Noradrenaline dose cutoffs to characterise the severity of cardiovascular failure: Data-based development and external validation.

BACKGROUND: The vasopressor dose needed is a common measure to assess the severity of cardiovascular failure, but there is no consensus on the ranges of vasopressor doses determining different levels of cardiovascular support. We aimed to identify cutoffs for determining low, intermediate and high doses of noradrenaline (norepinephrine), the primary vasopressor used in intensive care, based on association with hospital mortality. METHODS: We conducted a binational registry study to determine cutoffs between low, intermediate and high noradrenaline doses. We required the cutoffs to be statistically rational and practical (rounded to the first decimal and easy to remember), and to result in increasing mortality with increasing doses. The highest noradrenaline dose in the first 24 h after intensive care unit (ICU) admission was used. The cutoffs were developed using data from 8079 ICU patients treated in the ICU at Kuopio University Hospital, Finland, between 2013 and 2019. Subsequently, the cutoffs were validated in the eICU database, including 39,007 ICU admissions to 29 ICUs in the United States of America in 2014-2015. The log-rank statistic, with the Contal and O'Quigley method, was used to determine the cutoffs resulting in the most significant split between the noradrenaline dose groups with regard to hospital mortality. RESULTS: The two most prominent peaks in the log-rank statistic corresponded to noradrenaline doses 0.20 and 0.44 µg/kg/min. Accordingly, we determined three dose ranges: low (<0.2 µg/kg/min), intermediate (0.2-0.4 µg/kg/min) and high (>0.4 µg/kg/min). Mortality increased, whereas the number of patients decreased consistently with increasing noradrenaline doses in both cohorts. In the development cohort, hospital mortality was 6.5% in the group without noradrenaline administered and 14.0%, 26.4% and 40.2%, respectively, in the low-dose, intermediate-dose and high-dose groups. Compared to patients who received no noradrenaline, the hazard ratio for in-hospital death was 1.4 for the low-dose group, 4.0 for the intermediate-dose group and 7.5 for the high-dose group in the validation cohort (p < .001). CONCLUSIONS: The highest noradrenaline dose is a useful measure for quantifying circulatory failure. Cutoffs 0.2 and 0.4 µg/kg/min seem to be suitable for defining low, intermediate and high doses.

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.

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.

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.