < .01) compared with minimum SBP <100 mm Hg alone (OR, 1.20 [1.03-1.40]; P = .02). CONCLUSIONS: Intraoperative tachycardia and hypotension are associated with MINS. Further interventional research targeting HR/blood pressure is needed to define the optimum strategy to reduce MINS.

Age Does Not Affect Metoprolol's Effect on Perioperative Outcomes (From the POISE Database).

BACKGROUND: Perioperative ß-blockade reduces the incidence of myocardial infarction but increases that of death, stroke, and hypotension. The elderly may experience few benefits but more harms associated with ß-blockade due to a normal effect of aging, that of a reduced resting heart rate. The tested hypothesis was that the effect of perioperative ß-blockade is more significant with increasing age. METHODS: To determine whether the effect of perioperative ß-blockade on the primary composite event, clinically significant hypotension, myocardial infarction, stroke, and death varies with age, we interrogated data from the perioperative ischemia evaluation (POISE) study. The POISE study randomly assigned 8351 patients, aged ≥45 years, in 23 countries, undergoing major noncardiac surgery to either 200 mg metoprolol CR daily or placebo for 30 days. Odds ratios or hazard ratios for time to events, when available, for each of the adverse effects were measured according to decile of age, and interaction term between age and treatment was calculated. No adjustment was made for multiple outcomes. RESULTS: Age was associated with higher incidences of the major outcomes of clinically significant hypotension, myocardial infarction, and death. Age was associated with a minimal reduction in resting heart rate from 84.2 (standard error, 0.63; ages 45-54 years) to 80.9 (standard error, 0.70; ages >85 years; P < .0001). We found no evidence of any interaction between age and study group regarding any of the major outcomes, although the limited sample size does not exclude any but large interactions. CONCLUSIONS: The effect of perioperative ß-blockade on the major outcomes studied did not vary with age. Resting heart rate decreases slightly with age. Our data do not support a recommendation for the use of perioperative ß-blockade in any age subgroup to achieve benefits but avoid harms. Therefore, current recommendations against the use of ß-blockers in high-risk patients undergoing noncardiac surgery apply across all age groups.

Troponin T monitoring to detect myocardial injury after noncardiac surgery: a cost-consequence analysis.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is a mostly asymptomatic condition that is strongly associated with 30-day mortality; however, it remains mostly undetected without systematic troponin T monitoring. We evaluated the cost and consequences of postoperative troponin T monitoring to detect MINS. METHODS: We conducted a model-based cost-consequence analysis to compare the impact of routine troponin T monitoring versus standard care (troponin T measurement triggered by ischemic symptoms) on the incidence of MINS detection. Model inputs were based on Canadian patients enrolled in the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study, which enrolled patients aged 45 years or older undergoing inpatient noncardiac surgery. We conducted probability analyses with 10 000 iterations and extensive sensitivity analyses. RESULTS: The data were based on 6021 patients (48% men, mean age 65 [standard deviation 12] yr). The 30-day mortality rate for MINS was 9.6%. We determined the incremental cost to avoid missing a MINS event as $1632 (2015 Canadian dollars). The cost-effectiveness of troponin monitoring was higher in patient subgroups at higher risk for MINS, e.g., those aged 65 years or more, or with a history of atherosclerosis or diabetes ($1309). CONCLUSION: The costs associated with a troponin T monitoring program to detect MINS were moderate. Based on the estimated incremental cost per health gain, implementation of postoperative troponin T monitoring seems appealing, particularly in patients at high risk for MINS.

CONTEXTE: Les lésions myocardiques après chirurgie non cardiaque (CNC) sont majoritairement asymptomatiques et fortement associées au risque de mortalité dans les 30 jours; toutefois, dans la plupart des cas, elles ne sont pas détectées en l'absence d'une surveillance systématique de la troponine T. Nous avons évalué les coûts et les conséquences d'une telle surveillance pour détecter les lésions myocardiques après CNC. MÉTHODES: Nous avons mené une analyse coût-conséquence modélisée pour comparer la surveillance systématique de la troponine T aux soins habituels seuls (mesure de la troponine T seulement s'il y a présence de symptômes d'ischémie) sur la fréquence de détection de lésions myocardiques après CNC. Les données ayant servi à l'analyse provenaient des patients canadiens ayant participé à l'étude de cohorte VISION, qui visait à évaluer les complications vasculaires chez les patients de 45 ans et plus ayant subi une CNC. Nous avons mené des analyses de probabilité avec 10  000 itérations et des analyses de sensibilité approfondies. RÉSULTATS: Les données portaient sur 6021 patients (48 % du sexe masculin; âge moyen de 65 ans [écart-type de 12 ans]). Le taux de mortalité dans les 30 jours associé à une lésion myocardique après CNC était de 9,6 %. Nous avons déterminé que le coût marginal de la détection de la présence d'une lésion par surveillance de la troponine T était de 1632 $ (dollars canadiens en 2015). Le rapport coût-efficacité était plus bas pour les sous-groupes de patients à risque élevé de lésion myocardique après CNC, comme les patients de 65 ans et plus ou ceux ayant des antécédents d'athérosclérose ou de diabète (1309 $), que pour leurs pairs. CONCLUSION: Les coûts associés à un programme de surveillance de la troponine T pour détecter les lésions myocardiques après CNC étaient modérés. Le coût marginal estimé par gain de santé indique que la mise en œuvre de ce type de programme pourrait être une option intéressante, surtout pour les patients à risque élevé de lésion myocardique après CNC.

Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Chronic Low Back Pain (CLBP) is very common, with a lifetime prevalence between 51% and 80%. In majority, it is nonspecific in nature and multifactorial in etiology. Pregabalin (PG) and Gabapentin (GB) are gabapentinoids that have demonstrated benefit in neuropathic pain conditions. Despite no clear rationale, they are increasingly used for nonspecific CLBP. They necessitate prolonged use and are associated with adverse effects and increased cost. Recent guidelines from the National Health Service (NHS), England, expressed concerns on their off-label use, in addition to the risk of misuse. We aimed to assess the effectiveness and safety of gabapentinoids in adult CLBP patients. METHODS: Electronic databases of MEDLINE, EMBASE, and Cochrane were searched from their inception until December 20th, 2016. We included randomized control trials reporting the use of gabapentinoids for the treatment of CLBP of >3 months duration, in adult patients. Study selection and data extraction was performed independently by paired reviewers. Outcomes were guided by Initiative on Methods, Measurement and Pain Assessment in Clinical Trials guidelines, with pain relief and safety as the primary outcomes. Meta-analyses were performed for outcomes reported in 3 or more studies. Outcomes were reported as mean differences (MDs) or risk ratios (RRs) with their corresponding 95% confidence intervals (CIs), and I2 in percentage representing the percentage variability in effect estimates that could be explained by heterogeneity. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of evidence. RESULTS: Out of 1,385 citations, eight studies were included. Based on the interventions and comparators, studies were analyzed in 3 different groups. GB compared with placebo (3 studies, n = 185) showed minimal improvement of pain (MD = 0.22 units, 95% CI [-0.5 to 0.07] I2 = 0%; GRADE: very low). Three studies compared PG with other types of analgesic medication (n = 332) and showed greater improvement in the other analgesic group (MD = 0.42 units, 95% CI [0.20 to 0.64] I2 = 0; GRADE: very low). Studies using PG as an adjuvant (n = 423) were not pooled due to heterogeneity, but the largest of them showed no benefit of adding PG to tapentadol. There were no deaths or hospitalizations reported. Compared with placebo, the following adverse events were more commonly reported with GB: dizziness-(RR = 1.99, 95% CI [1.17 to 3.37], I2 = 49); fatigue (RR = 1.85, 95% CI [1.12 to 3.05], I2 = 0); difficulties with mentation (RR = 3.34, 95% CI [1.54 to 7.25], I2 = 0); and visual disturbances (RR = 5.72, 95% CI [1.94 to 16.91], I2 = 0). The number needed to harm with 95% CI for dizziness, fatigue, difficulties with mentation, and visual disturbances were 7 (4 to 30), 8 (4 to 44), 6 (4 to 15), and 6 (4 to 13) respectively. The GRADE evidence quality was noted to be very low for dizziness and fatigue, low for difficulties with mentation, and moderate for visual disturbances. Functional and emotional improvements were reported by few studies and showed no significant improvements. CONCLUSIONS AND RELEVANCE: Existing evidence on the use of gabapentinoids in CLBP is limited and demonstrates significant risk of adverse effects without any demonstrated benefit. Given the lack of efficacy, risks, and costs associated, the use of gabapentinoids for CLBP merits caution. There is need for large high-quality trials to more definitively inform this issue. TRIAL REGISTRATION: PROSPERO CRD42016034040.

Atorvastatin for high-risk statin-naïve patients undergoing noncardiac surgery: The Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD) randomized trial.

Preliminary evidence suggests that statins may prevent major perioperative vascular complications. METHODS: We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80 mg anytime within 18hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12hours after the surgery, and then 40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30days. RESULTS: The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group (hazard ratio [HR] 0.87, 95% CI 0.60-1.26, P=.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53-2.47, P=.74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P=.50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, P=.26), and stroke (0.9% vs 0%, P=.25). CONCLUSION: In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high-risk statin-naïve patients is feasible and should be done to definitely establish the efficacy and safety of statin in this patient population.

Comparison of the ability of double-robust estimators to correct bias in propensity score matching analysis. A Monte Carlo simulation study.

OBJECTIVE: As covariates are not always adequately balanced after propensity score matching and double- adjustment can be used to remove residual confounding, we compared the performance of several double-robust estimators in different scenarios. METHODS: We conducted a series of Monte Carlo simulations on virtual observational studies. After estimating the propensity scores by logistic regression, we performed 1:1 optimal, nearest-neighbor, and caliper matching. We used 4 estimators on each matched sample: (1) a crude estimator without double-adjustment, (2) double-adjustment for the propensity scores, (3) double-adjustment for the unweighted unbalanced covariates, and (4) double-adjustment for the unbalanced covariates, weighted by their strength of association with the outcome. RESULTS: The crude estimator led to highest bias in all tested scenarios. Double-adjustment for the propensity scores effectively removed confounding only when the propensity score models were correctly specified. Double-adjustment for the unbalanced covariates was more robust to misspecification. Double-adjustment for the weighted unbalanced covariates outperformed the other approaches in every scenario and using any matching algorithm, as measured by the mean squared error. CONCLUSION: Double-adjustment can be used to remove residual confounding after propensity score matching. The unbalanced covariates with the strongest confounding effects should be adjusted.

Undiagnosed Obstructive Sleep Apnea and Postoperative Outcomes: A Prospective Observational Study.

BACKGROUND: The prevalence of undiagnosed obstructive sleep apnea (OSA) during preoperative evaluation and the best method to screen OSA and its association with postoperative complications remain unclear. OBJECTIVES: To determine the prevalence of undiagnosed OSA in preoperative Indian patients undergoing noncardiac surgery, to compare the diagnostic accuracy of the STOP-BANG questionnaire to a preoperative level III sleep study, and to assess the association of OSA with postoperative complications. METHODS: A prospective cohort of 245 consecutive adults with ≥2 risk factors for OSA who underwent noncardiac surgery between July 2011 and February 2013 were studied. The STOP-BANG questionnaire was administered to all patients, and 182/245 (74.2%) patients underwent a preoperative level III sleep study. Patients were followed for postoperative complications in hospital and contacted at 30 days after surgery. RESULTS: 70/182 (38.5%) obtained a new diagnosis of OSA, including 11/182 (6%) with moderate to severe OSA (apnea-hypopnea index ≥15/h). On logistic regression analyses, the presence of OSA was independently associated with postoperative oxygen desaturation (OR 5.96, 95% CI 2.35-15.1, p < 0.01), a postoperative complication within 7 days (OR 3.63, 95% CI 1.77-7.45, p < 0.01) and within 30 days (OR 3.5, 95% CI 1.74-7.1, p < 0.01). The STOP-BANG questionnaire did not identify 12/70 (17%) of the patients diagnosed with OSA and classified 28% of the cohort as OSA when the level III sleep study was negative. CONCLUSIONS: Unrecognized OSA is common in preoperative patients and is independently associated with postoperative complications. The STOP-BANG questionnaire had a lower performance in the diagnosis of OSA in a South Indian population than the level III sleep study.

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery.

Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n = 960). AKI was defined as a ≥ 50% or ≥ 0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P = 0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.

Methylprednisolone Does Not Reduce Persistent Pain after Cardiac Surgery.

BACKGROUND: Persistent incisional pain is common after cardiac surgery and is believed to be in part related to inflammation and poorly controlled acute pain. Methylprednisolone is a corticosteroid with substantial antiinflammatory and analgesic properties and is thus likely to ameliorate persistent surgical pain. Therefore, the authors tested the primary hypothesis that patients randomized to methylprednisolone have less persistent incisional pain than those given placebo. METHODS: One thousand forty-three patients having cardiopulmonary bypass for cardiac surgery via a median sternotomy were included in this substudy of Steroids in Cardiac Surgery (SIRS) trial. Patients were randomized to 500 mg intraoperative methylprednisolone or placebo. Incisional pain was assessed at 30 days and 6 months after surgery, and the potential risk factors were also evaluated. RESULTS: Methylprednisolone administration did not reduce pain at 30 days or persistent incisional pain at 6 months, which occurred in 78 of 520 patients (15.7%) in the methylprednisolone group and in 88 of 523 patients (17.8%) in the placebo group. The odds ratio for methylprednisolone was 0.93 (95% CI, 0.79 to 1.09, P = 0.37). Furthermore, there was no difference in worst pain and average pain in the last 24 h, pain interference with daily life, or use of pain medicine at 6 months. Younger age, female sex, and surgical infections were associated with the development of persistent incisional pain. CONCLUSIONS: Intraoperative methylprednisolone administration does not reduce persistent incisional pain at 6 months in patients recovering from cardiac surgery.

Values and preferences for oral antithrombotic therapy in patients with atrial fibrillation: physician and patient perspectives.

BACKGROUND: Exploration of values and preferences in the context of anticoagulation therapy for atrial fibrillation (AF) remains limited. To better characterize the distribution of patient and physician values and preferences relevant to decisions regarding anticoagulation in patients with AF, we conducted interviews with patients at risk of developing AF and physicians who manage patients with AF. METHODS: We interviewed 96 outpatients and 96 physicians in a multicenter study and elicited the maximal increased risk of bleeding (threshold risk) that respondents would tolerate with warfarin vs. aspirin to achieve a reduction in three strokes in 100 patients over a 2-year period. We used the probabilistic version of the threshold technique. RESULTS: The median threshold risk for both patients and physicians was 10 additional bleeds (10 P = 0.7). In both groups, we observed large variability in the threshold number of bleeds, with wider variability in patients than clinicians [patient range: 0-100, physician range: 0-50]. We observed one cluster of patients and physicians who would tolerate <10 bleeds and another cluster of patients, but not physicians, who would accept more than 35. CONCLUSIONS: Our findings suggest wide variability in patient and physician values and preferences regarding the trade-off between strokes and bleeds. Results suggest that in individual decision making, physician and patient values and preferences will often be discordant; this mandates tailoring treatment to the individual patient's preferences.