Non-invasive mechanical ventilation

Non-invasive ventilation has been the subject of numerous past paper SAQs:

• Question 5 from the second paper of 2021 (in CCF, COPD and CAP)
• Question 1 from the second paper of 2015 ("critically evaluate" NIV in general)
• Question 24 from the second paper of 2014 (elective extubation on to NIV)
• Question 22 from the first  paper of 2014 (post Ivor Lewis)
• Question 1 from the first paper of 2007 (contraindications and complications)
• Question 13 from the first  paper of 2004 ("approach to")
• Question 3 from the second paper of 2000 (indications and contraindications)

The best resources for this topic are:

• LITFL: Non-Invasive Ventilation (NIV)
• LITFL: Non-invasive ventilation (NIV) and Asthma
• Gay et al (2009) "Complications of noninvasive ventilation in acute care"
• Kallet et al (2009) "Physiologic effects of NIV"

Physiology and rationale for NIV

Physiological basis of the treatment effect

• For respiratory failure in general:
  • Positive pressure ventilation in general has benefits which are common to both NIV and IPPV.
  • Increased inspiratory positive pressure decreases work of breathing by improving lung compliance by recruiting collapsed alveoli
  • Increased FRC due to increased closing capacity improves oxygenation
  • Tight-fitting mask ensures accurate delivery of prescribed FiO₂
• CCF:
  • Increased alveolar pressure decreases the effects of pulmonary oedema on gas exchange
  • Increased intrathoracic pressure improves LV performance:
    • Decreased LV transmural pressure = decreased afterload
    • Decreased venous return = decreased preload
  • Improvement in pulmonary oedema and respiratory distress also indirectly decrease myocardial oxygen demand by moderating the sympathetic response and decreasing the effort of breathing
• COPD:
  • Increased end-expiratory positive pressure decreases work of breathing vs. intrinsic PEEP
  • Increased expiratory air flow can improve CO2 clearance
  • Increased minute volume can better compensate for the increased dead space of emphysema
  • Splinting open of smaller airways allows better bronchodilator delivery
• Community-acquired pneumonia:
  • NIV does not tend to benefit this group of patients, because:
    • It can impair secretion clearance
    • It can increase shunt
  • However, the delivery of humidified oxygen by mask can improve secretion clearance
  • In patients with CCF or COPD and pneumonia, NIV can improve mortality ( Carrillo et al, 2012) 

Advantages when compared to invasive ventilation

• Decreased cost
• Better tolerated (no need for sedation)
• More convenient
• Better availability outside of the ICU setting (eg. domiciliary)
• Ability to interrupt therapy for breaks allows easier weaning from mechanical support

Disadvantages when compared to invasive ventilation

• More difficult to manage with an uncooperative patient
• Cannot be used in physically restrained patients (what if they vomit? They cannot remove the mask)
• Prevents the effective clearance of secretions and impairs physiotherapy access for suctioning
• Cannot be performed on patients with a decreased level of consciousnes
• Mask-face interface is difficult to manage: "one size fits all" masks do not in fact fit all; patients with unusual anatomy or little facial soft tissue (eg. in cachexia) will have more difficulty
• Mask leak is uncomfortable and decreaseas the effectiveness of the therapy
• Work of breathing may be increased

Strong indications for NIV

Cardiogenic pulmonary oedema

A Cochrane review of NIV in acute pulmonary oedema found that it dramatically improves survival (RR = 0.6) and decreases the rate of intubation and the length of ICU stay. LITFL mention "over 20 RCTs" in support of this therapy; the abovementioned Cochrane review actually found 32 eligible studies in total, all of which had something positive to say. Only the small studies had found a mortality benefit, but it was a substantial one (RR = 0.6). 

COPD

A Cochrane review of NIV in the COPD patient group has demonstrated that in comparison to the invasively ventilated group, patients treated with NIV have greatly reduced mortality (by half), reduced hospital stay, and reduced risk of pneumonia. LIFL mentions "over 14 RCTs" in support of this therapy, perhaps because 14 trials met the inclusion critearia for the abovementioned review. This issue is explored to a greater depth in the chapter on ventilation strategies for COPD.

Weaning COPD patients from invasive ventilation

As soon as they can breathe spontaneously, they should be extubated and supported with NIV. This Cochrane review suggests this strategy can halve mortality and reduce the rate of VAP to one third.

Obesity hypoventilation sydrome:

NIV is already the mainstay of chronic maintenance for OSA; a recent review by Carrillo et al (2012) has shown that in acute respiratory failure the OSA patients benefit from NIV even more than COPD patients. A 2015 summary of recent opinions (Shirley et al) concluded that it is a essential part of intensive care for the morbidly obese patient.

Rib fractures and chest trauma

A meta-analysis  by Chiumillo et al (2013) found ten studies meeting inclusion criteria; of these five studies reported mortality, with startling findings: NIV reduced the relative risk of mortality (RR = 0.26) when compared with just oxygen or straight-up intubation. NIV was was associated with a significant reduction in intubation rate, in the incidence of overall complications and infections.

Weak indications for NIV

Asthma

This issue is explored to a greater depth in the chapter on ventilation strategies for status asthmaticus. In brief, the most recent meta-analysis of evidence (Lim et al, 2012) has failed to demonstrate a clear mortality benefit. However, it does seem to prevent intubation and decrease the length of ICU stay, as well as allowing for improved delivery of nebulised drugs.

Elective extubation of patients at risk of post-extubation respiratory failure

Cooperative hypercapneic high-risk patients may benefit (Ferrer et al, 2006) but not all-comers (Su et al, 2012) and it may actually be dangerous in unselected patients (Esteban et al, 2004) as waiting for NIV to work in a patient who clearly requires re-intubation is a pointless time-wasting exercise with an associated increase in mortality.

Ventilation for cystic fibrosis patients awaiting lung transplant

The college model answer to Question 1 from the second paper of 2015 listed this as one of the indications for NIV. Support for it rests largely on small-scale observational studies. Alonso et al (2016) have performed a good review of this practice, but it is not available for free. Instead, one may look to the Cochrane review by Bright-Thomas et al (2013). None of the examined studies were particularly large, and none looked at survival as a specific variable (though in case series prolonged survival until transplant was observed).

Community-acquired pneumonia

Though classical teaching recommends against NIV in suppurative lung disease, a recent review by Carrillo et al (2012) has demonstrated that there is a group of pneumonia patients who benefit from NIV. These are patients with pre-existing cardiac or respiratory disease, i.e. those in whom the NIV has something to work on. In contrast, patients with healthy hearts and lungs have neither COPD nor heart failure, and thus nothing for the NIV to work on; in this group mortality was actually increased. Mortality increased in proportion to the hours of NIV, suggesting that these people just need to be intubated, and that NIV is a time-wasting exercise for them. These findings were confirmed in a more recent retrospective study of CAP patients (Murad et al, 2015) which found that NIV in this setting was associated with high failure rates (76% required intubation anyway) and with no improvement in mortality among those patients in whom it was used as first-line therapy. 

Post-operative respiratory failure

"Prophylactic NIV" in the post-operative setting has been promoted as a means of making more rapid the respiratoryr ecovery of at-risk patients (eg. cardiac, thoracic and abdominal surgery). Unfortunately, the data to support this is missing. A recent (2012) review by Jaber et al could only make lukewarm and nonspecific recommendations.

Lung infection in the neutropenic patient

Its not that noninvasive mechanical ventilation enhances the survival of immunocompromised patients; rather, invasive ventilation seems to be associated with a poorer outcome, perhaps because of the increased risk of nosocomial pneumonia and poorer secretion clearance. The college model answer to Question 4 from the second paper of 2015 urges against the use of invasive ventilation in the neutropenic patient ("Attempt to avoid invasive respiratory support if possible").

Most of the data in support of this is actually in support of NIV versus standard oxygen, not invasive ventilation. As an example, a small (n=52) trial by Gilles et al (2001) compared intermittent NIV to standard supplemental oxygen, and found that the NIV group managed to avoid intubation (12 vs 20 patients). . Earlier, Antonelli et al (2000) showed an improvement in ICU length of stay and rate of intubation among neutropenic patients with solid organ malignancy. However, NIV here was used in a very bizarre manner. Gilles et al used it in 45-minute bursts, for example.  Antonelli's team used continuous NIV, but aimed for high tidal volumes ( 8-10ml/kg) and used low PEEP. Even though varieous society clinical practice guidelines made recommendations for the use of NIV in these groups (eg. Keenan et al, 2011)

A more recent entry into this debate comes from Lemiale et al (2015, JAMA) who investigated the effects of NIV on 28-day mortality (n= 374). No mortality difference was found in these patients (whose PaO₂/FiO₂ ratios were all around 140 on average). There was no improvement in the rate of intubation. The only criticism is that the authors overestimated mortality from respiratory failure (they expected 35% but it was closer to 26%) and so the study ended up being underpowered.  An excellent discussion in response to this was published in the Journal of Thoracic Disease (Barbas and Neto, 2016). In summary, those who need intubation still need intubation, and using NIV to delay intubation only increases mortality.

Post-extubation stridor

This is explored in greater detail in the chapter on post-extubation stridor. In brief, the role of NIV in post-extubation stridor is unclear. It may benefit a select group of patients, but in others it delays an otherwise inevitable intubation. It may also make intubation more difficult, as the cords become more oedematous with time. The college mention CPAP as one of their solutions for stridor in the model answer for Question 27 from the second paper of 2008.

Limitations of therapy

if the patient requires intubation but is "not for " intubation, then NIV may a way of palliating them, or offering a sensibly non-aggressive therapy to give them a chance of survival. A review of this practice from Azoulay et al (2010) suggests that reversible causes of dyspnoea may be treated with NIV, and that it can provide comfort for transiently increased effort of breathing. However, the authors do caution against futile therapies, and describe terminal dyspnoea as one of the symptoms of the end of life. Azoulay et all then went to to perform a prospective observational study of 780 patients among 54 ICUs in 2013 which discovered an (unsurprisingly) high mortality among the patients that declined intubation. Surprisingly, among  survivors 90 day quality of life was similar to the intubated group, suggesting that NIV promotes a satisfactory level of survival in this "palliative" group.

Elective use of NIV following extubation

 Question 24 from the second paper of 2014 specifically asked about the role of planned NIV immediately following extubation. The candidates were encouraged to "explain how this differs from therapeutically applied (rescue) NIV used in the same context". The examiners quote several studies in their model answer:

• Ferrer et al (2006):  RCT; 162 patients who tolerated a spontaneous breathing trial (i.e. not in respiratory failure) who had at least one risk factor for post-extubation respiratory failure (eg. age over 65, APACHE-II score over 12 on the day of extubation, or cardiac failure as the cause of intubation). The investigators found reduced rates of respiratory failure in the electively NIVed group, but the 90 day mortality was only improved in the hypercapneic group.
• Su et al (2012): RCT, 406 patients who tolerated a spontaneous breathing trial randomised to NIV or standard care, looking at their rate of reintubation at 72 hours. There were no differences in extubation failure (13.2% in control and 14.9% in NIV), intensive care unit or hospital mortality. The conclusion reached by these investigators was that routine use of elective NIV will not prevent extubation failure.
• Esteban et al (2004): RCT, 221 unselected patients being extubated - randomised to NIV or standard therapy. There no difference in reintubation rate. However, recruitment was terminated early when interim analysis discovered an increased mortality rate in the NIV group, and a delay to intubation (i.e. more time was wasted on NIV, from the diagnosis of respiratory failure until the pointlessly delayed reintubation). However, only 10% of the patients in this study had COPD- the outcome would probably have been different if all of them had COPD, as in this highly positie Cochrane review of immediate elective NIV in extubated COPD patients.

In conclusion:

• Cooperative hypercapneic high-risk patients may benefit from elective NIV immediately following extubation.
• COPD patients probabyl benefit the most
• Normocapneic patients may still benefit, but their mortality may not be affected.
• Patients without risk factors for post-extubation respiratory failure will not benefit.
• There is no point in doing this routinely, and it may actually be dangerous, as it may delay re-intubation, and promote aspiration.

Contraindications for NIV

• Decreased level of consciousness
• Respiratory arrest
• Vomiting
• Hemodynamic instability
• Poor clearance of secretions, eg. absent cough and gag
• large sputum load and/or pneumonia
• surgical or traumatic damage to the airways or oesophagus

Complications  of  NIV

• Mask intolerance, agitation and claustrophobia
• Increased need for sedation
• Delay of intubation
• Aspiration
• Poor clearance of secretions
• Hypotension of hypovolemic patients
• Facial pressure areas
• Raised intracranial pressure
• Aerophagy
• Damage to facial, nasal and oesophageal surgical sites or traumatic injuries, leading to surgical emphysema, pneumothorax and pneumomediastinum

Adjustment of NIV

• Titrate IPAP and EPAP to work of breathing and tidal volume targets
• Adjust inspiratory flow rate and expiratory cycle-off to increase or decrease the expiratory phase
• Adjust delivery mechanism to suit patient needs (eg. nasal mask, full face mask or half face mask, or full helmet)

Is this patient failing NIV?

Question 5 from the second paper of 2021 asked the candidates to "explain how you would assess efficacy of NIV", which was basically a question about the endpoints of therapy and the factors which are associated with impending intubation. This was an example of excellent assessment blueprinting, as it tests a core area of  ICU knowledge. You'd want your grandma's intensivist to know the answer to this question.

Achievement of endpoints: When one embarks on a course of this treatment, one usually has some sort of goal in mind, even it may be something as nebulous and subjective as "improve the effort of breathing". For the use of NIV in acute respiratory failure, one could crudely frame this goal in terms of physiological parameters which were deranged prior to the start of NIV. These would be:

• Clinical endpoints:
  • Achievement of the SpO₂ goal, whatever it may be)
  • The FiO₂ should decrease with NIV (compared to what it was pre-NIV)
  • Improved tachycardia
  • Improvement in the respiratory rate (if the patient was tachypnoeic)
  • Subjective improvement in patient respiratory distress and reported comfort
  • Satisfactory mask tolerance, without the requirement for sedation
  • Improved level of consciousness
• Gas exchange and pulmonary function:
  • PaCO₂ decrease (if the patient was hypercapneic)
  • pH increase (if the patient was acidaemic to to hypercapnia)
  • Improvement of CXR appearance, specifically looking for radiological features of pulmonary oedema

These are not entirely arbitrary, and were assembled from a range of different COPD and CCF studies which assessed efficacy of NIV. Unfortunately, most studies look at better endpoints (eg. mortality or duration of ventilation), which would be completely useless here. 

Timeframe of the NIV trial: Again, a completely arbitrary number of hours can be plucked from thin air to describe the length of time one might wait before declaring the trial of NIV a success or a failure. In practice, this period tends to be decided by the time at which the intensivist intends to leave the unit. A more scientific approach might be to use studies which looked at NIV failure, borrowing the timeframes which they had published. For example, Nicolini et al (2014) found that 1 hour was enough (looking specifically at the heart rate). Carillo et al (2012) also used 1 hour as the timeframe, but gave 24 hours for pulmonary infiltrates to improve.

​​​​​​​Factors associated with NIV "failure"

From Sidhom et al (2009), Carillo et al (2012) and Nicolini et al (2014), we can cobble together a list of features which suggest that the patient is doing poorly, or is going to do poorly:

• Failure to achieve aforementioned endpoints within the specified timeframe
• De novo respiratory failure (i.e. never before diagnosed with respiratory disease)
• Hypotension
• Metabolic acidosis
• Poor mask tolerance and ventilator dyssynchrony
• Fluctuating or persistently decreased level of consciousness