Paradoxical ventilator associated pneumonia incidences among selective digestive decontamination studies versus other studies of mechanically ventilated patients: benchmarking the evidence base

Abstract

Introduction: Selective digestive decontamination (SDD) appears to have a more compelling evidence base than non-antimicrobial methods for the prevention of ventilator associated pneumonia (VAP). However, the striking variability in ventilator associated pneumonia-incidence proportion (VAP-IP) among the SDD studies remains unexplained and a postulated contextual effect remains untested for.

Methods: Nine reviews were used to source 45 observational (benchmark) groups and 137 component (control and intervention) groups of studies of SDD and studies of three non-antimicrobial methods of VAP prevention. The logit VAP-IP data were summarized by meta-analysis using random effects methods and the associated heterogeneity (tau2) was measured. As group level predictors of logit VAP-IP, the mode of VAP diagnosis, proportion of trauma admissions, the proportion receiving prolonged ventilation and the intervention method under study were examined in meta-regression models containing the benchmark groups together with either the control (models 1 to 3) or intervention (models 4 to 6) groups of the prevention studies.

Results: The VAP-IP benchmark derived here is 22.1% (95% confidence interval; 95% CI; 19.2 to 25.5; tau2 0.34) whereas the mean VAP-IP of control groups from studies of SDD and of non-antimicrobial methods, is 35.7 (29.7 to 41.8; tau2 0.63) versus 20.4 (17.2 to 24.0; tau2 0.41), respectively (P < 0.001). The disparity between the benchmark groups and the control groups of the SDD studies, which was most apparent for the highest quality studies, could not be explained in the meta-regression models after adjusting for various group level factors. The mean VAP-IP (95% CI) of intervention groups is 16.0 (12.6 to 20.3; tau2 0.59) and 17.1 (14.2 to 20.3; tau2 0.35) for SDD studies versus studies of non-antimicrobial methods, respectively.

Conclusions: The VAP-IP among the intervention groups within the SDD evidence base is less variable and more similar to the benchmark than among the control groups. These paradoxical observations cannot readily be explained. The interpretation of the SDD evidence base cannot proceed without further consideration of this contextual effect.

Figure 1

Caterpillar plot: observational (benchmark) groups and derived benchmark. Caterpillar plot of the group specific (small diamonds) VAP-IP and 95% CI of observational benchmark groups together with the summary VAP-IP (dotted green vertical line), 95% CI (large open diamond) and 95% prediction interval (solid green horizontal line). Note that the x axis is a logit scale. The VAP-IP data is as abstracted in four non-systematic and one systematic review [1-5].

Figure 2

Caterpillar plot: control groups of studies of non-antimicrobial methods of VAP prevention. Caterpillar plot of the group specific (small diamonds) and summary (broken vertical line) VAP-IP and 95% CI (large open diamond) of control groups of studies of non-antimicrobial methods of VAP prevention. The VAP-IP data is as abstracted in three systematic reviews [7-9]. For comparison, the VAP-IP benchmark (solid green vertical line) and prediction interval (solid green horizontal line) derived from the benchmark groups from Figure 1 is also shown. Note that the x axis is a logit scale.

Figure 3

Caterpillar plot: intervention groups of studies of non-antimicrobial methods of VAP prevention. Caterpillar plot of the group specific (small diamonds) and summary (broken vertical line) VAP-IP and 95% CI (large open diamond) of intervention groups of studies of non-antimicrobial methods of VAP prevention. The VAP-IP data is as abstracted in three systematic reviews [7-9]. For comparison, the VAP-IP benchmark (solid green vertical line) and prediction interval (solid green horizontal line) derived from the benchmark groups from Figure 1 is also shown. Note that the x axis is a logit scale.

Figure 4

Caterpillar plot: control groups of SDD studies. Caterpillar plot of the group specific (small diamonds) and summary (broken vertical line) VAP-IP and 95% CI (large open diamond) of control groups of SDD studies. Four control groups from duplex studies that is, all control group patients routinely received systemic antibiotics, are indicated by an asterix next to the author name and NC indicates non-concurrent. The VAP-IP data is as abstracted in Liberati et al. [6]. For comparison, the VAP-IP benchmark (solid green vertical line) and prediction interval (solid green horizontal line) derived from the benchmark groups from Figure 1 is also shown. Note that the x axis is a logit scale.

Figure 5

Caterpillar plot: intervention groups of SDD studies. Caterpillar plot of the group specific (small diamonds) and summary (broken vertical line) VAP-IP and 95% CI (large open diamond) of intervention groups of SDD studies. The VAP-IP data is as abstracted in Liberati et al.[6]. For comparison, the VAP-IP benchmark (solid green vertical line) and prediction interval (solid green horizontal line) derived from the benchmark groups from Figure 1 is also shown. Note that the x axis is a logit scale.