The next few posts will review those studies which have studied various strategies for fluid resuscitation in patients with sepsis. The first paper is the recent study by Andrews and colleagues performed in Zambia.

OBJECTIVE: To determine whether an early resuscitation protocol with administration of intravenous fluids, vasopressors, and blood transfusion decreases mortality among Zambian adults with sepsis and hypotension compared with usual care.

DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 212 adults with sepsis (suspected infection plus 2:2 systemic inflammatory response syndrome criteria) and hypotension (systolic blood pressure <90 mm Hg or mean arterial pressure <65 mm Hg) presenting to the emergency department at a 1500-bed referral hospital in Zambia between October 22, 2012, and November 11, 2013. Data collection concluded December 9, 2013.

INTERVENTIONS: Patients were randomized 1:1 to either (1) an early resuscitation protocol for sepsis (n = 107) that included intravenous fluid bolus administration with monitoring of jugular venous pressure, respiratory rate, and arterial oxygen saturation and treatment with vasopressors targeting mean arterial pressure (2:65 mm Hg) and blood transfusion (for patients with a hemoglobin level <7 g/dL) or (2) usual care (n = 105) in which treating clinicians determined hemodynamic management.

MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality and the secondary outcomes included the volume of intravenous fluid received and receipt of vasopressors.

RESULTS: Among 212 patients randomized to receive either the sepsis protocol or usual care, 3 were ineligible and the remaining 209 completed the study and were included in the analysis (mean [SD] age, 36.7 [12.4] years; 117 men [56.0%]; 187 [89.5%] positive for the human immunodeficiency virus). The primary outcome of in-hospital mortality occurred in 51 of 106 patients (48.1%) in the sepsis protocol group compared with 34 of 103 patients (33.0%) in the usual care group (between-group difference, 15.1% [95% CI, 2.0%-28.3%]; relative risk, 1.46 [95% CI, 1.04-2.05]; P = .03). In the 6 hours after presentation to the emergency department, patients in the sepsis protocol group received a median of 3.5 L (interquartile range, 2.7-4.0 L) of intravenous fluid compared with 2.0 L (interquartile range, 1.0-2.5 L) in the usual care group (mean difference, 1.2 L [95% CI, 1.0-1.5 L]; P < .001). Fifteen patients (14.2%) in the sepsis protocol group and 2 patients (1.9%) in the usual care group received vasopressors (between-group difference, 12.3% [95% CI, 5.1%-19.4%]; P < .001).

CONCLUSIONS AND RELEVANCE: Among adults with sepsis and hypotension, most of whom were positive for HIV, in a resource-limited setting, a protocol for early resuscitation with administration of intravenous fluids and vasopressors increased in-hospital mortality compared with usual care. Further studies are needed to understand the effects of administration of intravenous fluid boluses and vasopressors in patients with sepsis across different low- and middle-income clinical settings and patient populations.

COMMENTARY:

This study clearly demonstrates that an aggressive approach to fluid administration, mirroring the recommendations of the Surviving Sepsis Campaign, increases the risk of death in patients with SEPTIC SHOCK. The protocol patients received a 2L bolus within 1 hour of enrollment, followed by an additional 2 liters over the subsequent 4 hours. This strategy is remarkably similar to those of the Surviving Sepsis Campaign, namely “1) We recommend that, in the resuscitation from sepsis-induced hypoperfusion, at least 30 mL/kg (2L in 70kg patient) of IV crystalloid fluid be given within the first 3 hour. 2) We further recommend that, following initial fluid resuscitation, additional fluids be guided by frequent reassessment of hemodynamic status.”

Septic shock is a consequence of profound vasodilatation. Fluids (in themselves) cannot reverse vasodilatory shock, and indeed in the setting of sepsis fluid boluses may cause further vasodilatation. Attempts at restoring blood pressure in septic shock with aggressive fluid administration reflects a complete lack of understanding of human physiology and is reckless behavior. Furthermore, the hemodynamic benefit of those who actually respond to fluids (only 50% of patients) is short lived, being about 30 minutes at best and 10 minutes at worst with a minimal increase in blood pressure and no evidence that it increases urine output. The net effect is the rapid transfer of fluid from the IV bag into the tissues.

The religious followers of the Surviving Sepsis Campaign Guidelines (2004, 2008, 20012 and 2016) will argue that the patients in the current study are not typical of sepsis patients around the world. This is not correct. The pathophysiology of sepsis is similar whether the patient is in Africa or in Europe… vasodilatory shock is vasodilatory shock and this condition is not a fluid responsive condition. Furthermore, they may argue that the Surviving Sepsis Guidelines are not recommended for patients in resource-poor settings. This is however again completely wrong. Dr JL Vincent has publically stated that “these guidelines are not for you (meaning me), these guidelines are not for me (JLV), No My Friends, they are for the non-expert clinician (in resource poor settings). Dr Machado (the co-author of the accompanying editorial) has vigorously endorsed the use of the Surviving Sepsis Campaign in resource limited settings. However, the evidence is clear: a protocol of aggressive fluid administration kills septic patients by “salt water drowning”.