Management of the Difficult-to-Wean Patient: A Focus on Diaphragm Dysfunction

Dr Neeraj Manikath , claude.ai

Abstract

Prolonged mechanical ventilation affects approximately 10-15% of critically ill patients, with diaphragm dysfunction emerging as a critical determinant of weaning failure. ICU-acquired diaphragm weakness (ICUAW) develops rapidly—often within 18-24 hours of mechanical ventilation—and significantly increases mortality, ICU length of stay, and healthcare costs. This review synthesizes current evidence on the pathophysiology, diagnosis, and management of diaphragm dysfunction in difficult-to-wean patients, with emphasis on practical bedside assessment techniques, ventilator strategies to prevent ventilator-induced diaphragmatic dysfunction (VIDD), and emerging therapeutic interventions. Understanding and addressing diaphragm dysfunction is essential for optimizing weaning outcomes in the modern ICU.

ICU-Acquired Diaphragm Weakness: Pathophysiology and Risk Factors

Pathophysiological Mechanisms

ICU-acquired diaphragm weakness represents a multifactorial insult to the primary muscle of respiration, distinct from—yet frequently overlapping with—ICU-acquired weakness (ICUAW) affecting limb muscles. The diaphragm is uniquely vulnerable due to its continuous contractile activity and high metabolic demands.

Mechanical Ventilation-Induced Atrophy: Controlled mechanical ventilation leads to rapid diaphragm muscle fiber atrophy through multiple mechanisms. Disuse atrophy occurs within 18-69 hours of complete diaphragmatic inactivity, with myofiber cross-sectional area decreasing by 50% or more within the first week¹. This process is mediated by activation of proteolytic pathways, including the ubiquitin-proteasome system and calpain-mediated proteolysis, alongside suppression of protein synthesis through Akt-mTOR pathway inhibition².

Oxidative Stress and Mitochondrial Dysfunction: Mechanical ventilation triggers excessive production of reactive oxygen species (ROS) in diaphragm muscle fibers, leading to oxidative damage to contractile proteins, lipid membranes, and mitochondrial DNA³. Mitochondrial dysfunction perpetuates a vicious cycle of impaired energy production and further ROS generation, compromising diaphragm contractility even when muscle mass is preserved.

Inflammation and Cytokine-Mediated Injury: Systemic inflammatory states, particularly sepsis, induce diaphragm weakness through cytokine-mediated mechanisms. TNF-α, IL-1β, and IL-6 directly impair calcium handling, reduce myofibrillar force generation, and activate proteolytic pathways⁴. This "sepsis-induced diaphragm dysfunction" may occur independently of mechanical ventilation but is often synergistic with VIDD.

Neuromuscular Transmission Defects: Prolonged critical illness can impair phrenic nerve function and neuromuscular junction transmission. Critical illness polyneuropathy (CIP) and myopathy (CIM) frequently involve the diaphragm, though often to a lesser extent than limb muscles. Additionally, certain medications (neuromuscular blockers, corticosteroids, aminoglycosides) may contribute to transmission defects⁵.

Risk Factors

Ventilator-Related Factors:

Complete diaphragmatic unloading: Controlled modes (VC-CMV, PC-CMV) with absent spontaneous effort
Excessive assist: Over-assistance in pressure support or proportional modes
Deep sedation: Targeting RASS -4 to -5, eliminating respiratory drive
Duration of mechanical ventilation: Risk increases exponentially beyond 48-72 hours

Patient-Related Factors:

Sepsis and multiorgan failure: 2-3 fold increased risk⁶
Hyperglycemia: Poor glycemic control (>180 mg/dL) associated with accelerated atrophy
Malnutrition: Both protein-calorie malnutrition and overfeeding
Electrolyte derangements: Hypophosphatemia, hypomagnesemia, hypokalemia
Corticosteroid administration: Particularly high-dose or prolonged courses
Neuromuscular blocker use: Even single doses may contribute
Advanced age: Baseline sarcopenia amplifies VIDD susceptibility

Pearl: The concept of "myotrauma" parallels ventilator-induced lung injury—both too little (atrophy) and too much (eccentric injury from excessive effort) diaphragm loading cause dysfunction. The "safe zone" for diaphragm loading is the Goldilocks principle of mechanical ventilation.

Bedside Ultrasound for Diaphragm Assessment

Point-of-care ultrasound has revolutionized diaphragm assessment, providing real-time, radiation-free evaluation of diaphragm structure and function. Two primary techniques—diaphragm thickening fraction (DTF) and diaphragm excursion (DE)—offer complementary information.

Diaphragm Thickening Fraction (DTF)

Technique: Place a high-frequency linear probe (10-15 MHz) in the zone of apposition—the area where the diaphragm is apposed to the rib cage, typically between the 8th and 10th intercostal spaces in the midaxillary to anterior axillary line. Identify the diaphragm as a three-layered structure: pleura, diaphragm muscle (hypoechoic), and peritoneum⁷.

Measure diaphragm thickness at end-expiration (Tdi,ee) and end-inspiration (Tdi,ei) using M-mode or 2D imaging. Calculate DTF using:

DTF = [(Tdi,ei - Tdi,ee) / Tdi,ee] × 100%

Normal values: DTF >20-30% indicates adequate diaphragm contractility
Interpretation:

DTF <20%: Suggests diaphragm weakness or poor effort
DTF >30-40%: Normal contractility in most patients
DTF >50%: May indicate excessive respiratory effort or impending fatigue

Technical Tips:

Avoid excessive probe pressure (compresses diaphragm)
Ensure perpendicular beam alignment to muscle fibers
Average 3-5 respiratory cycles for accuracy
Bilateral assessment recommended—asymmetry >20% suggests unilateral dysfunction

Diaphragm Excursion (DE)

Technique: Use a low-frequency curvilinear probe (2-5 MHz) placed in the subcostal region, with the beam directed cephalad toward the diaphragm. Identify the liver (right side) or spleen (left side) as acoustic windows. Using M-mode, measure the craniocaudal displacement of the diaphragm during inspiration⁸.

Normal values: DE >1.0-1.4 cm during tidal breathing; >2.5 cm during deep inspiration
Interpretation:

DE <1.0 cm: Suggests diaphragm dysfunction or poor effort
Asymmetry (>50% difference): Consider unilateral phrenic nerve injury, paralysis
Paradoxical movement: Diagnostic of paralysis or severe dysfunction

Predictive Value for Weaning

Multiple studies demonstrate DTF and DE correlate with weaning success:

DTF >30% during spontaneous breathing trial (SBT): Positive predictive value 85-92% for successful extubation⁹
DE >1.4 cm during SBT: Sensitivity 85%, specificity 75% for weaning success¹⁰
Rapid shallow breathing index combined with DTF: Superior to RSBI alone (AUC 0.91 vs 0.73)

Oyster: Diaphragm ultrasound is operator-dependent. Formal training with at least 30 supervised scans is recommended for competency. Beware of overinterpretation—low DTF may reflect inadequate respiratory drive (sedation, metabolic alkalosis) rather than true weakness.

Emerging Ultrasound Parameters

Diaphragm Atrophy: Serial measurement of end-expiratory thickness predicts VIDD. A decrease >10% per day or >20% over 3-7 days strongly suggests clinically significant atrophy¹¹.

Echogenicity: Increased echointensity suggests muscle fiber injury and fibrosis, though quantification remains challenging.

Strain Imaging: Speckle-tracking ultrasound quantifies regional diaphragm deformation, potentially identifying subtle dysfunction before global contractility is impaired.

Ventilator Strategies to Minimize Ventilator-Induced Diaphragmatic Dysfunction (VIDD)

Prevention of VIDD requires balancing diaphragm protection (avoiding excessive load) with preservation of contractile activity (avoiding disuse atrophy). The following strategies form the foundation of lung- and diaphragm-protective ventilation.

Early Spontaneous Breathing

Light Sedation Protocols: Target-based sedation strategies aiming for RASS -1 to 0 (rather than deep sedation) preserve spontaneous respiratory effort and reduce VIDD risk by 40-60%¹². The ABCDEF bundle explicitly incorporates spontaneous breathing trials and minimization of sedation.

Spontaneous Breathing Modes: Transition from controlled modes (VC-CMV, PC-CMV) to assist modes (PSV, PRVC, PAV+, NAVA) as early as clinically feasible—ideally within 24-48 hours. Even partial preservation of diaphragm activity (10-30% of total work of breathing) may attenuate atrophy.

Daily Spontaneous Breathing Trials (SBT): Evidence supports daily SBT screening beginning when oxygenation is adequate (FiO₂ ≤0.5, PEEP ≤8 cmH₂O) and hemodynamics stable. SBTs identify patients ready for liberation while maintaining diaphragm activity in those who fail.

Optimizing Inspiratory Effort

The challenge is avoiding both extremes—excessive unloading (leading to atrophy) and excessive loading (causing eccentric injury and fatigue).

Monitoring Inspiratory Effort:

Esophageal manometry: Gold standard for quantifying respiratory effort. Target P₀.₁ (first 100 ms of inspiratory effort) of 1.5-3.5 cmH₂O, and peak esophageal pressure swing (ΔPes) of 5-10 cmH₂O during tidal breathing¹³
Occlusion pressure (P₀.₁): Non-invasive surrogate measured via ventilator; values >3.5 cmH₂O suggest excessive effort, <1.5 cmH₂O suggest over-assistance
Diaphragm ultrasound: DTF >50% during assisted breathing suggests excessive effort/load

Pressure Support Ventilation (PSV) Titration:

Adjust PS level to achieve tidal volumes of 6-8 mL/kg IBW
Target respiratory rate 15-30 breaths/min
Use inspiratory rise time and cycle-off criteria to optimize patient-ventilator synchrony
Hack: Gradually reduce PS by 2 cmH₂O increments every 6-12 hours as tolerated, rather than abrupt reduction—smoother diaphragm reconditioning

Proportional Modes: Neurally Adjusted Ventilatory Assist (NAVA) and Proportional Assist Ventilation Plus (PAV+) deliver pressure proportional to patient effort, potentially maintaining physiologic loading. NAVA uses diaphragm electrical activity (Edi) to trigger and cycle the ventilator, optimizing synchrony. While theoretically attractive, superiority over well-titrated PSV remains unproven in large trials.

Adjunctive Strategies

Neuromuscular Blockade Minimization: Avoid continuous infusions unless absolutely necessary (severe ARDS, ventilator dyssynchrony refractory to other interventions). When used, limit duration to <48 hours. The ROSE trial showed no benefit of early neuromuscular blockade in moderate ARDS¹⁴.

Glycemic Control: Maintain glucose 140-180 mg/dL. Both hypoglycemia and severe hyperglycemia (>250 mg/dL) worsen diaphragm function.

Nutrition Optimization: Target protein delivery of 1.2-2.0 g/kg/day. Avoid both underfeeding (protein-calorie malnutrition) and overfeeding (excess CO₂ production, increased respiratory load). Essential amino acids, particularly leucine, may attenuate muscle protein breakdown.

Physical Therapy and Early Mobilization: Whole-body rehabilitation improves respiratory muscle strength. Progressive mobility protocols (bed exercises → sitting → standing → walking) should incorporate respiratory muscle training when feasible.

Inspiratory Muscle Training (IMT): Threshold loading devices or resistive breathing exercises for 10-20 minutes, 2-3 times daily may accelerate diaphragm reconditioning during weaning¹⁵. Studies show 15-30% improvement in inspiratory muscle strength and shorter weaning duration.

Pearl: Use "ventilator gymnastics"—brief periods (30-60 seconds) of unsupported spontaneous breathing several times daily, even in patients requiring high support. This prevents complete disuse while avoiding fatigue. Think of it as "range of motion" exercises for the diaphragm.

Phrenic Nerve Stimulation and Other Novel Therapies

Despite optimal ventilator management, some patients develop severe diaphragm dysfunction requiring innovative interventions. Several novel therapies target different aspects of diaphragm pathophysiology.

Temporary Transvenous Phrenic Nerve Stimulation

The most extensively studied novel therapy is temporary transvenous diaphragm pacing. A stimulation catheter is placed via the right internal jugular or left subclavian vein into the left pericardiophrenic or right brachiocephalic vein, positioned near the phrenic nerves¹⁶.

Mechanism: Electrical impulses stimulate synchronized bilateral diaphragm contractions (typically 30-40 contractions/hour), preserving muscle fiber activity during mechanical ventilation.

Clinical Evidence: The pivotal DiPAC trial (n=108) randomized mechanically ventilated patients to standard care versus phrenic nerve stimulation. Stimulation therapy reduced time to successful extubation by 50% (hazard ratio 1.86) and increased ventilator-free days¹⁷. Subsequent studies confirmed feasibility and safety, though broader implementation awaits FDA approval and cost-effectiveness data.

Practical Considerations:

Initiate within 72 hours of intubation for maximal benefit
Contraindications: pacemaker/ICD, known phrenic nerve injury, severe coagulopathy
Requires specialized equipment and training
Cost approximately $10,000-15,000 per therapy course

Pharmacological Interventions

Levosimendan: This calcium sensitizer improves diaphragm contractility in experimental models, potentially through improved calcium handling and mitochondrial function¹⁸. Small human trials show promise, but large RCTs are lacking. Dosing: 0.1 µg/kg/min infusion for 24 hours (without bolus).

Methylxanthines: Theophylline and aminophylline improve diaphragm contractility through phosphodiesterase inhibition and enhanced calcium release. However, narrow therapeutic windows and side effects (tachycardia, arrhythmias) limit routine use. Reserve for refractory cases with therapeutic drug monitoring.

Antioxidants: N-acetylcysteine, vitamin E, and other antioxidants show benefit in animal models by reducing oxidative stress. Human data are limited and conflicting. Routine supplementation cannot be recommended based on current evidence.

Testosterone/Anabolic Agents: In theory, anabolic hormones could counter muscle catabolism. However, critical illness is a catabolic state resistant to anabolic interventions, and clinical evidence is insufficient.

Oyster: Beware of expensive, unproven interventions promoted based solely on mechanistic rationale or small case series. Critically appraise evidence quality before implementing novel therapies.

Cell-Based and Gene Therapies

Experimental approaches include:

Stem cell transplantation: Mesenchymal stem cells may promote muscle regeneration
Gene therapy: Upregulation of anti-apoptotic pathways or myogenic transcription factors
MicroRNA modulation: Targeting specific miRNAs involved in muscle atrophy

These remain investigational, with no human data supporting clinical use.

Non-Invasive Ventilation (NIV) for Diaphragm Rest

Paradoxically, periods of NIV-facilitated diaphragm rest may benefit patients with diaphragm fatigue from excessive loading. Brief intervals (2-4 hours) of full ventilator support via NIV allow recovery while maintaining overall respiratory muscle activity. This strategy is anecdotal and requires validation.

Hack: For patients with refractory weaning failure despite optimization, consider a 48-72 hour period of deeper sedation with controlled ventilation as "diaphragm rest," followed by structured reconditioning with progressive weaning trials. This approach lacks robust evidence but occasionally succeeds when other strategies fail.

The Role of Tracheostomy and Transfer to Long-Term Acute Care Hospital (LTACH)

Tracheostomy: Timing and Benefits

Tracheostomy facilitates management of patients requiring prolonged mechanical ventilation by enabling sedation reduction, improved secretion management, and enhanced patient comfort.

Timing Controversies: The optimal timing remains debated. The TracMan trial (n=909) found no mortality difference between early (≤4 days) versus late (≥10 days) tracheostomy, though early tracheostomy reduced sedation requirements¹⁹. A meta-analysis of 12 RCTs similarly showed no survival benefit but faster ICU discharge with early tracheostomy²⁰.

Current Recommendations:

Consider tracheostomy when anticipated ventilation duration exceeds 14-21 days
Individualize based on trajectory: improving patients may avoid tracheostomy; deteriorating patients benefit from earlier intervention
Use predictive models: APACHE II >17, failed multiple SBTs, and severe baseline comorbidities predict prolonged ventilation

Benefits Beyond Timing:

Enhanced patient comfort and communication
Facilitation of oral feeding (improved nutrition)
Reduced airway resistance (less respiratory work)
Easier secretion management and bronchoscopy
Psychological benefits (transition toward recovery)

Technique Considerations: Percutaneous dilatational tracheostomy (PDT) is equivalent to surgical tracheostomy in most patients, with lower cost and avoidance of OR transfer. Contraindications to PDT include difficult anatomy, coagulopathy, and high ventilator requirements (FiO₂ >0.8, PEEP >15).

Decannulation Protocols

Successful decannulation requires:

Adequate oxygenation without significant FiO₂/PEEP
Effective cough (peak cough flow >60 L/min)
Manageable secretions
Intact swallowing (if oral feeding desired)
Hemodynamic stability

Progressive approach:

Downsize tracheostomy tube
Capping trials (with deflated cuff) for increasing durations
Switch to fenestrated tube or speaking valve
Remove tube if 24-48 hour cap trial successful

Pearl: Don't rush decannulation. Failed decannulation with emergency reintubation carries high morbidity. A conservative approach with capping trials and gradual transitions is safer.

Long-Term Acute Care Hospitals (LTACH)

LTACHs are specialized facilities for patients requiring prolonged mechanical ventilation, typically defined as ≥21 days. They provide lower nurse-to-patient ratios than acute ICUs but higher than skilled nursing facilities, with specialized rehabilitation services.

Indications for LTACH Transfer:

Prolonged mechanical ventilation (typically >14-21 days) without expectation of rapid liberation
Medically stable (no ongoing organ dysfunction requiring ICU-level care)
Rehabilitation potential (not hospice-appropriate)
Geographic availability and insurance coverage

Outcomes: Studies show 50-60% of LTACH patients successfully wean from mechanical ventilation, with 40-50% survival to hospital discharge²¹. Predictors of successful weaning include:

Younger age (<65 years)
Non-septic admission diagnosis
Absence of severe malnutrition (albumin >2.5 g/dL)
Preserved functional status prior to acute illness
Evidence of diaphragm activity on ultrasound

Structured Weaning Programs: LTACHs employ protocolized approaches including:

Daily SBT screening with progressive extension
Aggressive secretion management
Intensive physical and respiratory therapy
Nutrition optimization
Treatment of underlying conditions (anemia, hypothyroidism, deconditioning)

Alternatives to LTACH:

In-hospital weaning units: Some academic centers have dedicated weaning units within the hospital
Skilled nursing facilities with ventilator units: Lower-cost alternative for stable patients
Home mechanical ventilation: Feasible for patients with permanent ventilator dependence but adequate home support

Palliative Care Integration

For patients with poor prognosis despite maximal therapy, palliative care consultation should be integral to decision-making. Indicators of poor prognosis include:

Age >75 with multiple comorbidities
Advanced malignancy or end-stage organ disease
Progressive diaphragm atrophy despite interventions
Multiple failed SBTs over 4-6 weeks
Patient/family preference for comfort-focused care

Oyster: LTACH transfer is not "giving up"—it's appropriate level-of-care matching. However, avoid LTACH transfer for patients unlikely to benefit (terminal illness, no rehabilitation potential), as this delays appropriate palliative interventions.

Integrated Approach: A Practical Framework

Successful management of difficult-to-wean patients requires systematic integration of the above principles:

Phase 1: Prevention (Days 0-3)

Minimize sedation (target RASS -1 to 0)
Avoid neuromuscular blockade unless essential
Early spontaneous breathing with assisted modes
Daily diaphragm ultrasound to establish baseline

Phase 2: Early Weaning (Days 3-7)

Daily SBT screening when oxygenation/hemodynamics permit
Titrate support to maintain diaphragm activity (DTF 30-50%)
Correct reversible factors (nutrition, electrolytes, thyroid)
Aggressive mobilization and rehabilitation

Phase 3: Difficult Weaning (Days 7-14)

Comprehensive diaphragm assessment (ultrasound, consider phrenic nerve studies)
Inspiratory muscle training
Consider novel therapies if available (phrenic stimulation)
Multidisciplinary team discussion regarding tracheostomy

Phase 4: Prolonged Weaning (>14 days)

Tracheostomy if not already performed
LTACH evaluation and transfer if appropriate
Structured weaning protocol with gradual support reduction
Address chronic comorbidities impeding liberation
Palliative care consultation for poor-prognosis patients

Conclusion

Diaphragm dysfunction is a critical, often under-recognized barrier to successful ventilator liberation. ICU-acquired diaphragm weakness develops rapidly through multiple pathophysiological mechanisms, yet remains modifiable with appropriate interventions. Point-of-care ultrasound enables bedside diagnosis and monitoring, while lung- and diaphragm-protective ventilation strategies prevent VIDD. For patients with established dysfunction, novel therapies like phrenic nerve stimulation show promise, and structured weaning programs in specialized facilities achieve successful liberation in the majority. A paradigm shift toward viewing the diaphragm as a vital organ requiring active protection and rehabilitation—rather than passive byproduct of critical illness—will improve outcomes for this challenging patient population.

Future research priorities include biomarkers for early VIDD detection, refinement of optimal ventilator titration targets, validation of novel therapeutics in large trials, and identification of patients most likely to benefit from advanced interventions versus palliative approaches. As critical care advances, so too must our understanding and management of the engine of respiration—the diaphragm.

References

Levine S, Nguyen T, Taylor N, et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008;358(13):1327-1335.
Powers SK, Wiggs MP, Sollanek KJ, Smuder AJ. Ventilator-induced diaphragm dysfunction: cause and effect. Am J Physiol Regul Integr Comp Physiol. 2013;305(5):R464-R477.
Hussain SN, Mofarrahi M, Sigala I, et al. Mechanical ventilation-induced diaphragm disuse in humans triggers autophagy. Am J Respir Crit Care Med. 2010;182(11):1377-1386.
Supinski GS, Morris PE, Dhar S, Callahan LA. Diaphragm dysfunction in critical illness. Chest. 2018;153(4):1040-1051.
Dres M, Goligher EC, Heunks LMA, Brochard LJ. Critical illness-associated diaphragm weakness. Intensive Care Med. 2017;43(10):1441-1452.
Jung B, Nougaret S, Conseil M, et al. Sepsis is associated with a preferential diaphragmatic atrophy: a critically ill patient study using tridimensional computed tomography. Anesthesiology. 2014;120(5):1182-1191.
Goligher EC, Laghi F, Detsky ME, et al. Measuring diaphragm thickness with ultrasound in mechanically ventilated patients: feasibility, reproducibility and validity. Intensive Care Med. 2015;41(4):642-649.
Umbrello M, Formenti P, Longhi D, et al. Diaphragm ultrasound as indicator of respiratory effort in critically ill patients undergoing assisted mechanical ventilation: a pilot clinical study. Crit Care. 2015;19:161.
DiNino E, Gartman EJ, Sethi JM, McCool FD. Diaphragm ultrasound as a predictor of successful extubation from mechanical ventilation. Thorax. 2014;69(5):423-427.
Kim WY, Suh HJ, Hong SB, Koh Y, Lim CM. Diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation. Crit Care Med. 2011;39(12):2627-2630.
Goligher EC, Dres M, Fan E, et al. Mechanical ventilation-induced diaphragm atrophy strongly impacts clinical outcomes. Am J Respir Crit Care Med. 2018;197(2):204-213.
Shehabi Y, Bellomo R, Reade MC, et al. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186(8):724-731.
Goligher EC, Dres M, Patel BK, et al. Lung- and diaphragm-protective ventilation. Am J Respir Crit Care Med. 2020;202(7):950-961.
National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med. 2019;380(21):1997-2008.
Vorona S, Sabatini U, Al-Maqbali S, et al. Inspiratory muscle rehabilitation in critically ill adults: a systematic review and meta-analysis. Ann Am Thorac Soc. 2018;15(6):735-744.
Reynolds S, Ebner A, Meffen T, et al. Diaphragm activation in ventilated patients using a novel transvenous phrenic nerve pacing catheter. Crit Care Med. 2017;45(7):e691-e694.
Reynolds SC, Metha S, Oczkowski S, et al. Diaphragm Activation in Ventilated Patients (DiPAC): a randomized controlled trial. Am J Respir Crit Care Med. 2022;205(9):1060-1070.
Doorduin J, Sinderby CA, Beck J, et al. The calcium sensitizer levosimendan improves human diaphragm function. Am J Respir Crit Care Med. 2012;185(1):90-95.
Young D, Harrison DA, Cuthbertson BH, Rowan K; TracMan Collaborators. Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial. JAMA. 2013;309(20):2121-2129.
Meng L, Wang C, Li J, Zhang J. Early vs late tracheostomy in critically ill patients: a systematic review and meta-analysis. Clin Respir J. 2016;10(6):684-692.
Scheinhorn DJ, Hassenpflug MS, Votto JJ, et al. Post-ICU mechanical ventilation at 23 long-term care hospitals: a multicenter outcomes study. Chest. 2007;131(1):85-93.

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Tuesday, November 4, 2025