NIVAS

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery

Jaber. JAMA 2016; 315(13): 1345-1353. doi:10.1001/jama.2016.2706

Clinical Question

  • In patients who develop acute hypoxaemic respiratory failure after abdominal surgery, does non-invasive ventilation compared to standard oxygen therapy prevent the need for re-intubation?

Design

  • Open-label, randomised, controlled trial
  • Design approved and registered in advance: clinicaltrials.gov Id: NCT01971892 
  • Computer generated randomisation and concealed allocation sequence
    • Stratified by study site, age (above or below 60 years), site of surgery (upper vs lower abdomen), use of post-operative epidural analgesia
  • Interim blinded reviews at ⅓ and ⅔ recruitment points
  • 90% Power to demonstrate superiority of non-invasive ventilation (NIV) against standard oxygen therapy (StdO2) if 300 patients recruited, based upon the following estimates from expert opinion:
    • 65% re-intubation rate in StdO2 group
    • 40% re-intubation rate in NIV group (i.e. absolute risk reduction of 25%)
    • 15% drop out or loss to follow-up

Setting

  • 20 Intensive Care Units in France
  • May 2013 to September 2014

Population

  • Inclusion: Adult patients (>18 years) who had undergone laparoscopic or non-laparoscopic elective or non-elective abdominal surgery under general anaesthesia who develop…
    • Acute respiratory failure within 7 days of surgery defined as presence of both
      • Hypoxaemia for > 30 minutes (PaO2 < 8 kPa breathing air OR < 10.6 kPa on 15 l/min O2 OR peripheral SpO2 ≤ 90% breathing air)
      • Clinical features of respiratory distress (respiratory rate > 30 /min OR intense respiratory muscle work)
  • Exclusion: Limits to life-sustaining treatment; contraindications to NIV; sleep apnoea syndrome; need for immediate re-intubation; need for immediate surgical procedure; previous recruitment in research trial
  • 535 screened, 300 randomised, 293 included in primary outcome analysis (2.3% loss to follow-up)
  • The groups had similar baseline characteristics (NIV vs StdO2):
    • Age 64.4 vs 62.5
    • BMI 27.1 vs 27.2
    • SOFA score 4.5 vs 4.3
    • Respiratory rate 28.8 vs 28.2
    • Laparoscopic approach 11.1% vs 11.0%
    • Epidural analgesia 14.5% vs 15.5%
    • Extubated within 6 hours of primary surgery 62.1% vs 63.5%

Intervention

  • Non-invasive ventilation (NIV)
    • Used from randomisation until day 30 or ICU discharge
    • Applied via face-mask using an ICU or NIV-dedicated ventilator with an HME or active humidification
    • Inspiratory positive airway pressure (IPAP) started at 5 cmH2O and increased to 15 cmH2O as needed targeting tidal volume (Vt) 6–8 ml/kg predicted body weight
    • Positive end-expiratory airway pressure (PEEP, or EPAP) started at 5 cmH2O and increased to 10 cmH2O as needed
      • PEEP and inspiratory fraction of oxygen (FiO2) were titrated to maintain SpO2 > 94%
    • “Encouraged” to use this for at least 6 hours a day, either continuously or intermittently
    • Standard O2 delivered between NIV treatments
    • Observed treatment of this group:
      • Mean IPAP: 6.7 cmH2O
      • Mean PEEP: 5.4 cmH2O
      • Mean FiO2: 50%
      • Mean Vt: 8.3 ml/kg
      • Mean duration of NIV during first day: 7.4 hours
      • Proportion given at least 6 hours as intended in first day: 68.9%
      • Median total duration of NIV: 4 days

Control

  • Standard oxygen therapy (StdO2)
    • Supplemental O2 up to 15 l/min to maintain SpO2 > 94%
    • Observed treatment of this group:
      • 10.4 l/min O2

Management common to both groups

  • High-flow oxygen via nasal cannulae were not permitted in either group
  • Management and treatment was at the treating clinician’s discretion
  • Criteria for re-intubation defined as objectively as possible
    • respiratory or cardiac arrest
    • respiratory pauses with loss of consciousness or gasping
    • massive aspiration
    • inability to clear secretions
    • heart rate less than 50 ppm with reduced consciousness
    • severe haemodynamic instability unresponsive to fluid or vasopressors
    • return to theatre (this category was removed for modified intention to treat analysis)
  • Invasive ventilation management was a low-tidal volume lung protective strategy

Outcome

  • Primary outcome: The incidence of re-intubation within 7 days of surgery was lower in the NIV group compared to the StdO2 group
    • NIV group 33.1% vs StdO2 group 45.5% (ARR 12.4%; 95% CI 1.3% to 23.5%; P=0.03)
      • This remained statistically significant in the modified Intention to Treat (mITT) analysis, with the 32 patients re-intubated for surgery removed (representing 11% of patients)
    • Number needed to treat (NNT) to prevent one re-intubation: 9 patients
    • Fragility Index: 2
  • Secondary outcome: see table for data
    • Re-intubation rate within 30 days was not different
    • Incidence of pneumonia and health-care associated infections was lower in the NIV group
    • Days alive and free of invasive mechanical ventilation were greater in the NIV group
    • The 30-day mortality ARR point estimate was 5.04%, which gives an NNT of 20 patients, but this was not statistically significant and the 95% confidence intervals of the ARR include -2.5% to 12.8% (slightly harmful to very beneficial)
    • There was no difference in the report of adverse events or intolerance to therapy

Authors’ Conclusions

  • In patients with established hypoxaemic respiratory failure after abdominal surgery, non-invasive ventilation reduces the risk of re-intubation within 7 days compared to standard oxygen therapy.

Strengths

  • Well designed and conducted trial with clear manuscript
  • Appropriate methodology for clinical question
  • Good internal validity of results however see point about Fragility in weakness section
    • Good randomisation and allocation strategy to minimise bias
    • Appropriate effort to make outcome objective given it is not possible to blind treating clinicians or patients to allocation
    • Small loss-to-follow up relative to primary outcome incidence, and intention-to-treat analysis to minimise bias
    • Appropriate statistical methods
  • Good external validity (generalisability)
    • Multi-centre trial design
    • Explicit patient group – high-risk patients having undergone major-complex abdominal surgery

Weaknesses

  • Observed rate of re-intubation was lower than expected, so some secondary outcomes that did not demonstrate statistical significance may be Type 2 errors due to the trial being underpowered (this is not relevant to the primary outcome since significance was demonstrated)
    • This is particularly relevant to mortality, which would have been a more meaningful outcome to patients and clinicians
  • Despite attempts to define an objective primary end-point, bias from unblinded clinicians may have contributed to the significant difference favouring NIV
  • The low Fragility Index of 2 highlights how this is not robust evidence – given 7 patients were lost to follow-up and the potential clinician bias in the primary outcome, this is a significant weakness
  • Generalising to all health-care systems and patients may not be possible as there was a heavy weighting towards laparotomy (91%) vs laparoscopic (11%) surgery (other surgical factors were reasonably well balanced)

The Bottom Line

  • In this trial, 6 hours of low-level non-invasive ventilation in patients with acute hypoxic respiratory failure after major abdominal surgery reduced the need for re-intubation compared to standard oxygen therapy
  • Although the significant result is relatively fragile, no clinically relevant harm or intolerance was identified and therefore this paper will change my practice
  • Further studies comparing this strategy to high-flow nasal oxygen therapy are urgently needed

External Links

Metadata

Summary author: Duncan Chambler
Summary date: 18 March 2017
Peer-review editor: Adrian Wong

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