Effects of the discontinuation sequence of norepinephrine and vasopressin on hypotension incidence in patients with septic shock: A meta-analysis✰
Introduction
Vasodilatory shock is a common pathology among critically ill patients. The Surviving Sepsis Guidelines recommend the use of norepinephrine as the first-choice vasopressor.1 Despite their efficacy, high doses of norepinephrine are associated with increased mortality.2, 3 This finding highlights the need for refining treatment strategies for patients with refractory shock.
The use of vasopressin as a supplementary vasopressor is an interesting option. Vasopressin is a potent vasopressor that acts on vasopressinergic receptors4 and functions as an endogenous hormone that is involved in neuroendocrine imbalance associated with septic shock.5 Experimental data indicate that treatment with a combination of vasopressin and norepinephrine exerts synergistic effects on the restoration of vascular tone in patients with vasodilatory septic shock.6 Although the role of vasopressin in managing septic shock is controversial, results of subgroup analyses of randomized trials and meta-analyses suggest that the use of vasopressin is associated with improved outcomes.7 The Surviving Sepsis Guidelines suggest the addition of vasopressin (up to 0.03 U/min) to norepinephrine to increase mean arterial pressure (MAP) to a minimal initial target level of 65 mmHg or to decrease norepinephrine dosage.1
However, limited information is available on vasopressor weaning. Moreover, the protocol for norepinephrine interruption has not been reported in guidelines. The use of dynamic elastance has made it possible to predict hypotension incidence during norepinephrine weaning.10, 11 Treatment weaning is challenging in patients receiving both norepinephrine and vasopressin. To our knowledge, no clear data are available on norepinephrine and vasopressin weaning in patients treated with a combination of these vasopressors.
We hypothesized that norepinephrine should be weaned only after weaning vasopressin because of the possible cardiac effect of norepinephrine. Therefore, we performed a meta-analysis to identify the discontinuation sequence of norepinephrine and vasopressin in patients with septic shock by using available data.
Section snippets
Methods
This meta-analysis was designed according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.8 Study methods and analysis plan were pre-published in the international Prospective Register of Systematic Reviews (PROSPERO) database under the number CRD42018110903.
Search results and study characteristics
Study flow diagram is presented in Fig. 1. This meta-analysis included nine original articles out of 650 screened publications that were retrieved by performing the literature search.16, 17, 18, 19, 20, 21, 22, 23, 24 Of the nine included studies, three were abstracts that reported the results of retrospective analyses and six were full-text articles, including five retrospective studies and one randomized clinical trial. One study reported a protocol for vasopressor weaning. In each study, the
Discussion
The results of our meta-analysis suggest that the risk of rebound hypotension increases in patients with septic shock in whom vasopressin is weaned before norepinephrine. This finding suggests that a weaning strategy involving the discontinuation of norepinephrine before that of vasopressin could provide an optimum outcome among patients with septic shock receiving the combination of these vasopressors. The strength of our study lies in is its large sample size. In addition, a consistent result
Conclusions
The results of our meta-analysis suggest that the risk of rebound hypotension increases in patients with septic shock or severe sepsis in whom vasopressin is tapered before norepinephrine. However, additional studies should be performed to determine the impact of these observations on the recovery of organ dysfunction in and survival of these patients.
Declarations
Ethics approval and consent to participate: not applicable.
Consent for publication: not applicable.
Availability of data and materials all the data generated or analyzed during this study are included in this published article (and its supplementary information files).
Competing interest: ML received lecture fees from MSD, Pfizer, LFB, Amomed, Baxter, and Aguettant
Funding: No funding was received for the design of the study, the collection, analysis or interpretation of the data or for writing
Author's contribution
Conception and Design: G.D., K.B. and M.L.
Provision of study materials: M.D. and M.L.
Data analysis and interpretation: K.B., G.D., L.Z. and M.L.
Manuscript writing and final approval: all authors.
Acknowledgments
Not applicable.
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Registration: This review was pre-published in the international Prospective Register of Systematic Reviews (PROSPERO) database (CRD42018110903).