The Rothman Index predicts unplanned readmissions to intensive care associated with increased mortality and hospital length of stay: a propensity-matched cohort study.

BACKGROUND: Patients with unplanned readmissions to the intensive care unit (ICU) are at high risk of preventable adverse events. The Rothman Index represents an objective real-time grading system of a patient's clinical condition and a predictive tool of clinical deterioration over time. This study was designed to test the hypothesis that the Rothman Index represents a sensitive predictor of unanticipated ICU readmissions. METHODS: A retrospective propensity-matched cohort study was performed at a tertiary referral academic medical center in the United States from January 1, 2022, to December 31, 2022. Inclusion criteria were adult patients admitted to an ICU and readmitted within seven days of transfer to a lower level of care. The control group consisted of patients who were downgraded from ICU without a subsequent readmission. The primary outcome measure was in-hospital mortality or discharge to hospice for end-of-life care. Secondary outcome measures were overall hospital length of stay, ICU length of stay, and 30-day readmission rates. Propensity matching was used to control for differences between the study cohorts. Regression analyses were performed to determine independent risk factors of an unplanned readmission to ICU. RESULTS: A total of 5,261 ICU patients met the inclusion criteria, of which 212 patients (4%) had an unanticipated readmission to the ICU within 7 days. The study cohort and control group were stratified by propensity matching into equal group sizes of n = 181. Lower Rothman Index scores (reflecting higher physiologic acuity) at the time of downgrade from the ICU were significantly associated with an unplanned readmission to the ICU (p < 0.0001). Patients readmitted to ICU had a lower mean Rothman Index score (p < 0.0001) and significantly increased rates of mortality (19.3% vs. 2.2%, p < 0.0001) and discharge to hospice (14.4% vs. 6.1%, p = 0.0073) compared to the control group of patients without ICU readmission. The overall length of ICU stay (mean 8.0 vs. 2.2 days, p < 0.0001) and total length of hospital stay (mean 15.8 vs. 7.3 days, p < 0.0001) were significantly increased in patients readmitted to ICU, compared to the control group. CONCLUSION: The Rothman Index represents a sensitive predictor of unanticipated readmissions to ICU, associated with a significantly increased mortality and overall ICU and hospital length of stay. The Rothman Index should be considered as a real-time objective measure for prediction of a safe downgrade from ICU to a lower level of care.

Dynamic and Personalized Risk Forecast in Step-Down Units. Implications for Monitoring Paradigms.

RATIONALE: Cardiorespiratory insufficiency (CRI) is a term applied to the manifestations of loss of normal cardiorespiratory reserve and portends a bad outcome. CRI occurs commonly in hospitalized patients, but its risk escalation patterns are unexplored. OBJECTIVES: To describe the dynamic and personal character of CRI risk evolution observed through continuous vital sign monitoring of individual step-down unit patients. METHODS: Using a machine learning model, we estimated risk trends for CRI (defined as exceedance of vital sign stability thresholds) for each of 1,971 admissions (1,880 unique patients) to a 24-bed adult surgical trauma step-down unit at an urban teaching hospital in Pittsburgh, Pennsylvania using continuously recorded vital signs from standard bedside monitors. We compared and contrasted risk trends during initial 4-hour periods after step-down unit admission, and again during the 4 hours immediately before the CRI event, between cases (ever had a CRI) and control subjects (never had a CRI). We further explored heterogeneity of risk escalation patterns during the 4 hours before CRI among cases, comparing personalized to nonpersonalized risk. MEASUREMENTS AND MAIN RESULTS: Estimated risk was significantly higher for cases (918) than control subjects (1,053; P ≤ 0.001) during the initial 4-hour stable periods. Among cases, the aggregated nonpersonalized risk trend increased 2 hours before the CRI, whereas the personalized risk trend became significantly different from control subjects 90 minutes ahead. We further discovered several unique phenotypes of risk escalation patterns among cases for nonpersonalized (14.6% persistently high risk, 18.6% early onset, 66.8% late onset) and personalized risk (7.7% persistently high risk, 8.9% early onset, 83.4% late onset). CONCLUSIONS: Insights from this proof-of-concept analysis may guide design of dynamic and personalized monitoring systems that predict CRI, taking into account the triage and real-time monitoring utility of vital signs. These monitoring systems may prove useful in the dynamic allocation of technological and clinical personnel resources in acute care hospitals.

Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation.

AIMS: Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation. RESULTS: Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25-500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-α and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100-500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets). CONCLUSION: These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted.

Inhaled, nebulized sodium nitrite protects in murine and porcine experimental models of hemorrhagic shock and resuscitation by limiting mitochondrial injury.

OBJECTIVE: The cellular injury that occurs in the setting of hemorrhagic shock and resuscitation (HS/R) affects all tissue types and can drive altered inflammatory responses. Resuscitative adjuncts hold the promise of decreasing such injury. Here we test the hypothesis that sodium nitrite (NaNO2), delivered as a nebulized solution via an inhalational route, protects against injury and inflammation from HS/R. METHODS: Mice underwent HS/R to a mean arterial pressure (MAP) of 20 or 25 mmHg. Mice were resuscitated with Lactated Ringers after 90-120 min of hypotension. Mice were randomized to receive nebulized NaNO2 via a flow through chamber (30 mg in 5 mL PBS). Pigs (30-35 kg) were anesthetized and bled to a MAP of 30-40 mmHg for 90 min, randomized to receive NaNO2 (11 mg in 2.5 mL PBS) nebulized into the ventilator circuit starting 60 min into the hypotensive period, followed by initial resuscitation with Hextend. Pigs had ongoing resuscitation and support for up to four hours. Hemodynamic data were collected continuously. RESULTS: NaNO2 limited organ injury and inflammation in murine hemorrhagic shock. A nitrate/nitrite depleted diet exacerbated organ injury, as well as mortality, and inhaled NaNO2 significantly reversed this effect. Furthermore, NaNO2 limited mitochondrial oxidant injury. In porcine HS/R, NaNO2 had no significant influence on shock induced hemodynamics. NaNO2 limited hypoxia/reoxia or HS/R-induced mitochondrial injury and promoted mitochondrial fusion. CONCLUSION: NaNO2 may be a useful adjunct to shock resuscitation based on its limitation of mitochondrial injury.

Effects of inhalation of low-dose nitrite or carbon monoxide on post-reperfusion mitochondrial function and tissue injury in hemorrhagic shock swine.

INTRODUCTION: Tissue reperfusion following hemorrhagic shock may paradoxically cause tissue injury and organ dysfunction by mitochondrial free radical expression. Both nitrite and carbon monoxide (CO) may protect from this reperfusion injury by limiting mitochondrial free radial production. We explored the effects of very small doses of inhaled nitrite and CO on tissue injury in a porcine model of hemorrhagic shock. METHODS: Twenty pigs (mean wt. 30.6 kg, range 27.2 to 36.4 kg) had microdialysis catheters inserted in muscle, peritoneum, and liver to measure lactate, pyruvate, glucose, glycerol, and nitrite. Nineteen of the pigs were bled at a rate of 20 ml/min to a mean arterial pressure of 30 mmHg and kept between 30 and 40 mmHg for 90 minutes and then resuscitated. One pig was instrumented but not bled (sham). Hemorrhaged animals were randomized to inhale nothing (control, n = 7), 11 mg nitrite (nitrite, n = 7) or 250 ppm CO (CO, n = 5) over 30 minutes before fluid resuscitation. Mitochondrial respiratory control ratio was measured in muscle biopsies. Repeated measures from microdialysis catheters were analyzed in a random effects mixed model. RESULTS: Neither nitrite nor CO had any effects on the measured hemodynamic variables. Following inhalation of nitrite, plasma, but not tissue, nitrite increased. Following reperfusion, plasma nitrite only increased in the control and CO groups. Thereafter, nitrite decreased only in the nitrite group. Inhalation of nitrite was associated with decreases in blood lactate, whereas both nitrite and CO were associated with decreases in glycerol release into peritoneal fluid. Following resuscitation, the muscular mitochondrial respiratory control ratio was reduced in the control group but preserved in the nitrite and CO groups. CONCLUSIONS: We conclude that small doses of nebulized sodium nitrite or inhaled CO may be associated with intestinal protection during resuscitation from severe hemorrhagic shock.

Effect of acute endotoxemia on analog estimates of mean systemic pressure.

Dynamic estimates of mean systemic pressure based on a Guytonian analog model (Pmsa) appear accurate under baseline conditions but may not remain so during septic shock because blood volume distribution and resistances between arterial and venous beds may change. Thus, we examined the effect of acute endotoxemia on the ability of Pmsa, estimated from steady-state cardiac output, right atrial pressure, and mean arterial pressure, to reflect our previously validated instantaneous venous return measure of mean systemic pressure (Pmsi), derived from beat-to-beat measures of right ventricular stroke volume and right atrial pressure during positive pressure ventilation. We studied 6 splenectomized pentobarbital-anesthetized close chested dogs. Right ventricular stroke volume was measured by a pulmonary arterial electromagnetic flow probe. Instantaneous venous return measure of mean systemic pressure and Pmsa were calculated during volume loading and removal (±100-mL bolus increments×5) both before (control) and 30 minutes after endotoxin infusion (endo). Cardiac output increased (2628±905 vs 3560±539 mL/min; P<.05) and mean arterial pressure decreased (107±16 vs 56±12 mm Hg; P<.01) during endo. Changes in Pmsi and Pmsa correlated during both control and endo (r2=0.7) with minimal bias by Bland-Altman analysis (mean difference±95% confidence interval, 0.47±5.04 mm Hg). We conclude that changes in Pmsa accurately tracts Pmsi under both control and endo.