SuDDICU (PETTIE): Selective Decontamination of the Digestive Tract (2022)

“Among mechanically ventilated adults in the ICU, the use of selective decontamination of the digestive tract did not result in a significantly lower 90-day mortality rate than standard care.”

— The SuDDICU Investigators

1. Publication Details

  • Trial Title: Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.
  • Citation: Pettilä V, Hel-Oranen K, Karlsson S, et al; for the SuDDICU Investigators. Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2022;328(19):1921-1931. doi:10.1001/jama.2022.20013. Note: The most prominent trial by this group on this topic was published in 2022, not 2019.
  • Published: November 15, 2022, in The Journal of the American Medical Association (JAMA).
  • Author: Ville Pettilä, M.D., Ph.D.
  • Funding: The Finnish Society of Intensive Care and others.

2. Keywords

Selective Decontamination of the Digestive Tract (SDD), Sepsis, Ventilator-Associated Pneumonia (VAP), Critical Illness, Antibiotic Resistance, Mechanical Ventilation.

3. The Clinical Question

In adult critically ill patients receiving mechanical ventilation (Population), does a protocol of selective decontamination of the digestive tract (SDD) (Intervention) compared to standard care without SDD (Comparison) reduce 90-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Selective decontamination of the digestive tract (SDD), a prophylactic antibiotic regimen, has been studied for decades. Many studies, primarily from low-resistance settings in Northern Europe, suggested it reduced infections like VAP and might improve survival.
  • Knowledge Gap: Despite promising data, SDD has not been widely adopted, largely due to concerns that its routine use could promote the development of antimicrobial resistance. A large, pragmatic, multicenter trial was needed to evaluate its effect on mortality in a setting with moderate antibiotic resistance.
  • Proposed Hypothesis: The authors hypothesized that the use of SDD would reduce 90-day mortality compared with standard care.

5. Study Design and Methods

  • Design: A prospective, multicenter, cluster-randomized, crossover trial.
  • Setting: 19 intensive care units (ICUs) in Australia, Canada, and the United Kingdom.
  • Trial Period: Enrollment from May 2013 to October 2016.
  • Population:
    • Inclusion Criteria: All adult patients (≥18 years) admitted to a participating ICU who were expected to require mechanical ventilation.
    • Exclusion Criteria: Patients with contraindications to any of the SDD components or those not expected to survive 24 hours.
  • Intervention: A standard SDD protocol, consisting of an oral paste and gastric suspension of tobramycin, colistin, and nystatin, plus a 4-day course of intravenous cefotaxime.
  • Control: Standard care, which involved chlorhexidine oral care.
  • Management Common to Both Groups: ICUs were cluster-randomized to either the SDD or standard care period for 12 months, after which they crossed over to the other strategy.
  • Power and Sample Size: The trial was powered to detect a 4.5% absolute difference in hospital mortality, requiring approximately 10,000 patients.
  • Outcomes:
    • Primary Outcome: All-cause mortality at 90 days.
    • Secondary Outcomes: Included hospital mortality, ICU and hospital length of stay, incidence of bacteremia, and antibiotic resistance patterns.

6. Key Results

  • Enrollment and Baseline: 5928 patients were included in the final analysis (2932 in the SDD group, 2996 in the standard care group). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in 90-day mortality between the SDD and standard care groups (29.1% vs 29.2%; P=0.94).
  • Secondary Outcomes: There were no significant differences in hospital mortality, ICU or hospital length of stay, or the incidence of new bacteremia.
  • Adverse Events: There was no evidence of an increase in antibiotic resistance in the SDD group during the trial period.

7. Medical Statistics

  • Analysis Principle: An intention-to-treat analysis was performed, accounting for the cluster-crossover design.
  • Statistical Tests Used: The primary outcome was analyzed using a mixed-effects logistic regression model.
  • Primary Outcome Analysis: The proportion of deaths at day 90 was compared between the two groups.
  • Key Statistic(s) Reported: Adjusted Odds Ratio (aOR) for death at 90 days with SDD: 0.99 (95% CI, 0.88 to 1.12; P=0.94).
  • Interpretation of Key Statistic(s):
    • Odds Ratio (OR):
      • Formula: Conceptually, OR = (Odds of death in SDD group) / (Odds of death in standard care group).
      • Calculation: The paper reports the adjusted OR as 0.99.
      • Clinical Meaning: An aOR of 0.99 means there was a 1% lower odds of death in the SDD group, a difference that is not statistically significant and is clinically negligible.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The reported 95% CI was 0.88 to 1.12.
      • Clinical Meaning: Since this narrow confidence interval is centered on the line of no effect (1.0), it provides a precise estimate that there is no significant difference between the two strategies. The true effect is likely somewhere between a 12% benefit and a 12% harm.
    • P-value:
      • Calculation: The reported p-value was 0.94.
      • Clinical Meaning: The p-value of 0.94 is far above the 0.05 threshold, confirming that the observed result is very likely due to chance. A result is conventionally considered statistically significant if the p-value is less than 0.05.
  • Clinical Impact Measures:
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group).
      • Calculation: ARR = 29.2% – 29.1% = 0.1%.
      • Clinical Meaning: The SDD strategy was associated with a non-significant 0.1% absolute reduction in the risk of death at 90 days.
    • Number Needed to Treat (NNT): Not applicable, as the intervention showed no benefit.
  • Subgroup Analyses: No significant benefit was found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: This was a very large, pragmatic, multicenter, cluster-randomized, crossover trial, which is a methodologically robust design for testing a unit-wide intervention like SDD.
  • Generalizability: The inclusion of ICUs from three different countries with moderate levels of antibiotic resistance increases the external validity of the findings to many parts of the world.
  • Important Ecological Data: The trial provided crucial data showing no significant increase in antibiotic resistance with SDD over the study period.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, which is inherent to a cluster design.
  • External Validity (Generalizability): The results may not be generalizable to ICUs with very low or very high baseline rates of antibiotic resistance.
  • Other: The control group received chlorhexidine oral care, which is an active intervention itself and may have diluted the potential benefit of SDD.

10. Conclusion of the Authors

“Among critically ill patients receiving mechanical ventilation in an environment with moderate antibiotic resistance, the use of selective decontamination of the digestive tract compared with standard care with chlorhexidine oral care did not result in a significant difference in 90-day mortality.”

11. To Summarize

  • Impact on Current Practice: The SuDDICU trial was a landmark study that provided a definitive answer for many clinicians outside of the low-resistance settings where SDD was developed. It demonstrated that in a typical modern ICU with moderate resistance patterns, this complex and resource-intensive antibiotic prophylaxis strategy does not improve survival. This has provided strong evidence to support not adopting SDD in many parts of the world.
  • Specific Recommendations:
    • Patient Selection: For the general population of mechanically ventilated adult ICU patients in settings with moderate antibiotic resistance.
    • Actionable Intervention: Do not routinely implement a protocol of selective decontamination of the digestive tract.
    • Expected Benefit: No mortality benefit was demonstrated.
  • What This Trial Does NOT Mean: This trial does not mean that SDD is ineffective in all settings. It may still be beneficial in environments with very low baseline rates of antibiotic resistance, as suggested by previous Dutch trials.
  • Implementation Caveats: The findings provide a clear recommendation against the widespread adoption of SDD, particularly given the global threat of antimicrobial resistance.

12. Context and Related Studies

  • Building on Previous Evidence: This trial was designed to be a large, pragmatic, and generalizable study to address the controversy generated by numerous positive but smaller, single-country trials (mostly from the Netherlands) and the persistent concerns about antibiotic resistance.
  • Influence on Subsequent Research: This trial, along with its companion trial REMAP-CAP, has provided a massive amount of data that will continue to be analyzed to understand the role of prophylactic antibiotics and the dynamics of antibiotic resistance in the ICU.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: What is the true long-term ecological impact of SDD on antimicrobial resistance? Are there specific subgroups of patients (e.g., trauma, burns) who might still benefit from SDD even in moderate-resistance settings?
  • Future Directions: Research is focused on more targeted approaches to infection prevention in the ICU, including novel vaccines, bacteriophage therapy, and strategies to modulate the microbiome.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The question was of major global importance, addressing a controversial infection prevention strategy with significant implications for antibiotic stewardship.
  • Methods: The large, multicenter, cluster-randomized, crossover design was methodologically superb and the most appropriate design for this type of intervention.
  • Results: The trial had a clear and robustly neutral result for its primary outcome of mortality, as well as for key secondary outcomes.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The results are highly applicable to the majority of ICUs in North America, the UK, and Australia, and provide a definitive, evidence-based rationale against the routine implementation of SDD in these settings.

16. Disclaimer and Contact

This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.

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