Fluid Resuscitation in Septic Shock

A Positive Fluid Balance and Elevated Central Venous Pressure Are Associated With Increased Mortality

John H. Boyd, MD, FRCP(C); Jason Forbes, MD; Taka-aki Nakada, MD, PhD; Keith R. Walley, MD, FRCP(C); James A. Russell, MD, FRCP(C)

Disclosures

Crit Care Med. 2011;39(2):259-65. 

In This Article

Abstract and Introduction

Abstract

Objective: To determine whether central venous pressure and fluid balance after resuscitation for septic shock are associated with mortality.
Design: We conducted a retrospective review of the use of intravenous fluids during the first 4 days of care.
Setting: Multicenter randomized controlled trial.
Patients: The Vasopressin in Septic Shock Trial (VASST) study enrolled 778 patients who had septic shock and who were receiving a minimum of 5 μg of norepinephrine per minute.
Interventions: None.
Measurements and Main Results: Based on net fluid balance, we determined whether one's fluid balance quartile was correlated with 28-day mortality. We also analyzed whether fluid balance was predictive of central venous pressure and furthermore whether a guideline-recommended central venous pressure of 8–12 mm Hg yielded a mortality advantage. At enrollment, which occurred on average 12 hrs after presentation, the average fluid balance was +4.2 L. By day 4, the cumulative average fluid balance was +11 L. After correcting for age and Acute Physiology and Chronic Health Evaluation II score, a more positive fluid balance at both at 12 hrs and day 4 correlated significantly with increased mortality. Central venous pressure was correlated with fluid balance at 12 hrs, whereas on days 1–4, there was no significant correlation. At 12 hrs, patients with central venous pressure <8 mm Hg had the lowest mortality rate followed by those with central venous pressure 8–12 mm Hg. The highest mortality rate was observed in those with central venous pressure >12 mm Hg. Contrary to the overall effect, patients whose central venous pressure was <8 mm Hg had improved survival with a more positive fluid balance.
Conclusions: A more positive fluid balance both early in resuscitation and cumulatively over 4 days is associated with an increased risk of mortality in septic shock. Central venous pressure may be used to gauge fluid balance ≤12 hrs into septic shock but becomes an unreliable marker of fluid balance thereafter. Optimal survival in the VASST study occurred with a positive fluid balance of approximately 3 L at 12 hrs.

Introduction

Septic shock is an extremely complex disorder whose deranged physiology results from the interplay among the initial infection, the host response, and subsequent medical interventions. Despite exciting new discoveries characterizing molecular events during septic shock,[1–3] some basic treatments remain understudied. Intravenous fluids, along with antibiotics, source control, vasopressors, inotropic agents, and mechanical ventilation, are a key component in the early management of septic shock.[4] Surprisingly, despite current mortality rates of approximately 40%,[5–8] dosing intravenous fluid during resuscitation of septic shock remains largely empirical. Too little fluid may result in tissue hypoperfusion and worsen organ dysfunction;[4] however, overprescription of fluid appears to carry its own risks. In a recent European survey of critically ill patients with sepsis, a positive fluid balance was associated with increased mortality,[9] whereas positive fluid balance increased time spent on mechanical ventilation and resulted in a trend toward increased mortality in a large randomized study of patients with acute lung injury.[10] The 2008 Surviving Sepsis guidelines suggest the infusion of intravenous fluids until achieving a central venous pressure of 8–12 mm Hg and raise this target to 12–15 mm Hg in the presence of impaired ventricular filling/mechanical ventilation[4] However, there are no recommendations as to when it is appropriate discontinue or reduce the rate of administration of intravenous fluids.

Given the uncertainty surrounding fluid therapy for patients with septic shock, we conducted a retrospective review of 778 patients from the VAsopressin in Septic Shock Trial (VASST). All patients had septic shock and were receiving a minimum of 5 μg norepinephrine per minute. Correcting for age and severity of illness, we analyzed whether a positive fluid balance in the first 12 hrs of resuscitation and during the next 4 days was associated with an increase in 28-day mortality. Most clinicians assign some weight to a patient's central venous pressure when deciding whether to administer fluids; therefore, we went on to determine whether central venous pressure was correlated with fluid balance at 12 hrs and during the subsequent 4 days. After correcting for age and severity of illness, we stratified patients into central venous pressure groups. Using the Surviving Sepsis guidelines, we grouped patients into those who fell into the recommended range (central venous pressure 8–12 mm Hg), those with a central venous pressure <8 mm Hg, and those with a central venous pressure >12 mm Hg and analyzed whether those with a central venous pressure of 8–12 mm Hg had a survival advantage.

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