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Papers by Johanna Hästbacka

Research paper thumbnail of Altered adrenal and gonadal steroids biosynthesis in patients with burn injury

Clinical Mass Spectrometry, 2016

Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, ... more Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury. Methods: For this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5-72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry. Results: Steroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r = 0.84), corticosterone (r = 0.73), 11-deoxycortisol (r = 0.72), androstenedione (r = 0.72), 17OH-progesterone (r = 0.68), 17OHpregnenolone (r = 0.64) and pregnenolone (r = 0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury. Conclusion: Burn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21 days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesisdriven study.

Research paper thumbnail of Glucocorticoid receptor expression and binding capacity in patients with burn injury

Acta Anaesthesiologica Scandinavica, 2015

Background: Burn injuries are associated with strong inflammation and risk of secondary sepsis wh... more Background: Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center. Methods: Blood was sampled from 13 patients on admission and days 7, 14 and 21, and once from 16 healthy subjects. Patients were grouped according to the extent of burn and to any sepsis on day 7. Expression and binding capacity of GR were determined as arbitrary units using flow cytometry. Results: GR expression and binding capacity were increased compared to healthy subjects in most circulating leucocyte subsets on admission irrespective of burn size. Patients with sepsis on day 7 displayed increased GR expression in T lymphocytes (51.8%, P < 0.01) compared to admission. There was a negative correlation between GR binding capacity in neutrophils and burn size after 14 days (P < 0.05). Conclusions: GR expression and binding capacity are increased in most types of circulating leucocytes of severely burned patients on their admission to specialized burn care. If sepsis is present after 1 week, it is associated with higher GR expression in T lymphocytes and NK cells. Editorial comments: what this article tells us This study shows that glucocorticoid receptor expression and binding capacity in leucocytes are higher in burn patients compared to healthy volunteers. If patients have sepsis at 1 week after burn injury, this expression increases further.

Research paper thumbnail of Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study

Critical Care

Background Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease... more Background Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU). Methods This prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients—ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)—with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change ...

Research paper thumbnail of Evaluating a novel formula for noninvasive estimation of arterial carbon dioxide during post‐resuscitation care

Acta Anaesthesiologica Scandinavica, 2020

Background Controlling arterial carbon dioxide is paramount in mechanically ventilated patients, ... more Background Controlling arterial carbon dioxide is paramount in mechanically ventilated patients, and an accurate and continuous noninvasive monitoring method would optimize management in dynamic situations. In this study, we validated and further refined formulas for estimating partial pressure of carbon dioxide with respiratory gas and pulse oximetry data in mechanically ventilated cardiac arrest patients. Methods A total of 4,741 data sets were collected retrospectively from 233 resuscitated patients undergoing therapeutic hypothermia. The original formula used to analyze the data is PaCO2-est1= PETCO2+k(PIO2-PETCO2)-PaO2. To achieve better accuracy, we further modified the formula to PaCO2-est2= k1*PETCO2 + k2*(PIO2-PETCO2)+k3*(100-SpO2). The coefficients were determined by identifying the minimal difference between the measured and calculated arterial carbon dioxide values in a development set. The accuracy of these two methods was compared with the estimation of the partial pressure of carbon dioxide using end-tidal carbon dioxide. Results With PaCO2-est1, the mean difference between the partial pressure of carbon dioxide, and the estimated carbon dioxide was 0.08 kPa (SE ± 0.003); with PaCO2-est2 the difference was 0.036 kPa (SE ± 0.009). The mean difference between the partial pressure of carbon dioxide and end-tidal carbon dioxide was 0.72 kPa (SE ± 0.01). In a mixed linear model, there was a significant difference between the estimation using end-tidal carbon dioxide and PaCO2-est1 (p<0.001) and PaCO2-est2 (p<0.001), respectively. Conclusions This novel formula appears to provide an accurate, continuous, and noninvasive estimation of arterial carbon dioxide.

Research paper thumbnail of Matrix Metalloproteinases -8 and -9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study

PLOS ONE, 2015

Introduction Matrix metalloproteinases (MMPs)-8 and-9 are released from neutrophils in acute infl... more Introduction Matrix metalloproteinases (MMPs)-8 and-9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8,-9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8,-9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8,-9, and TIMP-1 levels in burn blister fluids were also studied.

Research paper thumbnail of Voidaanko hiilidioksidi-, happi- tai verenpainetasoa säätelemällä vaikuttaa sydänpysähdyksestä elvytetyn potilaan aivovaurion laajuuteen?

Research paper thumbnail of Abstract 31: Low versus High Blood Pressure Targets After Out-Of-Hospital Cardiac Arrest

Circulation

Introduction: The optimal level of blood pressure after out-of-hospital cardiac arrest (OHCA) is ... more Introduction: The optimal level of blood pressure after out-of-hospital cardiac arrest (OHCA) is unknown. Hypotension may aggravate cerebral hypoperfusion exacerbating the post-anoxic brain injury. On the other hand, excessive vasopressor support may increase myocardial oxygen consumption and induce arrhythmias. We aimed to evaluate the effects of different blood pressure targets on the extent of brain injury and neurological outcome in patients resuscitated from OHCA. Methods: We performed a pooled post hoc analysis of OHCA patients randomised in the Neuroprotect (NCT02541591) and COMACARE (NCT02698917) trials to either mean arterial pressure (MAP) 65 mmHg or 80/85-100 mmHg targets for the first 36 h after ICU admission. We compared the serum neuron-specific enolase (NSE) concentrations between the groups at 24, 48 and 72 h after cardiac arrest and the neurological outcome according to the Cereberal Performance Category (CPC) scale at 6 months. We defined CPC 1-2 as good outcome an...

Research paper thumbnail of Factors Associated With Rebound Hyperthermia After Targeted Temperature Management in Out-of-Hospital Cardiac Arrest Patients: An Explorative Substudy of the Time-Differentiated Therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest Survivors Trial

Critical Care Explorations, 2021

Supplemental Digital Content is available in the text. OBJECTIVES: To investigate rebound hyperth... more Supplemental Digital Content is available in the text. OBJECTIVES: To investigate rebound hyperthermia following targeted temperature management after cardiac arrest and its impact on functional outcome. DESIGN: Post hoc analysis. SETTING: Ten European ICUs. PATIENTS: Patients included in the time-differentiated therapeutic hypothermia in out-of-hospital cardiac arrest survivors trial treated with targeted temperature management at 33°C for 48 or 24 hours. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 6 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 338 included patients, 103 (30%) experienced rebound hyperthermia defined as a maximum temperature after targeted temperature management and rewarming exceeding 38.5°C. Using multivariate logistic regression analysis, increasing age (odds ratio, 0.97; 95% CI, 0.95–0.99; p = 0.02) and severe acute kidney injury within 72 hours of ICU admission (odds ratio, 0.35; 95% CI, 0.13–0.91;...

Research paper thumbnail of Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome

Scientific Reports

Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. ... more Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1–2 as good and 3–5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter...

Research paper thumbnail of Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Intensive Care Medicine

Purpose: Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal... more Purpose: Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO 2), arterial oxygen tension (PaO 2), and mean arterial pressure (MAP). Methods: We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1-2 and poor outcome as CPC 3-5. Results: Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11-31) pg/ml in patients with good outcome and 2343 (587-5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97-1.00) at 24 h, 0.98 (0.97-1.00) at 48 h, and 0.98 (0.95-1.00) at 72 h. NfL concentrations were lower in the higher MAP (80-100 mmHg) group than in the lower MAP (65-75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO 2 and PaO 2 targets did not associate with NfL levels. Conclusions: NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.

Research paper thumbnail of Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac Arrest

Journal of the American College of Cardiology

Research paper thumbnail of New‐onset atrial fibrillation in the intensive care unit: Protocol for an international inception cohort study (AFIB‐ICU)

Acta Anaesthesiologica Scandinavica

New‐onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be... more New‐onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be associated with prolonged hospital stay and increased mortality. Considerable variation exists in the reported frequencies of NOAF due to the lack of a standardised definition and detection method. Importantly, there are limited data on NOAF in the intensive care unit (ICU). Thus, we aim to provide contemporary epidemiological data on NOAF in the ICU.

Research paper thumbnail of Interleukin 8 and hepatocyte growth factor in predicting development of severe acute pancreatitis

Cogent Medicine

Abstract Objectives: We aimed to study if interleukin (IL) 8 and hepatocyte growth factor (HGF) p... more Abstract Objectives: We aimed to study if interleukin (IL) 8 and hepatocyte growth factor (HGF) predict development of severe acute pancreatitis (SAP) among patients without organ dysfunction (OD) at presentation, and if they discriminate transient OD from persistent OD among patients presenting with OD. Methods: From prospectively collected cohort of 176 AP patients and 32 healthy controls, plasma levels of IL-8 and HGF were determined within 5 days after symptom onset using an enzyme-linked immunosorbent assay. Results: AP was severe in 23 patients, of whom 10 did not have clinical signs of OD at presentation. IL-8 and HGF levels increased along with the severity of AP (P < 0.001). In patients without OD at study entry, IL-8 and HGF values predicted the development of SAP with the AUCs of 0.73 (95% CI, 0.56–0.91) and 0.79 (95% CI, 0.66–0.93), respectively. Of all patients, 22 presented with OD, and among them IL-8 predicted persistence of OD with the AUC of 0.88 (95% CI 0.69–1.0). Combining IL-8 and HGF did not improve the models. Conclusions: In AP patients without OD at presentation, circulating levels of IL-8, or HGF, may predict the development of SAP. In patients presenting with OD, IL-8 level may discriminate the patients with transient OD from those with persistent OD.

Research paper thumbnail of Prevalence and impact of hazardous alcohol use in intensive care cohort: A multicenter, register‐based study

Acta Anaesthesiologica Scandinavica

Reports of the prevalence and impact of hazardous alcohol use among intensive care unit (ICU) pat... more Reports of the prevalence and impact of hazardous alcohol use among intensive care unit (ICU) patients are contradictory. We aimed to study the prevalence of hazardous alcohol use among ICU patients and its association with ICU length of stay (LOS) and mortality.

Research paper thumbnail of Association between first language and SARS-CoV-2 infection rates, hospitalization, intensive care admissions and death in Finland: a population-based observational cohort study

Clinical Microbiology and Infection

Research paper thumbnail of Male predominance in disease severity and mortality in a low Covid-19 epidemic and low case-fatality area – a population-based registry study

Infectious Diseases

Background: Men reportedly suffer from a more severe disease and higher mortality during the glob... more Background: Men reportedly suffer from a more severe disease and higher mortality during the global SARS-CoV-2 (Covid-19) pandemic. We analysed sex differences in a low epidemic area with low overall mortality in Covid-19 in a population based setting with patients treated in specialized healthcare. Methods: We entered all hospitalized laboratory-confirmed Covid-19 cases of all specialized healthcare hospitals of the Capital Province of Finland, into a population-based quality registry and described demographics, severity and case-fatality by sex of the first Covid-19 wave February-June 2020. Results: Altogether 5471 patients (49% male) were identified. Patients hospitalized in the specialist healthcare (N ¼ 585, 54% male, OR 1.25; 95% CI 1.05-1.48) were of the same age. Men had less asthma and thyroid insufficiency and more coronary artery disease compared to women. Mean time from symptom onset to diagnosis was at least one day longer for men (p¼.005). Men required intensive care unit (ICU) more often (27% vs. 17%) with longer lengths-of-stays at ICU. Male sex associated with significantly higher case-fatality at 90-days (15% vs. 8%) and all excess male deaths occurring after three weeks from onset. Men with fatal outcomes had delays in both Covid-19 testing and hospital admission after a positive test. The delays in patients with the most severe and fatal outcomes differed markedly by sex. In multivariable analysis, male sex associated independently with case-fatality (OR 2.37; 95% CI 1.22-4.59). Conclusions: Male sex associated with higher disease severity and case-fatality. Late presentation of male fatal cases could represent different treatment-seeking behaviour or disease progression by sex.

Research paper thumbnail of A descriptive study of the surge response and outcomes of ICU patients with COVID‐19 during first wave in Nordic countries

Acta Anaesthesiologica Scandinavica

Research paper thumbnail of High Oxygen Does Not Increase Reperfusion Injury Assessed with Lipid Peroxidation Biomarkers after Cardiac Arrest: A Post Hoc Analysis of the COMACARE Trial

Journal of Clinical Medicine

The products of polyunsaturated fatty acid peroxidation are considered reliable biomarkers of oxi... more The products of polyunsaturated fatty acid peroxidation are considered reliable biomarkers of oxidative injury in vivo. We investigated ischemia-reperfusion-related oxidative injury by determining the levels of lipid peroxidation biomarkers (isoprostane, isofuran, neuroprostane, and neurofuran) after cardiac arrest and tested the associations between the biomarkers and different arterial oxygen tensions (PaO2). We utilized blood samples collected during the COMACARE trial (NCT02698917). In the trial, 123 patients resuscitated from out-of-hospital cardiac arrest were treated with a 10–15 kPa or 20–25 kPa PaO2 target during the initial 36 h in the intensive care unit. We measured the biomarker levels at admission, and 24, 48, and 72 h thereafter. We compared biomarker levels in the intervention groups and in groups that differed in oxygen exposure prior to randomization. Blood samples for biomarker determination were available for 112 patients. All four biomarker levels peaked at 24 h...

Research paper thumbnail of Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial

American Journal of Respiratory and Critical Care Medicine

Research paper thumbnail of Mortality and HRQoL in ICU patients with delirium: Protocol for 1‐year follow‐up of AID‐ICU trial

Acta Anaesthesiologica Scandinavica

Research paper thumbnail of Altered adrenal and gonadal steroids biosynthesis in patients with burn injury

Clinical Mass Spectrometry, 2016

Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, ... more Introduction: Burn injury inevitably leads to changes in the endogenous production of cytokines, as well as adrenal and gonadal steroids. Previous studies have reported gender-related differences in outcome following burn injury, which suggests that gonadal steroids may play a role. The aim of this study was to assess alterations in concentration of endogenous steroids in patients with burn injury. Methods: For this single-center, prospective descriptive study, high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS)-based steroid quantification was used to determine longitudinal profiles of the concentrations of endogenous steroids in plasma from sixteen adult male patients with burn injury (14.5-72% of total body surface area). Steroids were extracted from plasma samples and analyzed using multiple reaction monitoring acquisition, with electrospray ionization on a triple quadruple mass spectrometer. Total protein concentration was measured in the samples using spectrophotometry. Results: Steroid and total protein concentration distributions were compared to reference intervals characteristic of healthy adult men. Concentrations of the following steroids in plasma of burn injured patients were found to correlate positively to the area of the burn injury: cortisol (r = 0.84), corticosterone (r = 0.73), 11-deoxycortisol (r = 0.72), androstenedione (r = 0.72), 17OH-progesterone (r = 0.68), 17OHpregnenolone (r = 0.64) and pregnenolone (r = 0.77). Concentrations of testosterone decreased during the acute phase and were up to ten-times lower than reference values for healthy adult men, while concentrations of estrone were elevated. By day 21 after injury, testosterone concentrations were increased in younger, but not older, patients. The highest concentrations of estrone were observed on day 3 after the injury and then declined by day 21 to concentrations comparable to those observed on the day of the injury. Conclusion: Burn injury alters endogenous steroid biosynthesis, with decreased testosterone concentrations and elevated estrone concentrations, during the first 21 days after the injury. Concentrations of glucocorticoids, progestagens and androgen precursors correlated positively with the area of burn injury. The finding of increased estrone following burn injury needs to be confirmed in a larger hypothesisdriven study.

Research paper thumbnail of Glucocorticoid receptor expression and binding capacity in patients with burn injury

Acta Anaesthesiologica Scandinavica, 2015

Background: Burn injuries are associated with strong inflammation and risk of secondary sepsis wh... more Background: Burn injuries are associated with strong inflammation and risk of secondary sepsis which both may affect the function of the glucocorticoid receptor (GR). The aim of this study was to determine GR expression and binding capacity in leucocytes from patients admitted to a tertiary burn center. Methods: Blood was sampled from 13 patients on admission and days 7, 14 and 21, and once from 16 healthy subjects. Patients were grouped according to the extent of burn and to any sepsis on day 7. Expression and binding capacity of GR were determined as arbitrary units using flow cytometry. Results: GR expression and binding capacity were increased compared to healthy subjects in most circulating leucocyte subsets on admission irrespective of burn size. Patients with sepsis on day 7 displayed increased GR expression in T lymphocytes (51.8%, P < 0.01) compared to admission. There was a negative correlation between GR binding capacity in neutrophils and burn size after 14 days (P < 0.05). Conclusions: GR expression and binding capacity are increased in most types of circulating leucocytes of severely burned patients on their admission to specialized burn care. If sepsis is present after 1 week, it is associated with higher GR expression in T lymphocytes and NK cells. Editorial comments: what this article tells us This study shows that glucocorticoid receptor expression and binding capacity in leucocytes are higher in burn patients compared to healthy volunteers. If patients have sepsis at 1 week after burn injury, this expression increases further.

Research paper thumbnail of Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study

Critical Care

Background Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease... more Background Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU). Methods This prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients—ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)—with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change ...

Research paper thumbnail of Evaluating a novel formula for noninvasive estimation of arterial carbon dioxide during post‐resuscitation care

Acta Anaesthesiologica Scandinavica, 2020

Background Controlling arterial carbon dioxide is paramount in mechanically ventilated patients, ... more Background Controlling arterial carbon dioxide is paramount in mechanically ventilated patients, and an accurate and continuous noninvasive monitoring method would optimize management in dynamic situations. In this study, we validated and further refined formulas for estimating partial pressure of carbon dioxide with respiratory gas and pulse oximetry data in mechanically ventilated cardiac arrest patients. Methods A total of 4,741 data sets were collected retrospectively from 233 resuscitated patients undergoing therapeutic hypothermia. The original formula used to analyze the data is PaCO2-est1= PETCO2+k(PIO2-PETCO2)-PaO2. To achieve better accuracy, we further modified the formula to PaCO2-est2= k1*PETCO2 + k2*(PIO2-PETCO2)+k3*(100-SpO2). The coefficients were determined by identifying the minimal difference between the measured and calculated arterial carbon dioxide values in a development set. The accuracy of these two methods was compared with the estimation of the partial pressure of carbon dioxide using end-tidal carbon dioxide. Results With PaCO2-est1, the mean difference between the partial pressure of carbon dioxide, and the estimated carbon dioxide was 0.08 kPa (SE ± 0.003); with PaCO2-est2 the difference was 0.036 kPa (SE ± 0.009). The mean difference between the partial pressure of carbon dioxide and end-tidal carbon dioxide was 0.72 kPa (SE ± 0.01). In a mixed linear model, there was a significant difference between the estimation using end-tidal carbon dioxide and PaCO2-est1 (p<0.001) and PaCO2-est2 (p<0.001), respectively. Conclusions This novel formula appears to provide an accurate, continuous, and noninvasive estimation of arterial carbon dioxide.

Research paper thumbnail of Matrix Metalloproteinases -8 and -9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study

PLOS ONE, 2015

Introduction Matrix metalloproteinases (MMPs)-8 and-9 are released from neutrophils in acute infl... more Introduction Matrix metalloproteinases (MMPs)-8 and-9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8,-9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8,-9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8,-9, and TIMP-1 levels in burn blister fluids were also studied.

Research paper thumbnail of Voidaanko hiilidioksidi-, happi- tai verenpainetasoa säätelemällä vaikuttaa sydänpysähdyksestä elvytetyn potilaan aivovaurion laajuuteen?

Research paper thumbnail of Abstract 31: Low versus High Blood Pressure Targets After Out-Of-Hospital Cardiac Arrest

Circulation

Introduction: The optimal level of blood pressure after out-of-hospital cardiac arrest (OHCA) is ... more Introduction: The optimal level of blood pressure after out-of-hospital cardiac arrest (OHCA) is unknown. Hypotension may aggravate cerebral hypoperfusion exacerbating the post-anoxic brain injury. On the other hand, excessive vasopressor support may increase myocardial oxygen consumption and induce arrhythmias. We aimed to evaluate the effects of different blood pressure targets on the extent of brain injury and neurological outcome in patients resuscitated from OHCA. Methods: We performed a pooled post hoc analysis of OHCA patients randomised in the Neuroprotect (NCT02541591) and COMACARE (NCT02698917) trials to either mean arterial pressure (MAP) 65 mmHg or 80/85-100 mmHg targets for the first 36 h after ICU admission. We compared the serum neuron-specific enolase (NSE) concentrations between the groups at 24, 48 and 72 h after cardiac arrest and the neurological outcome according to the Cereberal Performance Category (CPC) scale at 6 months. We defined CPC 1-2 as good outcome an...

Research paper thumbnail of Factors Associated With Rebound Hyperthermia After Targeted Temperature Management in Out-of-Hospital Cardiac Arrest Patients: An Explorative Substudy of the Time-Differentiated Therapeutic Hypothermia in Out-of-Hospital Cardiac Arrest Survivors Trial

Critical Care Explorations, 2021

Supplemental Digital Content is available in the text. OBJECTIVES: To investigate rebound hyperth... more Supplemental Digital Content is available in the text. OBJECTIVES: To investigate rebound hyperthermia following targeted temperature management after cardiac arrest and its impact on functional outcome. DESIGN: Post hoc analysis. SETTING: Ten European ICUs. PATIENTS: Patients included in the time-differentiated therapeutic hypothermia in out-of-hospital cardiac arrest survivors trial treated with targeted temperature management at 33°C for 48 or 24 hours. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 6 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 338 included patients, 103 (30%) experienced rebound hyperthermia defined as a maximum temperature after targeted temperature management and rewarming exceeding 38.5°C. Using multivariate logistic regression analysis, increasing age (odds ratio, 0.97; 95% CI, 0.95–0.99; p = 0.02) and severe acute kidney injury within 72 hours of ICU admission (odds ratio, 0.35; 95% CI, 0.13–0.91;...

Research paper thumbnail of Serum fibroblast growth factor 21 levels after out of hospital cardiac arrest are associated with neurological outcome

Scientific Reports

Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. ... more Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1–2 as good and 3–5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter...

Research paper thumbnail of Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial

Intensive Care Medicine

Purpose: Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal... more Purpose: Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO 2), arterial oxygen tension (PaO 2), and mean arterial pressure (MAP). Methods: We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1-2 and poor outcome as CPC 3-5. Results: Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11-31) pg/ml in patients with good outcome and 2343 (587-5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97-1.00) at 24 h, 0.98 (0.97-1.00) at 48 h, and 0.98 (0.95-1.00) at 72 h. NfL concentrations were lower in the higher MAP (80-100 mmHg) group than in the lower MAP (65-75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO 2 and PaO 2 targets did not associate with NfL levels. Conclusions: NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.

Research paper thumbnail of Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac Arrest

Journal of the American College of Cardiology

Research paper thumbnail of New‐onset atrial fibrillation in the intensive care unit: Protocol for an international inception cohort study (AFIB‐ICU)

Acta Anaesthesiologica Scandinavica

New‐onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be... more New‐onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be associated with prolonged hospital stay and increased mortality. Considerable variation exists in the reported frequencies of NOAF due to the lack of a standardised definition and detection method. Importantly, there are limited data on NOAF in the intensive care unit (ICU). Thus, we aim to provide contemporary epidemiological data on NOAF in the ICU.

Research paper thumbnail of Interleukin 8 and hepatocyte growth factor in predicting development of severe acute pancreatitis

Cogent Medicine

Abstract Objectives: We aimed to study if interleukin (IL) 8 and hepatocyte growth factor (HGF) p... more Abstract Objectives: We aimed to study if interleukin (IL) 8 and hepatocyte growth factor (HGF) predict development of severe acute pancreatitis (SAP) among patients without organ dysfunction (OD) at presentation, and if they discriminate transient OD from persistent OD among patients presenting with OD. Methods: From prospectively collected cohort of 176 AP patients and 32 healthy controls, plasma levels of IL-8 and HGF were determined within 5 days after symptom onset using an enzyme-linked immunosorbent assay. Results: AP was severe in 23 patients, of whom 10 did not have clinical signs of OD at presentation. IL-8 and HGF levels increased along with the severity of AP (P < 0.001). In patients without OD at study entry, IL-8 and HGF values predicted the development of SAP with the AUCs of 0.73 (95% CI, 0.56–0.91) and 0.79 (95% CI, 0.66–0.93), respectively. Of all patients, 22 presented with OD, and among them IL-8 predicted persistence of OD with the AUC of 0.88 (95% CI 0.69–1.0). Combining IL-8 and HGF did not improve the models. Conclusions: In AP patients without OD at presentation, circulating levels of IL-8, or HGF, may predict the development of SAP. In patients presenting with OD, IL-8 level may discriminate the patients with transient OD from those with persistent OD.

Research paper thumbnail of Prevalence and impact of hazardous alcohol use in intensive care cohort: A multicenter, register‐based study

Acta Anaesthesiologica Scandinavica

Reports of the prevalence and impact of hazardous alcohol use among intensive care unit (ICU) pat... more Reports of the prevalence and impact of hazardous alcohol use among intensive care unit (ICU) patients are contradictory. We aimed to study the prevalence of hazardous alcohol use among ICU patients and its association with ICU length of stay (LOS) and mortality.

Research paper thumbnail of Association between first language and SARS-CoV-2 infection rates, hospitalization, intensive care admissions and death in Finland: a population-based observational cohort study

Clinical Microbiology and Infection

Research paper thumbnail of Male predominance in disease severity and mortality in a low Covid-19 epidemic and low case-fatality area – a population-based registry study

Infectious Diseases

Background: Men reportedly suffer from a more severe disease and higher mortality during the glob... more Background: Men reportedly suffer from a more severe disease and higher mortality during the global SARS-CoV-2 (Covid-19) pandemic. We analysed sex differences in a low epidemic area with low overall mortality in Covid-19 in a population based setting with patients treated in specialized healthcare. Methods: We entered all hospitalized laboratory-confirmed Covid-19 cases of all specialized healthcare hospitals of the Capital Province of Finland, into a population-based quality registry and described demographics, severity and case-fatality by sex of the first Covid-19 wave February-June 2020. Results: Altogether 5471 patients (49% male) were identified. Patients hospitalized in the specialist healthcare (N ¼ 585, 54% male, OR 1.25; 95% CI 1.05-1.48) were of the same age. Men had less asthma and thyroid insufficiency and more coronary artery disease compared to women. Mean time from symptom onset to diagnosis was at least one day longer for men (p¼.005). Men required intensive care unit (ICU) more often (27% vs. 17%) with longer lengths-of-stays at ICU. Male sex associated with significantly higher case-fatality at 90-days (15% vs. 8%) and all excess male deaths occurring after three weeks from onset. Men with fatal outcomes had delays in both Covid-19 testing and hospital admission after a positive test. The delays in patients with the most severe and fatal outcomes differed markedly by sex. In multivariable analysis, male sex associated independently with case-fatality (OR 2.37; 95% CI 1.22-4.59). Conclusions: Male sex associated with higher disease severity and case-fatality. Late presentation of male fatal cases could represent different treatment-seeking behaviour or disease progression by sex.

Research paper thumbnail of A descriptive study of the surge response and outcomes of ICU patients with COVID‐19 during first wave in Nordic countries

Acta Anaesthesiologica Scandinavica

Research paper thumbnail of High Oxygen Does Not Increase Reperfusion Injury Assessed with Lipid Peroxidation Biomarkers after Cardiac Arrest: A Post Hoc Analysis of the COMACARE Trial

Journal of Clinical Medicine

The products of polyunsaturated fatty acid peroxidation are considered reliable biomarkers of oxi... more The products of polyunsaturated fatty acid peroxidation are considered reliable biomarkers of oxidative injury in vivo. We investigated ischemia-reperfusion-related oxidative injury by determining the levels of lipid peroxidation biomarkers (isoprostane, isofuran, neuroprostane, and neurofuran) after cardiac arrest and tested the associations between the biomarkers and different arterial oxygen tensions (PaO2). We utilized blood samples collected during the COMACARE trial (NCT02698917). In the trial, 123 patients resuscitated from out-of-hospital cardiac arrest were treated with a 10–15 kPa or 20–25 kPa PaO2 target during the initial 36 h in the intensive care unit. We measured the biomarker levels at admission, and 24, 48, and 72 h thereafter. We compared biomarker levels in the intervention groups and in groups that differed in oxygen exposure prior to randomization. Blood samples for biomarker determination were available for 112 patients. All four biomarker levels peaked at 24 h...

Research paper thumbnail of Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial

American Journal of Respiratory and Critical Care Medicine

Research paper thumbnail of Mortality and HRQoL in ICU patients with delirium: Protocol for 1‐year follow‐up of AID‐ICU trial

Acta Anaesthesiologica Scandinavica