Regional Opioid Analgesia

I: Anatomical, Pharmacological, Physiological and Technical Basis of Spinal Regional Opioid Administration.- 1. Developments, advantages and drawbacks of regional opioid analgesia.- 2. Anatomy and physiology.- 2.1 Nociception and nociceptive pathways.- 2.2 Anatomy of opioid receptors.- 2.3 Anatomy of the epidural and the intrathecal spinal space.- 3. Micropharmacology of antinociceptive substances in the spinal cord.- 3.1 Endorphins.- 3.2 Multiple opioid receptors.- 3.3 Opioid agonists, opioid antagonists.- 3.3.1 Agonists.- 3.3.2 Antagonists.- 3.3.2.1 Pure antagonists.- 3.3.2.2 Mixed agonist-antagonists.- 3.3.2.3 Partial agonist-antagonists.- 3.4 Endogenous non-opioid neuropeptides and neuroamines.- 3.4.1 Substance P.- 3.4.2 Other peptides and amines.- 3.5 Other exogenous substances with spinal antinociceptive action.- 4. Pharmacokinetics of opioids.- 4.1 Molecular weight [dalton].- 4.2 Lipid solubility, hydrosolubility.- 4.3 Ionization.- 4.4 Protein binding.- 4.5 Distribution volume.- 4.6 Plasma half life times.- 4.7 Clearance.- 4.8 Permeability across biological membranes.- 4.9 Diffusion of spinal opioids.- 4.10 Specific receptor binding activity.- 4.11 Rediffusion.- 4.12 Physical characteristics of opioid solutions.- 4.12.1 Volume, density, specific gravity, baricity.- 4.12 2 Changes in body temperature.- 4.12.3 Changes in intraspinal pressure.- 4.13 Special pharmacokinetics of spinal opioids.- 4.14 Pharmacokinetic variability.- 5. Pharmacodynamics of opioids.- 5.1 Analgesia.- 5.1.1 Relationship between administration route and dose.- 5.1.2 Relationship between dose and depth of analgesia.- 5.1.3 Relationship between dose and duration of analgesia.- 5.1.4 Relationship between lipid soluble substances and duration of analgesia.- 5.1.5 Relationship between analgesia and pain aetiology.- 5.2 Cardiovascular system and sympathetic nervous system.- 5.3 Respiratory system.- 5.4 Muscular system and gastrointestinal system.- 5.5 Central nervous system.- 5.6 Endocrine and metabolic system.- 6. Side effects.- 6.1 Generalities.- 6.2 Side effects of epidural opioids.- 6.2.1 Early and delayed respiratory depression.- 6.2.1.1 Aetiology and characteristics.- 6.2.1.2 Monitoring.- 6.2.1.3 Factors increasing or reducing the risk of delayed respiratory depression.- 6.2.1.4 Dose response curves.- 6.2.1.5 Prophylaxis.- 6.2.1.6 Treatment.- 6.2.2 Pruritus.- 6.2.3 Nausea and vomiting.- 6.2.4 Urinary retention.- 6.2.5 Constipation.- 6.2.6 Drowsiness.- 6.2.7 Other rarer side effects.- 6.2.8 Overdose, addiction, dependence, tolerance and withdrawal syndrome.- 6.3 Side effects of intrathecal opioids.- 6.3.1 Respiratory depression.- 6.3.2 Other side effects.- 6.3.3 Prevention of side effects after intrathecal administration.- 6.4 Tolerance, tachyphylaxis.- 6.4.1 Definition and characteristics.- 6.4.2 Rapidity of appearance.- 6.4.3 Reversibility of tolerance.- 6.4.4 Cross tolerance.- 6.4.5 Methods of delaying tolerance development.- 6.5 Side effects due to the technique used.- 6.5.1 Fibrotic reactions.- 6.5.2 Neuronal degeneration.- 6.5.3 Infection.- 6.5.4 Virus reactivation.- 7. Drugs.- 7.1 Pure opioid agonists.- 7.1.1 Morphine.- 7.1.2 Diamorphine (heroin).- 7.1.3 Pethidine (meperidine).- 7.1.4 Methadone.- 7.1.5 Hydromorphone.- 7.1.6 Nicomorphine.- 7.1.7 Fentanyl.- 7.1.8 Alfentanil.- 7.1.9 Sufentanil.- 7.1.10 Lofentanil.- 7.1.11 DADL.- 7.1.12 Metenkephalin.- 7.1.13 Beta-endorphin.- 7.1.14 Spiradoline 5 UI-62, 0066E.- 7.2 Mixed opioid agonist-antagonists and partial agonist-antagonists.- 7.2.1 Buprenorphine.- 7.2.2 Nalbuphine.- 7.2.3 Butorphanol.- 7.2.4 Pentazocine.- 7.2.5 Meptazinol.- 7.2.6 Tramadol.- 7.3 Pure opioid antagonists.- 7.3.1 Naloxone.- 7.3.2 Nalmefene.- 7.3.3 Naltrexone.- 7.4 Non-opioid drugs.- 7.4.1 Calcitonin.- 7.4.2 Droperidol.- 7.4.3 Baclofen.- 7.4.4 Midazolam.- 7.4.5 Ketamine.- 7.4.6 Clonidine.- 7.4.7 Lysine-acetylsalicylate.- 7.4.8 Somatostatin.- 7.4.9 Enkephalinase and aminopeptidase inhibitors.- 7.4.10 Cholecystokinin inhibitors: proglumide or xylamide.- 7.5 Adrenaline (Epinephrine).- 7.6 Drug-related problems.- 7.6.1 Physical properties.- 7.6.1.1 Solutions.- 7.6.1.2 Stereospecificity.- 7.6.1.3 pH.- 7.6.2 Preservative-free products.- 7.6.3 Doses.- 7.6.4 Drug interactions.- 7.6.5 Drug associations.- 7.6.5.1 Local anaesthetics.- 7.6.5.2 Other drug associations.- 7.6.6 Drug administration modalities.- 7.6.6.1 Patient’s position.- 7.6.6.2 Injection volumes.- 7.6.6.3 Level of administration.- 7.6.6.4 Injection routes.- 8. Equipment and drug delivery systems.- 8.1 Equipment.- 8.1.1 Epidural, intrathecal needles.- 8.1.2 Catheters.- 8.1.2.1 Materials and models.- 8.1.2.2 Catheter problems.- 8.1.2.3 Externalized or tunnelled catheter.- 8.1.2.4 Open or closed systems.- 8.1.3 Micropore filters.- 8.2 Drug delivery systems.- 8.2.1 Ports.- 8.2.2 Special drug delivery systems.- 8.2.2.1 Roquefeuil’s self-administration system.- 8.2.2.2 Muller and Laugner’s self-administration device.- 8.2.2.3 Self-administration device Secor.- 8.2.3 Pumps.- 8.2.3.1 Pros and cons of pump devices.- 8.2.3.2 External pumps.- 8.2.3.3 Implantable pumps.- 8.2.4 Dressings.- 8.2.4.1 Transparent dressing.- 8.2.4.2 Cross elastic wound dressing.- 8.2.4.3 Unguent.- 83 Drug administration techniques.- 8.3.1 Single shot technique.- 8.3.1.1 Epidural.- 8.3.1.2 Intrathecal.- 8.3.2 Catheter placement.- 8.3.3 Percutaneous catheter fixation.- 8.3.4 Subcutaneous tunneling.- 8.3.5 Port implantation.- 8.3.6 Pump implantation.- 8.3.6.1 Implantation technique for the Infusaid ® pump.- 8.3.6.2 Implantation technique for the Synchromed ® pump.- 8.3.7 Intracerebroventricular port implantation.- 8.3.8 Injection into a port, refill of a pump.- 8.3.9 Injection-infusion techniques.- 8.3.10 Pros and cons of continuous infusion.- 8.3.10.1 Advantages.- 8.3.10.2 Drawbacks.- 8.3.10.3 Drug selection for continuous infusion.- 8.4 Nursing.- 8.4.1 Catheter problems.- 8.4.2 Port problems.- 8.4.3 Pump problems.- II: Clinical Practice of Spinal Opioid Administration.- 9. Clinical applications, generalities.- 10. Intraoperative use.- 10.1 Epidural administration.- 10.1.1 Opioids in association with general anaesthesia.- 10.1.2 Epidural somatostatin.- 10.1.3. Epidural opioids in association with local anaesthetics.- 10.2 Intrathecal administration.- 10.2.1 Intrathecal morphine in association with thiopentone anaesthesia.- 10.2.2 Intrathecal pethidine for spinal anaesthesia in high doses (1 mg/kg).- 10.2.3 Intrathecal association of opioids with local anaesthetics.- 10.2.4 Intrathecal association of an opioid and clonidine.- 10.3 Particular problem: extracorporeal shock wave lithotripsy.- 11. Postoperative pain.- 11.1 Potential advantages and drawbacks.- 11.1.1 Better pain relief?.- 11.1.2 Improved pulmonary function?.- 11.1.3 Reduced side effects?.- 11.1.4 Better in selected groups of patients?.- 11.1.5 Superior to other analgesia methods?.- 11.1.6 Better clinical outcome?.- 11.2 Selection of patients.- 11.2.1 Spinal opioids in children.- 11.3 Selection of drugs and routes of administration.- 11.3.1 Morphine and methadone.- 11.3.2 Epidural lipophilic opioids.- 11.3.3 Associations of opioid and local anaesthetic.- 11.3.4 Non-opioid products.- 11.4 Selection of injection technique.- 11.4.1 Repeated bolus injection and patient controlled analgesia (PCA).- 11.4.2 Continuous infusion.- 11.4.3 Continuous plus on demand infusion.- 11.5 Selection of equipment: pumps and ports.- 11.6 Precautions and surveillance.- 11.7 Side effects.- 11.8 Indications and contra-indications for postoperative epidural opioid analgesia.- 11.9 Nursing.- 12. Other applications in acute pain situations.- 12.1 Posttraumatic pain.- 12.2 Intensive care unit patients.- 12.3 Myocardial infarction.- 12.4 Visceral pain after arterial embolisation.- 12.5 Acute pancreatitis.- 12.6 Headache following dural puncture.- 12.7 Diagnosis of pain aetiology.- 13. Obstetrics.- 13.1 Potential advantages, drawbacks and indications.- 13.1.1 Justification of better analgesia.- 13.1.2 Potential advantages.- 13.1.3 Potential disadvantages.- 13.1.4 Potential indications.- 13.2 Labour and delivery pain.- 13.2.1 Epidural opioids.- 13.2.1.1 Morphine.- 13.2.1.2 Pethidine.- 13.2.1.3 Fentanyl.- 13.2.1.4 Morphine + bupivacaine.- 13.2.1.5 Lipophilic opioid + local anaesthetic.- 13.2.2 Intrathecal opioids.- 13.2.2.1 Morphine.- 13.2.2.2 Beta-endorphin.- 13.2.2.3 Fentanyl + bupivacaine.- 13.2.2.4 Naloxone infusion for reduction of side effects.- 13.2.2.5 Naltrexone orally for reduction of side effects.- 13.2.3 Global evaluation.- 13.3 Postcaesarean section.- 13.3.1 Epidural opioids.- 13.3.1.1 Morphine.- 13.3.1.2 Methadone.- 13.3.1.3 Hydromorphone.- 13.3.1.4 Pethidine.- 13.3.1.5 Fentanyl.- 13.3.1.6 Sufentanil.- 13.3.1.7 Butorphanol.- 13.3.1.8 Meptazinol.- 13.3.1.9 Buprenorphine.- 13.3.1.10 Opioids associated with local anaesthetics.- 13.3.2 Intrathecal opioids.- 13.4 Side effects of spinal opioids in obstetrics.- 13.4.1 Maternal side effects.- 13.4.2 Foetal side effects.- 13.5 Post-partum episiotomy.- 13.6 Prostaglandin abortion.- 13.7 Pre-eclampsia.- 13.8 Precautions and surveillance.- 13.9 Survey of the principal clinical reports.- 14. Cancer pain.- 14.1 Analgesic ladder.- 14.2 Potential advantages.- 14.3 Selection of patients.- 14.4 Selection of drugs.- 14.4.1 Opioids.- 14.4.2 Associations of an opioid and a local anaesthetic.- 14.4.3 Associations of an opioid and another product.- 14.5 Administration modalities.- 14.5.1 Injection route: epidural or intrathecal?.- 14.5.2 Intrathecal isobaric or hyperbaric solution?.- 14.5.3 Repeated bolus or continuous plus on-demand infusion?.- 14.5.3.1 Percutaneous epidural catheter for bolus injection.- 14.5.3.2 Tunnelled epidural catheter.- 14.5.3.3 Tunnelled intrathecal catheter.- 14.5.3.4 External unidirectional valves.- 14.5.3.5 Implanted ports.- 14.5.4 Continuous plus on-demand infusion with pumps and ports.- 14.5.4.1 Portable infusion pump.- 14.5.4.2 Implanted infusion pump with epidural catheter.- 14.5.4.3 Implanted infusion pump with intrathecal catheter.- 14.6 Potential drawbacks of spinal opioid drugs.- 14.6.1 Side effects.- 14.6.2 Technical problems.- 14.6.2.1 Pain on epidural injection.- 14.6.2.2 Fibrous mass.- 14.6.2.3 Infection.- 14.6.2.4 Catheter dislodgement or occlusion.- 14.6.2.5 Port failure.- 14.6.2.6 Pump failure.- 14.6.3 Dose escalation and tolerance.- 14.7 Multicenter survey.- 14.7.1 Epidural administration.- 14.7.2 Intrathecal administration.- 14.8 Intracisternal opioids.- 14.9 Intracerebroventricular opioids.- 14.9.1 Indications and contra-indications.- 14.9.2 Technique.- 14.9.3 Effects.- 14.9.4 Reinjection and daily nursing.- 14.9.5 Side effects and complications.- 14.9.6 Results.- 14.10 Current care and nursing problems during regional opioid analgesia.- 15. Chronic non-malignant pain.- 15.1 Treatment with epidural opioids.- 15.2 Treatment with intrathecal opioids and/or non-opioid drugs.- 16. Perineural opioid analgesia (PNOA).- 17. Comparative evaluation of the risk/benefit ratio.- 17.1 Epidural opioid analgesia versus peroral, intravenous or intramuscular opioids.- 17.2 Epidural opioids versus intravenous patient controlled analgesia.- 17.3 Epidural opioids versus epidural anaesthesia with a local anaesthetic.- 17.4 Epidural opioid versus intrathecal opioid.- 17.5 Advantages and drawbacks of intrathecal opioid analgesia.- 17.6 Limits and contra-indications of regional opioid analgesia.- 18. Future directions in spinal opioid research and conclusions.- 19. What is regional opioid analgesia?.- 20. Technical data of equipment for spinal opioid therapy.- 20.1 Special needles.- 20.2 Epidural or intrathecal catheters.- 20.3 Filters.- 20.4 Extension tube for connection between pumps and ports and catheters.- 20.5 Implantable catheter access port.- 20.6 Infusion pumps.- 20.7 Monitoring devices.- Bibliography and references.- Addendum to the Bibliography and references.- Index of subjects.