ABC: Awakening and Breathing Controlled Trial (2008)

“Management with a daily SAT plus a SBT resulted in more ventilator-free days and a better 1-year survival than did management with sedation and weaning as directed by the clinical team.”

  • The Awakening and Breathing Controlled Trial Investigators

1. Publication Details

  • Trial Title: Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial
  • Citation: Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008;371(9607):126-134. DOI: 10.1016/S0140-6736(08)60105-1
  • Published: January 12, 2008, in The Lancet
  • Author: Timothy D. Girard, M.D., M.S.C.I.
  • Funding: United States National Institutes of Health (NIH)

2. Keywords

  • Sedation, Mechanical Ventilation, Weaning, Daily Sedation Interruption, Spontaneous Awakening Trial (SAT), Spontaneous Breathing Trial (SBT)

3. The Clinical Question

  • In mechanically ventilated adult ICU patients (Population), does a paired strategy of daily spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) (Intervention) compared to usual sedation and weaning practices (Comparison) increase ventilator-free days (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Deep sedation was common in the ICU but was known to be associated with prolonged mechanical ventilation, increased complications, and delirium. The landmark Kress et al. trial (2000) had already shown that daily interruption of sedative infusions (a SAT) was beneficial in reducing the duration of mechanical ventilation.
  • Knowledge Gap: It was unknown if a more structured approach that formally paired the daily awakening trial with a protocolized breathing trial (SBT) would lead to even better outcomes than simply letting the clinical team manage weaning as they saw fit.
  • Proposed Hypothesis: The authors hypothesized that a paired SAT-SBT protocol would lead to more ventilator-free days, a shorter ICU and hospital stay, and improved survival compared to usual care.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 4 tertiary care medical ICUs in the United States.
  • Trial Period: Enrollment ran from October 2003 to May 2006.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) who were expected to be mechanically ventilated for more than 12 hours.
    • Exclusion Criteria: Included severe neurologic deficits, status epilepticus, receipt of high-dose neuromuscular blockers, and patients deemed to be actively dying.
  • Intervention: Patients underwent a daily spontaneous awakening trial (SAT) by holding their sedative infusions. If they passed the SAT safety screen and were awake, they immediately underwent a spontaneous breathing trial (SBT) to assess their readiness for extubation.
  • Control: Patients received sedation which was titrated to a goal level of sedation as ordered by the clinical team. Weaning from the ventilator was managed by the clinical team without a formal protocol.
  • Management Common to Both Groups: Both groups were managed by the same clinical teams. The choice of sedative and analgesic agents was not protocolized.
  • Power and Sample Size: The authors calculated that a sample of 336 patients would be required to have 80% power to detect a 3-day difference in ventilator-free days. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: Ventilator-free days during a 28-day period.
    • Secondary Outcomes: Included 28-day and 1-year mortality, length of ICU and hospital stay, and delirium.

6. Key Results

  • Enrollment and Baseline: 336 patients were randomized (168 to the intervention group and 168 to the control group). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: Patients in the SAT-SBT group had significantly more ventilator-free days: a median of 14.7 days vs. 11.6 days in the control group (p=0.02).
  • Secondary Outcomes: Patients in the intervention group had a shorter duration of coma and were discharged from the ICU and hospital earlier. While 28-day mortality was lower in the intervention group, this difference was not statistically significant (25.5% vs 34.2%, p=0.09). However, 1-year mortality was significantly lower in the SAT-SBT group (44% vs 55%; p=0.04).
  • Adverse Events: The study monitored for complications such as self-extubation or reintubation. There was no significant increase in adverse events in the intervention group.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a Wilcoxon rank-sum test. Proportions were compared with a chi-square test, and time-to-event data with a log-rank test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the median number of ventilator-free days between the two groups.
  • Key Statistic(s) Reported: Median ventilator-free days: 14.7 vs 11.6 (p=0.02). Hazard Ratio for death at 1 year: 0.68 (95% CI, 0.47-0.99; p=0.04).
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.02 for the primary outcome indicates that the 3.1-day difference in ventilator-free days is statistically significant and unlikely to be due to chance.
    • Hazard Ratio (HR):
      • Formula: Conceptually, HR = (Hazard Rate in Intervention Group) / (Hazard Rate in Control Group).
      • Calculation: The paper reports the result as 0.68.
      • Clinical Meaning: The HR of 0.68 means that patients in the SAT-SBT group had a 32% lower risk of dying at any given time point over the year compared to the control group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI for the 1-year mortality HR was 0.47 to 0.99.
      • Clinical Meaning: Since this range is entirely below 1.0, it confirms that the survival benefit was statistically significant.
  • Clinical Impact Measures:
    • Absolute Risk Reduction (ARR) (for 1-year mortality):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group)
      • Calculation: ARR = 55% – 44% = 11%.
      • Clinical Meaning: For every 100 patients managed with the SAT-SBT protocol, about 11 additional deaths were prevented at 1 year.
    • Number Needed to Treat (NNT):
      • Formula: NNT = 1 / ARR
      • Calculation: NNT = 1 / 0.11 = 9.
      • Clinical Meaning: You would need to treat 9 patients with the SAT-SBT protocol to prevent one additional death at 1 year.
  • Subgroup Analyses: No significant subgroup analyses were reported.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design provides a high level of evidence.
  • Generalizability: The inclusion of four different academic medical centers increases the external validity of the findings.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The study focused on highly relevant outcomes like ventilator-free days, length of stay, and long-term survival.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, which is a significant limitation. Clinicians knew the group assignments, which could have influenced their decisions about co-interventions and extubation (performance bias).
  • External Validity (Generalizability): The study was conducted in academic medical ICUs, and the results may not be fully generalizable to other settings like surgical or community ICUs where sedation practices may differ.
  • Other: The control group represented “usual care,” which can be variable. The benefit seen might be smaller in centers that already practice a light sedation strategy.

10. Conclusion of the Authors

  • A strategy of a daily paired spontaneous awakening trial and spontaneous breathing trial resulted in more ventilator-free days, shorter ICU and hospital stays, and improved 1-year survival compared to usual care.

11. To Summarize

  • Impact on Current Practice: This trial was practice-changing. It provided strong evidence that a structured, protocolized approach to sedation and weaning is superior to physician-directed usual care. The “wake up and breathe” protocol has become a cornerstone of modern ICU sedation management.
  • Specific Recommendations:
    • Patient Selection: For all adult patients requiring mechanical ventilation in the ICU who are receiving continuous sedative infusions.
    • Actionable Intervention: Implement a daily, nurse-driven protocol of paired spontaneous awakening trials followed by spontaneous breathing trials for eligible patients.
    • Expected Benefit: This intervention can be expected to reduce the duration of ventilation and may improve long-term survival.
  • What This Trial Does NOT Mean: This trial does not dictate which specific sedative agents to use, only how to manage them.
  • Implementation Caveats: Successful implementation requires a multidisciplinary team approach with buy-in from nurses, respiratory therapists, and physicians to ensure the protocol is followed consistently and safely.

12. Context and Related Studies

  • Building on Previous Evidence: The ABC trial (2008) was a direct evolution of the Kress et al. trial (2000), which had established the benefit of SATs alone. The ABC trial showed that pairing this with a formal SBT was even more effective.
  • Influence on Subsequent Research: The findings of this trial were a major component in the development of the ABCDEF bundle for ICU care, which is now an international standard for improving outcomes in critically ill patients.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The trial did not determine the optimal sedative agents to facilitate a SAT-SBT protocol. It also did not address the management of patients who repeatedly fail their awakening or breathing trials.
  • Future Directions: Subsequent research has focused on the choice of sedatives (e.g., MENDS trial (2008)) and the management of ICU delirium, which is closely linked to deep sedation.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a common and important aspect of ICU care with the goal of reducing the harms of prolonged sedation and ventilation.
  • Methods: The multicenter RCT design was appropriate. The main methodological weakness is the lack of blinding, which introduces a significant risk of performance bias, as clinicians’ knowledge of the intervention could have influenced their overall care and extubation decisions.
  • Results: The study reported a clinically meaningful and statistically significant improvement in the primary outcome of ventilator-free days. The finding of a significant 1-year survival benefit is a major strength and adds to the clinical importance of the intervention.
  • Conclusions and Applicability: The authors’ conclusion is supported by the data. Despite the lack of blinding, the large and consistent benefits seen across multiple important outcomes have led to the widespread adoption of this practice. The intervention is highly applicable to most ICU 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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