Cameron Dezfulian1, Michele Olsufka2, Deborah Fly2, Sue Scruggs2, Rose Do2, Charles Maynard3, Graham Nichol2, Francis Kim4. 1. Department of Adult and Pediatric Critical Care Medicine, Safar Center for Resuscitation Research and Vascular Medicine Institute, University of Pittsburgh, United States. 2. Department of Medicine, Harborview Medical Center, University of Washington, United States. 3. Department of Health Services, University of Washington, United States. 4. Department of Medicine, Harborview Medical Center, University of Washington, United States. Electronic address: fkim@u.washington.edu.
Abstract
BACKGROUND:Patients resuscitated from cardiac arrest have brain and cardiac injury. Recent animal studies suggest that the administration of sodium nitrite after resuscitation from 12min of asystole limits acute cardiac dysfunction and improves survival and neurologic outcomes. It has been hypothesized that low doses of IV sodium nitrite given during resuscitation of out of hospital cardiac arrest (OHCA) will improve survival. Low doses of sodium nitrite (e.g., 9.6mg of sodium nitrite) are safe in healthy individuals, however the effect of nitrite on blood pressure in resuscitated cardiac arrest patients is unknown. METHODS: We performed a single-center, pilot trial of low dose sodium nitrite (1 or 9.6mg dose) vs. placebo in hospitalized out-of-hospital cardiac arrest patient to determine whether nitrite administration reduced blood pressure and whether whole blood nitrite levels increased in response to nitrite administration. RESULTS: This is the first reported study of sodium nitrite in cardiac arrest patients. Infusion of low doses of sodium nitrite in comatose survivors of OHCA (n=7) compared to placebo (n=4) had no significant effects on heart rate within 30min after infusion (70±20 vs. 78±3 beats per minute, p=0.18), systolic blood pressure (103±20 vs 108±15mmHg, p=0.3), or methemoglobin levels (0.92±0.33 vs. 0.70±0.26, p=0.45). Serum nitrite levels of 2-4μM were achieved within 15min of a 9.6mg nitrite infusion. CONCLUSIONS:Low dose sodium nitrite does not cause significant hemodynamic effect in patients with OHCA, which suggests that nitrite can be delivered safely in this critically ill patient population. Higher doses of sodium nitrite are necessary in order to achieve target serum level of 10μM.
RCT Entities:
BACKGROUND:Patients resuscitated from cardiac arrest have brain and cardiac injury. Recent animal studies suggest that the administration of sodium nitrite after resuscitation from 12min of asystole limits acute cardiac dysfunction and improves survival and neurologic outcomes. It has been hypothesized that low doses of IV sodium nitrite given during resuscitation of out of hospital cardiac arrest (OHCA) will improve survival. Low doses of sodium nitrite (e.g., 9.6mg of sodium nitrite) are safe in healthy individuals, however the effect of nitrite on blood pressure in resuscitated cardiac arrestpatients is unknown. METHODS: We performed a single-center, pilot trial of low dose sodium nitrite (1 or 9.6mg dose) vs. placebo in hospitalized out-of-hospital cardiac arrestpatient to determine whether nitrite administration reduced blood pressure and whether whole blood nitrite levels increased in response to nitrite administration. RESULTS: This is the first reported study of sodium nitrite in cardiac arrestpatients. Infusion of low doses of sodium nitrite in comatose survivors of OHCA (n=7) compared to placebo (n=4) had no significant effects on heart rate within 30min after infusion (70±20 vs. 78±3 beats per minute, p=0.18), systolic blood pressure (103±20 vs 108±15mmHg, p=0.3), or methemoglobin levels (0.92±0.33 vs. 0.70±0.26, p=0.45). Serum nitrite levels of 2-4μM were achieved within 15min of a 9.6mg nitrite infusion. CONCLUSIONS: Low dose sodium nitrite does not cause significant hemodynamic effect in patients with OHCA, which suggests that nitrite can be delivered safely in this critically ill patient population. Higher doses of sodium nitrite are necessary in order to achieve target serum level of 10μM.
Authors: Robert W Neumar; Jerry P Nolan; Christophe Adrie; Mayuki Aibiki; Robert A Berg; Bernd W Böttiger; Clifton Callaway; Robert S B Clark; Romergryko G Geocadin; Edward C Jauch; Karl B Kern; Ivan Laurent; W T Longstreth; Raina M Merchant; Peter Morley; Laurie J Morrison; Vinay Nadkarni; Mary Ann Peberdy; Emanuel P Rivers; Antonio Rodriguez-Nunez; Frank W Sellke; Christian Spaulding; Kjetil Sunde; Terry Vanden Hoek Journal: Circulation Date: 2008-10-23 Impact factor: 29.690
Authors: J B Mannick; A Hausladen; L Liu; D T Hess; M Zeng; Q X Miao; L S Kane; A J Gow; J S Stamler Journal: Science Date: 1999-04-23 Impact factor: 47.728
Authors: Nils Neye; Fabian Enigk; Sruti Shiva; Helmut Habazettl; Nikolaus Plesnila; Hermann Kuppe; Mark T Gladwin; Wolfgang M Kuebler Journal: Intensive Care Med Date: 2012-06-01 Impact factor: 17.440
Authors: Emile R Mohler; William R Hiatt; Heather L Gornik; Christopher G Kevil; Arshed Quyyumi; William G Haynes; Brian H Annex Journal: Vasc Med Date: 2013-12-20 Impact factor: 3.239
Authors: Cameron Dezfulian; Elizabeth Kenny; Andrew Lamade; Amalea Misse; Nicholas Krehel; Claudette St Croix; Eric E Kelley; Travis C Jackson; Thomas Uray; Justin Rackley; Patrick M Kochanek; Robert S B Clark; Hulya Bayir Journal: J Neurochem Date: 2016-10-03 Impact factor: 5.372
Authors: Andrew Webb; Richard Bond; Peter McLean; Rakesh Uppal; Nigel Benjamin; Amrita Ahluwalia Journal: Proc Natl Acad Sci U S A Date: 2004-09-03 Impact factor: 11.205
Authors: Tom P Aufderheide; Peter J Kudenchuk; Jerris R Hedges; Graham Nichol; Richard E Kerber; Paul Dorian; Daniel P Davis; Ahamed H Idris; Clifton W Callaway; Scott Emerson; Ian G Stiell; Thomas E Terndrup Journal: Resuscitation Date: 2008-05-19 Impact factor: 5.262
Authors: Jon O Lundberg; Mark T Gladwin; Amrita Ahluwalia; Nigel Benjamin; Nathan S Bryan; Anthony Butler; Pedro Cabrales; Angela Fago; Martin Feelisch; Peter C Ford; Bruce A Freeman; Michael Frenneaux; Joel Friedman; Malte Kelm; Christopher G Kevil; Daniel B Kim-Shapiro; Andrey V Kozlov; Jack R Lancaster; David J Lefer; Kenneth McColl; Kenneth McCurry; Rakesh P Patel; Joel Petersson; Tienush Rassaf; Valentin P Reutov; George B Richter-Addo; Alan Schechter; Sruti Shiva; Koichiro Tsuchiya; Ernst E van Faassen; Andrew J Webb; Brian S Zuckerbraun; Jay L Zweier; Eddie Weitzberg Journal: Nat Chem Biol Date: 2009-12 Impact factor: 15.040
Authors: Edward T Chouchani; Carmen Methner; Sergiy M Nadtochiy; Angela Logan; Victoria R Pell; Shujing Ding; Andrew M James; Helena M Cochemé; Johannes Reinhold; Kathryn S Lilley; Linda Partridge; Ian M Fearnley; Alan J Robinson; Richard C Hartley; Robin A J Smith; Thomas Krieg; Paul S Brookes; Michael P Murphy Journal: Nat Med Date: 2013-05-26 Impact factor: 53.440
Authors: Thomas Uray; Philip E Empey; Tomas Drabek; Jason P Stezoski; Keri Janesko-Feldman; Travis Jackson; Robert H Garman; Francis Kim; Patrick M Kochanek; Cameron Dezfulian Journal: Nitric Oxide Date: 2019-09-14 Impact factor: 4.427
Authors: Francis Kim; Cameron Dezfulian; Philip E Empey; Matthew Morrell; Michele Olsufka; Sue Scruggs; Peter Kudenchuk; Susanne May; Charles Maynard; Michael R Sayre; Graham Nichol Journal: Am J Cardiol Date: 2018-06-20 Impact factor: 2.778
Authors: Francis Kim; Charles Maynard; Cameron Dezfulian; Michael Sayre; Peter Kudenchuk; Thomas Rea; Deborah Sampson; Michele Olsufka; Susanne May; Graham Nichol Journal: JAMA Date: 2021-01-12 Impact factor: 157.335
Authors: Kei Hayashida; Santiago J Miyara; Koichiro Shinozaki; Ryosuke Takegawa; Tai Yin; Daniel M Rolston; Rishabh C Choudhary; Sara Guevara; Ernesto P Molmenti; Lance B Becker Journal: Front Med (Lausanne) Date: 2021-01-14
Authors: Dario A Vitturi; Charles Maynard; Michele Olsufka; Adam C Straub; Nick Krehel; Peter J Kudenchuk; Graham Nichol; Michael Sayre; Francis Kim; Cameron Dezfulian Journal: Redox Biol Date: 2020-02-14 Impact factor: 10.787