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  • Haywood, Kirstie L.; Pearson, Nathan; Morrison, Laurie J.; Castren, Maaret; Lilja, Gisela; Perkins, Gavin D. (2018)
    Aim: High quality evidence of out-of-hospital cardiac arrest (OHCA) survivors' health-related quality of life (HRQoL) can measure the long-term impact of CA. The aim of this study was to critically appraise the evidence of psychometric quality and acceptability of measures used in the assessment of HRQoL in cardiac arrest survivors. Methods: Systematic literature searches (2004-2017) and named author searches to identify articles pertaining to the measurement of HRQoL. Data on study quality, measurement and practical properties were extracted and assessed against international standards. Results: From 356 reviewed abstracts, 69 articles were assessed in full. 25 provided evidence for 10 measures of HRQoL: one condition-specific; three generic profile measures; two generic index; and four utility measures. Although limited, evidence for measurement validity was strongest for the HUI3 and SF-36. However, evidence for reliability, content validity, responsiveness and interpretability and acceptability was generally limited or not available in the CA population for all measures. Conclusions: This review has demonstrated that a measure of quality of life specific to OHCA survivors is not available. Limited evidence of validity exists for one utility measure - the HUI3 - and a generic profile - the SF-36. Robust evidence of the quality and acceptability of HRQoL measures in OHCA was limited or not available. Future collaborative research must seek to urgently establish the relevance and acceptability of these measures to OHCA survivors, to establish robust evidence of essential measurement and practical properties over the short and long-term, and to inform future HRQoL assessment in the OHCA population. (C) 2017 Elsevier B.V. All rights reserved.
  • Perkins, Gavin D.; Callaway, Clifton W.; Haywood, Kirstie; Neumar, Robert W.; Lilja, Gisela; Rowland, Matthew J.; Sawyer, Kelly N.; Skrifvars, Markus B.; Nolan, Jerry P. (2021)
    As more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes.
  • Pospelov, Alexey S.; Ala-Kurikka, Tommi; Kurki, Samu; Voipio, Juha; Kaila, Kai (2021)
    Objective Seizures are common in neonates recovering from birth asphyxia but there is general consensus that current pharmacotherapy is suboptimal and that novel antiseizure drugs are needed. We recently showed in a rat model of birth asphyxia that seizures are triggered by the post-asphyxia recovery of brain pH. Here our aim was to investigate whether carbonic anhydrase inhibitors (CAIs), which induce systemic acidosis, block the post-asphyxia seizures. Methods The CAIs acetazolamide (AZA), benzolamide (BZA), and ethoxzolamide (EZA) were administered intraperitoneally or intravenously to 11-day-old rats exposed to intermittent asphyxia (30 min; three 7+3 min cycles of 9% and 5% O-2 at 20% CO2). Electrode measurements of intracortical pH, Po-2, and local field potentials (LFPs) were made under urethane anesthesia. Convulsive seizures and blood acid-base parameters were examined in freely behaving animals. Results The three CAIs decreased brain pH by 0.14-0.17 pH units and suppressed electrographic post-asphyxia seizures. AZA, BZA, and EZA differ greatly in their lipid solubility (EZA > AZA > BZA) and pharmacokinetics. However, there were only minor differences in the delay (range 0.8-3.7 min) from intraperitoneal application to their action on brain pH. The CAIs induced a modest post-asphyxia elevation of brain Po-2 that had no effect on LFP activity. AZA was tested in freely behaving rats, in which it induced a respiratory acidosis and decreased the incidence of convulsive seizures from 9 of 20 to 2 of 17 animals. Significance AZA, BZA, and EZA effectively block post-asphyxia seizures. Despite the differences in their pharmacokinetics, they had similar effects on brain pH, which indicates that their antiseizure mode of action was based on respiratory (hypercapnic) acidosis resulting from inhibition of blood-borne and extracellular vascular carbonic anhydrases. AZA has been used for several indications in neonates, suggesting that it can be safely repurposed for the treatment of neonatal seizures as an add-on to the current treatment regimen.
  • Babini, Giovanni; Ameloot, Koen; Skrifvars, Markus (2021)
    Postcardiac arrest myocardial dysfunction (PCAMD) is a frequent complication faced during post-resuscitation care that adversely impacts survival and neurological outcome. Both mechanical and electrical factors contribute to the occurrence of PCAMD. Prearrest ventricular function, the cause of cardiac arrest, global ischemia, resuscitation factors, ischemia/reperfusion injury and post-resuscitation treatments contribute to the severity of PCMAD. the pathophysiology of PCAMD is complex and include myocytes energy failure, impaired contractility, cardiac edema, mitochondrial damage, activation of inflammatory pathways and the coagulation cascade, persistent ischemic injury and myocardial stiffness. Hypotension and low cardiac output with vasopressor/inotropes need are frequent after resuscitation. However, clinical, hemodynamic and laboratory signs of shock are frequently altered by cardiac arrest pathophysiology and post-resuscitation treatment, potentially being misleading and not fully reflecting the severity of postcardiac arrest syndrome. Even if validated criteria are lacking, an extensive hemodynamic evaluation is useful to define a "benign" and a "malign" form of myocardial dysfunction and circulatory shock, potentially having treatment and prognostic implications. cardiac output is frequently decreased after cardiac arrest, particularly in patients treated with target temperature management (TTM); however, it is not independently associated with outcome. sinus bradycardia during TTM seems independently associated with survival and good neurological outcome, representing a promising prognostic indicator. Higher mean arterial pressure (MAP) seems to be associated with improved survival and cerebral function after cardiac arrest; however, two recent randomized clinical trials failed to replicate these results. recommendations on hemodynamic optimization are relatively poor and are largely based on general principle of intensive care medicine.
  • 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.
  • Stevenson, Nathan J.; Vanhatalo, Sampsa (2018)
    Neonatal seizures are widely considered a neurological emergency with a need for prompt treatment, yet they are known to present a highly elusive target for bedside clinicians. Recent studies have suggested that the design of a neonatal seizure treatment trial will profoundly influence the sample size, which may readily increase to hundreds or even thousands as the achieved effect size diminishes to clinical irrelevance. The self-limiting and rapidly resolving nature of neonatal seizures diminishes the measurable treatment effect every hour after seizure onset and any effect may potentially be confused with spontaneous resolution, precluding the value of many observational studies. The large individual variability in seizure occurrence over time and between etiologies challenges group comparisons, while the absence of clinical signs mandates quantification of seizure occurrence with continuous multi-channel EEG monitoring. A biologically sound approach that views neonatal seizures as a functional cot-side biomarker rather than an object to treat can overcome these challenges. (C) 2018 Elsevier Ltd. All rights reserved.
  • 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.
  • Calabro, Lorenzo; Bougouin, Wulfran; Cariou, Alain; De Fazio, Chiara; Skrifvars, Markus; Soreide, Eldar; Creteur, Jacques; Kirkegaard, Hans; Legriel, Stephane; Lascarrou, Jean-Baptiste; Megarbane, Bruno; Deye, Nicolas; Taccone, Fabio Silvio (2019)
    Background Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. Methods We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Results Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75-0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62-1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Conclusions Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).
  • Kirkegaard, Hans; Grejs, Anders M.; Gudbjerg, Simon; Duez, Christophe; Jeppesen, Anni; Hassager, Christian; Laitio, Timo; Storm, Christian; Taccone, Fabio Silvio; Skrifvars, Markus B.; Soreide, Eldar (2022)
    Background Electrolyte disturbances can result from targeted temperature treatment (TTM) in out-of-hospital cardiac arrest (OHCA) patients. This study explores electrolyte changes in blood and urine in OHCA patients treated with TTM. Methods This is a sub-study of the TTH48 trial, with the inclusion of 310 unconscious OHCA patients treated with TTM at 33 degrees C for 24 or 48 h. Over a three-day period, serum concentrations were obtained on sodium potassium, chloride, ionized calcium, magnesium and phosphate, as were results from a 24-h diuresis and urine electrolyte concentration and excretion. Changes over time were analysed with a mixed-model multivariate analysis of variance with repeated measurements. Results On admission, mean +/- SD sodium concentration was 138 +/- 3.5 mmol/l, which increased slightly but significantly (p < .05) during the first 24 h. Magnesium concentration stayed within the reference interval. Median ionized calcium concentration increased from 1.11 (IQR 1.1-1.2) mmol/l during the first 24 h (p < .05), whereas median phosphate concentration dropped to 1.02 (IQR 0.8-1.2) mmol/l (p < .05) and stayed low. During rewarming, potassium concentrations increased, and magnesium and ionizes calcium concentration decreased (p < .05). Median 24-h diuresis results on days one and two were 2198 and 2048 ml respectively, and the electrolyte excretion mostly stayed low in the reference interval. Conclusions Electrolytes mostly remained within the reference interval. A temporal change occurred in potassium, magnesium and calcium concentrations with TTM's different phases. No hypothermia effect on diuresis was detected, and urine excretion of electrolytes mostly stayed low.
  • Ristagno, Giuseppe; Masson, Serge; Tiainen, Marjaana; Bendel, Stepani; Bernasconi, Roberto; Varpula, Tero M; Milani, Valentina; Vaahersalo, Jukka; Magnoli, Michela; Spanuth, Eberhard; Barlera, Simona; Latini, Roberto; Hoppu, Sanna; Pettila, Ville; Skrifvars, Markus; FINNRESUSCI Study Grp (2016)
    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.
  • EPO-TBI Investigators Anzics Clin; Skrifvars, Markus B. (2019)
    Background Acute kidney injury (AKI) in traumatic brain injury (TBI) is poorly understood and it is unknown if it can be attenuated using erythropoietin (EPO). Methods Pre-planned analysis of patients included in the EPO-TBI ( NCT00987454) trial who were randomized to weekly EPO (40 000 units) or placebo (0.9% sodium chloride) subcutaneously up to three doses or until intensive care unit (ICU) discharge. Creatinine levels and urinary output (up to 7 days) were categorized according to the Kidney Disease Improving Global Outcome (KDIGO) classification. Severity of TBI was categorized with the International Mission for Prognosis and Analysis of Clinical Trials in TBI. Results Of 3348 screened patients, 606 were randomized and 603 were analyzed. Of these, 82 (14%) patients developed AKI according to KDIGO (60 [10%] with KDIGO 1, 11 [2%] patients with KDIGO 2, and 11 [2%] patients with KDIGO 3). Male gender (hazard ratio [HR] 4.0 95% confidence interval [CI] 1.4-11.2, P = 0.008) and severity of TBI (HR 1.3 95% CI 1.1-1.4, P <0.001 for each 10% increase in risk of poor 6 month outcome) predicted time to AKI. KDIGO stage 1 (HR 8.8 95% CI 4.5-17, P <0.001), KDIGO stage 2 (HR 13.2 95% CI 3.9-45.2, P <0.001) and KDIGO stage 3 (HR 11.7 95% CI 3.5-39.7, P <0.005) predicted time to mortality. EPO did not influence time to AKI (HR 1.08 95% CI 0.7-1.67, P = 0.73) or creatinine levels during ICU stay (P = 0.09). Conclusions Acute kidney injury is more common in male patients and those with severe compared to moderate TBI and appears associated with worse outcome. EPO does not prevent AKI after TBI.
  • Nevalainen, Päivi; Marchi, Viviana; Metsäranta, Marjo; Lönnqvist, Tuula; Toiviainen-Salo, Sanna; Vanhatalo, Sampsa; Lauronen, Leena (2017)
    Objective: To evaluate the added value of somatosensory (SEPs) and visual evoked potentials (VEPs) recorded simultaneously with routine EEG in early outcome prediction of newborns with hypoxicischemic encephalopathy under modern intensive care. Methods: We simultaneously recorded multichannel EEG, median nerve SEPs, and flash VEPs during the first few postnatal days in 50 term newborns with hypoxic-ischemic encephalopathy. EEG background was scored into five grades and the worst two grades were considered to indicate poor cerebral recovery. Evoked potentials were classified as absent or present. Clinical outcome was determined from the medical records at a median age of 21 months. Unfavorable outcome included cerebral palsy, severe mental retardation, severe epilepsy, or death. Results: The accuracy of outcome prediction was 98% with SEPs compared to 90% with EEG. EEG alone always predicted unfavorable outcome when it was inactive (n = 9), and favorable outcome when it was normal or only mildly abnormal (n = 17). However, newborns with moderate or severe EEG background abnormality could have either favorable or unfavorable outcome, which was correctly predicted by SEP in all but one newborn (accuracy in this subgroup 96%). Absent VEPs were always associated with an inactive EEG, and an unfavorable outcome. However, presence of VEPs did not guarantee a favorable outcome. Conclusions: SEPs accurately predict clinical outcomes in newborns with hypoxic-ischemic encephalopathy and improve the EEG-based prediction particularly in those newborns with severely or moderately abnormal EEG findings. Significance: SEPs should be added to routine EEG recordings for early bedside assessment of newborns with hypoxic-ischemic encephalopathy. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Saarinen, Sini; Salo, Ari; Boyd, James; Laukkanen-Nevala, Päivi; Silfvast, Catharina; Virkkunen, Ilkka; Silfvast, Tom (2018)
    Patients resuscitated from out-of-hospital cardiac arrest (OHCA) with pulseless electrical activity (PEA) as initial cardiac rhythm are not always treated in intensive care units (ICUs): some are admitted to high dependency units with various level of care, others to ordinary wards. Aim of this study was to describe the factors determining level of hospital care after OHCA with PEA, post-resuscitation care and survival. Adult OHCA patients with PEA (n = 221), who were resuscitated in southern Finland between 2010 and 2013 were included, provided patient survived to hospital admission. The patients were divided into four groups according to the level of hospital care provided: ordinary ward and Level 1-3 ICUs. Differences in patient characteristics, post-resuscitation care and survival were compared between the groups. Most patients (62.4%) were treated at Level 2 ICUs. Longer time to ROSC and advanced age decreased admission rate to Level 2 or 3 post-resuscitation care, whereas good pre-arrest CPC (1-2) increased the admission rate to Level 2/3 ICUs independently. Treatment with targeted temperature management (TTM) (4.1%) or early coronary angiography (3.2%) were very rare. Prognostic decisions were made earlier in the lower treatment intensity groups (p <0.01). One-year survival rate was 24.0, 17.1% survived with good neurological outcome. Neurological outcome was better with more intensive care. After adjustment, level of care was not independent predictor for outcome: only return of spontaneous circulation (ROSC) time, cardiac arrest cause and pre-arrest performance affected independently to 1-year survival, age and ROSC for neurologic outcome. PEA are usually admitted to Level 2 ICUs for post-resuscitation care in the capital area of Finland. Age, ROSC and pre-arrest CPC were independent predictors for level of post-resuscitation care. TTM and early CAG were rare and provided only for Level 3 ICU patients. Prognostication was earlier in lower level of care units. Good neurologic survival was more common with more intensive level of post-resuscitation care. After adjustment, level of care was not independent predictor for survival or neurologic outcome: only ROSC, cardiac arrest cause and pre-arrest performance predicted 1-year survival; age and ROSC neurologic outcome.
  • 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.
  • 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.
  • Laurikkala, Johanna; Wilkman, Erika; Pettila, Ville; Kurola, Jouni; Reinikainen, Matti; Hoppu, Sanna; Ala-Kokko, Tero; Tallgren, Minna; Tiainen, Marjaana; Vaahersalo, Jukka; Varpula, Tero M; Skrifvars, Markus; FINNRESUSCI Study Grp (2016)
    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 1W 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Int Liaison Comm Resuscitation; Buick, Jason E.; Wallner, Clare; Aickin, Richard; Meaney, Peter A.; de Caen, Allan; Maconochie, Ian; Skrifvars, Markus B.; Welsford, Michelle (2019)
    Introduction: The International Liaison Committee on Resuscitation prioritized the need to update the review on the use of targeted temperature management (TTM) in paediatric post cardiac arrest care. In this meta-analysis, the effectiveness of TTM at 32-36 degrees C was compared with no target or a different target for comatose children who achieve a return of sustained circulation after cardiac arrest. Methods: Electronic databases were searched from inception to December 13, 2018. Randomized controlled trials and non-randomized studies with a comparator group that evaluated TTM in children were included. Pairs of independent reviewers extracted the demographic and outcome data, appraised risk of bias, and assessed GRADE certainty of effects. A random effects meta-analysis was undertaken where possible. Results: Twelve studies involving 2060 patients were included. Two randomized controlled trials provided the evidence that TTM at 32-34 degrees C compared with a target at 36-37.5 degrees C did not statistically improve long-term good neurobehavioural survival (risk ratio: 1.15; 95% CI: 0.69-1.93), long-term survival (RR: 1.14; 95% CI: 0.93-1.39), or short-term survival (risk ratio: 1.14; 95% CI: 0.96-1.36). TTM at 32-34 degrees C did not show statistically increased risks of infection, recurrent cardiac arrest, serious bleeding, or arrhythmias. A novel analysis suggests that another small RCT might provide enough evidence to show benefit for TTM in out-of-hospital cardiac arrest. Conclusion: There is currently inconclusive evidence to either support or refute the use of TTM at 32-34 degrees C for comatose children who achieve return of sustained circulation after cardiac arrest. Future trials should focus on children with out-of-hospital cardiac arrest.
  • Saarinen, Sini; Castren, Maaret; Virkkunen, Ilkka; Kamarainen, Antti (2015)
    Background: Aim of this study was to compare post resuscitation care of out-of-hospital cardiac arrest (OHCA) patients in Nordic (Denmark, Finland, Iceland, Norway, Sweden) intensive care units (ICUs). Methods: An online questionnaire was sent to Nordic ICUs in 2012 and was complemented by an additional one in 2014. Results: The first questionnaire was sent to 188 and the second one to 184 ICUs. Response rates were 51 % and 46 %. In 2012, 37 % of the ICUs treated all patients resuscitated from OHCA with targeted temperature management (TTM) at 33 degrees C. All OHCA patients admitted to the ICU were treated with TTM at 33 degrees C more often in Norway (69 %) compared to Finland (20 %) and Sweden (25 %), p 0.02 and 0.014. In 2014, 63 % of the ICUs still use TTM at 33 degrees C, but 33 % use TTM at 36 degrees C. Early coronary angiography (CAG) and possible percutaneous coronary intervention (PCI) was routinely provided for all survivors of OHCA in 39 % of the hospitals in 2012 and in 28 % of the hospitals in 2014. Routine CAG for all actively treated victims of OHCA was performed more frequently in Sweden (51 %) and in Norway (54 %) compared to Finland (13 %), p 0.014 and 0.042. Conclusions: Since 2012, TTM at 36 degrees C has been implemented in some ICUs, but TTM at 33 degrees C is used in majority of the ICUs. TTM at 33 or 36 degrees C and primary CAG are not routinely provided for all OHCA survivors and the criteria for these and ICU admission are variable. Best practices as a uniform approach to the optimal care of the resuscitated patient should be sought in the Nordic Countries.
  • TTH48 Investigators; De Fazio, Chiara; Skrifvars, Markus B.; Soreide, Eldar; Taccone, Fabio Silvio (2021)
    Background: No data are available on the quality of targeted temperature management (TTM) provided to out-of-hospital cardiac arrest (OHCA) patients and its association with outcome. Methods: Post hoc analysis of the TTH48 study (NCT01689077), which compared the effects of prolonged TTM at 33 degrees C for 48 h to standard 24-h TTM on neurologic outcome. Admission temperature, speed of cooling, rewarming rates, precision (i.e. temperature variability), overcooling and overshooting as post-cooling fever (i.e. >38.0 degrees C) were collected. A specific score, ranging from 1 to 9, was computed to define the "quality of TTM". Results: On a total of 352 patients, most had a moderate quality of TTM (n = 217; 62% - score 4-6), while 80 (23%) patients had a low quality of TTM (score 1-3) and only 52 (16%) a high quality of TTM (score 7-9). The proportion of patients with unfavorable neurological outcome (UO; Cerebral Performance Category of 3-5 at 6 months) was similar between the different quality of TTM groups (p = 0.90). Although a shorter time from arrest to target temperature and a lower proportion of time outside the target ranges in the TTM 48-h than in the TTM 24-h group, quality of TTM was similar between groups. Also, the proportion of patients with UO was similar between the different quality of TTM groups when TTM 48-h and TTM 24-h were compared. Conclusions: In this study, high quality of TTM was provided to a small proportion of patients. However, quality of TTM was not associated with patients' outcome.
  • Hiltunen, Pamela; Kuisma, Markku; Silfvast, Tom; Rutanen, Juha; Vaahersalo, Jukka; Kurola, Jouni; FINNRESUSCI Prehosp Study Grp (2012)