Sigh Ventilation in Patients With Trauma: The SiVent Randomized Clinical Trial.

Importance: Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ventilator-induced lung injury among trauma patients at risk of poor outcomes is unknown. Objective: To determine whether adding sigh breaths improves clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized trial of sigh breaths plus usual care conducted from 2016 to 2022 with 28-day follow-up in 15 academic trauma centers in the US. Inclusion criteria were age older than 18 years, mechanical ventilation because of trauma for less than 24 hours, 1 or more of 5 risk factors for developing acute respiratory distress syndrome, expected duration of ventilation longer than 24 hours, and predicted survival longer than 48 hours. Interventions: Sigh volumes producing plateau pressures of 35 cm H2O (or 40 cm H2O for inpatients with body mass indexes >35) delivered once every 6 minutes. Usual care was defined as the patient's physician(s) treating the patient as they wished. Main Outcomes and Measures: The primary outcome was ventilator-free days. Prespecified secondary outcomes included all-cause 28-day mortality. Results: Of 5753 patients screened, 524 were enrolled (mean [SD] age, 43.9 [19.2] years; 394 [75.2%] were male). The median ventilator-free days was 18.4 (IQR, 7.0-25.2) in patients randomized to sighs and 16.1 (IQR, 1.1-24.4) in those receiving usual care alone (P = .08). The unadjusted mean difference in ventilator-free days between groups was 1.9 days (95% CI, 0.1 to 3.6) and the prespecified adjusted mean difference was 1.4 days (95% CI, -0.2 to 3.0). For the prespecified secondary outcome, patients randomized to sighs had 28-day mortality of 11.6% (30/259) vs 17.6% (46/261) in those receiving usual care (P = .05). No differences were observed in nonfatal adverse events comparing patients with sighs (80/259 [30.9%]) vs those without (80/261 [30.7%]). Conclusions and Relevance: In a pragmatic, randomized trial among trauma patients receiving mechanical ventilation with risk factors for developing acute respiratory distress syndrome, the addition of sigh breaths did not significantly increase ventilator-free days. Prespecified secondary outcome data suggest that sighs are well-tolerated and may improve clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02582957.

Constant Vt Ventilation and Surfactant Dysfunction: An Overlooked Cause of Ventilator-induced Lung Injury.

Ventilator-induced lung injury (VILI) is currently ascribed to volutrauma and/or atelectrauma, but the effect of constant Vt ventilation (CVtV) has received little attention. This Perspective summarizes the literature documenting that CVtV causes VILI and reviews the mechanisms by which it occurs. Surfactant is continuously inactivated, depleted, displaced, or desorbed as a function of the duration of ventilation, the Vt, the level of positive end-expiratory pressure (PEEP), and possibly the respiratory rate. Accordingly, surfactant must be continuously replenished, and secretion primarily depends on intermittent delivery of large ventilatory excursions. The surfactant abnormalities resulting from CVtV result in atelectasis and VILI. Although surfactant secretion is reduced by the absence of intermittent deep breaths, continuous administration of large Vts depletes surfactant and impairs subsequent secretion. Low or normal lung volumes result in desorption of surfactant. PEEP can be protective by reducing surface film collapse and subsequent film rupture on reexpansion, and/or by reducing surfactant displacement into the airways, but PEEP can also downregulate surfactant release. The effect of CVtV on surfactant is complex. If attention is not paid to facilitating surfactant secretion and limiting its inactivation, depletion, desorption, or displacement, surface tension will increase and atelectasis and VILI will occur.

Impact of Proactive Integrated Care on Chronic Obstructive Pulmonary Disease.

BACKGROUND: Up to 50% of chronic obstructive pulmonary disease (COPD) patients do not receive recommended care for COPD. To address this issue, we developed Proactive Integrated Care (Proactive iCare), a health care delivery model that couples integrated care with remote monitoring. METHODS: We conducted a prospective, quasi-randomized clinical trial in 511 patients with advanced COPD or a recent COPD exacerbation, to test whether Proactive iCare impacts patient-centered outcomes and health care utilization. Patients were allocated to Proactive iCare (n=352) or Usual Care ( =159) and were examined for changes in quality of life using the St George's Respiratory Questionnaire (SGRQ), symptoms, guideline-based care, and health care utilization. FINDINGS: Proactive iCare improved total SGRQ by 7-9 units (p < 0.0001), symptom SGRQ by 9 units (p<0.0001), activity SGRQ by 6-7 units (p<0.001) and impact SGRQ by 7-11 units (p<0.0001) at 3, 6 and 9 months compared with Usual Care. Proactive iCare increased the 6-minute walk distance by 40 m (p<0.001), reduced annual COPD-related urgent office visits by 76 visits per 100 participants (p<0.0001), identified unreported exacerbations, and decreased smoking (p=0.01). Proactive iCare also improved symptoms, the body mass index-airway obstruction-dyspnea-exercise tolerance (BODE) index and oxygen titration (p<0.05). Mortality in the Proactive iCare group (1.1%) was not significantly different than mortality in the Usual Care group (3.8%; p=0.08). INTERPRETATION: Linking integrated care with remote monitoring improves the lives of people with advanced COPD, findings that may have been made more relevant by the coronavirus 2019 (COVID-19) pandemic.

Prone position in ARDS patients: why, when, how and for whom.

In ARDS patients, the change from supine to prone position generates a more even distribution of the gas-tissue ratios along the dependent-nondependent axis and a more homogeneous distribution of lung stress and strain. The change to prone position is generally accompanied by a marked improvement in arterial blood gases, which is mainly due to a better overall ventilation/perfusion matching. Improvement in oxygenation and reduction in mortality are the main reasons to implement prone position in patients with ARDS. The main reason explaining a decreased mortality is less overdistension in non-dependent lung regions and less cyclical opening and closing in dependent lung regions. The only absolute contraindication for implementing prone position is an unstable spinal fracture. The maneuver to change from supine to prone and vice versa requires a skilled team of 4-5 caregivers. The most frequent adverse events are pressure sores and facial edema. Recently, the use of prone position has been extended to non-intubated spontaneously breathing patients affected with COVID-19 ARDS. The effects of this intervention on outcomes are still uncertain.

Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis.

BACKGROUND: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations. RESEARCH QUESTION: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD. STUDY DESIGN AND METHODS: Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status. RESULTS: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001. INTERPRETATION: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Opioid Utilization and Perception of Pain Control in Hospitalized Patients: A Cross-Sectional Study of 11 Sites in 8 Countries.

BACKGROUND: Hospitalized patients are frequently treated with opioids for pain control, and receipt of opioids at hospital discharge may increase the risk of future chronic opioid use. OBJECTIVE: To compare inpatient analgesic prescribing patterns and patients' perception of pain control in the United States and non-US hospitals. DESIGN: Cross-sectional observational study. SETTING: Four hospitals in the US and seven in seven other countries. PARTICIPANTS: Medical inpatients reporting pain. MEASUREMENTS: Opioid analgesics dispensed during the first 24-36 hours of hospitalization and at discharge; assessments and beliefs about pain. RESULTS: We acquired completed surveys for 981 patients, 503 of 719 patients in the US and 478 of 590 patients in other countries. After adjusting for confounding factors, we found that more US patients were given opioids during their hospitalization compared with patients in other countries, regardless of whether they did or did not report taking opioids prior to admission (92% vs 70% and 71% vs 41%, respectively; P < .05), and similar trends were seen for opioids prescribed at discharge. Patient satisfaction, beliefs, and expectations about pain control differed between patients in the US and other sites. LIMITATIONS: Limited number of sites and patients/country. CONCLUSIONS: In the hospitals we sampled, our data suggest that physicians in the US may prescribe opioids more frequently during patients' hospitalizations and at discharge than their colleagues in other countries, and patients have different beliefs and expectations about pain control. Efforts to curb the opioid epidemic likely need to include addressing inpatient analgesic prescribing practices and patients' expectations regarding pain control.

Characteristics at the time of oxygen initiation associated with its adherence: Findings from the COPD Long-term Oxygen Treatment Trial.

RATIONALE: Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear. OBJECTIVES: To identify patient characteristics at the time of oxygen initiation associated with its adherence. METHODS: We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial. Participants were prescribed continuous (n = 214) or intermittent (n = 145) oxygen based on desaturation patterns at study entry. At the time of initial prescription, participants rated their perceived readiness, confidence, and importance to use oxygen on a 0-10 scale (0 = not at all, 10 = very much). During follow-up, they self-reported average hours per day of use (adherence). Adherence was averaged over short-term (0-30 days), medium-term (months 9-12), and long-term (month 13 to last follow-up) intervals. Multivariable logistic regression models explored characteristics associated with high adherence (≥16 h/day [continuous] or ≥8 h/day [intermittent]) during each time interval. RESULTS: Participant readiness, confidence, and importance at the time of oxygen initiation were associated with high short- and medium-term adherence. For each unit increase in baseline readiness, the odds of high short-term adherence increased by 21% (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05-1.40) and 94% (OR 1.94, 95% CI 1.45-2.59) in the continuous and intermittent groups, respectively. In both groups, high adherence in the medium-term was associated with high adherence in the long-term (continuous, OR 12.49, 95% CI 4.90-31.79; intermittent, OR 38.08, 95% CI 6.96-208.20). CONCLUSIONS: Readiness, confidence, and importance to use LTOT at initiation, and early high adherence, are significantly associated with long-term oxygen adherence.

Imaging in Acute Pyelonephritis: Utilization, Findings, and Effect on Management.

OBJECTIVES: To determine the frequency, timing, and types of imaging obtained in patients with a discharge diagnosis of acute pyelonephritis, and how often imaging findings affect therapy. METHODS: This was a retrospective chart review of 1062 adults with a diagnosis of acute pyelonephritis discharged from an urban, safety-net hospital between January 1, 2008 and December 31, 2012. From the 739 patients selected after exclusions, we determined the number and proportion of patients imaged within the first 24 hours of admission, stratified by risk factors for pyelonephritis complications, and the frequency of positive findings leading to invasive interventions. RESULTS: Of 739 patients, 468 (63%) were imaged within 24 hours of admission, 262/414 (63%) of whom had risk factors for complications and 206/325 of whom (63%) did not. Among these, studies were positive in 117/468 (25%), 78/262 (30%) in those with risk factors, and 39/206 (19%) of those without risk factors. Of the 117 patients with positive imaging findings within 24 hours of admission, 58 (50%) underwent invasive procedures, 47 (60%) with risk factors and 11 (28%) without. Among all of the patients, interventions were directed at relieving obstructions much more commonly than treating abscess (51 patients vs 8). CONCLUSIONS: Among this population, imaging is frequently done earlier than recommended. Because the majority of interventions targeted stone disease, ultrasound may be the preferred initial modality rather than contrasted tomography when obtaining imaging early. Current guidelines may need to be revisited.

Barriers to Early Hospital Discharge: A Cross-Sectional Study at Five Academic Hospitals.

BACKGROUND: Understanding the issues delaying hospital discharges may inform efforts to improve hospital throughput. OBJECTIVE: This study was conducted to identify and determine the frequency of barriers contributing to delays in placing discharge orders. DESIGN: This was a prospective, cross-sectional study. Physicians were surveyed at approximately 8:00 AM, 12:00 PM, and 3:00 PM and were asked to identify patients that were "definite" or "possible" discharges and to describe the specific barriers to writing discharge orders. SETTING: This study was conducted at five hospitals in the United States. PARTICIPANTS: The study participants were attending and housestaff physicians on general medicine services. PRIMARY OUTCOMES AND MEASURES: Specific barriers to writing discharge orders were the primary outcomes; the secondary outcomes included discharge order time for high versus low team census, teaching versus nonteaching services, and rounding style. RESULTS: Among 1,584 patient evaluations, the most common delays for patients identified as "definite" discharges (n = 949) were related to caring for other patients on the team or waiting to staff patients with attendings. The most common barriers for patients identified as "possible" discharges (n = 1,237) were awaiting patient improvement and for ancillary services to complete care. Discharge orders were written a median of 43-58 minutes earlier for patients on teams with a smaller versus larger census, on nonteaching versus teaching services, and when rounding on patients likely to be discharged first (all P < .003). CONCLUSIONS: Discharge orders for patients ready for discharge are most commonly delayed because physicians are caring for other patients. Discharges of patients awaiting care completion are most commonly delayed because of imbalances between availability and demand for ancillary services. Team census, rounding style, and teaching teams affect discharge times.