ABC Trial

Efficacy and Safety of a Paired Sedation and Ventilator Weaning Protocol for Mechanically Ventilated Patients

Girard. The Lancet 2008; 371:126-134. doi:10.1016/S0140-6736(08)60105-1

Clinical Question

  • In mechanically ventilated and sedated patients, do Spontaneous Awakening Trials (SAT) in addition to Spontaneous Breathing Trials (SBT) reduce dependence on mechanical ventilation?

Design

  • Multicentre, randomised controlled trial
  • 1:1 computer-generated block randomisation stratified by centre
  • Sealed envelope concealed assignment
  • Unblinded due to pragmatic limitations
  • Intention-to-treat analysis
  • Powered at 80% to detect a 25% increase in the primary end-point with a two sided significance level of 0.05, based on mean ventilator-free days of 12.9 (SD 10.4) in pilot study.
    • 20% chance of false negative
    • 5% change of false positive

Setting

  • Four large medical centers in the USA
  • October 2003 – March 2004

Population

  • Inclusion: adult, medical patients expected to receive mechanical ventilation for 12h or more
  • Exclusion: mechanical ventilation lasting longer than 2 weeks, cardiopulmonary arrest, profound neurological deficits, moribund, withdrawal of life support, enrolment in another trial
  • All new admissions screened according to enrolment criteria (1658 patients)
  • 338 patients randomised

Intervention

  1. Spontaneous Awakening Trial (SAT)
    • Process: de-sedated for up to 4 hours
      • Sedatives and analgesics used for sedation were interrupted
      • Analgesics for pain relief were continued
    • Criteria for failure were:
      • Did not open their eyes to verbal stimulation
      • Sustained anxiety, agitation or pain
      • Any of the SBT failure criteria (see below)
    • Contraindications:
      • indication for deep sedation (active seizures, alcohol withdrawal, ongoing agitation)
      • neuromuscular blockade
      • raised intracranial pressure (ICP)
      • myocardial infarct (MI) in the last 24 hours
    • If this was not tolerated, sedatives were restarted at half the previous rate and titrated back up.
  2. Spontaneous Breathing Trial (SBT) if successful SAT, performed as per control group (described below)

Control

  • Spontaneous Breathing Trial (SBT) if suitable each morning:
    • Process: breathing for 2 hours on any one of:
      • Pressure supported ventilation (PSV) of less than 7 cmH2O
      • Continuous positive pressure ventilation (CPAP) of 5 cmH2O
      • T-tube circuit
    • Criteria for failure were:
      • Tachypnoea > 35/min or Bradypnoea < 8/min
      • Hypoxaemia SpO2 < 88%
      • Acute mental status change
      • Acute cardiac arrhythmia
      • Any two signs of respiratory distress (tachycardia > 130 bpm; bradycardia < 60 bpm; accessory muscle use; abdominal paradoxical movement; diaphoresis; marked dyspnoea)
    • Contraindications:
      • no spontaneous respiratory effort
      • inadequate oxygenation (SpO2<88% or FiO2>0.5 or PEEP>8)
      • raised ICP
      • MI in previous 24 hours
      • agitation
      • significant vasopressors (Dop/Dob>5mcg/kg/min, NA>2mcg/min, vasopressin, milrinone)
    • If successful SBT, then clinicians had final decision regarding extubation

Both groups were sedated the same:

  • Patient-targeted sedation to a “level of arousal and comfort deemed clinically appropriate for each patient”

Outcome

  • Primary outcome: addition of SAT expedited weaning from mechanical ventilation
    • Increase in ‘ventilator-free days’ (mean days 14.7 [SD 0.0] v. 11.6 [0.9] p=0.02).
  • Secondary outcomes:
    • Significantly faster discharge from ICU (median days 9.1 [IQR 5.1-17.8] v. 12.9 [6.0-24.2] p=0.01).
    • Significantly faster discharge from hospital (median days 14.9 [8.9-26.8] v. 19.2 [10.3 to (>25% not discharged by 28 days)] p=0.04).
    • Trend towards reduced 28-day mortality (28% v. 35% p=0.21).
    • Significantly reduced 1-year mortality (44% v. 55% p=0.01).
    • Significantly reduced duration of coma RASS -4/-5 (median days 2 [0-4] v. 3 [1-7] p=0.002).
    • No difference in duration of delirium based on CAM-ICU score (median days 2 [0-5] v. 2 [0-6] p=0.5).
  • Complications:
    • Significantly more frequent self-extubation (10% v. 4%. p=0.03).
    • Not-significant reduction in frequency of tracheostomy (13% v. 20% p=0.06).
    • No difference in re-intubation rate (14% v. 13% p=0.73) even after self-extubation (3% v. 2% p=0.47)
    • Subsequent analysis showed no long-term psychological of functional differences

Authors’ Conclusions

  • “…use of a so-called wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials for the management of mechanically ventilated patients in intensive care results in better outcomes than current standard approaches and should become routine practice.“

Strengths

  • Addresses a widely applicable topic
  • Pragmatic design
  • Easy to replicate
  • Appropriate randomisation
  • Similar baseline characteristics both demographically and clinically
  • Good follow-up (99%)

Weaknesses

  • Potential biases inherent in study design:
    • Several eligible patients (a proportion of 324) were not enrolled due to physician refusal.
    • The performance of the study was necessarily unblinded and level of sedation and timing of extubation was at the clinicians discretion.
  • Complicated statistical analysis including bootstrapping was employed due to the unusual distribution of the variable. These make interpretation of the study’s findings more difficult.
  • The mechanism of the observed survival benefit is difficult to explain.
  • Rates of re-intubation (14% vs. 13%) and tracheostomy (13% vs. 20%) were high.
  • Generalisability:
    • No surgical patients were included due to their need for continuous analgesia.
    • Does the control group represent common practice? Modern practice targets lighter sedation than was common at the time.

The Bottom Line

  • The use of SATs during this trial appears to expedite weaning from mechanical ventilation, but the study findings may potentially reflect greater levels of oversedation in the control group or a bias towards early extubation in the intervention group. Their use may be associated with greater risk of self-extubation and increased nursing workload

External Links

Metadata

Summary author: Barnaby Dykes for the University Hospital Southampton GICU Journal Club (edited by @DuncanChambler)
Summary date: 5th December 2014
Peer-review editor: @stevemathieu75

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