Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Correlation of cough with disease activity and treatment with cyclophosphamide in scleroderma interstitial lung disease: findings from the Scleroderma Lung Study.

BACKGROUND: Cough is a significant symptom in patients with scleroderma interstitial lung disease (SSc-ILD), affecting 73% of the 158 patients enrolled in the Scleroderma Lung Study (SLS), a multicenter randomized trial of oral cyclophosphamide (CYC) vs placebo (PLA) in patients with active interstitial lung disease. METHODS: We examined the correlation of cough frequency and severity and phlegm production at baseline in 156 SLS participants with other baseline variables representing SSc-ILD disease activity and the cough response to 1 year of treatment with CYC vs PLA. RESULTS: Patients with cough at baseline had significantly lower diffusing capacity of the lung for carbon monoxide, dyspnea, the quality-of-life physical component summary, and the maximal fibrosis score on high-resolution CT imaging compared with those without cough at baseline. Cough severity and frequency correlated with FVC % predicted. After 12 months of treatment, cough frequency decreased in the CYC group compared with the PLA group and was significantly different from the PLA group at 18 months (6 months after discontinuation of CYC). However, the decreases in cough frequency did not correlate with the changes in FVC or diffusing capacity of the lung for carbon monoxide observed in the CYC group. Treatment-related improvements in cough frequency, as well as in FVC, were no longer apparent 12 months after discontinuation of CYC. CONCLUSIONS: Cough is a common symptom in SSc-ILD and correlates with the extent of fibrosis. Cough frequency decreases significantly in response to treatment with CYC but returns to baseline 1 year after withdrawal of treatment. Cough may be a symptom of ongoing fibrosis and an independent variable in assessing therapeutic response to CYC. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT000004563; URL: www.clinicaltrials.gov

Impact of a clinical pharmacist-enforced intensive care unit sedation protocol on duration of mechanical ventilation and hospital stay.

OBJECTIVE: While the use of a protocol to guide sedation and analgesia therapy in the intensive care unit has been shown to improve patient outcomes, compliance is often poor. We hypothesized that a formal, consistent intervention by pharmacists to promote adherence to our institution's sedation guidelines would improve clinical outcomes. The purpose of this study was to document the impact of daily pharmacist interventions on clinical outcomes of intensive care unit patients prescribed continuous sedative therapy. DESIGN: Before-after study. SETTING: Two medical intensive care units (total of 18 beds) at a university medical center. PATIENTS: Patients were 156 mechanically ventilated patients prescribed a continuous infusion of sedative medication while in the medical intensive care unit. INTERVENTIONS: In the retrospective group, data were collected on all mechanically ventilated patients receiving continuous sedative infusions over a 3-month period. In the prospective group, a pharmacist evaluated all mechanically ventilated patients on continuous sedation daily and made recommendations to adhere to the institution's previously approved sedation guidelines. MEASUREMENTS AND MAIN RESULTS: Data were collected for 78 control and 78 intervention patients. The groups were well matched in terms of baseline demographics. The mean duration of mechanical ventilation was reduced from 338 +/- 348 hrs (14 days) in the pre-intervention group to 178 +/- 178 hrs (7.4 days) in the postintervention group (p < .001). Durations of both intensive care unit stay (380 +/- 325 hrs vs. 238 +/- 206 hrs, p = .001) and hospital stay (537 +/- 350 hrs vs. 369 +/- 274 hrs, p = .001) were also significantly reduced in the post intervention group. CONCLUSIONS: The institution of a daily pharmacist-enforced intervention directed at improving sedation guideline adherence resulted in a significant decrease in the duration of mechanical ventilation in patients receiving continuous sedation.

Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines: a case series and prospective, observational pilot study.

STUDY OBJECTIVES: Benzodiazepines are commonly administered to medical ICU (MICU) patients. Propylene glycol (1,2-propanediol) is the solvent used to deliver lorazepam and diazepam IV. Although propylene glycol toxicity is increasingly recognized and reported, its incidence is unknown. Herein, we describe five MICU patients who acquired severe propylene glycol toxicity due to IV lorazepam or diazepam administration. Additionally, we evaluate the incidence of propylene glycol toxicity in MICU patients receiving IV lorazepam or diazepam. DESIGN: Case series and prospective, observational study. SETTING: Eighteen-bed MICU in a 550-bed urban academic hospital. PATIENTS AND METHODS: MICU patients administered IV benzodiazepines during a 3-month period were enrolled. Patients were categorized according to the IV benzodiazepine that they received. Laboratory data and highlights of their clinical course were recorded daily. The incidence of propylene glycol toxicity was determined and the groups compared. RESULTS: Forty-four patients were enrolled. Twenty-one patients received a benzodiazepine delivered in propylene glycol (lorazepam or diazepam), and 23 patients received a benzodiazepine delivered in an alternative solvent (midazolam). We found that four patients (19%) who received IV lorazepam or diazepam had metabolic evidence of propylene glycol toxicity. None of the patients had clinical deterioration. Neither metabolic abnormality nor clinical deterioration suggestive of propylene glycol toxicity were identified in subjects receiving IV midazolam. CONCLUSION: Propylene glycol toxicity is a potentially life-threatening iatrogenic complication that is common and preventable. It should be considered whenever a patient has an unexplained anion gap, unexplained metabolic acidosis, hyperosmolality, and/or clinical deterioration. Close monitoring of all patients receiving IV lorazepam or diazepam for early evidence of propylene glycol toxicity is warranted.

Measurement of interleukin 16.

Interleukin 16 (IL-16) is a chemoattractant immunomodulatory cytokine that initiates its cellular responses through interaction with membrane-expressed CD4. The protein may be detected by a number of methods; the choice of protocol will depend on the ultimate object of a particular experiment. The first method presented is the use of ELISA to measure IL-16 in cell culture supernatants or biological fluids. For some applications, such as identification of IL-16 in an unknown fluid or medium or direct assessment of its bioactivity, functional assays of IL-16-induced responses may be more appropriate. The chemotactic effects of IL-16 on CD4+ T cells and its specific inhibition may be measured using anti-IL-16 antibodies; the same approach may also be applied to monocytes or eosinophils. Another effect of IL-16 is the induction of CD25, which can be assayed using immunological staining. Finally, cell cycle progression in target cells can be measured by the incorporation of radiolabeled thymidine and confirmed by inhibition with neutralizing antibody.