ATS Reading List

Ventilation and Weaning

Invasive mechanical ventilation

See this ATS tutorial for an excellent in-depth description of ventilator waveform interpretation and analysis.

Disease-Specific Strategies for Invasive Ventilation

Darioli R, Perret C. Mechanical controlled hypoventilation in status asthmaticus. Am Rev Respir Dis 1984;129:385-7.  Noteworthy for being the first description of permissive hypercapnea and low tidal volumes during mechanical ventilation of asthmatics with high airway pressures.
PMID: 6703497

See "ARDS-Mechanical Ventilation"

Care of the intubated patient

Marini JJ, Pierson DJ, and Hudson LD. Acute lobar atelectasis: a prospective comparison of fiberoptic bronchoscopy and respiratory therapy. Am Rev Resp Dis 1979;119:971-8. This study found FOB, for the sole purpose of atelectasis, followed by RT was no better than RT alone at 24-48 hours.
PMID: 453712

Heiblum G, Chalumeau-Lemoine L, Joos V, et al. Comparison of routine and on-demand prescription of chest radiographs in mechanically ventilated adults: a multicentre cluster-randomised, two-period crossover study. Lancet 2009; 374:1687-93. This study randomized 849 patients to daily vs. on-demand chest radiographs as clinically indicated. The on-demand strategy reduced the mean number of radiographs per day of ventilation from 1.09 to 0.75 (32% absolute reduction) with no change in length of ventilation, ICU stay, or mortality.
PMID:19896184

Francois B, Bellissant E, Gissot V, et al. 12-h pretreatment with methylprednisolone versus placebo for prevention of post-exutbation laryngeal oedema: a randomized double-blind trial. Lancet 2008; 369:1083-89. The largest multicenter RCT of steroids for prevention of laryngeal edema. 698 adults intubated >36 hrs received methylprednisolone (20 mg IV) or placebo every 4 hours for 12 hours preceding extubation. Laryngeal edema was significantly reduced (22% vs 3%), as were overall reintubation rate (8% vs 4%) and reintubation due to laryngeal edema (54% vs 8%). Subsequent meta-analyses emphasize the benefit of multiple dose rather than single dose steroid administration.
PMID: 17398307

Ventilator Weaning

Yang KL, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 1991; 324:1445-50. Study in a VA population found the rapid shallow breathing index (RSBI = RR/Vtidal) was the single best predictor of weaning success (sensitivity 0.97, specificity 0.64).
PMID: 2023603
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Brochard L, Rauss A, Benito S, et al. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med 1994; 150:896-903. Prospective, randomized study found weaning with pressure support mode superior to SIMV mode and T-piece trials.
PMID: 7921460

Esteban A, Frutos F, Tobin MJ, et al. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995; 332:345-50. Prospective, randomized study found once daily or multiple daily trials of spontaneous breathing (T-piece or CPAP <5 cm) resulted in more rapid successful extubation than gradual weaning of pressure support or IMV.
PMID: 7823995
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Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335:1864-9. RCT found protocol of daily weaning parameters followed by trials of spontaneous breathing in appropriate patients and subsequent notification of physicians of successful trials reduced the duration of mechanical ventilation compared to usual care (daily weaning parameters only).
PMID: 8948561

Girard T, Kress J, Fuchs B, et al. Efficacy and safety of paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awake and Breathing Controlled trial): a randomized controlled trial. Lancet 2008;371:126-34. This RCT found the combination of daily sedation holiday and daily weaning trials resulted in reduced ventilator days and reduced mortality compared to daily weaning trials alone (HR 0.68, p = .01, NNT to save one life 7).
PMID: 18191684

Jubran A, Grant BJB, Duffner LA, et al. Effect of pressure support versus unassisted breathing through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical ventilation: A randomized trial. JAMA. 2013;309:671–677. This single center study required 10 years for patient recruitment. They found a shorter weaning time when using unassisted breathing via tracheostomy ("T-piece") as opposed to a pressure support method. These findings are balanced against a lack of mortality benefit at 6 and 12 months (>50% of patients in both groups had died after 6 months).
PMID:23340588
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The following citations address the utility of early, intensive rehabilitation in critically patients. While Schweickert, et al described an improvement in functional outcomes at discharge, delirium, and ventilator-free days, two recently published trials with longer follow up showed no benefit in ventilator-free days and either no (Moss, et al) or mixed (Morris, et al) long-term functional outcomes.

Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomized controlled trial. Lancet 2009;373:1874-82.
PMID: 19446324

Moss M, Nordon-Craft A, Malone D, et al. A randomized trial of an intensive physical therapy program for patients with acute respiratory failure. Am J Resp Crit Care Med. 2016; 193:1101-10.
PMID: 26651376

Morris PE, Berry MJ, Files DC, et al. Standardized rehabilitation and hospital length of stay among patients with acute respiratory failure: a randomized clinical trial. JAMA. 2016; 315:2694-702.
PMID: 27367766

Tracheostomy

Terragni P, Antonelli M, Fumagalli R, et al. Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a randomized controlled trial. JAMA 2010;303:1483-9. This trial of over 400 patients found a statistically non-significant reduction in VAP with early bedside tracheotomy (within 6-8 days of intubation) compared to late tracheostomy (13-15 days of intubation) (14% vs. 21%, p = 0.07). The early tracheotomy group had greater ventilator-free and ICU-free days but there was no difference in mortality or hospital length of stay. Only 69% assigned to the early group and 57% to the late group actually underwent tracheostomy, highlighting the difficulty of predicting the need for tracheostomy early in the course of illness.
PMID: 20407057
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Young D, Harrison DA, Cuthbertson BH. Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial. JAMA. 2013; 309;2121-2129. Open, randomized, multicenter clinical trial randomized 909 patients predicted to require >7 days of ventilation to early (day 4) or late (day 10) tracheostomy. There was no change in mortality, and, of note, only 44.9% of patients randomized to the late tracheostomy group required it, as opposed to 94% of the early tracheostomy group.
PMID: 23695482
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***See also ARDS, Neurology Critical Care, Sedation and Analgesia, Terragni PP et al. in "Prevention and Treatment" of Ventilator-associated Pneumonia and Squadrone V et al.

Noninvasive mechanical ventilation

COPD

Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of COPD. N Engl J Med 1995; 333:817-22. Landmark prospective, randomized study found use of NIPPV in selected patients with COPD exacerbations resulted in fewer intubations, complications, days in hospital, and lower in-hospital mortality compared to standard treatment.
PMID: 7651472
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Nava S, Ambrosino N, Clini E, et al. Non-invasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease. Ann Intern Med 1998; 128:721-8. Oft-cited RCT included 50 patients intubated for a COPD exacerbation who failed a T-piece trial. Patients randomized to immediate extubation to NIPPV had decreased duration of mechanical ventilation and improved survival compared to the control group undergoing PS wean with twice daily spontaneous breathing trials.
PMID: 9556465

Heart Disease

Bersten AD, Holt AW, Vedig AE, et al. Treatment of severe cardiogenic pulmonary edema with CPAP delivered by facemask. N Engl J Med 1991; 325:1825-30. Randomized study of 39 patients with hypercapnic cardiogenic respiratory failure found use of CPAP plus oxygen resulted in better gas exchange in the first 24 hours and less need for intubation than use of oxygen alone.
PMID: 1961221
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Masip J, Betbese AJ, Paez J, et al. Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary edema: a randomized trial. Lancet 2000; 356:2126-32. Study of 37 patients (of whom 43% had hypercapnia) found pressure support by mask reduced the need for intubation (5% vs. 33%). There was no difference in duration of hospital stay or mortality.
PMID: 11191538

Gray A, Goodacre S, Newby DE, et al. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med 2008; 359:142-51. The 3CPO study, performed in 26 emergency departments, randomized 1,156 patients to standard oxygen therapy, CPAP, or NIPPV. Neither form of noninvasive support reduced 7 or 30-day mortality, and patients receiving CPAP and NIPPV did not differ in need for intubation. The lack of benefit persisted after adjusting for severity of illness. These results differ from prior positive studies, possibly due to differences in study populations and design. Intubation rates and 30-day mortality were lower in the current study, and patients deteriorating with standard oxygen therapy were allowed rescue use of noninvasive support.

PMID: 18614781

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See also "Cowie MR, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure." In Sleep Medicine.

Hypoxemic respiratory failure (all types)

Declaux C, L'Her E, Alberti C, et al. Treatment of acute hypoxemic non-hypercapnic respiratory insufficiency with CPAP delivered by facemask. JAMA 2000; 284:2352-60. Prospective, randomized, multicenter study compared oxygen to oxygen plus CPAP in this population (123 patients; 17% cardiac etiology, 83% ARDS). Study found no difference in the need for intubation, length of hospital stay, or hospital mortality, and the CPAP group had an increased incidence of adverse events.
PMID: 11066186
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Ferrer M, Esquinas A, Leon M, et al. Non-invasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial. Am J Respir Crit Care Med 2003; 168:1140-4. Study of 105 non-hypercapnic patients found NIPPV decreased need for intubation and improved 90-day survival compared to oxygen therapy alone. Unlike some prior studies, subgroup analysis found the 34 patients with pneumonia had the greatest benefit while mask ventilation did not appear to reduce the need for intubation in patients with ARDS and cardiogenic edema.
PMID: 14500259

Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015; 372:2185-2196. This trial randomized patients with hypoxic respiratory failure to oxygen by facemask, NIPPV, or high flow nasal cannula. This was the first study to compare HFNC to NIPPV in this setting.  Investigators found no difference in the rate of intubation, although a post hoc analysis did find significantly decreased rate in patients with severe hypoxemia treated with HFNC. The HFNC group also had significantly more ventilator-free days and an unexpected decrease in 90 day all cause mortality. Weaknesses in this essentially negative trial include a low power to detect inter-group differences in intubation, and some crossover between interventions.
PMID: 25981908
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Following extubation

Ferrer M, Sellarés J, Valencia M, et al. Non-invasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomized controlled trial. Lancet 2009; 374:1082-8. In a randomized trial of over 100 patients with chronic lung disease who passed a spontaneous breathing trial but had hypercapnea post-extubation, NIPPV led to a significant reduction in subsequent respiratory failure (15% vs 48% in the control group). Rescue NIPPV averted the need for re-intubation in 17 of 27 control patients with post-extubation respiratory failure. In contrast to the Esteban study below, NIPPV in post-extubation hypercapnic respiratory failure appeared beneficial. Whether there is an advantage to immediate over prn NIPPV use in this population is unclear.
PMID: 19682735

Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med 2004; 350:2452-60. This trial of 221 patients with respiratory failure within 48 hours of being extubated after receiving at least 48 hours of mechanical ventilation randomized patients to noninvasive ventilation by face mask or standard medical therapy. Noninvasive ventilation did not reduce the need for re-intubation and the standard-therapy group had lower ICU mortality (14% vs. 25% in noninvasive group). These results suggest noninvasive positive-pressure ventilation should not be used in unselected patients failing extubation.
PMID: 15190137
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Hernández G, Vaquero C, Colinas L, et al. Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial. JAMA. 2016; 316:1565-74. A randomized multicenter noninferiority trial of 24 hours of non-invasive ventilation or HFNC following extubation in "high risk" patients, which included those with COPD and heart failure. They found that HFNC was noninferior to NIV with respect to preventing reintubation and post-extubation respiratory failure. The HFNC group had fewer adverse effects leading to withdrawal of therapy.
PMID: 27706464
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Hernández G, Vaquero C, González P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: A randomized clinical trial. JAMA. 2016;315:1354-61. From the same group as the preceding trial, this multicenter trial compared HFNC to conventional oxygen for prevention of reintubation in 527 mechanically ventilated patients that were considered "low risk" for reintubation. In the first 72 hours, they found use of HFNC significantly reduced reintubation rate (4.9 vs. 12.2%) and post-extubation respiratory failure. There was no difference in adverse events.
PMID: 26975498

Primary neuromuscular disease

Ambrosino N, Carpenè N, Gherardi M. Chronic respiratory care for neuromuscular diseases in adults. Eur Respir J. 2009;34:444-51. Concise review of the use of non-invasive ventilation and other respiratory care for patients with neuromuscular disorders.
PMID: 19648521
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Bourke SC, Tomlinson M, Williams TL, et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomized controlled trial. Lancet Neurol 2006; 5:140-7. This study of 41 patients found NIV improved survival by a median of 205 days (p < .01) in patients with normal or moderately impaired bulbar function. All patients had at least some degree of improved quality of life with NIV, but those with poor bulbar function did not have improved survival.
PMID: 16426990

Last Reviewed: June 2017