Effects of Norepinephrine and Vasopressin Discontinuation Order in the Recovery Phase of Septic Shock: A Systematic Review and Individual Patient Data Meta-Analysis.

OBJECTIVE: The impact of vasopressin and norepinephrine discontinuation order in the recovery phase of septic shock remains controversial. This systematic review and patient-level meta-analysis were performed to determine the impact of vasopressin and norepinephrine discontinuation order on clinically significant outcomes in the recovery phase of septic shock. METHODS: Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, and ClinicalTrials.gov were searched from inception through November 2018 for studies comparing outcomes after the discontinuation of vasopressin or norepinephrine in septic shock. Individual patient-level data were obtained from included studies and combined using a two-stage meta-analysis. RESULTS: Six studies of low or moderate risk of bias with 957 patients were included. Clinically significant hypotension occurred more frequently when vasopressin was discontinued first compared to norepinephrine (60.7% versus 43.3%, respectively). First discontinuation of norepinephrine compared to vasopressin had lower pooled odds of developing clinically significant hypotension (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.68, I2 87%). No differences were detected in short-term mortality (OR 1.12, 95% CI 0.67-1.86, I2 45%), intensive care unit length of stay (mean difference 0.15 day, 95% CI -1.58 to 1.88, I2 21%), or hospital length of stay (mean difference 1.65 days, 95% CI -0.47 to 3.76, I2 0%). CONCLUSIONS: Discontinuation of norepinephrine prior to vasopressin during the recovery phase of septic shock resulted in less clinically significant hypotension but no difference in mortality or lengths of stay. Larger, prospective studies evaluating the impact of relative vasopressin deficiency and norepinephrine and vasopressin discontinuation order and timing on patient-centered outcomes are needed.

Evaluating Vasopressor Discontinuation Strategies in Patients With Septic Shock on Concomitant Norepinephrine and Vasopressin Infusions.

BACKGROUND: There is little data guiding clinicians on how to discontinue vasopressors among septic shock patients on concomitant norepinephrine (NE) and vasopressin (VP). OBJECTIVE: To determine the incidence of hypotension within 24 hours of discontinuing NE (NE DC first) versus VP (VP DC first) first in septic shock patients. METHODS: This retrospective study evaluated septic shock patients admitted to the medical intensive care unit (MICU) and surgical ICU (SICU) receiving concomitant NE and VP. Receipt of additional vasopressors, mixed shock states, expired or care withdrawn, and NE and VP discontinued simultaneously were exclusion criteria. The primary outcome was incidence of hypotension within 24 hours of first vasopressor discontinuation. Secondary outcomes included time to hypotension, hospital length of stay (LOS), ICU LOS, and ICU mortality. RESULTS: A total of 80 patients were included (NE DC first [n = 35]; VP DC first [n = 45]), with a median age of 73 years and median modified Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores of 21 and 7, respectively. More patients in the NE DC first group were in the SICU (42.9% vs 20.0%; P = 0.048) with more intra-abdominal infections (40.0% vs 15.6%; P = 0.021) and fewer appropriate empirical antibiotics (62.9% vs 86.7%; P = 0.018). Hypotension within 24 hours of first agent discontinuation was higher in the VP DC first group (28.6% vs 62.2%; P = 0.004), with similar hospital LOS and ICU mortality. Multivariate analysis identified VP DC first as an independent predictor of hypotension (odds ratio = 7.2; CI = 2.3-22.7). CONCLUSION: Among septic shock patients on concomitant NE and VP, discontinuation of VP first was associated with an increased incidence of hypotension; future prospective control trials are warranted.