Coughing on the Ventilator: Clues to Tube Position, Secretions, or Worsening Lung Mechanics
A Comprehensive Review for Critical Care Postgraduates
Dr Neeraj Manikath, Claude.ai
Abstract
Background: Coughing in mechanically ventilated patients represents a complex physiological response that can provide crucial diagnostic information about endotracheal tube position, airway secretions, and evolving pulmonary pathophysiology. New-onset ventilator alarms accompanying coughing episodes often herald significant clinical deterioration requiring immediate intervention.
Objective: To provide a comprehensive analysis of coughing mechanisms in ventilated patients, differential diagnosis of associated ventilator alarms, and evidence-based management strategies with emphasis on recognizing microaspiration, airway irritation, and dynamic airway collapse.
Methods: Narrative review of current literature with clinical correlation and expert opinion on diagnostic and therapeutic approaches.
Results: Coughing in ventilated patients results from complex interactions between respiratory mechanics, neurological reflexes, and ventilator settings. Pattern recognition of associated alarms can guide rapid diagnosis and intervention. Key clinical scenarios include tube malposition, secretion retention, dynamic hyperinflation, and evolving pulmonary pathology.
Conclusions: Systematic evaluation of coughing with concurrent ventilator alarms enables early recognition of life-threatening complications and optimization of ventilatory support.
Keywords: Mechanical ventilation, cough reflex, ventilator alarms, endotracheal tube, airway management, critical care
Introduction
Coughing in mechanically ventilated patients presents a diagnostic and therapeutic challenge that demands immediate attention from critical care clinicians. Unlike spontaneous coughing in conscious patients, ventilator-associated coughing represents a complex interplay between preserved neurological reflexes, altered respiratory mechanics, and artificial airway dynamics. The simultaneous occurrence of new-onset ventilator alarms with coughing episodes often signals significant pathophysiological changes requiring rapid assessment and intervention.
The mechanically ventilated patient's ability to cough effectively is compromised by multiple factors including sedation, neuromuscular blockade, endotracheal tube presence, and altered respiratory mechanics. When coughing does occur, it provides valuable diagnostic information about airway integrity, secretion burden, and evolving pulmonary pathology. Understanding the mechanisms underlying ventilator-associated coughing and its relationship to alarm patterns enables clinicians to rapidly identify and address potentially life-threatening complications.
This review examines the pathophysiology of coughing in mechanically ventilated patients, provides a systematic approach to interpreting associated ventilator alarms, and offers evidence-based management strategies with particular emphasis on recognizing microaspiration, airway irritation, and dynamic airway collapse.
Pathophysiology of Cough in Mechanically Ventilated Patients
Normal Cough Reflex
The cough reflex involves a complex neurological pathway beginning with irritant receptor stimulation in the larynx, trachea, and bronchi. Afferent signals travel via the vagus nerve to the medullary cough center, which coordinates the characteristic four-phase cough sequence: inspiratory phase, compressive phase with glottic closure, expulsive phase with rapid glottic opening, and relaxation phase.
Altered Cough Mechanics in Ventilated Patients
Mechanical ventilation fundamentally alters normal cough physiology through several mechanisms:
Endotracheal Tube Effects: The endotracheal tube bypasses upper airway protective mechanisms and prevents effective glottic closure, reducing peak expiratory flow rates by 50-70%. The tube itself serves as a constant irritant stimulus while simultaneously impairing the mechanical effectiveness of cough.
Positive Pressure Ventilation: Continuous positive airway pressure alters the pressure gradients necessary for effective cough. The inability to generate significant negative inspiratory pressure reduces the driving force for secretion mobilization.
Sedation and Neuromuscular Blockade: These medications suppress both the afferent limb (reduced sensation) and efferent limb (impaired muscle contraction) of the cough reflex, creating a paradoxical situation where cough occurrence indicates either significant stimulus intensity or inadequate suppression.
Respiratory Muscle Weakness: Critical illness-associated weakness, prolonged mechanical ventilation, and corticosteroid use contribute to reduced cough strength even when neurological pathways remain intact.
Clinical Scenarios and Differential Diagnosis
Scenario 1: High Pressure Alarms with Coughing
Pathophysiology: Increased airway resistance or decreased respiratory system compliance triggers high pressure alarms when ventilator-delivered breaths encounter greater opposition.
Common Causes:
- Endotracheal tube obstruction: Secretions, blood clots, or tube kinking
- Bronchospasm: Drug-induced, allergic, or inflammatory
- Pneumothorax: Tension pneumothorax requires immediate intervention
- Pulmonary edema: Cardiogenic or non-cardiogenic
- Auto-PEEP: Dynamic hyperinflation with expiratory flow limitation
Clinical Assessment:
- Immediate auscultation for breath sound symmetry
- Rapid bedside ultrasound for pneumothorax
- Endotracheal tube position verification
- Assessment of secretion burden and character
Scenario 2: Low Tidal Volume Alarms with Coughing
Pathophysiology: Reduced delivered tidal volume despite preset parameters indicates air leak or altered respiratory mechanics.
Common Causes:
- Endotracheal tube malposition: Esophageal intubation or right main bronchus intubation
- Cuff leak: Deflated or damaged cuff allowing air escape
- Circuit disconnection: Partial or complete ventilator circuit disruption
- Massive air leak: Bronchopleural fistula or large pneumothorax
Diagnostic Approach:
- End-tidal CO2 monitoring for tube position confirmation
- Cuff pressure measurement and adjustment
- Circuit integrity inspection
- Chest imaging if air leak suspected
Scenario 3: Desaturation with Coughing
Pathophysiology: Impaired gas exchange during coughing episodes suggests ventilation-perfusion mismatch or shunt physiology.
Common Etiologies:
- Microaspiration: Gastric contents, oral secretions, or tube feeding
- Atelectasis: Secretion plugging or positioning-related
- Pulmonary embolism: Sudden onset with hemodynamic compromise
- Pneumonia: Ventilator-associated or aspiration pneumonia
- ARDS progression: Worsening inflammatory response
Microaspiration: Recognition and Management
Pathophysiology
Microaspiration in ventilated patients occurs through several mechanisms despite cuffed endotracheal tubes. Secretions can leak around inadequately inflated cuffs, reflux through the tube lumen during coughing, or accumulate above the cuff before trickling into the lungs during position changes or cuff deflation.
Clinical Recognition
Early Signs:
- New-onset coughing in previously stable patients
- Increased ventilator pressures with maintained tidal volumes
- Subtle oxygen desaturation during coughing episodes
- Change in secretion character or volume
Advanced Signs:
- Frank aspiration with witnessed regurgitation
- Rapid onset respiratory distress
- Hemodynamic instability
- New infiltrates on chest imaging
Diagnostic Pearls
🔍 Pearl 1: The "cough-desaturation cycle" - repetitive episodes of coughing followed by oxygen desaturation suggest ongoing microaspiration rather than a single event.
🔍 Pearl 2: Pepsin levels in tracheal aspirates can confirm gastric aspiration even when pH testing is inconclusive.
🔍 Pearl 3: Blue dye added to enteral feeds can help identify aspiration, though methylene blue use has fallen out of favor due to potential complications.
Management Strategies
Immediate Interventions:
- Head of bed elevation to 30-45 degrees
- Cuff pressure optimization (25-30 cmH2O)
- Gastric decompression and feeding cessation
- Bronchoscopy for direct visualization and lavage if indicated
Preventive Measures:
- Subglottic suctioning tubes when available
- Continuous lateral rotation therapy
- Prokinetic agents for gastric motility
- Post-pyloric feeding when feasible
Airway Irritation and Inflammatory Responses
Chemical Irritation
Inhaled Medications: Nebulized bronchodilators, particularly when delivered via metered-dose inhalers with propellant irritants, can trigger coughing. The timing relationship between medication administration and cough onset provides diagnostic clarity.
Gastric Acid: Low pH gastric contents cause immediate chemical pneumonitis with intense inflammatory response. Unlike bacterial pneumonia, chemical pneumonitis presents within hours with rapid progression.
Environmental Factors: Inadequate humidification of inspired gases leads to airway desiccation and irritation. Modern ventilators with heated wire circuits have reduced this complication, but equipment malfunction can still occur.
Infectious Irritation
Ventilator-Associated Pneumonia (VAP): New-onset coughing in ventilated patients beyond 48 hours should raise suspicion for VAP. The combination of coughing, purulent secretions, fever, and radiographic changes supports the diagnosis.
Tracheobronchitis: Bacterial colonization without pneumonia can cause significant airway irritation and coughing. Differentiation from pneumonia relies heavily on imaging findings.
Management Approach
🛠️ Clinical Hack 1: The "cough timing test" - coughing that occurs immediately after specific interventions (suctioning, medication delivery, position changes) suggests mechanical or chemical irritation rather than infectious causes.
🛠️ Clinical Hack 2: Temporary increase in sedation level can help differentiate between mechanical irritation (cough suppression) and pathological causes (persistent coughing despite adequate sedation).
Dynamic Airway Collapse and Auto-PEEP
Pathophysiology
Dynamic airway collapse occurs when expiratory airflow limitation prevents complete lung emptying before the next inspiratory cycle. This phenomenon, known as auto-PEEP or intrinsic PEEP, creates a positive end-expiratory pressure independent of ventilator PEEP settings.
Clinical Presentation
Patients with auto-PEEP often exhibit:
- Coughing triggered by ventilator breath delivery
- High peak inspiratory pressures
- Reduced expiratory tidal volumes
- Patient-ventilator dyssynchrony
- Hemodynamic compromise due to reduced venous return
Recognition Techniques
Expiratory Hold Maneuver: Briefly occluding the expiratory limb at end-expiration reveals auto-PEEP by measuring retained pressure in the circuit.
Flow-Time Curve Analysis: Failure of expiratory flow to return to zero before the next breath indicates incomplete emptying.
Pressure-Volume Loop Assessment: Clockwise hysteresis with failure to return to baseline pressure suggests auto-PEEP.
Management Strategies
Ventilator Adjustments:
- Reduce respiratory rate to allow longer expiratory time
- Decrease tidal volume to reduce minute ventilation
- Apply external PEEP to counterbalance auto-PEEP (typically 80% of measured auto-PEEP)
- Consider pressure support ventilation for improved patient synchrony
Pharmacological Interventions:
- Bronchodilators for reversible airway obstruction
- Sedation to reduce respiratory drive and allow longer expiratory time
- Neuromuscular blockade in severe cases with refractory dyssynchrony
Ventilator Alarm Patterns: A Systematic Approach
High-Priority Alarm Combinations
Pattern 1: High Pressure + Reduced Tidal Volume + Coughing
- Most Likely: Endotracheal tube obstruction
- Immediate Action: Manual bag ventilation, suction catheter passage, consider tube replacement
Pattern 2: Low Pressure + Low Tidal Volume + Coughing
- Most Likely: Circuit disconnection or massive air leak
- Immediate Action: Circuit inspection, bag-mask ventilation if needed
Pattern 3: Normal Pressures + Desaturation + Coughing
- Most Likely: Microaspiration or developing pneumonia
- Immediate Action: Bronchoscopy consideration, culture collection, imaging
Diagnostic Flow Chart Approach
New-onset coughing with ventilator alarms
↓
Check breath sounds bilaterally
↓
Asymmetric → Consider pneumothorax, tube malposition
↓
Symmetric → Assess secretion burden
↓
Heavy secretions → Bronchoscopy/lavage
↓
Minimal secretions → Consider auto-PEEP, bronchospasm, aspiration
Pearls and Oysters
Clinical Pearls 💎
Pearl 1: The "silent cough" phenomenon - patients with neuromuscular weakness may exhibit ventilator pressure spikes without audible coughing, representing ineffective cough attempts.
Pearl 2: Coughing immediately upon ventilator reconnection after suctioning suggests inadequate secretion clearance requiring deeper or more frequent suctioning.
Pearl 3: Unilateral breath sound changes with coughing often indicate selective bronchial intubation, even when initial chest X-ray appeared acceptable.
Pearl 4: The "cough reflex test" can assess neurological function in sedated patients - presence of cough reflex to suction catheter stimulation suggests adequate brain stem function.
Pearl 5: Coughing that improves with increased PEEP suggests recruitable atelectasis, while worsening suggests overdistension or pneumothorax.
Clinical Oysters 🦪
Oyster 1: Not all coughing indicates a problem - some patients maintain robust cough reflexes despite appropriate sedation levels, particularly those with chronic respiratory conditions.
Oyster 2: Absence of coughing doesn't guarantee airway stability - patients with significant sedation or neurological injury may not cough despite serious airway compromise.
Oyster 3: Coughing can be protective - overly aggressive cough suppression may lead to secretion retention and subsequent complications.
Oyster 4: The timing of cough onset matters more than frequency - new coughing in a previously stable patient warrants investigation regardless of cough intensity.
Advanced Diagnostic Techniques
Bedside Bronchoscopy
Indications:
- Suspected airway obstruction with failed conventional management
- Evaluation for aspiration with atypical presentation
- Direct visualization of endotracheal tube position
- Therapeutic intervention for thick secretions
Technique Considerations:
- Use of bronchoscopy-compatible connectors to maintain ventilation
- CO2 monitoring during procedure to assess ventilation adequacy
- Preparation for rapid tube exchange if severe obstruction found
Advanced Imaging
Chest CT: High-resolution imaging can identify subtle pneumothoraces, assess for aspiration pneumonitis patterns, and evaluate for pulmonary embolism when clinical suspicion exists.
Bedside Ultrasound: Rapid assessment for pneumothorax using lung sliding and comet tail artifacts. Diaphragmatic assessment can identify phrenic nerve injury contributing to altered cough mechanics.
Specialized Monitoring
Esophageal Pressure Monitoring: Can differentiate between lung and chest wall compliance changes when coughing accompanies pressure alarms.
Electrical Impedance Tomography: Emerging technology for real-time assessment of ventilation distribution and detection of regional lung collapse.
Clinical Hacks and Practical Tips
Bedside Assessment Hacks 🛠️
Hack 1: The "Bag Test" When multiple alarms occur with coughing, briefly disconnect the patient from the ventilator and manually bag ventilate. If pressures normalize, the problem is ventilator-related. If high pressures persist, the problem is patient-related.
Hack 2: The "Cuff Test" Temporarily deflate the endotracheal tube cuff while maintaining positive pressure. If coughing immediately stops, consider cuff over-inflation or tracheal irritation. If coughing persists, look for lower airway causes.
Hack 3: The "Position Test" Change patient position (if permissible) during coughing episodes. Improvement with lateral positioning suggests secretion pooling, while worsening suggests structural problems like pneumothorax.
Hack 4: The "Suction Response Test" Immediate improvement in ventilator parameters after suctioning confirms secretion-related causes. Lack of improvement despite secretion removal suggests other etiologies.
Ventilator Setting Optimizations 🔧
Hack 5: The "Expiratory Time Extension" For suspected auto-PEEP, temporarily reduce respiratory rate by 20% and observe coughing patterns. Improvement suggests expiratory flow limitation.
Hack 6: The "Pressure Support Trial" Switch to pressure support ventilation during coughing episodes. Patient-triggered breaths often improve synchrony and reduce irritation from mandatory breaths.
Hack 7: The "PEEP Titration Test" Incrementally increase PEEP by 2-3 cmH2O during coughing episodes. Improvement suggests recruitable atelectasis; worsening suggests overdistension.
Emergency Interventions 🚨
Hack 8: The "Emergency Circuit" Keep a pre-assembled bag-valve device connected to oxygen at bedside for immediate use during circuit problems. This eliminates connection delays during emergencies.
Hack 9: The "Rapid Cuff Assessment" Use a 10ml syringe to rapidly assess cuff pressure by feeling resistance during injection. Firm resistance at 8-10ml suggests appropriate pressure; easy injection suggests leak.
Hack 10: The "Two-Person Rule" During coughing emergencies, assign one person to manual ventilation and another to problem-solving. This prevents hypoxemia during diagnostic procedures.
Evidence-Based Management Protocols
Protocol 1: New-Onset Coughing with High Pressure Alarms
Immediate Assessment (0-2 minutes):
- Auscultate bilateral breath sounds
- Check endotracheal tube position at lip line
- Assess for visible secretions in tube
- Verify ventilator circuit connections
Secondary Assessment (2-5 minutes):
- Attempt passage of suction catheter
- Manual bag ventilation trial
- Chest X-ray if breath sounds asymmetric
- Arterial blood gas if desaturation present
Definitive Management:
- Bronchoscopy for persistent obstruction
- Tube replacement if unable to pass suction catheter
- Chest tube insertion for confirmed pneumothorax
Protocol 2: Suspected Microaspiration
Risk Stratification:
- High risk: Recent extubation/reintubation, feeding intolerance, neurological impairment
- Moderate risk: Prolonged supine positioning, high gastric residuals
- Low risk: Stable patient with appropriate precautions
Management Algorithm:
- Immediate: Stop enteral feeding, elevate head of bed, suction airway
- Short-term: Gastric decompression, prokinetic agents, imaging
- Long-term: Post-pyloric feeding, swallow evaluation when appropriate
Protocol 3: Auto-PEEP Management
Diagnostic Confirmation:
- Expiratory hold maneuver measurement
- Flow-time curve analysis
- Assessment of patient-ventilator synchrony
Therapeutic Intervention:
- First-line: Reduce respiratory rate, optimize expiratory time
- Second-line: Apply external PEEP (80% of measured auto-PEEP)
- Third-line: Bronchodilators, sedation adjustment
- Last resort: Neuromuscular blockade with permissive hypercapnia
Complications and Their Management
Ventilator-Induced Lung Injury (VILI)
Aggressive coughing against mechanical ventilation can exacerbate VILI through several mechanisms:
- Volutrauma: High transpulmonary pressures during cough attempts
- Atelectrauma: Repetitive opening and closing of alveolar units
- Biotrauma: Enhanced inflammatory response from mechanical stress
Prevention Strategies:
- Lung-protective ventilation strategies
- Appropriate sedation to minimize patient-ventilator dyssynchrony
- Early identification and treatment of underlying causes
Hemodynamic Compromise
Severe coughing episodes can cause significant hemodynamic changes:
- Venous Return Reduction: Increased intrathoracic pressure
- Cardiac Output Decrease: Impaired ventricular filling
- Blood Pressure Fluctuations: Alternating hypertension and hypotension
Management Approach:
- Continuous hemodynamic monitoring during coughing episodes
- Fluid resuscitation for preload-dependent hypotension
- Vasopressor support if necessary
- Treatment of underlying cause to reduce coughing intensity
Barotrauma
The combination of positive pressure ventilation and forceful coughing creates high peak pressures that can lead to:
- Pneumothorax: Most common complication
- Pneumomediastinum: Air tracking along fascial planes
- Subcutaneous Emphysema: Extension of air into soft tissues
Recognition and Management:
- High index of suspicion with sudden clinical deterioration
- Immediate needle decompression for tension pneumothorax
- Chest tube insertion for significant air leaks
- Consideration of lung-protective strategies
Special Populations
Neurological Patients
Patients with traumatic brain injury, stroke, or other neurological conditions present unique challenges:
- Altered Cough Reflex: May be hyperactive or absent
- Intracranial Pressure Concerns: Coughing can increase ICP significantly
- Medication Interactions: Sedatives and antiepileptics affect cough threshold
Management Considerations:
- ICP monitoring during coughing episodes
- Careful sedation titration
- Early tracheostomy consideration for prolonged ventilation
Post-Operative Patients
Surgical patients have specific risk factors and considerations:
- Pain-Related Cough Suppression: Inadequate analgesia reduces effective coughing
- Surgical Site Considerations: Thoracic and abdominal surgeries affect respiratory mechanics
- Anesthesia Effects: Residual neuromuscular blockade impairs cough effectiveness
Tailored Approach:
- Optimal pain management protocols
- Early mobilization when feasible
- Regional anesthesia techniques for ongoing pain control
Pediatric Considerations
Children require modified approaches due to:
- Size-Appropriate Equipment: Smaller endotracheal tubes more prone to obstruction
- Developmental Differences: Immature respiratory mechanics
- Medication Dosing: Weight-based calculations with narrow therapeutic windows
Pediatric-Specific Protocols:
- More frequent airway assessment
- Lower threshold for bronchoscopy
- Family-centered care considerations
Quality Improvement and Monitoring
Key Performance Indicators
Process Measures:
- Time from alarm to clinical assessment
- Frequency of preventable reintubations
- Compliance with ventilator bundles
Outcome Measures:
- Ventilator-associated pneumonia rates
- Duration of mechanical ventilation
- ICU length of stay
Balancing Measures:
- Sedation requirements
- Patient comfort scores
- Family satisfaction
Continuous Quality Improvement
Multidisciplinary Rounds: Regular discussion of ventilator management with respiratory therapists, nurses, and physicians ensures comprehensive care.
Protocol Adherence: Regular auditing of protocol compliance with feedback to clinical teams.
Education Programs: Ongoing education for all team members on recognition and management of ventilator-associated coughing.
Future Directions and Emerging Technologies
Artificial Intelligence Integration
Machine learning algorithms are being developed to:
- Pattern Recognition: Automated identification of concerning alarm patterns
- Predictive Analytics: Early warning systems for ventilator complications
- Decision Support: Real-time recommendations for ventilator adjustments
Advanced Monitoring Technologies
Wearable Sensors: Continuous monitoring of respiratory effort and patient comfort
Real-Time Imaging: Portable ultrasound and electrical impedance tomography for immediate bedside assessment
Biomarker Development: Point-of-care testing for aspiration and inflammation markers
Personalized Ventilation
Genetic Factors: Understanding individual variations in drug metabolism and inflammatory responses
Precision Medicine: Tailored ventilator strategies based on patient-specific factors
Adaptive Algorithms: Ventilators that automatically adjust settings based on patient response
Conclusion
Coughing in mechanically ventilated patients represents a complex clinical phenomenon that demands systematic evaluation and prompt intervention. The integration of clinical assessment, ventilator alarm interpretation, and evidence-based management strategies enables critical care clinicians to rapidly identify and address potentially life-threatening complications.
Key takeaways for clinical practice include:
Recognition Principles: New-onset coughing with ventilator alarms should trigger immediate systematic assessment beginning with airway patency and breath sound evaluation.
Diagnostic Approach: Pattern recognition of alarm combinations provides valuable diagnostic clues, with high-pressure alarms suggesting obstruction, low-volume alarms indicating leaks, and desaturation episodes raising concern for aspiration or pneumonia.
Management Strategies: Successful outcomes depend on rapid identification of underlying causes, appropriate use of diagnostic tools including bedside bronchoscopy, and implementation of targeted interventions ranging from simple position changes to complex ventilator adjustments.
Prevention Focus: Proactive measures including proper tube positioning, adequate humidification, secretion management, and aspiration precautions significantly reduce the incidence of ventilator-associated coughing complications.
As mechanical ventilation technology continues to evolve with artificial intelligence integration and advanced monitoring capabilities, the fundamental principles of careful clinical observation, systematic assessment, and evidence-based intervention remain paramount to optimizing patient outcomes.
The effective management of coughing in ventilated patients requires not only technical expertise but also clinical wisdom gained through experience and continuous learning. By understanding the pathophysiology, recognizing pattern variations, and implementing systematic approaches, critical care clinicians can transform potentially dangerous situations into opportunities for diagnostic clarity and therapeutic success.
Future research directions should focus on developing predictive models for ventilator complications, refining personalized ventilation strategies, and improving our understanding of the complex interactions between patient factors, ventilator settings, and clinical outcomes. The integration of these advances with traditional bedside clinical skills will continue to enhance our ability to provide optimal care for critically ill patients requiring mechanical ventilatory support.
References
Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):1S-23S.
Fontela PS, Piva JP, Garcia PC, et al. Risk factors for extubation failure in mechanically ventilated pediatric patients. Pediatr Crit Care Med. 2005;6(2):166-170.
Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013;369(22):2126-2136.
Torres A, Gatell JM, Aznar E, et al. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med. 1995;152(1):137-141.
Pepe PE, Marini JJ. Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction: the auto-PEEP effect. Am Rev Respir Dis. 1982;126(1):166-170.
Metheny NA, Clouse RE, Chang YH, et al. Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: frequency, outcomes, and risk factors. Crit Care Med. 2006;34(4):1007-1015.
Klompas M, Branson R, Eichenwald EC, et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(8):915-936.
Rello J, Soñora R, Jubert P, et al. Pneumonia in intubated patients: role of respiratory airway care. Am J Respir Crit Care Med. 1996;154(1):111-115.
Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107-1116.
Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308.
Blanch L, Villagra A, Sales B, et al. Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med. 2015;41(4):633-641.
Thille AW, Rodriguez P, Cabello B, et al. Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med. 2006;32(10):1515-1522.
Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest. 1997;112(1):186-192.
Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350(24):2452-2460.
Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134.
Kollef MH, Shapiro SD, Silver P, et al. A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit Care Med. 1997;25(4):567-574.
Metheny NA, Schallom L, Oliver DA, et al. Gastric residual volume and aspiration in critically ill patients receiving gastric feedings. Am J Crit Care. 2008;17(6):512-519.
Drakulovic MB, Torres A, Bauer TT, et al. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet. 1999;354(9193):1851-1858.
van Nieuwenhoven CA, Vandenbroucke-Grauls C, van Tiel FH, et al. Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study. Crit Care Med. 2006;34(2):396-402.
Dezfulian C, Shojania K, Collard HR, et al. Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med. 2005;118(1):11-18.
Muscedere J, Rewa O, McKechnie K, et al. Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care Med. 2011;39(8):1985-1991.
Rello J, Lode H, Cornaglia G, et al. A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med. 2010;36(5):773-780.
Tablan OC, Anderson LJ, Besser R, et al. Guidelines for prevention of health-care-associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep. 2004;53(RR-3):1-36.
Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.
Marini JJ, Crooke PS 3rd. A general mathematical model for respiratory dynamics relevant to the clinical setting. Am Rev Respir Dis. 1993;147(1):14-24.
Marini JJ. Dynamic hyperinflation and auto-positive end-expiratory pressure: lessons learned over 30 years. Am J Respir Crit Care Med. 2011;184(7):756-762.
Tuxen DV, Lane S. The effects of ventilatory pattern on hyperinflation, airway pressures, and circulation in mechanical ventilation of patients with severe air-flow obstruction. Am Rev Respir Dis. 1987;136(4):872-879.
Ranieri VM, Grasso S, Fiore T, et al. Auto-positive end-expiratory pressure and dynamic hyperinflation. Clin Chest Med. 1996;17(3):379-394.
Georgopoulos D, Mouloudi E, Kondili E, et al. Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of end-inspiratory pause. Eur Respir J. 2000;16(2):263-268.
Dhand R, Guntur VP. How best to deliver aerosol medications to mechanically ventilated patients. Clin Chest Med. 2008;29(2):277-296.
Maggiore SM, Lellouche F, Pigeot J, et al. Prevention of endotracheal suctioning-induced alveolar derecruitment in acute lung injury. Am J Respir Crit Care Med. 2003;167(9):1215-1224.
Stenqvist O, Odenstedt H, Lundin S. Dynamic respiratory mechanics in acute lung injury/ARDS: principles and clinical implications. Respir Care. 2003;48(9):842-853.
Gattinoni L, Pesenti A, Avalli L, et al. Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study. Am Rev Respir Dis. 1987;136(3):730-736.
Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338(6):347-354.
Brochard L, Rua F, Lorino H, et al. Inspiratory pressure support compensates for the additional work of breathing caused by the endotracheal tube. Anesthesiology. 1991;75(5):739-745.
MacIntyre NR, McConnell R, Cheng KC, et al. Patient-ventilator flow dyssynchrony: flow-limited versus pressure-limited breaths. Crit Care Med. 1997;25(10):1671-1677.
Chao DC, Scheinhorn DJ, Stearn-Hassenpflug M. Patient-ventilator trigger asynchrony in prolonged mechanical ventilation. Chest. 1997;112(6):1592-1599.
Kondili E, Prinianakis G, Georgopoulos D. Patient-ventilator interaction. Br J Anaesth. 2003;91(1):106-119.
Tobin MJ, Jubran A, Laghi F. Patient-ventilator interaction. Am J Respir Crit Care Med. 2001;163(5):1059-1063.
Parthasarathy S, Jubran A, Tobin MJ. Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1471-1478.
Jubran A, Van de Graaff WB, Tobin MJ. Variability of patient-ventilator interaction with pressure support ventilation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152(1):129-136.
Leung P, Jubran A, Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med. 1997;155(6):1940-1948.
Younes M. Proportional assist ventilation, a new approach to ventilatory support. Theory. Am Rev Respir Dis. 1992;145(1):114-120.
Sinderby C, Navalesi P, Beck J, et al. Neural control of mechanical ventilation in respiratory failure. Nat Med. 1999;5(12):1433-1436.
Beck J, Sinderby C, Lindström L, et al. Effects of lung volume on diaphragm EMG signal strength during voluntary contractions. J Appl Physiol. 1998;85(3):1123-1134.
Colombo D, Cammarota G, Bergamaschi V, et al. Physiologic response to varying levels of pressure support and neurally adjusted ventilatory assist in patients with acute respiratory failure. Intensive Care Med. 2008;34(11):2010-2018.
Schmidt M, Demoule A, Cracco C, et al. Neurally adjusted ventilatory assist increases respiratory variability and complexity in acute respiratory failure. Anesthesiology. 2010;112(3):670-681.
Piquilloud L, Vignaux L, Bialais E, et al. Neurally adjusted ventilatory assist improves patient-ventilator interaction. Intensive Care Med. 2011;37(2):263-271.
Spahija J, de Marchie M, Albert M, et al. Patient-ventilator interaction during pressure support ventilation and neurally adjusted ventilatory assist. Crit Care Med. 2010;38(2):518-526.
Terzi N, Pelieu I, Guittet L, et al. Neurally adjusted ventilatory assist in patients recovering spontaneous breathing after acute respiratory distress syndrome: physiological evaluation. Crit Care Med. 2010;38(9):1830-1837.
Patroniti N, Bellani G, Saccavino E, et al. Respiratory pattern during neurally adjusted ventilatory assist in acute respiratory failure patients. Intensive Care Med. 2012;38(2):230-239.
Cammarota G, Olivieri C, Costa R, et al. Noninvasive ventilation through a helmet in postextubation hypoxemic patients: physiologic comparison between neurally adjusted ventilatory assist and pressure support ventilation. Intensive Care Med. 2011;37(12):1943-1950.
Liu L, Liu H, Yang Y, et al. Neuroventilatory efficiency and extubation readiness in critically ill patients. Crit Care. 2012;16(4):R143.
Doorduin J, van Hees HW, van der Hoeven JG, et al. Monitoring of the respiratory muscles in the critically ill. Am J Respir Crit Care Med. 2013;187(1):20-27.
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.
Jaber S, Petrof BJ, Jung B, et al. Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. Am J Respir Crit Care Med. 2011;183(3):364-371.
Goligher EC, Fan E, Herridge MS, et al. Evolution of diaphragm thickness during mechanical ventilation. Impact of inspiratory effort. Am J Respir Crit Care Med. 2015;192(9):1080-1088.
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.
Dres M, Goligher EC, Heunks LMA, et al. Critical illness-associated diaphragm weakness. Intensive Care Med. 2017;43(10):1441-1452.
Hooijman PE, Beishuizen A, Witt CC, et al. Diaphragm muscle fiber weakness and ubiquitin-proteasome activation in critically ill patients. Am J Respir Crit Care Med. 2015;191(10):1126-1138.
Jung B, Moury PH, Mahul M, et al. Diaphragmatic dysfunction in patients with ICU-acquired weakness and its impact on extubation failure. Intensive Care Med. 2016;42(5):853-861.
Supinski GS, Morris PE, Dhar S, et al. Diaphragm dysfunction in critical illness. Chest. 2018;153(4):1040-1051.
Demoule A, Jung B, Prodanovic H, et al. Diaphragm dysfunction on admission to the intensive care unit. Prevalence, risk factors, and prognostic impact-a prospective study. Am J Respir Crit Care Med. 2013;188(2):213-219.
Kim WY, Suh HJ, Hong SB, et al. Diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation. Crit Care Med. 2011;39(12):2627-2630.
DiNino E, Gartman EJ, Sethi JM, et al. Diaphragm ultrasound as a predictor of successful extubation from mechanical ventilation. Thorax. 2014;69(5):423-427.
Conflicts of Interest: None declared
Funding: No external funding received
