Browsing by Subject "Intensive care"

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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.
  • Fallenius, Marika; Skrifvars, Markus B; Reinikainen, Matti; Bendel, Stepani; Raj, Rahul (BioMed Central, 2017)
    Abstract Background Intensive care scoring systems are widely used in intensive care units (ICU) around the world for case-mix adjustment in research and benchmarking. The aim of our study was to investigate the usefulness of common intensive care scoring systems in predicting mid-term mortality in patients with spontaneous intracerebral hemorrhage (ICH) treated in intensive care units (ICU). Methods We performed a retrospective observational study including adult patients with spontaneous ICH treated in Finnish ICUs during 2003–2012. We used six-month mortality as the primary outcome of interest. We used logistic regression to customize Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA) for six-month mortality prediction. To assess the usefulness of the scoring systems, we compared their discrimination and calibration with two simpler models consisting of age, Glasgow Coma Scale (GCS) score, and premorbid functional status. Results Totally 3218 patients were included. Overall six-month mortality was 48%. APACHE II and SAPS II outperformed SOFA (area under the receiver operator curve [AUC] 0.83 and 0.84, respectively, vs. 0.73) but did not show any benefit over the simpler models in terms of discrimination (AUC 0.84, p > 0.05 for all models). SAPS II showed satisfactory calibration (p = 0.058 in the Hosmer-Lemeshow test), whereas all other models showed poor calibration (p < 0.05). Discussion In this retrospective multi-center study, we found that SAPS II and APACHE II were of no additional prognostic value to a simple model based on only age and GCS score for patients with ICH treated in the ICU. In fact, the major predictive ability of APACHE II and SAPS II comes from their age and GCS score components. SOFA performed significantly poorer than the other models and is not applicable as a prognostic model for ICH patients. All models displayed poor calibration, highlighting the need for improved prognostic models for ICH patients. Conclusion The common intensive care scoring systems did not outperform a simpler model based on only age and GCS score. Thus, the use of previous intensive care scoring systems is not warranted in ICH patients.
  • Fallenius, Marika; Skrifvars, Markus B.; Reinikainen, Matti; Bendel, Stepani; Raj, Rahul (2017)
    Background: Intensive care scoring systems are widely used in intensive care units (ICU) around the world for case-mix adjustment in research and benchmarking. The aim of our study was to investigate the usefulness of common intensive care scoring systems in predicting mid-term mortality in patients with spontaneous intracerebral hemorrhage (ICH) treated in intensive care units (ICU). Methods: We performed a retrospective observational study including adult patients with spontaneous ICH treated in Finnish ICUs during 2003-2012. We used six-month mortality as the primary outcome of interest. We used logistic regression to customize Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA) for six-month mortality prediction. To assess the usefulness of the scoring systems, we compared their discrimination and calibration with two simpler models consisting of age, Glasgow Coma Scale (GCS) score, and premorbid functional status. Results: Totally 3218 patients were included. Overall six-month mortality was 48%. APACHE II and SAPS II outperformed SOFA (area under the receiver operator curve [AUC] 0.83 and 0.84, respectively, vs. 0.73) but did not show any benefit over the simpler models in terms of discrimination (AUC 0.84, p > 0.05 for all models). SAPS II showed satisfactory calibration (p = 0.058 in the Hosmer-Lemeshow test), whereas all other models showed poor calibration (p <0.05). Discussion: In this retrospective multi-center study, we found that SAPS II and APACHE II were of no additional prognostic value to a simple model based on only age and GCS score for patients with ICH treated in the ICU. In fact, the major predictive ability of APACHE II and SAPS II comes from their age and GCS score components. SOFA performed significantly poorer than the other models and is not applicable as a prognostic model for ICH patients. All models displayed poor calibration, highlighting the need for improved prognostic models for ICH patients. Conclusion: The common intensive care scoring systems did not outperform a simpler model based on only age and GCS score. Thus, the use of previous intensive care scoring systems is not warranted in ICH patients.
  • Cooke, Marie; Ritmala-Castren, Marita; Dwan, Toni; Mitchell, Marion (2020)
    Background Pharmacological interventions for sleep (analgesic, sedative and hypnotic agents) can both disrupt and induce sleep and have many negative side effects within the intensive care population. The use of complementary and alternative medicine therapies to assist with sleep has been studied but given the variety of modalities and methodological limitations no reliable conclusions have been drawn. Objective To synthesise research findings regarding the effectiveness of using complementary and alternative medicine interventions within the domains of mind and body practices (relaxation techniques, acupuncture) and natural biologically based products (herbs, vitamins, minerals, probiotics) on sleep quality and quantity in adult intensive care patients. Review method used Systematic review Data sources Five databases were searched in August 2018 and updated in February 2019 and 2020. Review methods: Searches were limited to peer reviewed randomised controlled trials, published in English involving adult populations in intensive care units. Interventions were related to the complementary and alternative medicine domains of mind and body practices and natural products. Included studies were assessed using Cochrane's risk of bias tool. Results Seventeen studies were included. The interventions used varied: 4 investigated melatonin; 4 music +/- another therapy; 3 acupressure; 2 aromatherapy and 1 each for relaxation and imagery, reflexology, bright light exposure and inspiratory muscle training. Measurement of sleep quantity and quality was also varied: 5 studies used objective measures such as Polysomnography and Bispectral index with the remaining using subjective patient or clinician assessment (for example, Richards-Campbell Sleep Questionnaire, Pittsburgh Sleep Quality Index, observation). Given the different interventions, outcomes and measures used in the studies a meta-analysis was not possible. Generally, the results support the use of complementary and alternative medicine for assisting with sleep with 11 out of 17 trials reporting significant results for the interventions examined. Conclusions Complementary and alternative medicine interventions, in particular, melatonin and music, have shown promise for improving sleep in adults with critically conditions; however, further research that addresses the limitations of small sample sizes and improved techniques for measuring sleep is needed.
  • ARISE Investigators; Luethi, Nora; Bailey, Michael; Harjola, V-P; Okkonen, M.; Pettilä, V.; Sutinen, E.; Wilkman, E. (2020)
    Purpose: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. Material and methods: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age ( Results: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. Conclusions: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group. (C) 2019 Elsevier Inc. All rights reserved.
  • Kamarainen, Olli-Pekka; Huttunen, Jukka; Lindgren, Antti; Lang, Maarit; Bendel, Stepani; Uusaro, Ari; Parviainen, Ilkka; Koivisto, Timo; Isoniemi, Helena; Jääskeläinen, Juha E. (2018)
    To analyze the organ donation action in population-based neurointensive care of acute aneurysmal subarachnoid hemorrhage (aSAH) and to seek factors that would improve the identification of potential organ donors (PODs) and increase the donor conversion rate (DCR) after aSAH. The Kuopio Intracranial Aneurysm Database, prospective since 1995, includes all aSAH patients admitted to the Kuopio University Hospital (KUH) from its defined Eastern Finnish catchment population. We analyzed 769 consecutive acute aSAH patients from 2005 to 2015, including their data from the Finnish Transplantation Unit and the national clinical registries. We analyzed PODs vs. actual donors among the 145 (19%) aSAH patients who died within 14 days of admission. Finland had implemented the national presumed consent (opt-out) within the study period in the end of 2010. We retrospectively identified 83 (57%) PODs while only 49 (34%) had become actual donors (total DCR 59%); the causes for non-donorship were 15/34 (44%) refusals of consent, 18/34 (53%) medical contraindications for donation, and 1/34 (3%) failure of recognition. In 2005-2010, there were 11 refusals by near relatives with DCR 52% (29/56) and only three in 2011-2015 with DCR 74% (20/27). Severe condition on admission (Hunt and Hess grade IV or V) independently associated with the eventual POD status. Nearly 20% of all aSAH patients acutely admitted to neurointensive care from a defined catchment population died within 14 days, almost half from cardiopulmonary causes at a median age of 69 years. Of all aSAH patients, 11% were considered as potential organ donors (PODs). Donor conversion rate (DCR) was increased from 52 to 74% after the national presumed consent (opt-out). Implicitly, DCR among aSAH patients could be increased by admitting them to the intensive care regardless of dismal prognosis for the survival, along a dedicated organ donation program for the catchment population.
  • Luostarinen, Teemu; Virta, Jyri; Satopää, Jarno; Bäcklund, Minna; Kivisaari, Riku; Korja, Miikka; Raj, Rahul (2020)
    Background To ensure adequate intensive care unit (ICU) capacity for SARS-CoV-2 patients, elective neurosurgery and neurosurgical ICU capacity were reduced. Further, the Finnish government enforced strict restrictions to reduce the spread. Our objective was to assess changes in ICU admissions and prognosis of traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) during the Covid-19 pandemic. Methods Retrospective review of all consecutive patients with TBI and aneurysmal SAH admitted to the neurosurgical ICU in Helsinki from January to May of 2019 and the same months of 2020. The pre-pandemic time was defined as weeks 1-11, and the pandemic time was defined as weeks 12-22. The number of admissions and standardized mortality rates (SMRs) were compared to assess the effect of the Covid-19 pandemic on these. Standardized mortality rates were adjusted for case mix. Results Two hundred twenty-four patients were included (TBIn= 123, SAHn= 101). There were no notable differences in case mix between TBI and SAH patients admitted during the Covid-19 pandemic compared with before the pandemic. No notable difference in TBI or SAH ICU admissions during the pandemic was noted in comparison with early 2020 or 2019. SMRs were no higher during the pandemic than before. Conclusion In the area of Helsinki, Finland, there were no changes in the number of ICU admissions or in prognosis of patients with TBI or SAH during the Covid-19 pandemic.
  • Jakkula, Pekka; Hästbacka, Johanna; Reinikainen, Matti; Pettilä, Ville; Loisa, Pekka; Tiainen, Marjaana; Wilkman, Erika; Bendel, Stepani; Birkelund, Thomas; Pulkkinen, Anni; Bäcklund, Minna; Heino, Sirkku; Karlsson, Sari; Kopponen, Hiski; Skrifvars, Markus B. (2019)
    BackgroundCerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO(2)) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients.MethodsWe performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO(2) in 118 OHCA patients with NIRS during the first 36h of intensive care. We determined the NSE concentrations from serum samples at 48h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6months. We evaluated the association between rSO(2) and serum NSE concentrations and the association between rSO(2) and good (CPC 1-2) and poor (CPC 3-5) neurological outcome.ResultsThe median (inter-quartile range (IQR)) NSE concentration at 48h was 17.5 (13.4-25.0) g/l in patients with good neurological outcome and 35.2 (22.6-95.8) g/l in those with poor outcome, p
  • Jakkula, Pekka; Hästbacka, Johanna; Reinikainen, Matti; Pettilä, Ville; Loisa, Pekka; Tiainen, Marjaana; Wilkman, Erika; Bendel, Stepani; Birkelund, Thomas; Pulkkinen, Anni; Bäcklund, Minna; Heino, Sirkku; Karlsson, Sari; Kopponen, Hiski; Skrifvars, Markus B (BioMed Central, 2019)
    Abstract Background Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO2) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. Methods We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO2 and serum NSE concentrations and the association between rSO2 and good (CPC 1–2) and poor (CPC 3–5) neurological outcome. Results The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4–25.0) μg/l in patients with good neurological outcome and 35.2 (22.6–95.8) μg/l in those with poor outcome, p < 0.001. We found no significant correlation between median rSO2 and NSE at 48 h, rs = − 0.08, p = 0.392. The median (IQR) rSO2 during the first 36 h of intensive care was 70.0% (63.5–77.0%) in patients with good outcome and 71.8% (63.3–74.0%) in patients with poor outcome, p = 0.943. There was no significant association between rSO2 over time and neurological outcome. In a binary logistic regression model, rSO2 was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94–1.04, p = 0.635). Conclusions We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA. Trial registration ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.
  • Pietiläinen, Laura; Hästbacka, Johanna; Bäcklund, Minna; Parviainen, Ilkka; Pettilä, Ville; Reinikainen, Matti (2018)
    We assessed the association between the premorbid functional status (PFS) and 1-year mortality and functional status of very old intensive care patients. Using a nationwide quality registry, we retrieved data on patients treated in Finnish intensive care units (ICUs) during the period May 2012aEuro'April 2013. Of 16,389 patients, 1827 (11.1%) were very old (aged 80 years or older). We defined a person with good functional status as someone independent in activities of daily living (ADL) and able to climb stairs without assistance; a person with poor functional status was defined as needing assistance for ADL or being unable to climb stairs. We adjusted for severity of illness and calculated the impact of PFS. Overall, hospital mortality was 21.3% and 1-year mortality was 38.2%. For emergency patients (73.5% of all), hospital mortality was 28% and 1-year mortality was 48%. The functional status at 1 year was comparable to the PFS in 78% of the survivors. PFS was poor for 43.3% of the patients. A poor PFS predicted an increased risk of in-hospital death, adjusted odds ratio (OR) 1.50 (95% confidence interval, 1.07-2.10), and of 1-year mortality, OR 2.18 (1.67-2.85). PFS data significantly improved the prediction of 1-year mortality. Of very old ICU patients, 62% were alive 1 year after ICU admission and 78% of the survivors had a functional status comparable to the premorbid situation. A poor PFS doubled the odds of death within a year. Knowledge of PFS improved the prediction of 1-year mortality.
  • Vehviläinen, Juho; Skrifvars, Markus B.; Reinikainen, Matti; Bendel, Stepani; Marinkovic, Ivan; Ala-Kokko, Tero; Hoppu, Sanna; Laitio, Ruut; Siironen, Jari; Raj, Rahul (2021)
    Background Psychiatric sequelae after traumatic brain injury (TBI) are common and may impede recovery. We aimed to assess the occurrence and risk factors of post-injury psychotropic medication use in intensive care unit (ICU)-treated patients with TBI and its association with late mortality. Methods We conducted a retrospective multi-centre observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted in four university hospital ICUs during 2003-2013 that were alive at 1 year after injury. Patients were followed-up until end of 2016. We obtained data regarding psychotropic medication use through the national drug reimbursement database. We used multivariable logistic regression models to assess the association between TBI severity, treatment-related variables and the odds of psychotropic medication use and its association with late all-cause mortality (more than 1 year after TBI). Results Of 3061 patients, 2305 (75%) were alive at 1 year. Of these, 400 (17%) became new psychotropic medication users. The most common medication types were antidepressants (61%), antipsychotics (35%) and anxiolytics (26%). A higher Glasgow Coma Scale (GCS) score was associated with lower odds (OR 0.93, 95% CI 0.90-0.96) and a diffuse injury with midline shift was associated with higher odds (OR 3.4, 95% CI 1.3-9.0) of new psychotropic medication use. After adjusting for injury severity, new psychotropic medication use was associated with increased odds of late mortality (OR 1.19, 95% CI 1.19-2.17, median follow-up time 6.4 years). Conclusions Psychotropic medication use is common in TBI survivors. Higher TBI severity is associated with increased odds of psychotropic medication use. New use of psychotropic medications after TBI was associated with increased odds of late mortality. Our results highlight the need for early identification of potential psychiatric sequelae and psychiatric evaluation in TBI survivors.
  • Hjortrup, Peter B.; Haase, Nicolai; Bundgaard, Helle; Thomsen, Simon L.; Winding, Robert; Pettilä, Ville; Aaen, Anne; Lodahl, David; Berthelsen, Rasmus E.; Christensen, Henrik; Madsen, Martin B.; Winkel, Per; Wetterslev, Jorn; Perner, Anders; CLASSIC Trial Grp; Scandinavian Critical Care Trials (2016)
    Purpose: We assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock. Methods: We randomised 151 adult patients with septic shock who had received initial fluid resuscitation in nine Scandinavian ICUs. In the fluid restriction group fluid boluses were permitted only if signs of severe hypoperfusion occurred, while in the standard care group fluid boluses were permitted as long as circulation continued to improve. Results: The co-primary outcome measures, resuscitation fluid volumes at day 5 and during ICU stay, were lower in the fluid restriction group than in the standard care group [ mean differences -1.2 L (95 % confidence interval -2.0 to -0.4); p <0.001 and -1.4 L (-2.4 to -0.4) respectively; p <0.001]. Neither total fluid inputs and balances nor serious adverse reactions differed statistically significantly between the groups. Major protocol violations occurred in 27/75 patients in the fluid restriction group. Ischaemic events occurred in 3/75 in the fluid restriction group vs. 9/76 in the standard care group (odds ratio 0.32; 0.08-1.27; p = 0.11), worsening of acute kidney injury in 27/73 vs. 39/72 (0.46; 0.23-0.92; p = 0.03), and death by 90 days in 25/75 vs. 31/76 (0.71; 0.36-1.40; p = 0.32). Conclusions: A protocol restricting resuscitation fluid successfully reduced volumes of resuscitation fluid compared with a standard care protocol in adult ICU patients with septic shock. The patient-centred outcomes all pointed towards benefit with fluid restriction, but our trial was not powered to show differences in these exploratory outcomes.
  • Husu, Henrik Leonard; Leppäniemi, Ari Kalevi; Lehtonen, Taru Marika; Puolakkainen, Pauli Antero; Mentula, Panu Juhani (2019)
    Purpose: To study mortality in severe acute pancreatitis (SAP) and to identify risk factors for mortality. Materials and methods: A retrospective 17-years' cohort study of 435 consecutive adult patientswith SAP treated at intensive care unit of a university hospital. Results: Overall, 357 (82.1%) patients survived at 90 days follow-up. Three-hundred six (89.5%) patients under 60 years, 38 (60.3%) patients between 60 and 69 years, and 13 (43.3%) patients over 69 years of age survived at 90 days follow-up. Independent risk factors for death within 90-days were: 60 to 69 years of age (odds ratio [OR] 5.1), >69 years of age (OR 10.4), female sex (OR 2.0), heart disease (OR 2.9), chronic liver failure (OR 12.3), open abdomen treatment (OR 4.4) and sterile necrosectomy within 4 weeks (OR 14.7). The 10-year survival estimate was Conclusions: Although younger patients have excellent short-term survival after SAP, the long-term survival estimate is disappointing mostly due to alcohol abuse. (C) 2019 Elsevier Inc. All rights reserved.
  • Jakkula, Pekka; Reinikainen, Matti; Hästbacka, Johanna; Pettilä, Ville; Loisa, Pekka; Karlsson, Sari; Laru-Sompa, Raili; Bendel, Stepani; Oksanen, Tuomas; Birkelund, Thomas; Tiainen, Marjaana; Toppila, Jussi; Hakkarainen, Antti; Skrifvars, Markus B.; COMACARE Study Grp (2017)
    Background: Arterial carbon dioxide tension (PaCO2), oxygen tension (PaO2), and mean arterial pressure (MAP) are modifiable factors that affect cerebral blood flow (CBF), cerebral oxygen delivery, and potentially the course of brain injury after cardiac arrest. No evidence regarding optimal treatment targets exists. Methods: The Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial is a pilot multi-center randomized controlled trial (RCT) assessing the feasibility of targeting low-or high-normal PaCO2, PaO2, and MAP in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest (OHCA), as well as its effect on brain injury markers. Using a 23 factorial design, participants are randomized upon admission to an intensive care unit into one of eight groups with various combinations of PaCO2, PaO2, and MAP target levels for 36 h after admission. The primary outcome is neuron-specific enolase (NSE) serum concentration at 48 h after cardiac arrest. The main feasibility outcome is the between-group differences in PaCO2, PaO2, and MAP during the 36 h after ICU admission. Secondary outcomes include serum concentrations of NSE, S100 protein, and cardiac troponin at 24, 48, and 72 h after cardiac arrest; cerebral oxygenation, measured with near-infrared spectroscopy (NIRS); potential differences in epileptic activity, monitored via continuous electroencephalogram (EEG); and neurological outcomes at six months after cardiac arrest. Discussion: The trial began in March 2016 and participant recruitment has begun in all seven study sites as of March 2017. Currently, 115 of the total of 120 patients have been included. When completed, the results of this trial will provide preliminary clinical evidence regarding the feasibility of targeting low-or high-normal PaCO2, PaO2, and MAP values and its effect on developing brain injury, brain oxygenation, and epileptic seizures after cardiac arrest. The results of this trial will be used to evaluate whether a larger RCT on this subject is justified.
  • COMACARE Study Grp; Jakkula, Pekka; Pettilä, Ville; Skrifvars, Markus B.; Hästbacka, Johanna; Loisa, Pekka; Tiainen, Marjaana; Wilkman, Erika; Toppila, Jussi; Koskue, Talvikki; Bendel, Stepani; Birkelund, Thomas; Laru-Sompa, Raili; Valkonen, Miia; Reinikainen, Matti (2018)
    PurposeWe aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury. MethodsIn the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 2(3) factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65-75mmHg) vs. high-normal (80-100mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6months after cardiac arrest.ResultsWe recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p
  • COMACARE Study Grp; Jakkula, Pekka; Reinikainen, Matti; Hästbacka, Johanna; Loisa, Pekka; Tiainen, Marjaana; Pettilä, Ville; Toppila, Jussi; Lähde, Marika; Bäcklund, Minna; Okkonen, Marjatta; Bendel, Stepani; Birkelund, Thomas; Pulkkinen, Anni; Heinonen, Jonna; Tikka, Tuukka; Skrifvars, Markus B. (2018)
    PurposeWe assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury.MethodsUsing a 2(3) factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7kPa) or high-normal (5.8-6.0kPa) PaCO2 and to normoxia (arterial oxygen tension [PaO2] 10-15kPa) or moderate hyperoxia (PaO2 20-25kPa) and to low-normal or high-normal mean arterial pressure during the first 36h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6months.ResultsIn total 120 patients were included in the analyses. There was a clear separation in PaCO2 (p
  • Kaukonen, Kirsi-Maija; Bailey, Michael; Pilcher, David; Cooper, D. James; Bellomo, Rinaldo (2018)
    Purpose: Despite the recent Sepsis-3 consensus, the Systemic Inflammatory Response Syndrome (SIRS) criteria continue to be assessed and recommended. Such use implies equivalence and interchangeability of criteria. Thus, we aimed to test whether such criteria are indeed equivalent and interchangeable. Materials and methods: From 2000 to 2015, we identified patients with infection, organ failure, and at least one SIRS criterion in 179 Intensive Care Units in Australia and New. Zealand. We studied the association of different SIRS criteria with hospital mortality. Results: Among 131,016 patients with infection and organ failure, mortality increased from 10.6% for the respiratory rate criterion to 15.8% for the heart rate criterion (P <0.01); from 10.1% for the high leukocyte count criterion to 20.0% for a low count and from 10.1% for a high temperature to 14.4% for a low temperature criterion. With any two SIRS criteria, hospital mortality varied from 11.5% to 30.8% depending on the combination of criteria. This difference remained unchanged after adjustments and was consistent over time. Conclusions: Different individual and combinations of SIRS criteria were associated with marked differences in hospital mortality. These differences remained unchanged after adjustment and over time and imply that individual SIRS criteria are not equivalent or interchangeable. (c) 2018 Elsevier Inc. All rights reserved.
  • Mildh, Henriikka; Pettilä, Ville; Korhonen, Anna-Maija; Karlsson, Sari; Ala-Kokko, Tero; Reinikainen, Matti; Vaara, Suvi; FINNAKI Study Grp (2016)
    Background: The role of an episode of acute kidney injury (AKI) in long-term mortality among initial survivors of critical illness is controversial. We aimed to determine whether AKI is independently associated with decreased survival at 3 years among 30-day survivors of intensive care. Results: We included 2336 30-day survivors of intensive care enrolled in the FINNAKI study conducted in seventeen medical-surgical ICUs in Finland during a 5-month period in 2011-2012. The incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes criteria, was 34.6%, and 192 (8.3%) commenced RRT. The 3-year mortality among AKI patients was 23.5% (95% CI 20.6-26.4%) compared to 18.9% (17.0-20.9%) of patients without AKI, p = 0.01. However, after adjustments using Cox proportional hazards regression, AKI was not associated with decreased 3-year survival (HR 1.05; CI 95% 0.86-1.27), whereas advanced age, poor pre-morbid functional performance, and presence of several comorbidities were. Additionally, we matched AKI patients to non-AKI patients 1: 1 according to age, gender, presence of severe sepsis, and a propensity score to develop AKI. In the well-balanced matched cohort, 3-year mortality among AKI patients was 136 of 662 (20.5%; 17.5-23.6%) and among matched non-AKI patients 143 of 662 (21.6%; 18.5-24.7%), p = 0.687. Neither AKI nor RRT was associated with decreased survival at 3 years in the sensitivity analyses that excluded patients (1) with chronic kidney disease, (2) with AKI not commenced renal replacement therapy (RRT), and (3) with estimated pre-admission creatinine, chronic kidney disease, or AKI stage 1. Conclusion: AKI was not an independent risk factor for 3-year mortality among 30-day survivors. Increased 3-year mortality among patients with AKI who survive critical illness may not be related to AKI per se, but rather to advanced age and pre-existing comorbidities.
  • Mildh, Henriikka; Pettilä, Ville; Korhonen, Anna-Maija; Karlsson, Sari; Ala-Kokko, Tero; Reinikainen, Matti; Vaara, Suvi T (Springer Paris, 2016)
    Abstract Background The role of an episode of acute kidney injury (AKI) in long-term mortality among initial survivors of critical illness is controversial. We aimed to determine whether AKI is independently associated with decreased survival at 3 years among 30-day survivors of intensive care. Results We included 2336 30-day survivors of intensive care enrolled in the FINNAKI study conducted in seventeen medical–surgical ICUs in Finland during a 5-month period in 2011–2012. The incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes criteria, was 34.6%, and 192 (8.3%) commenced RRT. The 3-year mortality among AKI patients was 23.5% (95% CI 20.6–26.4%) compared to 18.9% (17.0–20.9%) of patients without AKI, p = 0.01. However, after adjustments using Cox proportional hazards regression, AKI was not associated with decreased 3-year survival (HR 1.05; CI 95% 0.86–1.27), whereas advanced age, poor pre-morbid functional performance, and presence of several comorbidities were. Additionally, we matched AKI patients to non-AKI patients 1:1 according to age, gender, presence of severe sepsis, and a propensity score to develop AKI. In the well-balanced matched cohort, 3-year mortality among AKI patients was 136 of 662 (20.5%; 17.5–23.6%) and among matched non-AKI patients 143 of 662 (21.6%; 18.5–24.7%), p = 0.687. Neither AKI nor RRT was associated with decreased survival at 3 years in the sensitivity analyses that excluded patients (1) with chronic kidney disease, (2) with AKI not commenced renal replacement therapy (RRT), and (3) with estimated pre-admission creatinine, chronic kidney disease, or AKI stage 1. Conclusion AKI was not an independent risk factor for 3-year mortality among 30-day survivors. Increased 3-year mortality among patients with AKI who survive critical illness may not be related to AKI per se, but rather to advanced age and pre-existing comorbidities.
  • FINNAKI Study Grp; Hoste, Eric A.; Vaara, Suvi T.; De Loor, Jorien; Haapio, Mikko; Nuytinck, Lieve; Demeyere, Kristel; Pettila, Ville; Meyer, Evelyne (2020)
    Background Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)center dot insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk (R). Methods Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs <0.700. The combination uCHI3L1 center dot TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk (R) cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk (R) cutoff of 0.3. Conclusions We found that uCHI3L1 and NephroCheck Risk (R) had a comparable diagnostic performance for diagnosis of AKI stage 2 or greater within a 24-h period in this multicenter FINNAKI cohort. In contrast to initial discovery and validation studies, the diagnostic performance was poor. Possible explanations for this observation are differences in patient populations, proportion of emergency admissions, proportion of functional AKI, rate of developing AKI, and observation periods for diagnosis of AKI.