Alain Cariou

Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest ☆

OBJECTIVES The aim of the study was to assess the hemodynamic status of survivors of out-of-hospital cardiac arrest (OHCA). BACKGROUND The global prognosis after successfully resuscitated patients with OHCA remains poor. Clinical studies describing the hemodynamic status of survivors of OHCA and its impact on prognosis are lacking. METHODS Among 165 consecutive patients admitted after successful resuscitation from OHCA, 73 required invasive monitoring because of hemodynamic instability, defined as hypotension requiring vasoactive drugs, during the first 72 h. Clinical features and data from invasive monitoring were analyzed. RESULTS Hemodynamic instability occurred at a median time of 6.8 h (range 4.3 to 7.3) after OHCA. The initial cardiac index (CI) and filling pressures were low. Then, the CI rapidly increased 24 h after the onset of OHCA, independent of filling pressures and inotropic agents (2.05 [1.43 to 2.90] 8 h vs. 3.19 l/min per m(2) [2.67 to 4.20] 24 h after OHCA; p < 0.001). Despite a significant improvement in CI at 24 h, a superimposed vasodilation delayed the discontinuation of vasoactive drugs. No improvement in CI at 24 h was noted in 14 patients who subsequently died of multiorgan failure. Hemodynamic status was not predictive of the neurologic outcome. CONCLUSIONS In survivors of OHCA, hemodynamic instability requiring administration of vasoactive drugs is frequent and appears several hours after hospital admission. It is characterized by a low CI that is reversible in most cases within 24 h, suggesting post-resuscitation myocardial dysfunction. Early death by multiorgan failure is associated with a persistent low CI at 24 h.

Immediate Percutaneous Coronary Intervention Is Associated With Better Survival After Out-of-Hospital Cardiac Arrest Insights From the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) Registry

Background— Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results— Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions— Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.Background—Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results—Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions—Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.

Postresuscitation disease after cardiac arrest: a sepsis-like syndrome?

Purpose of reviewDespite advances in cardiac arrest resuscitation, neurologic impairments and other organ dysfunctions cause considerable mortality and morbidity after restoration of spontaneous cardiac activity. The mechanisms underlying this postresuscitation disease probably involve a whole-body ischemia and reperfusion syndrome that triggers a systemic inflammatory response. Recent findingsPostresuscitation disease is characterized by high levels of circulating cytokines and adhesion molecules, the presence of plasma endotoxin, and dysregulated leukocyte production of cytokines: a profile similar to that seen in severe sepsis. Transient myocardial dysfunction can occur after resuscitation, mainly as a result of myocardial stunning. However, early successful angioplasty is independently associated with better outcomes after cardiac arrest associated with myocardial infarction. Coagulation abnormalities occur consistently after successful resuscitation, and their severity is associated with mortality. For example, plasma protein C and S activities after successful resuscitation are lower in nonsurvivors than in survivors. Low baseline cortisol levels may be associated with an increased risk of fatal early refractory shock after cardiac arrest, suggesting adrenal dysfunction in these patients. SummaryPostresuscitation abnormalities after cardiac arrest mimic the immunologic and coagulation disorders observed in severe sepsis. This suggests that therapeutic approaches used recently with success in severe sepsis should be investigated in patients successfully resuscitated after cardiac arrest.

Immediate Percutaneous Coronary Intervention Is Associated With Better Survival After Out-of-Hospital Cardiac ArrestClinical Perspective

Background— Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results— Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions— Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.Background—Acute coronary occlusion is the leading cause of cardiac arrest. Because of limited data, the indications and timing of coronary angiography and angioplasty in patients with out-of-hospital cardiac arrest are controversial. Using data from the Parisian Region Out of hospital Cardiac ArresT prospective registry, we performed an analysis to assess the effect of an invasive strategy on hospital survival. Methods and Results—Between January 2003 and December 2008, 714 patients with out-of-hospital cardiac arrest were referred to a tertiary center in Paris, France. In 435 patients with no obvious extracardiac cause of arrest, an immediate coronary angiogram was performed at admission followed, if indicated, by coronary angioplasty. At least 1 significant coronary artery lesion was found in 304 (70%) patients, in 128 (96%) of 134 patients with ST-segment elevation on the ECG performed after the return of spontaneous circulation, and in 176 (58%) of 301 patients without ST-segment elevation. The hospital survival rate was 40%. Multivariable analysis showed successful coronary angioplasty to be an independent predictive factor of survival, regardless of the postresuscitation ECG pattern (odds ratio, 2.06; 95% CI, 1.16 to 3.66). Conclusions—Successful immediate coronary angioplasty is associated with improved hospital survival in patients with or without ST-segment elevation. Therefore, our findings support the use of immediate coronary angiography in patients with out-of-hospital cardiac arrest with no obvious noncardiac cause of arrest regardless of the ECG pattern.

European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015

Department of Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK School of Clinical Sciences, University of Bristol, UK Anaesthesia and Intensive Care Medicine, Southmead Hospital, Bristol, UK Cochin University Hospital (APHP) and Paris Descartes University, Paris, France Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden Adelante, Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands Cardiac Anaesthesia and Cardiac Intensive Care and NIHR Southampton Respiratory Biomedical Research Unit, University Hospital, Southampton, UK Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany Department of Clinical Sciences, Division of Anesthesia and Intensive Care Medicine, Lund University, Lund, Sweden Department of Anaesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, slo, Norway Department of Anaesthesiology and Intensive Care, Catholic University School of Medicine, Rome, Italy

Prognostication in comatose survivors of cardiac arrest: An advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine ☆

OBJECTIVES To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron specific enolase at 48 72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

Is Hypothermia After Cardiac Arrest Effective in Both Shockable and Nonshockable Patients? Insights From a Large Registry

Background— Although the level of evidence of improvement is significant in cardiac arrest patients resuscitated from a shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia [VF/VT]), the use of therapeutic mild hypothermia (TMH) is more controversial in nonshockable patients (pulseless electric activity or asystole [PEA/asystole]). We therefore assessed the prognostic value of hypothermia for neurological outcome at hospital discharge according to first-recorded cardiac rhythm in a large cohort. Methods and Results— Between January 2000 and December 2009, data from 1145 consecutive out-of-hospital cardiac arrest patients in whom a successful resuscitation had been achieved were prospectively collected. The association of TMH with a good neurological outcome at hospital discharge (cerebral performance categories level 1 or 2) was quantified by logistic regression analysis. TMH was induced in 457/708 patients (65%) in VF/VT and in 261/437 patients (60%) in PEA/asystole. Overall, 342/1145 patients (30%) reached a favorable outcome (cerebral performance categories level 1 or 2) at hospital discharge, respectively 274/708 (39%) in VF/VT and 68/437 (16%) in PEA/asystole (P<0.001). After adjustment, in VF/VT patients, TMH was associated with increased odds of good neurological outcome (adjusted odds ratio, 1.90; 95% confidence interval, 1.18 to 3.06) whereas in PEA/asystole patients, TMH was not significantly associated with good neurological outcome (adjusted odds ratio, 0.71; 95% confidence interval, 0.37 to 1.36). Conclusions— In this large cohort of cardiac arrest patients, hypothermia was independently associated with an improved outcome at hospital discharge in patients presenting with VF/VT. By contrast, TMH was not associated with good outcome in nonshockable patients. Further investigations are needed to clarify this lack of efficiency in PEA/asystole.

Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.

CONTEXT Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. OBJECTIVES To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. DESIGN, SETTING, AND PATIENTS A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. INTERVENTIONS Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). CONCLUSIONS Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00320099.

Association between a genomic polymorphism within the CD14 locus and septic shock susceptibility and mortality rate

ObjectiveGenetic differences in immune responses may affect susceptibility to and outcome of septic shock. CD14 seems to be an important part of the innate immune system, initiating antimicrobial response. We evaluated the frequency of a recently discovered CD14 promoter gene polymorphism (C to T transition at base pair −159) among patients with septic shock compared with those in a control group. DesignMultiple-center study. SettingHospital research department. PatientsNinety consecutive white patients with septic shock were included. The control group consisted of 122 age- and gender-matched white subjects. InterventionsIn both groups, the C−159T CD14 promoter genetic polymorphism was determined by using polymerase chain reaction and subsequent Hae III restriction enzyme digestion of the polymerase chain reaction products. Measurements and Main ResultsThe C−159T polymorphism and the TT genotype were significantly overrepresented among septic shock patients compared with controls. Within the septic shock group, the mortality of patients with TT genotype (71%) was significantly higher than in patients with other genotypes (48%; Pearson chi-square, p = .008). In a multiple logistic regression model, the TT genotype was independently associated with an increased relative risk of death (odds ratio, 5.30; 95% confidence interval, 1.20–22.50, p = .02). ConclusionsThe C−159T polymorphism affects susceptibility to septic shock and seems to be a new genetic risk factor for death.

Changes in aortic blood flow induced by passive leg raising predict fluid responsiveness in critically ill patients

IntroductionEsophageal Doppler provides a continuous and non-invasive estimate of descending aortic blood flow (ABF) and corrected left ventricular ejection time (LVETc). Considering passive leg raising (PLR) as a reversible volume expansion (VE), we compared the relative abilities of PLR-induced ABF variations, LVETc and respiratory pulsed pressure variations (ΔPP) to predict fluid responsiveness.MethodsWe studied 22 critically ill patients in acute circulatory failure in the supine position, during PLR, back to the supine position and after two consecutive VEs of 250 ml of saline. Responders were defined by an increase in ABF induced by 500 ml VE of more than 15%.ResultsTen patients were responders and 12 were non-responders. In responders, the increase in ABF induced by PLR was similar to that induced by a 250 ml VE (16% versus 20%; p = 0.15). A PLR-induced increase in ABF of more than 8% predicted fluid responsiveness with a sensitivity of 90% and a specificity of 83%. Corresponding positive and negative predictive values (PPV and NPV, respectively) were 82% and 91%, respectively. A ΔPP threshold value of 12% predicted fluid responsiveness with a sensitivity of 70% and a specificity of 92%. Corresponding PPV and NPV were 87% and 78%, respectively. A LVETc of 245 ms or less predicted fluid responsiveness with a sensitivity of 70%, and a specificity of 67%. Corresponding PPV and NPV were 60% and 66%, respectively.ConclusionThe PLR-induced increase in ABF and a ΔPP of more than 12% offer similar predictive values in predicting fluid responsiveness. An isolated basal LVETc value is not a reliable criterion for predicting response to fluid loading.