Original Article
A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality

https://doi.org/10.1053/j.jvca.2019.03.022Get rights and content

Objective

Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings.

Design

A systematic review of the literature followed by a consensus-based voting process.

Setting

A web-based international consensus conference.

Participants

Two hundred fifty-one physicians from 46 countries.

Interventions

The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines.

Measurements and Main Results

The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed.

Conclusion

The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

Section snippets

Methods

MEDLINE/PubMed, Scopus, and Embase were searched by 6 investigators to identify all RCTs concerning every kind of nonsurgical interventions influencing mortality in critically ill and perioperative patients, without publication time limits. The full MEDLINE/PubMed search strategy is available in the Supplemental Materials. These pieces of information also are reported in the mirror analysis on the intervention reducing mortality.15

Selected articles had to satisfy all the following criteria: (1)

Results

The authors report, for the first time, a list of all the RCTs ever performed in critically ill and perioperative settings showing a statistically significant increase in mortality. The complete list of the 262 identified manuscripts with mortality difference and the whole process of selection are reported in Supplemental Materials. The flowchart of the consensus process is summarized in Fig 1.

The journals that more frequently published the 15 ultimately selected manuscripts were the New

Key Findings

All nonsurgical interventions (drugs, techniques, strategies) that have been shown by at least 1 RCT to significantly affect unadjusted landmark mortality in critically ill adult patients, as well as in the perioperative period of any adult surgery, were identified systematically. Moreover, the authors assessed how these interventions were regarded by 251 clinicians (mostly anesthesiologists and/or intensivists) from around the world and the extent to which their opinions translate into

Conclusion

The updated international democracy-based, web-enabled consensus process identified 12 nonsurgical interventions (drugs, techniques, strategies) increasing mortality in critically ill or surgical patients according to at least 1 RCT and the results of a web-based survey involving 251 clinicians from 46 countries. Data on self-reported clinical practice about these interventions also were obtained. These findings may be useful to guide clinical practice and to direct future research.

The authors

Conflicts of Interest

There are no conflicts of interest for any of the authors.

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