Risk Factors and Outcomes Associated With Re-Intubation Secondary to Respiratory Failure in Patients With COVID-19 ARDS.

BACKGROUND: COVID-19 is associated with variable symptoms and clinical sequelae. Studies have examined the clinical course of these patients, finding a prolonged need for invasive ventilation and variable re-intubation rates. However, no research has investigated factors and outcomes related to re-intubation secondary to respiratory failure among patients with COVID-19 with ARDS. METHODS: We conducted a single-center, retrospective study on subjects intubated for ARDS secondary to COVID-19. The primary outcome was re-intubation status; secondary outcomes were hospital and ICU stay and mortality. Data were analyzed using between-group comparisons using chi-square testing for categorical information and Student t test for quantitative data. Univariate and multivariate logistic regression was performed to determine factors related to re-intubation and mortality as dependent variables. RESULTS: One hundred and fourteen subjects were included, of which 32% required re-intubation. No between-group differences were detected for most demographic variables or comorbidities. No differences were detected in COVID-19 treatments, noninvasive respiratory support, mechanical circulatory support, or duration of ventilation. Midazolam (odds ratio [OR] 5.55 [95% CI 1.83-16.80], P = .002), fentanyl (OR 3.64 [95% CI 1.26-10.52], P = .02), and APACHE II scores (OR 1.08 [95% CI 1.030-1.147], P = .005) were independently associated with re-intubation (area under the curve = 0.81). Re-intubated subjects had extended hospital (36.7 ± 22.7 d vs 26.1 ± 12.1 d, P = .01) and ICU (29.6 ± 22.4 d vs 15.8 ± 10.4 d, P < .001) stays. More subjects died who failed extubation (49% vs 3%, P < .001). Age (OR 1.07 [95% CI 1.02-1.23], P = .005), male sex (OR 4.9 [95% CI 1.08-22.35], P = .041), positive Confusion Assessment Method for the ICU (CAM-ICU) (OR 5.43 [95% CI 1.58-18.62], P = .007), and re-intubation (OR 12.75 [95% CI 2.80-57.10], P < .001) were independently associated with death (area under the curve = 0.93). CONCLUSIONS: Midazolam, fentanyl, and higher APACHE II scores were independently associated with re-intubation secondary to respiratory failure in subjects with COVID-19-related ARDS. Furthermore, age, male sex, positive CAM-ICU, and re-intubation were independently associated with mortality. Re-intubation also correlated with prolonged hospital and ICU stay.

Measuring Peak Inspiratory Flow in Patients with Chronic Obstructive Pulmonary Disease.

Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. However, practical and standardized recommendations for measuring peak inspiratory flow (PIF)-a potential indicator for effective DPI use in chronic obstructive pulmonary disease (COPD)-are lacking. To evaluate recommended PIF assessment approaches, we reviewed the Instructions for Use of the In-Check™ DIAL and the prescribing information for eight DPIs approved for use in the treatment of COPD in the United States. To evaluate applied PIF assessment approaches, we conducted a PubMed search from inception to August 31, 2021, for reports of clinical and real-life studies where PIF was measured using the In-Check™ DIAL or through a DPI in patients with COPD. Evaluation of collective sources, including 47 applicable studies, showed that instructions related to the positioning of the patient with their DPI, instructions for exhalation before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold times varied, and in many instances, appeared vague and/or incomplete. We observed considerable variation in how PIF was measured in clinical and real-life studies, underscoring the need for a standardized method of PIF measurement. Standardization of technique will facilitate comparisons among studies. Based on these findings and our clinical and research experience, we propose specific recommendations for PIF measurement to standardize the process and better ensure accurate and reliable PIF values in clinical trials and in daily clinical practice.

Analysis of Noninvasive Ventilation in Subjects With Sepsis and Acute Respiratory Failure.

BACKGROUND: Acute respiratory failure is among the sequelae of complications that can develop in response to severe sepsis. Research into sepsis-related respiratory failure has focused on ARDS and invasive mechanical ventilation. We studied the factors associated with success and failure of noninvasive ventilation (NIV) in the treatment of sepsis-related acute respiratory failure. METHODS: This retrospective study included 136 subjects with a diagnosis of acute respiratory failure and intrapulmonary or extrapulmonary sepsis who were placed on NIV. Subjects were divided into 2 groups based on the need for intubation from NIV: NIV failure (n = 70) and NIV success (n = 66). Demographic, clinical, and outcome data were collected and compared between groups, with the development of multivariate models to predict NIV failure and mortality. RESULTS: The overall NIV failure rate in subjects with a diagnosis of sepsis was 51%. There were no between-group differences in demographic or baseline characteristics. However, there were significant differences in clinical variables, with higher SOFA scores (NIV failure: 6.4 [± 3.0] vs NIV success: 4.9 [± 2.1]; P = .002), 2nd lactate levels (NIV failure: 2.6 [1.7 - 4.3] vs NIV success: 1.9 [1.4 - 2.6] mmol/L; P = .007), and initial NIV [Formula: see text] settings (NIV failure: 0.50 [0.40 - 0.70] vs NIV failure: 0.40 [0.35 - 0.50]; P = .003) in subjects who failed NIV. There were also more subjects in the NIV failure group who had a lactate ≥ 4 mmol/L prior to NIV start compared to those who succeeded on NIV (33% vs 15%, P = .02). At NIV start, subjects in the NIV failure group had lower mean arterial pressure (85 mm Hg [IQR 74-96] vs 91.7 mm Hg [IQR 78-108], P = .042) and Glasgow coma scale scores (14 [IQR 13-15] vs 15 [IQR 14-15], P < .002), while fewer subjects in the NIV failure group received a fluid bolus in the 24 h prior to NIV start (33% vs 53%, P = .02) or had signs of volume overload (36% vs 64%, P < .001). Multivariate analysis indicated that age (odds ratio 1.05 [95% CI 1.01-1.09], P = .02), SOFA score (odds ratio 1.49 [95% CI 1.15-1.94], P = .002), first systolic blood pressure (odds ratio 0.97 [95% CI 0.95-0.99], P = .02), signs of volume overload (odds ratio 0.23 [95% CI 0.07-0.68], P = .008], fluids prior to NIV (odds ratio 0.08 [95% CI 0.02-0.31], P < .001), and initial [Formula: see text] on NIV (odds ratio 1.04 [95% CI 1.01-1.08, P = .002) independently predicted NIV failure with an area under the curve of 0.88. Only NIV failure independently predicted death in multivariate analysis (area under the curve = 0.70). CONCLUSIONS: NIV failure in sepsis-related acute respiratory failure was independently predicted by patient acuity, first systolic blood pressure after sepsis alert, initial [Formula: see text] settings on NIV, fluid resuscitation, and signs of volume overload. However, only NIV failure independently predicted death in this cohort of subjects.

Comparison of Interfaces for the Delivery of Noninvasive Respiratory Support to Low Birthweight Infants.

BACKGROUND: Bench and clinical data indicate that techniques for applying noninvasive respiratory support may vary in terms of effectiveness, application, and tolerability. We implemented a new nasal interface and flow-generation system for the delivery of noninvasive respiratory support (NRS) to replace previously used systems. Our goal was to determine whether there were significant differences in clinically relevant outcomes between our new method and conventional systems. METHODS: We conducted a prospective observational study of preterm infants requiring noninvasive respiratory support during our initial implementation of a new nasal interface (RAM), and compared these data with a historic control group. Demographic, baseline, and clinical outcome data were collected. Clinical outcomes and comorbid conditions were compared by using the chi-square test for categorical information and the Student t test or Wilcoxon rank-sum test for quantitative data, depending on normality testing when using the Shapiro-Wilk test. Uni- and multivariate logistic regression were conducted to determine predictive factors for the development of bronchopulmonary dysplasia. RESULTS: There were no significant group differences in important comorbid conditions, invasive mechanical ventilation days (P = .16), or NRS failure within the first 7 d after birth (P = .10). Although there were no significant differences in the use of CPAP or noninvasive ventilation, settings with were significantly higher (P < .001) in the RAM group. There were more incidences of retinopathy of prematurity (P = .02) post RAM implementation, and the time to first reintubation was significantly shorter in the RAM group (P = .044). However, there were significant reductions post RAM in total days on any respiratory support (P = .009), total NRS days (P = .02), and supplemental O2 duration (P = .02). There was a trend toward reductions in bronchopulmonary dysplasia rates (P = .053), and the incidence of device-related tissue breakdown was significantly reduced (P < .001) post RAM. Multivariate logistic regression results showed the type of system (odds ratio [OR] 0.19, 95% CI 0.04-0.87; P = .032) and total invasive ventilation time (OR 0.94, 95% CI 0.89-0.99; P = .02) were predictors for the development of bronchopulmonary dysplasia. CONCLUSIONS: The ability to apply continuous distending pressure through consistent application of NRS with the RAM cannula attached to a ventilator may improve clinical outcomes, including the duration of respiratory support and pressure-ulcer rates. The influence of this system on the development of bronchopulmonary dysplasia and the significantly increased retinopathy of prematurity requires further study.

AARC Clinical Practice Guideline: Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients.

Aerosolized medications are used as airway clearance therapy to treat a variety of airway diseases. These guidelines were developed from a systematic review with the purpose of determining whether the use of these medications to promote airway clearance improves oxygenation and respiratory mechanics, reduces ventilator time and ICU stay, and/or resolves atelectasis/consolidation compared with usual care. Recombinant human dornase alfa should not be used in hospitalized adult and pediatric patients without cystic fibrosis. The routine use of bronchodilators to aid in secretion clearance is not recommended. The routine use of aerosolized N-acetylcysteine to improve airway clearance is not recommended. Aerosolized agents to change mucus biophysical properties or promote airway clearance are not recommended for adult or pediatric patients with neuromuscular disease, respiratory muscle weakness, or impaired cough. Mucolytics are not recommended to treat atelectasis in postoperative adult or pediatric patients, and the routine administration of bronchodilators to postoperative patients is not recommended. There is no high-level evidence related to the use of bronchodilators, mucolytics, mucokinetics, and novel therapy to promote airway clearance in these populations.

AARC clinical practice guideline: effectiveness of nonpharmacologic airway clearance therapies in hospitalized patients.

Airway clearance therapy (ACT) is used in a variety of settings for a variety of ailments. These guidelines were developed from a systematic review with the purpose of determining whether the use of nonpharmacologic ACT improves oxygenation, reduces length of time on the ventilator, reduces stay in the ICU, resolves atelectasis/consolidation, and/or improves respiratory mechanics, versus usual care in 3 populations. For hospitalized, adult and pediatric patients without cystic fibrosis, 1) chest physiotherapy (CPT) is not recommended for the routine treatment of uncomplicated pneumonia; 2) ACT is not recommended for routine use in patients with COPD; 3) ACT may be considered in patients with COPD with symptomatic secretion retention, guided by patient preference, toleration, and effectiveness of therapy; 4) ACT is not recommended if the patient is able to mobilize secretions with cough, but instruction in effective cough technique may be useful. For adult and pediatric patients with neuromuscular disease, respiratory muscle weakness, or impaired cough, 1) cough assist techniques should be used in patients with neuromuscular disease, particularly when peak cough flow is < 270 L/min; CPT, positive expiratory pressure, intrapulmonary percussive ventilation, and high-frequency chest wall compression cannot be recommended, due to insufficient evidence. For postoperative adult and pediatric patients, 1) incentive spirometry is not recommended for routine, prophylactic use in postoperative patients, 2) early mobility and ambulation is recommended to reduce postoperative complications and promote airway clearance, 3) ACT is not recommended for routine postoperative care. The lack of available high-level evidence related to ACT should prompt the design and completion of properly designed studies to determine the appropriate role for these therapies.

Incorporating tiotropium into a respiratory therapist-directed bronchodilator protocol for managing in-patients with COPD exacerbations decreases bronchodilator costs.

BACKGROUND: Tiotropium is used in maintenance treatment of chronic obstructive pulmonary disease (COPD), but there are no guidelines on when to start tiotropium following an exacerbation. OBJECTIVE: To determine whether the addition of tiotropium to a respiratory-therapist-directed bronchodilator protocol affects bronchodilator costs for patients hospitalized for COPD exacerbation. METHODS: We retrospectively analyzed data on the number and type of bronchodilator treatments administered to all patients admitted for COPD exacerbation during the 3-month period (January through March 2006) after tiotropium was added to our bronchodilator protocol, and compared that data to a historical control period (January through March 2004) before tiotropium was available in our hospital. We compared the costs of bronchodilator treatments, baseline patient characteristics, comorbidities, concomitant medications, length of stay, adverse events, and in-hospital deaths. RESULTS: Baseline characteristics, comorbidities, and concomitant medications were similar in the 2004 control group (n = 181) and the 2006 intervention group (n = 174). The mean +/- SD number of bronchodilator treatments per admission was significantly higher in the control period (13.6 +/- 15.6) than in the intervention period (10.6 +/- 9.4). That difference correlated to a reduction in combination therapy (short-acting inhaled beta(2) agonist plus ipratropium), which decreased from a per-admission average of 6.7 +/- 14.2 in the control period to 1.9 +/- 5.1 in the intervention period. Calculated bronchodilator costs were significantly lower in the intervention period than in the control period. Length of stay also significantly decreased, from 6.5 +/- 5.0 d to 5.5 +/- 4.0 d. There were no adverse events related to tiotropium. Pulmonary-related in-hospital deaths were not significantly different between the 2 periods. CONCLUSIONS: Early addition of maintenance-treatment tiotropium to a respiratory-therapist-directed bronchodilator protocol for patients hospitalized for COPD exacerbation reduced costs and produced no safety concerns.