Summary of main results
The effectiveness of either continuous negative extrathoracic pressure (CNEP) or non-invasive continuous positive airway pressure (Ni-CPAP) in acute hypoxaemic respiratory failure (AHRF) in children has not been evaluated in detail. We included two studies in this review, one of which is published in an abstract form only (Hartmann 1994a). Cam 2002 studied the effectiveness of CPAP over a 30-minute period in children with dengue fever and Hartmann 1994a studied the effectiveness of CNEP in children with AHRF over one hour. Short-term improvements in outcomes were reported in both studies with improvement in haemodynamic parameters. The severity of the underlying illness in both studies is difficult to assess from the data provided because in one study (Cam 2002) only four participants required mechanical ventilation whereas in the second study (Hartmann 1994a) only one of the control group infants required assisted ventilation.
Overall completeness and applicability of evidence
Samuels 1989 was the first to report on the use of CNEP in this population. The participants were not randomised. Reduction in oxygen requirements was evident in 75 out of 88 participants after two hours and in 74 out of 88 participants after 48 hours. There was no comparison group so it is difficult to assess the effectiveness of CNEP on mortality or other significant outcomes. Linney 1997 published a report from the same institution on a subgroup of patients with bronchiolitis. The authors showed that CNEP helped in avoiding intubation in the majority of participants (26 out of 27). This was a non-randomised study. Samuels 1996 reported on the use of CNEP in neonatal respiratory distress syndrome in a randomised controlled trial (RCT). Infants were randomised to standard therapy or standard therapy and CNEP. CNEP resulted in a reduction in the number of infants needing intubation (5%), reduced duration of oxygen therapy and subsequent reduction in the incidence of chronic lung disease of preterm infants. However, there was a statistically insignificant increase in mortality, cranial ultrasound abnormalities and pneumothoraces in the CNEP group.
Corrado 1998, in a retrospective case-control study, compared CNEP and conventional ventilation in the treatment of acute respiratory failure in chronic obstructive pulmonary disease (COPD) patients and found negative pressure ventilation to be equally efficacious in reducing in-hospital mortality. Corrado 2002, in a retrospective case-control study, compared negative pressure ventilation and non-invasive positive pressure ventilation in the treatment of acute chronic respiratory failure in adult patients with COPD in four intermediate respiratory intensive care units (ICUs) in Italy. Both ventilatory techniques were found to be equally effective in avoiding endotracheal intubation and death.
Gorini 2001 studied seven adult patients who had acute exacerbation of COPD using a microprocessor-based negative pressure ventilator and found that CNEP in association with negative pressure ventilation improved ventilatory patterns, arterial blood gases and reduced the work of inspiratory muscles. Negative pressure ventilation has a limitation of triggering capability. Gorini 2002 studied a microprocessor-based negative pressure ventilator capable of thermistor triggering in four normal participants and six patients with COPD. The authors found that this technique improved the synchrony between the patient and the negative pressure ventilator. Thus, in these uncontrolled studies negative pressure ventilation has been found to be equally as efficacious as conventional mechanical ventilation in adult patients with respiratory failure, however prospective studies comparing these interventions are lacking.
Soong 1993 studied 10 infants with bronchiolitis and impending respiratory failure in a non-randomised study. They reported improvement in symptoms, signs and physiologic parameters (heart rate, respiratory rate, PaCO2 and oxygenation index) after two hours of application of CPAP.
Hilbert 2000 evaluated adult patients who were neutropenic and had AHRF treated by CPAP. They reported that CPAP was successful in avoiding intubation in 25% of the patients.
Use of CPAP in neonates has shown some benefits but the trials were conducted in the pre-surfactant era (Ho 2010). Recently, Declaux 2000 in a RCT of CPAP in AHRF adults showed that after one hour of therapy the subjective response to treatment and PaO2/FiO2 ratio were better in the CPAP group compared to the standard therapy group, although this was not associated with a reduced rate of intubation or in-hospital mortality.
The use of CPAP in paediatric AHRF is increasing. Several pilot studies (Essouri 2008; Sanabria 2008; Stucki 2009) were identified recently which have used different forms of CPAP devices such as helmet, nasal prongs or high-flow nasal cannula to generate CPAP and effectively help patients to breath easily and support respiration during acute phases. The relative ease of application prior to invasive forms of ventilation has led clinicians to use CPAP without sufficient evidence. RCTs should be conducted in this population.
The role of non-invasive ventilation in modern clinical practice was evaluated at an international consensus conference (Evans 2001). Important issues were raised in terms of study designs. These included matching of patients in a non-randomised fashion, the small sample size of available studies and the influence of this on confounding variables, the potential for missing undetected adverse effects in a subgroup population, practical problems associated with unblinded studies of increased care and surveillance of study participants and non-standardised assessment of qualitative endpoints. Recommendations were made for identifying means of rapidly assessing patients who will benefit from non-invasive ventilatory modes. In adult patients with AHRF, evidence was pointing towards the effectiveness of non-invasive PPV in avoiding intubation, complications and mortality. However, the need for larger controlled trials was identified (Evans 2001). Recently there have been reports on the use of CNEP and CPAP. However, these were single-centre studies with no comparative cohort or, if a comparative cohort was included, the participants did not meet the criteria for hypoxaemic respiratory failure. In light of these reports, proper studies are warranted as this practice continues to be implemented in a random fashion.
For future studies it is important to decide the importance of various outcomes. Reduction of in-hospital mortality is a very important outcome and even a small reduction would be beneficial. However, as patients with the most severe disease are not going to be candidates for these experimental interventions, such trials would require very large sample sizes to achieve any significant reduction. Other outcomes of interest may include reduction in intubation rates, associated complications, duration of hospital stay and increased patient comfort. Standardised interventions in the control group and assessments are warranted to assess these outcomes. CNEP and Ni-CPAP are perceived to be potentially useful in certain clinical situations where avoidance of intubation or early extubation and management by CNEP or Ni-CPAP may be useful, but further studies are warranted.
Thus, there is insufficient evidence from randomised studies to conclude that CNEP is beneficial in AHRF in paediatric patients. Potential advantages, such as reduction in the intubation rate, intubation-associated complications and patient comfort (less restlessness, discomfort or dyspnoea), make this modality appealing. However, properly conducted RCTs are needed to assess the benefits and risks.
Quality of the evidence
The quality of the CPAP study (Cam 2002) was relatively good, whereas the quality of the CNEP study (Hartmann 1994a) was difficult to assess as it was only published in abstract form. Both studies reported on short-term outcomes only and had small sample sizes.
Agreements and disagreements with other studies or reviews
Guidelines for non-invasive management of respiratory failure have been published. However, most of the evidence stems from non-randomised studies.