Changes in health status and health related quality of life from six months to five years in out-of-hospital cardiac arrest survivors - A NORCAST sub study.

BACKGROUND: Brain injury in out-of-hospital cardiac arrest (OHCA) survivors affects health status and health-related quality of life (HRQoL). It is unknown how HRQoL evolves over time, and assessments at different time points may lead to different results. METHODS: In a NORCAST sub study, OHCA survivors eligible for health status (EQ-5D-3L) and HRQoL (SF-36) assessments were examinated six months and five years after OHCA. At five-year follow-up, survivors also retrospectively assessed their health status for each consecutive year following OHCA. The next of kin independently assessed health status and HRQoL of their respective OHCA survivors. RESULTS: Among 138 survivors alive after six months and 117 after five years, 80 (88% male) completed both follow-ups. Health status and HRQoL remained stable over time, except for increasing SF-36 mental summary score and decreasing physical functioning and physical component score. Anxiety and depression levels were generally low, although younger survivors stated more anxiety than older survivors. Retrospective assessment showed reduced health status for the first two years, which increased only from the third year. Explorative analyses revealed that younger age, longer time to return of spontaneous circulation (tROSC) and late awakening affected health status, particularly in the first two years post-arrest. CONCLUSIONS: OHCA survivors showed stable health status and HRQoL with only minor differences between six months and five years. Younger survivors with long tROSC, late awakening, and more anxiety and depression symptoms at six months, had reduced health status the first two years with significant improvements towards the fourth year.

Complement activation is associated with poor outcome after out-of-hospital cardiac arrest.

BACKGROUND: Cardiopulmonary resuscitation after cardiac arrest initiates a whole-body ischemia-reperfusion injury, which may activate the innate immune system, including the complement system. We hypothesized that complement activation and subsequent release of soluble endothelial activation markers were associated with cerebral outcome including death. METHODS: Outcome was assessed at six months and defined by cerebral performance category scale (1-2; good outcome, 3-5; poor outcome including death) in 232 resuscitated out-of-hospital cardiac arrest patients. Plasma samples obtained at admission and day three were analysed for complement activation products C3bc, the soluble terminal complement complex (sC5b-9), and soluble CD14. Endothelial cell activation was measured by soluble markers syndecan-1, sE-selectin, thrombomodulin, and vascular cell adhesion molecule. RESULTS: Forty-nine percent of the patients had good outcome. C3bc and sC5b-9 were significantly higher at admission compared to day three (p < 0.001 for both) and in patients with poor compared to good outcome (p = 0.03 and p < 0.001, respectively). Unadjusted, higher sC5b-9 at admission was associated with poor outcome (odds ratio 1.08 (95% CI 1.01-1.14), p = 0.024). Adjusted, sC5b-9 was still associated with outcome, but the association became non-significant when time to return-of-spontaneous-circulation above 25 min was included as a covariate. Endothelial cell activation markers increased from admission to day three, but only sE-selectin and thrombomodulin were significantly higher in patients with poor versus good outcome (p = 0.004 and p = 0.03, respectively) and correlated to sCD14 and sC5b-9/C3bc, respectively. CONCLUSION: Complement system activation, reflected by sC5b-9 at admission, leading to subsequent endothelial cell activation, was associated with poor outcome in out-of-hospital cardiac arrest patients.

Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest - results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST).

BACKGROUND: Outcome prediction after out-of-hospital cardiac arrest (OHCA) may lead to withdrawal of life-sustaining therapy if the prognosis is perceived negative. Single use of uncertain prognostic tools may lead to self-fulfilling prophecies and death. We evaluated prognostic tests, blinded to clinicians and without calls for hasty outcome prediction, in a prospective study. METHODS: Comatose, sedated TTM 33-treated OHCA patients of all causes were included. Clinical-neurological/-neurophysiological/-biochemical predictors were registered. Patients were dichotomized into good/poor outcome using cerebral performance category (CPC) six months and > four years post-arrest. Prognostic tools were evaluated using false positive rates (FPR). RESULTS: We included 259 patients; 49 % and 42 % had good outcome (CPC 1-2) after median six months and 5.1 years. Unwitnessed arrest, non-shockable rhythms, and no-bystander-CPR predicted poor outcome with FPR (CI) 0.05 (0.02-0.10), 0.13 (0.08-0.21), and 0.13 (0.07-0.20), respectively. Time to awakening was median 6 (0-25) days in good outcome patients. Among patients alive with sedation withdrawal >72 h, 49 % were unconscious, of whom 32 % still obtained good outcome. Only absence of pupillary light reflexes (PLR) -and N20-responses in somato-sensory evoked potentials (SSEP), as well as increased neuron-specific enolase (NSE) later than 24 h to >80 µg/L, had FPR 0. Malignant EEG (burst suppression/epileptic activity/flat) differentiated poor/good outcome with FPR 0.05 (0.01-0.15). CONCLUSION: Time to awakening was over six days in good outcome patients. Most clinical parameters had too high FPRs for prognostication, except for absent PLR and SSEP-responses >72 h after sedation withdrawal, and increased NSE later than 24 h to >80 µg/L.

Comparison of three haemodynamic monitoring methods in comatose post cardiac arrest patients.

OBJECTIVES: Haemodynamic monitoring during post arrest care is important to optimise treatment. We compared stroke volume measured by minimally-invasive monitoring devices with or without thermodilution calibration, and transthoracic echocardiography (TTE), and hypothesised that thermodilution calibration would give stroke volume index (SVI) more in agreement with TTE during targeted temperature management (TTM). DESIGN: Comatose out-of-hospital cardiac arrest survivors receiving TTM (33 °C for 24 hrs) underwent haemodynamic monitoring with arterial pulse contour analyses with (PiCCO2®) and without (FloTrac®/Vigileo® monitor®) transpulmonary thermodilution calibration. Haemodynamic parameters were collected simultaneously every fourth hour during TTM (hypothermia) and (normothermia). SVI was measured with TTE during hypothermia and normothermia. Bland-Altman analyses were used for determination of SVI bias (±1SD). RESULTS: Twenty-six patients were included, of whom 77% had initial shockable rhythm and 52% discharged with good outcome. SVI (bias ±2SD) between PiCCO (after thermodilution calibration) vs FloTrac/Vigileo, TTE vs FloTrac/Vigileo and TTE vs PiCCO were 1.4 (±25.8), -1.9 (±19.8), 0.06 (±18.5) ml/m2 during hypothermia and 9.7 (±23.9), 1.0 (±17.4), -7.2 (±12.8) ml/m2 during normothermia. Continuous SVI measurements between PiCCO and FloTrac/Vigileo during hypothermia at reduced SVI (<35 ml/m2) revealed low bias and relatively narrow limits of agreement (0.5 ± 10.2 ml/m2). CONCLUSION: We found low bias, but relatively wide limits of agreement in SV with PiCCO, FloTrac/Vigileo and TTE during TTM treatment. The methods are not interchangeable. Precision was not improved by transpulmonary thermodilution calibration during hypothermia.

Post-Resuscitation ECG for Selection of Patients for Immediate Coronary Angiography in Out-of-Hospital Cardiac Arrest.

BACKGROUND: We aimed to investigate coronary angiographic findings in unselected out-of-hospital cardiac arrest patients referred to immediate coronary angiography (ICA) irrespective of their first postresuscitation ECG and to determine whether this ECG is useful to select patients with no need of ICA. METHODS AND RESULTS: All resuscitated patients admitted after out-of-hospital cardiac arrest without a clear noncardiac cause underwent ICA. Patients were retrospectively grouped according to the postresuscitation ECG blinded for ICA results: (1) ST elevation or presumably new left bundle branch block, (2) other ECG signs indicating myocardial ischemia, and (3) no ECG signs indicating myocardial ischemia. All coronary angiograms were reevaluated blinded for postresuscitation ECGs. Two hundred and ten patients were included with mean age 62±12 years. Six-months survival with good neurological outcome was 54%. Reduced Thrombolysis in Myocardial Infarction flow (0-2) was found in 55%, 34%, and 18% and a ≥90% coronary stenosis was present in 25%, 27%, and 19% of patients in group 1, 2, and 3, respectively. An acute coronary occlusion was found in 11% of patients in group 3. ST elevation/left bundle branch block identified patients with reduced Thrombolysis in Myocardial Infarction (0-2) flow with 70% sensitivity and 62% specificity. Among patients with initial nonshockable rhythms (24%), 32% had significantly reduced Thrombolysis in Myocardial Infarction flow. CONCLUSIONS: Initial ECG findings are not reliable in detecting patients with an indication for ICA after experiencing a cardiac arrest. Even in the absence of ECG changes indicating myocardial ischemia, an acute culprit lesion may be present and patients may benefit from emergent revascularization. CLINICAL TRIAL REGISTRATIONURL: http://www.clinicaltrials.gov. Unique identifier: NCT01239420.

Bradycardia during therapeutic hypothermia is associated with good neurologic outcome in comatose survivors of out-of-hospital cardiac arrest.

OBJECTIVE: Comatose patients resuscitated after out-of-hospital cardiac arrest receive therapeutic hypothermia. Bradycardia is frequent during therapeutic hypothermia, but its impact on outcome remains unclear. We explore a possible association between bradycardia during therapeutic hypothermia and neurologic outcome in comatose survivors of out-of-hospital cardiac arrest. DESIGN: Retrospective cohort study, from January 2009 to January 2011. SETTING: University hospital medical and cardiac ICUs. PATIENTS: One hundred eleven consecutive comatose out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. INTERVENTIONS: Patients treated with standardized treatment protocol after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: All out-of-hospital cardiac arrest patients' records were reviewed. Hemodynamic data were obtained every fourth hour during the first days. The patients were in temperature target range (32-34°C) 8 hours after out-of-hospital cardiac arrest and dichotomized into bradycardia and nonbradycardia groups depending on their actual heart rate less than or equal to 60 beats/min or more than 60 beats/min at that time. Primary endpoint was Cerebral Performance Category score at hospital discharge. More nonbradycardia group patients received epinephrine during resuscitation and epinephrine and norepinephrine in the early in-hospital period. They also had lower base excess at admission. Survival rate with favorable outcome was significantly higher in the bradycardia than the nonbradycardia group (60% vs 37%, respectively, p = 0.03). For further heart rate quantification, patients were divided into quartiles: less than or equal to 49 beats/min, 50-63 beats/min, 64-77 beats/min, and more than or equal to 78 beats/min, with respective proportions of patients with good outcome at discharge of 18 of 27 (67%), 14 of 25 (56%), 12 of 28 (43%), and 7 of 27 (26%) (p = 0.002). Patients in the lowest quartile had significantly better outcome than the higher groups (p = 0.027), whereas patients in the highest quartile had significantly worse outcome than the lower three groups (p = 0.013). CONCLUSIONS: Bradycardia during therapeutic hypothermia was associated with good neurologic outcome at hospital discharge. Our data indicate that bradycardia should not be aggressively treated in this period if mean arterial pressure, lactate clearance, and diuresis are maintained at acceptable levels. Studies, both experimental and clinical, are warranted.