Pathophysiological effects of non-invasive ventilation

EFFECTS ON THE RESPIRATORY SYSTEM

Extrinsically applied positive end expiratory pressure (ePEEP) increases alveolar size and recruitment.^{2, 3} This expands the area available for gas exchange, reduces intrapulmonary shunt, improves lung compliance, and decreases the work of breathing.^3–6 It acts to negate the effects of intrinsic PEEP (iPEEP), which is the cause of dynamic airway compression and gas trapping.^{7, 8} Ventilation is improved with beneficial effects on the alveolar-arterial gradient, hypercarbia and, to a lesser extent, hypoxia.^{9, 10}

Pressure support (alone or as part of bilevel positive airway pressure, BiPAP) further augments alveolar ventilation and allows some respiratory muscle rest during the inspiratory phase.¹¹

EFFECTS ON THE CARDIOVASCULAR SYSTEM

PEEP reduces venous return to the right side of the heart.¹² Left ventricular preload, transmural pressure, and relative afterload are all decreased without altering myocardial contractility.^12–14 Thus, the ejection fraction improves without an increase in myocardial oxygen consumption.^{12, 15} It appears that those with worst ventricular dysfunction show the most significant improvement in stroke volume index with continuous positive airway pressure (CPAP).¹⁶

Overall, CPAP leads to a decrease in arterial pressure, heart rate, and rate-pressure product within 10 minutes, without exacerbation of hypotension.¹⁷

EFFECTS ON OTHER SYSTEMS

Intracranial pressure (ICP)—in patients with raised ICP there may be an increase in ICP by at least the same degree as the PEEP applied.¹⁸

Renal—PEEP causes decreased sodium excretion and urine output, possibly due to raised vena caval pressure reducing cortical blood flow.⁴

Applying non-invasive ventilation

EQUIPMENT

There are two major options for interface between patient and machine: nasal masks and (oronasal) facemasks. Nasal masks have traditionally been used in the setting of chronic, home therapy and have also been applied to the acute setting. They offer the advantages of a smaller dead space, less claustrophobia, and the ability to utilise the mouth quickly and easily (for communication, expectoration, vomiting, and oral intake), albeit with the loss of pressure. Dyspnoeic patients, however, are typically mouth breathers and the oral route offers less resistance to gas flow. Thus, facemasks are preferable for treatment of acute respiratory failure in the emergency department.

The use of a mouthpiece has also been described¹⁹ but requires nasal occlusion and a good mouth seal making leak avoidance difficult. A full facemask has recently been developed and is reported as having advantages over other means of applying non-invasive ventilation.²⁰

MONITORING

Monitoring of patients undergoing non-invasive ventilation should be similar to that generally used to manage patients with acute respiratory failure. Non-invasive blood pressure monitoring at intervals of 5–15 minutes, continuous electrocardiography (ECG) monitoring, ongoing pulse oximetry, assessment of respiratory rate, temperature, chest radiography, and 12 lead ECG is recommended.

Frequent arterial blood gas analysis will aid therapeutic decision making but will be limited by the means of arterial sampling employed (intermittent puncture compared with arterial line). The frequency of blood gas analysis in the major trials was quite variable; from every 30 minutes for six hours²¹ to at one hour, three days, and seven days.²² Blood gas analysis as soon as practical after presentation is recommended. Additional sampling should be performed to monitor progress. Depending on the patient's condition one to two hourly sampling should be sufficient.

LEVEL OF PEEP

The goals of acute respiratory therapy should be maintenance of an arterial oxygen saturation >90% or arterial oxygen tension (pao₂) >8.0 kPa (>60 mm Hg).^{3, 23} This degree of oxygenation should be maintained during weaning from non-invasive ventilation. The optimal level of PEEP to apply is one which closely matches iPEEP.^{7, 24, 25} Given the difficulty in measuring iPEEP in the emergency setting the most practical solution is a gradual increase in ePEEP (for example by 2.5–5.0 cm H₂O) until a satisfactory response is achieved.^{3, 24} It is recommended that PEEP (that is CPAP or expiratory positive airway pressure, EPAP) be started at 4–6 cm H₂O and inspiratory pressure (if used) at 8–14 cm H₂O.²⁶ The effect of changes in non-invasive ventilation on arterial blood gases is evident within 10–15 minutes with no further effect demonstrable at 30 minutes.^{27, 28} This suggests incremental increases in ventilatory therapy could be applied every 15 minutes, if needed, until a satisfactory degree of oxygenation is attained. The clinician should also observe an improvement in the clinical condition within one to two hours.

Evidence for the use of non-invasive ventilation

EVIDENCE FOR USE IN OBSTRUCTIVE AIRWAYS DISEASE

There are only four randomised controlled trials comparing non-invasive ventilation with standard treatment in acute exacerbations of obstructive airways disease carried out in intensive care units (table 1). Different modes of ventilation were used in each: nasal BiPAP,²⁹ facemask pressure support ventilation (no CPAP/EPAP component),³⁰ facemask BiPAP,³¹ and nasal volume cycled positive pressure ventilation.²²

Two of the studies using pressure cycled ventilation^{29, 30} demonstrated significantly decreased intubation rates compared with standard treatment (1/11 (9%) v 8/12 (67%) and 11/43 (26%) v 31/42 (74%), respectively). The other study using pressure cycled ventilation found BiPAP to be successful (defined as improvement in gas exchange, clinical parameters, and discharge from the hospital) in 14/15 (93%) compared with 9/15 (60%) with standard treatment alone.³¹ Those who failed with standard treatment received a trial of BiPAP that was successful in 4/6 (60%). All the studies using pressure cycled ventilation showed significant differences in some respiratory and cardiovascular parameters (respiratory rate, heart rate, pH, and Pao₂) after one and six hours of treatment, compared with standard treatment. There was no significant improvement in arterial carbon dioxide tension (Paco₂) compared with standard treatment. On subsequent days there was no difference in these parameters between treatment and control groups. The larger study, with 85 patients, had significantly reduced in-hospital mortality rates (4/43 (9%) compared with 12/42 (29%)), significantly decreased hospital length of stay (mean 23 v 35 days), and fewer life threatening complications (mainly pneumonia, complicated intubations, and cardiac arrest after weaning).³⁰

Volume cycled ventilation also demonstrated decreased mortality compared with controls (1/24 (4%) v 9/30 (30%)) when looking at efficacy with respect to 30 day survival.²² However intention-to-treat 30 day mortality (3/30 (10%)) was not significantly better than in the control group. Respiratory parameters were significantly better in the treatment group at one hour (pH, paco₂, and breathlessness) but not on days 3 or 7.

Case series studies of patients with acute exacerbations of obstructive airways disease report effective outcomes with both CPAP^{19, 32–38} and BiPAP^39–53 with respect to clinical parameters, arterial blood gases, and need for intubation compared with (often historical) controls and previously published data. When patients were cycled through a range of ventilatory modalities, CPAP and pressure support ventilation were similarly effective at improving blood gases and reducing the work of breathing; however, while the addition of EPAP to pressure support ventilation (that is BiPAP) further decreased the work of breathing there was no additive effect on the correction of gases.^{7, 54}

These studies indicate that non-invasive ventilation is beneficial to the acute treatment of chronic obstructive airways disease; it reduces the need for intubation and may reduce both hospital length of stay and mortality. Acidosis and hypoxia are more responsive to treatment than hypercarbia and show significant improvement within one hour of treatment.

EVIDENCE FOR USE IN ACUTE PULMONARY OEDEMA

There are four randomised controlled trials investigating non-invasive ventilation in acute pulmonary oedema (table 2). Three compare CPAP with standard treatment with high flow oxygen in intensive care settings^21–55 and one compares BiPAP with CPAP for emergency department treatment of pulmonary oedema.⁵⁶ Wood et al compared BiPAP with standard treatment in patients with various causes of acute respiratory failure in the emergency department.⁵⁷

Although the studies comparing CPAP with standard treatment contain relatively small numbers (39, 40, and 100 patients, respectively) some benefits are clearly demonstrated. All showed significant improvements with CPAP in subjective respiratory status and blood gas analysis over 30 minutes to six hours and, generally, improvement of various cardiovascular parameters without exacerbation of pre-existing hypotension. There was a decrease in need for endotracheal intubation and mechanical ventilation in all studies (combining study populations: 12/89 (13%, range 0%–30%) with CPAP, compared with 31/90 (34%, range 24%–60%) with standard treatment) but this was not statistically significant in one.²⁸ No complications of non-invasive ventilatory therapy were reported.

Medium to long term outcomes were no different in any of the studies comparing CPAP with standard treatment. Bersten et al demonstrated no significant differences in blood gas analysis at 24 hours.⁵⁵ Hospital mortality and length of stay was not significantly different in any of the studies. There was no difference in one year mortality.²¹

The one study comparing CPAP with BiPAP suggested more rapid improvement with BiPAP.⁵⁶ Patients receiving BiPAP had statistically significant improvements in Paco₂, pH, heart rate, respiratory rate, and dyspnoea scores at 30 minutes but CPAP showed only improvements in respiratory rate. This study was terminated early, with only 27 patients, because of a significantly higher incidence of myocardial infarction in patients receiving BiPAP: 10/14 (71%) compared with 4/13 (31%) with CPAP and 38% in a matched historical control group of 200. There were no statistically significant differences in baseline characteristics of the two study groups. Whether BiPAP caused the infarcts is unclear. Analysis of creatine kinase MB fractions suggests that a significant number of the infarctions may have been underway at enrolment. There was no significant difference in time on the device, mortality, or length of stay (intensive care unit and hospital) between the groups.

When BiPAP and standard treatment was compared with standard treatment alone in a heterogeneous group of emergency department patients⁵⁷ (10 with acute pulmonary oedema, six chronic obstructive airways disease, nine pneumonia, one interstitial lung disease, and one sepsis) a trend towards increased hospital mortality (4/16 (25%) compared with 0/11) and number of acquired organ system derangements was found in the group randomised to BiPAP. Those receiving BiPAP tended to improve their mean arterial pressure and Pao₂ faster than the control group. The authors suggest that the poorer outcome may be related to predetermined biases on the part of treating physicians and respiratory therapists in favour of non-invasive ventilation (a reluctance to abandon non-invasive ventilation until the last moment). As noted by the authors, the risk of both type one and two errors is increased in a study of this size. Although there was no statistically significant difference between the groups at presentation, a higher number of patients in the treatment group had pneumonia at presentation, 7/16 or 43.8% compared with 2/11 or 18.2% of those receiving standard treatment. It is not stated what the presenting diagnosis of the hospital non-survivors was but pneumonia has been associated with poorer outcome in patients receiving non-invasive ventilation.^{45, 52}

Case series studies also support the beneficial effect of BiPAP^{40, 45, 47, 58–61} and CPAP^{16, 62–64} on pulmonary oedema. The largest of the studies looking at CPAP on acute pulmonary oedema was a retrospective review of 75 patients treated in the emergency department in whom only 4% required intubation and mean time on CPAP was 1.9 hours.⁶⁴

Overall, the above studies indicate that non-invasive ventilation was effective in decreasing the intubation rate in acute pulmonary oedema and speeds the acute treatment of pulmonary oedema with few complications.⁶⁵ There is no significant improvement in length of stay or long term mortality compared with standard treatment.

EVIDENCE FOR USE IN OTHER RESPIRATORY DISORDERS

Non-invasive ventilation is widely used in non-acute settings such as home treatment of stable chronic obstructive airways disease,^{66, 67} postoperatively,^{68, 69} and in weaning from conventional mechanical ventilation.^{67, 70}

Case reports and small case series describe the use of non-invasive ventilation for acute respiratory failure of many aetiologies other than cardiogenic pulmonary oedema and obstructive airways disease. These include pneumonia,^{45 52 59 69} pulmonary embolism,⁵² stroke,⁵⁹ overdose,⁵⁹ restrictive lung diseases,^{20 71 72} acute respiratory distress syndrome of various aetiologies,^{69, 73, 74}Pneumocystis carinii pneumonia,⁷⁵ Goodpasture's disease,⁷⁶ fat embolism,⁷⁶ bronchiectasis,⁷⁷ mediastinitis,⁶⁰ laryngeal dyspnoea,⁶⁰ and as an option to traditional ventilation in palliative care.⁷⁸

PROBLEMS WITH NON-INVASIVE VENTILATION

Non-invasive ventilation appears to be remarkably free of serious complications and side effects. The primary disadvantage of non-invasive ventilation is its reliance on a spontaneously breathing patient who is able to protect their airway against the risk of aspiration. If either of these conditions are not met, endotracheal intubation and traditional ventilation is indicated.

The most commonly reported complications of non-invasive ventilation are nasal bridge skin abrasions^{29, 31, 42, 45, 62, 74, 79, 80} and patient intolerance of the treatment.^{29, 52, 62, 75, 80} Although a possibility with firmly applied masks, skin abrasions are usually only seen in long term use of non-invasive ventilation. Patient intolerance of non-invasive ventilation can be reduced by education before its application (although this is often difficult in an emergency setting) and ongoing explanation and reassurance. Hypoxic and hypercarbic effects on mental state may be in part responsible for this intolerance.

Gastric distension and aspiration is a frequently discussed side effect of non-invasive ventilation, but is relatively rarely described in clinical trials.^{31, 45, 81, 82} Studies of the pressure needed to inflate the stomach via non-invasive ventilation suggest that at least 25 cm H₂O is required^{26, 79}; this is significantly higher than the levels in general use. Some authors describe the routine placement of nasogastric tubes to prevent gastric distension,⁶² but this is probably unnecessary and can lead to excessive leaks.

Non-invasive ventilatory systems are, generally, quite tolerant of leaks but mouth leaks with nasal masks can lead to therapeutic failure.^{41, 79} Oral loss of pressure with nasal ventilation may be prevented by the soft palate being pressed against the tongue to give a seal.²⁶ When this is insufficient a chin strap²⁹ may be applied or changing to a facemask⁵⁶ may be indicated.

Case reports exist of other complications of non-invasive ventilation. A variety of arrhythmias (bradycardia, ventricular tachycardia, and ventricular standstill) have been reported during CPAP but were all probably related to underlying myocardial infarction.⁶⁴ Pneumothorax is reported to have complicated treatment of P carinii pneumonia, but these patients are at high risk of this when ventilated by traditional means.⁸³ A neonate is also reported to have suffered pulmonary venous air embolism while undergoing BiPAP treatment.⁸⁴ These cases serve as an important reminder of the potential for barotrauma with any form of positive pressure ventilation. Pneumocephalus has been described in one patient receiving CPAP after weaning from traditional ventilation who had an unrecognised base of skull fracture as a result of a motor vehicle accident.⁸⁵ One case of bilateral tympanic rupture and otorrhagia is reported in an agitated patient coughing against CPAP.⁸⁶ Subconjunctival emphysema⁸⁷ and corneal abrasions^{80, 88} have also been reported; a well fitting mask significantly reduces the risk of both of these.

Conclusions

Non-invasive ventilation, CPAP and BiPAP, appears to be an effective addition to standard treatment for acute exacerbations of obstructive airways diseases and pulmonary oedema. It seems to be a safe, readily applied modality of ventilatory assistance that decreases the need for endotracheal intubation, speeds recovery, and may shorten hospital length of stay.

Published experience, in the form of large randomised controlled trials, is remarkably limited and uniform recommendations with respect to indications, contraindications, and the exact manner in which non-invasive ventilation should be applied are lacking. Although there are some theoretical advantages of BiPAP over CPAP, there is no clinical evidence that one offers an advantage over the other in the treatment of acute respiratory failure in the emergency department. Further study is required to clarify these points.

Most of the evidence has been derived from intensive care settings. However, this therapy is extremely useful in an emergency department setting as a first line treatment for acute respiratory distress. Early intervention may avoid the risks and complications of endotracheal intubation and shorten or eliminate intensive care or high dependency admissions.

Clinicians should remain vigilant while using non-invasive ventilation as ongoing monitoring and reassessment remains the key to the successful application of this therapy. However, careful utilisation of non-invasive ventilation in appropriately selected patients will optimise the outcomes for patients with acute respiratory failure.