Beta test

I love it when a controversy pops up in the intensive care literature.  Especially when it doesn’t involve steroids.  My favourite paper of last year was definitely FEAST because I think it took a topic that we thought we knew so much about and turned it on it’s head.  There’s a few months left in 2012 but a big contender for my favourite paper of this year would have to be this little gem from Macchia et al in Italy.  They performed a large retrospective analysis of 9465 patients admitted to ICU with sepsis in 22 regions of Italy over a 5 year period between 2003 and 2008.  They found that 1061 patients had been taking beta blockers before their ICU admission and 8404 patients had not.

Surprisingly, despite their overall poorer baseline status, those who were taking beta blockers prior to ICU admission had a 28 day mortality rate 20% less than those who weren’t!  Overall 28 day mortality was 17.7% in the beta-blocker group and 22.1% in the control group.  So an absolute risk reduction of 4.4% and a relative risk reduction of 19%.  This gives an NNT of 23 patients to save one life with beta blockers.

Now obviously this was a retrospective analysis with all of the inherent risks and biases, but there is a plausible physiological mechanism underlying the observed effect.  Animal data has shown for some years that administering beta blockers to rats and pigs with septic shock induced myocardial dysfunction results in improved survival and, somewhat counter-intuitively seems to reduce myocardial dysfunction.  There are various theories as to why this may be, but the one that seems predominant is that there is an adrenergic storm associated with septic shock, resulting in increased cardiac workload at a time of limited oxygen supply.  This results in the myocardial dysfunction seen in 60% of patients with septic shock.  It is thought that beta blockers prevent this catecholamine storm from having a detrimental effect on the heart.

It’s food for thought anyway, and there’s a small trial underway at the moment that’s randomising patients with septic shock to either esmolol or placebo.  But they’re only recruiting 100 patients and many more will be required to give us the answer.  This sounds like a job for ANZICS….

1. Crit Care Med. 2012 Oct;40(10):2768-72.

Previous prescription of β-blockers is associated with reduced mortality among
patients hospitalized in intensive care units for sepsis*.

Macchia A, Romero M, Comignani PD, Mariani J, D'Ettorre A, Prini N, Santopinto M,
Tognoni G.

From the Laboratory of Pharmacoepidemiology (MA, RM, D'EA, TG), Consorzio Mario
Negri Sud, Santa Maria Imbaro (CH), Italy; Fundación GESICA (MA, MJ), Buenos
Aires, Argentina; and Critical Care Unit (MA, CPD, PN, SM), Hospital Alemán,
Buenos Aires, Argentina.

OBJECTIVES: : Results from basic science and narrative reviews suggest a
potential role of β-blockers in patients with sepsis. Although the hypothesis is 
physiologically appealing, it could be seen as clinically counterintuitive. We
sought to assess whether patients previously prescribed chronic β-blocker therapy
had a different mortality rate than those who did not receive treatment.
SETTING: : Record linkage of administrative databases of Italian patients
hospitalized for sepsis during years 2003-2008 were identified and followed up
for all-cause mortality at 28 days.
INTERVENTIONS: : None.
MEASUREMENTS AND MAIN RESULTS: : We identified 9,465 patients aged ≥40 yrs who
were hospitalized in critical care units for sepsis. Of these, 1,061 patients
were on chronic prescription with β-blockers and 8404 were not previously
treated. Despite a higher risk profile, patients previously prescribed with
β-blockers had lower mortality at 28 days (188/1061 [17.7%]) than those
previously untreated (1857/8404 [22.1%]) (odds ratio 0.78; 95% confidence
interval 0.66-0.93; p = .005 for unadjusted analysis, and odds ratio 0.81; 95%
confidence interval 0.68-0.97; p = .025 for adjusted analyses). Sensitivity and
pair-matched results confirm the primary findings.
CONCLUSIONS: : As far as we are aware, this pharmacoepidemiologic assessment is
the largest to examine the potential association of previous β-blocker
prescription and mortality in patients with sepsis. Chronic prescription of
β-blockers may confer a survival advantage to patients who subsequently develop
sepsis with organ dysfunction and who are admitted to an intensive care unit.
Prospective randomized clinical trials should formally test this hypothesis.

PMID: 22824934  [PubMed - in process]

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