Evaluation and Predictors of Fluid Resuscitation in Patients With Severe Sepsis and Septic Shock 08/08/2019 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3KirptPALrnC71pQBOooedCzq7X3ZCQuWqKFh7hy8XoKb5vHw25vvlg== by https://journals.lww.com/ccmjournal from Downloaded 1 2 1 3 Downloaded Hani I. Kuttab, MD ; Joseph D. Lykins, MD ; Michelle D. Hughes, MD ; Kristen Wroblewski, MS ; Eric P. Keast, MD1; Omobolawa Kukoyi, MD, MPH1; Jason A. Kopec, MD1; Stephen Hall, MS1; from 4 https://journals.lww.com/ccmjournal Michael A. Ward, MD Objectives: Rapid fluid resuscitation has become standard in Interventions: Administration of IV fluids by bolus. sepsis care, despite “low-quality” evidence and absence of guide- Measurements and Main Results: In total, 509 patients received by lines for populations “at risk” for volume overload. Our objectives 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3KirptPALrnC71pQBOooedCzq7X3ZCQuWqKFh7hy8XoKb5vHw25vvlg== include as follows: 1) identify predictors of reaching a 30 mL/ mortality in the shock group. Patients who were elderly (odds ratio, kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) 0.62; 95% CI, 0.46–0.83), male (odds ratio, 0.66; CI, 0.49–0.87), assess the impact of 30by3 and fluid dosing on clinical outcomes; obese (odds ratio, 0.18; CI, 0.13–0.25), or with end-stage renal 3) examine differences in perceived “at-risk” volume-sensitive disease (odds ratio, 0.23; CI, 0.13–0.40), heart failure (odds ratio, populations, including end-stage renal disease, heart failure, obe- 0.42; CI, 0.29–0.60), or documented volume “overload” (odds sity, advanced age, or with documentation of volume “overload” ratio, 0.30; CI, 0.20–0.45) were less likely to achieve 30by3. by bedside examination. Failure to meet 30by3 had increased odds of mortality (odds ratio, Design: Retrospective cohort study. All outcome analyses con- 1.52; CI, 1.03–2.24), delayed hypotension (odds ratio, 1.42; CI, trolled for sex, end-stage renal disease, heart failure, sepsis 1.02–1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5–3.6), severity (severe sepsis vs septic shock), obesity, Mortality in without differential effects for “at-risk” groups. Higher fluid volumes Emergency Department Sepsis score, and time to antibiotics. administered by 3 hours correlated with decreased mortality, with Setting: Urban, tertiary care center between January 1, 2014, and a plateau effect between 35 and 45 mL/kg (p < 0.05). May 31, 2017. Conclusions: Failure to reach 30by3 was associated with Patients: Emergency Department treated adults (age ≥18 yr; increased odds of in-hospital mortality, irrespective of comor- n = 1,032) with severe sepsis or septic shock. bidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These find- ings are retrospective and require future validation. (Crit Care 1Section of Emergency Medicine, Department of Medicine, University of Chicago Medical Center, Chicago, IL. Med 2019; XX:00–00) 2Department of Emergency Medicine and Internal Medicine, Virginia Key Words: fluids; morbidity; overload; resuscitation; sepsis; Commonwealth University Health System, Richmond, VA. shock 3Department of Public Health Sciences, University of Chicago, Chicago, IL. 4Department of Emergency Medicine, University of Wisconsin-Madison, on Madison, WI. 08/08/2019 espite significant improvements in care, mortality Supplemental digital content is available for this article. Direct URL cita- tions appear in the printed text and are provided in the HTML and PDF from sepsis remains high (1–5). The Surviving Sepsis versions of this article on the journal’s website (http://journals.lww.com/ Campaign (SSC) recommends that patients with ccmjournal). D “sepsis-induced hypoperfusion” receive a 30 mL/kg IV bolus Supported, in part, by grant from the National Center for Advancing of crystalloid fluids within 3 hours of identification, which Translational Sciences of the National Institutes of Health through Grant Number 5UL1TR002389-02 that funds the Institute for Translational has become a mandate by the Centers for Medicare & Medi- Medicine. The content is solely the responsibility of the authors and does caid Services (CMS) (5). The 30 mL/kg approach was derived not necessarily represent the official views of the National Institutes of based on average fluid volumes received in larger sepsis trials, Health. although the evidence behind this recommendation from the The authors have disclosed that they do not have any potential conflicts of interest. SSC is listed as “low-quality” and does not address exceptions For information regarding this article, E-mail: [email protected] for medical comorbidities or volume status (5). Copyright © 2019 by the Society of Critical Care Medicine and Wolters Numerous studies support the administration of early, aggres- Kluwer Health, Inc. All Rights Reserved. sive fluid resuscitation (6–9); however, the topic remains controver- DOI: 10.1097/CCM.0000000000003960 sial. A large, multicenter study found no mortality benefit of early Critical Care Medicine www.ccmjournal.org 1 Copyright © 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Kuttab et al fluids in patients with septic shock (10). Further, studies evaluating antibiotics within 12 hours of ED arrival were also flagged. A a more extended time course have highlighted deleterious effects of physician reviewed each chart using a standardized process to fluids in critically ill populations (11–15). There were noted ben- determine whether infection-related organ dysfunction occurred efits with a negative-fluid-balance strategy for ICU patients requir- within 8 hours of ED arrival. Identified cases were confirmed ing renal replacement therapy or with acute lung injury; however, with the treating providers and a multidisciplinary quality im- these were not exclusive to septic patients, nor do they evaluate the provement group. Computational algorithms were used to iden- effects of early fluid resuscitation (12, 13). Additionally, significant tify cases and demographics and, therefore, blinded to input increases in mortality have also been noted when the total volume variables for sepsis management and clinical endpoints. The phy- of fluids received during the first 24 hours of resuscitation is 7L or sician chart reviewer was not blinded, however, cases were not greater (14). Others have further demonstrated that greater fluid originally identified for the purpose of this study. balances are associated with an increased hazard of death on the third day of ICU admission, but not the first 24 hours (15). Sepsis Definitions Data on fluid resuscitation in septic patients who are per- Severe sepsis and septic shock were defined using Sepsis-2 crite- ceived to be “at risk” of volume overload remains inconclu- ria (Supplementary 1b, Supplemental Digital Content 1, http:// sive. Patients who are obese receive a lower weight-based fluid links.lww.com/CCM/E851) (1, 2). Time of onset was determined dose relative to nonobese patients, yet demonstrate improved when all the above criteria were met and/or when laboratory survival (16, 17). Additionally, patients with end-stage renal values resulted. Volume "overload" was defined as physician doc- disease (ESRD), heart failure (HF), and advanced age often umentation justifying the rationale for limiting IV fluids. This receive less fluids or have significant delays to fluid adminis- includes: bedside echocardiogram, ultrasound demonstrating a tration with differing effects on mortality (9, 18–20). These noncollapsible inferior vena cava, jugular venous distention or findings may offer some explanation for why practitioners crackles on physical exam, clinical concern for cardiogenic shock, hesitate to order fluids in septic patients, particularly in these or evidence of pulmonary edema by chest radiograph. perceived “at-risk” populations. The objectives of this study include as follows: 1) identify Inclusion and Exclusion Criteria predictors of reaching a 30 mL/kg crystalloid bolus within 3 Patients greater than or equal to 18 years old were included. hours of sepsis onset (30by3); 2) assess the impact of receiving Patients with a left ventricular assist device were excluded, unless 30by3 and dosing of fluids on various clinical outcomes; and the initial serum lactic acid level was greater than 2.0 mmol/L. 3) examine differences in these perceived “at-risk” populations, Additionally, patients who were made do-not-resuscitate or including ESRD, HF, obesity, advanced age, or with documen- comfort care within 12 hours of sepsis onset, having received IV tation of volume “overload” by bedside examination. antibiotics 24 hours prior to arrival, or transferred to the oper- ating room or cardiac catheterization laboratory within 3 hours of sepsis onset were also excluded. For patients with multiple MATERIALS AND METHODS encounters, a single visit was randomly selected for inclusion in Study Design and Population the analytic dataset (Supplementary Fig. 1, Supplemental Dig- This was a retrospective cohort study from January 1, 2014, to ital Content 1, http://links.lww.com/CCM/E851). April 30, 2015, and from February 1, 2016, to May 31, 2017, for patients treated in the emergency department (ED) at an urban, Data Collection and Accuracy tertiary care center with ~70,000 visits per year, predominantly Data