Acute respiratory failure in randomized trials of noninvasive respiratory support: A systematic review of definitions, patient characteristics, and criteria for intubation.

PURPOSE: To examine the definitions of acute respiratory failure, the characteristics of recruited patients, and the criteria for intubation used in randomized trials. METHODS: We searched MEDLINE for randomized trials of noninvasive respiratory support modalities in patients with de novo respiratory failure. We included trials from 1995 to 2017 that enrolled 40 or more patients and used intubation as an outcome. RESULTS: We examined the reports of 53 trials that enrolled 7225 patients. There was wide variation in the use of variables for defining acute respiratory failure. Dyspnea was rarely measured and the increase in breathing effort was poorly defined. The characteristics of patients enrolled in trials changed over time and differed by the cause of respiratory failure. Intubation was poorly characterized. The criteria for intubation had more variables than the criteria for respiratory failure. CONCLUSIONS: We identified deficiencies in the design and reporting of randomized trials, some of which can be remedied by investigators. We also found that patient characteristics differ by the type of respiratory failure. This knowledge can help clinician identify patients at the right moment to benefit from the tested interventions and investigators in developing criteria for enrollment in future trials.

Self-Extubation Revisited: A Case-Control Study.

BACKGROUND: To increase the understanding of the self-extubation phenomena, we assessed its rate in our medical ICU and aimed to identify the risk factors of self-extubation and the risk factors for re-intubation. METHODS: We prospectively identified subjects who self-extubated. Their baseline characteristics, including the Richmond Agitation Severity Scale score, reason for intubation, shift, distance of the endotracheal tube tip to the carina, and outcomes were collected retrospectively. For every subject who self-extubated, a control subject was selected from the mechanical ventilation database. RESULTS: During the study period, there were 2,578 admissions with 4,072 mechanical ventilation days. Fifty-three cases of self-extubation were recorded, which resulted in a self-extubation event rate of 1.3 per 100 days of mechanical ventilation. Forty-five controls were identified. The most common reason for intubation was hypoxic respiratory failure, followed by the need for airway protection and hypercapnic respiratory failure. Sedation was administered continuously in 34% of the subjects. Thirty-seven percent received no sedation. At the time of the event, the subjects who self-extubated had a higher Richmond Agitation Severity Scale score, a longer distance from the endotracheal tip to carina on the chest radiograph preceding the event, and a shorter duration of mechanical ventilation, and were more likely to be on volume-controlled mechanical ventilation. ICU mortality was lower in the self-extubation group, despite having a trend toward a higher Simplified Acute Physiology Score II. Sixteen subjects required re-intubation. Independent predictors of re-intubation were hypoxic respiratory failure as the reason for the initial intubation and self-extubation that occurred at night. The need for re-intubation was not associated with higher mortality. CONCLUSIONS: Results of our study showed that, in the era of reduced use of sedatives in the ICU, clinicians must be vigilant of the risk of self-extubation in the first 2 d of mechanical ventilation in patients who are agitated and with a longer endotracheal tube to carina distance on chest radiograph.

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

The clinical implications of tests confirming COPD in subjects hospitalized with exacerbations.

BACKGROUND: The diagnosis of COPD in patients hospitalized for AECOPD can be confirmed by spirometry showing obstruction or radiographs showing emphysema. The evidence for COPD is sometimes absent or contradicts this diagnosis. The inaccurate attribution of the exacerbation to COPD can lead to suboptimal care and worse outcome. OBJECTIVES: We determined if the presence of tests that confirm the diagnosis of COPD has any implications on the course of the hospitalization and readmission rate. METHODS: We selected subjects hospitalized between 2012 and 2014 for AECOPD. We divided them into four hierarchical, mutually exclusive groups based on the presence of tests that confirm the diagnosis of COPD: spirometry (COPDSPIRO), radiology (COPDRAD), clinical diagnosis (COPDCLIN), and no COPD by spirometry (NotCOPD). We compared the presentation, hospital course, outcome, and readmission rate between the four groups. RESULTS: We identified 974 subjects: COPDSPIRO 22%, COPDRAD 24%, COPDCLIN 46% and 7% NotCOPD. The vital signs, use of respiratory support, admission to the MICU, and length of stay were similar between the groups. The age, gender, BMI, presence of comorbidities, and readmission rate were different between the groups. The NotCOPD group had the highest BMI (38 kg/m2), comorbidities, and 30-day all-cause readmission (17%). Logistic regression showed that serum creatinine and presence of any comorbidity were the independent predictors of 30-day all-cause readmission. CONCLUSION: COPD was confirmed by spirometry or radiographs in half of the subjects hospitalized for AECOPD. The presence of confirmation did not influence the hospital course. The presence of confirmation was associated with different readmission rate, but was accounted for by the presence of comorbidities.

DiapHRaGM: A mnemonic to describe the work of breathing in patients with respiratory failure.

BACKGROUND: The assessment of the work of breathing in the definitions of respiratory failure is vague and variable. OBJECTIVE: Identify a parsimonious set of signs to describe the work of breathing in hypoxemic, acutely ill patients. METHODS: We examined consecutive medical ICU patients receiving oxygen with a mask, non-invasive ventilation, or T-piece. A physician inspected each patient for 10 seconds, rated the level of respiratory distress, and then examined the patient for vital signs and 17 other physical signs. We used the rating of distress as a surrogate for measuring the work of breathing, constructed three multivariate models to identify the one with the smallest number of signs and largest explained variance, and validated it with bootstrap analysis. RESULTS: We performed 402 observations on 240 patients. Respiratory distress was absent in 78, mild in 157, moderate in 107, and severe in 60. Respiratory rate, hypoxia, heart rate, and frequency of most signs increased as distress increased. Respiratory rate and hypoxia explained 43% of the variance in respiratory distress. Diaphoresis, gasping, and contraction of the sternomastoid explained an additional 28%. Heart rate, blood pressure, alertness, agitation, body posture, nasal flaring, audible breathing, cyanosis, tracheal tug, retractions, paradox, scalene or abdominal muscles contraction did not increase the explained variance in respiratory distress. CONCLUSION: Most of the variance is respiratory distress can be explained by five signs summarized by the mnemonic DiapHRaGM (diaphoresis, hypoxia, respiratory rate, gasping, accessory muscle). This set of signs may allow for efficient, standardized assessments of the work of breathing of hypoxic patients.

Effect of arterial puncture on ventilation.

BACKGROUND: Clinicians frequently assume that during arterial puncture for measuring arterial blood gases patients hyperventilate from pain and anxiety. This assumption leads clinicians to falsely interpret a PaCO2 and pH near the upper limit of normal as a chronic respiratory acidosis corrected by an acute respiratory alkalosis. OBJECTIVE: Determine if participants hyperventilate during arterial puncture from pain and anxiety. METHODS: We recruited participants from a pulmonary function laboratory referred for arterial blood gas measurement. We excluded those with heart failure and included those with any respiratory condition (COPD, asthma, sleep apnea). We measured end tidal PCO2 (PETCO2), respiratory rate, and heart rate 15 min before topical anesthesia, during anesthesia, during arterial puncture, and 15 min later. We assessed generalized anxiety before and measured pain during and after arterial puncture. RESULTS: 24 participants were recruited (age: 54 ± 12 years; men: 54%). PaCO2 was 41 ± 5 mmHg. One had acute respiratory alkalosis. Respiratory rate increased from (19 ± 6 breaths per minute (bpm)) before to a maximum (21 ± 6 bpm) during arterial puncture (p = 0.001). Heart rate was stable throughout. The lowest PETCO2 during the procedure (35 ± 5) was similar to PETCO2 before the procedure (p = 0.1). The change in PETCO2 and respiratory rate did not correlate with pain, anxiety, or lung function. CONCLUSION: Respiratory rate increased slightly during arterial puncture without any change in PETCO2. Hence, acid-base status must be interpreted without the assumption of procedure induced hyperventilation.

The effects of obesity on lung volumes and oxygenation.

INTRODUCTION: Obesity can cause hypoxemia by decreasing lung volumes to where there is closure of lung units during normal breathing. Studies describing this phenomenon are difficult to translate into clinical practice. We wanted to determine the lung volume measurements that are associated with hypoxemia in obese patients, and explore how we could use these measurements to identify them. METHODS: We collected pulmonary function test results and arterial blood gas data on 118 patients without obstruction on pulmonary function testing. We included only patients with normal chest imaging and cardiac testing within one year of the pulmonary function test, to exclude other causes of hypoxemia. RESULTS: We found that as BMI increases, the mean paO2, ERV % predicted, and ERV/TLC decrease (BMI 20-30 kg/m2: paO2=90±8 mmHg, ERV% predicted 112±50, ERV/TLC (%) 19.7±6.5; BMI 30-40 kg/m2: paO2=84±10 mmHg, ERV% predicted 84±40 ERV/TLC(%) 13.6±7.6; BMI>40 kg/m2: paO2 78 ±12 mmHg, ERV% predicted 64±27 ERV/TLC(%) 11.4±5.8, ANOVA p<0.001). The A-a gradient increases as BMI increases (r=0.42, p<0.001). This correlation was stronger in men (r=0.54) than in women (r=0.35). The paO2 is lower in patients with a low ERV than in those with a normal ERV (p<0.001). In a multivariate linear regression, only the ERV/TLC predicted (%), age, and BMI were associated with oxygenation (r2 for A-a gradient =0.28, p=0.036). CONCLUSIONS: In obese patients without cardiopulmonary disease, oxygen levels decrease as BMI increases. This effect is associated with the obesity-related reduction in ERV and is independent of hypoventilation.

Therapeutic hypothermia at an urban public hospital: Development, implementation, experience and outcomes.

BACKGROUND: Therapeutic hypothermia (TH) improves the outcome of comatose patients suffering an out-of-hospital sudden cardiac arrest (SCA) with shockable rhythm and return of spontaneous circulation (ROSC). Evidence supporting its use in other circumstances is weak and the adoption of TH remains limited. OBJECTIVE: Describe the development and implementation of a TH program at an urban public hospital and report outcomes of out-of-hospital and in-hospital SCA and important quality measures. METHODS: The protocol was developed at 464-bed urban public hospital. We assembled historical and prospective samples of patients suffering an SCA. We measured the neurologic outcome of patients at the time of hospital discharge who underwent TH after SCA. We compared outcomes and important quality measures (duration of arrest, time to cooling, and time to target temperature) to existing literature. We determined reasons for not using TH in patients with in-hospital SCA. RESULTS: We described the development of our TH program and the challenges we faced implementing it. Of 45 patients treated with TH after SCA, 23 (51%) survived to discharge, 14 (31%) with good neurologic outcomes. In comparison to historical controls, TH did not improve outcome of in-hospital SCA. SCA from a shockable rhythm was associated with the best outcome. The time from return of spontaneous circulation to initiation of TH was consistently within 8 h. CONCLUSIONS: Despite logistical and financial constraints, we were able to rapidly implement a TH program with quality and outcomes similar to published data. TH did not improve outcomes for patients with an in-hospital SCA.

The Accuracy of Portable Monitoring in Diagnosing Significant Sleep Disordered Breathing in Hospitalized Patients.

BACKGROUND: Polysomnograms are not always feasible when sleep disordered breathing (SDB) is suspected in hospitalized patients. Portable monitoring is a practical alternative; however, it has not been recommended in patients with comorbidities. OBJECTIVE: We evaluated the accuracy of portable monitoring in hospitalized patients suspected of having SDB. DESIGN: Prospective observational study. SETTING: Large, public, urban, teaching hospital in the United States. PARTICIPANTS: Hospitalized patients suspected of having SDB. METHODS: Patients underwent portable monitoring combined with actigraphy during the hospitalization and then polysomnography after discharge. We determined the accuracy of portable monitoring in predicting moderate to severe SDB and the agreement between the apnea hypopnea index measured by portable monitor (AHIPM) and by polysomnogram (AHIPSG). RESULTS: Seventy-one symptomatic patients completed both tests. The median time between the two tests was 97 days (IQR 25-75: 24-109). Forty-five percent were hospitalized for cardiovascular disease. Mean age was 52±10 years, 41% were women, and the majority had symptoms of SDB. Based on AHIPSG, SDB was moderate in 9 patients and severe in 39. The area under the receiver operator characteristics curve for AHIPM was 0.8, and increased to 0.86 in patients without central sleep apnea; it was 0.88 in the 31 patients with hypercapnia. For predicting moderate to severe SDB, an AHIPM of 14 had a sensitivity of 90%, and an AHIPM of 36 had a specificity of 87%. The mean±SD difference between AHIPM and AHIPSG was 2±29 event/hr. CONCLUSION: In hospitalized, symptomatic patients, portable monitoring is reasonably accurate in detecting moderate to severe SDB.

The validity and reliability of the clinical assessment of increased work of breathing in acutely ill patients.

BACKGROUND: Mechanical ventilation is frequently indicated to reduce the work of breathing. Because it cannot be measured easily at the bedside, physicians rely on surrogate measurements such as patient appearance of distress and increased breathing effort. OBJECTIVE: We determined the validity and reliability of subjectively rating the appearance of respiratory distress and the reliability of 11 signs of increased breathing effort. SUBJECTS: The study included consecutive, acutely ill patients requiring various levels of respiratory support. METHODS: Blinded to each other's observations, a fellow and a critical care consultant rated the severity of distress (absent, slight, moderate, severe) after observing subjects for 10 seconds and then determined the presence of the signs of increased breathing effort. RESULTS: A total of 149 paired examinations occurred 6±6 minutes apart. The rating of respiratory distress correlated with oxygenation, respiratory rate, and 9 signs of increased work of breathing. It had the highest intraclass correlation coefficient (0.69; 95% confidence interval, 0.59-0.78). Rating distress as moderate to severe had a sensitivity of 70%, specificity of 92%, and positive likelihood ratio of 8 for the presence of 3 or more of hypoxia, tachypnea, and any sign of increased breathing effort. Agreement was moderate (κ = 0.53-0.47) for rating of distress, nasal flaring, scalene contraction, gasping, and abdominal muscle contraction, and fair (κ = 0.36-0.23) for sternomastoid contraction, tracheal tug, and thoracoabdominal paradox. CONCLUSION: Assessing the increased work of breathing by rating the severity of respiratory distress based on subject appearance is a valid and moderately reliable sign that predicts the presence of serious respiratory dysfunction. The reliability of the individual signs of increased breathing effort is moderate at best.

Effect of Wakefulness-Promoting Agents on Sleepiness in Patients with Sleep Apnea Treated with CPAP: A Meta-Analysis.

STUDY OBJECTIVES: To perform a meta-analysis of the effect of wakefulness-promoting agents (modafinil and armodafinil) in patients with residual sleepiness after CPAP therapy for obstructive sleep apnea. METHODS: We conducted a systematic search of MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014) and Cochrane Database for randomized placebo controlled trials on modafinil or armodafinil in patients who met established criteria for diagnosis of obstructive sleep apnea, adequate continuous positive airway pressure use, and who complained of residual sleepiness. Risk of bias was assessed. Primary outcomes were the Epworth Sleepiness Scale and mean sleep latencies on the maintenance of wakefulness test. Secondary outcomes were the Clinical Global Impression of Change, change in daily continuous positive airway pressure use, and the frequency of headaches. RESULTS: Out of 118 abstracts screened and 12 full text articles reviewed, we included 6 studies (total of 1,479 participants) in our final meta-analysis: Three evaluated modafinil, and three armodafinil. Risk of bias was unclear in one or more key domains for four studies. When compared with placebo, wakefulness promoting agents decreased Epworth Sleepiness Scale by 2.51 points (95% CI, 2.00-3.02), increased sleep latency in maintenance of wakefulness test by 2.73 minutes (95% CI, 2.12-3.34), increased the reporting of minimal improvement on the Clinical Global Impression of Change by 26% (RR 1.59; 95% CI, 1.36-1.86), and increased the risk of headaches by 8% (RR 1.98; 95% CI, 1.48-2.63). Also, there was a trend for decreased continuous positive airway pressure after treatment with these agents. CONCLUSION: Wakefulness promoting agents improve objective and subjective measures of sleepiness, wakefulness, perception of disease severity in patients with residual sleepiness after CPAP therapy for OSA, and are generally well tolerated.

Association between rating of respiratory distress and vital signs, severity of illness, intubation, and mortality in acutely ill subjects.

BACKGROUND: When deciding whether mechanical ventilation is indicated, physicians integrate their findings on physical examination in a gestalt known as respiratory distress. Despite its importance, this gestalt is poorly understood. This study aims to describe the association between the rating of the severity of respiratory distress and vital signs, severity of illness, use of mechanical ventilation, and death. A prospective observational study with 1,134 consecutive subjects with uncertain triage evaluated by a critical care consult team was carried out in a public inner city teaching hospital. METHODS: After the initial evaluation of each patient, a critical care physician rated the level of respiratory distress. We recorded vital signs, diagnosis, and laboratory results and calculated the Acute Physiology and Chronic Health Evaluation (APACHE) II score. We recorded if mechanical ventilation was initiated by 72 h and if the subject died during the hospitalization. RESULTS: The most common diagnoses were respiratory illnesses. Higher distress levels were associated with higher breathing frequency (20, 22, 27, and 30 breaths/min, P < .001) and heart rate (96, 101, 109, and 116 beats/min, P < .001) and lower S(pO2) (97, 95, 93, and 92%, P < .001). These variables explain only a small portion of the variance of distress. Distress correlated weakly with the APACHE II score (r = 0.22, P = .001). Blood pressure, temperature, Glasgow coma scale score, and laboratory data were unrelated to the levels of distress. However, higher levels of distress correlated with intubation rates (5, 13, 27, and 41%, P < .001). The area under the receiver operating characteristic curve for respiratory distress predicting intubation (0.72) was larger than that for breathing frequency (0.65). Distress was an independent predictor of intubation but not of death. CONCLUSIONS: A physician's rating of respiratory distress is independently predictive of intubation in 72 h. Vital signs explain only a small proportion of variance in distress; the other observations contributing to a physician's rating of distress must be determined.

Is the content of textbooks on the evaluation of a patient in respiratory distress adequate?

BACKGROUND: The ability to rapidly and precisely evaluate patients in respiratory distress is essential. Due to limited opportunities for formal instruction during training, textbooks are the main educational source to teach junior physicians how to interpret the signs of respiratory distress. The quality of the textbook content relevant to respiratory distress is unknown. OBJECTIVE: To examine the content on the evaluation of a patient in respiratory distress in a representative sample of textbooks and Internet resources. METHODS: Two physicians individually reviewed the most recent edition of 21 standard textbooks from a variety of specialties. Smartphone applications, UptoDate, and MD Consult were examined. Each physician reviewed the source for 14 different signs. For each sign, the reviewers determined 3 parameters: a mention of the sign, its pathophysiology, and its detection. The reviews were compared for discrepancies, and a third reviewer resolved them. RESULTS: The normal respiratory rate was mentioned in 10 (48%) of textbooks, and ranged between 10 and 22 breaths/min. Each sign was mentioned by a mean of 45 ± 26% of the textbooks. The pathophysiology of the signs was described by a mean of 33 ± 30% of the textbooks. The most and least commonly mentioned inspection signs were cyanosis and retraction of suprasternal notch, respectively. They were mentioned in 20 (95%) and 4 (19%) textbooks, respectively. The most and least commonly mentioned palpation signs were thoracoabdominal asynchrony or paradox and tracheal tug, respectively. They were mentioned in 17 (81%) and 4 (19%) textbooks, and their pathophysiology was described in 15 (71%) and 4 (19%) textbooks, respectively. The reviewers also found inconsistency in the descriptions of the meaning of scalene muscle contraction and thoracoabdominal asynchrony and paradox. CONCLUSIONS: The content of the reviewed textbooks on the evaluation of respiratory distress is inconsistent and deficient.

Accuracy and reliability of extubation decisions by intensivists.

BACKGROUND: Mortality increases when extubations fail. Although predictors of extubation failure have been evaluated, physicians' reasoning to extubate a patient has received minimal attention. We hypothesized that the accuracy and reliability of physicians' extubation decisions are low. METHODS: We sent surveys to 55 physicians in the divisions of pulmonary and critical care medicine of 3 teaching hospitals in Chicago, Illinois. The survey comprised 32 clinical vignettes of real patients who were extubated after they tolerated a spontaneous breathing trial (16 failed extubations). Unaware of the outcomes of extubation, the physicians were asked if they would extubate each patient, and to give reasons if they opted not to. We quantified the agreement between and accuracy of the physicians' decisions, determined the patient characteristics that influence the extubation decision, and described the tradeoffs leading to that decision. RESULTS: Completed surveys were obtained from 45 physicians (82%). The physicians postponed extubation in 37% of the cases. Agreement between any 2 physicians was fair (mean ± SD phi 0.34 ± 0.15) and was highest between attending physicians from the same institution (0.37 ± 0.15). In deciding to extubate a patient, 33% of the physicians relied on the breathing pattern on pressure support ventilation, 49% relied on the acid-base status, 13% relied on the mental status, and 8% relied on the amount of secretions. The accuracy of the physicians' extubation decisions was low (area under the receiver operating characteristic curve 0.35). The sensitivity of the physicians identifying the patients who were successfully extubated was 57%, and the specificity was 31%. A model that comprises the same variables that influenced the physicians was more accurate in predicting extubation outcome (area under the receiver operating characteristic curve 0.88). CONCLUSIONS: For a decision made on an almost daily basis in intensive care units, physicians' extubation decisions are inaccurate and only fairly reliable.

Predicting extubation failure after successful completion of a spontaneous breathing trial.

OBJECTIVE: To derive a clinical prediction rule that uses bedside clinical variables to predict extubation failure (reintubation within 48 h) after a successful spontaneous breathing trial. METHODS: This prospective observational cohort study was performed at the Northwestern Memorial Hospital in Chicago, Illinois, which is a large tertiary-care university hospital. Among 673 consecutive patients who received mechanical ventilation during a 15-month period, 122 were ventilated for at least 2 days and did not undergo withdrawal of support or tracheostomy. These patients were followed after extubation to identify those who were reintubated within 48 h (extubation failure). We used logistic regression analysis to identify variables that predict reintubation, and we used bootstrap resampling to internally validate the predictors and adjust for overoptimism. RESULTS: Sixteen (13%) of the 122 patients required reintubation within 48 h. Three clinical variables predicted reintubation: moderate to copious endotracheal secretions (p = 0.001), Glasgow Coma Scale score < or =10 (p = 0.004), and hypercapnia (P(aCO(2)) > or = 44 mm Hg) during the spontaneous breathing trial (p = 0.001). Using logistic regression and bootstrap resampling to adjust for overfitting, we derived a clinical prediction rule that combined those 3 clinical variables (area under the receiver operating characteristic curve 0.87, 95% confidence interval 0.74-0.94). CONCLUSIONS: With our clinical prediction rule that incorporates an assessment of mental status, endotracheal secretions, and pre-extubation P(aCO(2)), clinicians can predict who will fail extubation despite a successful spontaneous breathing trial.