Outpatient beta-blockers and survival from sepsis: Results from a national cohort of Medicare beneficiaries

Singer, Kathleen E.; Collins, Courtney; Flahive, Julie; Wyman, Allison; Aytürk, Mehmet; Santry, Heena P.

doi:10.1016/j.amjsurg.2017.06.007

Cited by 17 publications

(27 citation statements)

References 24 publications

(25 reference statements)

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“…The definitions of sepsis, severe sepsis, septic shock, and premorbid β-blocker exposure varied slightly across the studies, but were reasonable and comparable to current definitions [1]. Two studies [10, 27] included patients with sepsis, severe sepsis, and septic shock, while seven studies [11, 21–26] included patients with severe sepsis and/or septic shock. One study (Alsolamy et al) included patients ≥ 14 years of age; all other studies included adult (18 years and above) patients.…”

Section: Resultsmentioning

confidence: 99%

“…The study populations described patients with sepsis, severe sepsis, or septic shock in an ED [21] or ICU [10, 11, 21–26] setting. The definitions of sepsis, severe sepsis, septic shock, and premorbid β-blocker exposure varied slightly across the studies, but were reasonable and comparable to current definitions [1].…”

Section: Resultsmentioning

confidence: 99%

“…All observational studies of premorbid medication use are at risk of bias because of confounding. Five studies included in this review [10, 11, 24, 26, 27] were judged to be of moderate risk of bias for the primary outcome of mortality as they reported adjustment of confounding variables via statistical analysis. Four studies [21–23, 25] were judged as having serious risk of bias due to confounding as the authors did not perform statistical analysis to correct for confounders.…”

Section: Resultsmentioning

confidence: 99%

“…Early administration of the short-acting β-blocker esmolol in a recent trial showed a reduction in 28-day sepsis mortality [8, 9]. Furthermore, some studies have suggested a benefit of premorbid β-blocker exposure on sepsis outcomes [10, 11]. Multiple systematic reviews have since concluded that there is limited preliminary evidence for the use of β-blockers during sepsis [12–14], while others are skeptical [15].…”

Section: Introductionmentioning

confidence: 99%

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The association between premorbid beta blocker exposure and mortality in sepsis—a systematic review

et al. 2019

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Background The effect of premorbid β-blocker exposure on clinical outcomes in patients with sepsis is not well characterized. We aimed to examine the association between premorbid β-blocker exposure and mortality in sepsis. Methods EMBase, MEDLINE, and Cochrane databases were searched for all studies of premorbid β-blocker and sepsis. The search was last updated on 22 June 2019. Two reviewers independently assessed, selected, and abstracted data from studies reporting chronic β-blocker use prior to sepsis and mortality. Main data extracted were premorbid β-blocker exposure, mortality, study design, and patient data. Two reviewers independently assessed the risk of bias and quality of evidence. Results In total, nine studies comprising 56,414 patients with sepsis including 6576 patients with premorbid exposure to β-blockers were eligible. For the primary outcome of mortality, two retrospective studies reported adjusted odds ratios showing a reduction in mortality with premorbid β-blocker exposure. One study showed that premorbid β-blocker exposure decreases mortality in patients with septic shock. Another study showed that continued β-blockade during sepsis is associated with decreased mortality. Conclusion This systematic review suggests that β-blocker exposure prior to sepsis is associated with reduced mortality. There was insufficient data to conduct a bona fide meta-analysis. Whether the apparent reduction in mortality may be attributed to the mitigation of catecholamine excess is unclear. Trial registration PROSPERO, CRD42019130558 registered June 12, 2019. Electronic supplementary material The online version of this article (10.1186/s13054-019-2562-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The association between premorbid beta blocker exposure and mortality in sepsis—a systematic review

et al. 2019

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“…Informative reviews focused on heart injury and dysfunction in sepsis provide an instructive analysis of heart-based changes in sepsis [7][8][9][10]. Other advances, including the potential benefit of preadmission b-blockers in reducing sepsis mortality are shedding a new light on the role of adrenergic system in sepsis [11], while the analysis of metabolic systems strives to stratify sepsis survivors from non-survivors [12,13].…”

Section: Introductionmentioning

confidence: 99%

Heartfelt sepsis: microvascular injury due to genomic storm

Hawiger¹

2018

Kardiol Pol

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Sepsis is one of the ten leading causes of death in developed and developing countries. In the United States, sepsis mortality approaches that of acute myocardial infarction and exceeds deaths from stroke. Neonates and the elderly are the most vulner-able patients, with these groups suffering from the highest sepsis mortality. In both groups, many survivors respectively display serious developmental disabilities and cognitive decline. The National Institute of Health/National Heart, Lung, and Blood Institute Panel redefined sepsis as a "severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure." Microvas-cular endothelial injury in sepsis due to microbial inflammation encompasses small blood vessels (< 100 μm in diameter). While the lungs remain the principal organ of interest due to sepsis-associated acute respiratory distress syndrome, "septic heart" or "septic cardiomyopathy" accelerates sepsis' transition to potentially lethal septic shock. This review analyses both new advances in understanding the septic mechanism and possible resolutions of sepsis. The concept of a "genomic storm," caused by microbes triggering florid production of inflammatory mediators, is based on septic reprogramming of the human genome. This genomic storm leads to microvascular endothelial injury, persistent hypotension, and organ failure. While very early control of sepsis-causing bacterial, fungal and viral infections remains crucial for the treatment of sepsis, supportive measures are likewise necessary to maintain blood pressure, respiration, and kidney function. New evidence indicates that preadmission b-blockers may reduce sepsis-associated mortality. The fundamental role of nuclear signalling in the progres-sion and resolution of sepsis was established with a new class of cell-penetrating nuclear transport modifiers (NTMs). NTMs target the translocation of proinflammatory and metabolic transcription factors to the cell's nucleus while also enhancing bacterial clearance in experimental polymicrobial sepsis models. The result is a 700-fold reduction in the bacterial burden of the lungs and improvement of sepsis-associated thrombocytopaenia and blood markers of endothelial injury. When added to anti-microbial therapy, NTM has increased survival from 30% to 55%, when compared to antimicrobial therapy alone. Yet, the prevention of sepsis remains the most rational and beneficial path. Anti-pneumococcal vaccination has reduced the incidence of pneumonia and sepsis caused by increasingly antibiotic-resistant Streptococcus pneumoniae in all age groups. Similarly, the incidence of meningococcal sepsis known as "purpura fulminans" has been reduced by a recently approved vaccine thereby preventing hearing loss, neurologic damage, and limb amputations in young survivors of septic outbreaks. We urgently need further preventive, diagnostic, and therapeutic measures as the tide of sepsis rises in the ...

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Mitigating the stress response to improve outcomes for older patients undergoing emergency surgery with the addition of beta-adrenergic blockade

Mohseni

Joseph

Peden

2021

Eur J Trauma Emerg Surg

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As population age, healthcare systems and providers are likely to experience a substantial increase in the proportion of elderly patients requiring emergency surgery. Emergency surgery, compared with planned surgery, is strongly associated with increased risks of adverse postoperative outcomes due to the short time available for diagnosis, optimization, and intervention in patients presenting with physiological derangement. These patient populations, who are often frail and burdened with a variety of co-morbidities, have lower reserves to deal with the stress of the acute condition and the required emergency surgical intervention. In this review article, we discuss topical areas where mitigation of the physiological stress posed by the acute condition and asociated surgical intervention may be feasible. We consider the impact of the adrenergic response and use of beta blockers for these high-risk patients and discuss common risk factors such as frailty and delirium. A proactive multidisciplinary approach to peri-operative care aimed at mitigation of the stress response and proactive management of common conditions in the older emergency surgical patient could yield more favorable outcomes.

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Outpatient beta-blockers and survival from sepsis: Results from a national cohort of Medicare beneficiaries

Abstract: Our data suggests that there may be a role for preadmission beta-blockers in reducing sepsis-related mortality.

Cited by 17 publications

References 24 publications

The association between premorbid beta blocker exposure and mortality in sepsis—a systematic review

The association between premorbid beta blocker exposure and mortality in sepsis—a systematic review

Heartfelt sepsis: microvascular injury due to genomic storm

Mitigating the stress response to improve outcomes for older patients undergoing emergency surgery with the addition of beta-adrenergic blockade

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