Effects of the discontinuation sequence of norepinephrine and vasopressin on hypotension incidence in patients with septic shock: A meta-analysis

Abstract

Background

Although the order of vasopressor initiation in patients with septic shock is established, limited information is available on the order of vasopressor discontinuation.

Methods

We performed a meta-analysis of nine studies involving 1245 patients in whom norepinephrine (n = 787) or vasopressin (n = 458) was withdrawn first to compare the risk of hypotension.

Results

The risk of hypotension increased in patients whom vasopressin was withdrawn first (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.3–8.9; p = 0.01). A sensitivity analysis indicated that this effect was observed in four studies with a high risk of bias (OR, 5.4; 95%CI, 1.3–23.5; p = 0.02) and was not observed in five studies with a low risk of bias (OR, 2.4; 95%CI, 0.6–8.4; p = 0.18).

Conclusion

Our results suggest that the risk of hypotension is higher in patients with septic shock in whom vasopressin is withdrawn before norepinephrine.

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.