Prophylactic versus clinically-driven antibiotics in comatose survivors of out-of-hospital cardiac arrest—A randomized pilot study

Ribarič, Suada Fileković; Turel, Matjaž; Knafelj, Rihard; Gorjup, Vojka; Stanic, Rade; Gradišek, Primož; Cerović, Ognjen; Mirkovic̆, Tomislav; Noč, Marko

doi:10.1016/j.resuscitation.2016.11.025

Cited by 35 publications

(31 citation statements)

References 27 publications

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“…There has been a recent interest in investigating the benefit of prophylactic antibiotics as a means to limit pathogen-associated systemic inflammatory responses particularly in patients with evidence of aspiration or those treated with systemic hypothermia (Hellenkamp, et al 2016, Ribaric, et al 2017). For example, Davies et al reported in a series of 138 patients that the early use of antibiotics was associated with a mortality benefit (Davies, et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion

Mai

Prifti

Rininger

et al. 2017

Experimental Neurology

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Post-ischemic neurodegeneration remains the principal cause of mortality following cardiac resuscitation. Recent studies have implicated gastrointestinal ischemia in the sepsis-like response associated with the post-cardiac arrest syndrome (PCAS). However, the extent to which the resulting low-grade endotoxemia present in up to 86% of resuscitated patients affects cerebral ischemia-reperfusion injury has not been investigated. Here we report that a single injection of low-dose lipopolysaccharide (50 μg/kg, IP) delivered after global cerebral ischemia (GCI) induces blood-brain barrier permeability, microglial activation, cortical injury, and functional decline in vivo, compared to ischemia alone. And while GCI was sufficient to induce neutrophil (PMN) activation and recruitment to the post-ischemic CNS, minimal endotoxemia exhibited synergistic effects on markers of systemic inflammation including PMN priming, lung damage, and PMN burden within the lung and other non-ischemic organs including the kidney and liver. Our findings predict that acute interventions geared towards blocking the effects of serologically occult endotoxemia in survivors of cardiac arrest will limit delayed neurodegeneration, multi-organ dysfunction and potentially other features of PCAS. This work also introduces lung-brain coupling as a novel therapeutic target with broad effects on innate immune priming and post-ischemic neurodegeneration following cardiac arrest and related cerebrovascular conditions.

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Section: Discussionmentioning

confidence: 99%

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion

Mai

Prifti

Rininger

et al. 2017

Experimental Neurology

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“…For the critical outcome of survival with favourable neurological outcome at ICU discharge or 30 days, we identified low-certainty evidence (downgraded for serious risk of bias and serious imprecision) from 2 RCTs 171 , 174 enrolling 254 patients, which showed no benefit of early/prophylactic antibiotic administration (RR, 0.89; 95% CI, 0.71-1.12; P = 0.31; risk difference, –0.06; 95% CI, 0.19-0.06; P = 0.30).…”

Section: Postresuscitation Carementioning

confidence: 99%

“…For the critical outcome of survival at ICU discharge or 30 days, we identified low-certainty evidence (downgraded for serious risk of bias and serious imprecision) from 2 RCTs 171 , 174 enrolling 254 patients, which showed no benefit (RR, 0.95; 95% CI, 0.79–1.14; P = 0.60; risk difference, –0.03; 95% CI, –0.15 to 0.08; P = 0.58). We also identified very low-certainty evidence (downgraded for serious indirectness) from 2 observational studies.…”

Section: Postresuscitation Carementioning

confidence: 99%

“…For the important outcome of infective complications (pneumonia) we identified low-certainty evidence (downgraded for serious risk of bias and serious imprecision) from 2 RCTs 171 , 174 enrolling 254 patients, which showed no benefit (RR, 0.75; 95% CI, 0.43-1.32; P = 0.32; risk difference, –0.12; 95% CI, –0.23-0.00; P = 0.05). There were differences between the studies in methods used to diagnose pneumonia.…”

Section: Postresuscitation Carementioning

confidence: 99%

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Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

et al. 2020

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This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

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“…Work by Davies et al 10 suggests that antibiotic treatment is associated with improved survival in OHCA with a number needed to treat of five; however, randomized trials are required in order to confirm this effect. While there is limited evidence to suggest that prophylactic antibiotics play a significant role in determining outcomes after PCAS in patients without signs of infection by tracheobronchial aspiration, 186 selective decontamination of the digestive tract (SDD) could prove to be an effective alternative. In randomized controlled trials of patients admitted to the ICU, SDD was shown to reduce mortality in critically ill patients with a reduction in MODS by 50% (OR 0.5, CI 0.34-0.74).…”

Section: Neutralizing the Gut Microbiomementioning

confidence: 99%

The post-cardiac arrest syndrome: A case for lung–brain coupling and opportunities for neuroprotection

Mai

Miller-Rhodes

Knowlden

et al. 2019

J Cereb Blood Flow Metab

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Systemic inflammation and multi-organ failure represent hallmarks of the post-cardiac arrest syndrome (PCAS) and predict severe neurological injury and often fatal outcomes. Current interventions for cardiac arrest focus on the reversal of precipitating cardiac pathologies and the implementation of supportive measures with the goal of limiting damage to at-risk tissue. Despite the widespread use of targeted temperature management, there remain no proven approaches to manage reperfusion injury in the period following the return of spontaneous circulation. Recent evidence has implicated the lung as a moderator of systemic inflammation following remote somatic injury in part through effects on innate immune priming. In this review, we explore concepts related to lung-dependent innate immune priming and its potential role in PCAS. Specifically, we propose and investigate the conceptual model of lung–brain coupling drawing from the broader literature connecting tissue damage and acute lung injury with cerebral reperfusion injury. Subsequently, we consider the role that interventions designed to short-circuit lung-dependent immune priming might play in improving patient outcomes following cardiac arrest and possibly other acute neurological injuries.

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Prophylactic versus clinically-driven antibiotics in comatose survivors of out-of-hospital cardiac arrest—A randomized pilot study

Cited by 35 publications

References 27 publications

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion

Endotoxemia induces lung-brain coupling and multi-organ injury following cerebral ischemia-reperfusion

Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations

The post-cardiac arrest syndrome: A case for lung–brain coupling and opportunities for neuroprotection

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