OPTIMISE

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery

Pearse. JAMA 2014; Published online 19 May 2014.

Clinical Question

  • In high-risk patients undergoing gastrointestinal surgery, does a cardiac output-guided haemodynamic therapy algorithm compared to clinician-guided standard therapy reduce death and major morbidity within 30 days?

Design

  • Randomised, controlled clinical trial
  • Dynamic, minimisation process during randomisation to limit between group differences in:
    • trial site
    • urgency of surgery
    • surgical procedure category
  • Assessor blinded (self-assessment of blinding reports ~95% successful)
  • Powered to detect absolute risk (AR) reduction of 12.5% from baseline incidence of 50% for primary outcome, if 690 patients recruited (90% power, type 1 error 5%)

Setting

  • 17 acute care NHS (state-funded) hospitals in UK
  • June 2010 to November 2012

Population

  • Inclusion: over 50 years old undergoing GI surgery > 90 minutes, with at least one ‘high-risk’ risk factor, such as:
    • age over 65 years old
    • cardiac or respiratory disease
    • exercise tolerance of ≤ 6 METS or AT ≤ 14 ml/min/kg on CPET
    • renal impairment
    • diabetes
    • emergency surgery
  • Exclusion: recent MI or pulmonary oedema; if clinician planned to use cardiac output (CO) monitoring for clinical reasons.
  • 1735 patients screened and 734 randomised.

Intervention

  • Algorithm-directed care dictating colloid and dopexamine administration from induction of anaesthesia to 6 hours after end of surgery using LiDCO CO monitor.
    • 250ml bolus colloid over 5 minutes – positive response if rise in stroke volume of at least 10% sustained for 20 minutes.
  • Identical routine care included: SpO2 > 94%; Hb > 80 g/L; temperature > 37C; HR < 100 bpm; BP 60–100 mmHg using vasoactive drugs; analgesia by epidural or intravenous opiates; 5% dextrose maintenance fluid at 1 ml/kg/h; and boluses of any fluid at clinician’s discretion.
  • 91.0% compliance with protocol.

Control

  • Clinician-directed care without the use of CO monitoring.
  • Identical routine care included: SpO2 > 94%; Hb > 80 g/L; temperature > 37C; HR < 100 bpm; BP 60–100 mmHg using vasoactive drugs; analgesia by epidural or intravenous opiates;  5% dextrose maintenance fluid at 1 ml/kg/h; and boluses of any fluid at clinician’s discretion.
  • 91.2% compliance with protocol

Outcome

  • Primary outcome: reduced incidence of composite outcome of 30-day mortality and mod/major complications favouring intervention, but not statistically significant.
    • Intervention arm: 36.6%
    • Control arm: 43.4%
    • AR reduction 6.8%; 95% CI -0.3% to 13.9%; p=0.07.
  • Secondary outcome: no statistically significant difference in outcomes
    • Post-Operative Morbidity Survey (POMS) at 7-days (66.2% intervention vs 67.9% usual care)
    • Infectious complications at 30-days (23.8% vs 29.7%)
    • Critical care-free days at 30-days (median 27 vs 28 days)
    • Mortality at 30-days and 180-days (3.3% vs 3.0% and 7.7% vs 11.6%)
    • Hospital length of stay (median 10 vs 11 days)

Authors’ Conclusions

  • In this trial, the use of cardiac output-guided haemodynamic therapy did not reduce a composite outcome of complications and 30-day mortality.
  • Inclusion in an updated meta-analysis indicates the intervention was associated with a reduction in complication rates.
  • @PeriopMedUCL: “Equipoise for a further trial?”; @rupert_pearse: “Absolutely”… “OPTIMISE 2 proposal will be submitted soon!” via Twitter 20 May 2014 12:11

Strengths

  • Very well designed and performed pragmatic study with high rate of compliance and assessor blinding.
  • Pre-defined statistical methods and outcome measure clinical criteria.
  • Excellent methodology and minimisation process has reduced systematic bias. Good internal validity.
  • Minimal loss-to-follow-up rate, which was well below primary outcome rate.
  • Combined with meta-analysis for strengthened conclusion.

Weaknesses

  • Baseline difference: higher incidence of renal impairment in intervention group may bias toward no difference in outcome.
  • Composite outcome is pragmatic and relevant to patient care, but this study cannot ascertain if individual components are associated with benefit, no effect or harm.
  • External generalisability:
    • median surgery was 4.5 hours, 70% received epidurals and 70% attended critical care for level 3 care; incidence of laparoscopic surgery not available. Although this appears to describe a very high-risk surgical cohort, 30-day mortality was only ~3%. Difficult to define which of my patients I can apply these findings to.
    • Additional staff were frequently present to provide advice and delivery of intervention. Despite this a learning curve was demonstrated (difference in effect demonstrated between first 10 vs all other patients). Can this algorithm be applied within routine staffing levels and case load for individual clinicians?

The Bottom Line

  • In patients undergoing major GI surgery who are over 50 years old, with risk factors for increased perioperative mortality and morbidity, using cardiac output monitoring with an algorithm directing fluid and dopexamine therapy probably reduces the likelihood of mortality and morbidity by about 7% and possibly up to 14%, but based on this study alone there may be no clinically significant effect or no effect at all.
  • It is difficult to know how to generalise and apply these findings on a day-to-day basis, especially if laparoscopic surgical techniques are used.
  • I do not believe this provides sufficient grounds to introduce routine dopexamine and 6 hours of post-operative stroke volume optimisation, but I shall continue to use CO monitoring to guide fluid therapy intra-operatively.

Links

Full text pdf / abstract / doi: 10.1001/jama.2014.5305

Editorial, Commentaries or Blogs

Metadata

Summary author: @DuncanChambler
Summary date: 20 May 2014
Peer-review editor: @stevemathieu75

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