Multicenter Study

. 2020 Oct;48(10):1445-1453.

doi: 10.1097/CCM.0000000000004476.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock

Russel J Roberts¹, Todd A Miano², Drayton A Hammond³, Gourang P Patel⁴, Jen-Ting Chen⁵, Kristy M Phillips¹, Natasha Lopez¹, Kianoush Kashani^{6

7}, Nida Qadir⁸, Charles B Cairns⁹, Kusum Mathews¹⁰, Pauline Park¹¹, Akram Khan¹², James F Gilmore¹³, Anne Rain Tanner Brown¹⁴, Betty Tsuei¹⁵, Michele Handzel¹⁶, Alfredo Lee Chang¹⁷, Abhijit Duggal¹⁸, Michael Lanspa¹⁹, James Taylor Herbert²⁰, Anthony Martinez²¹, Joseph Tonna²², Mahmoud A Ammar²³, Lama H Nazer²⁴, Mojdeh Heavner²⁵, Erin Pender²⁶, Lauren Chambers²⁷, Michael T Kenes²⁸, David Kaufman²⁹, April Downey³⁰, Brent Brown³¹, Darlene Chaykosky³², Armand Wolff³³, Michael Smith³⁴, Katie Nault³⁵, Michelle N Gong⁵, Jonathan E Sevransky³⁶, Ishaq Lat³⁷; Observation of VariatiOn in fLUids adMinistEred in shock-CHaracterizAtion of vaSoprEssor Requirements in Shock (VOLUME-CHASERS) Study Group and SCCM Discovery Network

Collaborators, Affiliations

Collaborators

Observation of VariatiOn in fLUids adMinistEred in shock-CHaracterizAtion of vaSoprEssor Requirements in Shock (VOLUME-CHASERS) Study Group and SCCM Discovery Network:
Tina McCurry, Jeremy R DeGrado, Kevin M Dube, Kenneth E Lupi, Andrei Hastings, Omar Mehkri, Raquel R Bartz, Angela L Pollak, Sarah Kendal Smith, Marguerite Stewart, Leona Wells, Jamie Kerestes, Kayla Kotch, Sarah Miller, Brent Armbruster, Valerie Aston, Katie Brown, Mardee Merrill, Nadeen Anabtawi, Katie Nault, Kerri L Federico, Peter-John Trapp, Joseph C Farmer, Pablo Moreno Franco, Shurong Gong, Rahul Kashyap, Sidhant Singh, Reagan D Collins, Jorge Ataucuri-Vargas, Vladyslav Dieiev, Ashley Kang, Ann Wang, Neha N Goel, Oscar Mitchell, Jordan DeWitt, Alex Heine, Abby Tyson, Dubier Matos, Ebaad Haq, Katie Dalton, Valentina Amaral, Jasmine Aulakh, Nauman Farooq, Kerra Cissne, Jose Camarena, Alexia Demitsas, Kristen Deupree, Karen Lutrick, Nora Elson, Dina Gomaa, John Shinn III, Anthony Spuzzillo, Devin Wakefield, Mehrnaz Pajoumand, Sharon Wilson, Siu Yan, Amy Yeung, Tina Chen, Sinan Hanna, Lauren Sinko, Kassidy Malone, Deamber Piel, Chloe Skidmore, Matt Flynn, Ji Yeon Seo, Nicole M Acquisto, Kathryn Connor, Samantha Delibert, Christine Groth, Jeff Huntress, Gregory Kelly, Therese Makhoul, Hannah Mierzwa, Stephen Rappaport, Daisy Rios, Bethany Crouse, Michael Kenes, Shamsuddin Akhtar, Abdalla A Ammar

Affiliations

¹ Department of Pharmacy, Massachusetts General Hospital, Boston, MA.
² Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
³ Department of Pharmacy, Rush Medical College, Rush University Medical Center, Chicago, IL.
⁴ Department of Pharmacy, University of Chicago Medical Center, Chicago, IL.
⁵ Division of Critical Care Medicine, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
⁶ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
⁷ Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
⁸ Division of Pulmonary and Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
⁹ Department of Emergency Medicine, University of Arizona, Tucson, AZ.
¹⁰ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Emergency Medicine, Mount Sinai Health System, New York, NY.
¹¹ Division of Acute Care Surgery, University of Michigan, Ann Arbor, MI.
¹² Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR.
¹³ Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
¹⁴ Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, TX.
¹⁵ Section of General Surgery, University of Cincinnati Department of Surgery, Cincinnati, OH.
¹⁶ Department of Emergency Medicine, University of Rochester Medical Center, Rochester, NY.
¹⁷ Division of Pulmonary and Critical Care, Department of Medicine, University of Southern California, Los Angeles, CA.
¹⁸ Department of Critical Care, Respiratory Institute, Cleveland Clinic, Cleveland, OH.
¹⁹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Intermountain Healthcare, Salt Lake City, UT.
²⁰ Division of Critical Care Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC.
²¹ Division of Critical Care, St Agnes Hospital, Baltimore, MD.
²² Division of Cardiothoracic Surgery, Department of Surgery, University of Utah Health, Salt Lake City, UT.
²³ Department of Pharmacy, Yale-New Haven Health, New Haven, CT.
²⁴ Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan.
²⁵ Department of Pharmacy Practice and Science, University of Maryland Medical Center, Baltimore, MD.
²⁶ Department of Pharmacy, Truman Medical Center, Kansas City, MO.
²⁷ Department of Pharmacy Services, Vidant Medical Center, Greenville, NC.
²⁸ Department of Pharmacy, Wake Forest Baptist Health, Winston-Salem, NC.
²⁹ Division of Pulmonary, Critical Care, and Sleep Medicine, New York University, New York, NY.
³⁰ Department of Pharmacy, Ohio Health Riverside Methodist Hospital, Columbus, OH.
³¹ Department of Medicine, Pulmonary and Critical Care, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
³² Department of Pharmacy, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA.
³³ Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Bridgeport Hospital, Bridgeport, CT.
³⁴ Department of Pharmacy, Lake Region General Healthcare, Laconia, NH.
³⁵ Department of Pharmacy, Lahey Hospital Medical Center, Burlington, MA.
³⁶ Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University Hospital, Atlanta, GA.
³⁷ Department of Pharmacy, Shirley Ryan Abilitylab, Chicago, IL.

PMID: 32706559
DOI: 10.1097/CCM.0000000000004476

Multicenter Study

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock

Russel J Roberts et al. Crit Care Med. 2020 Oct.

. 2020 Oct;48(10):1445-1453.

doi: 10.1097/CCM.0000000000004476.

Authors

Collaborators

Observation of VariatiOn in fLUids adMinistEred in shock-CHaracterizAtion of vaSoprEssor Requirements in Shock (VOLUME-CHASERS) Study Group and SCCM Discovery Network:
Tina McCurry, Jeremy R DeGrado, Kevin M Dube, Kenneth E Lupi, Andrei Hastings, Omar Mehkri, Raquel R Bartz, Angela L Pollak, Sarah Kendal Smith, Marguerite Stewart, Leona Wells, Jamie Kerestes, Kayla Kotch, Sarah Miller, Brent Armbruster, Valerie Aston, Katie Brown, Mardee Merrill, Nadeen Anabtawi, Katie Nault, Kerri L Federico, Peter-John Trapp, Joseph C Farmer, Pablo Moreno Franco, Shurong Gong, Rahul Kashyap, Sidhant Singh, Reagan D Collins, Jorge Ataucuri-Vargas, Vladyslav Dieiev, Ashley Kang, Ann Wang, Neha N Goel, Oscar Mitchell, Jordan DeWitt, Alex Heine, Abby Tyson, Dubier Matos, Ebaad Haq, Katie Dalton, Valentina Amaral, Jasmine Aulakh, Nauman Farooq, Kerra Cissne, Jose Camarena, Alexia Demitsas, Kristen Deupree, Karen Lutrick, Nora Elson, Dina Gomaa, John Shinn III, Anthony Spuzzillo, Devin Wakefield, Mehrnaz Pajoumand, Sharon Wilson, Siu Yan, Amy Yeung, Tina Chen, Sinan Hanna, Lauren Sinko, Kassidy Malone, Deamber Piel, Chloe Skidmore, Matt Flynn, Ji Yeon Seo, Nicole M Acquisto, Kathryn Connor, Samantha Delibert, Christine Groth, Jeff Huntress, Gregory Kelly, Therese Makhoul, Hannah Mierzwa, Stephen Rappaport, Daisy Rios, Bethany Crouse, Michael Kenes, Shamsuddin Akhtar, Abdalla A Ammar

Affiliations

¹ Department of Pharmacy, Massachusetts General Hospital, Boston, MA.
² Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
³ Department of Pharmacy, Rush Medical College, Rush University Medical Center, Chicago, IL.
⁴ Department of Pharmacy, University of Chicago Medical Center, Chicago, IL.
⁵ Division of Critical Care Medicine, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
⁶ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
⁷ Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
⁸ Division of Pulmonary and Critical Care Medicine, University of California Los Angeles, Los Angeles, CA.
⁹ Department of Emergency Medicine, University of Arizona, Tucson, AZ.
¹⁰ Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Emergency Medicine, Mount Sinai Health System, New York, NY.
¹¹ Division of Acute Care Surgery, University of Michigan, Ann Arbor, MI.
¹² Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR.
¹³ Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
¹⁴ Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, TX.
¹⁵ Section of General Surgery, University of Cincinnati Department of Surgery, Cincinnati, OH.
¹⁶ Department of Emergency Medicine, University of Rochester Medical Center, Rochester, NY.
¹⁷ Division of Pulmonary and Critical Care, Department of Medicine, University of Southern California, Los Angeles, CA.
¹⁸ Department of Critical Care, Respiratory Institute, Cleveland Clinic, Cleveland, OH.
¹⁹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Intermountain Healthcare, Salt Lake City, UT.
²⁰ Division of Critical Care Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC.
²¹ Division of Critical Care, St Agnes Hospital, Baltimore, MD.
²² Division of Cardiothoracic Surgery, Department of Surgery, University of Utah Health, Salt Lake City, UT.
²³ Department of Pharmacy, Yale-New Haven Health, New Haven, CT.
²⁴ Department of Pharmacy, King Hussein Cancer Center, Amman, Jordan.
²⁵ Department of Pharmacy Practice and Science, University of Maryland Medical Center, Baltimore, MD.
²⁶ Department of Pharmacy, Truman Medical Center, Kansas City, MO.
²⁷ Department of Pharmacy Services, Vidant Medical Center, Greenville, NC.
²⁸ Department of Pharmacy, Wake Forest Baptist Health, Winston-Salem, NC.
²⁹ Division of Pulmonary, Critical Care, and Sleep Medicine, New York University, New York, NY.
³⁰ Department of Pharmacy, Ohio Health Riverside Methodist Hospital, Columbus, OH.
³¹ Department of Medicine, Pulmonary and Critical Care, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
³² Department of Pharmacy, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA.
³³ Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Bridgeport Hospital, Bridgeport, CT.
³⁴ Department of Pharmacy, Lake Region General Healthcare, Laconia, NH.
³⁵ Department of Pharmacy, Lahey Hospital Medical Center, Burlington, MA.
³⁶ Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University Hospital, Atlanta, GA.
³⁷ Department of Pharmacy, Shirley Ryan Abilitylab, Chicago, IL.

PMID: 32706559
DOI: 10.1097/CCM.0000000000004476

Abstract

Objectives: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern.

Design: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents.

Setting: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1).

Patients: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset.

Interventions: None.

Measurements and main results: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 μg/min norepinephrine equivalents (3.4-18.1 μg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality.

Conclusions: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

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Comment in

Fluid Resuscitation and Vasopressors in Septic Shock: The Importance of Filling the Tank While Squeezing the Pipes.
Schellenberg M, Cobb JP. Schellenberg M, et al. Crit Care Med. 2020 Oct;48(10):1533-1535. doi: 10.1097/CCM.0000000000004539. Crit Care Med. 2020. PMID: 32925261 No abstract available.
Does Norepinephrine Exhibit a Time-Dose Relationship in Septic Shock?
Jones TW, Azimi H, Scott C, Newsome AS. Jones TW, et al. Crit Care Med. 2021 Mar 1;49(3):e345-e346. doi: 10.1097/CCM.0000000000004782. Crit Care Med. 2021. PMID: 33616370 Free PMC article. No abstract available.
The authors reply.
Miano TA, Roberts RJ, Lat I. Miano TA, et al. Crit Care Med. 2021 Mar 1;49(3):e346-e347. doi: 10.1097/CCM.0000000000004870. Crit Care Med. 2021. PMID: 33616371 No abstract available.

References

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1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315:801–810
1. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34:1589–1596
1. Beck V, Chateau D, Bryson GL, et al.; Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group: Timing of vasopressor initiation and mortality in septic shock: A cohort study. Crit Care 2014; 18:R97
1. Seymour CW, Gesten F, Prescott HC, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017; 376:2235–2244

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Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock

Collaborators

Affiliations

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock

Authors

Collaborators

Affiliations

Abstract

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources