Publications of the Week, June 12


Risk of acute myocardial infarction with NSAIDs

Bally M, Dendukuri N, Rich B, et al. Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ. 2017 May 9;357:j1909. doi: 10.1136/bmj.j1909. Review. PubMed PMID: 28487435; PubMed Central PMCID: PMC5423546.

Short-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of myocardial infarction (MI) without major differences between individual drugs.

This study combined observations from several databases examining the effects of NSAID use on MI risk. It concluded that the current use of all examined NSAIDs was associated with an increased risk of MI. In comparison with other drugs, the authors did not report different effects of naproxen and celecoxib. The increased risk was present and high already during the first week of use and was greatest in the first month. Higher doses were found to further increase the risk. The probability that any dose of celecoxib, diclofenac, ibuprofen, or naproxen increased the risk of MI during the first week of its use was over 95% for each drug; the probability that odds of having MI were increased 1.5-fold in comparison to not using the agents was about 12% for celecoxib and over 40% for other drugs. The longer-term use was still associated with an increased risk (especially for diclofenac and ibuprofen in maximum doses) but its magnitude was smaller than in the first month, indicating that the excess risk was concentrated in the initial period of drug use.

Impact of delay in treatment of sepsis – prompt administration of antibiotics matters!

Seymour CW, Gesten F, Prescott HC, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med. 2017 Jun 8;376(23):2235-2244. doi: 10.1056/NEJMoa1703058. Epub 2017 May 21. PubMed PMID: 28528569.

In this observational study, delaying implementation of sepsis-management interventions, especially the administration of broad-spectrum antibiotics, even by an hour was associated with increased mortality.

It is assumed as proven that major delays in recognizing and treating sepsis are associated with worse outcomes. In New York State, all hospitals are required to implement sepsis management protocols and monitor protocol adherence. Using data from the New York State Department of Health, this observational study was designed to quantify the magnitude of the time effect and included only patients in whom a sepsis protocol was initiated within 6 hours of arrival in the emergency department and who had the basic interventions completed by 12 hours (those included the “bundle” of obtaining blood cultures, administering broad-spectrum antibiotics, and measuring the lactate level). A separate analysis was directed at the time to completion of a 30 mL/kg fluid bolus in patients with hypotension and elevated lactate levels (≥4 mmol/L).

Among close to 50 000 of observed patients, the initial bundle was completed within 3 hours of activation of a sepsis protocol in 83% of patients, with the median time of obtaining blood cultures, measuring lactate levels, and delivering broad-spectrum antibiotics of 1.3 hours (!). The median time of antibiotic(s) delivery was 0.95 hours, with 75% of patients receiving antibiotic(s) within 2 hours. In this very rapidly treated group, each hour of delay in antibiotic delivery was associated with an increased risk of dying (odds ratio, 1.04 per hour; 95% confidence interval, 1.03 to 1.06). Rapid delivery of the fluid bolus (median time, 2.6 hours) was not demonstrated to have a significant effect.

Postoperative high-sensitivity troponin, myocardial injury, and mortality rates

Writing Committee for the VISION Study Investigators, Devereaux PJ, Biccard BM, Sigamani A, et al. Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery. JAMA. 2017 Apr 25;317(16):1642-1651. doi: 10.1001/jama.2017.4360. PubMed PMID: 28444280.

Elevated levels of high-sensitivity troponin T (hsTNT) are associated with a high risk of 30-day mortality following noncardiac surgery.

In this observational study, over 20 000 patients undergoing noncardiac surgery had hsTNT measured within 6 to 12 hours after surgery and then daily for 3 days. The assay manufacturer considered a level of 14 ng/L or higher as abnormal.

Within 30 days of surgery, 1.2% (266 out of 21 842) patients died. Mortality among over 5000 patients with the peak hsTNT level <5 ng/L was 0.1% (the reference group). Mortality in the group of patients with levels ranging from 5 through 13 ng/L (still within what is considered the reference range) was 0.5% (hazard ratio [HR], 3.7) and among those with minimally elevated levels, from 14 to 20 ng/L, was 1.1% (HR, 9.1). A further increase in the marker level was associated with an additional dramatic rise in the 30-day observed mortality rate, which for levels 20 to 65 ng/L was 3% (HR, 23.7); from 65 to 1000 ng/L, 9.1% (HR, 70); and for levels equal to or over 1000 ng/L, 29.6% (HR, 227).

Some patients had hsTNT levels measured before and after operation. The absolute increase in hsTNT levels between preoperative and peak postoperative levels was also associated with increased observed mortality: for a level difference <5 ng/L, the mortality rate was 0.4%; for an increase from 5 to 40 ng/L, it was 1.5%; and for a level difference equal to or over 40 ng/L, it was 9.7%.

The majority of patients with myocardial injury after noncardiac surgery have not experienced any ischemic symptoms. This publication has not considered any potential useful management strategies that could be applied in those patients.

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