PROBESE

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) with Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients

PROBESE Collaborative Group. JAMA. Published online June 03, 2019321(23):2292–2305. doi:10.1001/jama.2019.7505

Clinical Question

  • In obese patients, does the use of recruitment maneuvers with high PEEP, compared with low PEEP, decrease postoperative pulmonary complications?

Background

  • Prior studies have identified the use of PEEP and low tidal volumes for reduction of major pulmonary complications compared to high tidal volumes and zero PEEP
  • No benefit was found in these patients with the use of high PEEP and recruitment compared to low PEEP strategies
  • Obese patients have greater levels of atelectasis and impairments in respiratory function under general anesthesia compared to normal weight or overweight patients
  • There is uncertainty whether higher PEEP with recruitment is beneficial in preventing postoperative pulmonary complications in these patients
  • With an increasing prevalence of obesity, the burden of postoperative pulmonary complications may increase significantly

Design

  • International, multicentre RCT with protocol and statistical analysis plan published a priori
  • Centralized randomization and 1:1 allocation
  • Random block sizes, stratified by study site
  • Outcome assessors were blinded, intraoperative clinicians and assessors were not blinded
  • Sample size increased after initial interim analysis demonstrated that incidence of primary outcome was lower than expected
  • Assuming 20% rate of pulmonary complications, sample size of 2013 would have 80% power to detect Relative Risk of 0.75 for the primary outcome at a 2-sided alpha level of 0.05
  • Intention-to-treat analysis
  • Pre-specified subgroups: Laparoscopy vs non-laparoscopy, baseline SpO2 > 96% vs. < 96%, BMI > 40 vs. < 40, peripheral vs. upper abdominal procedures, waist-to-hip ratio < 1.0 vs. > 1.0

Setting

  • 77 sites in 23 countries internationally, primarily in Europe
  • Enrolment from July 2014 to February 2018

Population

  • Inclusion criteria:
    • BMI > 35
    • Surgery > 2 hours (laparoscopy or non-laparoscopy)
    • Intermediate to High risk of pulmonary complications as calculated by Assess Respiratory Risk in Surgical Patients in Catalonia Score (ARISCAT) > 26
  • Exclusion criteria:
    • Patient Factors:
      • Age < 18 years, previous lung surgery, mechanical ventilation in past 30 days for > 30 minutes, Chemotherapy and Radiotherapy in 2 months prior to surgery, concurrent participation in another study, persistent hemodynamic instability/intractable shock, severe COPD, severe cardiac disease, ARDS, pulmonary hypertension
    • Procedural Factors:
      • Cardiac/Neurological surgery, intraoperative one-lung ventilation, planned reintubation postoperatively, intraoperative prone or lateral positioning
  • 2013 patients randomized in total. 29 patients excluded post randomization. 8 patients lost to follow up. 1976 patient included in intention to treat analysis (989 intervention, 987 control)
  • Comparison of baseline demographics
    • Mean age of 48.8 years with 69.9% female, 90.1% undergoing abdominal surgery
    • No differences in:
      • Average BMI (43.8), ARISCAT score, total fluids, transfusion, use of epidural, neuromuscular blockade, surgical & anesthetic duration, anesthetic technique, type of surgery, use of NIV, ASA score, OSA, Tobacco use, COPD, Heart failure or preoperative hemoglobin, SpO2
    • Statistically significant intraoperative ventilation differences during 1st hour of surgery, comparing high vs. low PEEP groups:
      • Peak pressure: 27.9 vs 26.5cmH2O, Absolute Difference (AD) 1.4 (95% C.I. 1.0 to 1.9)
      • Driving pressure: 12.2 vs 17.9cmH2O, AD -5.7 (-6.1 to -5.2)
      • SpO2: 97.9 vs 96.6%, AD1.3 (1.1 to 1.5)
      • FiO2: 0.45 vs 0.48, AD 0.02 (-0.03 to -0.01)

Intervention

  • High PEEP with recruitment manoeuvre
    • PEEP of 12cmH2O (SD 1.1cmH2O)
      Hourly recruitment manoeuvre
    • Stepwise increase in tidal volume and PEEP to achieve Pplat of 40-50 cm H2
    • Hypoxemia treated primarily with increase in PEEP before FiO2 increased

Control

  • Low PEEP
    • PEEP of 4cmH2O (SD 0.5cmH2O)
    • Hypoxemia treated primarily with increase in FiO2 only

Management common to both groups

  • Volume controlled ventilation at 7mL/kg (Predicted Body Weight)
  • FiO2 titrated to keep SpO2 > 92% (not lower than 0.4)

Outcome

  • Primary outcome: Composite incidence of pulmonary complications including any respiratory failure, ARDS, bronchospasm, infiltrate, infection, aspiration, effusion, atelectasis, cardiopulmonary edema or pneumothorax that developed within the first 5 post-operative days
    • Comparing high PEEP vs. low PEEP groups – no significant difference
      • 21.3% vs 23.6%, AD -2.3 (-5.9 to 1.4), Relative Risk (RR) 0.93 (0.83-1.04) p = 0.23
  • Components of primary outcome
    • Mild respiratory failure: 12.7% vs. 15.6% , AD -1.9% (-5.1 to 1.2%), p=0.22
    • Pleural effusion: 4.3% vs 2.1%, AD2.2 (0.7-3.8), RR 1.35 (1.14 to 1.62), p = 0.005
    • No difference in any other components of composite score
  • No difference with pre-specified subgroup analysis
  • Secondary outcomes:
    • Intraoperative adverse events:
      • Hypoxemia with SpO2 < 92% for > 1 minute – significantly lower in high PEEP group
        • 5% vs 13.6%, AD -8.6 (-11.1 to -6.1), RR 0.51 (0.40 to 0.65), p < 0.001
      • Hypotension with SBP < 90mmHg for > 2 minutes – significantly greater in high PEEP group
        • 31.6% vs 17.2% , AD14.4 (10.7 to 18.2), RR 1.43 (1.31 to 1.56), p < 0.001
      • Bradycardia with HR < 50 prior to recruitment maneuver – significantly greater in high PEEP group
        • 9.9% vs 6.0%, AD3.9 (1.5 to 6.3), RR 1.27 (1.11 to 1.45), p = 0.001
    • Postoperative Events:
      • Extrapulmonary complications (sepsis, ACS, AKI, DIC, liver failure) – no significant difference
      • Hospital mortality – no significant difference
        • 1.2% vs. 0.5%, AD 0.7 (-0.1 to 1.5), p=0.09
  • Post Hoc Outcomes
    • Intra-operative rescue strategy for desaturation – significantly greater in low PEEP group
      • 6% vs. 16.8%, AD -10.8 (-13.6 to -8.1), p<0.001
    • Intra-operative need for vasoactive drugs – significantly greater in high PEEP group
      • 49.6% vs. 44.5%, AD 5.2 (0.8-9.6), p=0.02

Authors’ Conclusions

  • Intraoperative mechanical ventilation with a strategy involving high PEEP and recruitment did not reduce postoperative pulmonary complications compared to low PEEP strategy in obese patients under general anesthesia

Strengths

  • Adequately powered study with adjusted sample size
  • Multi-centre
  • Generalizable population with minimal inter-group differences, of questionable clinical importance
  • Intention to treat analysis with minimal exclusion post-randomization

Weaknesses

  • Lack of intraoperative blinding given pragmatic design
  • No individual PEEP titration
  • Lack of standardization of postoperative pulmonary management (ex CPAP vs HFNC vs FM, etc)
  • Use of composite outcome that included outcomes of variable importance

The Bottom Line

  • In obese patients undergoing general anesthesia, a strategy with higher PEEP and recruitment maneuvers does not prevent post-op pulmonary complications
  • Intra-operative oxygenation and pulmonary mechanics may be improved at the risk of increased vasopressor support

External Links

Metadata

Summary author: Vatsal Trivedi
Summary date: 25th July 2019
Peer-review editor: @davidslessor

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