Choice of Systemic Opioid in Perioperative Analgesia

N.Margarita RehattaFaculty of Medicine Airlangga University

Dr Sutomo Hospital

• Pain Pharmacotherapy certain medication – most effective for certain mechanism of pain + consideration factors ie - efficacy, safety, tolerability - disease modification - cost

• For the purposes of selecting treatment useful classification of basic mechanism - nociceptive,inflammatory,neurophatic.

Pain – produced by one or more mechanism - skin incisisionn : nociceptive - amputation of limb : nociceptive+ neurophatic - acute spine injury : nociceptive + inflammatory +neurophatic

Pain Intensity Nociceptive Inflammatory Neurophatic

Mild NSAID NSAID Lowdose Neuromodulating

Moderate NSAID-Opioid combination

NSAID – Opioid Combination

High dose neuromodulating

Severe, Opiod, NMDA inhibitor

Antiinflammatory agents +dis modifying

Multidrug(Anticonvulsan,antidepressan,opioid)Tramadol

Analgesic based on Pain Mechanism

Tramadol less effect on gastrointestinal motorfunction, significant lower resp depression similar nausea and vomiting

Low-tech Intermittent opioid bolus injection

High-tech

Painintensity

Oral / IV NSAID

Oral paracetamol +NSAID

Timepain decreases or goes away

ACUTE PAIN

• Opioid - Allfull agonist opioid in equianalgesic doses produces the same analgesic effect - Equianalgesic doses difficult to determine interindividual variabilities in kinetics and dynamics--- need to be titrated adult patient : better predictor – is age (Mintyre,Javis 1996,Gammaitni etal,2003)

* genetic,chronopharmacology issuesAcute pain: one opioid not superior over others but better but

better in some patient (level II)

Intensity of clinical effect determined by 1. Access of opioid to the receptor (distribution) 2. The “fit” of the opioid onto the receptor (the binding affinity)

Intensity of biologic response(Analgesia, respirator depresion etc)

Receptor binding & respons

Exogenus administrered opioids procedure analgesia by mimicking the actionof opioid peptides in specific receptors within CNS

Pharmacokinetic- Pharmacodynamic common opioid

Generic name

Route Equianalgesic dose(mg)

Peak(hr)

Duration(hr)

Half life(hr)

Comments Precautions

NaturallyAgonists

Morphine im 10-15 0.5-1 3-5 2-3.5 Gold Standar

ICPBronchial asthma,increased ICP

Synthetic Agonist

Pethidine im 75-100 0.5-1 2-3 10%potent as Mo

Accumulated metabolites CI in MOA tx

Fentanyl iv 0.1 0.75-1 1.7min Potent,cont infusion

Accumulation,prolonged effect

Alfentanyl iv 0.5-1 0.5 1.4min id

Remifenanyl : iv, rapid metabolism, by unspecified esterase blood and t issue ,-half life 3-4min

Opioid Morphine : Active Metabolite morphine 6 gluroronic

Pethidine : Metabolite accumulate - convulsion, CNS irritationAnticholnergic effectBetter than other opioid for colick pain

Fentanyl : Lipid soluble, high hepatic clearance Transdermal should not used in acute pain(delayed onset)

Tramadol : Atypical opioid centrally acting-analgesic efficacy & potency comparable to pethidine Not associated with respiratory depression sedationNo physical dependence and tolerance in long term use

Oral :- Codein (less effective for post of pain)- Hydromorphine (6x more potent than Mo)- Methadone (long onset, steady state)

Pain and sensitivity to opiod - Opiod Insensitivity pain - Opioid partially sensitive pain - Opiod sensitive pain (start with test dose in blocks) - Opioid sensitive but inappropriate

Drug Delivery Systems

Direct (to neuraxis)

EpiduralSubarachnoidIntraventricular

Indirect (via blood-borne carriage)Via sustemic absorption

OralSublingualrectalInhalational

Via depot formationTranscutaneousIntramuscularSubcutaneous

Direct instillationIntravenous

Clinical Issue

• Intratheca l Mo + GA in Cardiac Surgery (preventive analgesia)

• Intraoperative Epidural Mo for Spinal Surgery• (Newer)Ajuvant Analgesic:

ketamin,gabapentin,pregabalin,dexmetomidine• Fentanyl patch for acute pain ( iontophoretic PC

transdermal)• PCA regional

Pain is physiological antagonist of CNS depressan effects

Opioid need to be titrated :Opioid responsive pain (Pain sensitive

opioid)Combined analgesic therapy

ie after start with Mo and then adding nerve block,Mo dose should reduced

Opioid respiratory depression may occur if used for

indication other than analgesia

Opioid are mainly effective against steady, dull pain

less effective against pain on moving and coughing

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Opioid Issues

Important consideration in emergency conIdition

Physiologic DerangementRespiratory problem

(Trauma thorax, CNS, Pulmonary concussion

Airway problem, Spine trauma)Circulation problem

(Blood loss)

Anatomic DerangementAnatomic location and severity of the injuries

Pain level (Tissue injury & psychological response)

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