Weaning Analgosedation in Patients Requiring Prolonged Mechanical Ventilation.

Although research supports the minimization of sedation in mechanically ventilated patients, many patients with severe acute respiratory distress syndrome (ARDS) receive prolonged opioid and sedative infusions. ICU teams face the challenge of weaning these medications, balancing the risks of sedation with the potential to precipitate withdrawal symptoms. In this article, we use a clinical case to discuss our approach to weaning analgosedation in patients recovering from long-term mechanical ventilation. We believe that a protocolized, multimodal weaning strategy implemented by a multidisciplinary care team is required to reduce potential harm from both under- and over-sedation. At present, there is no strong randomized clinical trial evidence to support a particular weaning strategy in adult ICU patients, but appraisal of the existing literature in adults and children can guide decision-making to enhance the recovery of these patients.

The Association Between Antibiotic Delay Intervals and Hospital Mortality Among Patients Treated in the Emergency Department for Suspected Sepsis.

OBJECTIVES: Rapid delivery of antibiotics is a cornerstone of sepsis therapy, although time targets for specific components of antibiotic delivery are unknown. We quantified time intervals comprising the task of antibiotic delivery and evaluated the association between interval delays and hospital mortality among patients treated in the emergency department for suspected sepsis. DESIGN: Retrospective cohort. SETTING: Twelve hospitals in Southeastern United States from 2014 to 2017. PATIENTS: Twenty-four thousand ninety-three encounters among 20,026 adults with suspected sepsis in 12 emergency departments. MEASUREMENTS AND MAIN RESULTS: We divided antibiotic administration into two intervals: time from emergency department triage to antibiotic order (recognition delay) and time from antibiotic order to infusion (administration delay). We used generalized linear mixed models to evaluate associations between these intervals and hospital mortality. Median time from emergency department triage to antibiotic administration was 3.4 hours (interquartile range, 2.0-6.0 hr), separated into a median recognition delay (time from emergency department triage to antibiotic order) of 2.7 hours(interquartile range, 1.5-4.7 hr) and median administration delay (time from antibiotic order to infusion) of 0.6 hours (0.3-1.2 hr). Adjusting for other risk factors, both recognition delay and administration delay were associated with mortality, but pairwise comparison with a no-delay reference group was not significant for up to 6 hours of recognition delay or up to 1.5 hours of administration delay. CONCLUSIONS: Both recognition delays and administration delays were associated with increased hospital mortality, but only for longer delays. These results suggest that both metrics may be important to measure and improve for patients with suspected sepsis but do not support targets less than 1 hour.

First-to-second antibiotic delay and hospital mortality among emergency department patients with suspected sepsis.

OBJECTIVE: To evaluate whether delay between the first and second antibiotic administered for suspected sepsis is associated with hospital mortality. DESIGN: Retrospective cohort. SETTING: Twelve hospitals in Southeastern United States from 2014 to 2017. PATIENTS: 25,717 adults with suspected sepsis presenting to 12 Emergency Departments who received at least two antibiotics within 12 h. MEASUREMENTS AND MAIN RESULTS: The primary exposure was first-to-second antibiotic delay >1 h. We used generalized linear mixed models to model the association between first-to-second antibiotic delay and hospital death in the overall cohort, and in subgroups of patients with and without septic shock. Overall, 13,852 (54%) patients had first-to-second antibiotic delay >1 h and 1666 (7%) died. Adjusting for other risk factors, first-to-second antibiotic delay was associated with increased risk of hospital death in the subgroup of patients with septic shock (OR 1.34; 95% CI: 1.05-1.70), but not among patients without shock (OR 0.99; 95% CI: 0.88-1.12) or in the overall cohort (OR 1.08; 95% CI: 0.97-1.20). CONCLUSIONS: First-to-second antibiotic delay of greater than one hour was associated with an increased risk of hospital death among patients meeting criteria for septic shock but not all patients with suspected sepsis. Tracking and improving first-to-second antibiotic delays may be considered in septic shock.

Predictive Accuracy of Quick Sequential Organ Failure Assessment for Hospital Mortality Decreases With Increasing Comorbidity Burden Among Patients Admitted for Suspected Infection.

OBJECTIVES: Evaluate the accuracy of the quick Sequential Organ Failure Assessment tool to predict mortality across increasing levels of comorbidity burden. DESIGN: Retrospective observational cohort study. SETTING: Twelve acute care hospitals in the Southeastern United States. PATIENTS: A total of 52,187 patients with suspected infection presenting to the Emergency Department between January 2014 and September 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital mortality. We used electronic health record data to calculate quick Sequential Organ Failure Assessment risk scores from vital signs and laboratory values documented during the first 24 hours. We calculated Charlson Comorbidity Index scores to quantify comorbidity burden. We constructed logistic regression models to evaluate differences in the performance of quick Sequential Organ Failure Assessment greater than or equal to 2 to predict hospital mortality in patients with no documented (Charlson Comorbidity Index = 0), low (Charlson Comorbidity Index = 1-2), moderate (Charlson Comorbidity Index = 3-4), or high (Charlson Comorbidity Index ≥ 5) comorbidity burden. Among the cohort, 2,030 patients died in the hospital (4%). No comorbidities were documented for 5,038 patients (10%), 9,235 patients (18%) had low comorbidity burden, 12,649 patients (24%) had moderate comorbidity burden, and 25,265 patients (48%) had high comorbidity burden. Overall model discrimination for quick Sequential Organ Failure Assessment greater than or equal to 2 was the area under the receiver operating characteristic curve of 0.71 (95% CI, 0.69-0.72). A model including both quick Sequential Organ Failure Assessment and Charlson Comorbidity Index had improved discrimination compared with Charlson Comorbidity Index alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.76-0.78 vs area under the curve, 0.61; 95% CI, 0.59-0.62). Discrimination was highest among patients with no documented comorbidities (quick Sequential Organ Failure Assessment area under the receiver operating characteristic curve, 0.84; 95% CI; 0.79-0.89) and lowest among high comorbidity patients (quick Sequential Organ Failure Assessment area under the receiver operating characteristic curve, 0.67; 95% CI, 0.65-0.68). The strength of association between quick Sequential Organ Failure Assessment and mortality ranged from 30.5-fold increased likelihood in patients with no comorbidities to 4.7-fold increased likelihood in patients with high comorbidity. CONCLUSIONS: The accuracy of quick Sequential Organ Failure Assessment to predict hospital mortality diminishes with increasing comorbidity burden. Patients with comorbidities may have baseline abnormalities in quick Sequential Organ Failure Assessment variables that reduce predictive accuracy. Additional research is needed to better understand quick Sequential Organ Failure Assessment performance across different comorbid conditions with modification that incorporates the context of changes to baseline variables.

Hospital Differences Drive Antibiotic Delays for Black Patients Compared With White Patients With Suspected Septic Shock.

OBJECTIVE: Evaluate racial disparities in sepsis processes of care. DESIGN: Observational cohort study. SETTING: Nine hospitals in the Southeastern United States between 2014 and 2016. PATIENTS: Two thousand two hundred twenty-one white and 707 black patients treated in the emergency department through "code sepsis" pathway for suspected septic shock. MEASUREMENTS AND MAIN RESULTS: Black patients were less likely to receive timely antibiotics than were white patients using multiple definitions (1 hr from code sepsis activation [odds ratio, 0.57; 95% CI, [0.44-0.74]; 85.6% vs. 91.2%; p < 0.0001]; 1 hr from triage [odds ratio, 0.83; 95% CI, [0.69-1.00]; 28.0% vs. 31.8%; p = 0.06]; 3 hr from triage [odds ratio, 0.71; 95% CI, [0.57-0.88]; 80.1% vs. 85.0%; p = 0.002]). Focusing on antibiotic administration within 1 hour of triage, these differences were enhanced after adjusting for patient-level factors (adjusted odds ratio, 0.80; 95% CI, [0.66-0.96]; p = 0.02), but attenuated after adjusting for hospital-level differences (adjusted odds ratio, 0.90; 95% CI, [0.81-1.01]; p = 0.07). Black and white patients did not differ on other sepsis quality indicators or adjusted mortality. CONCLUSIONS: Black patients appear to be less likely than white patients to receive timely antibiotic therapy for sepsis. These differences were largely explained by variation in care among hospitals, such that hospitals that disproportionately treat black patients were less likely to provide timely antibiotic therapy overall. There were no differences between races in other sepsis quality measures or adjusted mortality.

Health care-associated pneumonia in haemodialysis patients: clinical outcomes in patients treated with narrow versus broad spectrum antibiotic therapy.

BACKGROUND AND OBJECTIVE: Although the 2005 American Thoracic Society/Infectious Disease Society of America antibiotic guidelines classify pneumonia occurring in patients receiving chronic haemodialysis as health care-associated pneumonia (HCAP), and thus recommend treatment with broad-spectrum antibiotics for these patients, little data support this classification. We compared clinical outcomes in haemodialysis patients hospitalized with pneumonia, who were treated with broad-spectrum antibiotics versus narrow-spectrum antibiotics. METHODS: One hundred twenty-five haemodialysis patients with pneumonia met eligibility criteria. Categorization into the community-acquired pneumonia (CAP) group or HCAP group was based on antibiotic therapy patients received. Time to oral therapy, time to clinical stability, length of stay and mortality were compared. RESULTS: CAP and HCAP patients did not differ in Pneumonia Severity Index and Charlson Comorbidity index scores, but HCAP patients were more likely to meet criteria for severe pneumonia. Patients treated with HCAP therapy had a significantly longer time to oral therapy than CAP patients (9.2 vs 3.2 days, P < 0.001) and a significantly longer length of stay (11.9 vs 5.1 days, P < 0.001). Time to clinical stability was marginally longer in the HCAP group (3.1 vs 2.4 days, P = 0.07). Patients treated with HCAP therapy had longer continuation of intravenous antibiotics after reaching clinical stability (5.5 vs 0.78 days, P < 0.001). CONCLUSIONS: This study is the first to our knowledge to describe clinical outcomes in patients with haemodialysis as their only HCAP risk factor. Narrow-spectrum antibiotics may be safe in haemodialysis patients with no other HCAP risk factors. HCAP therapy delayed de-escalation to oral antibiotics was associated with increased duration of intravenous antibiotics and length of stay.

Heart failure due to tension hydrothorax after left pneumonectomy.

Tension hydrothorax is a rare complication of pneumonectomy for pleural mesothelioma and an exceptionally rare cause of heart failure. We describe a patient who had undergone extrapleural pneumonectomy, chemotherapy, and radiation for pleural mesothelioma and who developed heart failure symptoms within months of the completion of treatment. Investigation showed a massive left pleural effusion resulting in tension hydrothorax, mediastinal shift, and evidence of right heart failure with constrictive physiology and low cardiac output. Therapeutic thoracentesis resulted in increase in cardiac output and symptomatic improvement.

Awake Prone Positioning Strategy for Nonintubated Hypoxic Patients with COVID-19: A Pilot Trial with Embedded Implementation Evaluation.

Rationale: Prone positioning is an appealing therapeutic strategy for nonintubated hypoxic patients with coronavirus disease (COVID-19), but its effectiveness remains to be established in randomized controlled trials. Objectives: To identify contextual factors relevant to the conduct of a definitive clinical trial evaluating a prone positioning strategy for nonintubated hypoxic patients with COVID-19. Methods: We conducted a cluster randomized pilot trial at a quaternary care teaching hospital. Five inpatient medical service teams were randomly allocated to two treatment arms: 1) usual care (UC), consisting of current, standard management of hypoxia and COVID-19; or 2) the Awake Prone Positioning Strategy (APPS) plus UC. Included patients had positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing or suspected COVID-19 pneumonia and oxygen saturation less than 93% or new oxygen requirement of 3 L per minute or greater and no contraindications to prone positioning. Oxygenation measures were collected within 48 hours of eligibility and included nadir oxygen saturation to fraction of inspired oxygen (S/F) ratio and time spent with S/F ratio less than 315. Concurrently, we conducted an embedded implementation evaluation using semistructured interviews with clinician and patient participants to determine contextual factors relevant to the successful conduct of a future clinical trial. The primary outcomes were drawn from an implementation science framework including acceptability, adoption, appropriateness, effectiveness, equity, feasibility, fidelity, and penetration. Results: Forty patients were included in the cluster randomized trial. Patients in the UC group (n = 13) had a median nadir S/F ratio over the 48-hour study period of 216 (95% confidence interval [95% CI], 95-303) versus 253 (95% CI, 197-267) in the APPS group (n = 27). Patients in the UC group spent 42 hours (95% CI, 13-47) of the 48-hour study period with an S/F ratio below 315 versus 20 hours (95% CI, 6-39) for patients in the APPS group. Mixed-methods analyses uncovered several barriers relevant to the conduct of a successful definitive randomized controlled trial, including low adherence to prone positioning, large differences between physician-recommended and patient-tolerated prone durations, and diffusion of prone positioning into usual care. Conclusions: A definitive trial evaluating the effect of prone positioning in nonintubated patients with COVID-19 is warranted, but several barriers must be addressed to ensure that the results of such a trial are informative and readily translated into practice.

A rapid pre-implementation evaluation to inform a family engagement navigator program during COVID-19.

BACKGROUND: Innovative models of family engagement and support are needed in the intensive care unit (ICU) during times of restricted visitation such as the COVID-19 pandemic. Limited understanding of the factors affecting the uptake and outcomes of different family support models hinders the implementation of best practices. We aimed to conduct a rapid pre-implementation evaluation of stakeholder-perceived facilitators and barriers to design implementation strategies to support a novel program using medical students to facilitate family-centered care in the ICU. METHODS: We conducted a 2-step process. In step 1, we gathered contextual data via interview-style open-ended questions sent to clinicians and navigator stakeholders via email. We used electronic data collection due to the physical distancing requirements, the need to prioritize brief data collection for respondent burden, and the need for rapid knowledge gain. A codebook based on the Consolidated Framework for Implementation Research (CFIR), an integrated framework from the field of implementation science, was used to analyze the findings. In step 2, a pilot of the intervention was implemented with 3 navigators over 2 weeks. Implementation strategies were developed to target barriers identified by the pre-implementation evaluation. RESULTS: Fourteen (70%) of the identified stakeholders responded to the survey. Ten constructs encompassing all five CFIR domains were present in responses as implementation influencers, with the Intervention domain most frequently represented. Through these results and operational feedback from navigators during the pilot period, stakeholders selected multiple implementation strategies: audit and provide feedback, develop educational materials, conduct ongoing training, promote adaptability, assess and redesign workflow, identify and prepare champions, and engage community resources. CONCLUSIONS: We demonstrated how a conceptually based pre-implementation program evaluation can be used to rapidly inform optimal implementation strategies. We report key factors to inform design and implementation strategies for a novel ICU family engagement navigator program that may be useful to others wishing to adopt similar programs.

Association between Adherence to Recommended Care and Outcomes for Adult Survivors of Sepsis.

Rationale: Postsepsis care recommendations target specific deficits experienced by sepsis survivors in elements such as optimization of medications, screening for functional impairments, monitoring for common and preventable causes of health deterioration, and consideration of palliative care. However, few data are available regarding the application of these elements in clinical practice.Objectives: To quantify the delivery of postsepsis care for patients discharged after hospital admission for sepsis and evaluate the association between receipt of postsepsis care elements and reduced mortality and hospital readmission within 90 days.Methods: We conducted a retrospective chart review of a random sample of patients who were discharged alive after an admission for sepsis (identified from International Classification of Diseases, 10th Revision discharge codes) at 10 hospitals during 2017. We used a structured chart abstraction to determine whether four elements of postsepsis care were provided within 90 days of hospital discharge, per expert recommendations. We used multivariable logistic regression to evaluate the association between receipt of care elements and 90-day hospital readmission and mortality, adjusted for age, comorbidity, length of stay, and discharge disposition.Results: Among 189 sepsis survivors, 117 (62%) had medications optimized, 123 (65%) had screening for functional or mental health impairments, 86 (46%) were monitored for common and preventable causes of health deterioration, and 110 (58%) had care alignment processes documented (i.e., assessed for palliative care or goals of care). Only 20 (11%) received all four care elements within 90 days. Within 90 days of discharge, 66 (35%) patients were readmitted and 33 (17%) died (total patients readmitted or died, n = 82). Receipt of two (odds ratio [OR], 0.26; 95% confidence interval [95% CI], 0.10-0.69) or more (three OR, 0.28; 95% CI, 0.11-0.72; four OR, 0.12; 95% CI, 0.03-0.50) care elements was associated with lower odds of 90-day readmission or 90-day mortality compared with zero or one element documented. Optimization of medications (no medication errors vs. one or more errors; OR, 0.44; 95% CI, 0.21-0.92), documented functional or mental health assessments (physical function plus swallowing/mental health assessments vs. no assessments; OR, 0.14; 95% CI, 0.05-0.40), and documented goals of care or palliative care screening (OR, 0.52; 95% CI, 0.25-1.05; not statistically significant) were associated with lower odds of 90-day readmission or 90-day mortality.Conclusions: In this retrospective cohort study of data from a single health system, we found variable delivery of recommended postsepsis care elements that were associated with reduced morbidity and mortality after hospitalization for sepsis. Implementation strategies to efficiently overcome barriers to adopting recommended postsepsis care may help improve outcomes for sepsis survivors.

Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock.

OBJECTIVE: The optimal initial fluid resuscitation strategy for obese patients with septic shock is unknown. We evaluated fluid resuscitation strategies across BMI groups. MATERIALS AND METHODS: Retrospective analysis of 4157 patients in a multicenter activation pathway for treatment of septic shock between 2014 and 2016. RESULTS: 1293 (31.3%) patients were obese (BMI≥30). Overall, higher BMI was associated with lower mortality, however this survival advantage was eliminated in adjusted analyses. Patients with higher BMI received significantly less fluid per kilogram at 3h than did patients with lower BMI (p≤0.001). In obese patients, fluid given at 3h mimicked a dosing strategy based on actual body weight (ABW) in 780 (72.2%), adjusted body weight (AdjBW) in 95 (8.8%), and ideal body weight (IBW) in 205 (19.0%). After adjusting for condition- and treatment-related variables, dosing based on AdjBW was associated with improved mortality compared to ABW (OR 0.45; 95% CI [0.19, 1.07]) and IBW (OR 0.29; 95% CI [0.11,0.74]). CONCLUSIONS: Using AdjBW to calculate initial fluid resuscitation volume for obese patients with suspected shock may improve outcomes compared to other weight-based dosing strategies. The optimal fluid dosing strategy for obese patients should be a focus of future prospective research.

A Case of Chyloperitoneum Secondary to Follicular Lymphoma and a Review of Prognostic Implications.

Chyloperitoneum, or chylous ascites, is a rare condition characterized by milky-appearing fluid with elevated triglyceride content and the presence of chylomicrons. Malignancy, specifically lymphoma, is reported to be the predominant cause in Western countries. Previously, the prognosis for patients with chyloperitoneum due to lymphoma has been reported as poor. We present a case of chyloperitoneum and chylothorax due to follicular lymphoma with excellent response to bendamustine and Rituxan. A review of the literature indicates that patients with chyloperitoneum associated with lymphoma generally have a favorable response to contemporary treatment regimens.

Azithromycin for the Prevention of COPD Exacerbations: The Good, Bad, and Ugly.

Long-term azithromycin therapy has been shown to reduce exacerbations of chronic obstructive pulmonary disease (COPD), and is recommended by recent society guidelines for use in COPD patients who are at risk for recurrent exacerbations. However, concerns about adverse effects have limited its widespread adoption. Physicians deciding whether to use long-term azithromycin therapy must weigh each patient's individual risk of cardiovascular complications and both the individual and population impact of macrolide resistance against the expected benefit. This review will summarize evidence on the effectiveness and safety of chronic azithromycin for the prevention of COPD exacerbations.