Four Methods of Weaning Off Mechanical Ventilation

In Review

Esteban A, et al. "A comparison of four methods of weaning patients from mechanical ventilation". The New England Journal of Medicine. 1995. 332(6):345-350.
PubMed • Full text • PDF

Clinical Question

In patients who show signs of poor tolerance to discontinuation of ventilator support, what method among intermittent mandatory ventilation, pressure support ventilation, and trials of spontaneous breathing confers the highest rate of successful weaning?

Bottom Line

Among intubated adult ICU patients with difficulty weaning, once daily or intermittent trial of spontaneous breathing were associated with the highest rate of successful weaning. However, the analytic plan was questionable as it adjusted for multiple factors, a method not typically required in RCTs. The statistically significant differences may have been an artifact of this analytical plan rather than represent a true difference between the groups.

Major Points

Prior to this comparison of extubation practices in patients with initial respiratory distress, weaning patients from a mechanical ventilator had not been studied in an empiric fashion. The general principle of weaning a patient from a ventilator is based on progressive reduction in ventilator contribution, causing subsequent increase in patient contribution to respiratory support. Available techniques included: 1. Spontaneous breathing trials, wherein a patient breaths through a T-tube or continuous flow circuit with continuous positive ventilation once or multiple times per day, 2. Intermittent mandatory ventilation, the administration of preset ventilator-delivered breaths per minute with gradual reduction of the number of breaths and 3. Pressure support ventilation, in which each breath is supported by positive pressure. Intermittent mandatory ventilation was thought to provide support to respiratory muscles and to decrease work of breathing, whereas pressure-support ventilation could counteract additional work of breathing from endotracheal tubes.

The Comparison of Four Methods of Weaning Patients from Mechanical Ventilation established that spontaneous breathing trials best expedite extubation without additional risk of reintubation. In contrast, pressure support and intermittent mandatory ventilation exhibited a longer time to extubation. Whether the superiority of once daily trial of spontaneous breathing demonstrated in this study resulted from an improved conditioning inherent to the method, or from earlier recognition of candidates for extubation is unknown. The generalizability of these findings to other protocols and specifics of underlying lung disease is a continuous area of interest.

Guidelines

Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine.

• Patients receiving mechanical ventilation for respiratory failure should undergo a formal assessment of discontinuation potential if the following criteria are satisfied:
  • 1.Evidence for some reversal of the underlying cause for respiratory failure;
  • 2.Adequate oxygenation (eg, Pao2/Fio2ratio > 150 to 200; requiring positive end-expiratory pressure [PEEP] ≤ 5 to 8 cm H2O; Fio2≤ 0.4 to 0.5); and pH (eg, ≥ 7.25);
  • 3.Hemodynamic stability, as defined by the absence of active myocardial ischemia and the absence of clinically significant hypotension (ie, a condition requiring no vasopressor therapy or therapy with only low-dose vasopressors such as dopamine or dobutamine, < 5 μg/kg/min); and
  • 4.The capability to initiate an inspiratory effort.
• Formal discontinuation assessments for patients receiving mechanical ventilation for respiratory failure should be performed during spontaneous breathing rather than while the patient is still receiving substantial ventilatory support. An initial brief period of spontaneous breathing can be used to assess the capability of continuing onto a formal SBT.
• Patients receiving mechanical ventilation for respiratory failure who fail an SBT should have the cause for the failed SBT determined. Once reversible causes for failure are corrected, and if the patient still meets the criteria listed (see Table 3 in reference), subsequent SBTs should be performed every 24 h.
• Patients receiving mechanical ventilation for respiratory failure who fail an SBT should receive a stable, nonfatiguing, comfortable form of ventilatory support.

BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults

• Evidence statement: Progressive Reduction of pressure support and daily SBTs are satisfactory methods of weaning

Design

• Multicenter, prospective, randomized study
• N=130 difficult to wean patients
  • Intermittent mandatory ventilation (n=29)
  • Pressure support ventilation (n=37)
  • Intermittent spontaneous SBT (n=33)
  • Once daily SBT (n=31)
• Setting: 14 centers Spain
• Enrollment: 1992-1993
• Analysis: Intention-to-treat vs. per-protocol not specified
• Primary outcome: Adjusted rate of successful weaning

Population

Inclusion Criteria

• Mechanical ventilation for >24 hours due to acute respiratory failure
• Improvement in or resolution of underlying cause of acute respiratory failure
  • PaO₂:FiO₂ ratio >200 with PEEP <5 cm H₂O
• Temperature <38°C
• Hemoglobin >10 g/dL
• No indication for vasopressors or sedative agents
• Clinically stable as determined by attending physician

Exclusion Criteria

• Tracheostomy

Baseline Characteristics

From the intermittent mandatory ventilation group or overall from the 546 patients where specified.

• Demographics: Males 69% (overall), age 64 years
• PMH (overall): COPD 23%, neurologic issues 16%, ALI 58%
  • Causes of ALI: Surgery 23%, infection 23%, HF 22%, trauma 16%, ARDS 7%, other 9%
• APACHE II score: 21
• Physiological parameters: PaO₂:FiO₂ 243, maximum inspiratory pressure 26 cm H₂O, V_T 5.3 mL/kg, RR 28
• Duration of ventilation: 6 days
• Time to failure of 1st SBT: 48 min

Interventions

• 546 intubated patients thought to be ready to wean underwent a 2 hour SBT, those with respiratory distress (n=120) were deemed difficult to wean and were randomized to a technique, with stratification by center:
  • Intermittent mandatory ventilation - Ventilator rate was set to ~10 breaths/min then decreased ~2x/day by 2-4 breaths/min
  • Pressure support ventilation - Pressure support set at ~18 cm H₂O and reduced ~2x/day by 2-4 cm H₂O
  • Intermittent SBT - ≥2x/day
  • Once daily SBT
• Specific details for each intervention are on pages 346-347.
• Reintubation in ≤48 hours or weaning was not possible within 14 days were considered failures

Outcomes

Comparisons are presented as intervention 1 vs. intervention 2, as described below"

Primary Outcomes

Rate of successful weaning

Adjusted for age, APACHE II score, PaO₂:FiO₂, maximal inspiratory pressure, spontaneous respiratory frequency, spontaneous V_T/kg, duration of ventilator support, and length of time to the failure of the initial SBT. These were included using backwards elimination.

Once-daily SBT vs. intermittent mandatory ventilation: HR 2.83 (95% CI 1.36-5.89; P<0.006)

Once-daily SBT vs. pressure-support ventilation: HR 2.05 (95% CI 1.04-4.04; P<0.04)

Once-daily SBT vs. intermittent SBT: HR 1.24 (95% CI 0.64-2.21; P=0.54)

Intermittent SBT vs. intermittent mandatory ventilation: HR 2.28 (95% CI 1.11-4.68; P=0.024)

Intermittent SBT vs. pressure-support ventilation: HR 1.66 (95% CI 0.87-3.16 P=0.126)

Pressure-support ventilation vs. intermittent mandatory ventilation: HR 1.38 (95% CI 0.68-2.79 P=0.32)

Secondary Outcomes

Reported P-values are below.

Intermittent mandatory ventilation

Median (IQR) days to successful extubation: 5 (3-11)

Successful weaning and extubation: 69%

Reintubation: 14%

Continued mechanical ventilation after 14 days: 17%

Greater than intermittent SBT, P=0.06

Greater than once-daily SBT, P=0.07

Pressure-support ventilation

Median (IQR) days to successful extubation: 4 (2-12)

Successful weaning and extubation: 62%

Reintubation: 19%

Continued mechanical ventilation after 14 days: 11%

Intermittent SBT

Median (IQR) days to successful extubation: 3 (2-6)

Successful weaning and extubation: 82%

Reintubation: 15%

Continued mechanical ventilation after 14 days: 3%

Once-daily SBT

Median (IQR) days to successful extubation: 3 (1-6)

Successful weaning and extubation: 71%

Reintubation: 23%

Continued mechanical ventilation after 14 days: 3%

Subgroup Analysis

None

Adverse Events

• Data censored on
  • 2 patients who died during the study
  • 2 patients in whom weaning interrupted due to illness
  • 23 patients who required reintubation within 48 hours of extubation
  • 11 patients still on ventilator 14 days after initial trial

Criticisms

• The study used model building with backwards elimination to determine which covariates to include in their primary analysis. Contemporary RCTs are designed to assess a primary outcome without the need for adjustment as randomization (when used in conjunction with other methods like stratification and concealment of allocation) reduces systematic bias. As unadjusted models are not presented, it is unclear if this analytic strategy identified spurious P-values that met statistical significance. The Kaplan-Meier curves on page 347 demonstrate some spread between treatment arms, though not dramatic spread.
• Study powered to detect 80% difference in weaning times between groups of 2 days (31 patients), and thus potentially susceptible to outliers (difficult to extubate patients). Although no statistically significant differences existed between potentially difficult to ventilate conditions among the comparison groups, a large range existed (i.e. COPD, 27% - 48%).
• Baseline and follow up PFT data not available
• High proportions of reintubation, especially in once-daily trial of spontaneous breathing group (22%)
• Spontaneous breathing trials may not be appropriate for patients with tenuous hemodynamic status, given the risk of substantial changes in intra-thoracic pressure

Funding

Not disclosed