Association Between Volume of Fluid Resuscitation and Intubation in High-Risk Patients With Sepsis, Heart Failure, End-Stage Renal Disease, and Cirrhosis

doi:10.1016/j.chest.2019.09.029

Chest

Volume 157, Issue 2, February 2020, Pages 286-292

Part of this article has been presented in abstract form at the Society of Critical Care Medicine Annual Congress, February 25-28, 2018, San Antonio, TX.

https://doi.org/10.1016/j.chest.2019.09.029 Get rights and content

Background

Initial fluid resuscitation volume for sepsis is controversial, particularly in patients at high baseline risk for complications. This study was designed to assess the association between 30 mL/kg crystalloids and intubation in patients with sepsis or septic shock and heart failure, end-stage renal disease, or cirrhosis.

Methods

This propensity score-matched retrospective cohort study included patients with sepsis or septic shock admitted to a large medical ICU. Primary exposure was IV fluid volume in the first 6 h following sepsis diagnosis, divided into two cohorts: ≥ 30 mL/kg (standard group) and < 30 mL/kg (restricted group). The primary outcome was need for mechanical ventilation within 72 h following initiation of fluid resuscitation. Secondary outcomes were length of stay, ventilator days, and time to intubation.

Results

A total of 208 patients were included, with 104 (50%) in the restricted group (< 30 mL/kg) and 104 in the standard group (≥ 30 mL/kg). No difference in intubation incidence was detected between the two groups, with 36 patients (35%) in the restricted group and 33 (32%) in the standard group (adjusted OR, 0.75; 95% CI, 0.41-1.36; P = .34) intubated. There was no difference between standard and restricted groups in alive ICU-free days (17 ± 11 days vs 17 ± 10 days; P = .64), duration of mechanical ventilation (10 ± 12 days vs 11 ± 16 days; P = .96), or hours to intubation (16 ± 19 h vs 14 ± 15; P = .55).

Conclusions

No differences were detected in the incidence of intubation in patients with sepsis and cirrhosis, end-stage renal disease, or heart failure who received guideline-recommended fluid resuscitation with 30 mL/kg compared with patients initially resuscitated with a lower fluid volume.

Section snippets

Study Design

This study was performed at the Cleveland Clinic and was approved by the Institutional Review Board (study no. 16-751). We conducted a retrospective cohort study of the patients admitted to the medical ICU between 2014 and 2016 with administrative coding for sepsis and septic shock who also had a comorbidity of CHF, ESRD, or cirrhosis. Patients transferred from outside hospital facilities, missing primary outcome data, with sepsis episodes from a second or subsequent ICU admission, and shock

Study Population

A total of 2,517 patients were admitted to the medical ICU with administrative coding for sepsis and septic shock between 2014 and 2016. After excluding 2,231 patients, the dataset included 286 patients, and 208 patients (104 patients per group) were matched by propensity score (Fig 1). A histogram shows the distribution of the patients according to the fluid bolus volume they received (Fig 2).

Table 1 shows the comparison of baseline clinical characteristics between the standard fluid

Discussion

In this single-center retrospective cohort study of patients at risk for volume overload with sepsis and septic shock, no differences were detected in the development of respiratory failure requiring intubation between patients who were fluid resuscitated per SSC guidelines vs a lower resuscitation volume. Since the advent of early goal-directed therapy in the study by Rivers et al,² there has been increasing importance on early and aggressive fluid resuscitative efforts in septic shock, which

Conclusions

We detected no difference in the incidence of intubation in the high-risk cohort of cirrhotic, heart failure, and ESRD patients with sepsis who received SSC guideline-concordant (30 mL/kg) vs restricted fluid resuscitation. Based on our results, we suggest that guideline-based early fluid resuscitative efforts should not be omitted in patients with cirrhosis, CHF, and ESRD solely for concern of acute respiratory failure.

Acknowledgments

Author contributions: R. A. K., N. A. K., and A. J. R. had access to all of the data in the study and take responsibility for the integrity of the data and content of the manuscript. All authors contributed substantially to the study design, data analysis and interpretation, and writing and review of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. R. B. has served as a consultant for Wolters Kluwer. None declared (R. A. K., N. A. K., M.

References (18)

T.N. Truong et al.
Adherence to fluid resuscitation guidelines and outcomes in patients with septic shock: reassessing the "one-size-fits-all" approach
J Crit Care
(2019)
W.H. Self et al.
Liberal versus restrictive intravenous fluid therapy for early septic shock: rationale for a randomized trial
Ann Emerg Med
(2018)
M. Singer et al.
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
JAMA
(2016)
E. Rivers et al.
Early goal-directed therapy in the treatment of severe sepsis and septic shock
N Engl J Med
(2001)
A. Rhodes et al.
Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock. 2016
Crit Care Med
(2017)
A. Perner et al.
The intensive care medicine research agenda on septic shock
Intensive Care Med
(2017)
A. Rhodes et al.
The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study)
Intensive Care Med
(2015)
C. Rhee et al.
Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014
JAMA
(2017)
P.C. Austin
Type I error rates, coverage of confidence intervals, and variance estimation in propensity-score matched analyses
Int J Biostat
(2009)

There are more references available in the full text version of this article.

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Impact of initial fluid resuscitation volume on clinical outcomes in patients with heart failure and septic shock
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Fluid resuscitation is a key treatment for sepsis, but limited data exists in patients with existing heart failure (HF) and septic shock. The objective of this study was to determine the impact of initial fluid resuscitation volume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with septic shock.
This multicenter, retrospective, cohort study included patients with known HF (LVEF ≤50%) presenting with septic shock. Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h; <30 mL/kg or ≥30 mL/kg. The primary outcome was a composite of in-hospital mortality or renal replacement therapy (RRT) within 7 days. Secondary outcomes included acute kidney injury (AKI), initiation of mechanical ventilation, and length of stay (LOS). All related data were collected and compared between the two groups. A generalized logistic mixed model was used to assess the association between fluid groups and the primary outcome while adjusting for baseline LVEF, Acute Physiology and Chronic Health Evaluation (APACHE) II score, inappropriate empiric antibiotics, and receipt of corticosteroids.
One hundred and fifty-four patients were included (93 patients in <30 mL/kg group and 61 patients in ≥30 mL/kg group). The median weight-based volume in the first 6 h was 17.7 (12.2–23.0) mL/kg in the <30 mL/kg group vs. 40.5 (34.2–53.1) mL/kg in the ≥30 mL/kg group (P <0.01). No statistical difference was detected in the composite of in-hospital mortality or RRT between the <30 mL/kg group compared to the ≥30 mL/kg group (55.9% vs. 45.9%, P=0.25), respectively. The <30 mL/kg group had a higher incidence of AKI, mechanical ventilation, and longer hospital LOS.
In patients with known reduced or mildly reduced LVEF presenting with septic shock, no difference was detected for in-hospital mortality or RRT in patients who received ≥30 mL/kg of resuscitation fluid compared to less fluid, although this study was underpowered to detect a difference. Importantly, ≥30 mL/kg fluid did not result in a higher need for mechanical ventilation.
Is Left Ventricular Systolic Dysfunction Associated With Increased Mortality Among Patients With Sepsis and Septic Shock?
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Is LV systolic dysfunction associated with increased mortality among patients with sepsis and septic shock?
Retrospective cohort study comprising all adult patients admitted to the medical ICU from January 1, 2011, through December 31, 2020, with sepsis and septic shock as defined by the Third International Consensus Definitions for Sepsis and Septic Shock guidelines. All adult patients with sepsis or septic shock who underwent transthoracic echocardiography within 3 days from admission to the medical ICU were included. We divided patients into five groups based on LV ejection fraction (LVEF). In addition to univariate analysis, we also performed multivariate logistic regression analysis adjusting for patients’ baseline characteristics and severity of illness. The primary outcome was the association between each classification of LVEF and in-hospital mortality.
A total of 3,151 patients were included in this study (LVEF < 25%, 133 patients; 25% ≤ LVEF < 40%, 305 patients; 40% ≤ LVEF < 55%, 568 patients; 55% ≤ LVEF < 70%, 1,792 patients; and LVEF ≥ 70%, 353 patients). In-hospital mortalities in each LVEF category were 51.1%, 34.8%, 26.6%, 26.2%, and 41.9%, respectively. In the multivariate logistic regression analysis, LVEF of < 25% (OR, 2.75; 95% CI, 1.82-4.17; P < .001) and LVEF of ≥ 70% (OR, 1.70; 95% CI, 1.09-1.88; P = .010) were associated independently with significantly higher in-hospital mortality compared with the reference LVEF category of 55% to 70%.
The association of LVEF to in-hospital mortality in sepsis and septic shock was U-shaped. Both severe LV systolic dysfunction (LVEF < 25%) and hyperdynamic LVEF (LVEF ≥ 70%) were associated independently with significantly higher in-hospital mortality.
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Citation Excerpt :
Recommended sepsis management includes volume resuscitation and vasopressor administration for septic shock. Some studies have found that there is no difference in mortality with the delivery of 30 mLs/kg of fluid in septic patients with heart failure.12,13 Others recommend that protocolized and individualized management may decrease mortality, reduce the length of stay, and improve ventilator outcomes.12,14
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For subgroup analysis comparing type of FO (kidney disease only vs. mixed types of FO), studies among patients with chronic kidney disease (CKD) [26] and ESRD [24,25] reported a non-significant risk of mortality favoring aggressive fluid therapy (OR 0.96, 95% CI 0.55–1.67, P = 0.89, I2 = 0). There was no difference of mortality odds ratio when studies with matching versus unmatched patients were compared (Table 2), although studies with matching patients [24,27] reported an I2 value of 0. The unadjusted rate of invasive mechanical ventilation during hospitalization for the non-aggressive fluid resuscitation group was 4% (221/5209), compared with 12% (60/492) among the aggressive fluid group.
The outcomes of large-volume IVF administration to septic shock patients with comorbid congestive heart failure (CHF) and/or end-stage renal disease (ESRD) are uncertain and widely debated in the existing literature. Despite this uncertainty, CMS continues to recommend that 30 ml/kg of an intravenous crystalloid solution be administered to patients in septic shock starting within 3 h of presentation. We performed a systematic review and meta-analysis to assess the relationship between adherence to this guideline and outcomes among patients whose underlying comorbidities present a risk of fluid overload.
Our search was conducted on PubMed and Scopus through November 5, 2021 to identify studies that evaluated clinical outcomes among septic patients with CHF/ESRD based on volume of fluid administered. The primary outcome measured was mortality at 30 days post-hospital discharge. Other outcomes included the rates of vasopressor requirements, invasive mechanical ventilation during hospitalization, as well as length of stay in the intensive care unit and/or hospital. We used random effects meta-analysis when two or more studies reported the same outcome.
We included five studies in the final meta-analysis, which comprised 5804 patients, 5260 (91%) of whom received non-aggressive fluid resuscitation, as defined by the studies' authors. Random-effects meta-analysis for all-cause mortality showed that aggressive fluid resuscitation was associated with statistically non-significant increased odds of mortality (OR 1.42, 95% CI 0.88–2.3, P = 0.15, I² = 35%). There was no statistical association between volume of IVF administration and other outcomes evaluated.
Among septic shock patients with CHF and/or ESRD, administration of greater than or equal to 30 ml/kg IVF was associated with a non-significant increase in odds of mortality. All other outcomes measured were found to be non-significant, although there was a trend toward better outcomes among patients in the restricted-volume compared to the standard-volume IVF groups. Since this meta-analysis only included five observational studies, more studies are needed to guide an optimal volume and rate of fluid administration in this patient population.

View all citing articles on Scopus

: FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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Chest

Critical Care: Original ResearchAssociation Between Volume of Fluid Resuscitation and Intubation in High-Risk Patients With Sepsis, Heart Failure, End-Stage Renal Disease, and Cirrhosis

Background

Methods

Results

Conclusions

Section snippets

Study Design

Study Population

Discussion

Conclusions

Acknowledgments

J Crit Care

Ann Emerg Med

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

JAMA

Early goal-directed therapy in the treatment of severe sepsis and septic shock

N Engl J Med

Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock. 2016

Crit Care Med

The intensive care medicine research agenda on septic shock

Intensive Care Med

The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study)

Intensive Care Med

Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014

JAMA

Type I error rates, coverage of confidence intervals, and variance estimation in propensity-score matched analyses

Int J Biostat

Critical Care: Original Research
Association Between Volume of Fluid Resuscitation and Intubation in High-Risk Patients With Sepsis, Heart Failure, End-Stage Renal Disease, and Cirrhosis