We Can Move Mucus: But Is That Enough?

The Movement of Mucus During Intubation and Mechanical Ventilation

Intubation and mechanical ventilation lead to impairment of the primary mechanisms of both peripheral (mucociliary transport, gas-liquid interaction) and central airways secretion clearance (cough).¹ With the absence of cough during mechanical ventilation, flow bias can be altered by the ventilation settings (inspiration to expiration time) and may move secretions in large airways both in the cephalad (expiratory flow bias, through prolongation of inspiratory time) and caudad direction (inspiratory flow bias, with reduced inspiratory time).² The balance between the peak inspiratory flow (PIF) and the peak expiratory flow (PEF) can result in an inspiratory or expiratory flow bias.³ More simply, if inspiratory flow is lower than expiratory flow, secretions move cephalad. Various flow bias thresholds have demonstrated impact on the movement of mucus in vitro and in vivo, but the PEF-PIF difference of > 33 L/min is believed to be clinically relevant to the facilitation of clearance of mucus in mechanically ventilated patients.²

Konrad et al⁴ provided preliminary insights into the impact of intubation and mechanical ventilation on the movement of mucus in the major airways in humans. They investigated 32 ventilated subjects in a surgical ICU. The methods they used would be very challenging from an ethical and practical perspective in today’s ICU, where bronchial mucus transport velocity was measured with a small volume of technetium-99m–labeled albumin microspheres deposited at the distal end of the right and left main bronchus via flexible bronchoscopy. The movement of the radiolabeled microspheres was visualized and recorded using a scintillation camera. At the level of the main bronchi, the median bronchial transport velocity in the right primary bronchus was 0.8 mm/min and in the left at 1.4 mm/min. Of note, stagnant mucus transport was evident in 9 subjects. In 14 subjects, a total of 19 pulmonary complications occurred (10 occasions of secretion retention, 9 occasions of pneumonia).

A mainstay recommendation in most ICUs is the use of semi-recumbent positioning to prevent ventilator-pneumonia (VAP), optimize oxygen transport,⁵ and to improve arterial oxygenation.^6,7 Head-down positioning in intubated and ventilated animal models demonstrates increased cephalad movement of airway secretions with reduced development of VAP.⁸ Even though replication of this trial in ICU resulted in statistically significant reductions in microbiologically confirmed VAP, the study failed to provide any significant clinical benefit.⁹

The Outcome Measures Used to Detect Secretion Retention

Bedside methods to detect secretions have often used traditional tools such as lung auscultation, palpation of the patient chest wall and/or ventilator tubing for fremitus, and patient observation for chest wall movement during respiration. These clinical methods may not be very reliable¹⁰ or necessarily valid unless major airway obstruction is present. Nearly 40 years ago¹¹ it was demonstrated that hemodynamic alterations (increase/decreases in systolic and diastolic blood pressure) were significantly associated with the volume of airway secretions obtained with airway suctioning. Somewhat surprisingly traditional assessments such as breath sounds/added breath sounds on lung auscultation, paradoxical chest wall movement, or increases in ventilator airway pressure (volume controlled ventilation) were not associated with the volume of airway secretions suctioned.¹¹ Factors such as endotracheal tube diameter, body habitus, tidal volume, inspiratory flow setting, mucus viscosity, mucus volume, and the mucus location(s) may impact on the detection of airway secretions by clinical methods such as auscultation (added sounds), chest palpation (for chest wall fremitus), and flow-waveform analysis (expiratory flow “sawtooth pattern”). Increased peak airway pressure in volume control modes or loss of tidal volume may only become evident with major artificial airway obstruction.^12,13 The progressive loss of endotracheal tube diameter due to secretion accumulation averages 10–15%,¹⁴ which may explain why peak pressure in volume control or loss of tidal volume in pressure modes may not be a sensitive means to detect secretion accumulation unless airway obstruction is severe.¹³ Increased peak pressure or loss of tidal volume may also be caused by a myriad of other clinical problems (eg, bronchospasm, pulmonary edema, patient-ventilator asynchrony, patient biting of the endotracheal tube),¹⁵ which complicates the detection of secretion retention at the bedside. The presence of the sawtooth expiratory flow waveform pattern combined with added sounds on tracheal auscultation is currently the most accurate method available for the bedside detection of secretion retention or more appropriately the need for airway suctioning^16,17 and chest physiotherapy.¹⁸

The Impact of Secretion Retention

Secretion retention may lead to occlusion of the endotracheal tube,¹⁹ increase airway resistance, and an increase in hypoxemic events during the ICU stay.^4,14,20-25 Severe impairment of gas exchange or lobar/lung collapse may also occur during routine procedures such as patient repositioning,^26-28 as a result of the migration of airway secretions due to gravity²⁹ and/or flow bias.³ The detection of secretion retention may thus rely on the development of severe hypoxemia, loss of tidal volume/raised peak airway pressure during mechanical ventilation, and/or lobar/lung collapse on the portable chest radiograph.²³ These adverse events may lead to interventions such as a bronchoscopy or the need for an endotracheal tube change.

The Optimal Methods to Enhance Secretion Clearance

Airway suctioning via the artificial airway is considered the primary means to maintain airway patency and assist with secretion clearance of the major airways if an effective cough can be elicited (up to the third-generation bronchi).³⁰ Therefore, for the mobilization of secretions from the peripheral airways to more central airways, additional interventions may be required. The methods used to optimize secretion clearance in the intubated and ventilated patient³¹ include the appropriate humidification of inspired gas, increasing lung volumes (eg, manual and ventilator hyperinflation), increasing the expiratory flow bias (manual assisted cough, manual chest wall compressions/vibrations, and mechanical insufflation-exsufflation [MI-E]), in addition to airway suctioning. Specifically, patient positioning head down (gravity-assisted drainage), airway suctioning, and manual and ventilator lung hyperinflation demonstrate significant short-term improvements in lung function such as dynamic lung/thorax compliance and clearance of the wet weight of secretions.^32,33 Some, however, criticize the primary focus by clinicians on secretion retention as it addresses only one aspect of the oxygen transport pathway, namely ventilation.⁵

Without an accepted standard for the diagnosis of secretion retention in intubated and mechanically ventilated patients, this may result in disparate management of secretion retention. For example, it may seem appropriate to opt for a therapeutic bronchoscopy for secretion retention rather than chest physiotherapy especially in hospitals where access to 24/7 physiotherapy is not available,³⁴ yet the evidence is supportive of early chest physiotherapy before resorting to the use of bronchoscopy.³⁵

Berry and Martí³⁶ provide a comprehensive overview of management of secretion retention in the intubated and mechanically ventilated subject. Additional physiotherapy interventions may include normal saline lavage prior to airway suctioning,³⁷ manual chest physiotherapy techniques (chest wall percussion/vibrations/compressions), head-down patient positioning, rotational bed therapy, manual/ventilator lung hyperinflation, MI-E, intrapulmonary percussive ventilation, and oscillatory vests to apply high-frequency chest wall compressions.^30,38 These chest physiotherapy interventions may provide small benefits in terms of lung function, gas exchange duration of mechanical ventilation, pneumonia, and mortality,^33,38-41 but the findings are not consistent.

MI-E provides lung inflation with a positive pressure, followed by a rapid negative-pressure exhalation (delivered via a face mask or the artificial airway) that creates an expiratory flow bias to move mucus cephalad for either patient coughing and/or airway suctioning. As MI-E can create a simulated cough in patients who are sedated, unconscious, or globally weak, it is seen to be a useful means to enhance mucus clearance in these scenarios.⁴² MI-E has been be used in the ICU setting predominantly for patients with spinal cord injury and neuromuscular disease as the patient groups have severe respiratory muscle weakness.⁴³ MI-E (−50/+50 cm H₂O) in the intubated and ventilated patient may assist with greater clearance of airway secretions and improvements in respiratory mechanics than airway suctioning alone.⁴⁴ However, there is very little evidence in how MI-E is used and reported.⁴⁵ Martí et al⁴⁶ in this issue report on an experimental intubated/ventilated heavily sedated animal model to objectively evaluate the effects of different pressure combinations of MI-E on simulated tracheal mucus displacement, inspiratory and expiratory flows, respiratory mechanics, and hemodynamic safety. They studied the effects of 8 combinations of MI-E pressures on the movement of a mucus simulant placed in the trachea. They measured the tracheal mucus velocity through fluoroscopic images of the lateral trachea to track radio-opaque tantalum discs placed into the trachea. Fluoroscopic images were obtained before interventions to establish baseline movement of mucus simulant and immediately after each of the 8 cycles of MI-E. The key findings from this study were that MI-E set at +40/−70 cm H₂O led to an approximate 5-fold greater displacement in the cephalad direction of simulant airway secretions in the trachea. The authors are to be commended on this ongoing work led by their group in the area of secretion retention and its management in the mechanically ventilated patient.⁴⁶ However, some aspects of this work require further discussion and investigation. The animal model was nursed in a supine flat position, which differs from the conventional positioning of the ICU patient with the head of bed elevated to 30–45 degrees; hence, the impact of the MI-E on cephalad mucus movement may have also been assisted by gravity.²¹ The deep sedation used in the study to eliminate cough reflex contrasts to most ICU patients who will have cough reflex intact, and it may be presumed the cough response in addition to MI-E will have a significant impact on the mucus clearance. The investigators used a mucus simulant placed in the trachea; therefore, it is unknown what the impact of MI-E is on the lower and peripheral airways. The PEEP setting of 3 cm H₂O (lower than the normal values used in ICU) limits the generalizability to the ICU scenario. For example, the disconnection of the patient for MI-E with a PEEP > 3 cm H₂O may lead to lung de-recruitment and increased shear stress, which requires further evaluation. The baseline tracheal mucus clearance rate of 2.85±2.29 mm/min in cephalad direction in this study by Martí et al⁴⁶ was higher than the findings of Konrad et al⁴ with baseline median bronchial transport velocity in the right primary bronchus at 0.8 mm/min and in the left at 1.4 mm/min, presumably due the gravity-assisted drainage with the supine flat positioning of the animals. The authors⁴⁶ also demonstrated that with an increasing mean inspiratory flow there was a reduction of the mucus displacement rate in the cephalad direction. This may be of concern considering that conventional ventilator settings favor an inspiratory flow bias,²⁴ which may promote secretion retention.

The work by Martí et al⁴⁶ should be commended, but we have many aspects that require further investigation before we can implement MI-E into clinical practice in the intubated and mechanically ventilated patient. Table 1 lists key issues regarding MI-E use and future research directions.