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Given our recent guest speaker and spirited discussion, I thought it would be worthwhile to discuss a review from the September ‘06 Annals: the Use of Noninvasive Ventilation in ED Patients with Acute Cardiogenic Pulmonary Edema. We know ACEP will soon be publishing a new clinical policy on heart failure, it’ll be interesting to see how their interpretation of the literature squares with that of Collins et al.

And, even though we’ve all seen these masks in action, it’s probably worth repeating that CPAP is continuous positive airway pressure, regardless of inspiration or expiration. CPAP has been shown to reduce the work of breathing and decrease LV afterload, while maintaining cardiac index.

Noninvasive positive pressure support — sold under the trade name BiPAP – works similarly, but with less positive pressure during exhalation; it’s inspiratory pressure support plus PEEP (this variant called C-Flex kind of demonstrates it, but with an exhalation pression of zero). In theory, BiPAP should reduce the work of breathing even more than CPAP, and physiologically would seem to be of more benefit in obstruction airway disease (asthma, COPD).

For a more in-depth review of the mechanisms, indications and contraindications, check out this eMedicine article. For a practical guide with some key citations, see EMCrit.org. Basically, both CPAP and BiPAP work in part by raising intrathoracic pressure, which decreases preload AND afterload (which probably benefits patients with cardiac dysfunction). Neither therapy is definitive for cardiogenic pulmonary edema; they’re temporizing measures while your nitrates and diuretics kick in.

Previous studies have shown that CPAP decreases intubation rates in patients with acute cardiogenic pulmonary edema (ACPE). A systemic review in 1998 bolstered the claim, but that review included trials with non-ED patients.

The first big BiPAP study (Mehta, 1997) showed an increase in respiratory function and hemodynamic improvement compared to CPAP, but similar rates of mortality in hospital, and similar intubation rates. Plus, notably, the BiPAP patients experienced more MI! (it’s worth noting that that arm of the study received, by chance more patients complaining of substernal chest pain, and a 2004 study comparing CPAP and BiPAP showed no difference in MI).

Since then, many small trials between CPAP and BiPAP suggested no difference between these noninvasive ventilatory modes compared to standard-of-care, which other studies suggested a decrease in intubation and mortality. But this paper is the first systematic review of CPAP and BiPAP in ED ACPE patients.

The authors looked at RCT’s in adults with ACPE treated in the ED with outcomes of intubation and mortality. They excluded those whose pulmonary edema was the result of an acute MI. They used the Jadad system for assessing randomization, blinding and followup, then calculated relative risks and 95% confidence intervals. They also looked at publication bias with Egger’s Test, which assesses the likelihood of unpublished negative data affecting this analysis in the future.

They eventually chose 11 articles, all of which involved ED patients with acute cardiogenic pulmonary edema, as determined by PMHx, CXR, ECG, etc). All studies had inadequeate blinding (because doctors know when a giant mask is blowing air into their patient’s faces).

By pooling the studies, the authors found noninvasive ventilation (CPAP or BiPAP), compared to standard care, was associated with a significant reduction in hospital mortality (RR = 0.61, with 95%CI of 0.41-0.91, with minimal heterogeneity between studies and no publication bias). Noninvasive ventilation was also associated with a significant reduction in intubation (RR = 0.43, 95%CI of 0.21-0.87, moderate heterogeneity, no significant publication bias).

By pooling six studies of CPAP vs. NPPV (BiPAP) they found no difference in hospital mortality (RR=1.23, 95%CI 0.41-3.29), minimal heterogeneity, no publication bias). There was also no difference between the two in risk of intubation (RR=0.78, 95%CI  of 0.28 to 2.2, minimal heterogeneity, negative Egger’s).

In a comparison of CPAP alone vs. standard of care, with respect to hospital mortality, five pooled trials showed a trend toward decreasing mortality (RR = 0.44, 95%CI 0.19 to 1.03) and five pooled trials showed a significant decrease in intubations (RR = 0.34, 95%CI 0.14 to 0.84).

 In a comparison of BiPAP (NPPV) alone vs. standard of care, with respect to hospital mortality, the pooled four studies showed a trend toward decreased mortality (RR=0.66, 95%CI 0.37-1.19) with no effect on the risk of intubation (RR=0.58, 95%CI 0.2 to 1.2).

A sensitivity analysis showed no effect from any single poor-quality study on the above relative risk calculations. But the authors note, wisely, that meta-analyses aren’t the same as well-powered randomized controlled trials. In fact, we now know that meta-analyses differ from subsequent RCTs as much as 35% of the time. So we seem right back where we started — until a bigger study is done, doubts still linger as to BiPAP’s effectiveness. At least we’re more sure that CPAP is clearly useful in reducing mortality and preventing intubation. Reach for it before you tube.

Posted on Thursday, October 12th, 2006 at 3:19 am by Nick. Filed under Ventilation, Journal Club.
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