Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

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Article Reviewed:

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A Randomized Clinical Trial of Intermittent Subglottic Secretion Drainage in Patients Receiving Mechanical Ventilation.

Smulders K, van der Hoeven H, Weers-Pothoff I, Vandenbroucke-Grauls C.

Chest 2002;121: 858-862 [abstract]

Reviewed by Moushumi Sehgal MD, Texas Children's Hospital, Houston, TX

Review posted February 2, 2004

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I. What is being studied?:

The study objective:

Effect of subglottic secretions drainage on the incidence of ventilator-associated pneumonia (VAP) in patients receiving mechanical ventilation.

The study design:

A randomized, controlled clinical trial

The patients included:

Patients admitted to a single, 12-bed general adult ICU between May 1999 and June 2000 who were expected to receive mechanical ventilation for > 72 hours (n=150).

The patients excluded:

Patients in whom mechanical ventilation was not expected to last beyond 72 hours. There does not seem to be any other exclusion criteria.

The interventions compared:

Intermittent drainage (8 sec of suctioning every 20 sec) of subglottic secretions via an endotracheal tube with a dorsal lumen in the study group versus a conventional endotracheal tube in the control group.

The outcomes evaluated:

1. Incidence of VAP (clinically diagnosed when a new or progressive radiographic infiltrate developed in conjunction with either radiographic evidence for cavitation, histologic evidence of pneumonia, a positive blood culture without other source of infection, a positive pleural fluid culture, or with any two of the following symptoms or signs: fever (increase in rectal temperature > 38.0 degrees Celsius,), leukopenia, or leukocytosis (WBC < 3 x 10⁶/L and > 10 x 10⁶/L, respectively) or a purulent tracheal aspirate.
2. Duration of mechanical ventilation
3. Length of ICU stay
4. Length of hospital stay
5. Mortality

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Maybe. Investigators drew a treatment card from a sealed envelope but there was no mention how the treatment cards were assigned to the envelopes (e.g., random numbers table).

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes, all patients were accounted for and attributed at its conclusion. A large number (42 of 150 [28%] patients) of subjects enrolled received mechanical ventilation < 72 hours due to early extubation (37 patients) or death (5 patients). All subjects were followed until hospital discharge.

Were patients analyzed in the groups to which they were randomized?

Yes. Outcomes were compared on an intention-to-treat basis, i.e., all subjects in both groups were included in the analysis regardless of whether they were treated or not and following exclusion of patients who received mechanical ventilation < 72 hours.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

Unsure. Patients were probably unaware of their treatment status as they were presumably sedated. However, the authors did not mention if health workers could be blinded, as the experimental group required a special endotracheal tube along with an obvious subglottic secretion drainage protocol. The radiologists interpreting chest radiographs were the only exception. To the best of our knowledge, study personnel were part of the health worker team and hence, not blinded.

4. Were the groups similar at the start of the trial?

Yes, both groups were similar in age, demographic characteristics, severity of illness (measured by Apache II score), risk factors for VAP and reason for intubation.

5. Aside from the experimental intervention, were the groups treated equally?

Yes. Standard institutional protocol for infection prevention in mechanically ventilated patients (i.e., change in body position every 4 hours, routine endotracheal suction every 4 hours or with an increase in airway resistance or audible or visible secretions in the endotracheal tube) was followed in both groups. However, other interventions may not have been equal, considering the health workers were not blinded. One example of possible bias could be the preferential administration of antibiotics to subjects in one of the groups during the study period which was not mentioned.

III. What were the results?

1. How large was the treatment effect?

A significant reduction in incidence of VAP was noted (16% in the control group to 4% in the study group) with the intention-to-treat analysis. This yielded a RR of 0.22 (p = 0.014) according to the authors, though our calculations showed a slightly different RR of 0.25. We also got a RRR of 75% (95% CI 15, 93), an ARR of 12% (95% CI 2.6, 21) and a NNT of 8 (95% CI 5, 38). In fact, a RR of 0.22 was obtained when analysis was done after excluding patients who received mechanical ventilation < 72 hours. This analysis also yielded a RRR of 77%, (95% CI 0.7, 0.95) an ARR of 14% (95% CI 2, 25) and a NNT of 7 (95% CI 4, 43). There was no difference measured in the other outcomes including mortality.

2. How precise was the estimate of the treatment effect?

A C.I. of 0.06 to 0.81 was reported by the authors for the reduction in incidence of VAP. Since this C.I. does not include 1, it supports that the treatment effect was significantly different between the two groups. However, this is a very wide confidence intervals, consistent with low precision from a relatively small study.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

VAP is a major morbidity in pediatric as well as adult ICUs and hence, the pediatric population would likely benefit from a strategy that reduces the incidence of VAP. However, it may not be technically feasible to use special endotracheal tubes with a dorsal lumen for subglottic secretions drainage in the smaller pediatric airway.

Also, it is curious that parameters like duration of mechanical ventilation or length of ICU stay were not affected by the therapeutic strategy. This lack of effect on these other important outcomes may be because the study was not powered adequately to detect a difference in these criteria. Further studies are needed to elucidate whether the observed reduction in incidence of VAP will translate into more vital reductions in ICU stay or mortality. Randomized controlled trials of other strategies successful in reducing VAP (e.g., selective decontamination of the digestive tract [1], oral decontamination [2]) were not associated with a reduction in mortality either suggesting that there may not be a significant increase in risk of mortality associated with VAP in critically ill patients.

2. Were all clinically important outcomes considered?

Yes, all important outcomes were considered, though the study did not have a sufficient number of subjects to detect differences in important outcomes like mortality. A cost comparison between routine use of intermittent subglottic drainage vs. cost of VAP would have been interesting.

3. Are the likely treatment benefits worth the potential harms and costs?

There does not appear to be any potential harm with this therapy, at least in adult patients. The added cost might be offset by the decreased use of resources like antibiotics for the treatment of VAP.

References

1. Sanchez Garcia MS, Cambronero Galache JA, Lopez Diaz J, et al. Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial. Am J Respir Crit Care Med 1998;158: 908-916. [abstract] See PedsCCM EBJC Review by P Johnson and B Markovitz.
2. Bergmans DCJJ, Bonten MJM, Gaillard CA, et al. Prevention of ventilator Ðassociated pneumonia by oral decontamination. Am J Respir Crit Care Med 2001; 164:382-388. [abstract] See PedsCCM EBJC Review by P Kamat and J Stockwell.

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