Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy. (Betters)

Beesley SJ, Wilson EL, Lanspa MJ, et al. Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy. Crit Care Med. 2017 Feb; 45(2) :225-233.

OBJECTIVES: Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate, < 80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock.

DESIGN: Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013.

SETTING: One large academic referral hospital and two community hospitals.

PATIENTS: Adult patients with septic shock requiring vasopressors.

INTERVENTION: None.

MEASUREMENTS: Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score.

RESULTS: We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p < 0.001). Relatively bradycardic patients were older (65 vs 60 yr; p < 0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p < 0.001).

CONCLUSIONS: Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.

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Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. (Williams)

Avni T, Lador A, Lev S, et al. Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. PLoS One. 2015 Aug 3; 10(8): e0129305.

OBJECTIVE: International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents inseptic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock.

METHODS: Systematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing differentvasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled.

RESULTS: Thirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels.

CONCLUSIONS: Evidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment ofseptic shock.

The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial. (Singh)

Gordon AC, Mason AJ, Perkins GD, Stotz M, Terblanche M, Ashby D, Brett SJ. The
interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial*. Crit Care Med. 2014 Jun;42(6):1325-33.

OBJECTIVES: Vasopressin and corticosteroids are both commonly used adjunctive therapies in septic shock. Retrospective analyses have suggested that there may be an interaction between these drugs, with higher circulating vasopressin levels and improved outcomes in patients treated with both vasopressin and corticosteroids. We aimed to test for an interaction between vasopressin and corticosteroids in septic shock.

DESIGN: Prospective open-label randomized controlled pilot trial.

SETTING: Four adult ICUs in London teaching hospitals.

PATIENTS: Sixty-one adult patients who had septic shock.

INTERVENTIONS: Initial vasopressin IV infusion titrated up to 0.06 U/min and then IV hydrocortisone (50 mg 6 hourly) or placebo. Plasma vasopressin levels were measured at 6-12 and 24-36 hours after hydrocortisone/placebo administration.

MEASUREMENTS AND MAIN RESULTS: Thirty-one patients were allocated to vasopressin + hydrocortisone and 30 patients to vasopressin + placebo. The hydrocortisone group required a shorter duration of vasopressin therapy (3.1 d; 95% CI, 1.1-5.1; shorter in hydrocortisone group) and required a lower total dose of vasopressin (ratio, 0.47; 95% CI, 0.32-0.71) compared with the placebo group. Plasma vasopressin levels were not higher in the hydrocortisone group compared with the placebo group (64 pmol/L difference at 6- to 12-hour time point; 95% CI, -32 to 160 pmol/L). Early vasopressin use was well tolerated with only one serious adverse event possibly related to study drug administration reported. There were no differences in mortality rates (23% 28-day mortality in both groups) or organ failure assessments between the two treatment groups.

CONCLUSIONS: Hydrocortisone spared vasopressin requirements, reduced duration, and reduced dose, when used together in the treatment of septic shock, but it did not alter plasma vasopressin levels. Further trials are needed to assess the clinical effectiveness of vasopressin as the initial vasopressor therapy with or without corticosteroids.

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