Recent Trends in Admission Diagnosis and Related Mortality in the Medically Critically Ill.

PURPOSE: With decades of declining ICU mortality, we hypothesized that the outcomes and distribution of diseases cared for in the ICU have changed and we aimed to further characterize them. STUDY DESIGN AND METHODS: A retrospective cohort analysis of 287,154 nonsurgical-critically ill adults, from 237 U.S. ICUs, using the manually abstracted Cerner APACHE Outcomes database from 2008 to 2016 was performed. Surgical patients, rare admission diagnoses (<100 occurrences), and low volume hospitals (<100 total admissions) were excluded. Diagnoses were distributed into mutually exclusive organ system/disease-based categories based on admission diagnosis. Multi-level mixed-effects negative binomial regression was used to assess temporal trends in admission, in-hospital mortality, and length of stay (LOS). RESULTS: The number of ICU admissions remained unchanged (IRR 0.99, 0.98-1.003) while certain organ system/disease groups increased (toxicology [25%], hematologic/oncologic [55%] while others decreased (gastrointestinal [31%], pulmonary [24%]). Overall risk-adjusted in-hospital mortality was unchanged (IRR 0.98, 0.96-1.0004). Risk-adjusted ICU LOS (Estimate -0.06 days/year, -0.07 to -0.04) decreased. Risk-adjusted mortality varied significantly by disease. CONCLUSION: Risk-adjusted ICU mortality rate did not change over the study period, but there was evidence of shifting disease burden across the critical care population. Our data provides useful information regarding future ICU personnel and resource needs.

National Trends and Variation of Functional Status Deterioration in the Medically Critically Ill.

OBJECTIVES: Physical and psychologic deficits after an ICU admission are associated with lower quality of life, higher mortality, and resource utilization. This study aimed to examine the prevalence and secular changes of functional status deterioration during hospitalization among nonsurgical critical illness survivors over the past decade. DESIGN: We performed a retrospective longitudinal cohort analysis. SETTING: Analysis performed using the Cerner Acute Physiology and Chronic Health Evaluation outcomes database which included manually abstracted data from 236 U.S. hospitals from 2008 to 2016. PATIENTS: We included nonsurgical adult ICU patients who survived their hospitalization and had a functional status documented at ICU admission and hospital discharge. Physical functional status was categorized as fully independent, partially dependent, or fully dependent. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional status deterioration occurred in 38,116 patients (29.3%). During the past decade, functional status deterioration increased in each disease category, as well as overall (prevalence rate ratio, 1.15; 95% CI, 1.13-1.17; p < 0.001). Magnitude of functional status deterioration also increased over time (odds ratio, 1.03; 95% CI, 1.03-1.03; p < 0.001) with hematological, sepsis, neurologic, and pulmonary disease categories having the highest odds of severe functional status deterioration. CONCLUSIONS: Following nonsurgical critical illness, the prevalence of functional status deterioration and magnitude increased in a nationally representative cohort, despite efforts to reduce ICU dysfunction over the past decade. Identifying the prevalence of functional status deterioration and primary etiologies associated with functional status deterioration will elucidate vital areas for further research and targeted interventions. Reducing ICU debilitation for key disease processes may improve ICU survivor mortality, enhance quality of life, and decrease healthcare utilization.

Respiratory Tract Colonization by Candida species Portends Worse Outcomes in Immunocompromised Patients.

BACKGROUND: The significance and clinical management of Candida colonization of the respiratory tract are ill-defined. We now report the frequency of Candida species from the lower respiratory tract in hematopoietic stem cell transplant recipients (HSCT) undergoing bronchoscopy with broncheoalveolar lavage (BAL) for pneumonitis post-HSCT. METHODS: The University of Michigan Clinical Microbiology Lab Database was queried for all respiratory cultures positive for Candida species between 2000-2012. We concurrently performed a retrospective analysis of 515 HSCT recipients with pneumonitis at our institution between 2001-2012. RESULTS: During this twelve-year period, there were 2524 unique Candida isolates (78% Candida albicans). Of the 515 HSCT patients with suspected pneumonitis,127 (24.7%) HSCT subjects were culture positive for a fungal pathogen, with Candida species identified in 27 cases (5.2%). When compared with other HSCT subjects, those cultures positive for Candida had significantly increased mortality (p=0.04). CONCLUSIONS: Candida sp. are commonly cultured from the respiratory tract of HSCT recipients, with increased mortality in affected patients. While there is insufficient evidence for anti-fungal treatment of Candida species colonization, the presence of the yeast may be useful as a surrogate marker of disease severity.

High PEEP extubation as guided by esophageal manometry.

The ventilatory management of morbidly obese patients presents an ongoing challenge in the Intensive Care Unit (ICU) as multiple physiologic changes in the respiratory system complicate weaning efforts and make extubation more difficult, often leading to increased time on the ventilator. We report the case of a young adult male who presented to our ICU on two separate occasions with hypoxemic respiratory failure requiring intubation. Esophageal manometry (EM) guided positive end expiratory pressure (PEEP) titration was utilized during both ICU admissions to improve oxygenation and aid in extubation with spontaneous breathing trials performed on higher-than-normal PEEP settings and successful liberation on both occasions.

Patient Outcomes and Unit Composition With Transition to a High-Intensity ICU Staffing Model: A Before-and-After Study.

Provider staffing models for ICUs are generally based on pragmatic necessities and historical norms at individual institutions. A better understanding of the role that provider staffing models play in determining patient outcomes and optimizing use of ICU resources is needed. OBJECTIVES: To explore the impact of transitioning from a low- to high-intensity intensivist staffing model on patient outcomes and unit composition. DESIGN SETTING AND PARTICIPANTS: This was a prospective observational before-and-after study of adult ICU patients admitted to a single community hospital ICU before (October 2016-May 2017) and after (June 2017-November 2017) the transition to a high-intensity ICU staffing model. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause mortality. Secondary outcomes included in-hospital mortality, ICU length of stay (LOS), and unit composition characteristics including type (e.g., medical, surgical) and purpose (ICU-specific intervention vs close monitoring only) of admission. RESULTS: For the primary outcome, 1,219 subjects were included (779 low-intensity, 440 high-intensity). In multivariable analysis, the transition to a high-intensity staffing model was not associated with a decrease in 30-day (odds ratio [OR], 0.90; 95% CI, 0.61-1.34; p = 0.62) or in-hospital (OR, 0.89; 95% CI, 0.57-1.38; p = 0.60) mortality, nor ICU LOS. However, the proportion of patients admitted to the ICU without an ICU-specific need did decrease under the high-intensity staffing model (27.2% low-intensity to 17.5% high-intensity; p < 0.001). CONCLUSIONS AND RELEVANCE: Multivariable analysis showed no association between transition to a high-intensity ICU staffing model and mortality or LOS outcomes; however, the proportion of patients admitted without an ICU-specific need decreased under the high-intensity model. Further research is needed to determine whether a high-intensity staffing model may lead to more efficient ICU bed usage.

Successful hemostasis in refractory alveolar hemorrhage using low-dose recombinant activated factor VII.

Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring prompt recognition. Conventional therapy, even when initiated early, may not have an immediate effect, and in severe cases, bleeding can persist despite treatment. We report the case of a previously healthy 33-year-old male who developed DAH secondary to granulomatosis with polyangiitis, resulting in respiratory failure and the need for mechanical ventilation. High-dose corticosteroids, plasma exchange, and remission induction with cyclophosphamide failed to control bleeding, leading to severely impaired gas exchange. 20 mcg/kg of systemic recombinant activated Factor VII (rFVIIa), a dose lower than previously reported for management of DAH, resulted in hemostasis and improved oxygenation after only three doses. No complications were observed, and our patient was liberated from ventilatory support eight days later. In the setting of DAH with refractory bleeding, hemostasis may be achievable with a lower dose of rFVIIa than commonly used, potentially mitigating the risk of dose-dependent side effects.

Factors Associated with Mortality in Patients with COVID-19 Receiving Prolonged Ventilatory Support.

Background: Since its emergence in early 2020, coronavirus disease 2019 (COVID-19)-associated pneumonia has caused a global strain on intensive care unit (ICU) resources with many intubated patients requiring prolonged ventilatory support. Outcomes for patients with COVID-19 who receive prolonged intubation (>21 days) and possible predictors of mortality in this group are not well established. Patients and Methods: Data were prospectively collected from adult patients with COVID-19 requiring mechanical ventilation from March 2020 through December 2021 across a system of 11 hospitals. The primary end point was in-hospital mortality. Factors associated with mortality were evaluated using univariable and multivariable logistic regression analyses. Results: Six hundred six patients were placed on mechanical ventilation for COVID-19 pneumonia during the study period, with in-hospital mortality of 40.3% (n = 244). Increased age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.03-1.09), increased creatinine (OR, 1.40; 95% CI, 1.08-1.82), and receiving corticosteroids (OR, 2.68; 95% CI, 1.20-5.98) were associated with mortality. Intubations lasting longer than 21 days (n = 140) had a lower in-hospital mortality of 25.7% (n = 36; p < 0.001). Increasing Elixhauser comorbidity index (OR, 1.12; 95% CI, 1.04-1.19) and receiving corticosteroids (OR, 1.92; 95% CI, 1.06-3.47) were associated with need for prolonged ventilation. In this group, increased age (OR, 1.06; 95% CI, 1.01-1.08) and non-English speaking (OR, 3.74; 95% CI, 1.13-12.3) were associated with mortality. Conclusions: In-hospital mortality in mechanically ventilated patients with COVID-19 pneumonia occurs primarily in the first 21 days after intubation, possibly related to the early active inflammatory process. In patients on prolonged mechanical ventilation, increased age and being non-English speaking were associated with mortality.

Ketamine Infusion for Sedation and Analgesia during Mechanical Ventilation in the ICU: A Multicenter Evaluation.

Methods: We reviewed the electronic medical record of critically ill adults who received a continuous infusion of ketamine for ≥24 hours during invasive mechanical ventilation in three hospitals over a two-year period. We captured data including ketamine indication, dose, unintended effects, and adjustments to coadministered sedatives or opioids. We analyzed these data to determine the incidence of reported unintended effects of ketamine infusion (primary outcome) and changes in exposure to coadministered sedatives or opioids during ketamine use (secondary outcome). Results: 95 mechanically ventilated adults received a ketamine infusion for a median duration of 75 hours (interquartile range [IQR] 44-115) at a mean ± standard deviation (SD) infusion rate of 1.3 ± 0.5 mg/kg/hour for the first 24 hours. At least one unintended effect attributed to ketamine was documented in 24% of cases, most frequently tachycardia (6%) and sialorrhea (6%). Other sedative or opioid infusions were administered with ketamine in 76% and 92% of cases, respectively. Comparing the total amount of sedative or opioid administered in the 24 hours prior to ketamine infusion with the total amount administered during the first 24 hours on ketamine, there were no significant differences in propofol, midazolam, or dexmedetomidine exposure, but the average fentanyl exposure was higher after ketamine (2740 ± 1812 mcg) than before (1975 ± 1860 mcg) (absolute difference 766 mcg, 95% confidence interval [CI] 442 to 1089 mcg). Conclusions: In this multicenter cohort of critically ill, mechanically ventilated adults, ketamine infusion was primarily used as an adjunct to conventional sedative and opioid infusions, with noticeable but unintended effects potentially related to ketamine in nearly one-quarter of cases.

Benefits of collaborative patient care rounds in the intensive care unit.

BACKGROUND: Improving care of critically ill patients requires using an interprofessional care model and care standardisation. OBJECTIVES: Determine whether collaborative patient care rounds in the intensive care unit increases practice consistency with respect to common considerations such as delirium prevention, device use, and indicated prophylaxis, among others. Secondary objective to assess whether collaborative interprofessional format improved nursing perceptions of collaboration. METHODS: Single centre, pre- and post- intervention design. collaborative patient care rounding format implemented in three intensive care units in an academic tertiary care centre. format consisted of scripted nursing presentation, provider checklist of additional practice considerations, and daily priority goals documentation. measurements included nursing participation, consideration of selected practice items, daily goal verbalisation, and nursing perception of collaboration. RESULTS: Pre- and post-intervention measurements indicate gains in consideration of eight of thirteen bundle items (p < 0.05), with the greatest gains seen in nurse-presented items. Increases were observed in verbalisation of daily goals (59.8% versus 89.1%, p < 0.0001), nurse participation (83.9% versus 91.8%, p = 0.056), and nurse collaboration ratings (p < 0.0001). CONCLUSION: This study describes implementation of collaborative patient care rounds with corresponding increases in consideration of selected practice items, verbalisation of daily goals, and perceptions of collaboration.

Discordant Cardiopulmonary Resuscitation and Code Status at Death.

CONTEXT: One fundamental way to honor patient autonomy is to establish and enact their wishes for end-of-life care. Limited research exists regarding adherence with code status. OBJECTIVES: This study aimed to characterize cardiopulmonary resuscitation (CPR) attempts discordant with documented code status at the time of death in the U.S. and to elucidate potential contributing factors. METHODS: The Cerner Acute Physiology and Chronic Health Evaluation (APACHE) outcomes database, which includes 237 U.S. hospitals that collect manually abstracted data from all critical care patients, was queried for adults admitted to intensive care units with a documented code status at the time of death from January 2008 to December 2016. The primary outcome was discordant CPR at death. Multivariable logistic regression models were used to identify patient-level and hospital-level associated factors after adjustment for age, hospital, and illness severity (APACHE III score). RESULTS: A total of 21,537 patients from 56 hospitals were included. Of patients with a do-not-resuscitate code status, 149 (0.8%) received CPR at death, and associated factors included black race, higher APACHE III score, or treatment in small or nonteaching hospitals. Of patients with a full code status, 203 (9.0%) did not receive CPR at death, and associated factors included higher APACHE III score, primary neurologic or trauma diagnosis, or admission in a more recent year. CONCLUSION: At the time of death, 1.6% of patients received or did not undergo CPR in a manner discordant with their documented code statuses. Race and institutional factors were associated with discordant resuscitation, and addressing these disparities may promote concordant end-of-life care in all patients.

Morbidity and Mortality Trends of Pancreatitis: An Observational Study.

Background: Pancreatitis accounts for more than $2.5 billion of healthcare costs and remains the most common gastrointestinal (GI) admission. Few contemporary studies have assessed temporal trends of incidence, complications, management, and outcomes for acute pancreatitis in hospitalized patients at the national level. Methods: We used data from one of the largest hospital-based databases available in the United States, the Healthcare Cost and Utilization Project's (HCUP) State Inpatient Database, from 10 states between 2008 and 2015. We included patients with a diagnosis of acute pancreatitis (ICD-9 CM 577.0). Patient- and hospital-level data were used to estimate incidence and inpatient mortality rates. Results: From 80,736,256 hospitalizations, 929,914 (1.15%) cases of acute pancreatitis were identified, 186,226 (20.2%) of which were caused by gallbladder disease). The median age was 53 years (interquartile range [IQR], 41-67) and 50.8% were men. In-hospital mortality was 2.5% and crude mortality rates declined from 2.9% to 2.0% over the study period. Admission year remained significant after adjusting for patient demographics and comorbidities (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.89-0.90; p < 0.001). Gallbladder disease was associated with decreased odds of mortality (OR, 0.60; 95% CI, 0.57-0.62). Median length of stay was four days (IQR, 2-7) and decreased over time. The rates of surgical and endoscopic interventions were highest in 2011 (peak incidence of 16.1% and 9.5%, respectively) and have been decreasing since. Surgical providers were, on average, more likely than medical providers to perform surgery in both those with and without gallbladder disease etiology (gallbladder disease OR, 7.11; 95% CI, 5.46-9.25; non-gallbladder disease OR, 20.50; 95% CI, 16.81-25.01), endoscopy (gallbladder disease OR, 1.22; 95% CI, 0.87-1.72; non-gallbladder disease OR, 1.60; 95% CI, 1.18-2.16), or both (gallbladder disease OR, 7.00; 95% CI, 5.22-9.37; non-gallbladder disease OR, 8.85; 95% CI, 5.61-13.96). Conclusions: The incidence of pancreatitis, from 2008 to 2015, has increased whereas inpatient mortality (i.e., case fatality) has decreased. Understanding temporal trends in outcomes and management along with provider, hospital, and regional variation can better identify areas for future research and collaboration in managing these patients.

Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis.

BACKGROUND: Type 2 diabetes and obesity, as states of chronic inflammation, are risk factors for severe COVID-19. Metformin has cytokine-reducing and sex-specific immunomodulatory effects. Our aim was to identify whether metformin reduced COVID-19-related mortality and whether sex-specific interactions exist. METHODS: In this retrospective cohort analysis, we assessed de-identified claims data from UnitedHealth Group (UHG)'s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged 18 years or older; had type 2 diabetes or obesity (defined based on claims); at least 6 months of continuous enrolment in 2019; and admission to hospital for COVID-19 confirmed by PCR, manual chart review by UHG, or reported from the hospital to UHG. The primary outcome was in-hospital mortality from COVID-19. The independent variable of interest was home metformin use, defined as more than 90 days of claims during the year before admission to hospital. Covariates were comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. For the Cox proportional hazards, censoring was done on the basis of claims made after admission to hospital up to June 7, 2020, with a best outcome approach. Propensity-matched mixed-effects logistic regression was done, stratified by metformin use. FINDINGS: 6256 of the 15 380 individuals with pharmacy claims data from Jan 1 to June 7, 2020 were eligible for inclusion. 3302 (52·8%) of 6256 were women. Metformin use was not associated with significantly decreased mortality in the overall sample of men and women by either Cox proportional hazards stratified model (hazard ratio [HR] 0·887 [95% CI 0·782-1·008]) or propensity matching (odds ratio [OR] 0·912 [95% CI 0·777-1·071], p=0·15). Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0·785, 95% CI 0·650-0·951) and propensity matching (OR 0·759, 95% CI 0·601-0·960, p=0·021). There was no significant reduction in mortality among men (HR 0·957, 95% CI 0·82-1·14; p=0·689 by Cox proportional hazards). INTERPRETATION: Metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive. FUNDING: National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Patient-Centered Outcomes Research Institute; Minnesota Learning Health System Mentored Training Program, M Health Fairview Institutional Funds; National Center for Advancing Translational Sciences; and National Cancer Institute.

The Oral-Lung Axis: The Impact of Oral Health on Lung Health.

Poor oral health has long been recognized as a clinical risk factor for developing lung infections. Recent data using culture-independent techniques assessing the microbiome in healthy subjects have demonstrated that chronic microaspiration establishes a very similar microbial community between the mouth and lung, suggesting these 2 anatomic regions are closely intertwined. Dental disease is driven and aided by a dysbiosis in the oral microbiome, and evidence is mounting that implicates the microbiome in a variety of lung diseases including asthma, COPD, pulmonary fibrosis, and pneumonia. This review describes common dental conditions and potential mechanisms by which poor oral health may contribute to lung disease. We also review the current literature drawing associations between poor oral health and lung disease.

Epidemiological trends of surgical admissions to the intensive care unit in the United States.

BACKGROUND: Epidemiologic assessment of surgical admissions into intensive care units (ICUs) provides a framework to evaluate health care system efficiency and project future health care needs. METHODS: We performed a 9-year (2008-2016), retrospective, cohort analysis of all adult admissions to 88 surgical ICUs using the prospectively and manually abstracted Cerner Acute Physiology and Chronic Health Evaluation Outcomes database. We stratified patients into 13 surgical cohorts and modeled temporal trends in admission, mortality, surgical ICU length of stay (LOS), and change in functional status (FS) using generalized mixed-effects and Quasi-Poisson models to obtain risk-adjusted outcomes. RESULTS: We evaluated 78,053 ICU admissions and observed a significant decrease in admissions after transplant and thoracic surgery, with a concomitant increase in admissions after otolaryngological and facial reconstructive procedures (all p < 0.05). While overall risk-adjusted mortality remained stable over the study period; mortality significantly declined in orthopedic, cardiac, urologic, and neurosurgical patients (all p < 0.05). Cardiac, urologic, gastrointestinal, neurosurgical, and orthopedic admissions showed significant reductions in LOS (all p < 0.05). The overall rate of FS deterioration increased per year, suggesting ICU-related disability increased over the study period. CONCLUSION: Temporal analysis demonstrates a significant change in the type of surgical patients admitted to the ICU over the last decade, with decreasing mortality and LOS in selected cohorts, but an increasing rate of FS deterioration. Improvement in ICU outcomes may highlight the success of health care advancements within certain surgical cohorts, while simultaneously identifying cohorts that may benefit from future intervention. Our findings have significant implications in health care systems planning, including resource and personnel allocation, education, and surgical training. LEVEL OF EVIDENCE: Economic/decision, level IV.Epidemiologic, level IV.

Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19.

Background Type 2 diabetes (T2DM) and obesity are significant risks for mortality in Covid19. Metformin has been hypothesized as a treatment for COVID19. Metformin has sex specific immunomodulatory effects which may elucidate treatment mechanisms in COVID-19. In this study we sought to identify whether metformin reduced mortality from Covid19 and if sex specific interactions exist. Methods De-identified claims data from UnitedHealth were used to identify persons with at least 6 months continuous coverage who were hospitalized with Covid-19. Persons in the metformin group had at least 90 days of metformin claims in the 12 months before hospitalization. Unadjusted and multivariate models were conducted to assess risk of mortality based on metformin as a home medication in individuals with T2DM and obesity, controlling for pre-morbid conditions, medications, demographics, and state. Heterogeneity of effect was assessed by sex. Results 6,256 persons were included; 52.8% female; mean age 75 years. Metformin was associated with decreased mortality in women by logistic regression, OR 0.792 (0.640, 0.979); mixed effects OR 0.780 (0.631, 0.965); Cox proportional-hazards: HR 0.785 (0.650, 0.951); and propensity matching, OR of 0.759 (0.601, 0.960). TNF-alpha inhibitors were associated with decreased mortality in the 38 persons taking them, by propensity matching, OR 0.19 (0.0378, 0.983). Conclusions Metformin was significantly associated with reduced mortality in women with obesity or T2DM in observational analyses of claims data from individuals hospitalized with Covid-19. This sex-specific finding is consistent with metformin reducing TNF-alpha in females over males, and suggests that metformin conveys protection in Covid-19 through TNF-alpha effects. Prospective studies are needed to understand mechanism and causality.

The significance of Candida in the human respiratory tract: our evolving understanding.

Candida is an opportunistic pathogen and the most commonly isolated fungal genus in humans. Though Candida is often detected in respiratory specimens from humans with and without lung disease, its significance remains undetermined. While historically considered a commensal organism with low virulence potential, the status of Candida as an innocent bystander has recently been called into question by both clinical observations and animal experimentation. We here review what is currently known and yet to be determined about the clinical, microbiological and pathophysiological significance of the detection of Candida spp. in the human respiratory tract.