Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock

St Paul's Hospital, iCAPTURE Centre, Canada.
Critical care medicine (Impact Factor: 6.15). 04/2009; 37(3):811-8. DOI: 10.1097/CCM.0b013e3181961ace
Source: PubMed

ABSTRACT Vasopressin and corticosteroids are often added to support cardiovascular dysfunction in patients who have septic shock that is nonresponsive to fluid resuscitation and norepinephrine infusion. However, it is unknown whether vasopressin treatment interacts with corticosteroid treatment.
Post hoc substudy of a multicenter randomized blinded controlled trial of vasopressin vs. norepinephrine in septic shock.
Twenty-seven Intensive Care Units in Canada, Australia, and the United States.
: Seven hundred and seventy-nine patients who had septic shock and were ongoing hypotension requiring at least 5 microg/min of norepinephrine infusion for 6 hours.
Patients were randomized to blinded vasopressin (0.01-0.03 units/min) or norepinephrine (5-15 microg/min) infusion added to open-label vasopressors. Corticosteroids were given according to clinical judgment at any time in the 28-day postrandomization period.
The primary end point was 28-day mortality. We tested for interaction between vasopressin treatment and corticosteroid treatment using logistic regression. Secondary end points were organ dysfunction, use of open-label vasopressors and vasopressin levels.
There was a statistically significant interaction between vasopressin infusion and corticosteroid treatment (p = 0.008). In patients who had septic shock and were also treated with corticosteroids, vasopressin, compared to norepinephrine, was associated with significantly decreased mortality (35.9% vs. 44.7%, respectively, p = 0.03). In contrast, in patients who did not receive corticosteroids, vasopressin was associated with increased mortality compared with norepinephrine (33.7% vs. 21.3%, respectively, p = 0.06). In patients who received vasopressin infusion, use of corticosteroids significantly increased plasma vasopressin levels by 33% at 6 hours (p = 0.006) to 67% at 24 hours (p = 0.025) compared with patients who did not receive corticosteroids.
There is a statistically significant interaction between vasopressin and corticosteroids. The combination of low-dose vasopressin and corticosteroids was associated with decreased mortality and organ dysfunction compared with norepinephrine and corticosteroids.

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    ABSTRACT: The effect of norepinephrine in patients with septic shock remains controversial. We conducted a meta-analysis to compare the mortality rates and benefits of norepinephrine and vasopressin. PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I (2) statistic, we used a fixed effects model (P ≥ 0.1) and expressed the results as risk ratios (RRs) for dichotomous outcomes or as standardized mean differences (SMDs) for continuous data with 95% confidence intervals (CIs). Meta-analysis was conducted using Review Manager 5.1 software. Seven trials (n = 2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2% (840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin (RR 1.07; 95%CI 0.97-1.20; P = 0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate (HR) (SMD 0.21; 95%CI -0.08-0.50; P = 0.15), mean arterial pressure (MAP) (SMD 0.15; 95%CI -0.15-0.44; P = 0.33), cardiac index (CI) (SMD -0.10; 95%CI -0.64-0.44; P = 0.73), systemic vascular resistance index (SVRI) (SMD 0.15; 95%CI -0.39-0.70; P = 0.58), oxygen delivery (DO2) (SMD -0.06; 95%CI -0.62-0.49; P = 0.82), oxygen consumption (VO2) (SMD 0.03; 95%CI -0.52-0.59; P = 0.91) or lactic acid (SMD 0.07; 95%CI -0.23-0.36; P = 0.66). No significant heterogeneity was found in these comparisons (P ≥ 0.1). There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.
    05/2014; 1(1):6. DOI:10.1186/2054-9369-1-6
  • Critical Care Medicine 08/2014; 42(8):1944-1945. DOI:10.1097/CCM.0000000000000372 · 6.15 Impact Factor
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    ABSTRACT: This is a guideline for the management of sepsis, developed by the Sepsis Registry Committee of The Japanese Society of Intensive Care Medicine (JSICM) launched in March 2007. This guideline was developed on the basis of evidence-based medicine and focuses on unique treatments in Japan that have not been included in the Surviving Sepsis Campaign guidelines (SSCG), as well as treatments that are viewed differently in Japan and in Western countries. Although the methods in this guideline conform to the 2008 SSCG, the Japanese literature and the results of the Sepsis Registry Survey, which was performed twice by the Sepsis Registry Committee in intensive care units (ICUs) registered with JSICM, are also referred. This is the first and original guideline for sepsis in Japan and is expected to be properly used in daily clinical practice. This article is translated from Japanese, originally published as "The Japanese Guidelines for the Management of Sepsis" in the Journal of the Japanese Society of Intensive Care Medicine (J Jpn Soc Intensive Care Med), 2013; 20:124-73. The original work is at

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