Trends in ICU mortality and underlying risk over three decades among mechanically ventilated patients. A group level analysis of cohorts from infection prevention studies

Abstract

Background: Has either the underlying risk or the mortality incidence among ICU patients receiving mechanical ventilation (MV) in the literature changed in recent decades? Interpreting ICU mortality trends requires an adjusted analysis accounting for changes in underlying patient risk.

Methods: Control and intervention groups from 147 randomized concurrent control trials (RCCT) of various VAP prevention interventions, as listed primarily within 13 Cochrane reviews and 63 observational studies listed primarily within four systematic reviews. Eligible studies were those including ICU patients with > 50% of patients receiving > 24 h of MV with mortality data available. ICU mortality (censored day 21 or before) or late (after day 21) mortality together with group-mean age, and group-mean APACHE II scores were extracted from all groups. These incidences were summarized in five meta-regression models versus publication year being variously adjusted for age, APACHE II scores, type of study intervention and other group level parameters.

Results: Among 210 studies published between 1985 and 2021, 169 being found in systematic reviews, the increase per decade in mean mortality incidence, group-mean APACHE II scores, and group-mean age, were < 1 percentage point (p = 0.43), 1.83 (95% CI; 0.51-3.15) points, and 3.9 (95% CI; 1.1-6.7) years, respectively. Only in the model with risk adjustment for both group-mean age and group-mean APACHE II score was a significant decline in mortality apparent. In all models, the mortality incidence among concurrent control groups of decontamination studies was paradoxically five percentage points higher than benchmark and showed greater dispersion.

Conclusion: Mortality incidence has changed little over 35 years among ICU infection prevention studies whilst the patient age and underlying disease severity, measured as APACHE II, have both increased. The paradoxically high mortality among concurrent control groups within studies of decontamination methods of infection prevention remains unaccounted for.

Keywords: APACHE II; Decontamination; Infection prevention; Mortality.

Fig. 1

Search method, screening criteria and resulting classification of eligible studies and subsequent decant of component groups. The four numbered arrows are as follows; (1) An electronic search for systematic reviews containing potentially eligible studies using search terms; “ventilator associated pneumonia prevention”, “mechanical ventilation”, “intensive care unit”, each combined with either “meta-analysis” or “systematic review” up to December 2021 within The Cochrane database of systematic reviews. The systematic reviews were streamed into one of three categories; studies in which there was no intervention (observational studies), studies of various non-decontamination methods such as methods delivered either via the gastric route, the airway route or via the oral care route, studies of decontamination methods including studies with either an anti-septic or topical antibiotic (in any formulation)-based intervention. (2) The systematic reviews and meta-analyses were then searched for studies meeting the following inclusion criteria; (1) patient populations requiring prolonged (> 24 h) ICU admission; > (2) 50% of patients receiving mechanical ventilation for > 24 h; (3) mortality data available. (4) APACHE II score data available. And exclusion criteria; (1) Studies limited to paediatric ICU’s [mean age < 18 years]. (2) Studies limited to populations of ARDS patients (3) Studies limited to populations of Cardiac surgery patients. (3) Any duplicate or ineligible studies were removed and studies identified outside of systematic reviews, obtained by ‘snow ball sampling using the ‘related studies’ function in Google Scholar, were included. (4) The component groups were decanted from each study being control (rectangles), intervention (ovals) and observation (diamond) groups. NCC = non-concurrent control; CC = concurrent control. The total numbers do not tally as some systematic reviews provided studies in more than one category and some studies provided groups in more than one category. Also, some studies contribute both ICU and late mortality data

Fig. 2

Scatter plot and linear regression of ICU mortality [mortality censured at day 21 or less] incidence versus year of study publication for observational groups and control and interventions groups from studies of non-decontamination and decontamination interventions. The linear regression line in each plot, derived using the observational groups, increased non-significantly versus year of study publication (slope is + 1.2 percentage points per decade; 95% confidence interval − 1.9 to + 4.3; p = 0.64) and serves as a benchmark for all plots [symbols; filled triangle = non-concurrent control groups; filled square = groups receiving PPAP; open circle = all other groups; NCC groups appear as observational groups]. PPAP is protocolized parenteral antibiotic prophylaxis. The equivalent plot for late mortality is shown as Additional file 1: Fig S3 and plots with the originating studies indicated in Additional file 1: Figs. S2, S3. Note the y-axis is a logit scale

Fig. 3

Scatter plot and linear regression of group-mean APACHE II score versus year of study publication for observational groups and control and interventions groups from studies of non-decontamination and decontamination interventions. The linear regression line of APACHE II score versus publication year, derived using the observational groups, increases by + 1.8 points per decade; 95% confidence interval + 0.51 to + 3.2; p = 0.007) and serves as a benchmark for all plots [symbols; filled triangle = non-concurrent control groups; filled square = groups receiving PPAP; open circle = all other groups; NCC groups appear as observational groups].The same plot showing each individual group traceable to the original study is shown in Additional file 1: Fig. S4

Fig. 4

Scatter plot and linear regression of group mean age versus year of publication for groups from studies of infection prevention interventions. The linear regression line in each plot, derived using the observational groups, increased versus year of study publication (slope is + 5.4 years per decade; 95% confidence interval + 2.7 to + 7.9; p = 0.001) and serves as a benchmark for all plots [symbols; filled triangle = non-concurrent control groups; filled square  = groups receiving PPAP; open circle = all other groups; NCC groups appear as observational groups]. The same plot showing each individual group traceable to the original study is shown in Additional file 1: Fig. S5

Fig. 5

Scatter plot and linear regression of ICU mortality [mortality censured at day 21 or less] incidence versus group mean APACHE II score for groups from studies of infection prevention interventions. The linear regression line in each plot, derived using the observational groups, increased versus year of study publication (slope is + 0.7 percentage points per APACHE II score point; 95% confidence interval + 0.2 to + 1.2; p = 0.003) and serves as a benchmark for all plots. Note the y-axis is a logit scale [symbols; filled triangle = non-concurrent control groups; filled square = groups receiving PPAP; open circle = all other groups; NCC groups appear as observational groups]. The same plot showing each individual group traceable to the original study is shown in Additional file 1: Fig. S6. An equivalent plot showing the trend for late mortality versus group mean APACHE II score is shown in the Additional file 1: Fig. S7