Jukka Vaahersalo

Arterial Blood Gas Tensions After Resuscitation From Out-of-hospital Cardiac Arrest: Associations With Long-term Neurologic Outcome*

ObjectivesOptimal 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. DesignProspective observational cohort study. SettingTwenty-one ICUs in Finland. PatientsOut-of-hospital cardiac arrest patients treated in ICUs in Finland between March 2010 and February 2011. InterventionsNone. 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.

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).

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

IntroductionMyocardial 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.MethodsA 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.ResultsAdmission hs-TnT levels were higher than the 99-percentile of the general population (14 ng/L) in all patients (range 18 to 17837 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.Conclusionhs-TnT levels are elevated in critically ill patients with OHCA-VF/VT, but do not improve risk prediction.

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

Abstract 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.

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.

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.

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.

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.

Plasma Heme Oxygenase-1 in Patients Resuscitated from out-of-Hospital Cardiac Arrest

ABSTRACT 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.