Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction.

BACKGROUND: The outcome of resuscitated patients after cardiac arrest complicating acute myocardial infarction remains poor, primarily because of the relatively low success rates of cardiopulmonary resuscitation management. Existing data suggest potential beneficial effects of early myocardial reperfusion, but the predictors of survival in these patients remain unknown. METHODS AND RESULTS: From 1995 to 2005, 186 patients (78% men; mean age, 60.4+/-13.8 years) underwent immediate percutaneous coronary intervention after successful resuscitation for cardiac arrest complicating acute myocardial infarction. Prompt prehospital management was performed by mobile medical care units in 154 of 186 patients, whereas 32 had in-hospital cardiac arrest. Infarct location was anterior in 105 patients (56%), and shock was present on admission in 96 (52%). Percutaneous coronary intervention (stenting rate 90%) was successful in 161 of 186 patients (87%). Six-month survival rate was 100 of 186 (54%), and 6-month survival free of neurological sequelae was 46%. By multivariate analysis, predictors of 6-month survival were a shorter interval between the onset of cardiac arrest and arrival of a first responder (odds ratio, 0.67; 95% CI, 0.54 to 0.84), a shorter interval between the onset of cardiac arrest and return of spontaneous circulation (odds ratio, 0.91; 95% CI, 0.87 to 0.96), and absence of diabetes (odds ratio, 7.30; 95% CI, 1.80 to 29.41). CONCLUSIONS: In patients with resuscitated cardiac arrest complicating acute myocardial infarction, prompt prehospital management and early revascularization were associated with a 54% survival rate at 6 months. A strategy including adequate prehospital management, early revascularization, and specific care in dedicated intensive care units should be strongly considered in resuscitated patients after cardiac arrest complicating acute myocardial infarction.

Is myocardial adrenergic responsiveness depressed in human septic shock?

OBJECTIVE: To assess left ventricular (LV) contractile function and adrenergic responsiveness in septic patients. METHODS: We used echocardiographically defined fractional area of contraction (FAC), and LV area to end-systolic arterial pressure estimates of end-systolic elastance (E'es) and its change in response to dobutamine (5 microg/kg/min) in 10 subjects in septic shock admitted to an intensive care unit of an academic medical center. Subjects were studied on admission and again at both 5 days and 8-10 days after admission. RESULTS: Three of the 10 subjects died as a result of their acute process, while the others were discharged from hospital. Nine out of 10 subjects required intravenous vasopressor therapy on day 1, while only 1 of 9 subjects required vasopressor support at day 5. LV end-diastolic area (EDA) increased from day 1 to day 5 and days 8-10 (p<0.05), but neither FAC nor E'es was altered by time (EDA 15.7+/-5.8, 21.4+/-5.1, and 19.4+/-5.6 cm2; FAC 0.46+/-0.19, 0.50+/-0.20, and 0.48+/-0.15%; E'es 21.6+/-12.6, 23.2+/-8.5, and 19.2+/-6.3 mmHg/cm2, mean+/-SD, for days 1, 5 and 8-10 respectively). Although dobutamine did not alter E'es on day 1 or day 5, E'es increased in all of the 5 subjects studied on days 8-10 (p<0.05). CONCLUSIONS: Adrenergic hyporesponsiveness is present in septic shock and persists for at least 5 days into recovery, resolving by days 8-10 in survivors.

An underrecognized source of organ donors: patients with brain death after successfully resuscitated cardiac arrest.

OBJECTIVE: To identify predictors of brain death after successful resuscitation of out-of-hospital cardiac arrest (OHCA), with the goal of improving the detection of brain death, and to evaluate outcomes of solid organs harvested from these patients. DESIGN AND SETTING: Prospective observational cohort study in a medical and surgical unit of a nonuniversity hospital. PATIENTS: Patients with successfully resuscitated OHCA were prospectively included in a database over a 7-year period. We looked for early predictors of brain death and compared outcomes of organ transplants from these patients to those from patients with brain death due to head injury or stroke. RESULTS: Over the 7-year period 246 patients were included. No early predictors of brain death were found. Of the 40 patients (16%) who met criteria for brain death, after a median ICU stay of 2.5 days (IQR 2.0-4.2), 19 donated 52 solid organs (29 kidneys, 14 livers, 7 hearts, and 2 lungs). Outcomes of kidneys and livers did not differ between donors with and without resuscitated cardiac arrest. CONCLUSIONS: Brain death may occur in about one-sixth of patients after successfully resuscitated OHCA, creating opportunities for organ donation.

Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke.

AIM OF THE REVIEW: To review the epidemiology, pathophysiology, treatment and prognostication in relation to the post-cardiac arrest syndrome. METHODS: Relevant articles were identified using PubMed, EMBASE and an American Heart Association EndNote master resuscitation reference library, supplemented by hand searches of key papers. Writing groups comprising international experts were assigned to each section. Drafts of the document were circulated to all authors for comment and amendment. RESULTS: The 4 key components of post-cardiac arrest syndrome were identified as (1) post-cardiac arrest brain injury, (2) post-cardiac arrest myocardial dysfunction, (3) systemic ischaemia/reperfusion response, and (4) persistent precipitating pathology. CONCLUSIONS: A growing body of knowledge suggests that the individual components of the post-cardiac arrest syndrome are potentially treatable.

Increased plasma levels of soluble triggering receptor expressed on myeloid cells 1 and procalcitonin after cardiac surgery and cardiac arrest without infection.

Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) and procalcitonin (PCT) are often considered to be specific markers for infection. We evaluated plasma levels of sTREM-1 and PCT in patients with systemic inflammatory response syndrome but no sepsis. Noninfected patients undergoing elective heart surgery with cardiopulmonary bypass (n = 76) and patients admitted after out-of-hospital cardiac arrest (n = 54) were followed up for 3 days. Patients with severe sepsis (n = 55) and healthy volunteers (n = 31) were included as positive and negative controls, respectively. Plasma levels of PCT were higher in sepsis patients than in patients who survived after cardiac arrest or after heart surgery. In contrast, peak plasma levels of sTREM-1 in heart surgery and in cardiac arrest patients overlapped with those measured in patients with sepsis. Both sTREM-1 and PCT were significantly higher in cardiac arrest patients who died of refractory shock than in those who died of neurological failure or survived without major neurological damage. In the cardiac arrest patients with refractory shock, sTREM-1 and PCT levels were similar to those in the patients with severe sepsis. In conclusion, sTREM-1 and PCT are not specific for infection and can increase markedly in acute inflammation without infection.

High-volume hemofiltration after out-of-hospital cardiac arrest: a randomized study.

OBJECTIVES: The study examined the effect of isovolumic high-volume hemofiltration (HF) alone or combined with mild hypothermia (HT) on survival after out-of-hospital cardiac arrest (OHCA) with initial ventricular fibrillation or asystole. BACKGROUND: Global inflammation in response to whole-body ischemia-reperfusion is common after OHCA and may worsen the overall prognosis. METHODS: Sixty-one patients admitted between May 2000 and March 2002 in the intensive care units of two hospitals in France were randomized to one of three groups: control, HF (200 ml/kg/h over 8 h) or HF+HT (32 degrees C for 24 h) induced by cooling the HF substitution fluid. Standard supportive care was provided in all three groups. The primary end point was survival with a follow-up time of six months. The effect of HF on death by intractable shock was the secondary end point. RESULTS: The six-month survival curves of the three groups were significantly different, with better survival in the HF group (p = 0.026) and in the HF+HT group (p = 0.018). After adjustment on baseline characteristics of cardiac arrest, HF (with or without HT) was associated with improved survival (logistic regression odds ratio, 4.4; 95% confidence interval [CI], 1.1 to 16.6). Compared to control group, the relative risk of death by intractable shock was 0.29 (95% CI, 0.09 to 0.91) in the HF+HT group and 0.21 (95% CI, 0.05 to 0.85) in the HF group. CONCLUSIONS: The HF may improve the overall prognosis after resuscitation from OHCA. Combination of HF with mild HT is feasible and should be evaluated in larger trials.

Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway.

OBJECTIVES: We investigated coagulation abnormalities in out-of-hospital cardiac arrest (OHCA) patients, with special attention to the protein C anticoagulant pathway. BACKGROUND: Successfully resuscitated cardiac arrest is followed by a systemic inflammatory response and by activation of coagulation, both of which may contribute to organ failure and neurological dysfunction. METHODS: Coagulation parameters were measured in all patients admitted after successfully resuscitated OHCA. RESULTS: At admission, 67 patients had a systemic inflammatory response with increased interleukin-6 and coagulation activity (thrombin-antithrombin complex), reduced anticoagulation (antithrombin, protein C, and protein S), activated fibrinolysis (plasmin-antiplasmin complex), and, in some cases, inhibited fibrinolysis (increased plasminogen activator inhibitor-1 with a peak on day 1). These abnormalities were more severe in patients who died within two days (50 of 67, 75%) and were most severe in patients dying from early refractory shock. Protein C and S levels were low compared to healthy volunteers and discriminated OHCA survivors from nonsurvivors. Furthermore, a subgroup of patients had a transient increase in plasma-activated protein C at admission followed by undetectable levels. This, along with an increase in soluble thrombomodulin over time, suggests secondary endothelial injury and dysfunction of the protein C anticoagulant pathway similar to that observed in severe sepsis. CONCLUSIONS: Major coagulation abnormalities were found after successful resuscitation of cardiac arrest. These abnormalities are consistent with secondary down-regulation of the thrombomodulin-endothelial protein C receptor pathway.

Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome.

BACKGROUND: We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome. METHODS AND RESULTS: Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell-derived IL-10 and interferon-gamma were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients' leukocytes and that an immunosuppressive activity was also present in their plasma. CONCLUSIONS: Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.

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.

Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation.

The postresuscitation phase after out-of-hospital circulatory arrest shares similarities with severe sepsis. Corticosteroid replacement is beneficial in patients with septic shock and adrenal dysfunction. The goal of this study was to assess baseline cortisol and adrenal reserve of out-of-hospital circulatory arrest patients after recovery of spontaneous circulation. Thirty-three consecutive patients successfully resuscitated after cardiac arrest were prospectively included between March 2002 and June 2003. A serum cortisol assay and a corticotropin test (250 microg i.v.) were done 6 to 36 h after circulatory arrest. A cortisol increase smaller than 9 microg/dL after corticotropin (nonresponders) defined adrenal reserve insufficiency. Response status was compared in the three outcome groups: survival with full neurologic recovery (n = 4), early death from refractory shock (n = 10), or later death from neurologic dysfunction (n = 19). Patients who died of early refractory shock had lower baseline cortisol levels than patients who died of neurologic dysfunction (27 microg/dL [15-47] vs. 52 microg/dL [28-73], respectively; P < 0.01), suggesting an inadequate adrenal response to severe systemic inflammation. Corticotropin response status was not associated with standard severity markers and seemed uninfluenced by therapeutic hypothermia. In conclusion, patients who die of early refractory shock after cardiopulmonary resuscitation may have an inadequate adrenal response to the stress associated with this condition. Thresholds for cortisol levels at baseline and after corticotropin need to be determined in this clinical setting.

Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication: a scientific statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke (Part II).

AIM OF THE REVIEW: To review the epidemiology, pathophysiology, treatment and prognostication in relation to the post-cardiac arrest syndrome. METHODS: Relevant articles were identified using PubMed, EMBASE and an American Heart Association EndNote master resuscitation reference library, supplemented by hand searches of key papers. Writing groups comprising international experts were assigned to each section. Drafts of the document were circulated to all authors for comment and amendment. RESULTS: The 4 key components of post-cardiac arrest syndrome were identified as (1) post-cardiac arrest brain injury, (2) post-cardiac arrest myocardial dysfunction, (3) systemic ischaemia/reperfusion response, and (4) persistent precipitating pathology. CONCLUSIONS: A growing body of knowledge suggests that the individual components of the post-cardiac arrest syndrome are potentially treatable.

Post-cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication: A scientific statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke (Part 1).

AIM OF THE REVIEW: To review the epidemiology, pathophysiology, treatment and prognostication in relation to the post-cardiac arrest syndrome. METHODS: Relevant articles were identified using PubMed, EMBASE and an American Heart Association EndNote master resuscitation reference library, supplemented by hand searches of key papers. Writing groups comprising international experts were assigned to each section. Drafts of the document were circulated to all authors for comment and amendment. RESULTS: The 4 key components of post-cardiac arrest syndrome were identified as (1) post-cardiac arrest brain injury, (2) post-cardiac arrest myocardial dysfunction, (3) systemic ischaemia/reperfusion response, and (4) persistent precipitating pathology. CONCLUSIONS: A growing body of knowledge suggests that the individual components of the postcardiac arrest syndrome are potentially treatable.

Predicting survival with good neurological recovery at hospital admission after successful resuscitation of out-of-hospital cardiac arrest: the OHCA score.

AIMS: Out-of-hospital cardiac arrest (OHCA) is common and carries a bleak prognosis. Early prediction of unfavourable outcomes is difficult but crucial to improve resource allocation. The aim of this study was to develop a simple tool for predicting survival with good neurological function in the overall population of patients with successfully resuscitated cardiac arrest. METHODS AND RESULTS: We used logistic regression analysis to identify clinical and laboratory variables that were both readily available at admission and predictive of poor outcomes (death or severe neurological impairment) in a development cohort of 130 consecutive OHCA patients admitted to a French intensive care unit (ICU) between 1999 and 2003. To test the prediction score built from these variables, we used a validation cohort of 210 patients recruited in four French ICUs between 2003 and 2005. Initial rhythm, estimated no-flow and low-flow intervals, blood lactate, and creatinine levels determined using whole blood analyzers were independently associated with poor outcomes and were used to build a continuous severity score. Goodness-of-fit tests indicated good performance (P=0.79 in the development cohort and P=0.13 in the validation cohort). The area under the receiver-operating characteristics curve was 0.82 in the development cohort and 0.88 in the validation cohort. CONCLUSION: The outcome can be accurately predicted after OHCA using variables that are readily available at ICU admission.

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

PURPOSE OF REVIEW: Despite 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 FINDINGS: Postresuscitation 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. SUMMARY: Postresuscitation 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.