Effect of mortality prediction models on resource use benchmarking of intensive care units.

PURPOSE: Intensive care requires extensive resources. The ICUs' resource use can be compared using standardized resource use ratios (SRURs). We assessed the effect of mortality prediction models on the SRURs. MATERIALS AND METHODS: We compared SRURs using different mortality prediction models: the recent Finnish Intensive Care Consortium (FICC) model and the SAPS-II model (n = 68,914 admissions). We allocated the resources to severity of illness strata using deciles of predicted mortality. In each risk and year stratum, we calculated the expected resource use per survivor from our modelling approaches using length of ICU stay and Therapeutic Intervention Scoring System (TISS) points. RESULTS: Resource use per survivor increased from one length of stay (LOS) day and around 50 TISS points in the first decile to 10 LOS-days and 450 TISS in the tenth decile for both risk scoring systems. The FICC model predicted mortality risk accurately whereas the SAPS-II grossly overestimated the risk of death. Despite this, SRURs were practically identical and consistent. CONCLUSIONS: SRURs provide a robust tool for benchmarking resource use within and between ICUs. SRURs can be used for benchmarking even if recently calibrated risk scores for the specific population are not available.

Physicians' perceptions of intensive care patients' 1-year prognoses compared to realistic prognoses.

BACKGROUND: It is unknown whether physicians treating critically ill patients have realistic perceptions of their patients' prognoses. METHODS: We sent a survey by email to Finnish anesthesiologists to investigate their ability to estimate the probability of 1-year survival of intensive care unit (ICU) patients based on data available at the beginning of intensive care. We presented 12 fictional but real-life-based patient cases and asked the respondent to estimate the probability of 1-year survival in each case by choosing one of the alternatives 5%, 10%-90% in 10% intervals and 95%. We compared the physicians' estimates to registry data-based realistic prognoses of comparable patients treated in the ICU. Based on the difference between the estimate and the realistic prognosis, we categorized the estimates into three groups: (1) difference less than 10 percentage points, (2) difference between 10 and 20 percentage points, and (3) difference over 20 percentage points. RESULTS: We received 210 responses (totally 2520 estimates). Of the respondents, 43 (20.5%) were specialists working mainly in the ICU, 81 (38.6%) were specialists working occasionally in the ICU, 47 (22.4%) were specialists not working in the ICU, and 39 (18.6%) were doctors in training. The difference between the estimate and the realistic prognosis was less than 10 percentage points for 1083 (43.0%) estimates, between 10 and 20 percentage points for 645 (25.6%) estimates, and over 20 percentage points for 792 (31.4%) estimates, out of which 612 (24.3% of all estimates) underestimated and 180 (7.1%) overestimated the likelihood of survival. The median error (the median of the differences between the estimate and the realistic prognosis) for all estimates was -8.8 [interquartile range (IQR), -20.0 to -0.2], which means that the most typical response underestimated the likelihood of survival by 9 percentage points. Based on the 12 estimates, we calculated the median error for each respondent. The median (IQR) of these median errors was -8.6 (-12.6 to -5.0) for specialists working mainly in the ICU, -8.1 (-13.0 to -5.2) for specialists working occasionally in the ICU, -9.7 (-17.7 to -6.3) for specialists not working in the ICU, and -9.1 (-14.5 to -5.1) for doctors in training (p = .29). CONCLUSION: Finnish anesthesiologists commonly misestimate the long-term prognoses of ICU patients, more often underestimating than overestimating the likelihood of 1-year survival. More education about critically ill patients' prognoses and better prediction tools are needed.

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 Influence of Potential Organ Donors on Standardized Mortality Ratios and ICU Benchmarking.

OBJECTIVES: The standardized mortality ratio (SMR) is a common metric to benchmark ICUs. However, SMR may be artificially distorted by the admission of potential organ donors (POD), who have nearly 100% mortality, although risk prediction models may not identify them as high-risk patients. We aimed to evaluate the impact of PODs on SMR. DESIGN: Retrospective registry-based multicenter study. SETTING: Twenty ICUs in Finland, Estonia, and Switzerland in 2015-2017. PATIENTS: Sixty thousand forty-seven ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used a previously validated mortality risk model to calculate the SMRs. We investigated the impact of PODs on the overall SMR, individual ICU SMR and ICU benchmarking. Of the 60,047 patients admitted to the ICUs, 514 (0.9%) were PODs, and 477 (93%) of them died. POD deaths accounted for 7% of the total 6738 in-hospital deaths. POD admission rates varied from 0.5 to 18.3 per 1000 admissions across ICUs. The risk prediction model predicted a 39% in-hospital mortality for PODs, but the observed mortality was 93%. The ratio of the SMR of the cohort without PODs to the SMR of the cohort with PODs was 0.96 (95% CI, 0.93-0.99). Benchmarking results changed in 70% of ICUs after excluding PODs. CONCLUSIONS: Despite their relatively small overall number, PODs make up a large proportion of ICU patients who die. PODs cause bias in SMRs and in ICU benchmarking. We suggest excluding PODs when benchmarking ICUs with SMR.

A novel score for predicting 1-year mortality of intensive care patients.

BACKGROUND: We aimed to develop a simple scoring table for predicting probability of death within 1-year after admission to an intensive care unit. We analysed data on emergency admissions from the nationwide Finnish intensive care quality registry. METHODS: We included first admissions of adult patients with data available on 1-year vital status (dead or alive) and all five variables included in a premorbid functional status score, which is the number of activities the person can manage independently of the following five: get out of bed, move indoors, dress, climb stairs and walk 400 m. We analysed data on patient characteristics and admission-associated factors from 2012 to 2014 to find predictors of 1-year mortality and to develop a score for predicting probability of death. We tested the performance of this score in data from 2015. We assessed the 1-year functional status score of survivors with data available. RESULTS: Out of 25,261 patients, 20,628 (81.7%) patients were able to perform all five functional activities independently prior to the intensive care unit admission. At 1-year post admission, 19,625 (77.7%) patients were alive. 1-year functional status score was known for 11,011 patients and 8970 (81.5%) patients achieved functional status score 5, managing all five activities independently. The score based on age, sex, preceding functional status, type of intensive care unit admission, severity of acute illness and the most significant diagnoses predicted 1-year mortality with an area under the receiver operating characteristic curve 0.78 (95% CI, 0.76-0.79). The calibration of our prediction model was good, with calibration intercept -0.01 (-0.07 to 0.05) and calibration slope 0.96 (0.90 to 1.02). CONCLUSION: Our score based on data available at intensive care unit admission predicted 1-year mortality with fairly good discrimination. Most survivors achieved good functional recovery.

Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Dysnatremia at ICU admission and functional outcome of cardiac arrest: insights from four randomised controlled trials.

PURPOSE: To evaluate the potential association between early dysnatremia and 6-month functional outcome after cardiac arrest. METHODS: We pooled data from four randomised clinical trials in post-cardiac-arrest patients admitted to the ICU with coma after stable return of spontaneous circulation (ROSC). Admission natremia was categorised as normal (135-145 mmol/L), low, or high. We analysed associations between natremia category and Cerebral Performance Category (CPC) 1 or 2 at 6 months, with and without adjustment on the modified Cardiac Arrest Hospital Prognosis Score (mCAHP). RESULTS: We included 1163 patients (581 from HYPERION, 352 from TTH48, 120 from COMACARE, and 110 from Xe-HYPOTHECA) with a mean age of 63 ± 13 years and a predominance of males (72.5%). A cardiac cause was identified in 63.6% of cases. Median time from collapse to ROSC was 20 [15-29] minutes. Overall, mean natremia on ICU admission was 137.5 ± 4.7 mmol/L; 211 (18.6%) and 31 (2.7%) patients had hyponatremia and hypernatremia, respectively. By univariate analysis, CPC 1 or 2 at 6 months was significantly less common in the group with hyponatremia (50/211 [24%] vs. 363/893 [41%]; P = 0.001); the mCAHP-adjusted odds ratio was 0.45 (95%CI 0.26-0.79, p = 0.005). The number of patients with hypernatremia was too small for a meaningful multivariable analysis. CONCLUSIONS: Early hyponatremia was common in patients with ROSC after cardiac arrest and was associated with a poorer 6-month functional outcome. The mechanisms underlying this association remain to be elucidated in order to determine whether interventions targeting hyponatremia are worth investigating. Registration ClinicalTrial.gov, NCT01994772, November 2013, 21.

Effect of antiplatelet and anticoagulant medication use on injury severity and mortality in patients with traumatic brain injury treated in the intensive care unit.

BACKGROUND: Antiplatelet and anticoagulant medication are increasingly common and can increase the risks of morbidity and mortality in traumatic brain injury (TBI) patients. Our study aimed to quantify the association of antiplatelet or anticoagulant use in intensive care unit (ICU)-treated TBI patients with 1-year mortality and head CT findings. METHOD: We conducted a retrospective, multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted to four university hospital ICUs during 2003-2013. The patients were followed up until the end of 2016. The national drug reimbursement database provided information on prescribed medication for our study. We used multivariable logistic regression models to assess the association between TBI severity, prescribed antiplatelet and anticoagulant medication, and their association with 1-year mortality. RESULTS: Of 3031 patients, 128 (4%) had antiplatelet and 342 (11%) anticoagulant medication before their TBI. Clopidogrel (2%) and warfarin (9%) were the most common antiplatelets and anticoagulants. Three patients had direct oral anticoagulant (DOAC) medication. The median age was higher among antiplatelet/anticoagulant users than in non-users (70 years vs. 52 years, p < 0.001), and their head CT findings were more severe (median Helsinki CT score 3 vs. 2, p < 0.05). In multivariable analysis, antiplatelets (OR 1.62, 95% CI 1.02-2.58) and anticoagulants (OR 1.43, 95% CI 1.06-1.94) were independently associated with higher odds of 1-year mortality. In a sensitivity analysis including only patients over 70, antiplatelets (OR 2.28, 95% CI 1.16-4.22) and anticoagulants (1.50, 95% CI 0.97-2.32) were associated with an increased risk of 1-year mortality. CONCLUSIONS: Both antiplatelet and anticoagulant use before TBI were risk factors in our study for 1-year mortality. Antiplatelet and anticoagulation medication users had a higher radiological intracranial injury burden than non-users defined by the Helsinki CT score. Further investigation on the effect of DOACs on mortality should be done in ICU-treated TBI patients.

The effect of higher or lower mean arterial pressure on kidney function after cardiac arrest: a post hoc analysis of the COMACARE and NEUROPROTECT trials.

BACKGROUND: We aimed to study the incidence of acute kidney injury (AKI) in out-of-hospital cardiac arrest (OHCA) patients treated according to low-normal or high-normal mean arterial pressure (MAP) targets. METHODS: A post hoc analysis of the COMACARE (NCT02698917) and Neuroprotect (NCT02541591) trials that randomized patients to lower or higher targets for the first 36 h of intensive care. Kidney function was defined using the Kidney Disease Improving Global Outcome (KDIGO) classification. We used Cox regression analysis to identify factors associated with AKI after OHCA. RESULTS: A total of 227 patients were included: 115 in the high-normal MAP group and 112 in the low-normal MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 in the high-normal MAP group and 46 in the low-normal MAP group (p = 0.51). The median creatinine and daily urine output were 85 µmol/l and 1730 mL/day in the high-normal MAP group and 87 µmol/l and 1560 mL/day in the low-normal MAP group. In a Cox regression model, independent AKI predictors were no bystander cardiopulmonary resuscitation (p < 0.01), non-shockable rhythm (p < 0.01), chronic hypertension (p = 0.03), and time to the return of spontaneous circulation (p < 0.01), whereas MAP target was not an independent predictor (p = 0.29). CONCLUSION: Any AKI occurred in four out of ten OHCA patients. We found no difference in the incidence of AKI between the patients treated with lower and those treated with higher MAP after CA. Higher age, non-shockable initial rhythm, and longer time to ROSC were associated with shorter time to AKI. CLINICAL TRIAL REGISTRATION: COMACARE (NCT02698917), NEUROPROTECT (NCT02541591).

Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline.

BACKGROUND: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? METHODS: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. RESULTS: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis. CONCLUSIONS: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged.

Higher versus lower blood pressure targets after cardiac arrest: Systematic review with individual patient data meta-analysis.

PURPOSE: Guidelines recommend targeting mean arterial pressure (MAP) > 65 mmHg in patients after cardiac arrest (CA). Recent trials have studied the effects of targeting a higher MAP as compared to a lower MAP after CA. We performed a systematic review and individual patient data meta-analysis to investigate the effects of higher versus lower MAP targets on patient outcome. METHOD: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, BIOSIS, CINAHL, Scopus, the Web of Science Core Collection, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, Google Scholar and the Turning Research into Practice database to identify trials randomizing patients to higher (≥71 mmHg) or lower (≤70 mmHg) MAP targets after CA and resuscitation. We used the Cochrane Risk of Bias tool, version 2 (RoB 2) to assess for risk of bias. The primary outcomes were 180-day all-cause mortality and poor neurologic recovery defined by a modified Rankin score of 4-6 or a cerebral performance category score of 3-5. RESULTS: Four eligible clinical trials were identified, randomizing a total of 1,087 patients. All the included trials were assessed as having a low risk for bias. The risk ratio (RR) with 95% confidence interval for 180-day all-cause mortality for a higher versus a lower MAP target was 1.08 (0.92-1.26) and for poor neurologic recovery 1.01 (0.86-1.19). Trial sequential analysis showed that a 25% or higher treatment effect, i.e., RR < 0.75, can be excluded. No difference in serious adverse events was found between the higher and lower MAP groups. CONCLUSIONS: Targeting a higher MAP compared to a lower MAP is unlikely to reduce mortality or improve neurologic recovery after CA. Only a large treatment effect above 25% (RR < 0.75) could be excluded, and future studies are needed to investigate if relevant but lower treatment effect exists. Targeting a higher MAP was not associated with any increase in adverse effects.

Vasoactive Inotropic Score compared to the sequential organ failure assessment cardiovascular score in intensive care.

BACKGROUND: The cardiovascular component of the sequential organ failure assessment (cvSOFA) score may be outdated because of changes in intensive care. Vasoactive Inotropic Score (VIS) represents the weighted sum of vasoactive and inotropic drugs. We investigated the association of VIS with mortality in the general intensive care unit (ICU) population and studied whether replacing cvSOFA with a VIS-based score improves the accuracy of the SOFA score as a predictor of mortality. METHODS: We studied the association of VIS during the first 24 h after ICU admission with 30-day mortality in a retrospective study on adult medical and non-cardiac emergency surgical patients admitted to Kuopio University Hospital ICU, Finland, in 2013-2019. We determined the area under the receiver operating characteristic curve (AUROC) for the original SOFA and for SOFAVISmax , where cvSOFA was replaced with maximum VIS (VISmax ) categories. RESULTS: Of 8079 patients, 1107 (13%) died within 30 days. Mortality increased with increasing VISmax . AUROC was 0.813 (95% confidence interval [CI], 0.800-0.825) for original SOFA and 0.822 (95% CI: 0.810-0.834) for SOFAVISmax , p < .001. CONCLUSION: Mortality increased consistently with increasing VISmax . Replacing cvSOFA with VISmax improved the predictive accuracy of the SOFA score.

Incidence and risk factors of posttraumatic hydrocephalus and its association with outcome following intensive care unit treatment for traumatic brain injury: a multicenter observational study.

OBJECTIVE: Posttraumatic hydrocephalus (PTH) is a recognized long-term complication of traumatic brain injury (TBI). The authors assessed the incidence and risk factors of PTH and its association with outcome in patients with TBI who were treated in the intensive care unit (ICU). METHODS: The authors used the Finnish Intensive Care Consortium (FICC) database to retrospectively identify all adult patients with TBI treated in 4 Finnish tertiary ICUs during 2003-2013. All patients were followed up from hospital discharge to a diagnosis of PTH, death, or the end of 2016. PTH was defined as a need for a postdischarge ventriculoperitoneal or ventriculoatrial shunt. The authors collected data on shunt-insertion procedures, mortality, and disability status from nationwide registries cross-linked to the FICC database. The authors calculated the occurrence and incidence rates of PTH and used multivariable logistic regression modeling to determine risk factors for PTH and its association with outcome. RESULTS: Sixty-one of 2882 patients (2.1%) developed PTH during a median follow-up time of 4.6 years, with a median of 102 days (interquartile range 54-220 days) between hospital discharge and PTH. Risk factors for PTH were increasing age (OR 1.02 per year, 95% CI 1.01-1.04); a midline shift of > 5 mm (OR 1.88, 95% CI 1.01-3.48); traumatic subarachnoid hemorrhage (OR 3.59, 95% CI 1.79-7.21); external ventricular drainage (OR 3.54, 95% CI 1.68-7.46); and decompressive craniectomy (OR 3.68, 95% CI 1.37-9.88). PTH was independently associated with permanent disability after case-mix adjustment (OR 3.62, 95% CI 2.11-6.22). CONCLUSIONS: PTH is an uncommon long-term complication of TBI, with several risk factors that are identifiable early during neurointensive care. The development of PTH is independently associated with poor functional outcome. Whether earlier detection and treatment of PTH leads to improved outcomes remains unknown, highlighting the importance of adequate follow-up and prompt detection and treatment of the condition.

Ubiquitin C-terminal hydrolase L1 after out-of-hospital cardiac arrest.

BACKGROUND: We studied the prognostic ability of serum ubiquitin C-terminal hydrolase L1 (UCH-L1) after out-of-hospital cardiac arrest (OHCA), compared to that of neuron-specific enolase (NSE). METHODS: In this post-hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH-L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010-2011. We evaluated the ability of UCH-L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3-5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE. RESULTS: The concentrations of UCH-L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5-18.5 ng/mL) versus 7.8 ng/mL (5.9-11.8 ng/mL) at 24 h (p < .001), and 16.2 ng/mL (12.2-27.7 ng/mL) versus 11.5 ng/mL (9.0-17.2 ng/mL) (p < .001) at 48 h after OHCA. For UCH-L1 as a 12-month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60-0.73) at 24 h and 0.66 (0.59-0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59-0.73) at 24 h and 0.72 (0.65-0.80) at 48 h. The prognostic ability of UCH-L1 was not different from that of NSE at 24 h (p = .82) and at 48 h (p = .23). CONCLUSION: Concentrations of UCH-L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH-L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Markers of neutrophil mediated inflammation associate with disturbed continuous electroencephalogram after out of hospital cardiac arrest.

BACKGROUND: Achieving an acceptable neurological outcome in cardiac arrest survivors remains challenging. Ischemia-reperfusion injury induces inflammation, which may cause secondary neurological damage. We studied the association of ICU admission levels of inflammatory biomarkers with disturbed 48-hour continuous electroencephalogram (cEEG), and the association of the daily levels of these markers up to 72 h with poor 6-month neurological outcome. METHODS: This is an observational, post hoc sub-study of the COMACARE trial. We measured serum concentrations of procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), osteopontin (OPN), myeloperoxidase (MPO), resistin, and proprotein convertase subtilisin/kexin type 9 (PCSK9) in 112 unconscious, mechanically ventilated ICU-treated adult OHCA survivors with initial shockable rhythm. We used grading of 48-hour cEEG monitoring as a measure for the severity of the early neurological disturbance. We defined 6-month cerebral performance category (CPC) 1-2 as good and CPC 3-5 as poor long-term neurological outcome. We compared the prognostic value of biomarkers for 6-month neurological outcome to neurofilament light (NFL) measured at 48 h. RESULTS: Higher OPN (p = .03), MPO (p < .01), and resistin (p = .01) concentrations at ICU admission were associated with poor grade 48-hour cEEG. Higher levels of ICU admission OPN (OR 3.18; 95% CI 1.25-8.11 per ln[ng/ml]) and MPO (OR 2.34; 95% CI 1.30-4.21) were independently associated with poor 48-hour cEEG in a multivariable logistic regression model. Poor 6-month neurological outcome was more common in the poor cEEG group (63% vs. 19% p < .001, respectively). We found a significant fixed effect of poor 6-month neurological outcome on concentrations of PCT (F = 7.7, p < .01), hsCRP (F = 4.0, p < .05), and OPN (F = 5.6, p < .05) measured daily from ICU admission to 72 h. However, the biomarkers did not have independent predictive value for poor 6-month outcome in a multivariable logistic regression model with 48-hour NFL. CONCLUSION: Elevated ICU admission levels of OPN and MPO predicted disturbances in cEEG during the subsequent 48 h after cardiac arrest. Thus, they may provide early information about the risk of secondary neurological damage. However, the studied inflammatory markers had little value for long-term prognostication compared to 48-hour NFL.

Interactions in the 2×2×2 factorial randomised clinical STEPCARE trial and the potential effects on conclusions: a protocol for a simulation study.

BACKGROUND: Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2×2×2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest. METHODS: By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all-cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errors ≤ 5% and the risk of type-2 errors ≤ 10%, we will quantify the maximum interaction effect we can accept if the planned sample size is increased by 5% to take into account possible interaction between the trial interventions. Secondly, we will assess how interaction effects influence the minimal detectable difference we may confirm or reject to take into account 5% (small interaction effect), 10% (moderate), or 15% (large) positive interactions in simulations with no 'true' intervention effect (type-1 errors) and small (5%), moderate (10%), or large negative interactions (15%) in simulations with 'true' intervention effects (type-2 errors). Moreover, we will investigate how much the sample size must be increased to account for a small, moderate, or large interaction effects. DISCUSSION: This protocol for a simulation study will inform the design of a 2×2×2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results. TRIAL REGISTRATION: Not relevant.

One-year healthcare costs of patients with spontaneous intracerebral hemorrhage treated in the intensive care unit.

Background: Spontaneous intracerebral hemorrhage (ICH) entails significant mortality and morbidity. Severely ill ICH patients are treated in intensive care units (ICUs), but data on 1-year healthcare costs and patient care cost-effectiveness are lacking. Methods: Retrospective multi-center study of 959 adult patients treated for spontaneous ICH from 2003 to 2013. The primary outcomes were 12-month mortality or permanent disability, defined as being granted a permanent disability allowance or pension by the Social Insurance Institution by 2016. Total healthcare costs were hospital, rehabilitation, and social security costs within 12 months. A multivariable linear regression of log transformed cost data, adjusting for case mix, was used to assess independent factors associated with costs. Results: Twelve-month mortality was 45% and 51% of the survivors were disabled at the end of follow-up. The mean 12-month total cost was €49,754, of which rehabilitation, tertiary hospital and social security costs accounted for 45%, 39%, and 16%, respectively. The highest effective cost per independent survivor (ECPIS) was noted among patients aged >70 years with brainstem ICHs, low Glasgow Coma Scale (GCS) scores, larger hematoma volumes, intraventricular hemorrhages, and ICH scores of 3. In multivariable analysis, age, GCS score, and severity of illness were associated independently with 1-year healthcare costs. Conclusions: Costs associated with ICHs vary between patient groups, and the ECPIS appears highest among patients older than 70 years and those with brainstem ICHs and higher ICH scores. One-third of financial resources were used for patients with favorable outcomes. Further detailed cost-analysis studies for patients with an ICH are required.