Delirium in Survivors of Cardiac Arrest Treated With Mild Therapeutic Hypothermia.

BACKGROUND: Mild therapeutic hypothermia is recommended for comatose patients resuscitated from cardiac arrest. However, the prevalence of delirium and its associated risk factors have not been assessed in survivors of cardiac arrest treated with therapeutic hypothermia. OBJECTIVE: To determine the prevalence of and risk factors for delirium among survivors of cardiac arrest who were treated with therapeutic hypothermia. METHODS: A retrospective observational study of patients treated with therapeutic hypothermia after cardiac arrest from 2007 through 2014. Baseline demographic data and daily delirium assessments throughout the intensive care unit stay were obtained. The association between duration of delirium and various risk factors was assessed. RESULTS: Of 251 patients, 107 (43%) awoke from coma. Among the 107 survivors, all had at least 1 day of delirium during their intensive care unit stay. Median number of days of delirium was 4.0 (interquartile range, 2.0-7.5). Multivariable analysis revealed that age (odds ratio, 1.72; 95% CI, 1.0-2.95; P = .05), time from cardiopulmonary resuscitation to return of spontaneous circulation (odds ratio 1.52; 95% CI, 1.11-2.07; P = .01), and total dose of prewarming propofol (odds ratio, 0.02; 95% CI, 0.00-0.48; P = .02) were associated with duration of delirium. CONCLUSIONS: All survivors of cardiac arrest treated with mild therapeutic hypothermia had at least 1 day of delirium. Age and time from initiation of cardiopulmonary resuscitation to return of spontaneous circulation were associated with prolonged delirium, whereas exposure to propofol was protective against delirium. These findings are limited to this unique cohort and may not be generalizable to different populations.

Outcomes of Comatose Cardiac Arrest Survivors With and Without ST-Segment Elevation Myocardial Infarction: Importance of Coronary Angiography.

OBJECTIVES: The aim of this study was to compare outcomes and coronary angiographic findings in post-cardiac arrest patients with and without ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The 2013 STEMI guidelines recommend performing immediate angiography in resuscitated patients whose initial electrocardiogram shows STEMI. The optimal approach for those without STEMI post-cardiac arrest is less clear. METHODS: A retrospective evaluation of a post-cardiac arrest registry was performed. RESULTS: The database consisted of 746 comatose post-cardiac arrest patients including 198 with STEMI (26.5%) and 548 without STEMI (73.5%). Overall survival was greater in those with STEMI compared with those without (55.1% vs. 41.3%; p = 0.001), whereas in all patients who underwent immediate coronary angiography, survival was similar between those with and without STEMI (54.7% vs. 57.9%; p = 0.60). A culprit vessel was more frequently identified in those with STEMI, but also in one-third of patients without STEMI (80.2% vs. 33.2%; p = 0.001). The majority of culprit vessels were occluded (STEMI, 92.7%; no STEMI, 69.2%; p < 0.0001). An occluded culprit vessel was found in 74.3% of STEMI patients and in 22.9% of no STEMI patients. Among cardiac arrest survivors discharged from the hospital who had presented without STEMI, coronary angiography was associated with better functional outcome (93.3% vs. 78.7%; p < 0.003). CONCLUSIONS: Early coronary angiography is associated with improved functional outcome among resuscitated patients with and without STEMI. Resuscitated patients with a presumed cardiac etiology appear to benefit from immediate coronary angiography.

Higher achieved mean arterial pressure during therapeutic hypothermia is not associated with neurologically intact survival following cardiac arrest.

INTRODUCTION: To determine if higher achieved mean arterial blood pressure (MAP) during treatment with therapeutic hypothermia (TH) is associated with neurologically intact survival following cardiac arrest. METHODS: Retrospective analysis of a prospectively collected cohort of 188 consecutive patients treated with TH in the cardiovascular intensive care unit of an academic tertiary care hospital. RESULTS: Neurologically intact survival was observed in 73/188 (38.8%) patients at hospital discharge and in 48/162 (29.6%) patients at a median follow up interval of 3 months. Patients in shock at the time of admission had lower baseline MAP at the initiation of TH (81 versus 87mmHg; p=0.002), but had similar achieved MAP during TH (80.3 versus 83.7mmHg; p=0.11). Shock on admission was associated with poor survival (18% versus 52%; p<0.001). Vasopressor use among all patients was common (84.6%) and was not associated with increased mortality. A multivariable analysis including age, initial rhythm, time to return of spontaneous circulation, baseline MAP and achieved MAP did not demonstrate a relationship between MAP achieved during TH and poor neurological outcome at hospital discharge (OR 1.28, 95% CI 0.40-4.06; p=0.87) or at outpatient follow up (OR 1.09, 95% CI 0.32-3.75; p=0.976). CONCLUSION: We did not observe a relationship between higher achieved MAP during TH and neurologically intact survival. However, shock at the time of admission was clearly associated with poor outcomes in our study population. These data do not support the use of vasopressors to artificially increase MAP in the absence of shock. There is a need for prospective, randomized trials to further define the optimum blood pressure target during treatment with TH.

Effectiveness of mild therapeutic hypothermia following cardiac arrest in adult patients with congenital heart disease.

Mild therapeutic hypothermia (TH) is an established therapy to improve survival and reduce neurologic injury after cardiac arrest. Adult patients with congenital heart disease (ACHD) are at increased risk of sudden cardiac death. The use of TH in this population has not been extensively studied. The aim of this study is to report our institutional experience using this treatment modality in patients with ACHD after cardiac arrest. We performed a retrospective observational study of a cohort of 245 consecutive patients treated with TH after cardiac arrest from 2007 to 2013. Five patients were identified as having complex ACHD with a mean age of 28 years. All were treated with TH according to an institutional protocol utilizing active surface cooling to maintain a core body temperature of 32°C to 34°C for 24 hours after cardiac arrest. Congenital lesions in these 5 patients included anomalous left coronary artery from the pulmonary artery; l-transposition of the great arteries; d-transposition of the great arteries status post atrial switch; unoperated tricuspid atresia, atrial septal defect, and ventricular septal defect with Eisenmenger's physiology; and surgically corrected atrial septal defect, cleft mitral valve, and subaortic membrane. All 5 patients suffered cardiac arrest due to ventricular arrhythmia and all survived to discharge without significant neurologic impairment. Therapeutic interventions included anomalous left coronary artery from the pulmonary artery ligation, percutaneous coronary intervention, and defibrillator implantation. In conclusion, in 5 patients with ACHD, the use of TH after cardiac arrest resulted in 100% survival to hospital discharge with good neurologic outcome postresuscitation.

Sequential moderate coronary artery fistula and moderate coronary artery stenosis causing ischemia demonstrated by fractional flow reserve and relieved following percutaneous coronary intervention.

Coronary artery fistulae are rare anomalous connections arising from the coronary circulation. We report a case of anterior wall myocardial ischemia caused by the combination of sequential coronary-to-pulmonary artery fistula and moderate (50-60%) stenosis of the left anterior descending coronary artery. Ischemia was demonstrated by myocardial stress perfusion imaging as well as fractional flow reserve. Percutaneous coronary intervention of the lesion resulted in resolution of ischemia.

A history of smoking is associated with improved survival in patients treated with mild therapeutic hypothermia following cardiac arrest.

OBJECTIVES: To assess the association between smoking and survival with a good neurologic outcome in patients following cardiac arrest treated with mild therapeutic hypothermia (TH). METHODS: We conducted a retrospective observational study of a prospectively collected cohort of 188 consecutive patients following cardiac arrest treated with TH between May 2007 and January 2012. Smoking status was retrospectively collected via chart review and was classified as "ever" or "never". Primary endpoint was survival to hospital discharge with a good neurologic outcome and was compared between smokers and nonsmokers. Logistic regression analysis was used to assess the association between smoking status and neurologic outcome at hospital discharge; adjusting for age, initial rhythm, time to return of spontaneous circulation (ROSC), bystander CPR, and time to initiation of TH. RESULTS: Smokers were significantly more likely to survive to hospital discharge with good neurologic outcome compared to nonsmokers (50% vs. 28%, p=0.003). After adjusting for age, initial rhythm, time to ROSC, bystander CPR, and time to initiation of TH, a history of smoking was associated with increased odds of survival to hospital discharge with good neurologic outcome (OR 3.54, 95% CI 1.41-8.84, p=0.007). CONCLUSIONS: Smoking is associated with improved survival with good neurologic outcome in patients following cardiac arrest. We hypothesize that our findings reflect global ischemic conditioning caused by smoking.

Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI.

AIM: To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent. METHODS: We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest. RESULTS: A total of 269 (35.7%) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH. Of these, 122 (45.4%) received CC while comatose (early CC). Acute coronary occlusion was discovered in 26.6% of patients treated with early CC compared to 29.3% of patients treated with late CC (p=0.381). Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC (65.6% vs. 48.6%; p=0.017). In a multivariate regression model that included study site, age, bystander CPR, shock on admission, comorbid medical conditions, witnessed arrest, and time to return of spontaneous circulation, early CC was independently associated with a significant reduction in the risk of death (OR 0.35, 95% CI 0.18-0.70, p=0.003). CONCLUSIONS: In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality. The incidence of acute coronary occlusion is high, even when STEMI is not present on the postresuscitation electrocardiogram.

Early bispectral index and sedation requirements during therapeutic hypothermia predict neurologic recovery following cardiac arrest.

OBJECTIVES: To test the hypothesis that low bispectral index scores and low sedative requirements during therapeutic hypothermia predict poor neurologic outcome. DESIGN: Observational study of a prospectively collected cohort. SETTING: Cardiovascular ICU. PATIENTS: One hundred sixty consecutive cardiac arrest patients treated with therapeutic hypothermia. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Eighty-four of the 141 subjects (60%) who survived hypothermia induction were discharged from the ICU with poor neurologic outcome, defined as a cerebral performance category score of 3, 4, or 5. These subjects had lower bispectral index (p < 0.001) and sedative requirements (p < 0.001) during hypothermia compared with the 57 subjects discharged with good outcome. Early prediction of neurologic recovery was best 7 hours after ICU admission, and median bispectral index scores at that time were 31 points lower in subjects discharged with poor outcome (11 [interquartile range, 4-29] vs 42 [37-49], p < 0.001). Median sedation requirements decreased by 17% (interquartile range, -50 to 0%) 7 hours after ICU admission in subjects with poor outcome but increased by 50% (interquartile range, 0-142%) in subjects with good outcome (p < 0.001). Each 10-point decrease in bispectral index was independently associated with a 59% increase in the odds of poor outcome (95% CI, 32-76%; p < 0.001). The model including bispectral index and sedative requirement correctly reclassified 15% of subjects from good to poor outcome and 1% of subjects from poor to good outcome. The model incorrectly reclassified 1% of subjects from poor to good outcome but did not incorrectly reclassify any from good to poor outcome. CONCLUSIONS: Bispectral index scores and sedative requirements early in the course of therapeutic hypothermia improve the identification of patients who will not recover from brain anoxia. The ability to accurately predict nonrecovery after cardiac arrest could facilitate discussions with families, reduce patient suffering, and limit use of ICU resources in futile cases.

Hereditary hemochromatosis: missed diagnosis or misdiagnosis?

BACKGROUND: Hereditary hemochromatosis is a disorder that can cause iron overload and organ damage. Hereditary hemochromatosis is characterized by mutations in the HFE gene. HFE C282Y homozygotes and compound heterozygotes (C282Y/H63D) are at risk of developing manifestations of hemochromatosis. Abnormal iron study results also occur in many liver and hematologic diseases. The aim of this study was to evaluate the accuracy of diagnosis of hereditary hemochromatosis. METHODS: Pertinent clinical and laboratory data, including HFE genotype, were tabulated from the electronic medical records of patients with the International Classification of Diseases 9th Revision code 275, "disorders of iron metabolism," who were seen at a tertiary referral center between January 2002 and May 2012. RESULTS: HFE genotyping was obtained in only 373 of 601 patients (62%); 200 were C282Y homozygotes or compound heterozygotes. Of the 173 patients with nonhereditary hemochromatosis genotypes, 53% were misdiagnosed with hereditary hemochromatosis and 38% underwent phlebotomy. In two thirds of these cases, the misdiagnosis was made by a nonspecialist. In the remaining 228 patients who were not genotyped, 80 were diagnosed with hereditary hemochromatosis and 64 were phlebotomized. Of patients misdiagnosed with hemochromatosis, 68% had known liver disease and 5% had a hematologic cause of abnormal iron study results. CONCLUSIONS: Abnormal iron study results in patients with nonhereditary hemochromatosis genotypes commonly lead to a misdiagnosis of hereditary hemochromatosis and inappropriate treatment with phlebotomy. This error often is seen in the setting of elevated iron study results secondary to chronic liver diseases. Furthermore, hereditary hemochromatosis is commonly diagnosed and treated without HFE genotyping. We suggest that phlebotomy centers require a documented HFE genotype before initiating phlebotomy.

Hyperoxia is associated with increased mortality in patients treated with mild therapeutic hypothermia after sudden cardiac arrest.

OBJECTIVE: To determine whether higher levels of PaO2 are associated with in-hospital mortality and poor neurological status at hospital discharge in patients treated with mild therapeutic hypothermia after sudden cardiac arrest. DESIGN: Retrospective analysis of a prospective cohort. PATIENTS: A total of 170 consecutive patients treated with therapeutic hypothermia in the cardiovascular care unit of an academic tertiary care hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 170 patients, 77 (45.2%) survived to hospital discharge. Survivors had a significantly lower maximum PaO2 (198 mm Hg; interquartile range, 152.5-282) measured in the first 24 hrs following cardiac arrest compared to nonsurvivors (254 mm Hg; interquartile range, 172-363; p = .022). A multivariable analysis including age, time to return of spontaneous circulation, the presence of shock, bystander cardiopulmonary resuscitation, and initial rhythm revealed that higher levels of PaO2 were significantly associated with increased in-hospital mortality (odds ratio 1.439; 95% confidence interval 1.028-2.015; p = .034) and poor neurological status at hospital discharge (odds ratio 1.485; 95% confidence interval 1.032-2.136; p = .033). CONCLUSIONS: Higher levels of the maximum measured PaO2 are associated with increased in-hospital mortality and poor neurological status on hospital discharge in patients treated with mild therapeutic hypothermia after sudden cardiac arrest.

Implementation of a standardized pathway for the treatment of cardiac arrest patients using therapeutic hypothermia: "CODE ICE".

Out-of-hospital cardiac arrest is common and is associated with high mortality. The majority of in-hospital deaths from resuscitated victims of cardiac arrest are due to neurologic injury. Therapeutic hypothermia (TH) is now recommended for the management of comatose survivors of cardiac arrest. The rapid triage and standardized treatment of cardiac arrest patients can be challenging, and implementation of a TH program requires a multidisciplinary team approach. In 2010, we revised our institution's TH protocol, creating a "CODE ICE" pathway to improve the timely and coordinated care of cardiac arrest patients. As part of CODE ICE, we implemented comprehensive care pathways including measures such as a burst paging system and computerized physician support tools. "STEMI on ICE" integrates TH with our regional ST-elevation myocardial infarction network. Retrospective data were collected on 150 consecutive comatose cardiac arrest victims treated with TH (n = 82 pre-CODE ICE and n = 68 post-CODE ICE) from 2007 to 2011. After implementation of CODE ICE, the mean time to initiation of TH decreased from 306 ± 165 minutes to 196 ± 144 minutes (P < 0.001), and the time to target temperature decreased from 532 ± 214 minutes to 392 ± 215 minutes (P < 0.001). There was no significant change in survival or neurologic outcome at hospital discharge. Through the implementation of CODE ICE, we were able to reduce the time to initiation of TH and time to reach target temperature. Additional studies are needed to determine the effect of CODE ICE and similar pathways on clinical outcomes after cardiac arrest.