Arrhythmias and heart rate variability during and after therapeutic hypothermia for cardiac arrest.

OBJECTIVE: To evaluate the effects of therapeutic hypothermia (HT) of 33 degrees C after cardiac arrest (CA) on cardiac arrhythmias, heart rate variability (HRV), and their prognostic value. DESIGN: Prospective, comparative substudy of a randomized controlled trial of mild HT after out-of-hospital CA, the European Hypothermia After Cardiac Arrest study. SETTING: Intensive care unit of a tertiary referral hospital (Helsinki University Hospital). PATIENTS: Seventy consecutive adult patients resuscitated from out-of-hospital ventricular fibrillation were randomly assigned either to therapeutic HT of 33 degrees C or normothermia. INTERVENTIONS: Patients randomized to HT were cooled with an external cooling device for 24 hours and then allowed to rewarm slowly during 12 hours. In the normothermia group, the core temperature was kept <38 degrees C by antipyretics and physical means. All patients received standard intensive care for at least 2 days. MEASUREMENTS AND MAIN RESULTS: Twenty-four hour ambulatory electrocardiography recordings were performed at 0-24 hours, at 24-48 hours, and at 14 days. The clinical outcome was assessed at 6 months after CA. The occurrence of premature ventricular beats was increased in the HT-treated group during the first two recordings, with no difference in the number of ventricular tachycardia or ventricular fibrillation episodes. All HRV values were significantly higher during the HT (p < 0.01), but no differences were observed 2 weeks later. In multivariate analysis, only shorter delay to restoration of spontaneous circulation (p = 0.009) and the sd of individual normal-to-normal intervals >100 msec of the 24-48-hour recording in the HT group (p = 0.018) predicted good outcome. CONCLUSIONS: The use of therapeutic HT of 33 degrees C for 24 hours after CA was not associated with an increase in clinically significant arrhythmias. Preserved 24 to 48-hour HRV may be a predictor of favorable outcome in patients with CA treated with HT.

Cognitive and neurophysiological outcome of cardiac arrest survivors treated with therapeutic hypothermia.

BACKGROUND AND PURPOSE: Cognitive deficits are common in survivors of cardiac arrest (CA). The aim of this study was to examine the effect of therapeutic hypothermia after CA on cognitive functioning and neurophysiological outcome. METHODS: A cohort of 70 consecutive adult patients resuscitated from out-of-hospital ventricular fibrillation CA were randomly assigned to therapeutic hypothermia of 33 degrees C for 24 hours accomplished by external cooling or normothermia. Neuropsychological examination was performed to 45 of the 47 conscious survivors of CA (27 in hypothermia and 18 in normothermia group) 3 months after the incident. Quantitative electroencephalography (Q-EEG) and auditory P300 event-related potentials were studied on 42 patients at the same time point. RESULTS: There were no differences between the 2 treatment groups in demographic variables, depression, or delays related to the resuscitation. No differences were found in any of the cognitive functions between the 2 groups. 67% of patients in hypothermia and 44% patients in normothermia group were cognitively intact or had only very mild impairment. Severe cognitive deficits were found in 15% and 28% of patients, respectively. All Q-EEG parameters were better in the hypothermia-treated group, but the differences did not reach statistical significance. The amplitude of P300 potential was significantly higher in hypothermia-treated group. CONCLUSIONS: The use of therapeutic hypothermia was not associated with cognitive decline or neurophysiological deficits after out-of-hospital CA.

Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia.

BACKGROUND AND PURPOSE: High serum levels of neuron-specific enolase (NSE) and S-100B protein are known to be associated with ischemic brain injury and poor outcome after cardiac arrest. Therapeutic hypothermia has been shown to improve neurological outcome after cardiac arrest. The aim of this study was to evaluate the effect of therapeutic hypothermia on levels of serum NSE and S-100B protein, their time course, and their prognostic value in predicting unfavorable outcome after out-of-hospital cardiac arrest. METHODS: Seventy patients resuscitated from ventricular fibrillation were randomly assigned to hypothermia of 33+/-1 degrees C for 24 hours or to normothermia. Serum NSE and S-100B were sampled at 24, 36, and 48 hours after cardiac arrest. Neurological outcome was dichotomized into good or poor at 6 months after cardiac arrest. RESULTS: The levels of NSE (P=0.007 by analysis of variance for repeated measurements) but not S-100B were lower in hypothermia- than normothermia-treated patients. A decrease in NSE values between 24 and 48 hours was observed in 30 of 34 patients (88%) in the hypothermia group and in 16 of 32 patients (50%) in the normothermia group (P<0.001). The decrease in NSE values was associated with good outcome at 6 months after cardiac arrest (P=0.005), recovery of consciousness (P<0.001), and survival for at least 6 months after cardiac arrest (P=0.012). CONCLUSIONS: Decreasing levels of serum NSE but not S-100B over time may indicate selective attenuation of delayed neuronal death by therapeutic hypothermia in victims of cardiac arrest.

Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin-4 and -10 levels in critically ill patients with sepsis.

It has been suggested that excessive activation of the anti-inflammatory pathways in sepsis may lead to poor outcome of patients with sepsis. The aim of this study was to test the value of histocompatibility leukocyte antigen (HLA)-DR-expression on blood monocytes and plasma levels of interleukin (IL)-4 and -10 in prediction of hospital mortality in patients with sepsis. Sixty-one critically ill patients with sepsis were prospectively enrolled to this study in two university hospital intensive care units. Survivors (n = 41) and nonsurvivors (n = 20) differed significantly in HLA-DR expression at admission: survivors' median 84% (interquartile range 64%-98%) versus nonsurvivors' median 62% (interquartile range 47%-83%, P = 0.025 by Mann-Whitney test). Similarly, the analysis revealed statistically significant differences between survivors and nonsurvivors in admission plasma IL-10 levels and in admission Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, but not in IL-4 levels. The areas under receiver operating curves (AUC) showed that both monocyte HLA-DR expression and plasma IL-4 level showed poor discriminative power in prediction of hospital mortality (AUC < 0.70). Only IL-10 levels on days 1 and 2 showed reasonable predictive power (AUCs 0.706 and 0.725, respectively). The highest AUC values were those of APACHE-II (0.786) and admission SOFA score (0.763). In conclusion, APACHE II and SOFA scores on admission showed better discriminatory power than HLA-DR expression and IL-10 and IL-4 levels in prediction of hospital mortality in critically ill patients with sepsis.

A prospective study of inflammation markers in patients at risk of indirect acute lung injury.

Systemic inflammation triggered by insults like sepsis and acute pancreatitis may play a role in development of indirect acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Because little is known about the course of systemic inflammation on the days preceding diagnosis of ARDS, we prospectively monitored immune inflammatory status in 52 patients at risk and we assessed the presence of ALI and ARDS on day 7 after admission to the intensive care unit. On admission, serum interleukin (IL) 8, IL-6, and soluble IL-2 receptor concentrations were significantly higher in patients with subsequent ALI (n = 18) than in patients without ALI (n = 30). During a 4-day follow-up, IL-8 and IL-6 levels of ALI patients remained high and those of non-ALI patients decreased. None of the markers discriminated ARDS patients (n = 9) from non-ARDS ALI patients (n = 9). Among 11 patients with acute pancreatitis, ALI patients had significantly higher IL-8, IL-6, and phagocyte CD11b expression levels than did non-ALI patients, whereas among 14 patients with massive transfusion, respective findings in ALI and non-ALI patients were comparable. Results give credence to the view that systemic inflammation plays a role in development of ALI triggered by pancreatitis, but not in that by massive transfusion. This finding, if confirmed in studies with sufficient statistical power, suggests that the patients with massive transfusion do not necessarily benefit from novel biotherapies aimed at altering the course of systemic inflammation.

Characteristics of discrepancies between clinical and autopsy diagnoses in the intensive care unit: a 5-year review.

OBJECTIVES: To characterise discrepancies between clinical and autopsy diagnoses in patients who die in the intensive care unit. DESIGN: Retrospective chart review. SETTING: Ten-bed closed mixed adult intensive care unit in a tertiary referral teaching hospital. PARTICIPANTS: All the clinical notes and autopsy reports of 346 patients who died in the intensive care unit in 1996-2000. INTERVENTIONS: Discrepancies between clinical and autopsy diagnoses were reviewed by two intensivists, a specialist in infectious diseases, a pathologist and an anaesthesiologist. New findings which would have changed current therapy in the intensive care unit were categorised as a Class I discrepancy, and those related to death but which would not have altered therapy as a Class II discrepancy. RESULTS: Of 2370 patients admitted, 388 (16.4%) died. An autopsy was performed in 346 (89%) of the deceased patients. A Class I discrepancy was found in 8 patients (2.3%) and a Class II discrepancy in 11 patients (3.2%). Five of the eight (62%) Class I discrepancies were infections which occurred in patients already treated for another infections. CONCLUSION: Despite the availability of advanced diagnostic facilities, especially infectious complications seem to remain undiagnosed. Autopsy is a valuable tool with which to monitor diagnostic accuracy in these patients.

Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis.

OBJECTIVE: To evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein, leukocyte count, D-dimer, and antithrombin III at onset of septic episode and 24 h later in prediction of hospital mortality in critically ill patients with suspected sepsis. DESIGN AND SETTING: Prospective, cohort study in two university hospital intensive care units. PATIENTS: 61 critically ill patients with suspected sepsis. MEASUREMENTS AND RESULTS: The outcome measure was hospital mortality. Hospital survivors ( n=41) and nonsurvivors ( n=20) differed statistically significantly on day 1 (admission) in PCT, IL-6, SOFA score, and APACHE II score, and 24 h later in PCT, IL-6, and D-dimer values. AT III, CRP, and leukocyte count did not differ. The areas under receiver operating curves showed reasonable discriminative power (>0.75) in predicting hospital mortality only for day 2 IL-6 (0.799) and day 2 PCT (0.777) values which were comparable to that of APACHE II (0.786), and which remained the only independent predictor of mortality. CONCLUSIONS: Admission and day 2 IL-6, and day 2 PCT, and day 2 D-dimer values differed significantly between hospital survivors and nonsurvivors among critically ill patients with suspected sepsis. However, in prediction of hospital mortality, only the discriminative power of day 2 PCT and IL-6 values, and APACHE II was reasonable as judged by AUC analysis (>0.75).

Somatosensory and brainstem auditory evoked potentials in cardiac arrest patients treated with hypothermia.

OBJECTIVE: To evaluate the prognostic value of short-latency median nerve somatosensory evoked potentials and brainstem auditory evoked potentials in outcome prediction for comatose cardiac arrest patients treated with hypothermia. DESIGN: Prospective, randomized, controlled trial of mild hypothermia after out-of-hospital cardiac arrest; a substudy of the European Hypothermia After Cardiac Arrest study. SETTING: Intensive care unit of a tertiary referral hospital (Helsinki University Central Hospital). PATIENTS: Sixty consecutive patients (aged 18-75 yrs) resuscitated from out-of-hospital ventricular fibrillation and comatose at 24 hrs after cardiac arrest; all patients were randomly assigned either to therapeutic hypothermia of 33 degrees C or normothermia. INTERVENTIONS: All patients received standard intensive care for at least 2 days. Patients randomized to hypothermia were cooled with an external cooling device for 24 hrs and then allowed to rewarm slowly for 12 hrs. In the normothermia group, the core temperature was kept below 38 degrees C with antipyretics and by physical means. The clinical outcome was assessed 6 months after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Somatosensory evoked potentials and brainstem auditory evoked potentials were recorded 24-28 hrs after cardiac arrest. All wave latencies were significantly prolonged in the hypothermia group. Bilaterally absent N20 waves predicted permanent coma with a specificity of 100% in both treatment groups. Brainstem auditory evoked potential recordings did not correlate with the outcome in either treatment group. CONCLUSIONS: The prognostic ability of median nerve short-latency somatosensory evoked potentials does not seem to be affected by therapeutic hypothermia. Brainstem auditory evoked potentials had no additional value in outcome prediction.

Comparison of multiple organ dysfunction scores in the prediction of hospital mortality in the critically ill.

OBJECTIVE: To compare the scales and predictive power for hospital mortality of three recent multiple organ dysfunction scores. DESIGN: Prospective, observational, validation cohort study. SETTING: A ten-bed medical-surgical intensive care unit in a Finnish tertiary care hospital. PATIENTS: Among the 591 consecutive patients admitted, 520 patients who stayed >4 hrs were studied. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory data were collected daily. Acute Physiology and Chronic Health Evaluation (APACHE) III, Multiple Organ Dysfunction Score, Logistic Organ Dysfunction score, and Sequential Organ Failure Assessment score all were calculated and compared for hospital mortality. The areas under receiver operating curves (SE) for day-1 scores were 0.825 (0.02) for APACHE III, 0.805 (0.02) for Logistic Organ Dysfunction, 0.776 (0.02) for SOFA, and 0.695 (0.02) for Multiple Organ Dysfunction Score in prediction of hospital mortality. The highest discriminative power was revealed with total maximum scores. No statistical differences existed between the total maximum scores (p values,.06 to.97). Calibration was good for all scores of day-1 multiple organ dysfunction scales and APACHE III by chi-square test (values between 10.14 and 5.42). CONCLUSIONS: Discriminative power (ability to distinguish between patients who die and those who live) of day-1, of daily maximum, and especially of total maximum multiple organ dysfunction scores, were rather good, comparable with each other, and comparable with APACHE III in prediction of hospital mortality.

Predictive value of antithrombin III and serum C-reactive protein concentration in critically ill patients with suspected sepsis.

OBJECTIVE: To evaluate at admission the performance of serum antithrombin III, serum C-reactive protein, white blood cell and platelet counts, and thromboplastin time values in prediction of hospital mortality rates in critically ill patients with suspected sepsis. DESIGN: Prospective, cohort study. SETTING: University hospital medical-surgical intensive care unit. PATIENTS: One hundred eight consecutive critically ill patients with suspected sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The outcome measure was hospital mortality rate. Hospital survivors (n = 66) and nonsurvivors (n = 42) differed statistically significantly in admission antithrombin III activity (percentage of normal): survivors' median 66% (interquartile range, 48% to 82%) vs. nonsurvivors' median 46% (37% to 65%, p =.0002 by Mann-Whitney test). Analysis revealed similarly statistically significant differences between survivors and nonsurvivors in admission platelet count, admission thromboplastin time, day 1 Logistic Organ Dysfunction score, and Acute Physiology and Chronic Health Evaluation III score, but not in serum C-reactive protein concentrations or in white blood cells. However, the areas under the receiver operating curves (AUC) showed significantly worse discriminative power for admission antithrombin III concentration (AUC, 0.71; SE, 0.05), platelet count (AUC, 0.67; SE, 0.05), thromboplastin time (AUC, 0.65; SE, 0.05), C-reactive protein concentration (AUC, 0.60; SE, 0.05), and white blood cell count (AUC, 0.53; SE, 0.06) than did the day 1 Logistic Organ Dysfunction score (AUC, 0.82; SE, 0.04) and the Acute Physiology and Chronic Health Evaluation III score (AUC, 0.84; SE, 0.04). Multivariate logistic regression analysis revealed that only the Acute Physiology and Chronic Health Evaluation III score was independently associated with hospital mortality rate. CONCLUSIONS: Admission antithrombin III concentrations, but not C-reactive protein concentrations, differ significantly between hospital survivors and nonsurvivors among critically ill patients with septic infection. However, in prediction of hospital mortality rate, the discriminative power of admission antithrombin III concentration is poor, as judged by analysis of areas under the receiver operating curves, and is not independently associated with hospital mortality rate.