Transcript Protocol Development: Insights from New Anticoagulants

Anaesthesia protocol development:
Insights from National societies
regarding new antiplatelets, new
anticoagulants and haemostatic
agents
G Ogweno
Dept Of Medical Physiology
Kenyatta University
Factors contributing to protocol based
healthcare
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Cost pressures
Technological advances
Increase in management-led decision making
Consumer awareness
Value for money movement
Availability of information
Non-clinicians with the authority to question
effectiveness
• International consensus
• Professional accountability
• Changing demographic profile
Why protocols in anaesthesia?
• To ‘standadize’ medical care, increase quality ,
effectiveness, specificity, sensitivity,
resoluteness and patient outcomes=clinical
pathways
• ‘Experts’ best faith efforts to offer reasonable
pathways for patient management
• To enhance best evidence based practice
What are protocols?
• Special set of rules defining
relationship=communication
• Based on current evidence
• Identify most important questions related to
clinical practice, possible options and
outcomes=decision points and course of
action
• Identify, summarise, evaluate highest quality
evidence, risk vs benefit and cost effectiveness
Forms of protocols
• Summarized consensus statements on best
practice
• Guidelines: diagnosis, treatment by national
associations
• Clinical pathways
• Trials: clinical, research
Levels of Evidence
Hierachies of evidence
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Clinical trials
I-well designed randomised controlled trials
II-1a: well –designed controlled trials with pseudorandomisation
II-1b: well-designed controlled trials with no
randomisation
Cohort studies
II-2a: well designed cohort (prospective) with
concurrent controls
II-2b: well designed cohort(prospective) with
historical controls
II-2c: well designed cohort (retrospective) with
concurrent controls
II-3: well designed case –controlled (retrospective)
III- large differences from comparisons between
times and/or places with or without intervention
Iv-opinions of respected authorities based on
clinical experience, descriptive studies and reports
from expert committees
Forms of evidence
Randomized
controlled trials
Case-controlled
study
Cohort study
Survey
Qualitative
studies
professional
consensus
Classes of recommendations and
levels of evidence
• Classes of recommendations
 Class I Evidence and/or general agreement that a given treatment or procedure is
beneficial
 Class II Conflicting evidence and/or divergence of opinion about the
usefulness/efficacy of the treatment or procedure
 Class IIa Weight of evidence/opinion in favour of usefulness/efficacy
 Class IIb Usefulness/efficacy is less well established by evidence/opinion
 Class III Evidence or general agreement that the treatment or procedure is not
useful or effective and in some cases may be harmful
• Level of evidence
 Level A Data derived from multiple randomised clinical trials or meta-analyses
 Level B Data derived from a single randomised clinical trial or large nonrandomised studies
 Level C Consensus of opinion of the experts and/or small studies, retrospective
studies, registries
Perioperative Anticoagulation
Indications
• Patients on Anticoagulation undergoing
surgery
 Pitfalls
• Over Anticoagulation or premature use results
in significantly increased bleeding
complications
• Bleeding complications result in transfusions
and stopping Anticoagulation which risks clots
Points ↘of action of anticoagulants
Laboratory testing
Common
• Blood counts, including
platelets
• Routine Kinetic: PT,aPTT, TT,
ACT, INR
• Bleeding time
• Not predictive of bleeding
Research
• Kinetic: ECT
• Factor assays: anti-Xa
• Capacitative:
Thrombelastography,
Thrombogram
• Platelets: optical
aggregometry,
plateletworks,multiplate
• Promising though not
readily available
Perioperative anticoagulation
Protocols: sources of information
• Analysis of published studies with LMWHs and
the type of anaesthesia is reported
• Case reports in the literature
• Calculations from cases reported to
manufacturers
• Questionnaires to anaesthesiology societies
Risk stratification
Bleeding
Thromboembolism
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High risk procedures:
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High:
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Neurosurgery
Abdominal or pelvic procedures
Orthopedic joint procedures
Major ENT or oral surgery
Endoscopy with biopsy
Epidural Anesthesia
Prolonged general anesthesia with
intubation
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Very Low Risk Procedures:
– Procedures
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Dental procedures
Cataract Surgery
Dermatologic procedures
Pacemaker and IACD placement
Endoscopy without biopsy
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Intermediate:
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Very Low Risk:
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Deep Vein Thrombosis within last 3 months
Pulmonary Embolism within last 3 months
Cardiac thromboembolism (any cause) within 1 month
Recurrent Venous Thromboembolism
Strong Thrombophilia
– Active cancer
– Antiphospholipid Antibody Syndrome
(uncommon)
– Antithrombin III deficiency (rare)
– Protein C Deficiency
– Protein S Deficiency
Mechanical heart valves
– Mitral valve replacement
– Ball-Cage or other older cardiac valve
– Higher risks
» Comorbidity (e.g. Congestive Heart
Failure)
» Atrial Fibrillation with mechanical
valve
Atrial Fibrillation with CHADS-2 Score 4 or higher
No DVT for 3 months
Chronic Atrial Fibrillation without stroke
New bileaflet aortic valves (St. Jude or Medtronic)
Central neural blockade (CNB) in
anticoagulated patients: Risks
• Symptomatic spinal/epidural haematoma
• greatest risk appears effective during insertion or
removal of spinal or epidural needles or catheters
• SSEH do NOT necessarily progress to permanent
neurological damage
• Risk of SSEH appears higher for epidural than
spinal-especially traumatic or difficult access
• Not all vascular traumatic damage recognizable
LMWH and spinal Haematoma In US
• Enoxaparin introduced US in 1992=dose 30mg bd
• More than 40 cases of spinal haematomas for 1st
5 years of use
• 1997: FDA issued warning, manufacturers to
adjust insert
• ASRA tasked to provide guidelines
• Horlocker et al analysed case reports/ series of
complications introduction of enoxaparin
• ASRA consesus conferences in 1998, 2002, 2007
and 2007
Highlights of US Guidelines
• Anticoagulation is not an absolute
contraindication for regional anesthesia
• Regional anesthesia may be safely performed
provided risk stratification is done
• No added risk at prophylactic doses
• Complications may be independent of drug
action: patient related, procedure specific
• Cases to be judged on individual basis and
exercise caution= continous vigilance
• Recognizes data insufficiency
European perspectives
• LMWH-enoxaparin many years
experience@40mg od
• Moen et al 2004 review of severe neurological
complications between 1990-1999
1,260, 000 spinal blocks
450, 000 epidurals including 200,000 labor
epidurals
Results of Moen et al
Findings
• 127 complications
 Spinal haematomas=33
 Cauda equina syndrome=32
 Meningitis=29
 Epidural abscess=13
 Miscellanous=20
• Permanent neurological
damage in 85 patients
Severe neurological
complications
• 1: 20-30,000 in all groups
• 1:25,000 after obstetric
epidurals
• 1:3,600 in all others
• Rates less in obstetrics
• Epidurals higher than spinal
• Osteoporosis risk factor
Haemostatic agents
• Whole blood and plasma products as
haemostatic agents limited efficacy and
associated with complications
• Available systemic alternatives:
Fibrinogen concentrate
Prothrombin complex concentrate (PCC)
Recombinant factor vii
Recombinant factor vii
• Efficacy demonstrated in haemophilia-level 1a
• Trials ongoing in trauma= level iii
• Case reports of post administration
thrombophilia
• Most guidelines indicated only in bleeding
haemophilia
• Other uses experimental=must warn of grave
consequences
European perspectives on haemostatic
agents
• Efforts to eradicate use of FFP
• Use of capacitative tests strongly
recommended, if available
• Strong recommendation on identification and
replacement of individual factors
• Austrian OGARI: use of fibrinogen and PCC as
opposed to FFP in trauma
Anesthetic management of patients
receiving antiplatelet medications
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Exert diverse effects on platelet function
Impossible to extrapolate between groups
No wholly accepted test to guide therapy
Appear to represent no added risk for CNB
complications-actual risk unknown
• Bleeding risk may be increased by concurrent use
of other antithrombotic medications
• Cyclooxygenase-2 inhibitors minimal effect on
platelets, could be considered as alternatives
Limitations of Guidelines
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Desired level of evidence does not exist
Subject to major flaws
Failure to account for multiple comorbidities
Tend to produce an average result
Unintended consequences
Poorly understood factors
Too complicated
Misuse of guidelines
Conclusions
• Perioperative management of haemostatic
agents pose significant challenge
• Guidelines may help minimize risks
• Risks vs benefit should be carefully weighed in
any protocol development
• Good protocols should be simple to follow and
based on facts
• Unfortunately, NO such data exist for
perioperative antithrombotic agents