Prognostication after cardiac arrest and hypothermia: a prospective study.

Current American Academy of Neurology (AAN) guidelines for outcome prediction in comatose survivors of cardiac arrest (CA) have been validated before the therapeutic hypothermia era (TH). We undertook this study to verify the prognostic value of clinical and electrophysiological variables in the TH setting. A total of 111 consecutive comatose survivors of CA treated with TH were prospectively studied over a 3-year period. Neurological examination, electroencephalography (EEG), and somatosensory evoked potentials (SSEP) were performed immediately after TH, at normothermia and off sedation. Neurological recovery was assessed at 3 to 6 months, using Cerebral Performance Categories (CPC). Three clinical variables, assessed within 72 hours after CA, showed higher false-positive mortality predictions as compared with the AAN guidelines: incomplete brainstem reflexes recovery (4% vs 0%), myoclonus (7% vs 0%), and absent motor response to pain (24% vs 0%). Furthermore, unreactive EEG background was incompatible with good long-term neurological recovery (CPC 1-2) and strongly associated with in-hospital mortality (adjusted odds ratio for death, 15.4; 95% confidence interval, 3.3-71.9). The presence of at least 2 independent predictors out of 4 (incomplete brainstem reflexes, myoclonus, unreactive EEG, and absent cortical SSEP) accurately predicted poor long-term neurological recovery (positive predictive value = 1.00); EEG reactivity significantly improved the prognostication. Our data show that TH may modify outcome prediction after CA, implying that some clinical features should be interpreted with more caution in this setting as compared with the AAN guidelines. EEG background reactivity is useful in determining the prognosis after CA treated with TH.

Urological surgery and antiplatelet drugs after cardiac and cerebrovascular accidents.

PURPOSE: The perioperative treatment of patients on dual antiplatelet therapy after myocardial infarction, cerebrovascular event or coronary stent implantation represents an increasingly frequent issue for urologists and anesthesiologists. We assess the current scientific evidence and propose strategies concerning treatment of these patients. MATERIALS AND METHODS: A MEDLINE and PubMed search was conducted for articles related to antiplatelet therapy after myocardial infarction, coronary stents and cerebrovascular events, as well as the use of aspirin and/or clopidogrel in the context of surgery. RESULTS: Early discontinuation of antiplatelet therapy for secondary prevention is associated with a high risk of coronary thrombosis, which is further increased by the hypercoagulable state induced by surgery. Aspirin has recently been recommended as a lifelong therapy. Clopidogrel is mandatory for 6 weeks after myocardial infarction and bare metal stents, and for 12 months after drug-eluting stents. Surgery must be postponed beyond these waiting periods or performed with patients receiving dual antiplatelet therapy because withdrawal therapy increases 5 to 10 times the risk of postoperative myocardial infarction, stent thrombosis or death. The shorter the waiting period between revascularization and surgery the greater the risk of adverse cardiac events. The risk of surgical hemorrhage is increased approximately 20% by aspirin and 50% by clopidogrel. CONCLUSIONS: The risk of coronary thrombosis when antiplatelet agents are withdrawn before surgery is generally higher than the risk of surgical hemorrhage when antiplatelet agents are maintained. However, this issue has not yet been sufficiently evaluated in urological patients and in many instances during urological surgery the risk of bleeding can be dangerous. A thorough dialogue among surgeon, cardiologist and anesthesiologist is essential to determine all risk factors and define the best possible strategy for each patient.

Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia.

OBJECTIVES: Therapeutic hypothermia and pharmacological sedation may influence outcome prediction after cardiac arrest. The use of a multimodal approach, including clinical examination, electroencephalography, somatosensory-evoked potentials, and serum neuron-specific enolase, is recommended; however, no study examined the comparative performance of these predictors or addressed their optimal combination. DESIGN: Prospective cohort study. SETTING: Adult ICU of an academic hospital. PATIENTS: One hundred thirty-four consecutive adults treated with therapeutic hypothermia after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Variables related to the cardiac arrest (cardiac rhythm, time to return of spontaneous circulation), clinical examination (brainstem reflexes and myoclonus), electroencephalography reactivity during therapeutic hypothermia, somatosensory-evoked potentials, and serum neuron-specific enolase. Models to predict clinical outcome at 3 months (assessed using the Cerebral Performance Categories: 5 = death; 3-5 = poor recovery) were evaluated using ordinal logistic regressions and receiving operator characteristic curves. Seventy-two patients (54%) had a poor outcome (of whom, 62 died), and 62 had a good outcome. Multivariable ordinal logistic regression identified absence of electroencephalography reactivity (p < 0.001), incomplete recovery of brainstem reflexes in normothermia (p = 0.013), and neuron-specific enolase higher than 33 μg/L (p = 0.029), but not somatosensory-evoked potentials, as independent predictors of poor outcome. The combination of clinical examination, electroencephalography reactivity, and neuron-specific enolase yielded the best predictive performance (receiving operator characteristic areas: 0.89 for mortality and 0.88 for poor outcome), with 100% positive predictive value. Addition of somatosensory-evoked potentials to this model did not improve prognostic accuracy. CONCLUSIONS: Combination of clinical examination, electroencephalography reactivity, and serum neuron-specific enolase offers the best outcome predictive performance for prognostication of early postanoxic coma, whereas somatosensory-evoked potentials do not add any complementary information. Although prognostication of poor outcome seems excellent, future studies are needed to further improve prediction of good prognosis, which still remains inaccurate.

Neurological Prognostication after Cardiac Arrest and Therapeutic Hypothermia: a Prospective Validation Study

Introduction: Clinical examination and electroencephalography study (EEG) have been recommended to predict functional recovery in comatose survivors of cardiac arrest (CA), however their prognostic value in patients treated with induced hypothermia (IH) has not been evaluated. Hypothesis: We aimed to validate the prognostic ability of clinical examination and EEG in predicting outcome of patients with coma after CA treated with IH and sought to derive a score with high predictive value for poor functional outcome in this setting. Methods: We prospectively studied 100 consecutive comatose survivors of CA treated with IH. Repeated neurological examination and EEG were performed early after passive rewarming and off sedation. Mortality was assessed at hospital discharge, and functional outcome at 3 to 6 months with Cerebral Performance Categories (CPC), and was dichotomized as good (CPC 1-2) vs. poor (CPC 3-5). Independent predictors of outcome were identified by multivariable logistic regression and used to assess the prognostic value of a Reproducible Electro-clinical Prognosticators of Outcome Score (REPOS). Results: Patients (20/100) with good outcome had all a reactive EEG background. Incomplete recovery of brainstem reflexes, myoclonus, time to return of spontaneous circulation (ROSC) > 25 min, and unreactive EEG background were all independent predictors of death and severe disability, and were added to construct the REPOS. Using a cut-off of 0 or 1 variables for good vs. 2 to 4 for poor outcome, the REPOS had a positive predictive value of 1.00 (95% CI: 0.92-1.00), a negative predictive value of 0.43 (95% CI: 0.29-0.58) and an accuracy of 0.81 for poor functional recovery at 3 to 6 months. Conclusions: In comatose survivors of CA treated with IH, a prognostic score, including clinical and EEG examination, was highly predictive of death and poor functional outcome at 3 to 6 months. Lack of EEG background reactivity strongly predicted poor neurological recovery after CA. Our findings show that clinical and electrophysiological studies are effective in predicting long-term outcome of comatose survivors after CA and IH, and suggest that EEG improves early prognostic assessment in the setting of therapeutic cooling.

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia). RESULTS: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased. CONCLUSION: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.

Impact of duration of chest tube drainage on pain after cardiac surgery.

OBJECTIVE: This study was designed to analyze the duration of chest tube drainage on pain intensity and distribution after cardiac surgery. METHODS: Two groups of 80 cardiac surgery adult patients, operated on in two different hospitals, by the same group of cardiac surgeons, and with similar postoperative strategies, were compared. However, in one hospital (long drainage group), a conservative policy was adopted with the removal the chest tubes by postoperative day (POD) 2 or 3, while in the second hospital (short drainage group), all the drains were usually removed on POD 1. RESULTS: There was a trend toward less pain in the short drainage group, with a statistically significant difference on POD 2 (P=0.047). There were less patients without pain on POD 3 in the long drainage group (P=0. 01). The areas corresponding to the tract of the pleural tube, namely the epigastric area, the left basis of the thorax, and the left shoulder were more often involved in the long drainage group. There were three pneumonias in each group and no patient required repeated drainage. CONCLUSIONS: A policy of early chest drain ablation limits pain sensation and simplifies nursing care, without increasing the need for repeated pleural puncture. Therefore, a policy of short drainage after cardiac surgery should be recommended.

Sudden cardiac death in the young (5-39 years) in the canton of Vaud, Switzerland.

BACKGROUND: Sudden cardiac death (SCD) among the young is a rare and devastating event, but its exact incidence in many countries remains unknown. An autopsy is recommended in every case because some of the cardiac pathologies may have a genetic origin, which can have an impact on the living family members. The aims of this retrospective study completed in the canton of Vaud, Switzerland were to determine both the incidence of SCD and the autopsy rate for individuals from 5 to 39 years of age. METHODS: The study was conducted from 2000 to 2007 on the basis of official statistics and analysis of the International Classification of Diseases codes for potential SCDs and other deaths that might have been due to cardiac disease. RESULTS: During the 8 year study period there was an average of 292'546 persons aged 5-39 and there were a total of 1122 deaths, certified as potential SCDs in 3.6% of cases. The calculated incidence is 1.71/100'000 person-years (2.73 for men and 0.69 for women). If all possible cases of SCD (unexplained deaths, drowning, traffic accidents, etc.) are included, the incidence increases to 13.67/100'000 person-years. However, the quality of the officially available data was insufficient to provide an accurate incidence of SCD as well as autopsy rates. The presumed autopsy rate of sudden deaths classified as diseases of the circulatory system is 47.5%. For deaths of unknown cause (11.1% of the deaths), the autopsy was conducted in 13.7% of the cases according to codified data. CONCLUSIONS: The incidence of presumed SCD in the canton of Vaud, Switzerland, is comparable to the data published in the literature for other geographic regions but may be underestimated as it does not take into account other potential SCDs, as unexplained deaths. Increasing the autopsy rate of SCD in the young, better management of information obtained from autopsies as well developing of structured registry could improve the reliability of the statistical data, optimize the diagnostic procedures, and the preventive measures for the family members.

Evaluation of postmortem MDCT and MDCT-angiography for the investigation of sudden cardiac death related to atherosclerotic coronary artery disease.

The goal of this study was to evaluate the diagnostic value of postmortem multi-computed tomography (MDCT) and MDCT-angiography for sudden cardiac deaths related to ischemic heart disease. Twenty three cases were selected based on clinical history and the results of native MDCT, multiphase post-mortem CT-angiography and conventional autopsy were compared. Radiological examination showed calcification of coronary arteries in 78% of the cases, most of which were not detailed at autopsy. MDCT-angiography allowed better visualization of the coronary arteries than MDCT and permitted the evaluation of stenoses and occlusions. Of the 14 cases of coronary thrombosis detected at conventional autopsy, 11 were visible as stop of perfusion with CT-angiography and three were found to be partly perfused. One case had an old thrombosis with collateral circulation. One case had a coronary artery postmortem clot found with MDCT-angiography. Coronary artery calcifications are more easily detected and documented with radiological examination than with conventional autopsy. MDCT is of limited diagnostic value for ischemic heart disease. MDCT-angiography, when correctly interpreted, is a reasonable tool to view the morphology of coronary arteries, rule out significant coronary artery stenoses, identify occlusions and direct sampling for histological examination.

Effect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia.

AIM: Improving cerebral perfusion is an essential component of post-resuscitation care after cardiac arrest (CA), however precise recommendations in this setting are limited. We aimed to examine the effect of moderate hyperventilation (HV) and induced hypertension (IH) on non-invasive cerebral tissue oxygenation (SctO2) in patients with coma after CA monitored with near-infrared spectroscopy (NIRS) during therapeutic hypothermia (TH). METHODS: Prospective pilot study including comatose patients successfully resuscitated from out-of-hospital CA treated with TH, monitored with NIRS. Dynamic changes of SctO2 upon HV and IH were analyzed during the stable TH maintenance phase. HV was induced by decreasing PaCO2 from ∼40 to ∼30 mmHg, at stable mean arterial blood pressure (MAP∼70 mmHg). IH was obtained by increasing MAP from ∼70 to ∼90 mmHg with noradrenaline. RESULTS: Ten patients (mean age 69 years; mean time to ROSC 19 min) were studied. Following HV, a significant reduction of SctO2 was observed (baseline 74.7±4.3% vs. 69.0±4.2% at the end of HV test, p<0.001, paired t-test). In contrast, IH was not associated with changes in SctO2 (baseline 73.6±3.5% vs. 74.1±3.8% at the end of IH test, p=0.24). CONCLUSIONS: Moderate hyperventilation was associated with a significant reduction in SctO2, while increasing MAP to supra-normal levels with vasopressors had no effect on cerebral tissue oxygenation. Our study suggests that maintenance of strictly normal PaCO2 levels and MAP targets of 70mmHg may provide optimal cerebral perfusion during TH in comatose CA patients.

Body temperature regulation and outcome after cardiac arrest and therapeutic hypothermia.

OBJECTIVE: Therapeutic temperature modulation is recommended after cardiac arrest (CA). However, body temperature (BT) regulation has not been extensively studied in this setting. We investigated BT variation in CA patients treated with therapeutic hypothermia (TH) and analyzed its impact on outcome. METHODS: A prospective cohort of comatose CA patients treated with TH (32-34°C, 24h) at the medical/surgical intensive care unit of the Lausanne University Hospital was studied. Spontaneous BT was recorded on hospital admission. The following variables were measured during and after TH: time to target temperature (TTT=time from hospital admission to induced BT target <34°C), cooling rate (spontaneous BT-induced BT target/TTT) and time of passive rewarming to normothermia. Associations of spontaneous and induced BT with in-hospital mortality were examined. RESULTS: A total of 177 patients (median age 61 years; median time to ROSC 25 min) were studied. Non-survivors (N=90, 51%) had lower spontaneous admission BT than survivors (median 34.5 [interquartile range 33.7-35.9]°C vs. 35.1 [34.4-35.8]°C, p=0.04). Accordingly, time to target temperature was shorter among non-survivors (200 [25-363]min vs. 270 [158-375]min, p=0.03); however, when adjusting for admission BT, cooling rates were comparable between the two outcome groups (0.4 [0.2-0.5]°C/h vs. 0.3 [0.2-0.4]°C/h, p=0.65). Longer duration of passive rewarming (600 [464-744]min vs. 479 [360-600]min, p<0.001) was associated with mortality. CONCLUSIONS: Lower spontaneous admission BT and longer time of passive rewarming were associated with in-hospital mortality after CA and TH. Impaired thermoregulation may be an important physiologic determinant of post-resuscitation disease and CA prognosis. When assessing the benefit of early cooling on outcome, future trials should adjust for patient admission temperature and use the cooling rate rather than the time to target temperature.

La mort subite: de l' épidémiologie à la prévention [Sudden cardiac death: epidemiology and modern therapy].

Sudden Cardiac Death (SCD) has become an important public health challenge in the Western World. In Switzerland near 10,000 people suffer each year from SCD. The survival from SCD to hospital discharge is discouraging (near 5%). Large majority of events occur unexpectedly in the out-of-hospital environment and are not predicted with great accuracy by risk profiling. Because the majority of SCD occur by the mechanism of ventricular fibrillation, community-based defibrillation strategies have emerged as one approach to SCD problem. Newer strategies of defibrillation designed to respond faster to out-of-hospital cardiac arrest, including public access defibrillation, as well as aggressive primary and secondary prevention of coronary artery disease appears as the best approach for successful management of SCD.

Influence of deep sternal wound infection on long-term survival after cardiac surgery.

BACKGROUND: This study aimed to investigate the influence of deep sternal wound infection on long-term survival following cardiac surgery. MATERIAL AND METHODS: In our institutional database we retrospectively evaluated medical records of 4732 adult patients who received open-heart surgery from January 1995 through December 2005. The predictive factors for DSWI were determined using logistic regression analysis. Then, each patient with deep sternal wound infection (DSWI) was matched with 2 controls without DSWI, according to the risk factors identified previously. After checking balance resulting from matching, short-term mortality was compared between groups using a paired test, and long-term survival was compared using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS: Overall, 4732 records were analyzed. The mean age of the investigated population was 69.3±12.8 years. DSWI occurred in 74 (1.56%) patients. Significant independent predictive factors for deep sternal infections were active smoking (OR 2.19, CI95 1.35-3.53, p=0.001), obesity (OR 1.96, CI95 1.20-3.21, p=0.007), and insulin-dependent diabetes mellitus (OR 2.09, CI95 1.05-10.06, p=0.016). Mean follow-up in the matched set was 125 months, IQR 99-162. After matching, in-hospital mortality was higher in the DSWI group (8.1% vs. 2.7% p=0.03), but DSWI was not an independent predictor of long-term survival (adjusted HR 1.5, CI95 0.7-3.2, p=0.33). CONCLUSIONS: The results presented in this report clearly show that post-sternotomy deep wound infection does not influence long-term survival in an adult general cardio-surgical patient population.

Increased blood glucose variability during therapeutic hypothermia and neurological recovery after cardiac arrest

INTRODUCTION. Recent studies suggest that increased blood glucose variability (BGV) is associated with ICU mortality1. Hypothermia is known to induce insulin resistance, thus potentially increasing BGV. No studies however have examined the effect of therapeutic hypothermia (TH) on insulin requirements and BGV. OBJECTIVES. To examine the effect of TH on BGV and its relationship to outcome in patients with coma after cardiac arrest (CA). METHODS. We prospectively studied 132 consecutive comatose CA patients treated with TH (target core temp 33_C for 24 h, using surface cooling). All patients were treated with intravenous insulin (blood glucose target 6-8 mM), according to a written algorithm, with nurse-driven adjustment of insulin dose. For each patient, standard deviation of repeated blood glucose samples was used to calculate BGV. Two time-points, comparable in duration, were studied: TH (stable maintenance phase, i.e. 6-24 h, core temp ± 33_C) vs. Normothermia (NT, i.e. after rewarming, stable normothermic phase, core temp ± 37_C). Mortality and neurological recovery (Glasgow-Pittsburgh Cerebral Performance Categories, CPC, dichotomized as good = CPC 1-2 vs. poor = CPC 3-5) were assessed at hospital discharge. Statistical analysis was performed with ANOVA for repeated measures. RESULTS. Compared to NT, TH was associated with increased intravenous insulin dose (0.8 ± 1.1 vs. 1.6 ± 2 U/h, P\0.0001), higher mean (6.9 ± 1.3 vs. 7.7 ± 1.8 mM, P\0.0001) and maximum (9.1 ± 3.7 vs. 10.9 ± 3.6 mM, P\0.0001) blood glucose, and increased BGV (1.3 ± 1.2 vs. 1.7 ± 1.1 mM, P = 0.004). Increased BGV was strongly associated with mortality (2.5 ± 1.5 mM in non-survivors vs. 1.6 ± 1 mM in survivors, P\0.001) and worse outcome (2.3 ± 1.4 mM in patients with poor vs. 1.5 ± 0.8 mM in those with good neurological recovery, P\0.0001). CONCLUSIONS. Therapeutic hypothermia is associated with increased insulin requirements and higher blood glucose variability,which in turn correlateswithworse prognosis in patientswith post- CA coma. Strategies aimed to maintain stable glycemic profile and avoid blood glucose variability might contribute to optimize the management of TH and may translate into better outcome.