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.

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.

Global-, regional- and country-level estimates of the work-related burden of diseases and accidents in 2019.

OBJECTIVE: This study provides the global-, regional- and country-level estimates on the work-related burden of diseases and accidents for 2019, including deaths, disability adjusted life years (DALY) and economic losses. METHODS: Data on occupational illnesses and injuries from international organizations, institutions, and public websites were used. Risk ratios (RR) and population attributable fractions (PAF) for the risk factor-outcome pairs were derived from the literature. Estimated mortality and DALY for a group of seven major diseases covering 120 risk-outcome pairs attributable to work were calculated for 181 countries. RESULTS: Globally, 2.9 million deaths were attributed to work, with 2.58 million deaths due to work-related diseases and 0.32 million related to occupational injuries. Globally, work-related diseases with a long latency period are increasing, while the number of occupational injuries has decreased. Work-related circulatory diseases were the major cause of 912 000 deaths globally, followed by 843 000 work-related malignant neoplasms. In high-income, American, Eastern European and Western Pacific World Health Organization (WHO) regions, however, work-related malignant neoplasms comprised the biggest disease group. DALY attributable to work were estimated to be 180 million in 2019, with an associated economic loss of 5.8% of global GDP. New estimates of psychosocial factors increased the global loss. CONCLUSIONS: The burden of work-related diseases and injuries increased by 26% from 2.3 million annual deaths in 2014 to 2.9 million in 2019. The DALY attributable to work have also substantially increased from 123 million in 2014 to 180 million in 2019 (47% increase). We found large regional and country variations.

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.

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III).

Rationale: The SPICE III (Sedation Practice in Intensive Care Evaluation) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation. Objectives: To quantify the association of different infusion rates of dexmedetomidine and propofol, given in combination, with mortality and to determine if this is modified by age. Methods: We included 1,177 patients randomized in SPICE III to receive dexmedetomidine and given supplemental propofol, stratified by age (>65 or ⩽65 yr). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality. Measurements and Main Results: Younger patients (598 of 1,177 [50.8%]) received significantly higher doses of both sedatives compared with older patients to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 µg/kg/h) was associated with reduced adjusted mortality in younger but not older patients. This was consistent with multivariable regression modeling (hazard ratio, 0.59; 95% confidence interval, 0.43-0.78; P < 0.0001) adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients, using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality (hazard ratio, 1.30; 95% confidence interval, 1.03-1.65; P = 0.029). Conclusions: In patients ⩽65 years of age sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registered with www.clinicaltrials.gov (NCT01728558).

A Systematized Overview of Published Reviews on Biological Hazards, Occupational Health, and Safety.

Introduction: The COVID-19 pandemic turned biological hazards in the working environment into a global concern. This systematized review of published reviews aimed to provide a comprehensive overview of the specific jobs and categories of workers exposed to biological hazards with the related prevention. Methods: We extracted reviews published in English and French in PubMed, Embase, and Web of Science. Two authors, working independently, subsequently screened the potentially relevant titles and abstracts recovered (step 1) and then examined relevant full texts (step 2). Disagreements were resolved by consensus. We built tables summarizing populations of exposed workers, types of hazards, types of outcomes (types of health issues, means of prevention), and routes of transmission. Results: Of 1426 studies initially identified, 79 studies by authors from every continent were selected, mostly published after 2010 (n = 63, 79.7%). About half of the reviews dealt with infectious hazards alone (n = 38, 48.1%). The industrial sectors identified involved healthcare alone (n = 16), laboratories (n = 10), agriculture (including the animal, vegetable, and grain sectors, n = 32), waste (n = 10), in addition of 11 studies without specific sectors. The results also highlighted a range of hazards (infectious and non-infectious agents, endotoxins, bioaerosols, organic dust, and emerging agents). Conclusion: This systematized overview allowed to list the populations of workers exposed to biological hazards and underlined how prevention measures in the healthcare and laboratory sectors were usually well defined and controlled, although this was not the case in the agriculture and waste sectors. Further studies are necessary to quantify these risks and implement prevention measures that can be applied in every country.

Global Estimates on Biological Risks at Work.

Introduction: Biological risks are a major global problem in the workplace. The recent COVID-19 pandemic has highlighted the need for a more comprehensive understanding of the biological risks at work. This study presents data on both communicable infectious biological agents and noncommunicable factors leading to death and disability for the year 2021. Methods: We followed the methodology established by the International Labour Organization (ILO) in their past global estimates on occupational accidents and work-related diseases. We used relevant ILO estimates for hazardous substances and related population attributable fractions derived from literature, which were then applied to World Health Organization mortality data. The communicable diseases included in the estimates were tuberculosis, pneumococcal diseases, malaria, diarrheal diseases, other infectious diseases, neglected tropical diseases, influenza associated respiratory diseases and COVID-19. Noncommunicable diseases and injuries considered were Chronic Obstructive Diseases (COPD) due to organic dusts, asthma, allergic reactions and risks related to animal contact. We estimated death attributable to biological risk at work and disability in terms of disability adjusted life years (DALYs). Results: We estimated that in 2022, 550,819 deaths were caused by biological risk factors, with 476,000 deaths attributed to communicable infectious diseases and 74,000 deaths caused by noncommunicable factors. Among these, there were 223,650 deaths attributed to COVID-19 at work. We calculated the rate of 584 DALYs per 100,000 workers, representing an 11% increase from the previous estimate of the global burden of work-related disabilities measured by DALYs. Conclusion: This is a first update since previous 2007 ILO estimates, which has now increased by 74% and covers most biological risks factors. However, it is important to note that there may be other diseases and deaths are missing from the data, which need to be included when new information becomes available. It is also worth mentioning that while deaths caused by major communicable diseases including COVID-19 are relatively rare within the working population, absences from work due to these diseases are likely to be very common within the active workforce.

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.

Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Delayed Cerebral Ischemia.

BACKGROUND: We demonstrated experimentally that inhaled nitric oxide (iNO) dilates hypoperfused arterioles, increases tissue perfusion, and improves neurological outcome following subarachnoid hemorrhage (SAH) in mice. We performed a prospective pilot study to evaluate iNO in patients with delayed cerebral ischemia after SAH. METHODS: SAH patients with delayed cerebral ischemia and hypoperfusion despite conservative treatment were included. iNO was administered at a maximum dose of 40 ppm. The response to iNO was considered positive if: cerebral artery diameter increased by 10% in digital subtraction angiography (DSA), or tissue oxygen partial pressure (PtiO2) increased by > 5 mmHg, or transcranial doppler (TCD) values decreased more than 30 cm/sec, or mean transit time (MTT) decreased below 6.5 secs in CT perfusion (CTP). Patient outcome was assessed at 6 months with the modified Rankin Scale (mRS). RESULTS: Seven patients were enrolled between February 2013 and September 2016. Median duration of iNO administration was 23 h. The primary endpoint was reached in all patients (five out of 17 DSA examinations, 19 out of 29 PtiO2 time points, nine out of 26 TCD examinations, three out of five CTP examinations). No adverse events necessitating the cessation of iNO were observed. At 6 months, three patients presented with a mRS score of 0, one patient each with an mRS score of 2 and 3, and two patients had died. CONCLUSION: Administration of iNO in SAH patients is safe. These results call for a larger prospective evaluation.

Association of Sequential Organ Failure Assessment (SOFA) components with mortality.

BACKGROUND: Sequential Organ Failure Assessment (SOFA) is a practical method to describe and quantify the presence and severity of organ system dysfunctions and failures. Some proposals suggest that SOFA could be employed as an endpoint in trials. To justify this, all SOFA component scores should reflect organ dysfunctions of comparable severity. We aimed to investigate whether the associations of different SOFA components with in-hospital mortality are comparable. METHODS: We performed a study based on nationwide register data on adult patients admitted to 26 Finnish intensive care units (ICUs) during 2012-2015. We determined the SOFA score as the maximum score in the first 24 hours after ICU admission. We defined organ failure (OF) as an organ-specific SOFA score of three or higher. We evaluated the association of different SOFA component scores with mortality. RESULTS: Our study population comprised 63,756 ICU patients. Overall hospital mortality was 10.7%. In-hospital mortality was 22.5% for patients with respiratory failure, 34.8% for those with coagulation failure, 40.1% for those with hepatic failure, 14.9% for those with cardiovascular failure, 26.9% for those with neurologic failure and 34.6% for the patients with renal failure. Among patients with comparable total SOFA scores, the risk of death was lower in patients with cardiovascular OF compared with patients with other OFs. CONCLUSIONS: All SOFA components are associated with mortality, but their weights are not comparable. High scores of other organ systems mean a higher risk of death than high cardiovascular scores. The scoring of cardiovascular dysfunction needs to be updated.

Experimental validation of a mean systemic pressure analog against zero-flow measurements in porcine VA-ECMO.

The mean systemic pressure analog (Pmsa), calculated from running hemodynamic data, estimates mean systemic filling pressure (MSFP). This post hoc study used data from a porcine veno-arterial extracorporeal membrane oxygenation (ECMO) model [n = 9; Sus scrofa domesticus; ES breed (Schweizer Edelschwein)] with eight experimental conditions; Euvolemia [a volume state where ECMO flow produced normal mixed venous saturation (SVO2) without vascular collapse]; three levels of increasing norepinephrine infusion (Vasoconstriction 1-3); status after stopping norepinephrine (Post Vasoconstriction); and three steps of volume expansion (10 mL/kg crystalloid bolus) (Volume Expansion 1-3). In each condition, Pmsa and a "reduced-pump-speed-Pmsa" (Pmsared) were calculated from baseline and briefly reduced pump speeds, respectively. We calculated agreement for absolute values (per condition) and changes (between consecutive conditions) of Pmsa and Pmsared, against MSFP at zero ECMO flow. Euvolemia venous return driving pressure was 5.1 ± 2.0 mmHg. Bland-Altman analysis for Pmsa vs. MSFP (all conditions; 72 data pairs) showed bias (confidence interval) 0.5 (0.1-0.9) mmHg; limits of agreement (LoA) -2.7 to 3.8 mmHg. Bias for ΔPmsa vs. ΔMSFP (63 data pairs): 0.2 (-0.2 to 0.6) mmHg, LoA -3.2 to 3.6 mmHg. Bias for Pmsared vs. MSFP (72 data pairs): 0.0 (-0.3 to -0.3) mmHg; LoA -2.3 to 2.4 mmHg. Bias for ΔPmsared vs. ΔMSFP (63 data pairs) was 0.2 (-0.1 to 0.4) mmHg; LoA -1.8 to 2.1 mmHg. In conclusion, during veno-arterial ECMO, under clinically relevant levels of vasoconstriction and volume expansion, Pmsa accurately estimated absolute and changing values of MSFP, with low between-method precision. The within-method precision of Pmsa was excellent, with a least significant change of 0.15 mmHg.NEW & NOTEWORTHY This is the first study ever to validate the mean systemic pressure analog (Pmsa) against the reference mean systemic filling pressure (MSFP) determined at full arterio-venous pressure equilibrium. Using a porcine ECMO model with clinically relevant levels of vasoconstriction and volume expansion, we showed that Pmsa accurately estimated absolute and changing values of MSFP, with a poor between-method precision. The within-method precision of Pmsa was excellent.

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.

Should Vasopressors Be Started Early in Septic Shock?

Sepsis can influence blood volume, its distribution, vascular tone, and cardiac function. Persistent hypotension or the need for vasopressors after volume resuscitation is part of the definition of septic shock. Since increased positive fluid balance has been associated with increased morbidity and mortality in sepsis, timing of vasopressors in the treatment of septic shock seems crucial. However, conclusive evidence on timing and sequence of interventions with the goal to restore tissue perfusion is lacking. The aim of this narrative review is to depict the pathophysiology of hypotension in sepsis, evaluate how common interventions to treat hypotension interfere with physiology, and to give a resume of the results from clinical studies focusing on targets and timing of vasopressor in sepsis. The majority of studies comparing early versus late administration of vasopressors in septic shock are rather small, single-center, and retrospective. The range of "early" is between 1 and 12 hours. The available studies suggest a mean arterial pressure of 60 to 65 mm Hg as a threshold for increased risk of morbidity and mortality, whereas higher blood pressure targets do not seem to add further benefits. The data, albeit mostly from observational studies, speak for combining vasopressors with fluids rather "early" in the treatment of septic shock (within a 0-3-hour window). Nevertheless, the optimal resuscitation strategy should take into account the source of infection, the pathophysiology, the time and clinical course preceding the diagnosis of sepsis, and also comorbidities and sepsis-induced organ dysfunction.

Development of the "National Asbestos Profile" to Eliminate Asbestos-Related Diseases in 195 Countries.

Worldwide, 230,000+ people die annually from asbestos-related diseases (ARDs). The World Health Organization (WHO) recommends that countries develop a National Asbestos Profile (NAP) to eliminate ARDs. For 195 countries, we assessed the global status of NAPs (A: bona fide NAP, B: proxy NAP, C: relevant published information, D: no relevant information) by national income (HI: high, UMI: upper-middle, LMI: lower-middle, LI: low), asbestos bans (banned, no-ban) and public data availability. Fourteen (7% of 195) countries were category A (having a bona fide NAP), while 98, 51 and 32 countries were categories B, C and D, respectively. Of the 14 category-A countries, 8, 3 and 3 were LMI, UMI and HI, respectively. Development of a bona fide NAP showed no gradient by national income. The proportions of countries having a bona fide NAP were similar between asbestos-banned and no-ban countries. Public databases useful for developing NAPs contained data for most countries. Irrespective of the status of national income or asbestos ban, most countries have not developed a NAP despite having the potential. The global status of NAP is suboptimal. Country-level data on asbestos and ARDs in public databases can be better utilized to develop NAPs for globally eliminating ARDs.