Factors associated with fever after cardiac arrest: A post-hoc analysis of the FINNRESUSCI study.

BACKGROUND: Fever after cardiac arrest may impact outcome. We aimed to assess the incidence of fever in post-cardiac arrest patients, factors predicting fever and its association with functional outcome in patients treated without targeted temperature management (TTM). METHODS: The FINNRESUSCI observational cohort study in 2010-2011 included intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients from all five Finnish university hospitals and 14 of 15 central hospitals. This post hoc analysis included those FINNRESUSCI study patients who were not treated with TH. We defined fever as at least one temperature measurement of ≥37.8°C within 72 h of ICU admission. The primary outcome was favourable functional outcome at 12 months, defined as cerebral performance category (CPC) of 1 or 2. Binary logistic regression models including witnessed arrest, bystander cardiopulmonary resuscitation (CPR), initial rhythm and delay of return of spontaneous circulation were used to compare the functional outcomes of the groups. RESULTS: There were 67,428 temperature measurements from 192 patients, of whom 89 (46%) experienced fever. Twelve-month CPC was missing in 7 patients, and 51 (28%) patients had favourable functional outcome at 12 months. The patients with shockable initial rhythms had a lower incidence of fever within 72 h of ICU admission (28% vs. 72%, p < .01), and the patients who experienced fever had a longer median return of spontaneous circulation (ROSC) delay (20 [IQR 10-30] vs. 14 [IQR 9-22] min, p < .01). Only initial non-shockable rhythm (OR 2.99, 95% CI 1.51-5.94) was associated with increased risk of fever within the first 72 h of ICU admission. Neither time in minutes nor area (minutes × degree celsius over threshold) over 37°C, 37.5°C, 38°C, 38.5°C, 39°C, 39.5°C or 40°C were significantly different in those with favourable functional outcome compared to those with unfavourable functional outcome within the first 24, 48 or 72 h from ICU admission. Fever was not associated with favourable functional outcome at 12 months (OR 0.90, 95% CI 0.44-1.84). CONCLUSIONS: Half of OHCA patients not treated with TTM developed fever. We found no association between fever and outcome.

Variation in Severity-Adjusted Resource use and Outcome for Neurosurgical Emergencies in the Intensive Care Unit.

BACKGROUND: The correlation between the standardized resource use ratio (SRUR) and standardized hospital mortality ratio (SMR) for neurosurgical emergencies is not known. We studied SRUR and SMR and the factors affecting these in patients with traumatic brain injury (TBI), nontraumatic intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: We extracted data of patients treated in six university hospitals in three countries (2015-2017). Resource use was measured as SRUR based on purchasing power parity-adjusted direct costs and either intensive care unit (ICU) length of stay (costSRURlength of stay) or daily Therapeutic Intervention Scoring System scores (costSRURTherapeutic Intervention Scoring System). Five a priori defined variables reflecting differences in structure and organization between the ICUs were used as explanatory variables in bivariable models, separately for the included neurosurgical diseases. RESULTS: Out of 28,363 emergency patients treated in six ICUs, 6,162 patients (22%) were admitted with a neurosurgical emergency (41% nontraumatic ICH, 23% SAH, 13% multitrauma TBI, and 23% isolated TBI). The mean costs for neurosurgical admissions were higher than for nonneurosurgical admissions, and the neurosurgical admissions corresponded to 23.6-26.0% of all direct costs related to ICU emergency admissions. A higher physician-to-bed ratio was associated with lower SMRs in the nonneurosurgical admissions but not in the neurosurgical admissions. In patients with nontraumatic ICH, lower costSRURs were associated with higher SMRs. In the bivariable models, independent organization of an ICU was associated with lower costSRURs in patients with nontraumatic ICH and isolated/multitrauma TBI but with higher SMRs in patients with nontraumatic ICH. A higher physician-to-bed ratio was associated with higher costSRURs for patients with SAH. Larger units had higher SMRs for patients with nontraumatic ICH and isolated TBI. None of the ICU-related factors were associated with costSRURs in nonneurosurgical emergency admissions. CONCLUSIONS: Neurosurgical emergencies constitute a major proportion of all emergency ICU admissions. A lower SRUR was associated with higher SMR in patients with nontraumatic ICH but not for the other diagnoses. Different organizational and structural factors seemed to affect resource use for the neurosurgical patients compared with nonneurosurgical patients. This emphasizes the importance of case-mix adjustment when benchmarking resource use and outcomes.

The Nordic perioperative and intensive care registries-Collaboration and research possibilities.

BACKGROUND: The Nordic perioperative and intensive care registries have been built up during the last 25 years to improve quality in intensive and perioperative care. We aimed to describe the Nordic perioperative and intensive care registries and to highlight possibilities and challenges in future research collaboration between these registries. MATERIAL AND METHOD: We present an overview of the following Nordic registries: Swedish Perioperative Registry (SPOR), the Danish Anesthesia Database (DAD), the Finnish Perioperative Database (FIN-AN), the Icelandic Anesthesia Database (IS-AN), the Danish Intensive Care Database (DID), the Swedish Intensive Care Registry (SIR), the Finnish Intensive Care Consortium, the Norwegian Intensive Care and Pandemic Registry (NIPaR), and the Icelandic Intensive Care Registry (IS-ICU). RESULTS: Health care systems and patient populations are similar in the Nordic countries. Despite certain differences in data structure and clinical variables, the perioperative and intensive care registries have enough in common to enable research collaboration. In the future, even a common Nordic registry could be possible. CONCLUSION: Collaboration between the Nordic perioperative and intensive care registries is both possible and likely to produce research of high quality. Research collaboration between registries may have several add-on effects and stimulate international standardization regarding definitions, scoring systems, and benchmarks, thereby improving overall quality of care.

A descriptive study of the surge response and outcomes of ICU patients with COVID-19 during first wave in Nordic countries.

BACKGROUND: We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. METHODS: Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. RESULTS: Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6%-6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%-85%) in all countries, the proportion of patients receiving renal replacement therapy (7%-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0%-85%). Crude ICU mortality ranged from 11% to 33%. CONCLUSION: There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.

Lung function and exercise capacity 6 months after hospital discharge for critical COVID-19.

BACKGROUND: The significant morbidity caused by COVID-19 necessitates further understanding of long-term recovery. Our aim was to evaluate long-term lung function, exercise capacity, and radiological findings in patients after critical COVID-19. METHODS: Patients who received treatment in ICU for COVID-19 between March 2020 and January 2021 underwent pulmonary function tests, a 6MWD and CXR 6 months after hospital discharge. RESULTS: A restrictive ventilatory defect was found in 35% (23/65) and an impaired diffusing capacity in 52% (32/62) at 6 months. The 6-minute walk distance was reduced in 33% (18/55), and 7% (4/55) of the patients had reduced exercise capacity. Chest X-ray was abnormal in 78% (52/67) at 6 months after hospital discharge. CONCLUSION: A significant number of patients had persisting lung function impairment and radiological abnormalities at 6 months after critical COVID-19. Reduced exercise capacity was rare.

Prognostic Value of Secretoneurin in Critically Ill Patients With Infections.

OBJECTIVES: Secretoneurin is produced in neuroendocrine cells, and the myocardium and circulating secretoneurin levels provide incremental prognostic information to established risk indices in cardiovascular disease. As myocardial dysfunction contributes to poor outcome in critically ill patients, we wanted to assess the prognostic value of secretoneurin in two cohorts of critically ill patients with infections. DESIGN: Two prospective, observational studies. SETTING: Twenty-four and twenty-five ICUs in Finland. PATIENTS: A total of 232 patients with severe sepsis (cohort #1) and 94 patients with infections and respiratory failure (cohort #2). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured secretoneurin levels by radioimmunoassay in samples obtained early after ICU admission and compared secretoneurin with other risk indices. In patients with severe sepsis, admission secretoneurin levels (logarithmically transformed) were associated with hospital mortality (odds ratio, 3.17 [95% CI, 1.12-9.00]; p = 0.030) and shock during the hospitalization (odds ratio, 2.17 [1.06-4.46]; p = 0.034) in analyses that adjusted for other risk factors available on ICU admission. Adding secretoneurin levels to age, which was also associated with hospital mortality in the multivariate model, improved the risk prediction as assessed by the category-free net reclassification index: 0.35 (95% CI, 0.06-0.64) (p = 0.02). In contrast, N-terminal pro-B-type natriuretic peptide levels were not associated with mortality in the multivariate model that included secretoneurin measurements, and N-terminal pro-B-type natriuretic peptide did not improve patient classification on top of age. Secretoneurin levels were also associated with hospital mortality after adjusting for other risk factors and improved patient classification in cohort #2. In both cohorts, the optimal cutoff for secretoneurin levels at ICU admission to predict hospital mortality was ≈ 175 pmol/L, and higher levels were associated with mortality also when adjusting for Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. CONCLUSIONS: Secretoneurin levels provide incremental information to established risk indices for the prediction of mortality and shock in critically ill patients with severe infections.

Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest.

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.

Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

BACKGROUND: A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. METHODS: PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. RESULTS: In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. CONCLUSIONS: Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest: associations with long-term neurologic outcome.

OBJECTIVES: Optimal oxygen and carbon dioxide levels during postcardiac arrest care are currently undefined and observational studies have suggested harm from hyperoxia exposure. We aimed to assess whether mean and time-weighted oxygen and carbon dioxide levels during the first 24 hours of postcardiac arrest care correlate with 12-month neurologic outcome. DESIGN: Prospective observational cohort study. SETTING: Twenty-one ICUs in Finland. PATIENTS: Out-of-hospital cardiac arrest patients treated in ICUs in Finland between March 2010 and February 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood PaO2 and PaCO2 during the first 24 hours from admission were divided into predefined categories from the lowest to the highest. Proportions of time spent in different categories and the mean PaO2 and PaCO2 values during the first 24 hours were included in separate multivariable regression models along with resuscitation factors. The cerebral performance category at 12 months was used as primary endpoint. A total of 409 patients with arterial blood gases analyzed at least once and with a complete set of resuscitation data were included. The average amount of PaO2 and PaCO2 measurements was eight per patient. The mean 24 hours PaCO2 level was an independent predictor of good outcome (odds ratio, 1.054; 95% CI, 1.006-1.104; p = 0.027) but the mean PaO2 value was not (odds ratio, 1.006; 95% CI, 0.998-1.014; p = 0.149). With multivariate regression analysis, time spent in the PaCO2 band higher than 45 mm Hg was associated with good outcome (odds ratio, 1.015; 95% CI, 1.002-1.029; p = 0.024, for each percentage point increase in time) but time spent in different oxygen categories were not. CONCLUSIONS: In this multicenter study, hypercapnia was associated with good 12-month outcome in patients resuscitated from out-of-hospital cardiac arrest. We were unable to verify any harm from hyperoxia exposure. Further trials should focus on whether moderate hypercapnia during postcardiac arrest care improves outcome.

Serum MMP-8 and TIMP-1 in critically ill patients with acute respiratory failure: TIMP-1 is associated with increased 90-day mortality.

BACKGROUND: Matrix metalloproteinases (MMPs) likely have an important role in the pathophysiology of acute lung injury. In a recent study, high matrix metalloproteinases (MMP-8) levels in tracheal aspirates of pediatric acute respiratory distress syndrome (ARDS) patients were associated with worse outcome. In patients with sepsis, an imbalance between MMPs and their tissue inhibitors (TIMPs) has been associated with impaired survival. We hypothesized that the elevated systemic MMP-8 and TIMP-1 are associated with worse outcome in acute respiratory failure. METHODS: This was a substudy of the observational FINNALI study conducted in 25 Finnish intensive care units over an 8-week period. All patients older than 16 years requiring mechanical ventilation for >6 hours were included. MMP-8 and TIMP-1 levels were analyzed from blood samples taken on enrollment in the study and 48 hours later. Laboratory analyses were performed by using immunofluorometric assay for MMP-8 and ELISA for TIMP-1. MMP-8 and TIMP-1 levels were compared between 90-day survivors and nonsurvivors. Survival was compared in quartiles based on TIMP-1 levels, and ROC analysis was performed to calculate areas under the curves. The relationship between MMP-8 and TIMP-1 levels and degree of hypoxemia was examined. RESULTS: The final analyses included 563 patients. Admission TIMP-1 levels were higher in nonsurvivors, median 367 ng/mL (interquartile range 199-562), than survivors, median 240 ng/mL (interquartile range 142-412), WMWodds 1.68 (95% confidence interval [CI], 1.43-2.08). MMP-8 levels may have differed between survivors and nonsurvivors, WMWodds 1.20 (95% CI, 1.01-1.43), but no difference was found in the MMP-8/TIMP-1 molar ratio, WMWodds 0.83 (95% CI, 0.67-1.04). Difference in survival between quartiles based on TIMP-1 was significant (log-rank, P < 0.001). ROC analysis produced an area under the curve 0.63 (95% CI, 0.58-0.69) for TIMP-1. TIMP-1 was associated with severity of hypoxemia. TIMP-1 levels were higher in an ARDS subgroup than in the whole cohort, WMWodds 1.65 (95% CI, 1.15-2.44). CONCLUSIONS: MMP-8 levels were possibly higher in 90-day nonsurvivors but performed poorly in predicting outcome. Increased systemic levels of TIMP-1 were associated with more severe hypoxemia and worse outcome in a large cohort of mechanically ventilated critically ill patients and in a subgroup of ARDS patients.

Impact of cardiac surgery and neurosurgery patients on variation in severity-adjusted resource use in intensive care units.

PURPOSE: The resource use of cardiac surgery and neurosurgery patients likely differ from other ICU patients. We evaluated the relevance of these patient groups on overall ICU resource use. METHODS: Secondary analysis of 69,862 patients in 17 ICUs in Finland, Estonia, and Switzerland in 2015-2017. Direct costs of care were allocated to patients using daily Therapeutic Intervention Scoring System (TISS) scores and ICU length of stay (LOS). The ratios of observed to severity-adjusted expected resource use (standardized resource use ratios; SRURs), direct costs and outcomes were assessed before and after excluding cardiac surgery or cardiac and neurosurgery. RESULTS: Cardiac surgery and neurosurgery, performed only in university hospitals, represented 22% of all ICU admissions and 15-19% of direct costs. Cardiac surgery and neurosurgery were excluded with no consistent effect on SRURs in the whole cohort, regardless of cost separation method. Excluding cardiac surgery or cardiac surgery plus neurosurgery had highly variable effects on SRURs of individual university ICUs, whereas the non-university ICU SRURs decreased. CONCLUSIONS: Cardiac and neurosurgery have major effects on the cost structure of multidisciplinary ICUs. Extending SRUR analysis to patient subpopulations facilitates comparison of resource use between ICUs and may help to optimize resource allocation.

Variation in severity-adjusted resource use and outcome in intensive care units.

PURPOSE: Intensive care patients have increased risk of death and their care is expensive. We investigated whether risk-adjusted mortality and resources used to achieve survivors change over time and if their variation is associated with variables related to intensive care unit (ICU) organization and structure. METHODS: Data of 207,131 patients treated in 2008-2017 in 21 ICUs in Finland, Estonia and Switzerland were extracted from a benchmarking database. Resource use was measured using ICU length of stay, daily Therapeutic Intervention Scoring System Scores (TISS) and purchasing power parity-adjusted direct costs (2015-2017; 17 ICUs). The ratio of observed to severity-adjusted expected resource use (standardized resource use ratio; SRUR) was calculated. The number of expected survivors and the ratio of observed to expected mortality (standardized mortality ratio; SMR) was based on a mortality prediction model covering 2015-2017. Fourteen a priori variables reflecting structure and organization were used as explanatory variables for SRURs in multivariable models. RESULTS: SMR decreased over time, whereas SRUR remained unchanged, except for decreased TISS-based SRUR. Direct costs of one ICU day, TISS score and ICU admission varied between ICUs 2.5-5-fold. Differences between individual ICUs in both SRUR and SMR were up to > 3-fold, and their evolution was highly variable, without clear association between SRUR and SMR. High patient turnover was consistently associated with low SRUR but not with SMR. CONCLUSION: The wide and independent variation in both SMR and SRUR suggests that they should be used together to compare the performance of different ICUs or an individual ICU over time.

Mortality prediction in intensive care units including premorbid functional status improved performance and internal validity.

OBJECTIVE: Prognostic models are key for benchmarking intensive care units (ICUs). They require up-to-date predictors and should report transportability properties for reliable predictions. We developed and validated an in-hospital mortality risk prediction model to facilitate benchmarking, quality assurance, and health economics evaluation. STUDY DESIGN AND SETTING: We retrieved data from the database of an international (Finland, Estonia, Switzerland) multicenter ICU cohort study from 2015 to 2017. We used a hierarchical logistic regression model that included age, a modified Simplified Acute Physiology Score-II, admission type, premorbid functional status, and diagnosis as grouping variable. We used pooled and meta-analytic cross-validation approaches to assess temporal and geographical transportability. RESULTS: We included 61,224 patients treated in the ICU (hospital mortality 10.6%). The developed prediction model had an area under the receiver operating characteristic curve 0.886, 95% confidence interval (CI) 0.882-0.890; a calibration slope 1.01, 95% CI (0.99-1.03); a mean calibration -0.004, 95% CI (-0.035 to 0.027). Although the model showed very good internal validity and geographic discrimination transportability, we found substantial heterogeneity of performance measures between ICUs (I-squared: 53.4-84.7%). CONCLUSION: A novel framework evaluating the performance of our prediction model provided key information to judge the validity of our model and its adaptation for future use.

Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are associated with fatal outcome in a multicentre, prospective cohort study. Hypothetical impact of tetracyclines.

Recent evidence suggests that matrix metalloproteinases (MMPs) and their endogenous inhibitors are involved in the pathogenesis of sepsis. We studied serum levels of MMP-8, MMP-9 and TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) in a multicentre, prospective cohort study of patients with sepsis treated in Intensive Care Units (ICUs). We analyzed serum samples taken on ICU admission from 248 critically ill sepsis patients. MMP-8, -9 and TIMP-1 serum levels were analyzed by enzyme-linked immunosorbent assays. Serum MMP-8, MMP-9 and TIMP-1 levels were significantly higher in patients with severe sepsis than in healthy controls. Serum MMP-8 levels among non-survivors (n=33) were significantly (p=0.006) higher than among survivors (n=215). Serum TIMP-1 but not MMP-9 levels were significantly higher among non-survivors than survivors (p<0.0001, p=0.079, respectively). Systemic MMP-8 is upregulated in sepsis suggesting that MMP-8 may contribute to the host response during sepsis. High serum MMP-8 and TIMP-1 levels at ICU admission were seen among patients with fatal outcome. With this background, clinical studies examining the ability of MMP-inhibitors (such as the non-antimicrobial properties of tetracyclines) to diminish the MMP-mediated inflammatory response are needed to develop novel therapies in order to improve the outcome of sepsis.

Plasma cell-free DNA in patients needing mechanical ventilation.

INTRODUCTION: Concentrations of plasma cell-free DNA are increased in various diseases and have shown some prognostic value in many patient groups, including critically ill patients. Pathophysiological processes behind the need for mechanical ventilation and the treatment itself could raise plasma levels of cell-free DNA. We evaluated levels of plasma cell-free DNA and their prognostic value in patients needing mechanical ventilation. METHODS: We studied prospectively 580 mechanically ventilated critically ill patients. Blood samples were taken at study admission (Day 0) and on Day 2. Plasma cell-free DNA concentrations were measured by real-time quantitative PCR assay for the ß-globin gene and are expressed as genome equivalents (GE)/ml. RESULTS: Median (interquartile range, IQR) plasma cell-free DNA concentration was 11,853 GE/ml (5,304 to 24,620 GE/mL) at study admission, and 11,610 GE/mL (6,411 to 21,558 GE/mL) on Day 2. Concentrations at admission were significantly higher in 90-day non-survivors than survivors, 16,936 GE/mL (7,262 to 46,866 GE/mL) versus 10,026 GE/mL (4,870 to 19,820 GE/mL), P < 0.001. In a multivariate logistic regression analysis plasma cell-free DNA concentration over 16,000 GE/ml remained an independent predictor of 90-day mortality (adjusted odds ratio 2.16, 95% confidence interval CI 1.37 to 3.40). Positive likelihood ratio of plasma cell-free DNA at admission for the prediction of 90-day mortality was 1.72 (95% CI 1.40 to 2.11). CONCLUSIONS: Plasma levels of cell-free DNA were significantly higher in non-survivors than survivors. Plasma DNA level at baseline was an independent predictor of 90-day mortality. However, its clinical benefit as a prognostic marker seems to be limited.

One-year mortality, quality of life and predicted life-time cost-utility in critically ill patients with acute respiratory failure.

INTRODUCTION: High daily intensive care unit (ICU) costs are associated with the use of mechanical ventilation (MV) to treat acute respiratory failure (ARF), and assessment of quality of life (QOL) after critical illness and cost-effectiveness analyses are warranted. METHODS: Nationwide, prospective multicentre observational study in 25 Finnish ICUs. During an eight-week study period 958 consecutive adult ICU patients were treated with ventilatory support over 6 hours. Of those 958, 619 (64.6%) survived one year, of whom 288 (46.5%) answered the quality of life questionnaire (EQ-5D). We calculated EQ-5D index and predicted lifetime quality-adjusted life years (QALYs) gained using the age- and sex-matched life expectancy for survivors after one year. For expired patients the exact lifetime was used. We divided all hospital costs for all ARF patients by the number of hospital survivors, and by all predicted lifetime QALYs. We also adjusted for those who died before one year and for those with missing QOL to be able to estimate the total QALYs. RESULTS: One-year mortality was 35% (95% CI 32 to 38%). For the 288 respondents median [IQR] EQ-5D index after one year was lower than that of the age- and sex-matched general population 0.70 [0.45 to 0.89] vs. 0.84 [0.81 to 0.88]. For these 288, the mean (SD) predicted lifetime QALYs was 15.4 (13.3). After adjustment for missing QOL the mean predicted lifetime (SD) QALYs was 11.3 (13.0) for all the 958 ARF patients. The mean estimated costs were 20.739 euro per hospital survivor, and mean predicted lifetime cost-utility for all ARF patients was 1391 euro per QALY. CONCLUSIONS: Despite lower health-related QOL compared to reference values, our result suggests that cost per hospital survivor and lifetime cost-utility remain reasonable regardless of age, disease severity, and type or duration of ventilation support in patients with ARF.

[Incidence, treatment and prognosis of acute respiratory failure in Finland--the FINNALI study]. / Akillisen hengitysvajauksen esiintyvyys, hoito ja ennuste Suomessa--FINNALI-tutkimus.

In a cohort study covering whole Finland, the incidence of acute respiratory failure was higher than in previous international studies. The number of patients fulfilling the diagnostic criteria for acute lung injury and acute respiratory failure remained, however, smaller than that reported in international comparative data. The 90-day mortality was 31% and one-year mortality 35%. Recommended airway pressure levels were followed in ventilatory support treatment, but tidal volumes were larger than those in recent therapeutic trials. Patients outcome could probably be further improved by centralizing intensive care services.

Long-term outcome and quality-adjusted life years after severe sepsis.

OBJECTIVE: To study long-term mortality, quality of life (QOL), quality-adjusted life years (QALYs), and costs per QALY in an unselected intensive care unit (ICU) patient population with severe sepsis. DESIGN: Prospective observational cohort study. SETTING: Twenty-four ICUs in Finland. PATIENTS: A total of 470 adult patients with severe sepsis who were treated in ICUs between November 1, 2004 and February 28, 2005. The QOL before critical illness was assessed in 252 patients and QOL after severe sepsis in 156 patients (58% of the patients surviving in April 30, 2006). Ninety-eight patients responded to both questionnaires. QOL was assessed by a generic EuroQol-5D (EQ-5D) measurement with summary index (EQsum) and visual analogue scale (VAS). MEASUREMENTS AND MAIN RESULTS: The 2-year mortality after severe sepsis was 44.9% (211 of 470). The median response time for QOL assessment after severe sepsis was 17 months (interquartile range [IQR] 16-18). The median EQsum (75, IQR 56-92) and EQ VAS (66, IQR 50-80) were lower after severe sepsis than age- and sex-adjusted reference values (p < 0.001 and p < 0.001). The decrease between the mean EQsum reference value and that of severe sepsis patients was 12 (95% confidence interval [CI], 9-16). The difference between the mean EQ VAS reference values and the mean EQ VAS was 8 (95% CI, 5-11). The mean calculated QALYs after severe sepsis were 10.9 (95% CI, 9.7-12.1) and the calculated cost for one QALY was only 2139 [Euro sign] for all survivors and nonsurvivors. CONCLUSIONS: Two-year mortality after severe sepsis was high (44.9%) and the QOL was lower after severe sepsis than before critical illness as assessed by EQ-5D. However, the mean QALYs for the surviving patients were reasonable and the cost for one QALY was reasonably low, which makes intensive care in patients with severe sepsis cost effective.

Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia.

AIM OF THE STUDY: To determine the predictive power of the out-of-hospital cardiac arrest (OHCA) score and serum neuron-specific enolase (NSE) in patients resuscitated from ventricular fibrillation treated with therapeutic hypothermia (TH) and glucose control. METHODS: An analysis of prospectively collected data of 90 TH patients. Serum NSE was measured at 24 and 48 h. Outcome was measured by neurologic exam 6 months after cardiac arrest with good outcome defined as a Cerebral Performance Category (CPC) of 1 or 2. RESULTS: In multiple logistic regression analysis, age (odds ratio [OR], 95% confidence interval 1.1 [1.03-1.18]/year), NSE at 48 h (OR 1.1 [1.02-1.26]/microg/l), and increase in NSE levels (OR 7.2 [1.7-31.3]) were predictors of poor outcome, but the OHCA score was not. Cut-off points with 100% specificity in predicting poor outcome were 33microg/l for NSE at 48h (sensitivity 43% [28-60%]) and 6.4microg/l for delta NSE 24-48 h (sensitivity 44% [28-60%]). CONCLUSION: Increase in NSE between 24 and 48h and NSE at 48h is specific but only moderately sensitive markers of 6-month outcome. Outcome prediction at ICU admission using the OHCA score was not possible in this selected patient population.

Treatment of serious calcium channel blocker overdose with levosimendan, a calcium sensitizer.

Calcium channel blocker (CCB) overdose is often lethal. Conventional medical treatment includes i.v. calcium, high doses of catecholamines, insulin, and glucagon. A new inotropic drug, levosimendan, should be considered in severe CCB poisoning. Levosimendan's pharmacologic features differ from other inotropic drugs. It is a calcium sensitizer and improves contraction without increasing intracytosolic calcium concentration. We describe two patients with serious CCB overdose. Despite intensive medical and mechanical cardiovascular support, both patients remained in shock. Hemodynamics gradually improved after administration of levosimendan.