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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Article Reviewed:

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A Randomized Trial of Prolonged Prone Positioning in Children With Acute Respiratory Failure.

Kornecki A, Frndova H, Coates AL, Shemie SD..

Chest 2001 119: 211-218. [Abstract] [Full-text for subscribers]

Reviewed by Lisa Faberowski, MD, Children's Hospital, Boston

Review posted June 7, 2001

I. What is being studied?:

The study objective:

To compare the effect of prone position versus supine position on oxygenation in children with acute respiratory failure.

The study design:

Prospective, two-crossover, randomized controlled trial

The patients included:

Ten children (age 3 mos to 11 years) with acute respiratory failure as defined by an oxygenation index (OI) > 12 with a FiO2 > 50% for greater than 12 hours in addition to bilateral lung infiltrates on radiological exam without evidence of cardiogenic edema.

The patients excluded:

Patients were excluded on the basis of OI > 40, hemodynamic instability, chronic lung disease or congenital heart disease.

The interventions compared:

The interventions evaluated were the effect of position on respiratory mechanics and oxygenation index. Patients were randomized to one of two groups. Group 1: supine to prone sequence and group 2: prone to supine sequence. Each position was maintained for twelve hours. Both groups received nitric oxide (iNO) in each position at 30 ppm for 40 minutes.

The outcomes evaluated:

The outcomes evaluated included the effect of position on oxygenation index, hemodynamics, respiratory mechanics and fluid balance. Respiratory mechanics included the evaluation for changes in total static respiratory system compliance and total respiratory resistance as a result of position. In addition, the effects on the above parameters were evaluated for each position in the presence of 30ppm inhaled iNO for 40 minutes.

II. Are the results of the study valid?

1. Is there a strong, independent, consistent association between the surrogate end point and the clinical end point?

There is not a strong independent, consistent association between improvement in OI in respiratory failure, as examined in this study, and reduction in mortality or length of stay. In particular there is no evidence in the literature that improvement in the OI at any point during a patient's course, i.e. three days, results in an improved real outcome.

2. Is there evidence from randomized trials in other drug classes that improvement in the surrogate end point has consistently led to improvement in the target outcome?

In a randomized controlled study by Dobyns (1), OI and PaO2/FiO2 is improved with iNO and improvement is sustained (~ 12 hours); but without a reduction in mortality. However, mortality was not an endpoint to the Dobyn's study.

3. Is there evidence from randomized trials in the same drug class that improvement in the surrogate end point has consistently led to improvement in the target outcome?

No studies in both the adult or pediatric literature have demonstrated a reduction in secondary lung injury, increase in ventilator-free days or reduction of mortality with the use of prone positioning. This is the first pediatric study to demonstrate a sustained improvement in OI with prone positioning. Previous investigation in pediatric patients demonstrated improvement in OI with brief periods of prone positioning (30 min and 1 hour) (2,3). Adult studies have demonstrated conflicting results in regards to sustained improvement in OI (4,5,6). This is also the first pediatric study to address the effects of iNO in the presence of prone versus supine position. Both groups demonstrated no improvement in the OI; however, pre-existing pulmonary hypertension was not identified.

IIa. Validity Questions for Therapy Articles:

Primary questions:

1. Was the assignment of patients to treatments randomized?

Patients were randomized to one of two groups supine/prone or prone/supine. The method of randomization was not discussed; however, it was a two-crossover design. All patients were placed in the prone position for 12 hours and the supine position for 12 hours for total study duration of 24 hours. All patients received a short trial of iNO in both positions. The two-crossover study design was used to eliminate response differences as a function of the natural history of the disease or as a result of the position sequence effect.

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

Was followup complete? and were patients analyzed in the groups to which they were randomized?

Twelve patients were enrolled in the study. Two patients were excluded due to physical restrictions preventing prone positioning (abdominal burns, cervical collar). All ten patients included in the study were properly accounted for and had complete follow-up during the 24-hour study period. Early exit criteria included significant deterioration in cardiorespiratory status, or compromised comfort as judged by the clinical attending. No patients in the study met these exit criteria.

The patients were analyzed according to the group to which they were initially assigned. Response to iNO was also determined by group assignment. Patients were not reassigned to a different study group based on response to positioning. All positions whether supine or prone were maintained for 12 hours.

Secondary questions:

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

The nature of the study does not allow for blinding. All patients received a short trial of non-blinded iNO administration as well.

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

Except for diagnosis, the groups were similar at the start of the trial. All patients had a period of stabilization in the steady-state supine position at which point baseline data were obtained.

	Group 1 n=5	Group 2 n=5
Age (yr)	4.1+/- 1.2	6 +/- 5
Weight (kg)	19.2 +/- 6.7	25.8 +/- 18.7
Baseline OI	21.3 +/- 7.9	22.7 +/- 9.9
Baseline PaO2/FiO2	106 +/- 21	88 +/- 35
No. days intubated before study	2.6 +/- 1.5	3.4 +/-2.3
Outcome (No. deaths)	2	2

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

All patients were ventilated using a lung protective strategy, low tidal volumes (5-10 cc/kg) and permissive hypercapnea. Ventilator weaning parameters were similar between both groups. Patients were weaned to 50% FiO2, followed by a reduction in PEEP, PIP to maintain a PaO2 > 60 mmHg. High frequency ventilation was used in one patient, the group was not identified. The other nine patients received synchronized intermittent mandatory ventilation with pressure or volume control.

Differences among the patients that may have occurred, yet not identified, include diuretic use, level of inotropic support, level of sedation and the use of paralytics. These parameters could influence not only the respiratory mechanics measured but also the oxygenation index.

III. What were the results?

1. How large, precise, and lasting was the treatment effect? (Effect should be large, precise, and lasting to consider a surrogate trial as possible basis for offering patients the intervention.)

Treatment effect, improvement in OI > 20% at 2 hours occurred in nine of the ten patients (p = 0.002) as compared to baseline or last supine position with prone positioning. The effect was noted as early as 30 minutes and was usually well established by 2 hours. The mean OI improvement and standard deviation of the after 2 hours in the prone position was 34 +/- 17% with 95% confidence interval 22%, 46%. However, 3 patients demonstrated transient mild deterioration over the twelve-hour period. Improvement in OI (mean for 10 patients) was noted over 12 hours and was statistically different than the supine position (p = 0.0016 by ANOVA). Effects persisting greater than 12 hours were not evaluated.

Improvement in fluid balance was noted in both groups in the prone position; however, the statistical significance was not identified. In both groups there was no improvement in lung mechanics nor was there an improvement in OI with the administration of iNO.

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

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

Prone positioning is an easy maneuver in pediatric patients with a small body habitus and has limited risks. The improvement in OI, though sustained for twelve hours is still temporary because with resumption of supine position, the OI increases. How this differs from baseline is uncertain.

The mechanism for improvement in OI with prone positioning is speculated to be secondary to improvement in fluid balance rather than respiratory mechanics; however, this was not statistically correlated, only inferred. One could argue that with aggressive diuresis a similar effect may be observed. A study of a subgroup of patients, as determined possibly by severity of disease, in whom such positioning may be more beneficial may be more helpful. However, it is true that based on the OI of the study patients we can conclude that the benefit can be seen in patients that are quite ill.

It can be said that this is another intervention that demonstrates short-term oxygenation improvement. The advantage of this intervention over something like iNO, is that it is essentially free and of low risk. Based on this and other studies, using the prone position, it seems reasonable to use the prone position in children with respiratory failure, if one realizes the limitations of this study and the lack of a true outcome.

2. Were all clinically important outcomes considered?

Though improvement in OI with prone positioning was noted, the ability to wean the ventilator, decrease number of ventilator days and/or secondary injury and improve mortality was not noted. Of note, patients with higher OIÕs improved more (figure 4 in the paper).

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

The cost is minimal with prone positioning. A potential harm is the inability to resuscitate in the prone position. Resuscitation would require a return to the supine position and if done with urgency, may lead to extubation and dislodgment of existing, indeed valuable, intravenous and arterial access. Moreover, with routine turning from supine to prone there is the risk of catheter and tube dislodgment.

References

1. Dobyns EL, Cornfield DN, Anas NG, Fortenberry JD, Tasker RC, Lynch A, Liu P, Eells PL, Griebel J, Baier M, Kinsella JP, Abman SH: Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxic respiratory failure. J Pediatr 1999. 134: 406-12. [abstract] [PedsCCM EBJC Review]
2. Murdoch IA, Storman MO. Improved arterial oxygenation in children with adult respiratory distress syndrome: the prone position. Acta Pediatr 1994. 83:1043-6. [abstract]
3. Numa Ah, Hammer J, Newth CJ. Effect of prone and supine position on functional residual capacity, oxygenation and respiratory mechanics in ventilated infants and children. Am J Resp Crit Care Med 1997. 156:1185-1189. [abstract]
4. Langer M, Mascheroni D, Marcolin R, Gattinoni L. The prone position in ARDS patients: a clinical study. Chest. 1988 94:103-107. [abstract]
5. Mure M, Martling CR, Lindahl SGE. Dramatic effect on oxygenation in patients with severe acute lung insufficiency treated in the prone position. Crit Care Med.1997. 25:1539-1544 [abstract]
6. Papazian L, Fabienne B, Gaillat F et al: Respective and combined effects of prone position and inhaled nitric oxide in patients with acute respiratory distress syndrome. Am J Resp Crit Care Med. 1998. 157:580-585. [abstract]

 

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