KDIGO Clinical Practice Guideline for Acute Kidney Injury
Protocolized hemodynamic management strategies in septic shock

Protocolized hemodynamic management strategies in septic shock

Early fluid resuscitation in the management of hypotensive patients with septic shock has been a standard treatment paradigm for decades.^93,113,114 What has not been clear, however, is how much fluid to give, for how long, or what type of fluid therapy is optimal in the physiologic support of septic shock.^93,113,114 In 2001, Rivers et al.¹¹⁵ published the results of a small (n = 263), open-label, single-center study that compared a treatment protocol that the authors referred to as EGDT in the emergency management of septic shock. EGDT is predicated upon the premise that an early, protocolized resuscitation program with predefined physiologic end-points will prevent organ failure and improve the outcome of patients presenting with septic shock.

Hypotensive patients with severe infection are rapidly assessed for evidence of tissue hypoperfusion and microcirculatory dysfunction by mean arterial blood pressure measurement and plasma lactate levels.¹¹⁵ Blood lactate levels are neither sensitive nor specific but are readily available measures of tissue hypoperfusion and do correlate with adverse outcomes in sepsis.^116,117 Early recognition of septic shock then initiates a protocol of resuscitation with the goal of reestablishing tissue perfusion in patients within 6 hours of diagnosis. The physiologic goals are: i) return of mean arterial blood pressure to ≥ 65mm Hg; ii) central venous pressure between 8–12mm Hg; iii) improvement in blood lactate levels; iv) central venous oxygen saturation (ScvO₂) > 70%; and v) a urine output of ≥0.5 ml/kg/h.

In the study by Rivers et al. the protocol-driven process resulted in more rapid use of fluids, more blood transfusions, and in a small number of patients, earlier use of dobutamine over the 6-hour time period than standard emergency care. The in-hospital mortality rate in the control group was 46.5% vs. 30.5% in the EGDT group (P<0.01).¹¹⁵ Follow-up, predominantly observational studies, have found less dramatic but generally similar effects,^118-122 though not without exception.¹²³

The Rivers study did not specifically look at AKI outcomes, but multiple-organ function-scoring systems (i.e., APACHE II and SAPS 2) both showed significant improvements with EGDT. In a subsequent study, prevention of AKI was significantly improved in patients randomized to a modified EGDT strategy (without measurement of ScvO₂) compared to a standard-care group.¹¹⁹ Criticisms of the Rivers study include: i) a complex, multistep protocol for which individual interventions have not been validated; ii) the use of a treatment team in the active-therapy arm, thus risking a Hawthorn effect; iii) high mortality in the standardcare arm; and iv) the study was a small single-center study. Three large multicenter clinical trials in the USA, UK, and Australia are currently underway to definitively evaluate this promising therapy.