Vasopressor Discontinuation Order in the Recovery Phase of Septic Shock: A Systematic Review and Meta-Analysis

@#BACKGROUND: Septic shock causes life threatening organ dysfunction needing vasopressor despite adequate fluid resuscitation. Numerous studies and meta-analysis have proven norepinephrine as the initial vasopressor of choice in septic shock with vasopressin as add-on. Although guidelines have established the goal monitoring response in septic shock, optimal approach in discontinuation of the vasopressors in the recovery phase of septic shock remains limited. METHODS: A systematic review and meta-analysis was performed on randomized controlled trials (RCTs) and nonrandomized studies comparing incidence of hypotension within 24 hours of discontinuing norepinephrine first versus vasopressin. Three reviewers independently selected studies, assessed their quality, and extracted the following data: the number and characteristics of patients enrolled, inclusion and exclusion criteria for each study, the description of interventions (discontinuing norepinephrine first versus discontinuing vasopressin first) and outcomes (incidence of hypotension within 24 hours). RESULTS: Seven retrospective cohort studies and one prospective randomized control trial were included. Compared with norepinephrine, risk of hypotension is higher when vasopressin is discontinued first among patients in the recovery phase of septic shock (RR 2.06; 95% CI [1.11,3.82]; I 2 91%). Results were consistent in the subgroup analysis after excluding abstract-only and poor-quality studies (RR 1.73; 95% CI [0.74, 4.03]; I 2 93%). There is no difference in ICU (RR 0.97; 95% CI [0.71, 1.32]; I 2 38%) and in-hospital mortality (RR 0.88; 95% CI [0.66, 1.16]; I 2 41%) between the two vasopressor weaning strategies. Finally ICU length of stay was reported on 5 studies with no significant difference between the two strategies. CONCLUSION: Based on the results, there is increased risk of hypotension when vasopressin is discontinued first versus norepinephrine.

Blood pressure-lowering efficacy of Spironolactone in patients with Resistant Hypertension: A meta-analysis

Introduction@#Resistant hypertension (RH) is defined as a blood pressure (BP) reading that remains above goal despite concurrent use of three optimally dosed antihypertensives of different classes, including a diuretic. Spironolactone, a mineralocorticoid receptor antagonist, has shown significant benefit in reduction of BP in recent trials and is used empirically as an add-on therapy for RH. The researchers’ objective is to evaluate the BP-lowering efficacy of spironolactone in patients with resistant hypertension.@*Methods@#A meta-analysis was performed on randomized controlled trials (RCTs) comparing office or home BP reduction using spironolactone with placebo or an alternative drug regimen on top of standard-triple drug therapy among patients with RH. The study was conducted in reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).@*Results@#Five RCTs were included comprising a total of 662 patients. Three of these studies were found to have low risk of bias while two had unclear risk of bias. Compared to placebo, the addition of spironolactone significantly decreased office systolic BP (weighted mean difference [WMD]= -16.33, 95% confidence interval [CI]=-24.68 to -7.97, P=0.0001) and office diastolic BP (WMD=-6.12, 95% CI= -9.35 to -2.89, P=0.0002). Compared to an alternative drug regimen, additional spironolactone resulted in a significantly greater reduction in office systolic BP (WMD=-4.58mmHg, 95% CI=-7.19, -1.97, P= 0.0006) and home systolic BP (WMD= -4.33, 95% CI= 5.55, -3.12, P< 0.00001); while the addition of spironolactone had no significant difference compared to an alternative drug regimen in reducing office diastolic BP (WMD=-3.35, 95% CI=-12.08 to +5.38, P=0.45) and home diastolic BP (WMD= 0.00, 95 % CI=-0.73 to 0.73, P=1.0).@*Conclusion@#Spironolactone, when added to triple-drug anti-hypertensive therapy, showed significant reduction of systolic office and home BP. It should be considered as the add-on medication of choice for BP reduction in patients with RH.