Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

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Noninvasive Ventilation for Treatment of Acute Respiratory Failure in Patients Undergoing Solid Organ Transplantation; A Randomized Trial

Antonelli M, Conti G, Bufi M, et al.

JAMA. 2000;283:235-241. [abstract] [full-text free for limited time]

Reviewed by Priya Prabhakaran and Michele Mariscalco, Baylor College of Medicine, Houston, TX

Review posted July 22, 1999

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I. What is being studied?:

The study objective:

To compare non-invasive ventilation (NIV) with standard treatment using supplemental oxygen administration to avoid endotracheal intubation in recipients of solid organ transplantation with acute hypoxemic respiratory failure.

The study design:

Prospective randomized controlled trial conducted at a 14 bed general ICU of a University Hospital

The patients included:

All consecutive solid organ transplant recipients (238 patients during the study period) with acute respiratory failure were potential enrollees (51 total, 3 of whom were excluded and 8 of whom refused to participate).

Eligibility requirements were: acute respiratory distress, RR > 35/min, PaO2/FiO2 < 200 on O2 through a Venturi Mask, and active contraction of accessory muscles of respiration. A total of 40 patients were enrolled in the study (20 in the NIV group and 20 in the standard treatment group). Liver, lung, and renal transplant recipients were included in both group.The NIV group included 10 patients with liver transplants, 4 with lung transplants, and 6 with renal transplants. In the Standard treatment group, there were 12 patients with liver, 2 with lung and 6 with renal transplants.

The patients excluded:

Patients who needed emergent intubation for cardiopulmonary resuscitation, severe hemodynamic compromise, decreased mental status, respiratory failure secondary to asthma or neurological disease, > 2 new organ failures, tracheostomy, facial deformities or recent oral/esophageal or gastric surgery. Two of the three patients that were excluded had altered mental status and one was excluded secondary to having a tracheostomy.

The interventions compared:

NIV versus standard therapy with supplemental oxygen.

For patients assigned to NIV, the ventilator was connected with conventional tubing to a full clear face mask. Pressure support was increased to obtain an exhaled tidal volume of 8-10 ml/kg, a respiratory rate < 25/min, disappearance of accessory muscle activity, and patient comfort. PEEP was raised in increments of 2-3 cm H2O until the FiO2 requirement was < 0.6. Settings were altered based on oximetry and ABGs. Patients were not sedated. Ventilation was standardized according to the protocol of Wysocki et al. (1)

Patients assigned to the standard treatment group received supplemental oxygen via a Venturi mask starting at a FiO2 > 0.4 adjusted to achieve oxygen saturations of > 90%.

The outcomes evaluated:

Primary: Need for endotracheal intubation or mechanical ventilation. The need for endotracheal intubation was strictly defined.

Secondary: Development of complications not present on admission, length of hospital stay, duration of ventilatory assistance and ICU morbidity.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes. Computer generated random assignments concealed in sealed envelopes were used.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes. All patients completed the study and no patients were unaccounted for.

Were patients analyzed in the groups to which they were randomized?

Yes. There was no cross over between the two groups.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

The study personnel were not blinded due to the nature of the interventions being compared.

4. Were the groups similar at the start of the trial?

Yes. The two groups were similar with respect to mean age, APACHE scores, and baseline blood gases. The causes of respiratory failure in the two groups were also similar - pneumonia, cardiogenic pulmonary edema, ARDS, atelectasis with mucous plugging in decreasing order of frequency.

5. Aside from the experimental intervention, were the groups treated equally?

Medical management of acute respiratory failure (with antibiotics, antiviral or antifungal agents, aerosols, chest physiotherapy, diuretics), immunosuppression, monitoring, fluid and nutrition therapy were similar in both groups. Both groups were treated by the same medical and nursing staff.

III. What were the results?

1. How large was the treatment effect?

The use of NIV was associated with a significant reduction in the rate of intubation (20% vs 70% in the standard group, p = 0.002), rate of fatal complications (20% vs 50% p = 0.05) and ICU mortality.(20% vs 50%, p = 0.05). The absolute relative risk (ARR) for intubation is 0.5. Risk reduction (RR) was 0.28. The number needed to treat is 2, which suggests that NIV is an effective way to avoid intubation in this group of patients.

Of the patients with pneumonia, 50% required intubation, regardless of group assignment (1/2 in the NIV group and 1/2 in the Standard Treatment group). The mortality experienced by these patients was also the same in both groups (50% in each group).

None of the patients with Cardiogenic Pulmonary Edema (0/4) in the NIV group needed intubation as opposed to 5/5 in the Standard Treatment group (p = 0.007). None of the patients with Cardiogenic Pulmonary Edema in the NIV group died as opposed to 4/5 in the Standard Treatment group (p = 0.04).

100% of patients with mucous plugging/atelectasis managed with noninvasive ventilation avoided intubation, while 40% of such patients in the Standard Treatment group went on to be intubated.

2. How precise was the estimate of the treatment effect?

The 95 % confidence intervals for the ARR of 0.5 are 0.23 and 0.77. Therefore, we can be 95% certain that the true ARR lies between these values.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

Uncertain, since this was a study on adult patients. There are significant problems with obtaining a good fit of the mask for NIV, and patient cooperation without much sedation in children can be problematic. In addition there appear to be treatment effect differences which have implications for pediatric post-transplant patients. (See following discussion.) Half of the patients (9 of 18) who required intubation in this study were patients with cardiogenic pulmonary edema which is seen less often in pediatric post-transplant patients. This group is also the group which derived the maximum benefit from NIV in the study under consideration. As pointed out above, the patients with pneumonia, which is a far more common reason for respiratory failure in pediatric post-transplant patients did not derive much benefit from NIV.

2. Were all clinically important outcomes considered?

Yes. The authors have addressed intubation rates, mortality, length of ICU stay, duration of mechanical ventilation. They also studied the fatal complications, especially ventilator-associated pneumonia, severe sepsis and septic shock in both groups.

3. Are the likely treatment benefits worth the potential harms and costs?

Yes, intubation and mechanical ventilation are associated with significant complications which can prolong hospital/ICU stay and have a significant impact on costs. NIV has a much lower complication rate and might be effective in selected groups of patients.

Discussion

Compared to adults, the experience in noninvasive ventilation in pediatric patients is limited. Meduri et al (2) examined facemask mechanical ventilation (FMMV) in 18 adults (13 with COPD exacerbations, 1 with pneumonia, 1 with fibrothorax and 2 with status asthmaticus) with acute hypercapnic respiratory failure. FMMV was successful in preventing intubation in 13/18 patients. Among the 5 patients that failed FMMV, 2 had COPD/CHF, 1 had COPD/ESRD and 2 had COPD exacerbations. FMMV was well tolerated and only 2 patients had complications (1 with aspiration and 1 with mild skin breakdown).

Padman et al.(3) showed in a prospective clinical study of 34 patients (6 months to 20 years old), with impending respiratory failure (excluding patients < 6 months, patients with multiorgan failure and absent gag reflex) that bilevel positive airway pressure support ventilation helped avoid intubation.

Fortenberry et al.(4) performed a retrospective chart review that showed that noninvasive positive pressure mask ventilation could be safely and effectively used in children to improve oxygenation in mild to moderate hypoxemic respiratory failure. The conclusions from this study are limited by its retrospective nature.

Further prospective studies are needed to demonstrate the utility of NIV in children with acute respiratory failure. However, full face mask ventilation is problematic in much of our patient population. The benefits of BiPAP (as opposed to full face mask) include the possibility of using this mode on younger children who may not cooperate fully or those with mental status changes. Perhaps this mode should be considered in children with early acute respiratory distress, who would otherwise require an artificial airway to support gas exchange.

References

1. Wysocki M, Tric L, Wolff MA, Millet H, Herman B. Noninvasive pressure support ventilation in patients with acute respiratory failure. A randomized comparison with conventional therapy. Chest. 1995;107(3):761-8. [abstract]
2. Meduri GU, Abou-Shala N, Fox RC, Jones CB, Leeper KV, Wunderink RG. Noninvasive face mask mechanical ventilation in patients with acute hypercapnic respiratory failure. Chest. 1991;100(2):445-54. [abstract]
3. Padman R, Lawless ST, Kettrick RG. Noninvasive ventilation via bilevel positive airway pressure support in pediatric practice. Crit Care Med. 1998;26(1):169-73. [abstract]
4. Fortenberry JD, Del Toro J, Jefferson LS, Evey L, Haase D. Management of pediatric acute hypoxemic respiratory insufficiency with bilevel positive pressure (BiPAP) nasal mask ventilation. Chest. 1995;108(4):1059-64. . [abstract]

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