Continuous Versus Intermittent Subglottic Secretion Drainage to Prevent Ventilator-Associated Pneumonia: A Systematic Review

We planned, performed, and reported this meta-analysis in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.²³  We searched PubMed, Embase, Science Direct, the Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, and Wanfang Data for relevant articles published in English or Chinese from January 1, 1970, to November 30, 2015, using the following search terms in both English and Chinese: “subglottic suctioning,” “subglottic drainage,” “subglottic secretion,” “ventilator-associated pneumonia,” “VAP,” “artificial airway,” “ventilation,” and “intubation.” We also reviewed and manually searched the reference lists of the retrieved studies, reviews, and meta-analyses. We made no attempt to identify unpublished reports.

We selected studies first by screening identified titles or abstracts and next by checking full-text articles. Eligible studies met the following criteria: (1) the study was a randomized controlled trial, the study design that provides the strongest evidence; (2) study participants were critically ill patients receiving invasive mechanical ventilation or endotracheal intubation; (3) the comparison groups included CSSD and ISSD; and (4) the outcome data were the incidence of VAP, time from intubation to the diagnosis of VAP, results of tests for occult blood in SSD, duration of mechanical ventilation, length of hospital or ICU stay, and mortality rate.

Two reviewers extracted the following data: first author, year of publication, study design, patient population, methods of SSD, concurrent interventions, and main outcomes. The 2 reviewers selected studies and extracted data independently, solving disagreements by discussion. The main outcomes were (1) incidence of VAP, which was identified by clinical, laboratory, or imaging findings; (2) time to VAP occurrence; (3) results of tests for occult blood in SSD; (4) duration of mechanical ventilation; (5) length of hospital or ICU stay; and (6) mortality rate.

We used the Cochrane Risk of Bias Tool²⁴  to evaluate the methodological quality and risk of bias of the included studies. This tool measures 7 domains: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other issues. Domains are classified as low risk of bias, high risk of bias, or unclear risk of bias.²⁴ 

Extracted data were processed and analyzed with Review Manager (RevMan) version 5.3 (Cochrane). Binary outcomes (such as VAP and mortality) were presented as Mantel-Haenszel–style odds ratios with 95% CIs, and continuous outcomes were reported as inverse-variance–weighted mean differences with 95% CIs. A random-effects model was chosen for data-synthesized analysis regardless of heterogeneity. Publication bias was evaluated by funnel plots, and asymmetry was assessed by means of the Egger regression test (P < 0.1 was considered significant funnel plot asymmetry). Sensitivity analyses addressing the influence of a single study on the overall risk estimate were conducted by omitting a study one by one.

The comprehensive search yielded 365 relevant papers, and we reviewed the abstracts of all these citations. We identified 70 potential studies for further full-text review and excluded studies that did not meet the intervention criteria. Eight randomized controlled trials were included in the final analysis.^25–32 

The characteristics of the 8 included studies are presented in the Table. All studies included in the analysis were conducted in China because none of the studies conducted in other countries directly compared the efficacy of CSSD and ISSD. The 8 included studies involved 1071 patients (512 receiving CSSD, 446 receiving ISSD, and 113 receiving routine care). The main inclusion criteria were based on the duration of mechanical ventilation. The duration of mechanical ventilation was greater than 48 hours in 3 studies,^26,27,30  greater than 72 hours in 2 studies,^25,27  and unclear in 2 studies.^28,31  One study³²  did not mention duration of mechanical ventilation. Other interventions, such as use of a rinse after ISSD, were also mentioned in some studies.^{25–27,29,30}  The methods used to drain subglottic secretions varied from intermittent aspiration with a syringe to continuous suction with a central negative-pressure suction system.

The methodological quality of the included studies, with bias classifications of low, high, and unclear risk, is shown in Figure 1. Figure 2 illustrates the bias classifications by cross-tabulating the included studies. Although all 8 studies mentioned randomization, only 6 included detailed descriptions of the method used to produce the random sequence; these were classified as having low risk of bias.^{26–28,30–32}  In general, sequentially numbered, opaque, sealed envelopes were assigned to each participant to prevent selection bias. Six of the 8 studies described adequate allocation concealment, which reduces ascertainment bias, and were therefore classified as having low risk of bias.^{25,26,28–31}  Adequate blinding of personnel, participants, and outcome assessment prevents intentional bias. However, only 1 study reported a blinding design for participants, indicating a low risk of bias.²⁷  The other studies included no details of participant blinding. Six studies reported special training programs regarding outcome assessment and were classified as having a high risk of bias.^{25–27,29,30,32}  The other 2 studies did not indicate a blinding design for participants and personnel. Six studies^{25,26,28–30,32}  reported complete outcome data, indicating a low risk of bias; 2 were classified as having a high risk of bias because of deficiencies in outcome data.^26,28  Verifying selective reporting of outcomes is necessary to evaluate the integrity of outcome reporting and to protect against bias. One trial selectively reported the study results and was therefore classified as having a high risk of bias.³¹  Four studies reported the number of patients lost to follow-up during the study period because the patients stopped treatment or were transferred.^25,28–30 

Seven studies reported the incidence of VAP.^25–30,32  The reported incidence of VAP was similar in 4 studies, most of which found no obvious differences between CSSD and ISSD.^{25,26,27,28,29}  However, in 2 studies, CSSD was associated with a low incidence of VAP.^27,30  The summary odds ratio for the incidence of VAP between CSSD and ISSD was 0.83 (95% CI, 0.61–1.13), with no evidence of heterogeneity (P = .56, I² = 0%).

The time to VAP occurrence was reported in only 3 studies.^26,28,30  Of these, one study found that ISSD delayed the onset of VAP²⁶ ; the other 2 found that the onset of VAP was the same for CSSD and ISSD. The summary weighted mean difference in the time to VAP occurrence (in days) between CSSD and ISSD was 2.73 (95% CI, −0.39 to 5.85), with evidence of heterogeneity (P < .001, I² = 91%).

Results of testing for occult blood were reported in only 3 studies.^29–31  The summary odds ratio for occult blood testing between CSSD and ISSD was 2.34 (95% CI, 0.25–21.88), with evidence of heterogeneity (P < .001, I² = 91%).

The duration of mechanical ventilation was reported in only 3 studies.^25,26,28  The summary weighted mean difference for the duration of mechanical ventilation (days) between CSSD and ISSD was −0.89 (95% CI, −2.72 to 0.94), with evidence of heterogeneity (P = .004, I² = 70%).

The length of ICU stay was reported in only 2 studies.^25,26  Yang concluded that ISSD was more beneficial than CSSD for the length of ICU stay,²⁶  whereas Bian et al²⁵  found no significant difference between CSSD and ISSD in the length of ICU stay. The summary weighted mean difference for the length of ICU stay (days) between CSSD and ISSD was 3.98 (95% CI, −4.44 to 12.41), with evidence of heterogeneity (P < .001, I² = 97%).

Two studies reported mortality in the CSSD and ISSD groups.^25,32  The summary odds ratio for mortality between CSSD and ISSD was 0.80 (95% CI, 0.48–1.31), with no evidence of heterogeneity (P = .99, I² = 0%).

A funnel plot indicates the intervention effect estimates from each study plotted against a measure of study size or precision.²⁴  Because funnel plots require 10 or more studies to provide significant evidence, we did not perform funnel plot analysis. Similarly, because of the limitation of the study data, we did not perform subgroup analyses. Our sensitivity analysis suggested that the overall risk estimates were not substantially changed by any single study.

The evidence from previously published randomized controlled trials regarding CSSD and ISSD is not conclusive. Our meta-analysis indicated that CSSD and ISSD may have similar effects on the incidence of VAP, time to VAP occurrence, presence of occult blood in SSD, duration of mechanical ventilation, length of ICU stay, and mortality rate. To the best of our knowledge, this is the first meta-analysis comparing CSSD and ISSD for VAP prophylaxis.

The value of SSD for VAP prophylaxis is unclear, although numerous studies of SSD have been published on this topic. Lorente et al³³  examined costs of care and found that using an endotracheal tube with a lumen to accommodate SSD together with a system providing continuous cuff pressure control can reduce health care costs. Several meta-analyses and guidelines have also highly recommended using SSD for VAP prophylaxis.^{5,7,11–14,16}  However, a recent meta-analysis concluded that although SSD may significantly lower the incidence of VAP, it did not reduce the duration of mechanical ventilation, length of hospital stay, ventilator-associated events, mortality rate, or antibiotic use, raising concerns about the usefulness of SSD.⁸  We conducted our study under the assumption that SSD is beneficial, but because the efficacy of SSD remains unclear, our results should be interpreted with caution. Whether CSSD and ISSD prevent VAP to a similar degree also remains unknown. Surprisingly, our literature review yielded few studies comparing the efficacy and appropriateness of CSSD and ISSD, and all of them were from China.

In our meta-analysis, we found that CSSD had no advantage over ISSD in the incidence of VAP, time to VAP occurrence, presence of occult blood, duration of mechanical ventilation, length of ICU stay, or mortality rate. One potential explanation is that differences in methodology, end points, and study groups among the included studies prevented us from being able to find differences between CSSD and ISSD.

Opinions on the appropriateness and superiority of CSSD versus ISSD vary. CSSD may work because continuous pressure control combats the downward movement of contaminated secretions. However, the continuous negative pressure of CSSD may lead to mucosal injury.^29,31  Animal studies have revealed that continuous control could give rise to ischemic tracheal lesions.³⁴  Dragoumanis et al³⁵  reported that aspiration failure might occur because of herniation of tracheal mucosa into the suction port, and Girou et al³⁶  found a higher-than-expected rate of laryngeal edema in patients receiving CSSD at a pressure of −30 mm Hg, possibly necessitating reintubation. The timing and choice of pressure for CSSD therefore warrants further investigation.

Compared with CSSD, ISSD is less likely to cause mucosal injury; its intermittent interruption of mucosal blood flow may allow time for temporary recovery. However, Suys et al³⁷  revealed that ISSD might cause tracheal damage in patients with scant oropharyngeal secretions, so oropharyngeal secretions should be evaluated before performing SSD. The lack of standardization of ISSD technique could have affected our results. Confounding factors such as differences in suction pressure could have introduced bias. Most ISSD procedures in studies included in our meta-analysis were performed with 5- or 10-mL syringes, but in some studies, ISSD was performed with wall-mounted suctioning systems or automated vacuum suctioning devices.¹⁸  These devices may be useful clinically, although standardization of parameters such as the strength and frequency of suctioning is necessary.

Factors such as secretion viscosity, suction pressure, and secretion volume may affect SSD efficacy. Patients requiring more-intensive nursing care may have subglottic secretions of disproportionately higher viscosity. O’Neal et al³⁸  demonstrated that secretions of higher viscosity were easier to remove than those of lower viscosity. Kollef et al³⁹  suggested that for patients with higher Acute Physiology and Chronic Health Evaluation II scores, increasing the suction pressure from 20 mm Hg to 30 mm Hg may optimize suction efficiency. Establishing appropriate SSD pressure will ensure safe and effective practice, and further investigation of how these factors interact with SSD is needed.

Several limitations of this study should be considered. First, all of the included studies are from China; therefore, population factors and study bias may have affected the results. Second, the included studies have significant heterogeneity, including different CSSD and ISSD techniques, VAP definitions, concurrent interventions, and patient populations (such as patients with severe cerebral injuries and chronic obstructive pulmonary disease). The extreme heterogeneity in this small number of studies may reflect different SSD effects in different populations. More homogeneous studies are warranted. Third, we did not perform subgroup or funnel plot analysis because of data limitations, potentially introducing publication bias. Finally, the small number of studies in this meta-analysis was a limitation. Only 2 or 3 studies were included in some of the outcome analyses, which warrants further validation.

Our meta-analysis suggests that the incidence of VAP, time to VAP occurrence, presence of occult blood, duration of mechanical ventilation, length of ICU stay, and mortality rate are the same for CSSD and ISSD. The evidence is not sufficient to confirm that CSSD is more beneficial than ISSD. Although the role of SSD remains unclear, SSD is in wide clinical use. Because evidence of the efficacy of CSSD and ISSD for VAP prophylaxis remains weak, large and rigorous randomized controlled trials are warranted.

CSSD and ISSD may have similar effects on the incidence of VAP, time to VAP occurrence, mucosal bleeding, duration of mechanical ventilation, length of ICU stay, and mortality rate. However, CSSD and ISSD should be performed with caution. Future studies focusing on the role of CSSD and ISSD and standardization of CSSD and ISSD techniques are needed.