• 1 Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • 2 E. Meshalkin National Medical Research Center, Novosibirsk, Russia
  • 3 Division of Cardiac Anesthesia and Intensive Care Unit, AORN dei Colli - Monaldi Hospital, Naples, Italy
  • 4 Institute for Clinical and Experimental Medicine, Prague, Czech Republic
  • 5 Hospital Universitari de Bellvitge, Barcelona, Spain
  • 6 Instituto do Coracao do Hospital das Clinicas, Sao Paulo, Brazil
  • 7 Department of Anesthesiology and Intensive Care, Sechenov First Moscow State Medical University, and Moscow Regional Clinical and Research Institute, Moscow, Russian Federation
  • 8 Department of Cardiovascular Anesthesiology and Cardiac Intensive Medicine, University Hospital Dubrava, Zagreb, Croatia
  • 9 San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy
  • 10 Anaesthesia and Intensive Care, University of Malaya, Kuala Lumpur, Malaysia
  • 11 Saint Petersburg State University, Saint Petersburg, Russia
  • 12 Anaesthesia and Intensive Care, San Carlo Hospital, Potenza, Italy
  • 13 Institute of Cardiovascular Diseases "Dedinje", Belgrade, Serbia
  • 14 AOU Mater Domini Germaneto, Catanzaro, Italy
  • 15 Department of Anaesthesia and Intensive Care, Ospedale Cardinal Massaia di Asti, Asti, Italy
  • 16 Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
  • 17 Anesthesia and Intensive Care, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
  • 18 S. Antonio Hospital, Padova, Italy
  • 19 Department of Anesthesia and Intensive Care Unit, Policlinico Duilio Casula AOU, Cagliari, Italy
  • 20 Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy
  • 21 IRCCS Istituto Giannina Gaslini, Ospedale Pediatrico, Genoa, Italy
  • 22 E.O. Ospedali Galliera, Genova, Italy and Università degli Studi di Pisa, Italy
  • 23 Anaesthesia and Intensive Care, Hospital Pulau Pinang, Georgetown, Malaysia
  • 24 Department of Anesthesia and Intensive Care, A.O.U. Cittàdella Salute e della Scienza, Turin, Italy
  • 25 Hospital Santa Chiara, Pisa, Italy
  • 26 Department Morphology, Surgery and Experimental Medicine, Intensive Care Unit, University of Ferrara, Italy
  • 27 Mater Dei Hospital, Bari, Italy
  • 28 Anesthesia and Intensive Care A.O.U Città della salute e della Scienza, Turin, Italy
  • 29 Australian and New Zealand Intensive Care Research Centre, Melbourne, Australia
  • 30 Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
  • 31 Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address:
J Cardiothorac Vasc Anesth, 2019 Oct;33(10):2685-2694.
PMID: 31064730 DOI: 10.1053/j.jvca.2019.03.022


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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.