Transcript Document
Peri-operative haemodynamic therapy: The OPTIMISE trial
Rupert Pearse Senior Lecturer in Intensive Care Medicine William Harvey Research Institute Barts and the London School of Medicine and Dentistry
Surgery can and should be survivable
Why measure cardiac output….?
Shoemaker WC. Chest 1992
Pulmonary artery catheterisation does not affect outcome
Minimally invasive measurement of cardiac output
Intra-operative Goal Directed Therapy
8 6 4 2 0 0 4 8 12 Right atrial pressure (mmHg) Fluid challenge 16
Prof David Bennett
Preliminary work: Georges trial
SaO 2
94%, Hb
8-10 g dl -1 , Temperature
37
C, Heart rate <100bpm or <20% increase Normal saline at 1.5 ml kg -1 hr -1 Fluid challenge with 250 ml boluses of colloid until CVP reaches plateau value for 20 minutes and continue as required Fluid challenge with 250 ml boluses of colloid until stroke volume reaches plateau for 20 minutes and continue as required If DO 2 I < 600 ml min -1 m -2 up to 1.0 µg kg -1 min -1 add dopexamine to reach this goal Maintain mean arterial pressure between 60 and 100 mmHg using GTN or Noradrenaline as required Urine output below 0.5 ml kg -1 hr -1 for two hours or two consecutive hourly serum lactate rises (to >2 mmol l -1 ) then reveal cardiac output data to clinical staff Cardiac index
2.5 ml min -1 m -2 then continue current management Cardiac index <2.5 ml min -1 m commence epinephrine -2 then
750 650 Control GDT 550 450 0 1 2 3 4 5 6 Time (hours) 7 8 9 Oxygen delivery in GDT and control groups Pearse et al. Crit Care 2005 9: R687
90 75 60 45 * 30 15 0 To tal ** Complications in GDT and control groups Pearse et al. Crit Care 2005 9: R687 Control GDT
9.0
8.5
1.0
0.5
0.0
1.5
1.0
0.5
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3.0
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0 1 Post-operative day 2 0 1 Post-operative day 2 Incidence of myocardial injury following post-operative GDT Pearse et al. Cardiovasc Disorders 2007 7: 10
Peri-op haemodynamic therapies: Systematic reviews
Oesophageal Doppler guided fluid therapy: Complications after major abdominal surgery Abbas S, Hill A. Anaesthesia 2008; 63: 44 –51.
Oesophageal Doppler guided fluid therapy: Mortality after major abdominal surgery Abbas S, Hill A. Anaesthesia 2008; 63: 44 –51.
Odds ratio = 0.50
(0.3
–0.9)
Low dose dopexamine and surgical mortality Pearse R et al. Crit Care Med; 2008 36: 1323-9.
Relative risk = 0.75
(0.5
–1.2)
Low dose dopexamine and surgical mortality Gopal S et al. Anaesthesia; 2009 64: 589-94.
JJ Pandit Meta-analyses of the effects of dopexamine in major surgery: Do all roads lead to Rome?
Both analyses support the argument for a large clinical trial
Preliminary work: Barts & The London
6 5 4 3 2 1 0 ** ** Sham Control Dop 0.5
Dop 1.0
Dop 2.0
5 0 -5 -10 -15 * Sham Control Dop 0.5
Dop 1.0
Dop 2.0
Effect of dopexamine on tissue hypoperfusion due to surgery and endotoxaemia Bangash et al. 2009 unpublished data
** ** ** 250 200 150 100 50 0 Sham Control Dop 0.5
Dop 1.0
Dop 2.0
750 500 250 * * 0 Sham Control Dop 0.5
Dop 1.0
Dop 2.0
Effect of dopexamine on liver injury due to surgery and endotoxaemia Bangash et al. 2009 unpublished data
1 0 3 2 * * * 0 2 4 6 Time after Surgery (Hours) 8 Microvascular flow after major surgery Jhanji S et al. Intensive Care Med 2009; 35: 671-7.
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700 600 500 400 0 2 4 Time (hours) 6 8 SV plus dopex SV Control Effect of flow guided therapy on DO 2 Jhanji et al. 2009 unpublished data
2 -1 -2 1 0 0
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SV plus dopex SV Control 2 4 Time (hours) 6 8 Effect of flow guided therapy on sublingual microvascular flow Jhanji et al. 2009 unpublished data
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120 100 80 60 40 0 2 4 Time (hours) 6 8 SV plus dopex SV Control Effect of flow guided therapies on cutaneous microvascular flow Jhanji et al. 2009 unpublished data
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0 -1 3 2 1 0 2 4 Time (hours) 6 8 SV plus dopex SV Control Effect of flow guided therapy on tissue oxygenation Jhanji et al. 2009 unpublished data
O 2 & Airway maintenance CPAP or Ventilation Trachea Alveolus Arterial blood Goal Directed Therapy Vasodilators Future agents ?
Microcirculation Mitochondria
Peri-operative oxygen cascade
O ptimisation of P eri-opera t ive Card i ovascular M anagement to I mprove S urgical Outcom e
OPTIMISE Trial
Research Question
Does the use of minimally invasive cardiac output monitoring to guide intra-venous fluid and low dose inotropic therapy decrease the number of patients who develop complications within 28 days of major gastro-intestinal surgery?
Participants
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Major abdominal surgery involving gut
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Age over 65 years or…
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Age over 50 years plus high-risk criteria:
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Urgent & Emergency surgery
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Risk factors for Cardiac or Respiratory disease
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Diabetes
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Renal impairment
Organisation
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12 NHS Trusts in England and Scotland
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Trial management hosted by ICNARC
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Sponsor: Queen Mary’s University of London
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Funder: National Institute for Health Research
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NIHR portfolio trial
Duration & Location
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Theatre and Post-Anaesthetic or Critical Care Unit
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Induction of anaesthesia to six hours post-op
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Critical care admission not essential
SaO 2
94%, Hb
8 g/dl, Temperature 37
C, Heart rate <100bpm Mean arterial pressure between 60 and 100 mmHg 5% Dextrose at 1 ml/kg/hr 250 ml colloid boluses according to conventional assessment (Central Venous Pressure) 250 ml colloid boluses to achieve sustained rise in Stroke Volume Dopexamine at 0.5 µg/kg/min
Intervention Group
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250ml fluid challenges with colloid solution to achieve a sustained 10% rise in stroke volume
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Dopexamine at fixed rate of 0.5
g/kg/min
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Reduce dose if patient develops tachycardia Effectiveness trial
Control Group
Usual care: 250ml colloid challenges as indicated by conventional clinical assessment (central venous pressure recommended)
Choice of iv colloid
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Pragmatic trial
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Not possible to restrict fluid selection
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Available data suggest dose more important
Monitoring
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Minimally invasive arterial waveform analysis
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Uncalibrated technology
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Requires arterial catheter
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Suitable for conscious patients
Randomisation
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Web-based
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Open study group allocation
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Stratified by …
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Centre
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Surgical procedure category
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Urgency of surgery
Outcome Data
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Complications (pre-defined criteria)
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Complications (POMS)
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Mortality to 180 days (ONS tagging)
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Duration of hospital stay
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Critical care free days
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EQ-5D
Primary outcome measure
Difference in the number of patients developing post-operative complications within 28 days following randomisation between study groups
Secondary outcome measures
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28 day mortality
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180 day mortality
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POMS morbidity (day 8)
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Duration of hospital stay
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Infectious complications
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Critical care free days
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Cost effectiveness
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Healthcare costs
Sample size
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Reduction in number of patients developing complications from 50% to 37.5%
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90% power and 5% Type I error rate 5%
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3% cross-over
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367 patients per group ( 734 in total )
Recruitment rate
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One patient per centre per week
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12 centres x 46 weeks = 16 months recruitment
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+ 6 month follow-up = 22 months
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Expect to commence recruitment late 2009
Protocol ‘violatons’
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Incorrect dopexamine dose / not administered
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Use of dopexamine in control group patient
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Cardiac output monitoring in control group patient
OPTIMISE
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Large pragmatic effectiveness trial
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Major ‘high-risk’ surgery involving the gut
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Usual care vs ‘Goal directed’ algorithm
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Open study group allocation
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Critical care admission optional