Post-cardiac Arrest Syndrome Patients Research Articles

Status of Systemic Oxidative Stress during Therapeutic Hypothermia in Patients with Post-Cardiac Arrest Syndrome

Therapeutic hypothermia (TH) is thought to be due to the downregulation of free radical production, although the details of this process remain unclear. Here, we investigate changes in oxidative stress and endogenous biological antioxidant potential during TH in patients with post-cardiac arrest syndrome (PCAS). Nineteen PCAS patients were enrolled in the study. Brain temperature was decreased to the target temperature of 33°C, and it was maintained for 24 h. Patients were rewarmed slowly (0.1°C/h, <1°C/day). The generation of reactive oxygen metabolites (ROMs) was evaluated in plasma samples by d-ROM test. Plasma antioxidant capacity was measured by the biological antioxidant potential (BAP) test. Levels of d-ROMs and BAP levels during the hypothermic stage (33°C) were suppressed significantly compared with pre-TH induction levels (P < 0.05), while both d-ROM and BAP levels increased with rewarming (33–36°C) and were correlated with brain temperature. Clinical monitoring of oxidative stress and antioxidant potential is useful for evaluating the redox state of patients undergoing TH after PCAS. Additional therapy to support the antioxidant potential in the rewarming stage following TH may reduce some of the observed side effects associated with the use of TH.

Abstract 9991: The Product of Blood Hemoglobin and Regional Brain Oxygen Saturation is a Simple and Excellent Predictor for a Short-term Neurological Outcome in Patients with Post Cardiac Arrest Syndrome

BACKGROUND: It has been suggested that brain tissue oxygenation (rSO2) and blood hemoglobin (Hb) at hospital arrival are independently crucial for a prognosis in post cardiac arrest syndrome (PCAS). Although it has been reported that rSO2 correlates with Hb in perioperative patients, this correlation has not been demonstrated during CPR. The product of Hb and rSO2 might represent tissue oxy-Hb level, theoretically. Therefore, it was speculated that the product during CPR predicts neurological outcome in PCAS. AIM: To investigate the relationship between the product of Hb and rSO2 on hospital arrival and good neurological outcome at 30 days in PCAS patients. METHODS: The database of the J-POP registry (multicenter observational study) has prospectively enrolled 764 OHCA patients. Of these, 193 PCAS patients admitted to the wards after ROSC were included in this study. Hb and rSO2 were obtained during resuscitation within 3 min after hospital arrival. The neurological outcome was evaluated by CPC at 30 days, and CPC1 and 2 were defined as favorable neurological outcome. RESULTS: Among 193 PCAS patients, 27 presented favorable outcome (14%) and median [IQR] of Hb and rSO2 were 12.0g/dL [10.4-13.8] and 35% [15-55]. The favorable outcome group showed higher Hb (13.8+/-2.5 vs. 11.7+/-2.7, p&lt;0.001) and rSO2 (58.6 +/- 20.5 vs. 30.6+/-21.0, p&lt;0.001) compared to the unfavorable group. The ROC analysis revealed the product of Hb and rSO2 significantly predicted the favorable outcome (AUC, 0.861; optimal cut-off point, 411; sensitivity, 0.917; specificity, 0.709). When divided into 4 groups by quartile of the product of Hb and rSO2 level, the ratio of patients with favorable outcome was 4.2% in the first quartile (Q1, the product&lt;182), 4.2% in Q2 (183-257), 16.6% in Q3 (258-627), and 75.0% in Q4 (&gt;628), respectively (chi-square test: p&lt;0.001). CONCLUSIONS: The product of blood Hb and rSO2 level during resuscitation is a simple and excellent predictor for a 30-day neurological outcome in patients with PCAS.

Abstract 260: Relationship Between the Blood Hemoglobin Level at Hospital Arrival and Post--Cardiac Arrest Neurological Outcome

OBJECTIVE: Recent studies have revealed that regional brain oxygen saturation (rSO2) is an excellent predictor for a neurological outcome in OHCA. It also has been suggested that brain tissue oxygenation is crucial for a post cardiac arrest syndrome (PCAS). Hemoglobin (Hb) is an indispensable for oxygen delivery to peripheral tissue. Therefore, it is considered that Hb plays an important role in PCAS. In the present study, we aim to elucidate the relationship between blood Hb level and the neurological outcome in PCAS. METHODS: The database of the J-POP registry (multicenter observational study) has prospectively enrolled 764 OHCA patients. Of these, 193 PCAS patients admitted to the wards after ROSC were included in this study. Blood Hb level (median 12.0g/dL, [IQR 10.4-13.8]) and rSO2 (35%, [15-55]) were obtained during resuscitation within 3 min after hospital arrival. The neurological outcome was evaluated by CPC at 30 days, and CPC1 and 2 were defined as favorable neurologic outcome. RESULTS: Among 193 PCAS patients, 27 showed favorable outcome (14%). There was no significant correlation between rSO2 and Hb level (P=0.43). Univariate analyses revealed that the favorable outcome group was characterized as younger, male, witnessed CA, initial shockable rhythm, higher Hb level, rSO2&gt;35%, and shorter transport interval from the scene to the hospital. Coronary angiography (CAG) and therapeutic hypothermia were also associated with the favorable outcome. The multivariate analysis showed that rSO2&gt;35% (OR 35.0 [7.5-163.4]), Hb (1.48 [1.08-2.01]), CAG (45.8 [7.7-271.1]) were independent predictors for the favorable outcome. CONCLUSIONS: A higher blood Hb level was associated with a favorable short-term neurological outcome in patients with PCAS regardless of rSO2.

Abstract 310: Evaluation of the Appropriate Timing for Inducing Therapeutic Hypothermia with Extracorporeal Membrane Oxygenation for Out-of-Hospital Cardiac Arrest in Acute Coronary Syndrome

Purpose: Mild therapeutic hypothermia has been integrated into management strategies for improving the neurological outcome of cardiac arrest for out of hospital cardiac arrest. On the other hand, acute coronary syndrome (ACS) cases should be treated as earlier. We have the dilemma between two procedures when we face any cases of post cardiac arrest syndrome (PCAS). We reported rapid and safe hypothermia induction with Less Invasive Cardiopulmonary bypass Hypothermia (LICH) before. This study aimed to evaluate an appropriate timing to induce LICH ‘before or after’ investigations for coronary angiography (CAG). Methods: Sixteen PCAS patients for ACS were treated with LICH. These patients were divided into before CAG (Group B, N=12) and after CAG (Group A, N=4) groups. The LICH procedure was indicated for unconscious ROSC patients under 75 years of age, and excluded with brain hemorrhage, traumatic cardiac arrest, and any risk of bleeding. Target temperature was set at 34 to 35°C for 36 to 48 hours. The specifications LICH procedure were quickly induced hypothermia via narrow pediatric cannulas on low-perfusion (1 l/min) artery-venous extra corporeal membranous oxygenation with minimal anticoagulation. Any complications, time to target temperature, temperature stability, cytokines and neurological outcomes were compared. A favorable outcome was defined as a Cerebral Performance Category (CPC) of 1-2. Results: There were no significant characteristic differences except the time to target temperature (69min vs. 161min, p&lt;0.01) between group B and A. Any complications and favorable outcomes were no significant differences in both groups. Conclusions: We suggest that we can choice both way early and late induction for hypothermia with LICH. These results mean an early coronary reperfusion is acceptable because of the advantages of quick induction to the target temperature.

Abstract 221: The Use of Invasive Hemodynamic Monitoring in Evaluating Resuscitative End Points in Post--Cardiac Arrest Therapeutic Hypothermia (COMICA Study Group)

Introduction: Patients who suffer from post-cardiac arrest syndrome (PCAS) often exhibit an inflammatory response similar to a sepsis syndrome. Invasive hemodynamic monitoring of resuscitative endpoints has been proven to impart better mortality outcomes in sepsis and has been recommended for goal-directed management of PCAS patients. Hypothesis: Centers engaged in aggressive post-cardiac arrest care will utilize invasive hemodynamic monitoring to ascertain adequacy of resuscitative endpoints including central venous pressure (CVP) and central venous oxygen saturation (ScvO 2 ). Methods: This study is a collaboration of 4 centers with aggressive PCAS and therapeutic hypothermia protocols. It is a secondary analysis from prospectively collected data of out-of-hospital cardiac arrest patients who underwent TH. The primary objective was to determine the use of invasive hemodynamic monitoring in the care of PCAS patients undergoing TH. The secondary objective was to determine if either CVP or ScvO 2 were associated with neurologic outcome measured as cerebral performance category (CPC), dichotomized into “good” (1 or 2) or “poor” (3, 4 or 5). Study variables were abstracted at baseline, 12, 24, 36 and 48 hrs. Results: A total of 111 patients were enrolled. Patients were 61 ± 16.8 yrs, 59.5% male, and had an initial rhythm of VF/VT in 50.5% of cases. At baseline, 11% (12/111) of patients had a CVP recorded and 3.6% (4/111) has ScvO 2 measured. During the middle 24 hrs, an average of 65% (72) of patients had CVP recordings and 21.6% (24) of patients had ScvO 2 recorded. ScvO 2 values were not different between patients with good versus poor neurologic outcome. Lower CVP measurement was associated with better neurologic outcome. Conclusion: ScvO 2 was infrequently utilized in this cohort of PCAS patients undergoing TH. CVP was utilized at higher rates, and lower CVP recordings were correlated with better neurologic outcome.

The use of invasive hemodynamic monitoring in evaluating resuscitative endpoints in post-cardiac arrest patientsStatus: PendingCategory: Post Resuscitation Care

Purpose: Patients who suffer from post-cardiac arrest syndrome (PCAS) often exhibit an inflammatory response similar to a sepsis syndrome. Invasive hemodynamic monitoring of resuscitation endpoints has been recommended for PCAS patients but few real-world data have been published. We hypothesized that centers engaged in PCAS management would routinely utilize invasive hemodynamic monitoring in the early hours after return of spontaneous circulation (ROSC) to measure central venous pressure (CVP) and central venous oxygen saturation (ScvO2) to help guide resuscitation.

The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia

AimThe incidence and timing of electrographic seizures and epileptiform activity in comatose, adult, post-cardiac arrest syndrome (PCAS) patients treated with therapeutic hypothermia (TH) have not been extensively investigated. We hypothesized that onset most frequently occurs within the first 24h post-arrest and is associated with poor neurologic outcome. MethodsSingle-center, retrospective analysis of a cohort of 38 comatose PCAS patients treated with TH and continuous-EEG-monitoring (cEEG), initiated as soon as possible after ICU admission. All raw cEEG waveform records were cleared of annotations and clinical information and classified by two fellowship-trained electroencephalographers. ResultsTwenty-three percent (9/38) of patients had electrographic seizures (median onset 19h post-arrest); 5/9 (56%) had seizure-onset prior to rewarming; 7/9 (78%) had status epilepticus. Forty-five percent (17/38) had evidence of epileptiform activity (electrographic seizures or interictal epileptiform discharges), typically occurring during first 24h post-arrest. Interictal epileptiform activity was highly associated with later detection of electrographic seizures (6/14, 43%, p=0.001). Ninety-four percent (16/17) of patients with epileptiform activity had poor neurologic outcome or death at discharge (Cerebral Performance Category scale 3–5; p=0.002) as did all (9/9) patients with electrographic seizures (p=0.034). ConclusionsElectrographic seizures and epileptiform activity are common cEEG findings in comatose, PCAS patients treated with TH. In this preliminary study, most seizures were status epilepticus, had onset prior to rewarming, evolved from prior interictal epileptiform activity, and were associated with short-term mortality and poor neurologic outcome. Larger, prospective studies are needed to further characterize seizure activity in comatose post-arrest patients.

Early findings on brain computed tomography and the prognosis of post-cardiac arrest syndrome: Application of the score for stroke patients

AimTo examine whether early findings of the brain computed tomography (CT) evaluated by the modified Alberta stroke programme early CT (m-ASPECT) score is useful for determining the prognosis of post-cardiac arrest syndrome (PCAS) patients or not. MaterialsFrom 2003 through 2010, 149 consecutive PCAS patients: (1) with various aetiologies but neither from haemorrhagic stroke nor trauma, (2) who were 15years old or older and (3) whose brain CT was available were admitted to our intensive care unit. Early findings on all of their CT images were rated with the m-ASPECT scoring system by three raters, and an inter-rater comparison was conducted. Next, the images within 24h from arrest were collected from 133 patients (89 males, age 60.2±17.6years), and a relation of the scores with outcome at day 30 of the patients was analysed. ResultsAccording to the inter-rater comparison based on a linear regression analysis, agreement between the raters was good (correlation coefficient 0.76–0.88). A receiver operating curve analysis revealed that the m-ASPECT scores within 24h were a good predictor of poor outcome (dead or vegetative state) with an area under the curve of 0.905. An m-ASPECT score ≤13 was 100% predictive of a poor outcome, with a negative predictive value of 0.57. The m-ASPECT score was the best predictor of poor outcome (odds ratio 45.62) among various factors including cause or duration of arrest. ConclusionThe m-APSECT score evaluated within 24h from arrest was found to be the most predictive factor for outcome at day 30.

Abstract 262: Slight Therapeutic Hypothermia (35°C to 36°C) for Post--Cardiac Arrest Syndrome Due to Ventricular Fibrillation with Low Left Cardiac Function Is a Feasible and Safe Possibility

Background: Mild therapeutic hypothermia (32-34°C, 24-48 hours: mild TH) for post cardiac arrest syndrome (PCAS) due to ventricular fibrillation (VF) had been recommended in the American Heart Association (AHA) Guidelines 2005 (class IIa) and the International Liaison Committee on Resuscitation (ILCOR). In the AHA guidelines 2010, it has been recommended more strongly (class I). But it is still unknown what temperature is best for low cardiac function patients including acute myocardial infarction (AMI) cases. Sometimes executing mild TH for patients with severe left ventricular dysfunction are not so easy and safe because of hypotension, arrhythmias, unstable vital signs and so on. So we studied whether slight therapeutic hypothermia (35-36°C: Slight TH) was effective and safe compare with mild TH for PCAS due to VF. Methods: Consecutive PCAS patients who were witnessed, done by-stander cardiopulmonary resuscitation (CPR), confirmed VF caused by cardiac or coronary events and introduced therapeutic hypothermia for the latest 45 months were sorted into the GroupM (Mild TH, 34°C, 24-72 hours) and the GroupS (Slight TH, 35-36°C, 24-72 hours).The primary end point was a favorable neurologic outcome (cerebral performance category: CPC 1 or 2) in 28th days after cardiac arrest. Secondary end points were the changes of cardiac index (CI) after introducing therapeutic hypothermia, the time required to reach target temperature and the rate of complications (infections, bleeding, arrhythmias etc.) within fourteen days. Results: Thirty-five patients (twenty AMI cases) were studied (GroupM 20 patients and GroupS 15 patients). The rate of favorable neurologic outcome was available and did not differ significantly between the two groups (50% vs. 53%, p=0.85). The time to reach target temperature was significantly shorter in the GroupS (5.9h vs. 0.9h, p&lt;0.01). The decrease of CI was remarkable in the groupM (before TH/during TH, GroupM 2.8/2.2, GroupS 1.9/2.1, the changes of them were Δ32% vs. +0.05%, p&lt;0.01). The rate of complications did not differ significantly between them and there were no major complications. Conclusion: Slight therapeutic hypothermia for PCAS due to VF with low cardiac function is possibility feasible and safe.

Bispectral index and suppression ratio during hypothermia after cardiac arrest

Dear Editor, I read with interest the paper written by Dr. Seder et al. [1]. Neurological outcome is challenging to predict in unconscious postcardiac arrest syndrome (PCAS) patients especially during therapeutic hypothermia. Dr. Seder’s paper reported that a low bispectral index (BIS) value and a high suppression ratio (SR) could predict poor outcome even in the very early phase (mean time of 280 min) after the resumption of spontaneous circulation (ROSC) in PCAS patients [1]. We have examined serial data of BIS and SR in PCAS patients for determining the neurological outcome under the continuous administration of muscle relaxant from soon after ROSC [2]. In these series, we had a case of very low BIS (near zero) and high SR (around 90) soon after ROSC, which were followed by a gradual increase in BIS values and a decrease in SRs within 12 h after admission. Thereafter, these changes were so apparent that BIS values elevated to higher levels than those of SRs 40 h after admission. This patient eventually recovered to cerebral performance category (CPC) level 2. Dr. Seder’s group obtained intermittent data of BIS and SR after bolus injection of neuromuscular blockade and concluded that a BIS value less than 22 (sensitivity 0.86 and specificity 0.94) and SR more than 48 (sensitivity 0.84 and specificity 0.93) could predict poor outcome of CPC 3–5 even in the very early phase after ROSC. However, such data obviously included false positive cases. In this letter, we emphasize a potential failure to predict neurological outcome when using intermittent sampling of BIS value in unconscious PCAS patients treated with hypothermia in the very early phase as Dr. Seder’s group indicated.

Neither institutional therapeutic hypothermia protocols nor published implementation studies specify goal arterial oxygen levels in post-arrest patients

Background: Therapeutic hypothermia (TH) improves outcomes in comatose post-cardiac arrest syndrome (PCAS) patients and the 2008 AHA Consensus Statement on PCAS suggests adoption of a comprehensive clinical pathway, or bundle of care, for management of PCAS patients. One aspect of that bundle of care is management of the fraction of inspired oxygen (FiO2) provided to the patient, targeting a specific partial pressure of arterial oxygen (PaO2) or peripheral oxygen saturation (SO2). Animal studies suggest that the FiO2 should be rapidly titrated down over the first hour after arrest to optimize outcomes.

Management of Brain Injury after Post-cardiac Arrest Syndrome

In spite of improvement in cardiopulmonary resuscitation (CPR) techniques, post-CPR mortality and brain injury rates have not changed significantly. The post-cardiac arrest syndrome has been suggested to be the major reason for the high mortality rate after CPR. Post-cardiac arrest syndrome, including brain injury, myocardial dysfunction, and septic shock-like syndrome after CPR, result in complicated multiple organ failure. Physicians who work in the ICU should have a good understanding of thepathophysiology of post-cardiac arrest syndrome. Recently, therapeutic hypothermia treatment for protection of brain injuries has been applied as a therapeutic regimen in spite of various side effects during the hypothermic procedure. Finally, therapeutic hypothermic treatment to reduce brain injury in post-cardiac arrest syndrome patients is strongly recommended to physiciansmanaging CPR. I would like to briefly review the therapeutic hypothermic procedure for the management of post-cardiac arrest syndrome.

25. Coagulation factor XI: rather a fibrinolytic inhibitor than a coagulation factor

Post-cardiac arrest syndrome (PCAS) is often associated with disseminated intravascular coagulation (DIC), thus leading to the development of multiple organ dysfunction syndrome (MODS). The aim of this study was to examine the pathophysiological relationships between coagulation, fibrinolysis and fibrinolytic shutdown by evaluating the levels of coagulofibrinolytic markers, including soluble fibrin, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPAIC), plasmin-alpha2 plasmin inhibitor complex (PPIC), neutrophil elastase and fibrin degradation product by neutrophil elastase (EXDP).Fifty-two resuscitated patients were divided into two groups: 22 DIC and 30 non-DIC patients.The levels of soluble fibrin, PPIC, tPAIC, EXDP and neutrophil elastase in the DIC patients with PCAS were significantly higher than those observed in the non-DIC patients. The values of the tPAIC and JAAM DIC scores were found to be independent predictors of increased SOFA scores in the DIC patients. The MODS patients demonstrated significantly higher levels of soluble fibrin and tPAIC; however, the levels of TAFI and EXDP were identical between the patients with and without MODS. In addition, positive correlations were observed between the levels of tPAIC and EXDP in the patients with non-MODS; however, no correlations were observed between these markers in the MODS patients.Thrombin activation and fibrinolytic shutdown play important roles in the development of organ dysfunction in PCAS patients. Neutrophil elastase-mediated fibrinolysis cannot overcome the fibrinolytic shutdown that occurs in DIC patients with PCAS, thus resulting in the development of MODS.