Browsing by Subject "RESUSCITATION"

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  • Kirkegaard, Hans; Pedersen, Asger Roer; Pettilä, Ville; Hjort, Jakob; Rasmussen, Bodil Steen; de Haas, Inge; Nielsen, Jorgen Feldbaek; Ilkjaer, Susanne; Kaltoft, Anne; Jeppesen, Anni Norgaard; Grejs, Anders Morten; Duez, Christophe Henri Valdemar; Larsen, Alf Inge; Toome, Valdo; Arus, Urmet; Taccone, Fabio Silvio; Storm, Christian; Laitio, Timo; Skrifvars, Markus; Soreide, Eldar (2016)
    Background: The TTH48 trial aims to determine whether prolonged duration (48 hours) of targeted temperature management (TTM) at 33 (+/- 1) degrees C results in better neurological outcomes compared to standard duration (24 hours) after six months in comatose out-of-hospital cardiac arrest (OHCA) patients. Methods: TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised, controlled superiority trial of 24 and 48 hours of TTM at 33 (+/- 1) degrees C performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to ten intensive care units (ICUs) in six Northern European countries. The primary outcome of the study is the Cerebral Performance Category (CPC) score observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor neurological outcomes. The secondary outcomes are as follows: mortality within six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the presence of any adverse events such as cerebral, circulatory, respiratory, gastrointestinal, renal, metabolic measures, infection or bleeding. With the planned sample size, we have 80% power to detect a 15% improvement in good neurological outcomes at a two-sided statistical significance level of 5%. Discussion: We present a detailed statistical analysis protocol (SAP) that specifies how primary and secondary outcomes should be evaluated. We also predetermine covariates for adjusted analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned SAP will reduce analysis bias and add validity to the findings of this trial on the effect of length of TTM on important clinical outcomes after cardiac arrest.
  • Holm, Aki; Kirkegaard, Hans; Taccone, Fabio; Soreide, Eldar; Grejs, Anders; Duez, Christophe; Jeppesen, Anni; Toome, Valdo; Hassager, Christian C.; Rasmussen, Bodil S.; Laitio, Timo; Storm, Christian; Hästbacka, Johanna; Skrifvars, Markus B. (2020)
    Background: Pre-intensive care unit (ICU) induction of targeted temperature management (TTM) with cold intravenous (i.v.) fluids does not appear to improve outcomes after in out-of-hospital cardiac arrest (OHCA). We hypothesized that this may be due to ineffective cooling and side effects. Methods: A post hoc analysis of a sub-group of patients (n = 352) in the TTH48 trial (NCT01689077) who received or did not receive pre-ICU cooling using cold i.v. fluids. Data collection included patient characteristics, cardiac arrest factors, cooling methods, side effects and continuous core temperature measurements. The primary endpoint was the time to target temperature (TTT, Results: Of 352 patients included in the present analysis, 110 received pre-ICU cold fluids. The median time to the return of spontaneous circulation (ROSC) and TTT in the pre-ICU cold fluids group was longer than that of the group that did not receive pre-ICU cold fluids (318 vs. 281 min, p <0.01). In a linear regression model including the treatment centre, body mass index (BMI), chronic heart failure, diabetes mellitus and time to ROSC, the use of preICU cold i.v. fluids was not associated with a shorter time to the target temperature (standardized beta coefficient: 0.06, 95% CI for B -49 and 16, p = 0.32). According to the receipt or not of pre-ICU cold i.v. fluids, there was no difference in the proportion of patients with hypoxia (1.8% vs. 3.3%, p= 0.43) or the proportion of patients with electrolyte abnormalities (hyponatremia: 1.8% vs. 2.9% p= 0.54; hypokalaemia: 1.8% vs. 4.5%, p= 0.20). Furthermore, there was no difference in hospital mortality between the groups. Conclusions: The initiation of TTM with cold i.v. fluids before ICU arrival did not decrease the TTT. We detected no significant between-group difference in mortality or the incidence of side effects according to the administration or not of pre-ICU cold i.v fluids.
  • Young, Paul J.; Bailey, Michael; Bellomo, Rinaldo; Bernard, Stephen; Bray, Janet; Jakkula, Pekka; Kuisma, Markku; Mackle, Diane; Martin, Daniel; Nolan, Jerry P.; Panwar, Rakshit; Reinikainen, Matti; Skrifvars, Markus B.; Thomas, Matt (2020)
    Aim: The effect of conservative versus liberal oxygen therapy on mortality rates in post cardiac arrest patients is uncertain. Methods: We undertook an individual patient data meta-analysis of patients randomised in clinical trials to conservative or liberal oxygen therapy after a cardiac arrest. The primary end point was mortality at last follow-up. Results: Individual level patient data were obtained from seven randomised clinical trials with a total of 429 trial participants included. Four trials enrolled patients in the pre-hospital period. Of these, two provided protocol-directed oxygen therapy for 60 min, one provided it until the patient was handed over to the emergency department staff, and one provided it for a total of 72 h or until the patient was extubated. Three trials enrolled patients after intensive care unit (ICU) admission and generally continued protocolised oxygen therapy for a longer period, often until ICU discharge. A total of 90 of 221 patients (40.7%) assigned to conservative oxygen therapy and 103 of 206 patients (50%) assigned to liberal oxygen therapy had died by this last point of followup; absolute difference; odds ratio (OR) adjusted for study only; 0.67; 95% CI 0.45 to 0.99; P = 0.045; adjusted OR, 0.58; 95% CI 0.35 to 0.96; P = 0.04. Conclusion: Conservative oxygen therapy was associated with a statistically significant reduction in mortality at last follow-up compared to liberal oxygen therapy but the certainty of available evidence was low or very low due to bias, imprecision, and indirectness. PROSPERO registration number: CRD42019138931.
  • Meyhoff, Tine Sylvest; Hjortrup, Peter Buhl; Moller, Morten Hylander; Wetterslev, Jorn; Lange, Theis; Kjaer, Maj-Brit Norregaard; Jonsson, Andreas Bender; Hjortso, Carl Johan Steensen; Cronhjort, Maria; Laake, Jon Henrik; Jakob, Stephan M.; Nalos, Marek; Pettilä, Ville; van der Horst, Iwan; Ostermann, Marlies; Mouncey, Paul; Rowan, Kathy; Cecconi, Maurizio; Ferrer, Ricard; Malbrain, Manu L. N. G.; Ahlstedt, Christian; Hoffmann, Soren; Bestle, Morten Heiberg; Nebrich, Lars; Russell, Lene; Vang, Marianne; Rasmussen, Michael Lindhardt; Solling, Christoffer; Rasmussen, Bodil Steen; Brochner, Anne Craveiro; Perner, Anders (2019)
    Introduction Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock. Methods CLASSIC trial is an investigator-initiated, international, randomised, stratified, and analyst-blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health-related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre-defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention-to-treat (ITT) population. Discussion The CLASSIC trial results will provide important evidence to guide clinicians' choice regarding the IV fluid therapy in adults with septic shock.
  • Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M.; Wilkman, Erika; Perner, Anders; Takala, Jukka (2016)
    The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.
  • Ristagno, Giuseppe; Latini, Roberto; Plebani, Mario; Zaninotto, Martina; Vaahersalo, Jukka; Masson, Serge; Tiainen, Marjaana; Kurola, Jouni; Gaspari, Flavio; Milani, Valentina; Pettila, Ville; Skrifvars, Markus Benedikt; FINNRESUSCI Study Grp (2015)
    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 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.
  • EPO-TBI Investigators; ANZICS Clinical Trials Grp; Knott, Rachel J.; Harris, Anthony; Higgins, Alisa; Pettilä, Ville; Skrifvars, Markus B. (2019)
    The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p <0.001) higher in the EPO group, with an adjusted QALY increment of 0.014 (0.000-0.028; p = 0.04). Mean unadjusted costs (95% CI) were $US5668 (-9191 to -2144; p = 0.002) lower in the treatment group; controlling for baseline IMPACT-TBI score and regional heterogeneity reduced this difference to $2377 (-12,446 to 7693; p = 0.64). For a willingness-to-pay threshold of $US50,000 per QALY, 71.8% of replications were considered cost-effective. Therefore, we did not find evidence that EPO was significantly cost-effective in the treatment of moderate or severe TBI at 6-month follow-up.
  • Kortelainen, Jukka; Ala-Kokko, Tero; Tiainen, Marjaana; Strbian, Daniel; Rantanen, Kirsi; Laurila, Jouko; Koskenkari, Juha; Kallio, Mika; Toppila, Jussi; Väyrynen, Eero; Skrifvars, Markus B.; Hästbacka, Johanna (2021)
    Aim of the study: EEG slow wave activity (SWA) has shown prognostic potential in post-resuscitation care. In this prospective study, we investigated the accuracy of continuously measured early SWA for prediction of the outcome in comatose cardiac arrest (CA) survivors. Methods: We recorded EEG with a disposable self-adhesive frontal electrode and wireless device continuously starting from ICU admission until 48 h from return of spontaneous circulation (ROSC) in comatose CA survivors sedated with propofol. We determined SWA by offline calculation of C-Trend (R) Index describing SWA as a score ranging from 0 to 100. The functional outcome was defined based on Cerebral Performance Category (CPC) at 6 months after the CA to either good (CPC 1-2) or poor (CPC 3-5). Results: Outcome at six months was good in 67 of the 93 patients. During the first 12 h after ROSC, the median C-Trend Index value was 38.8 (interquartile range 28.0-56.1) in patients with good outcome and 6.49 (3.01-18.2) in those with poor outcome showing significant difference (p < 0.001) at every hour between the groups. The index values of the first 12h predicted poor outcome with an area under curve of 0.86 (95% CI0.61-0.99). With a cutoff value of 20, the sensitivity was 83.3% (69.6%-92.3%) and specificity 94.7% (83.4%-99.7%) for categorization of outcome. Conclusion: EEG SWA measured with C-Trend Index during propofol sedation offers a promising practical approach for early bedside evaluation of recovery of brain function and prediction of outcome after CA.
  • Vlasov, Hanna; Juvonen, Tatu; Hiippala, Seppo; Suojaranta, Raili; Peltonen, Markku; Schramko, Alexey; Arvonen, Kaapo; Salminen, Ulla-Stina; Kleine Budde, Ilona; Eränen, Tiina; Mazanikov, Maxim; Meinberg, Mihkel; Vähäsilta, Tommi; Wilkman, Erika; Pettilä, Ville; Pesonen, Eero (2020)
    Background In cardiac surgery with cardiopulmonary bypass (CPB), large amounts of fluids are administered. CPB priming with crystalloid solution causes marked hemodilution and fluid extravasation. Colloid solutions may reduce fluid overload because they have a better volume expansion effect than crystalloids. The European Medicines Agency does not recommend the use of hydroxyethyl starch solutions (HES) due to harmful renal effects. Albumin solution does not impair blood coagulation but the findings on kidney function are conflicting. On the other hand, albumin may reduce endothelial glycocalyx destruction and decrease platelet count during CPB. No large randomized, double-blind, clinical trials have compared albumin solution to crystalloid solution in cardiac surgery. Methods/design In this single-center, double-blind, randomized controlled trial comprising 1386 adult cardiac surgery patients, 4% albumin solution will be compared to Ringer's acetate solution in CPB priming and volume replacement up to 3200 mL during surgery and the first 24 h of intensive care unit stay. The primary efficacy outcome is the number of patients with at least one major adverse event (MAE) during 90 postoperative days (all-cause death, acute myocardial injury, acute heart failure or low output syndrome, resternotomy, stroke, major arrhythmia, major bleeding, infection compromising post-procedural rehabilitation, acute kidney injury). Secondary outcomes are total number of MAEs, incidence of major adverse cardiac events (MACE; cardiac death, acute myocardial injury, acute heart failure, arrhythmia), amount of each type of blood product transfused (red blood cells, fresh frozen plasma, platelets), total fluid balance at the end of the intervention period, total measured blood loss, development of acute kidney injury, days alive without mechanical ventilation in 90 days, days alive outside intensive care unit at 90 days, days alive at home at 90 days, and 90-day mortality. Discussion The findings of this study will provide new evidence regarding efficacy and safety of albumin solution in adult patients undergoing cardiac surgery with CPB.
  • Lillemae, Kadri; Laine, Antti T.; Schramko, Alexey; Niemi, Tomi T. (2018)
    Background:Albumin and mannitol may interfere with hemostasis, but their coinfluence is unclear. We aimed to determine the effects of albumin alone and in combination with mannitol or Ringer acetate (RAC) on hemostasis in crossover in vitro study.Materials and Methods:From citrated fresh whole blood withdrawn from 10 volunteers, we prepared 2.5, 5, 10, 15, and 20 vol% dilutions of 4% albumin (Alb group). Each sample was thereafter diluted by 15% mannitol (Alb/Man group) or RAC (Alb/RAC group) at a ratio of 9:1. Using thromboelastometry, FibTEM (fibrinogen ROTEM) and ExTEM (extrinsic ROTEM) tests were performed.Results:A 20 vol%, but not 2.5 to 15 vol% dilution of albumin caused a prolonged clot formation time, -angle decrease, and maximum clot firmness (MCF) weakening compared with undiluted sample (P
  • Babini, Giovanni; Ristagno, Giuseppe; Boccardo, Antonio; De Giorgio, Daria; De Maglie, Marcella; Affatato, Roberta; Ceriani, Sabina; Zani, Davide; Novelli, Deborah; Staszewsky, Lidia; Masson, Serge; Pravettoni, Davide; Latini, Roberto; Belloli, Angelo; Scanziani, Eugenio; Skrifvars, Markus (2019)
    Aim of the study: To evaluate in an established porcine post cardiac arrest model the effect of a mild hypercapnic ventilatory strategy on outcome. Methods: The left anterior descending coronary artery was occluded in 14 pigs and ventricular fibrillation induced and left untreated for 12 min. Cardiopulmonary resuscitation was performed for 5 min prior to defibrillation. After resuscitation, pigs were assigned to either normocapnic (end-tidal carbon dioxide (EtCO2) target: 35-40 mmHg) or hypercapnic ventilation (EtCO2 45-50 mmHg). Hemodynamics was invasively measured and EtCO2 was monitored with an infrared capnometer. Blood gas analysis, serum neuron-specific enolase (NSE) and high sensitive cardiac troponin T (hs-cTnT) were assessed. Survival and functional recovery were evaluated up to 96 h. Results: Twelve pigs were successfully resuscitated and eight survived up to 96 h, with animals in the hypercapnic group showing trend towards a longer survival. EtCO2 and arterial partial pressure of CO2 were higher in the hypercapnic group compared to the normocapnic one (p <0.01), during the 4-hour intervention. Hypercapnia was associated with higher mean arterial pressure compared to normocapnia (p <0.05). No significant differences were observed in hs-cTnT and in NSE between groups, although the values tended to be lower in the hypercapnic one. Neuronal degeneration was lesser in the frontal cortex of hypercapnic animals compared to the normocapnic ones (p <0.05). Neurological recovery was equivalent in the two groups. Conclusion: Mild hypercapnia after resuscitation was associated with better arterial pressure and lesser neuronal degeneration in this model. Nevertheless, no corresponding improvements in neurological recovery were observed.
  • Annane, Djillali; Fuchs-Buder, Thomas; Zoellner, Christian; Kaukonen, Maija; Scheeren, Thomas W. L. (2018)
  • Rentola, Raisa; Hästbacka, Johanna; Heinonen, Erkki; Rosenberg, Per H.; Häggblom, Tom; Skrifvars, Markus B. (2018)
    Arterial blood gas (ABG) analysis is the traditional method for measuring the partial pressure of carbon dioxide. In mechanically ventilated patients a continuous noninvasive monitoring of carbon dioxide would obviously be attractive. In the current study, we present a novel formula for noninvasive estimation of arterial carbon dioxide. Eighty-one datasets were collected from 19 anesthetized and mechanically ventilated pigs. Eleven animals were mechanically ventilated without interventions. In the remaining eight pigs the partial pressure of carbon dioxide was manipulated. The new formula (Formula 1) is PaCO2 = PETCO2 + k(PETO2 - PaO2) where PaO2 was calculated from the oxygen saturation. We tested the agreements of this novel formula and compared it to a traditional method using the baseline PaCO2 - ETCO2 gap added to subsequently measured, end-tidal carbon dioxide levels (Formula 2). The mean difference between PaCO2 and calculated carbon dioxide (Formula 1) was 0.16 kPa (+/- SE 1.17). The mean difference between PaCO2 and carbon dioxide with Formula 2 was 0.66 kPa (+/- SE 0.18). With a mixed linear model excluding cases with cardiorespiratory collapse, there was a significant difference between formulae (p <0.001), as well as significant interaction between formulae and time (p <0.001). In this preliminary animal study, this novel formula appears to have a reasonable agreement with PaCO2 values measured with ABG analysis, but needs further validation in human patients.
  • Kupari, Petteri; Skrifvars, Markus; Kuisma, Markku (2017)
    Background: The return of spontaneous circulation (ROSC) after cardiac arrest (RACA) score may have implications as a quality indicator for the emergency medical services (EMS) system. We aimed to validate this score externally in a physician staffed urban EMS system. Methods: We conducted a retrospective cohort study. Data on resuscitation attempts from the Helsinki EMS cardiac arrest registry from 1.1.2008 to 31.12.2010 were collected and analyzed. For each attempted resuscitation the RACA score variables were collected and the score calculated. The endpoint was ROSC defined as palpable pulse over 30 s. Calibration was assessed by comparing predicted and observed ROSC rates in the whole sample, separately for shockable and non-shockable rhythm, and separately for resuscitations lead by a specialist, registrar or medical supervisor (i.e., senior paramedic). Data are presented as medians and interquartile ranges. Statistical testing included chi-square test, the Mann-Whitney U test, Hosmer-Lemeshow goodness of fit test and calculation of 95% confidence intervals (CI) for proportions. Results: A total of 680 patients were included of whom 340 attained ROSC. The RACA score was higher in patients with ROSC (0.62 [0.46-0.69] than in those without (0.46 [0.36-0.57]) (p <0.001). Observed against predicted ROSC indicated reasonable calibration overall (p = 0.30), with better calibration in patients with a shockable initial rhythm (p = 0.75) than in patients with a non-shockable rhythm (p = 0.04). There was no statistical difference between observed and predicted ROSC rates in resuscitations attended by a specialist (50% vs 53%, 95% CI 45-55) or registrar (55% vs 53%, 95% CI 48-62), but rates were lower than predicted in resuscitations lead by a medical supervisor (36% vs 49%, 95% CI 25-47). Discussion: Developing a practical severity-of-illness scoring system for out-of-hospital cardiac arrest patients would allow patient heterogeneity adjustment and measurement of quality of care in analogy to commoly used severity-of-illness-scores developed for the similar purposes for the general intensive care unit population. However, transferring RACA score to another country with different population and EMS system might affect the performance and generalizability of the score. Conclusions: This study found a good overall calibration and moderate discrimination of the RACA score in a physician staffed urban EMS system which suggests external validity of the score. Calibration was suboptimal in patients with a non-shockable rhythm which may due to a local do-not-attempt-resuscitation policy. The lower than expected overall ROSC rate in resuscitations attended by medical supervisors requires further study.
  • Tiainen, Marjaana; Poutiainen, Erja; Oksanen, Tuomas; Kaukonen, Kirsi-Maija; Pettila, Ville; Skrifvars, Markus; Varpula, Tero; Castren, Maaret (2015)
  • Skrifvars, Markus B.; Soreide, Eldar; Sawyer, Kelly N.; Taccone, Fabio S.; Toome, Valdo; Storm, Christian; Jeppesen, Anni; Grejs, Anders; Duez, Christophe H.; Tiainen, Marjaana; Rasmussen, Bodil S.; Laitio, Timo; Hassager, Christian; Kirkegaard, Hans (2020)
    Background We studied the associations between ischemia and hypothermia duration, that is, the hypothermic to ischemic ratio (H/I ratio), with mortality in patients included in a trial on two durations of targeted temperature management (TTM) at 33 degrees C. Methods The TTH48 (NCT01689077) trial compared 24 and 48 hours of TTM in patients after cardiac arrest. We calculated the hypothermia time from return of spontaneous circulation (ROSC) until the patient reached 37 degrees C after TTM and the ischemic time from CA to ROSC. We compared continuous variables with the Mann-Whitney U test. Using COX regression, we studied the independent association of the logarithmically transformed H/I ratio and time to death as well as interaction between time to ROSC, hypothermia duration, and intervention group. We visualized the predictive ability of variables with receiver operating characteristic curve analysis. Results Of the 338 patients, 237 (70%) survived for 6 months. The H/I ratio was 155 (IQR 111-238) in survivors and 114 (IQR 80-169) in non-survivors (P <.001). In a Cox regression model including factors associated with outcome in univariate analysis, the logarithmically transformed H/I ratio was a significant predictor of outcome (hazard ratio 0.52 (0.37-0.72, P = .001)). After removing an outlier, we found no interaction between time to ROSC and intervention group (P = .55) or hypothermia duration in quartiles (P = .07) with mortality. There was no significant difference in the area under the curve (AUC) between time to ROSC and H/I ratio (Delta AUC 0.03 95% CI -0.006-0.07, P = .10). Conclusions We did not find any consistent evidence of a modification of the effect of TTM based on ischemia duration.
  • Skrifvars, Markus B.; Aneman, Anders; Ameloot, Koen (2020)
    Purpose of review To discuss recent findings relevant to optimizing blood pressure targets in adult, postcardiac arrest (PCA) patients and whether to tailor these based on specific patient, cardiac arrest or treatment characteristics. Recent findings Observational data suggest that mean arterial pressure (MAP) below 65-75 mmHg in PCA patients is associated with worse outcome. A higher MAP could be beneficial in patients with chronic hypertension who more frequently have a right shift of the cerebral autoregulation curve. Two recent randomized pilot trials compared lower and higher MAP targets during PCA care and found no significant effect on biomarkers of neurological injury. The haemodynamic interventions in those studies did not use any cerebral perfusion endpoints beyond a static MAP targets during ICU stay. Individualized, dynamic MAP targets based on assessments of cerebral perfusion and tailored to the specifics of the patient, cardiac arrest circumstances and treatment responses may be more conducive to improved outcomes. Pilot data suggest that near infrared spectroscopy monitoring may be used to determine the cerebral autoregulatory capacity and an optimal MAP, but this approach is yet to be tested in clinical trials. Current evidence suggests targeting a MAP of at least 65-75 mmHg in PCA patients. Future studies should focus on whether certain patient groups could benefit from higher and dynamic MAP targets.
  • Holmström, Ester; Efendijev, Ilmar; Raj, Rahul; Pekkarinen, Pirkka T.; Litonius, Erik; Skrifvars, Markus B. (2021)
    BackgroundCardiac arrest (CA) is a leading cause of death worldwide. As population ages, the need for research focusing on CA in elderly increases. This study investigated treatment intensity, 12-month neurological outcome, mortality and healthcare-associated costs for patients aged over 75 years treated for CA in an intensive care unit (ICU) of a tertiary hospital.MethodsThis single-centre retrospective study included adult CA patients treated in a Finnish tertiary hospital's ICU between 2005 and 2013. We stratified the study population into two age groups: 75 years. We compared interventions defined by the median daily therapeutic scoring system (TISS-76) between the age groups to find differences in treatment intensity. We calculated cost-effectiveness by dividing the total one-year healthcare-associated costs of all patients by the number of survivors with a favourable neurological outcome. Favourable outcome was defined as a cerebral performance category (CPC) of 1-2 at 12 months after cardiac arrest. Logistic regression analysis was used to identify independent associations between age group, mortality and neurological outcome.ResultsThis study included a total of 1,285 patients, of which 212 (16%) were >= 75 years of age. Treatment intensity was lower for the elderly compared to the younger group, with median TISS scores of 116 and 147, respectively (p
  • FINNRESUSCI Study Grp; Oksanen, Tuomas; Tiainen, Marjaana; Vaahersalo, Jukka; Bendel, Stepani; Varpula, Tero; Skrifvars, Markus; Pettilä, Ville; Wilkman, Erika (2018)
    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.