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IMPORTANCE: Physical functional impairment is one of three components of postintensive care syndrome (PICS) that affects up to 60% of ICU survivors. OBJECTIVES: To explore the prevalence of objective physical functional impairment among a diverse cohort of ICU survivors, both at discharge and longitudinally, and to highlight sociodemographic factors that might be associated with the presence of objective physical functional impairment. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of 37 patients admitted to the ICU in New Orleans, Louisiana, and Denver, Colorado between 2016 and 2019 who survived with longitudinal follow-up data. MAIN OUTCOMES AND MEASURES: Our primary outcome of physical functional impairment was defined by handgrip strength and the short physical performance battery. We explored associations between functional impairment and sociodemographic factors that included race/ethnicity, sex, primary language, education status, and medical comorbidities. RESULTS: More than 75% of ICU survivors were affected by physical functional impairment at discharge and longitudinally at 3- to 6-month follow-up. We did not see a significant difference in the proportion of patients with physical functional impairment by race/ethnicity, primary language, or education status. Impairment was relatively higher in the follow-up period among women, compared with men, and those with comorbidities. Among 18 patients with scores at both time points, White patients demonstrated greater change in handgrip strength than non-White patients. Four non-White patients demonstrated diminished handgrip strength between discharge and follow-up. CONCLUSIONS AND RELEVANCE: In this exploratory analysis, we saw that the prevalence of objective physical functional impairment among ICU survivors was high and persisted after hospital discharge. Our findings suggest a possible relationship between race/ethnicity and physical functional impairment. These exploratory findings may inform future investigations to evaluate the impact of sociodemographic factors on functional recovery.
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Unidades de Terapia Intensiva , Sobreviventes , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Unidades de Terapia Intensiva/estatística & dados numéricos , Sobreviventes/estatística & dados numéricos , Idoso , Fatores Sociodemográficos , Força da Mão/fisiologia , Estudos Longitudinais , Desempenho Físico Funcional , Colorado/epidemiologia , Adulto , Alta do Paciente/estatística & dados numéricos , Louisiana/epidemiologia , Estado TerminalRESUMO
BACKGROUND: Alcohol misuse is overlooked frequently in hospitalized patients, but is common among patients with pneumonia and acute hypoxic respiratory failure. Investigations in hospitalized patients rely heavily on self-report surveys or chart abstraction, which lack sensitivity. Therefore, our understanding of the prevalence of alcohol misuse before and during the COVID-19 pandemic is limited. RESEARCH QUESTION: In critically ill patients with respiratory failure, did the proportion of patients with alcohol misuse, defined by the direct biomarker phosphatidylethanol, vary over a period including the COVID-19 pandemic? STUDY DESIGN AND METHODS: Patients with acute hypoxic respiratory failure receiving mechanical ventilation were enrolled prospectively from 2015 through 2019 (before the pandemic) and from 2020 through 2022 (during the pandemic). Alcohol use data, including Alcohol Use Disorders Identification Test (AUDIT)-C scores, were collected from electronic health records, and phosphatidylethanol presence was assessed at ICU admission. The relationship between clinical variables and phosphatidylethanol values was examined using multivariable ordinal regression. Dichotomized phosphatidylethanol values (≥ 25 ng/mL) defining alcohol misuse were compared with AUDIT-C scores signifying misuse before and during the pandemic, and correlations between log-transformed phosphatidylethanol levels and AUDIT-C scores were evaluated and compared by era. Multiple imputation by chained equations was used to handle missing phosphatidylethanol data. RESULTS: Compared with patients enrolled before the pandemic (n = 144), patients in the pandemic cohort (n = 92) included a substantially higher proportion with phosphatidylethanol-defined alcohol misuse (38% vs 90%; P < .001). In adjusted models, absence of diabetes, positive results for COVID-19, and enrollment during the pandemic each were associated with higher phosphatidylethanol values. The correlation between health care worker-recorded AUDIT-C score and phosphatidylethanol level was significantly lower during the pandemic. INTERPRETATION: The higher prevalence of phosphatidylethanol-defined alcohol misuse during the pandemic suggests that alcohol consumption increased during this period, identifying alcohol misuse as a potential risk factor for severe COVID-19-associated respiratory failure. Results also suggest that AUDIT-C score may be less useful in characterizing alcohol consumption during high clinical capacity.
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OBJECTIVES: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death. DESIGN: A retrospective multicenter cohort study. SETTING: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States. PATIENTS: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40). CONCLUSIONS: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice.
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Hipnóticos e Sedativos , Ventilação não Invasiva , Humanos , Ventilação não Invasiva/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estados Unidos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Insuficiência Respiratória/terapia , Insuficiência Respiratória/mortalidade , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Adulto , Analgesia/métodos , Analgesia/estatística & dados numéricos , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/mortalidade , Benzodiazepinas/uso terapêutico , Benzodiazepinas/administração & dosagemRESUMO
Alcohol misuse has been associated with increased morbidity in the setting of pulmonary infections, including the need for critical care resource utilization and development of delirium. How alcohol misuse impacts morbidity and outcomes among patients admitted with COVID-19 pneumonia is not well described. We sought to determine if alcohol misuse was associated with an increased need for critical care resources and development of delirium among patients hospitalized with COVID-19 pneumonia. DESIGN: Retrospective cohort study. SETTING: Twelve University of Colorado hospitals between March 2020 and April 2021. PATIENTS: Adults with a COVID-19 diagnosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was admission to the ICU. Secondary outcomes included need for mechanical ventilation, development of delirium, and in-hospital mortality. Alcohol misuse was defined by International Classification of Diseases, 10th Revision codes. Of 5,979 patients hospitalized with COVID-19, 26% required ICU admission and 15.4% required mechanical ventilation. Delirium developed in 4.5% and 10.5% died during hospitalization. Alcohol misuse was identified in 4%. In analyses adjusted for age, sex, body mass index, diabetes, and liver disease, alcohol misuse was associated with increased odds of ICU admission (adjusted odds ratio [aOR], 1.46; p < 0.01), mechanical ventilation (aOR, 1.43; p = 0.03), and delirium (aOR, 5.55; p < 0.01) compared with patients without misuse. Mortality rates were not associated with alcohol misuse alone, although the presence of both alcohol misuse and in-hospital delirium significantly increased odds of in-hospital death (aOR, 2.60; p = 0.04). CONCLUSIONS: Among patients hospitalized with COVID-19, alcohol misuse was associated with increased utilization of critical care resources including ICU admission and mechanical ventilation. Delirium was an important modifiable risk factor associated with worse outcomes in hospitalized patients with alcohol misuse, including increased odds of death.
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BACKGROUND: Asthma exacerbations with respiratory failure (AERF) are associated with hospital mortality of 7% to 15%. Extracorporeal membrane oxygenation (ECMO) has been used as a salvage therapy for refractory AERF, but controlled studies showing its association with mortality have not been performed. RESEARCH QUESTION: Is treatment with ECMO associated with lower mortality in refractory AERF compared with standard care? STUDY DESIGN AND METHODS: This is a retrospective, epidemiologic, observational cohort study using a national, administrative data set from 2010 to 2020 that includes 25% of US hospitalizations. People were included if they were admitted to an ECMO-capable hospital with an asthma exacerbation, and were treated with short-acting bronchodilators, systemic corticosteroids, and invasive ventilation. People were excluded for age < 18 years, no ICU stay, nonasthma chronic lung disease, COVID-19, or multiple admissions. The main exposure was ECMO vs No ECMO. The primary outcome was hospital mortality. Key secondary outcomes were ICU length of stay (LOS), hospital LOS, time receiving invasive ventilation, and total hospital costs. RESULTS: The study analyzed 13,714 patients with AERF, including 127 with ECMO and 13,587 with No ECMO. ECMO was associated with reduced mortality in the covariate-adjusted (OR, 0.33; 95% CI, 0.17-0.64; P = .001), propensity score-adjusted (OR, 0.36; 95% CI, 0.16-0.81; P = .01), and propensity score-matched models (OR, 0.48; 95% CI, 0.24-0.98; P = .04) vs No ECMO. Sensitivity analyses showed that mortality reduction related to ECMO ranged from OR 0.34 to 0.61. ECMO was also associated with increased hospital costs in all three models (P < .0001 for all) vs No ECMO, but not with decreased ICU LOS, hospital LOS, or time receiving invasive ventilation. INTERPRETATION: ECMO was associated with lower mortality and higher hospital costs, suggesting that it may be an important salvage therapy for refractory AERF following confirmatory clinical trials.
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Asma , COVID-19 , Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Humanos , Adolescente , Estudos Retrospectivos , Asma/complicações , Asma/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Resultado do TratamentoRESUMO
Colorado issued a month long statewide lockdown on March 26, 2020, during the initial surge of the COVID-19 pandemic. The impact of this mandate on non-COVID-19 ICU admission rates and outcomes is unclear. DESIGN: We performed a retrospective analysis of all medical ICU admissions in the University of Colorado Health System in four predefined periods: 1) prepandemic (2 mo prior to lockdown period 1); 2) mandated lockdown from March 26 to April 26, 2020 (period 2); 3) between surges (period 3); and 4) nonmandated lockdown surge (between November 1, 2020, and March 31, 2021, period 4). SETTING: Nonsurgical ICU admissions at the University of Colorado Health Systems, including 10 hospitals throughout Colorado. SUBJECTS: All ICU admissions in four predefined time periods. MEASUREMENTS AND MAIN RESULTS: We included 13,787 patients who were admitted during the four study periods. The 28-day mortality rates for non-COVID-19 ICU admissions following index ICU admission were 13.6%, 18.0%, 13.5%, and 16.0% across periods 1-4, respectively. However, the increased odds in non-COVID-19 ICU mortality during the mandated lockdown period relative to prepandemic 1 (odds ratio [OR], 1.39; 95% CI, 1.11-1.72; p = 0.0.04) was attenuated and nonsignificant after adjustment for demographics, comorbidities, diagnosis flags, and severity (OR, 1.15; 95% CI, 0.89-1.48; p = 0.27). Similar results were found in time-to-event analyses. The most common diagnosis in each time period was acute respiratory failure (ARF), and we found it to have increased during lockdown (p < 0.001), whereas sepsis admissions increased during and decreased after lockdown (p = 0.004). Admissions for alcohol withdrawal syndrome (AWS) increased during lockdown and 6 months afterwards (p = 0.005). CONCLUSIONS: For non-COVID-19-related ICU admissions, mortality rate was similar before, during, and after Colorado's month long lockdown after confounder adjustment, including typical ICU admission flags. Primary admission diagnoses shifted throughout the predefined study periods with more admissions for severe critical diagnoses (i.e., ARF, sepsis, AWS) occurring during the mandated lockdown and nonmandated lockdown periods compared with the prepandemic and between surge period. This would suggest that the perceived increase in mortality during the lockdown for non-COVID-19 ICU admissions may be related to a shift inpatient demographics.
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OBJECTIVES: Recent evidence suggests that half-dose thrombolysis for pulmonary embolism may provide similar efficacy with reduced bleeding risk compared with full-dose therapy, but comparative studies are lacking. We aimed to evaluate the effectiveness and safety of half-dose versus full-dose alteplase for treatment of pulmonary embolism. DESIGN: A retrospective cohort study comparing outcomes in patients receiving half-dose (50 mg) versus full-dose (100 mg) alteplase for pulmonary embolism. We used propensity score matching and sensitivity analyses to address confounding and hospital-level clustering. SETTING: Data from 420 hospitals obtained from the Premier Healthcare Database between January 2010 and December 2014. SUBJECTS: Adult critically ill patients with acute pulmonary embolism treated with IV alteplase therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study included 3,768 patients: 699 (18.6%) in the half-dose and 3,069 (81.4%) in the full-dose group. At baseline, patients receiving half-dose alteplase required vasopressor therapy (23.3% vs 39.4%; p < 0.01) and invasive ventilation (14.3% vs 28.5%; p < 0.01) less often, compared with full dose. After propensity matching (n = 548 per group), half-dose alteplase was associated with increased treatment escalation (53.8% vs 41.4%; p < 0.01), driven mostly by secondary thrombolysis (25.9% vs 7.3%; p < 0.01) and catheter thrombus fragmentation (14.2% vs 3.8%; p < 0.01). Hospital mortality was similar (13% vs 15%; p = 0.3). There was no difference in cerebral hemorrhage (0.5% vs 0.4%; p = 0.67), gastrointestinal bleeding (1.6% vs 1.6%; p = 0.99), acute blood loss anemia (6.9% vs 4.6%; p = 0.11), use of blood products (p > 0.05 for all), or documented fibrinolytic adverse events (2.6% vs 2.8%; p = 0.82). CONCLUSIONS: Compared with full-dose alteplase, half-dose was associated with similar mortality and rates of major bleeding. Treatment escalation occurred more often in half-dose-treated patients. These results question whether half-dose alteplase provides similar efficacy with improved safety, and highlights the need for further study before use of half-dose alteplase therapy can be routinely recommended in patients with pulmonary embolism.
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Fibrinolíticos/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Ventilação Pulmonar , Ativador de Plasminogênio Tecidual/administração & dosagem , Adulto , Circulação Coronária/efeitos dos fármacos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/terapia , Estudos Retrospectivos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
OBJECTIVES: To assess the impact of a discharge diagnosis of critical illness polyneuromyopathy on health-related outcomes in a large cohort of patients requiring ICU admission. DESIGN: Retrospective cohort with propensity score-matched analysis. SETTING: Analysis of a large multihospital database. PATIENTS: Adult ICU patients without preexisting neuromuscular abnormalities and a discharge diagnosis of critical illness polyneuropathy and/or myopathy along with adult ICU propensity-matched control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,567 ICU patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy, we matched 3,436 of these patients to 3,436 ICU patients who did not have a discharge diagnosis of critical illness polyneuropathy and/or myopathy. After propensity matching and adjusting for unbalanced covariates, we used conditional logistic regression and a repeated measures model to compare patient outcomes. Compared to patients without a discharge diagnosis of critical illness polyneuropathy and/or myopathy, patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy had fewer 28-day hospital-free days (6 [0.1] vs 7.4 [0.1] d; p < 0.0001), had fewer 28-day ventilator-free days (15.7 [0.2] vs 17.5 [0.2] d; p < 0.0001), had higher hospitalization charges (313,508 [4,853] vs 256,288 [4,470] dollars; p < 0.0001), and were less likely to be discharged home (15.3% vs 32.8%; p < 0.0001) but had lower in-hospital mortality (13.7% vs 18.3%; p < 0.0001). CONCLUSIONS: In a propensity-matched analysis of a large national database, a discharge diagnosis of critical illness polyneuropathy and/or myopathy is strongly associated with deleterious outcomes including fewer hospital-free days, fewer ventilator-free days, higher hospital charges, and reduced discharge home but also an unexpectedly lower in-hospital mortality. This study demonstrates the clinical importance of a discharge diagnosis of critical illness polyneuropathy and/or myopathy and the need for effective preventive interventions.
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Unidades de Terapia Intensiva/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Polineuropatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Preços Hospitalares/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Pontuação de Propensão , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: To evaluate the differences in the composition and quantities of urine peptides in regular cannabis users and nonusers by liquid chromatography tandem mass spectrometry analysis. MATERIALS AND METHODS: Urine specimens from healthy control subjects and cannabis users were utilized to identify the differences in the number and quantity of urine proteins by liquid chromatography tandem mass spectrometry analysis. Significantly altered proteins were determined by a permutation testing statistical method. Heat map, dendrogram, pathway, and network analyses were performed to assess the degree of expression and the potential relationships between proteins in both groups. RESULTS: A total of 1337 proteins were detected in both groups with 19 proteins being significantly altered in cannabis users. Innate immunity and carbohydrate metabolic pathways were highly linked with upregulated proteins in the cannabis group. Additionally, 91 proteins were present and 46 proteins were absent only in cannabis users in comparison with the control cohort. Our results suggest that regular use of cannabis is associated with significant alterations in a number of urinary peptides, with a large number of proteins present or absent only in cannabis users. Pathway analyses demonstrated an increased immune response in cannabis users compared with controls. CONCLUSION: Our observations potentially indicate activation (or inhibition) of specific signaling pathways in the lower urinary tract during chronic exposure to exogenous cannabinoids. Our study provides initial proteomic knowledge for future investigations on the potential role of exocannabinoids in the development of intravesical therapies to treat lower urinary tract disorders.
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Biomarcadores/urina , Canabinoides/farmacologia , Uso da Maconha/urina , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo , Cromatografia Líquida , Feminino , Humanos , Masculino , Uso da Maconha/metabolismo , Projetos Piloto , ProteômicaRESUMO
Recent legislative successes allowing expanded access to recreational and medicinal cannabis have been associated with its increased use by the public, despite continued debates regarding its safety within the medical and scientific communities. Despite legislative changes, cannabis is most commonly used by smoking, although alternatives to inhalation have also emerged. Moreover, the composition of commercially available cannabis has dramatically changed in recent years. Therefore, developing sound scientific information regarding its impact on lung health is imperative, particularly because published data conducted prior to widespread legalization are conflicting and inconclusive. In this commentary, we delineate major observations of epidemiologic investigations examining cannabis use and the potential associated development of airways disease and lung cancer to highlight gaps in pulmonary knowledge. Additionally, we review major histopathologic alterations related to smoked cannabis and define specific areas in animal models and human clinical translational investigations that could benefit from additional development. Given that cannabis has an ongoing classification as a schedule I medication, federal funding to support investigations of modern cannabis use in terms of medicinal efficacy and safety profile on lung health have been elusive. It is clear, however, that the effects of inhaled cannabis on lung health remain uncertain and given increasing use patterns, are worthy of further investigation.
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Cannabis/química , Pneumopatias/etiologia , Fumar Maconha/efeitos adversos , Animais , Humanos , Pneumopatias/epidemiologia , Fumar Maconha/epidemiologia , Fumar Maconha/legislação & jurisprudência , Prevalência , Pesquisa Translacional Biomédica , Estados Unidos/epidemiologiaRESUMO
Acute respiratory distress syndrome (ARDS) continues to be a major healthcare problem, affecting >190,000 people in the USA annually, with a mortality of 27-45%, depending on the severity of the illness and comorbidities. Despite advances in clinical care, particularly lung protective strategies of mechanical ventilation, most survivors experience impaired health-related quality of life for years after the acute illness. While most patients survive the acute illness, a subset of ARDS survivors develops a fibroproliferative response characterised by fibroblast accumulation and deposition of collagen and other extracellular matrix components in the lung. Historically, the development of severe fibroproliferative lung disease has been associated with a poor prognosis with high mortality and/or prolonged ventilator dependence. More recent studies also support a relationship between the magnitude of the fibroproliferative response and long-term health-related quality of life. The factors that determine which patients develop fibroproliferative ARDS and the cellular mechanisms responsible for this pathological response are not well understood. This article reviews our current understanding of the contribution of pulmonary dysfunction to mortality and to quality of life in survivors of ARDS, the mechanisms driving pathological fibroproliferation and potential therapeutic approaches to prevent or attenuate fibroproliferative lung disease.