Results
Our electronic search retrieved 1647 citations, 34 of which were
selected for full-text review (Figure 1). Twelve studies
with a combined population of 194 patients fulfilled the inclusion
criteria (Table 1). 136 patients reached an endpoint of weaning from
ECMO or death while the rest were still on ECMO. Overall study validity
was acceptable, with a median score of 6 on the Newcastle Ottawa scale
NOS appraising the quality of observational studies, without being
opposed by their non-randomized design. The median Berlin score for ARDS
prior to starting ECMO was III. Patients received mechanical ventilation
before ECMO implementation for a median of four days and ECMO was
maintained for a median of 13 days (Table 2,3)
Random-effect pooled estimates suggested an overall in-hospital
mortality risk ratio of 0.49 (95% confidence interval 0.259 to 0.721;
I2 = 94%) (Figure 2). Most of the preliminary studies
were from China (seven studies with 41 patients having endpoints).
Larger studies then followed from the USA, Japan and France (Five
studies with 95 patients with endpoints).
To investigate the overall inter-study heterogenicity, a subgroup
analysis was performed according to the country of origin of each study
(Figure 3) This showed persistent heterogeneity only in
the 7 Chinese studies with pooled
mortality risk ratio of 0.66 (I2 = 87%) (95% CI = 0.39-0.93), while
the later larger studies coming from the USA showed pooled estimate
mortality risk ratio of 0.41 (95% CI 0.28-0.53) with homogeneity
(p=0.67) similar to France with a pooled mortality risk ratio of 0.26
(95% CI 0.08-0.43) with homogeneity (p=0.86)
In four of our studies, there was a control group who received
mechanical ventilation for severe ARDS. The mortality rate was 87.5% in
the ECMO patients and 69.2% in conventional therapy patients.
The pooled odds of mortality in
ECMO versus conventional therapy were not significantly different
(p=0.273, 95%CI: 0.06–1.111). There was no observable heterogeneity
(I2 = 0%, Cochran’s Q, p-value = 0.57 ( (Figure 4)
Moderators tested were age, Pre ECMO-Berlin score of ARDS, ventilation
days before ECMO, and duration of days on ECMO. Exploratory
meta-regression identified age as a significant negative moderator of
mortality (P =0.02) with younger age patients at a higher risk of death.
No other factors demonstrated a significant moderator but this lack of a
statistical significance for likely or established prognostic factors
should be viewed with consideration of the limited statistical power of
meta-regression when applied to a limited data-set. Publication bias was
excluded by visualizing the funnel plot of standard error
(Figure 5). The funnel plot is symmetrical with only 2
studies outside the threshold (20,23). Exclusion of bias
was also proven with an Egger’s test value p=0.566 and Begg&Mazumdar
test value with p=0.373