Manipulating the Microcirculation in Sepsis – the Impact of Vasoactive Medications on Microcirculatory Blood Flow. A Systematic Review

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Abstract

Background:

Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. Disturbed microvascular blood flow is associated with excess mortality and is a potential future target for interventions. This review addresses the evidence for pharmacological manipulation of the microcirculation in sepsis assessed by techniques that evaluate the sublingual microvasculature.

Methods:

Systematic review using a published protocol. Eligibility criteria were studies of septic patients published from Jan 2000 – February 2018. Interventions were drugs aimed at improving perfusion. Outcome was improvement in microvascular flow using OPS, SDF or IDF imaging (GRADE criteria used).

Results:

2606 articles were screened and 22 included. (6 RCTs, 12 Interventional, 3 Observational, 1 Pilot, n = 572 participants). Multiple measurement techniques were described, including: automated analyses, subjective and composite scoring systems. Norepinepherine was not found to improve microvascular flow (low grade evidence, n = 6 studies); except in chronic hypertension (low, n = 1 study). Addition of arginine vasopressin or terlipressin to norepinepherine maintained flow whilst decreasing norepinepherine requirements (high, n = 2 studies). Neither dobutamine nor glyceryl trinitrate (GTN) consistently improved flow (low, n = 6 studies). A single study (n = 40 participants) demonstrated improved flow with levosimendan (high). In a risk of bias assessment 16/16 interventional, pilot and observational studies were found to be high risk.

Conclusions:

There is no robust evidence to date that any one agent can reproducibly lead to improved microvascular flow. Furthermore, no study demonstrated outcome benefit of one therapeutic agent over another. Updated consensus guidelines could improve comparable reporting of measurements and reduce bias, to enable meaningful comparisons around the effects of individual pharmacological agents.

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