The Impact of Heart Rate Circadian Rhythm on In-hospital Mortality in Stroke and Critically Ill Patients: Insights from the eICU Collaborative Research Database

Background: The dysregulation of the heart rate circadian rhythm has been documented to be an independent risk factor in multiple diseases. However, data showing the impact of dysregulated heart rate circadian rhythm in stroke and critically ill patients are scarce.Methods: Stroke and critically ill patients in the ICU between 2014 and 2015 from the recorded eICU Collaborative Research Database were included in the current analyses. The impact of circadian rhythm of heart rate on in-hospital mortality was analyzed. Three variables, Mesor (rhythm-adjusted mean of heart rate), Amplitude (distance from the highest point of circadian rhythm of heart rate to Mesor), and Peak time (time when the circadian rhythm of heart rate reaches the highest point) were used to evaluate the heart rate circadian rhythm. The incremental value of circadian rhythm variables in addition to Acute Physiology and Chronic Health Evaluation (APACHE) IV score to predict in-hospital mortality was also explored.Results: A total of 6,201 eligible patients were included. The in-hospital mortality was 16.2% (1,002/6,201). The circadian rhythm variables of heart rate, Mesor, Amplitude, and Peak time, were identified to be independent risk factors of in-hospital mortality. After adjustments, Mesor per 10 beats per min (bpm) increase was associated with a 1.17-fold (95%CI: 1.11, 1.24, P<0.001) and Amplitude per 5 bpm was associated with a 1.14-fold (95%CI: 1.06, 1.24, P<0.001) increase in the risk of in-hospital mortality, respectively. The risk of in-hospital mortality was lower in patients who had Peak time reached between 18:00-24:00 or 00:00-06:00; whereas the risk was highest in patients who had Peak time reached between 12:00-18:00 (OR: 1.33, 95%CI: 1.05, 1.68, P=0.017). Compared with APACHE IV score only (c-index=0.757), combining APACHE IV score and circadian rhythm variables of heart rate (c-index=0.766) was associated with increased discriminative ability (P=0.003).Conclusion: Circadian rhythm of heart rate is an independent risk factor of the in-hospital mortality in stroke and critically ill patients. Including circadian rhythm variables regarding heart rate might increase the discriminative ability of the risk score to predict the short-term prognosis of patients.

Five-Year Outcomes After Implementing a Pain, Agitation, and Delirium Protocol in a Mixed Intensive Care Unit

Objective: Assess for continued improvements in patient outcomes after updating our institutional sedation and analgesia protocol to include recommendations from the 2013 Society of Critical Care Medicine (SCCM) Pain, Agitation, and Delirium (PAD) guidelines. Methods: Retrospective before-and-after study in a mixed medical/surgical intensive care unit (ICU) at an academic medical center. Mechanically ventilated adults admitted from September 1, 2011 through August 31, 2012 (pre-implementation) and October 1, 2012 through September 30, 2017 (post-implementation) were included. Measurements included number of mechanically ventilated patients, APACHE IV scores, age, type of patient (medical or surgical), admission diagnosis, ICU length of stay (LOS), hospital LOS, ventilator days, number of self-extubations, ICU mortality, ICU standardized mortality ratio, hospital mortality, hospital standardized mortality ratio, medication data including as needed (PRN) analgesic and sedative use, and analgesic and sedative infusions, and institutional savings. Results: Ventilator days (Pre-PAD = 4.0 vs. Year 5 post = 3.2, P < .0001), ICU LOS (Pre-PAD = 4.8 days vs. Year 5 post = 4.1 days, P = .0004) and hospital LOS (Pre-PAD = 14 days vs. Year 5 post = 12 days, P < .0001) decreased after protocol implementation. Hospital standardized mortality ratio (Pre-PAD = 0.69 vs. Year 5 post = 0.66) remained constant; while, APACHE IV scores (Pre-PAD = 77 vs. Year 5 post = 89, P < .0001) and number of intubated patients (Pre-PAD = 1146 vs. Year 5 post = 1468) increased over the study period. Using the decreased ICU and hospital LOS estimates, it is projected the institution saved $4.3 million over the 5 years since implementation. Conclusions: Implementation of an updated PAD protocol in a mixed medical/surgical ICU was associated with a significant decrease in ventilator time, ICU LOS, and hospital LOS without a change in the standardized mortality ratio over a five-year period. These favorable outcomes are associated with a significant cost savings for the institution.

APACHE IV system helps to determine role of cholecystostomy in elderly patients with acute cholecystitis

Objective Cholecystostomy is a palliative treatment for patients unfit to undergo immediate cholecystectomy. Nevertheless, the role of cholecystostomy in the clinical management of such patients remains unclear. The Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scoring system is useful for estimating the hospital mortality of high-risk patients. We evaluated the therapeutic effect of cholecystostomy by the APACHE IV scoring system in patients aged >65 years with acute cholecystitis. Methods In total, 597 patients aged >65 years with acute cholecystitis were retrospectively analyzed using APACHE IV scores. Results The fitness of the APACHE IV score prediction was good, with an area under the receiver operating characteristic curve of 0.894. The chi square independence test indicated that compared with conservative treatment, cholecystostomy may have different effects on mortality for patients whose estimated mortality rate was >10%. Comparison of the estimated mortality of patients before and after cholecystostomy indicated that the estimated mortality was significantly lower after than before puncture, both in the whole patient group and in the group with an estimated mortality of >10%. Conclusion The APACHE IV scoring system showed that cholecystostomy is a safe and effective treatment for elderly high-risk patients with acute cholecystitis.

Development and validation of a score to predict mortality in ICU patients with sepsis: a multicenter retrospective study

Background Early and accurate identification of septic patients at high risk for ICU mortality can help clinicians make optimal clinical decisions and improve the patients’ outcomes. This study aimed to develop and validate (internally and externally) a mortality prediction score for sepsis following admission in the ICU. Methods We extracted data retrospectively regarding adult septic patients from one teaching hospital in Wenzhou, China and a large multi-center critical care database from the USA. Demographic data, vital signs, laboratory values, comorbidities, and clinical outcomes were collected. The primary outcome was ICU mortality. Through multivariable logistic regression, a mortality prediction score for sepsis was developed and validated. Results Four thousand two hundred and thirty six patients in the development cohort and 8359 patients in three validation cohorts. The Prediction of Sepsis Mortality in ICU (POSMI) score included age ≥ 50 years, temperature < 37 °C, Respiratory rate > 35 breaths/min, MAP ≤ 50 mmHg, SpO2 < 90%, albumin ≤ 2 g/dL, bilirubin ≥ 0.8 mg/dL, lactate ≥ 4.2 mmol/L, BUN ≥ 21 mg/dL, mechanical ventilation, hepatic failure and metastatic cancer. In addition, the area under the receiver operating characteristic curve (AUC) for the development cohort was 0.831 (95% CI, 0.813–0.850) while the AUCs ranged from 0.798 to 0.829 in the three validation cohorts. Moreover, the POSMI score had a higher AUC than both the SOFA and APACHE IV scores. Notably, the Hosmer–Lemeshow (H–L) goodness-of-fit test results and calibration curves suggested good calibration in the development and validation cohorts. Additionally, the POSMI score still exhibited excellent discrimination and calibration following sensitivity analysis. With regard to clinical usefulness, the decision curve analysis (DCA) of POSMI showed a higher net benefit than SOFA and APACHE IV in the development cohort. Conclusion POSMI was validated to be an effective tool for predicting mortality in ICU patients with sepsis.

Impact of Red Cell and Platelet Distribution Width in Patients of Medical Intensive Care Unit

Introduction The red blood cell distribution width (RDW) is a measurement of variations in the size of red blood cells. As the width increases, the rate of mortality also increases, although the reason for it is still not known. On the other hand, platelet distribution width (PDW) is also useful in predicting morbidity and mortality in sepsis and other critically ill patients. In our study, we planned to study the impact of both RDW and PDW and evaluate their prognostic importance with outcome in patients admitted in medicine intensive care unit (MICU). Material and Method In these cross-sectional observational studies, 1,300 patients were included who were admitted in MICU. Critically ill patients were defined on the basis of qSOFA score greater than 2. PDW and RDW were obtained from Coulter report of complete blood count. Parameters included in Acute Physiology and Chronic Health Evaluation (APACHE) IV scores were taken and APACHE IV score was calculated. Correlation of RDW and PDW with outcomes such as length of ICU stay, use of mechanical ventilator, and discharge/death was done. Result The mean RDW (%) for the entire study population was 15.17 ± 3.01. The RDW (%) was significantly on the higher side in patients who succumbed to the disease as compared with the patients who were discharged. The correlation between the length of ICU stay (days) and RDW (%) was moderately positive and was significant (rho = 0.37, p ≤ 0.001). The correlation between the length of ICU stay (days) and PDW (%) was moderately positive and was significant (rho = 0.5, p ≤ 0.001). Conclusion RDW and PDW were found as significant indicators for period of stay in ICU, requirement for mechanical ventilation, and mortality rate in patients admitted to ICUs. As these are simple, easy to conduct, universally available tests, they can be regularly incorporated in patients admitted in ICUs.

Validation of the Acute Physiology and Chronic Health Evaluation (APACHE) II and IV Score in COVID-19 Patients

Background. Severity scoring systems are inherent to ICU practice for multiple purposes. Acute Physiology and Chronic Health Evaluation (APACHE) scoring systems are designed for ICU mortality prediction. This study aims to validate APACHE IV in COVID-19 patients admitted to the ICU. Methods. All COVID-19 patients admitted to the ICU between March 13, 2020, and October 17, 2020, were retrospectively analyzed. APACHE II and APACHE IV scores as well as SOFA scores were calculated within 24 hours after admission. Discrimination for mortality of all three scoring systems was assessed by receiver operating characteristic curves. Youden index was determined for the scoring system with the best discriminative performance. The Hosmer–Lemeshow goodness-of-fit test was used to assess calibration. All analyses were performed for both the overall population as in a subgroup treated with anti-Xa adjusted dosages of LMWHs. Results. 116 patients were admitted to our ICU during the study period. 13 were excluded for various reasons, leaving 103 patients in the statistical analysis of the overall population. 57 patients were treated with anti-Xa adjusted prophylactic dosages of LMWH and were supplementary analyzed in a subgroup analysis. APACHE IV had the best discriminative power of the three scoring systems, both in the overall population (APACHE IV ROC AUC 0.67 vs. APACHE II ROC AUC 0.63) as in the subgroup (APACHE IV ROC AUC 0.82 vs. APACHE II ROC AUC 0.7). This model exhibits good calibration. Hosmer–Lemeshow p values for APACHE IV were 0.9234 for the overall population and 0.8017 for the subgroup. Calibration p values of the APACHE II score were 0.1394 and 0.6475 for the overall versus subgroup, respectively. Conclusions. APACHE IV provided the best discrimination and calibration of the considered scoring systems in critically ill COVID-19 patients, both in the overall group and in the subgroup with anti-Xa adjusted LMWH doses. Only in the subgroup analysis, discriminative abilities of APACHE IV were very good. This trial is registered with NCT04713852.

Critical Care Utilization and Outcomes of Interhospital Medical Transfers at Lower Risk of Death

Purpose: To evaluate utilization and mortality outcomes of interhospital transferred critically-ill medical patients with lower predicted risk of hospital mortality. Materials & Methods: Multisite retrospective cohort analysis of patients with Acute Physiology and Chronic Health Evaluation (APACHE) IV-a predicted mortality of ≤20% from 335 ICUs in 208 hospitals in the Philips eICU database between 2014-2015. Differences in length-of-stay (LOS) and mortality between transferred and local patients were evaluated using negative binomial logistic regression and logistic regression, respectively. Stratified analyses were conducted for subgroups of predicted mortality: 0%-5%, 6%-10%, 11%-15%, and 16%-20%. Results: Transfers had a higher risk of longer ICU and hospital LOS across all risk strata (IRR 1.12; 95% CI 1.09-1.16, P < 0.001 and IRR 1.11; 95% CI 1.07-1.14, P < 0.001 respectively). Mortality was higher among transfers, largely driven by the 6%-10% mortality risk strata (OR 1.30; 95% CI 1.09-1.54, P = 0.003). Conclusions: Interhospital transfer of critically-ill medical patients with lower illness severity is associated with higher ICU and hospital utilization and increased mortality. Better understanding of factors driving patient selection for and characteristics of interhospital transfer for this population will have an impact on ICU resource utilization, care efficiency, and hospital quality.

Comparison of Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II and IV (APACHE) Scoring System Validity as Mortality Predictors in ICU Patients with Multiple Organ Dysfunction Syndrome in Sepsis

BACKGROUND Multiple organ dysfunction syndrome (MODS) has recently been considered as a defining syndrome of sepsis and is responsible for a high mortality rate among the patients in the intensive care units (ICUs). Prognostication of the ICU patients is an integral part of the management of the critically ill patients and many scoring systems, for that matter, have been devised and compared for their efficiency at predicting mortality. This study was conducted to evaluate and compare the validity of sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE II) and APACHE IV as mortality predictors in intensive care unit (ICU) patients suffering from MODS in sepsis. METHODS Hundred patients diagnosed with MODS in sepsis were carefully examined, followed by relevant laboratory investigations. The SOFA score was calculated daily, and the APACHE II and IV scores were calculated on the day of admission. The scores were further compared among the survivors and the non-survivors, followed by receiver operating characteristic (ROC) curve analysis of the SOFA D1, D2, and D3 and the APACHE II and IV scores to estimate their capability of mortality prediction. RESULTS The means of the APACHE II, IV and SOFA D1 were 16.57 ± 6.49, 71.91 ± 16.19 and 8.75 ± 2.20, respectively. There was a statistically significant difference in the mean APACHE II scores (14.23 ± 5.20 vs. 21.12 ± 6.38) and the mean APACHE IV scores (67.27 ± 13.21 vs. 80.91 ± 17.77) in the survivors and the nonsurvivors. A statistically significant difference was also evident in the mean ages of the survivors and the non-survivors (52.82 ± 14.67 years vs. 63.25 ± 16.98 years). The SOFA score was high among the non-survivors than the survivors right from day-1 (10.24 ± 2.08 vs. 7.98 ± 1.86) to day-20 (15.00 ± 0.00 vs. 3.14 ± 0.38). Furthermore, ROC analysis showed that the best discrimination was provided by SOFA D3 followed by the APACHE II and SOFA D1 scores, with APACHE IV score showing the least. CONCLUSIONS SOFA score on day 3 provides the best mortality prediction in patients with MODS in sepsis, as compared to APACHE II and IV scores. KEYWORDS SOFA, APACHE II, APACHE IV, Multiple Organ Dysfunction Syndrome, Sepsis