Perioperative haemodynamic therapy:

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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
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Surgery can and should be survivable
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Why measure cardiac output.? Shoemaker WC. Chest
1992
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Pulmonary artery catheterisationdoes not affect
outcome
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Minimally invasive measurement of cardiac output
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Intra-operative Goal Directed Therapy
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Fluid challenge
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Preliminary work Georges trial
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SaO2 ? 94, Hb ? 8-10 g dl-1, Temperature ? 37
?C, Heart rate lt100bpm or lt20 increase Normal
saline at 1.5 ml kg-1hr-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 DO2I lt 600
ml min-1m-2 add dopexamine up to 1.0 µg kg-1
min-1 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-1hr-1 for two hours
or two consecutive hourly serum lactate rises (to
gt2 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 lt2.5 ml min-1 m-2 then commence
epinephrine
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Oxygen delivery in GDT and control groupsPearse
et al. Crit Care 2005 9 R687
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Complications in GDT and control groups Pearse et
al. Crit Care 2005 9 R687
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Incidence of myocardial injury following
post-operative GDT Pearse et al. Cardiovasc
Disorders 2007 7 10
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Peri-op haemodynamic therapiesSystematic
reviews
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Oesophageal Doppler guided fluid
therapy Complications after major abdominal
surgery Abbas S, Hill A. Anaesthesia 2008 63
4451.
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Oesophageal Doppler guided fluid
therapy Mortality after major abdominal
surgery Abbas S, Hill A. Anaesthesia 2008 63
4451.
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Odds ratio 0.50 (0.30.9)
Low dose dopexamine and surgical mortality Pearse
R et al. Crit Care Med 2008 36 1323-9.
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Relative risk 0.75 (0.51.2)
Low dose dopexamine and surgical mortality Gopal
S et al. Anaesthesia 2009 64 589-94.
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Both analyses support the argument for a large
clinical trial
JJ Pandit
Meta-analyses of the effects of dopexamine in
major surgery Do all roads lead to Rome?
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Peri-op haemodynamic therapiesDo we understand
how they work?
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Preliminary work Barts The London
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Effect of dopexamine on tissue hypoperfusion due
to surgery and endotoxaemiaBangash et al. 2009
unpublished data
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Effect of dopexamine on liver injury due to
surgery and endotoxaemiaBangash et al. 2009
unpublished data
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Effect of dopexamine on renal injury due to
surgery and endotoxaemiaBangash et al. 2009
unpublished data
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Microvascular flow after major surgeryJhanji S
et al. Intensive Care Med 2009 35 671-7.
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Effect of flow guided therapy on DO2Jhanji et
al. 2009 unpublished data
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Effect of flow guided therapy on sublingual
microvascular flowJhanji et al. 2009 unpublished
data
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Effect of flow guided therapies on cutaneous
microvascular flow Jhanji et al. 2009 unpublished
data
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Effect of flow guided therapy on tissue
oxygenationJhanji et al. 2009 unpublished data
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Effect of fluid and inotropes on DO2 and
ScvO2Jhanji et al 2009 unpublished data
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O2 Airway maintenance
CPAP or Ventilation
Trachea
Goal Directed Therapy
Alveolus
Vasodilators
Arterial blood
Future agents ?
PO2
Microcirculation
Mitochondria
Peri-operative oxygen cascade
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Optimisation of Peri-operative Cardiovascular
Management to Improve Surgical Outcome OPTIMISE
Trial
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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?
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Participants

• Major abdominal surgery involving gut
• Age over 65 years or
• Age over 50 years plus high-risk criteria
• Urgent Emergency surgery
• Risk factors for Cardiac or Respiratory disease
• Diabetes
• Renal impairment

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Organisation

• 12 NHS Trusts in England and Scotland
• Trial management hosted by ICNARC
• Sponsor Queen Marys University of London
• Funder National Institute for Health Research
• NIHR portfolio trial

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Duration Location

• Theatre and Post-Anaesthetic or Critical Care
  Unit
• Induction of anaesthesia to six hours post-op
• Critical care admission not essential

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SaO2 ? 94, Hb ? 8 g/dl, Temperature 37 ?C, Heart
rate lt100bpm 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
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Intervention Group

• 250ml fluid challenges with colloid solution to
  achieve a sustained 10 rise in stroke volume
• Dopexamine at fixed rate of 0.5 ?g/kg/min
• Reduce dose if patient develops tachycardia
• Effectiveness trial

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Control Group
Usual care 250ml colloid challenges as indicated
by conventional clinical assessment (central
venous pressure recommended)?
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Choice of iv colloid

• Pragmatic trial
• Not possible to restrict fluid selection
• Available data suggest dose more important

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Monitoring

• Minimally invasive arterial waveform analysis
• Uncalibrated technology
• Requires arterial catheter
• Suitable for conscious patients

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Randomisation

• Web-based
• Open study group allocation
• Stratified by
• Centre
• Surgical procedure category
• Urgency of surgery

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Outcome Data

• Complications (pre-defined criteria)?
• Complications (POMS)?
• Mortality to 180 days (ONS tagging)
• Duration of hospital stay
• Critical care free days
• EQ-5D

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Primary outcome measure
Difference in the number of patients developing
post-operative complications within 28 days
following randomisation between study groups
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Secondary outcome measures

• Infectious complications
• Critical care free days
• Cost effectiveness
• Healthcare costs

• 28 day mortality
• 180 day mortality
• POMS morbidity (day 8)
• Duration of hospital stay

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Sample size

• Reduction in number of patients developing
  complications from 50 to 37.5
• 90 power and 5 Type I error rate 5
• 3 cross-over
• 367 patients per group (734 in total)

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Recruitment rate

• One patient per centre per week
• 12 centres x 46 weeks 16 months recruitment
• 6 month follow-up 22 months
• Expect to commence recruitment late 2009

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Protocol violatons

• Incorrect dopexamine dose / not administered
• Use of dopexamine in control group patient
• Cardiac output monitoring in control group
  patient

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OPTIMISE

• Large pragmatic effectiveness trial
• Major high-risk surgery involving the gut
• Usual care vs Goal directed algorithm
• Open study group allocation
• Critical care admission optional

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Questions..?