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  • Pekkarinen, Pirkka T.; Bäcklund, Minna; Efendijev, Ilmar; Raj, Rahul; Folger, Daniel; Litonius, Erik; Laitio, Ruut; Bendel, Stepani; Hoppu, Sanna; Ala-Kokko, Tero; Reinikainen, Matti; Skrifvars, Markus B. (2019)
    BackgroundOrgan dysfunction is common after cardiac arrest and associated with worse short-term outcome, but its impact on long-term outcome and treatment costs is unknown.MethodsWe used nationwide registry data from the intensive care units (ICU) of the five Finnish university hospitals to evaluate the association of 24-h extracerebral Sequential Organ Failure Assessment (24h-EC-SOFA) score with 1-year survival and healthcare-associated costs after cardiac arrest. We included adult cardiac arrest patients treated in the participating ICUs between January 1, 2003, and December 31, 2013. We acquired the confirmed date of death from the Finnish Population Register Centre database and gross 1-year healthcare-associated costs from the hospital billing records and the database of the Finnish Social Insurance Institution.ResultsA total of 5814 patients were included in the study, and 2401 were alive 1year after cardiac arrest. Median (interquartile range (IQR)) 24h-EC-SOFA score was 6 (5-8) in 1-year survivors and 7 (5-10) in non-survivors. In multivariate regression analysis, adjusting for age and prior independency in self-care, the 24h-EC-SOFA score had an odds ratio (OR) of 1.16 (95% confidence interval (CI) 1.14-1.18) per point for 1-year mortality.Median (IQR) healthcare-associated costs in the year after cardiac arrest were Euro47,000 (Euro28,000-75,000) in 1-year survivors and Euro12,000 (Euro6600-25,000) in non-survivors. In a multivariate linear regression model adjusting for age and prior independency in self-care, an increase of one point in the 24h-EC-SOFA score was associated with an increase of Euro170 (95% CI Euro150-190) in the cost per day alive in the year after cardiac arrest. In the same model, an increase of one point in the 24h-EC-SOFA score was associated with an increase of Euro4400 (95% CI Euro3300-5500) in the total healthcare-associated costs in 1-year survivors.ConclusionsExtracerebral organ dysfunction is associated with long-term outcome and gross healthcare-associated costs of ICU-treated cardiac arrest patients. It should be considered when assessing interventions to improve outcomes and optimize the use of resources in these patients.
  • Humaloja, Jaana; Litonius, Erik; Efendijev, Ilmar; Folger, Daniel; Raj, Rahul; Pekkarinen, Pirkka T.; Skrifvars, Markus B. (2019)
    Aim: Studies suggest that hyperoxemia increases short-term mortality after cardiopulmonary resuscitation (CPR), but the effect of hyperoxemia on long-term outcomes is unclear. We determined the prevalence of early hyperoxemia after CPR and its association with long-term neurological outcome and mortality. Methods: We analysed data from adult cardiac arrest patients treated after CPR in tertiary ICUs during 2005-2013. We retrieved data from the resuscitation and the first arterial blood sample collected after return of spontaneous circulation (ROSC) (severe hyperoxemia defined as PaO2 > 40 kPa and moderate as PaO2 16-40 kPa). We inspected two outcomes, neurological performance at one year after resuscitation according to the Cerebral Performance Category and one-year mortality. We used logistic regression to test associations between hyperoxemia and the outcome and interaction analyses to test the effect of hyperoxemia exposure on the outcomes in smaller subgroups. Results: Of 1110 patients 11% had severe hyperoxemia, prevalence was 10% for out-of-hospital arrests, 13% for in-hospital arrests and 9% for in-ICU arrests. In total 585(53%) patients had an unfavourable neurological outcome. Compared to normoxemia, severe (Odds ratio [OR] 0.81, 95% confidence interval [CI] 0.50-1.30) and moderate hyperoxemia (OR 0.94 95%CI 0.69-1.27) did not associate with neurological outcome. Additionally, hyperoxemia had no association with mortality. In subgroup analyses there were no significant associations between severe hyperoxemia and outcomes regardless of cardiac arrest location, initial rhythm or time-to-ROSC. Conclusion: We found no association between early post-arrest hyperoxemia and unfavourable outcome, Subgroup analysis found no differential effect depending on arrest location, initial rhythm or time-to-ROSC.
  • COMACARE Study Groups; Humaloja, Jaana J; Lähde, Marika; Ashton, Nicholas J.; Reinikainen, Matti; Hästbacka, Johanna; Jakkula, Pekka; Friberg, Hans; Cronberg, Tobias; Pettilä, Ville; Blennow, Kaj; Zetterberg, Henrik; Skrifvars, Markus (2022)
    Aim: To determine the ability of serum glial fibrillary acidic protein (GFAp) and tau protein to predict neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods: We measured plasma concentrations of GFAp and tau of patients included in the previously published COMACARE trial (NCT02698917) on intensive care unit admission and at 24, 48, and 72 h after OHCA, and compared them to neuron specific enolase (NSE). NSE concentrations were determined already during the original trial. We defined unfavourable outcome as a cerebral performance category (CPC) score of 3-5 six months after OHCA. We determined the prognostic accuracy of GFAp and tau using the receiver operating characteristic curve and area under the curve (AUROC). Results: Overall, 39/112 (35%) patients had unfavourable outcomes. Over time, both markers were evidently higher in the unfavourable outcome group (p < 0.001). At 48 h, the median (interquartile range) GFAp concentration was 1514 (886-4995) in the unfavourable versus 238 (135-463) pg/ ml in the favourable outcome group (p < 0.001). The corresponding tau concentrations were 99.6 (14.5-352) and 3.0 (2.2-4.8) pg/ml (p < 0.001). AUROCs at 48 and 72 h were 0.91 (95% confidence interval 0.85-0.97) and 0.91 (0.85-0.96) for GFAp and 0.93 (0.86-0.99) and 0.95 (0.89-1.00) for tau. Corresponding AUROCs for NSE were 0.86 (0.79-0.94) and 0.90 (0.82-0.97). The difference between the prognostic accuracies of GFAp or tau and NSE were not statistically significant. Conclusions: At 48 and 72 h, serum both GFAp and tau demonstrated excellent accuracy in predicting outcomes after OHCA but were not superior to NSE. Clinical trial registration: NCT02698917 (
  • Pasquier, Mathieu; Hugli, Olivier; Paal, Peter; Darocha, Tomasz; Blancher, Marc; Husby, Paul; Silfvast, Tom; Carron, Pierre-Nicolas; Rousson, Valentin (2018)
    Aims: Currently, the decision to initiate extracorporeal life support for patients who suffer cardiac arrest due to accidental hypothermia is essentially based on serum potassium level. Our goal was to build a prediction score in order to determine the probability of survival following rewarming of hypothermic arrested patients based on several covariates available at admission. Methods: We included consecutive hypothermic arrested patients who underwent rewarming with extracorporeal life support. The sample comprised 237 patients identified through the literature from 18 studies, and 49 additional patients obtained from hospital data collection. We considered nine potential predictors of survival: age; sex; core temperature; serum potassium level; mechanism of hypothermia; cardiac rhythm at admission; witnessed cardiac arrest, rewarming method and cardiopulmonary resuscitation duration prior to the initiation of extracorporeal life support. The primary outcome parameter was survival to hospital discharge. Results: Overall, 106 of the 286 included patients survived (37%; 95% CI: 32-43%), most (84%) with a good neurological outcome. The final score included the following variables: age, sex, core temperature at admission, serum potassium level, mechanism of cooling, and cardiopulmonary resuscitation duration. The corresponding area under the receiver operating characteristic curve was 0.895 (95% CI: 0.859-0.931) compared to 0.774 (95% CI: 0.720-0.828) when based on serum potassium level alone. Conclusions: In this large retrospective study we found that our score was superior to dichotomous triage based on serum potassium level in assessing which hypothermic patients in cardiac arrest would benefit from extracorporeal life support. External validation of our findings is required.
  • Tirkkonen, Joonas; Tamminen, Tero; Skrifvars, Markus B. (2017)
    Background: An abundance of studies have investigated the impact of rapid response teams (RRTs) on in-hospital cardiac arrest rates. However, existing RRT data appear highly variable in terms of both study quality and reported uses of limitations of care, patient survival and patient long-term outcome. Methods: A systematic electronic literature search (January, 1990-March, 2016) of the PubMed and Cochrane databases was performed. Bibliographies of articles included in the full-text review were searched for additional studies. A predefined RRT cohort quality score (range 0-17) was used to evaluate studies independently by two reviewers. Results: Twenty-nine studies with a total of 157,383 RRT activations were included in this review. The quality of data reporting related to RRT patients was assessed as modest, with a median quality score of 8 (range 2-11). Data from the included studies indicate that a median 8.1% of RRT reviews result in limitations of medical treatment (range 2.1-25%) and 23% (8.2-56%) result in a transfer to intensive care. A median of 29% (6.9-35%) of patients transferred to intensive care died during that admission. The median hospital mortality of patients reviewed by RRT is 26% (12-60%), and the median 30-day mortality rate is 29% (8-39%). Data on long-term survival is minimal. No data on functional outcomes was identified. Conclusions: Patients reviewed by rapid response teams have a high and variable mortality rate, and limitations of care are commonly used. Data on the long-term outcomes of RRT are lacking and needed. (C) 2017 Elsevier B.V. All rights reserved.
  • Efendijev, Ilmar; Folger, Daniel; Raj, Rahul; Reinikainen, Matti; Pekkarinen, Pirkka T.; Litonius, Erik; Skrifvars, Markus B. (2018)
    Background: Despite the significant socioeconomic burden associated with cardiac arrest (CA), data on CA patients' long-term outcome and healthcare-associated costs are limited. The aim of this study was to determine one-year survival, neurological outcome and healthcare-associated costs for ICU-treated CA patients. Methods: This is a single-centre retrospective study on adult CA patients treated in Finnish tertiary hospital's ICUs between 2005 and 2013. Patients' personal identification number was used to crosslink data between several nationwide databases in order to obtain data on one-year survival, neurological outcome, and healthcare-associated costs. Healthcare-associated costs were calculated for every patient stratified by cardiac arrest location (OHCA = out-of-hospital cardiac arrest, IHCA = all in-hospital cardiac arrest, ICU-CA = in-ICU cardiac arrest) and initial cardiac rhythm. Cost-effectiveness was estimated by dividing total healthcare-associated costs for all patients from the respective group by the number of survivors and survivors with favourable neurological outcome. Results: The study population included 1,024 ICU-treated CA patients. The sum of costs for all patients was (sic)50,847,540. At one-year after CA, 58% of OHCAs, 44% of IHCAs, and 39% of ICU-CAs were alive. Of one-year survivors 97% of OHCAs, 88% of IHCAs, and 93% of ICU-CAs had favourable neurological outcome. Effective cost per one-year survivor was (sic)76,212 for OHCAs, (sic)144,168 for IHCAs, and (sic)239,468 for ICU-CAs. Effective cost per one-year survivor with favourable neurological outcome was (sic)81,196 for OHCAs, (sic)164,442 for IHCAs, and _(sic)257,207 for ICU-CAs. Conclusions: In-ICU CA patients had the lowest one-year survival with the effective cost per survivor three times higher than for OHCAs.
  • Kirkegaard, Hans; Rasmussen, Bodil S.; de Haas, Inge; Nielsen, Jorgen Feldbaek; Ilkjaer, Susanne; Kaltoft, Anne; Jeppesen, Anni Norregaard; Grejs, Anders; Duez, Christophe Henri Valdemar; Larsen, Alf Inge; Pettila, Ville; Toome, Valdo; Arus, Urmet; Taccone, Fabio Silvio; Storm, Christian; Skrifvars, Markus; Soreide, Eldar (2016)
    Background: The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 +/- 1 degrees C for 48 hours compared to 24 hours results in a better long-term neurological outcome. Methods: The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 +/- 1 degrees C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. Discussion: This is the first randomised trial to investigate the effect of the duration of TTM at 33 +/- 1 degrees C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients.