Refractory septic shock and alternative wordings: A systematic review of literature

Background: We reviewed the different studies using the terms "refractory septic shock" and/or "catecholamine resistance" and/or "high dose norepinephrine" so as to highlight the heterogeneity of the definitions used by authors addressing such concepts.

Method: A systematic review was conducted assessing the papers reporting data on refractory septic shock. We used keywords as exact phrases and subject headings according to database syntax.

Results: Of 276 papers initially reviewed, we included 8 studies - 3 randomized controlled trials, 3 prospective studies and 2 retrospective studies, representing a total of 562 patients with septic shock. Catecholamine resistance was generally defined as "a decreased vascular responsiveness to catecholamine independently of the administered norepinephrine dose". Refractory septic shock was broadly defined as "a clinical condition characterized by persistent hyperdynamic shock even though adequate fluid resuscitation (individualized doses) and high doses of norepinephrine (≥ 1 μg/kg/min)". Reported "high doses" of norepinephrine were often ≥1 μg/kg/min. However, wide variability was found throughout the literature on the use of these terms.

Discussion: Marked inconsistencies were identified in the usage of the terms for refractory septic shock. There is a pressing need to determine consensus definitions so as to establish a common language in the medical literature and to harmonize future studies.