Factors associated with fever after cardiac arrest: A post-hoc analysis of the FINNRESUSCI study.

BACKGROUND: Fever after cardiac arrest may impact outcome. We aimed to assess the incidence of fever in post-cardiac arrest patients, factors predicting fever and its association with functional outcome in patients treated without targeted temperature management (TTM). METHODS: The FINNRESUSCI observational cohort study in 2010-2011 included intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients from all five Finnish university hospitals and 14 of 15 central hospitals. This post hoc analysis included those FINNRESUSCI study patients who were not treated with TH. We defined fever as at least one temperature measurement of ≥37.8°C within 72 h of ICU admission. The primary outcome was favourable functional outcome at 12 months, defined as cerebral performance category (CPC) of 1 or 2. Binary logistic regression models including witnessed arrest, bystander cardiopulmonary resuscitation (CPR), initial rhythm and delay of return of spontaneous circulation were used to compare the functional outcomes of the groups. RESULTS: There were 67,428 temperature measurements from 192 patients, of whom 89 (46%) experienced fever. Twelve-month CPC was missing in 7 patients, and 51 (28%) patients had favourable functional outcome at 12 months. The patients with shockable initial rhythms had a lower incidence of fever within 72 h of ICU admission (28% vs. 72%, p < .01), and the patients who experienced fever had a longer median return of spontaneous circulation (ROSC) delay (20 [IQR 10-30] vs. 14 [IQR 9-22] min, p < .01). Only initial non-shockable rhythm (OR 2.99, 95% CI 1.51-5.94) was associated with increased risk of fever within the first 72 h of ICU admission. Neither time in minutes nor area (minutes × degree celsius over threshold) over 37°C, 37.5°C, 38°C, 38.5°C, 39°C, 39.5°C or 40°C were significantly different in those with favourable functional outcome compared to those with unfavourable functional outcome within the first 24, 48 or 72 h from ICU admission. Fever was not associated with favourable functional outcome at 12 months (OR 0.90, 95% CI 0.44-1.84). CONCLUSIONS: Half of OHCA patients not treated with TTM developed fever. We found no association between fever and outcome.

Ubiquitin C-terminal hydrolase L1 after out-of-hospital cardiac arrest.

BACKGROUND: We studied the prognostic ability of serum ubiquitin C-terminal hydrolase L1 (UCH-L1) after out-of-hospital cardiac arrest (OHCA), compared to that of neuron-specific enolase (NSE). METHODS: In this post-hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH-L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010-2011. We evaluated the ability of UCH-L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3-5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE. RESULTS: The concentrations of UCH-L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5-18.5 ng/mL) versus 7.8 ng/mL (5.9-11.8 ng/mL) at 24 h (p < .001), and 16.2 ng/mL (12.2-27.7 ng/mL) versus 11.5 ng/mL (9.0-17.2 ng/mL) (p < .001) at 48 h after OHCA. For UCH-L1 as a 12-month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60-0.73) at 24 h and 0.66 (0.59-0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59-0.73) at 24 h and 0.72 (0.65-0.80) at 48 h. The prognostic ability of UCH-L1 was not different from that of NSE at 24 h (p = .82) and at 48 h (p = .23). CONCLUSION: Concentrations of UCH-L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH-L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE.

Usefulness of neuron specific enolase in prognostication after cardiac arrest: Impact of age and time to ROSC.

AIM OF THE STUDY: We evaluated the impact of patient age and time from collapse to return of spontaneous circulation (ROSC) on the prognostic accuracy of neuron specific enolase (NSE) after out-of-hospital cardiac arrest (OHCA). METHODS: Using electrochemiluminescence immunoassay, we measured serum concentrations of NSE in 249 patients who were admitted to intensive care units after resuscitation from OHCA. In each quartile according to age and time to ROSC, we evaluated the ability of NSE at 48 h after OHCA to predict poor outcome (Cerebral Performance Category 3-5) at 12 months. RESULTS: The outcome at 12 months was poor in 121 (49%) patients. The prognostic performance of NSE was excellent (area under the receiver operating characteristic curve, AUROC, 0.91 [95% confidence interval, 0.81-1.00]) in the youngest quartile (18-56 years), but worsened with increasing age, and was poor (AUROC 0.53 [0.37-0.70]) in the oldest quartile (72 years or more). The prognostic performance of NSE was worthless (AUROC 0.45 [0.30-0.61]) in the quartile with the shortest time to ROSC (1-13 min), but improved with increasing time to ROSC, and was good (AUROC 0.84 [0.74-0.95]) in the quartile with the longest time to ROSC (29 min or over). CONCLUSION: NSE at 48 h after OHCA is a useful predictor of 12-month-prognosis in young patients and in patients with a long time from collapse to ROSC, but not in old patients or patients with a short time to ROSC.

Early Lactate Values After Out-of-Hospital Cardiac Arrest: Associations With One-Year Outcome.

BACKGROUND: Previous studies have shown associations between high admission serum lactate, lower lactate clearance, and increased short-term mortality after out-hospital cardiac arrest (OHCA). We studied whether lactate levels predict long- term outcome after OHCA. METHODS: We included 458 OHCA patients with lactate measurements during intensive care unit (ICU) stay from the prospective FINNRESUSCI study. We evaluated thresholds for time-weighted (TW) mean lactate values for the first 24, 48, and 72 h. We analyzed lactate clearance and used multivariate regression to assess the prognostic value of the different measurement time points. RESULTS: The admission lactate (median [IQR] 3.06 [2.68-3.44] mmol/L vs 4.76 [4.29-5.23] mmol/L) and the last measured lactate (0.98 [0.90-1.06] mmol/L vs 2.40 [2.03-2.78] mmol/L) were higher in non-survivors than in survivors, as were the lowest (0.73 [0.67-0.79] mmol/L vs 1.83 [1.52-2.14] mmol/L) and the highest (3.44 [3.05-3.83] mmol/L vs 5.25 [4.76-5.74] mmol/L) lactate values (all P < 0.001). Time-weighted mean lactate values for the first 24, 48, 72, and for the entire ICU stay were lower in patients with good outcome (P < 0.001). In multivariate backward regression models, time-weighted mean lactate for the entire ICU stay (OR 1.41 per mmol/L, CI 95% 1.08-1.86, P = 0.013) and the last measured lactate in the ICU (OR 2.16 per mmol/L, CI 95% 1.47-3.18, P < 0.001) were independent predictors of poor 1-year outcome. CONCLUSIONS: In the present study time-weighted mean lactate values for the entire ICU stay, and the last measured lactate value in the ICU, but not admission lactate or lactate clearance were independent predictors of poor 1-year outcome.

Surviving out-of-hospital cardiac arrest: The neurological and functional outcome and health-related quality of life one year later.

BACKGROUND: Data on long-term functional outcome and quality of life (QoL) after out-of-hospital cardiac arrest (OHCA) are limited. We assessed long-term functional outcome and health-related QoL of OHCA survivors regardless of arrest aetiology. METHODS: All adult unconscious OHCA patients treated in 21 Finnish ICUs between March 2010 and February 2011 were followed. Barthel Index (BI), activities of daily living (ADL), accommodation, help needed and received, working status, car driving and self-experienced cognitive deficits were assessed in 1-year survivors (N = 206, 40.9% of the original FINNRESUSCI cohort) with a structured telephone interview. Health-related QoL and more complex ADL-functions were evaluated by EQ-5D and instrumental ADL questionnaires. RESULTS: Good outcome, defined as Cerebral Performance Categories 1 or 2, had been reached by 90.3% of survivors. The median BI score was 100, and 91.3% of survivors were independent in basic ADL-functions. The great majority of survivors were living at home, only 8.7% lived in a sheltered home or needed institutionalized care. Of home-living survivors 71.4% scored high in instrumental ADL assessment. The majority (72.6%) of survivors who were working previously had returned to work. Health-related QoL was similar as in age- and gender-adjusted Finnish population. CONCLUSIONS: Long-term functional outcome was good in over 90% of patients surviving OHCA, with health-related quality of life similar to that of an age and gender matched population.

Lower heart rate is associated with good one-year outcome in post-resuscitation patients.

BACKGROUND: Optimal hemodynamic goals in post-resuscitation patients are not clear. Previous studies have reported an association between lower heart rate and good outcome in patients receiving targeted temperature management (TTM) after out-of-hospital cardiac arrest. METHODS: We analyzed heart rate (HR) and outcome data of 504 post-resuscitation patients from the prospectively collected database of the FINNRESUSCI study. One-year neurologic outcome was dichotomized by the Cerebral Performance Category (CPC) to good (1-2) or poor (3-5). RESULTS: Of 504 patients, 40.1% (202/504) had good and 59.9% (302/ 504) had poor one-year neurologic outcome. Patients with good outcome had lower time-weighted mean HR during the first 48 h in the ICU (69.2 bpm [59.2-75.1] vs. 76.6 bpm [65.72-89.6], p < 0.001) and the first 72 h in the ICU (71.2 bpm [65.0-79.0] vs. 77.1 bpm [69.1-90.1, p < 0.001]). The percentage of HR registrations below HR threshold values (60, 80 and 100 bpm) were higher for patients with good neurologic outcome, p < 0.001 for all. Lower time-weighted HR for 0-48 h and 0-72 h, and a higher percentage of HR recordings below threshold values were independently associated with good neurological one-year outcome (p < 0.05 for all). When TTM and non-TTM patients were analyzed separately, HR parameters were independently associated with one-year neurologic outcome only in non-TTM patients. CONCLUSION: Lower heart rate was independently associated with good neurologic outcome. Whether HR in post-resuscitation patients is a prognostic indicator or an important variable to be targeted by treatment, needs to be assessed in future prospective controlled clinical trials.

Procalcitonin and Presepsin as Prognostic Markers After Out-of-Hospital Cardiac Arrest.

BACKGROUND: Patients resuscitated from cardiac arrest commonly develop an inflammatory response called post-cardiac arrest syndrome that clinically resembles septic shock.Procalcitonin and presepsin are associated with inflammation. We hypothesized that these biomarkers reflect the severity of post-cardiac arrest syndrome and predict short-term hemodynamical instability and long-term neurological outcome after cardiac arrest. METHODS: As a subcohort analysis of a prospective, observational, multicenter study "FINNRESUSCI," we obtained plasma from 277 intensive care unit (ICU) patients treated following out-of-hospital cardiac arrest (OHCA). Procalcitonin and presepsin levels were measured 0 to 6 h from ICU admission and 24, 48, and 96 h thereafter. We defined poor outcome as a 12-month Cerebral Performance Category of 3 to 5. We tested statistical associations between biomarkers and hemodynamical parameters and outcome with regression models. RESULTS: Plasma procalcitonin had best predictive value for 12-month poor outcome at 96 h (AUC 0.76; 95% CI 0.68-0.83) and presepsin at ICU admission (AUC 0.72; 95% CI 0.65-0.78). Elevated procalcitonin concentration at ICU admission predicted unstable hemodynamics in the following 48 h in a linear regression model. In a multivariate logistic regression model with clinical variables, only procalcitonin at 96 h had independent prognostic value for poor 12-month neurological outcome. CONCLUSIONS: Elevated procalcitonin is associated with hemodynamical instability and worsened long-term outcome in OHCA patients. The association is not strong enough for it to be used as a single predictor. Presepsin did not provide clinically relevant information for risk stratification after OHCA.

Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest.

BACKGROUND: An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome. METHODS: Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score ≥ 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed. RESULTS: Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48 h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p < 0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p < 0.0001; AUC = 0.70 ± 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p < 0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p < 0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74 ± 0.04 (p < 0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076-2.399], p = 0.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834-1.596], p = 0.387). CONCLUSIONS: Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.

Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest: Associations with one-year neurologic outcome.

THE AIM OF THE STUDY: There are limited data on blood pressure targets and vasopressor use following cardiac arrest. We hypothesized that hypotension and high vasopressor load are associated with poor neurological outcome following out-of-hospital cardiac arrest (OHCA). METHODS: We included 412 patients with OHCA included in FINNRESUSCI study conducted between 2010 and 2011. Hemodynamic data and vasopressor doses were collected electronically in one, two or five minute intervals. We evaluated thresholds for time-weighted (TW) mean arterial pressure (MAP) and outcome by receiver operating characteristic (ROC) curve analysis, and used multivariable analysis adjusting for co-morbidities, factors at resuscitation, an illness severity score, TW MAP and total vasopressor load (VL) to test associations with one-year neurologic outcome, dichotomized into either good (1-2) or poor (3-5) according to the cerebral performance category scale. RESULTS: Of 412 patients, 169 patients had good and 243 patients had poor one-year outcomes. The lowest MAP during the first six hours was 58 (inter-quartile range [IQR] 56-61) mmHg in those with a poor outcome and 61 (59-63) mmHg in those with a good outcome (p<0.01), and lowest MAP was independently associated with poor outcome (OR 1.02 per mmHg, 95% CI 1.00-1.04, p=0.03). During the first 48h the median (IQR) of the TW mean MAP was 80 (78-82) mmHg in patients with poor, and 82 (81-83) mmHg in those with good outcomes (p=0.03) but in multivariable analysis TWA MAP was not associated with outcome. Vasopressor load did not predict one-year neurologic outcome. CONCLUSIONS: Hypotension occurring during the first six hours after cardiac arrest is an independent predictor of poor one-year neurologic outcome. High vasopressor load was not associated with poor outcome and further randomized trials are needed to define optimal MAP targets in OHCA patients.

NT-proBNP in patients with out-of-hospital cardiac arrest: Results from the FINNRESUSCI Study.

AIM: To assess whether the established cardiovascular biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) provides prognostic information in patients with out-of-hospital cardiac arrest due to ventricular tachycardia or fibrillation (OHCA-VT/VF). METHODS: We measured NT-proBNP levels in 155 patients with OHCA-VT/VF enrolled into a prospective multicenter observational study in 21 ICUs in Finland. Blood samples were drawn <6h of OHCA-VT/VF and later after 24h, 48h, and 96h. The end-points were mortality and neurological outcome classified according to Cerebral Performance Category (CPC) after one year. NT-proBNP levels were compared to high-sensitivity troponin T (hs-TnT) levels and established risk scores. RESULTS: NT-proBNP levels were higher in non-survivors compared to survivors on study inclusion (median 1003 [quartile (Q) 1-3 502-2457] vs. 527 [179-1284]ng/L, p=0.001) and after 24h (1913 [1012-4573] vs. 1080 [519-2210]ng/L, p<0.001). NT-proBNP levels increased from baseline to 96h after ICU admission (p<0.001). NT-proBNP levels were significantly correlated to hs-TnT levels after 24h (rho=0.27, p=0.001), but not to hs-TnT levels on study inclusion (rho=0.05, p=0.67). NT-proBNP levels at all time points were associated with clinical outcome, but only NT-proBNP levels after 24h predicted mortality and poor neurological outcome, defined as CPC 3-5, in models that adjusted for SAPS II and SOFA scores. hs-TnT levels did not add prognostic information to NT-proBNP measurements alone. CONCLUSION: NT-proBNP levels at 24h improved risk assessment for poor outcome after one year on top of established risk indices, while hs-TnT measurements did not further add to risk prediction.

PLASMA HEME OXYGENASE-1 IN PATIENTS RESUSCITATED FROM OUT-OF-HOSPITAL CARDIAC ARREST.

Heme oxygenase-1 (HO-1) is an enzyme induced by hypoxia and reperfusion injury, and is associated with organ dysfunction in critically ill patients. Patients resuscitated from out-of-hospital cardiac arrest (OHCA) are subjected to hypoxemia, brain injury, and organ dysfunction. Accordingly, we studied HO-1 among these patients. A total of 143 OHCA patients resuscitated from a shockable initial rhythm and admitted to an ICU were included, with plasma HO-1 measured at ICU admission and at 24 h. We analyzed the associations between plasma HO-1 and time to return of spontaneous circulation (ROSC), 90-day mortality, and 12-month Cerebral Performance Category (CPC). HO-1 plasma concentrations were higher after OHCA compared with controls. HO-1 concentrations at admission and on day 1 associated with ROSC (P = 0.002 to P = 0.003). Admission and day 1 HO-1 plasma concentrations were higher in 90-day non-survivors than in survivors (P = 0.017, 0.026). In addition, poor neurological outcome (CPC 3-5) was associated with higher HO-1 plasma levels at admission (P = 0.024). Admission plasma HO-1 levels had an AUC of 0.623 to predict 90-day mortality and an AUC of 0.611 to predict CPC 3 to 5. In conclusion, we found that higher HO-1 plasma levels are associated with longer ROSC and poor long-term outcome.

Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

BACKGROUND: A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. METHODS: PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. RESULTS: In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. CONCLUSIONS: Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

Copeptin levels are associated with organ dysfunction and death in the intensive care unit after out-of-hospital cardiac arrest.

INTRODUCTION: We studied associations of the stress hormones copeptin and cortisol with outcome and organ dysfunction after out-of-hospital cardiac arrest (OHCA). METHODS: Plasma was obtained after consent from next of kin in the FINNRESUSCI study conducted in 21 Finnish intensive care units (ICUs) between 2010 and 2011. We measured plasma copeptin (pmol/L) and free cortisol (nmol/L) on ICU admission (245 patients) and at 48 hours (additional 33 patients). Organ dysfunction was categorised with 24-hour Sequential Organ Failure Assessment (SOFA) scores. Twelve-month neurological outcome (available in 276 patients) was classified with cerebral performance categories (CPC) and dichotomised into good (CPC 1 or 2) or poor (CPC 3 to 5). Data are presented as medians and interquartile ranges (IQRs). A Mann-Whitney U test, multiple linear and logistic regression tests with odds ratios (ORs) 95% confidence intervals (CIs) and beta (B) values, repeated measure analysis of variance, and receiver operating characteristic curves with area under the curve (AUC) were performed. RESULTS: Patients with a poor 12-month outcome had higher levels of admission copeptin (89, IQR 41 to 193 versus 51, IQR 29 to 111 pmol/L, P = 0.0014) and cortisol (728, IQR 522 to 1,017 versus 576, IQR 355 to 850 nmol/L, P = 0.0013). Copeptin levels fell between admission and 48 hours (P <0.001), independently of outcome (P = 0.847). Cortisol levels did not change between admission and 48 hours (P = 0.313), independently of outcome (P = 0.221). The AUC for predicting long-term outcome was weak for copeptin (0.62, 95% CI 0.55 to 0.69) and cortisol (0.62, 95% CI 0.54 to 0.69). With logistic regression, admission copeptin (standard deviation (SD) increase OR 1.4, 95% CI 1.03 to 1.98) and cortisol (SD increase OR 1.5, 95% CI 1.1 to 2.0) predicted ICU mortality but not 12-month outcome. Admission factors correlating with SOFA were shockable rhythm (B -1.3, 95% CI -2.2 to -0.5), adrenaline use (B 1.1, 95% CI 0.2 to 2.0), therapeutic hypothermia (B 1.3 95% CI 0.4-2.2), and copeptin (B 0.04, 95% CI 0.02 to 0.07). CONCLUSIONS: Admission copeptin and free cortisol were not of prognostic value regarding 12-month neurological outcome after OHCA. Higher admission copeptin and cortisol were associated with ICU death, and copeptin predicted subsequent organ dysfunction.

Prognostic value of high-sensitivity troponin T levels in patients with ventricular arrhythmias and out-of-hospital cardiac arrest: data from the prospective FINNRESUSCI study.

INTRODUCTION: Myocardial dysfunction is common after out-of-hospital cardiac arrest (OHCA) and high-sensitivity troponin T (hs-TnT) levels may provide incremental prognostic information to established risk indices. METHODS: A total of 155 patients with OHCA and a shockable rhythm (98% ventricular fibrillation; OHCA-VF/VT) had blood samples drawn within six hours of admission. Blood samples were also available after 24 hours, 48 hours, and 96 hours in subsets of patients. The endpoints of the study were hospital mortality and neurological status and mortality after one year. RESULTS: Admission hs-TnT levels were higher than the 99-percentile of the general population (14 ng/L) in all patients (range 18 to 17,837 ng/L). Admission hs-TnT levels were associated with acute coronary artery occlusion, time to return of spontaneous circulation, heart failure, and renal function. Admission hs-TnT levels were higher in one-year non-survivors compared to survivors (median 747 (quartile 1 to 3, 206 to 1061) ng/L versus 345 (184 to 740) ng/L, P =0.023) and in patients with a poor versus a favorable neurological outcome (739 (191 to 1061) ng/L versus 334 (195 to 716) ng/L, P =0.028). However, hs-TnT measurements did not add prognostic information to established risk variables in multivariate analyses. hs-TnT levels measured during the hospitalization for OHCA-VF/VT correlated closely with admission levels (r ≥0.63) and were inferior to Simplified Acute Physiology Score II (SAPS II) scores for the prediction of events during follow-up. hs-TnT dynamics did not discriminate between survivors and non-survivors or between a poor versus a favorable neurological outcome. CONCLUSION: hs-TnT levels are elevated in critically ill patients with OHCA-VF/VT, but do not improve risk prediction.

Admission interleukin-6 is associated with post resuscitation organ dysfunction and predicts long-term neurological outcome after out-of-hospital ventricular fibrillation.

AIM OF THE STUDY: To study plasma concentrations of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and S-100B during intensive care after out-of-hospital cardiac arrest from ventricular fibrillation (OHCA-VF), and their associations with the duration of ischemia, organ dysfunction and long-term neurological outcome. MATERIALS AND METHODS: A 12-month prospective observational multicentre study was conducted in 21 Finnish intensive care units in 2011. IL-6, hs-CRP and S-100B were measured at 0-6 h, 24 h, 48 h and 96 h after ICU admission. Associations with the time to return of spontaneous circulation (ROSC), sequential organ failure assessment (SOFA) scores divided into tertiles and 12-month cerebral performance category (CPC) were tested. RESULTS: Of 186 OHCA-VF patients included in the study, 110 (59.1%) patients survived with good neurological outcome (CPC 1-2) 12 months after cardiac arrest. Admission plasma concentrations of IL-6 but not hs-CRP were higher with prolonged time to ROSC (p<0.001, 0.203, respectively), in patients with subsequent higher SOFA scores (p<0.001, 0.069) and poor long-term neurological outcome (CPC 3-5) (p<0.001, 0.315). S-100B concentrations over time were higher in patients with CPC of 3-5 (p<0.001). The area under the curve for prediction of poor 12-month outcome for admission levels was 0.711 IL-6, 0.663 for S-100B and 0.534 for hs-CRP. With multivariate logistic regression analysis only admission IL-6 (p=0.046, OR 1.006, 95% CI 1.000-1.011/ng/L) was an independent predictor of poor neurological outcome. CONCLUSION: Admission high IL-6, but not hs-CRP or S-100B, is associated with extra-cerebral organ dysfunction and along with age and time to ROSC are independent predictors for 12-month poor neurologic outcome (CPC 3-5).

The predictive value of soluble urokinase plasminogen activator receptor (SuPAR) regarding 90-day mortality and 12-month neurological outcome in critically ill patients after out-of-hospital cardiac arrest. Data from the prospective FINNRESUSCI study.

AIM: The whole body ischaemia-reperfusion after cardiac arrest (CA) induces a systemic inflammation-reperfusion response. The expression of urokinase plasminogen activator receptor (uPAR) is known to be induced after hypoxia and increased levels of soluble form suPAR have been measured after hypoxia and ischaemia. Our aim was to evaluate, whether ischaemia/reperfusion injury after out-of-hospital cardiac arrest (OHCA) increases suPAR concentrations in serum and to evaluate the prognostic value of suPAR regarding 90-day mortality and 12-month neurological outcome. METHODS: This is a pre-determined substudy of prospective FINNRESUSCI study. Total of 287 patients treated in the intensive care units after OHCA and with consent from the next-of-kin and serum samples between baseline and day 4 were included. Outcome and neurological outcome were evaluated according the Pittsburgh Cerebral Performance Categories (CPC). Kaplan-Meier survival curves, areas under receiver operational characteristics curves and positive likelihood ratios for mortality and poor neurological outcome were calculated. RESULTS: Non-survivors had higher levels of suPAR after OHCA. Kaplan-Meier survival curves indicated high 90-day mortality in the highest concentration quintiles. LR+ for 1-year CPC 3-5 was 1.8-2.7 for the whole patient cohort and in shockable rhythms 2.0-2.4. In therapeutic hypothermia prognostic value remained. CONCLUSIONS: We found that high SuPAR concentrations were associated with poor outcome in patients with OHCA admitted to critical care. However, suPAR alone had inadequate predictive value for poor outcome and did not associate with 12-month neurological outcome.

Early activation of the kynurenine pathway predicts early death and long-term outcome in patients resuscitated from out-of-hospital cardiac arrest.

BACKGROUND: The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post-cardiac arrest shock, early death, and long-term outcome. METHODS AND RESULTS: Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12-month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3-hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3-hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3-hydroxyanthranilic acid had lower 24-hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3-hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12-month poor outcome and significantly improved risk reclassification. CONCLUSIONS: KP is activated early after cardiac arrest and is associated with severity of post-cardiac arrest shock, early death, and poor long-term outcome.

Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest: associations with long-term neurologic outcome.

OBJECTIVES: Optimal oxygen and carbon dioxide levels during postcardiac arrest care are currently undefined and observational studies have suggested harm from hyperoxia exposure. We aimed to assess whether mean and time-weighted oxygen and carbon dioxide levels during the first 24 hours of postcardiac arrest care correlate with 12-month neurologic outcome. DESIGN: Prospective observational cohort study. SETTING: Twenty-one ICUs in Finland. PATIENTS: Out-of-hospital cardiac arrest patients treated in ICUs in Finland between March 2010 and February 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood PaO2 and PaCO2 during the first 24 hours from admission were divided into predefined categories from the lowest to the highest. Proportions of time spent in different categories and the mean PaO2 and PaCO2 values during the first 24 hours were included in separate multivariable regression models along with resuscitation factors. The cerebral performance category at 12 months was used as primary endpoint. A total of 409 patients with arterial blood gases analyzed at least once and with a complete set of resuscitation data were included. The average amount of PaO2 and PaCO2 measurements was eight per patient. The mean 24 hours PaCO2 level was an independent predictor of good outcome (odds ratio, 1.054; 95% CI, 1.006-1.104; p = 0.027) but the mean PaO2 value was not (odds ratio, 1.006; 95% CI, 0.998-1.014; p = 0.149). With multivariate regression analysis, time spent in the PaCO2 band higher than 45 mm Hg was associated with good outcome (odds ratio, 1.015; 95% CI, 1.002-1.029; p = 0.024, for each percentage point increase in time) but time spent in different oxygen categories were not. CONCLUSIONS: In this multicenter study, hypercapnia was associated with good 12-month outcome in patients resuscitated from out-of-hospital cardiac arrest. We were unable to verify any harm from hyperoxia exposure. Further trials should focus on whether moderate hypercapnia during postcardiac arrest care improves outcome.

Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units: the FINNRESUSCI study.

PURPOSE: We aimed to evaluate post-resuscitation care, implementation of therapeutic hypothermia (TH) and outcomes of intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients in Finland. METHODS: We included all adult OHCA patients admitted to 21 ICUs in Finland from March 1, 2010 to February 28, 2011 in this prospective observational study. Patients were followed (mortality and neurological outcome evaluated by Cerebral Performance Categories, CPC) within 1 year after cardiac arrest. RESULTS: This study included 548 patients treated after OHCA. Of those, 311 patients (56.8%) had a shockable initial rhythm (incidence of 7.4/100,000/year) and 237 patients (43.2%) had a non-shockable rhythm (incidence of 5.6/100,000/year). At ICU admission, 504 (92%) patients were unconscious. TH was given to 241/281 (85.8%) unconscious patients resuscitated from shockable rhythms, with unfavourable 1-year neurological outcome (CPC 3-4-5) in 42.0% with TH versus 77.5% without TH (p < 0.001). TH was given to 70/223 (31.4%) unconscious patients resuscitated from non-shockable rhythms, with 1-year CPC of 3-4-5 in 80.6% (54/70) with TH versus 84.0% (126/153) without TH (p = 0.56). This lack of difference remained after adjustment for propensity to receive TH in patients with non-shockable rhythms. CONCLUSIONS: One-year unfavourable neurological outcome of patients with shockable rhythms after TH was lower than in previous randomized controlled trials. However, our results do not support use of TH in patients with non-shockable rhythms.

Regional variation and outcome of out-of-hospital cardiac arrest (ohca) in Finland - the Finnresusci study.

BACKGROUND: Despite the efforts of the modern Emergency Medical Service Systems (EMS), survival rates for sudden out-of-hospital cardiac arrest (OHCA) have been poor as approximately 10% of OHCA patients survive hospital discharge. Many aspects of OHCA have been studied, but few previous reports on OHCA have documented the variation between different sizes of study areas on a regional scale. The aim of this study was to report the incidence, outcomes and regional variation of OHCA in the Finnish population. METHODS: From March 1st to August 31st, 2010, data on all OHCA patients in the southern, central and eastern parts of Finland was collected. Data collection was initiated via dispatch centres whenever there was a suspected OHCA case or if a patient developed OHCA before arriving at the hospital. The study area includes 49% of the Finnish population; they are served by eight dispatch centres, two university hospitals and six central hospitals. RESULTS: The study period included 1042 cases of OHCA. Resuscitation was attempted on 671 patients (64.4%), an incidence of 51/100,000 inhabitants/year. The initial rhythm was shockable for 211 patients (31.4%). The survival rate at one-year post-OHCA was 13.4%. Of the witnessed OHCA events with a shockable rhythm of presumed cardiac origin (n=140), 64 patients (45.7%) were alive at hospital discharge and 47 (33.6%) were still living one year hence. Surviving until hospital admission was more likely if the OHCA occurred in an urban municipality (41.5%, p=0.001). CONCLUSIONS: The results of this comprehensive regional study of OHCA in Finland seem comparable to those previously reported in other countries. The survival of witnessed OHCA events with shockable initial rhythms has improved in urban Finland in recent decades.