Analgesic and anaesthetic drugs in Obstetrics and Gynaecology

1. Analgesic and anaesthetic drugs in Obstetrics and Gynaecology Sim-Daisy Amanor-Boadu Dept of Anaesthesia, COMUI, UI, Ibadan

2. Introduction • Ketamine anaesthesia more rampant in the developing world than orthodoxy anaesthetic techniques • Dearth of anaesthetists persists • Good knowledge of anaesthetic agents essential in planning of any HC establishment • Anaesthetic and analgesic agents??????????? • Important to know the consequences of the use of classes of anaesthetic drugs

3. Objectives • We shall learn the basic pharmacology and the clinical applications of anaesthetic and analgesic agents

4. Defining Anaesthesia • Anaesthesia- no feeling • Essentially a drug based speciality • Monotherapy with ether now polypharmacy of balanced anaesthesia • GA or LA or Combined • Balanced anaesthesia comprises Hypnosis, analgesia and muscle relaxation • LA aka regional anaesthesia

5. ?Perioperative medicine • Anaesthetic management commences from the preoperative>>>>intraoperative>>>postoperative period • Management of each period usually entails use of specific agents e.g. antacids, anxiolytics, analgesics; inhalational agents etc

6. Preoperative period • The pharmacologic management of this period has changed over the years in line with advances in surgical and anaesthetic techniques. Ambulatory surgery and endoscopic technique are increasingly employed. • Traditionally the premed: -Anxiolysis -Anticholinergic -Concurrent medication -Antacids Trends in the surgical management will dictate avoidance of agents with long lasting effects

7. Preoperative period • Anxiolytics: BDZ, barbiturates, opioids BDZ: Midazolam or Lorazepam Barbiturates not favoured and Opioids only when patient is in pain or has a cardiac condition BDZ act by stimulating the GABA receptors, improving chloride transmission thro the channels and thus hyperpolarising the membrane.

8. Preoperative period: BDZ • Use in Gynae and non- delivery obstetrics. • Obstetric use might lead to floppy baby • Regardless Diazepam useful in PIH.

9. Preoperative period • Routine use of atropine and its congeners no longer part of the premed. • Antacids: Imperative in Obstetric surgery -H2 receptor blocker ranitidine -Proton pump inhibitors -Gastrokinetic agents metoclopramide Indication: “full stomach” states viz pregnancy, emergencies, hiatus hernia, obesity, raised intra abdominal pressure

10. Preoperative period: Drugs for concurrent illnesses • Hypertensive agents, bronchodilators, steroids should be continued to the morning of the surgery. • ACE inhibitors are associated with intraoperative hypotension

11. Induction Agents • Barbiturates • Phenols • Phencyclidines • BDZ • Opioids

12. Barbiturates Thiopentone Gaba agonist Hypnotic, anticonvulsant, reduces ICP ? Ultra short acting Prolonged action ½ life 5-10 hrs up to 30% in body after 24 hrs>>>>hang over effect Not analgesic Cumulative in repeated doses Cardio-respiratory depressant Dose: 3.5- 5mg/kg bd wt Uses O&G Phenol Propofol ??Popular LMA + Propofol for Ambulatory surgery white emulsion 10% Soya bean oil 1.2 % egg phosphatide 2.25% glycerol. Characteristics similar to thio but short acting Elimination half life = 1-5 hrs Bradycardia CVS, Resp, CNS similar to thio Dose “-2.5 mg/ kg body wt Sweet dreams Not commonly used in ObS due to short action which may promote awareness Used for Induction and TIVA Induction agents

13. Phencyclidine • Ketamine -Much favoured in the developing world -Total anaesthetic with hypnotic and potent analgesic properties -Dissociative anaesthesia -Half life about 3 hours, metabolised in the liver to norketamine which is weakly active -Can be given by all routes -Useful for TIVA in areas with limited facilities

14. Phencyclidine • Ketamine CVS: Stimulates ↑HR, ↑BP, ↑Cardiac Work by release of catecholamine RS: Favourable unless drug given too rapidly respiration is maintained. Bronchodilatation + ↑secretions. Pharyngeal reflexes held to be intact but aspiration can still occur. Laryngospasm can occur in children

15. Phencyclidine • Ketamine CNS: Neuro protective??? ↑ICP intense analgesia Hallucinations GIT: N&V Musculoskeletal: Purposeless movements Roving eyes, nystagmus

16. Ketamine • Indications: Analgesia and anaesthesia • Contraindications: Hypertensive disease, CAD, Psychiatric diseases, Allergies • Dose: 1-2 mg/kg IV, 5-10mg/kg IM, SC Oral • Prevention of Hallucinations with Diazepam and other hypnotic or amnesic agents • Recommended by WHO for C/S in regions with limited facilities (check the website)

17. Opioids • Very essential to medical practice but often erratically supplied in the institutions. • Morphine, meperidine (pethidine), Codeine, fentanyl, Sufentanil, alfentanil. • Oral morphine is the third step of the WHO Analgesic Ladder for pain management in terminally ill patients • Cervical cancer is the second most common cancer in women • Opioids are agonists at opioid receptors and thus prevent pain transmission

18. Morphine • This is the prototype and is most commonly used in the developed world • The drug against which other agents are compared • Naturally occurring in Poppy seeds and has been in use for more than 5 millenia • It is potent analgesic and sedative (peace pipe) • Has many effects on the systems • IV IM SC ORAL RECTAL EPIDURAL INTRASPINAL etc routes are all possible

19. CNS: Central depression, respi, sedating, analgesia, -Miosis, nausea and vomiting, muscle rigidity, suppresses cough reflex. -Dependence tolerance and addiction -Histamine release CVS well maintained unless histamine release profound -Increased tone of biliary and GUT systems -Lowers the LOS pressure Constipation Dose 0.1-0.15 mg/kg bd wt by the parenteral routes Epidural dose is 1/10th Sub arachnoid dose is 1/10th epidural dose Thus 0.1mg of morphine in the CSF is associated with significant analgesia Contraindications: allergies, asthma, Coma Side effects: As follows Morphine

20. Opioids • Meperidine -Favoured in obstetric analgesia -Synthetic, metabolised in the liver to norpethidine excreted by the kidneys. In renal dysfunction Norpethidine cumulates and provokes convulsions. Duration of action 2-4 hrs; ½ life 3-4h Dose 1mg/kg body wt

21. Neuraxial opioids • LA+ opioids for analgesia • Synergistic action • Highly lipid bound opioids advised e.g.fentanyl, alfentanil as the drug remains relatively confined to the lower spinal area • Cephalad migration of the poorly lipid bound opioid e.g. morphine >>> delayed respiratory depression which may be seen as late as 6-12hrs post admin

22. Complications of opioid Analgesics • Sedation • Respiratory depression • Nausea and vomiting • Constipation • Pruritus • Tolerance and dependence

23. Complications…Sedation • Opioids centrally acting thus sedative effect • Sedation and respiratory depression frequently occur together • Codeine and mixed agonists such as pentazocine are not as sedative as pure agonists • Sedation may be due to overt or relative overdosage • Sedation worse with other depressants • In disease states such as hepato renal disease metabolic dx and cerebral mets

24. Complications…Sedation • How deep is deep? • Consequences • Management -Observe -Withhold -Reverse with Naloxone -Adjust further doses - OR Change to another formulation

25. Complications…Respiratory Depression • Most feared of the complications • Consequences are hypoxia and carbon dioxide retention • Patient may suffer apnoea • Clinically respiratory rate and oxygen saturation • Oxygen saturation more indicative of the degree of depression than RR • If RR < 10 and patient sedated observe more frequently and monitor oxygen saturation

26. Complications…Respiratory Depression • If RR 8 or < emergency -Continue oxygen - Reverse with naloxone -Dose 200-400mcg in the adult -Naloxone reverses analgesia -Titrate naloxone just to relieve -Consider other analgesic options • If patient apnoeic support respiration i.e. IPPV

27. Complications….Nausea & Vomiting • Common in the acute setting and the opioid naive especially with ambulation. • 15-70% of patients on opioids have N&V. • Opioids stimulate the vomiting centre • Is it less common in blacks (Nigerians) • Other causes of vomiting: -anaesthetic agents, pathologic states, metabolic dx, cancer care

28. Complications….Nausea & Vomiting • Evidence based effectiveness of prophylactic anti-emetic on N&V • Commonly used anti-emetics are: • Drug Adult Dose Dexamethasone 4-8mg q8h Phenothiazines (promethazine) 25mg q12h Butyrophenones (droperidol) 0.5 mg q8h Metoclopramide 10mg q8h Ondansetrone 4-8mg q12h • 5HT3 receptor antagonists e.g. Ondansetrone are very effective and have fewer side effects but they are more expensive. • Ondansetrone lack the sedation of phenothiazines, dyskinesia of metoclopramide and the gastric erosion of dexamethasone.

29. Complications….Pruritus • The itch on the tip of the nose • Minor effect with the oral transmucosal and transdermal routes • Occurs in more than 50% of patients on Neuraxial opioids and can be distressing for some of them. • Exact cause unknown but may be histamine release • Responds to antihistamine and naloxone.

30. Complications….Constipation • Occurs in 40-70% of patients on opioids. • More common with agents taken orally e.g codeine and oral morphine. • Constipation not a serious problem in the acute short term use of opioid such as in postoperative pain or trauma care but in chronic therapy in cancer care it is worrisome. • Treatment is with faecal softeners such as Dulcolax or lactulose.

31. Complications….Others • Confusional states • Slow mentation • Muscle spasms Common in long term use and have to balance between analgesia and side effects May be reduced with opioid rotation or the use of another route such as epidural analgesia

32. Muscle relaxants • These are agents that reversibly block NMT • Depolarising and competitive • Depolarising Suxa, pride of place in rapid induction (C/S, emergencies, full stomach) • Succinyl choline therefore cholinergic actions -Muscle fasciculation, bradycardia, histamine release, salivation. Causes release of potassium which is marked in denervation states, after burn injury, and in renal failure. Metabolised by plasma cholinesterase Dose; 1-1.5 mg/kg bd wt

33. Non depolarising relaxants • Prototype: Tubocurarine • Many others since including pancuronium, vecuronium, and atracurium. • Recent: Rocuronium and Cis-atracurium • Obsolete: Fazadinium, gallamine • Compete with Acetyl choline for the receptor site at the post junctional membrane and thus block NMtransmission

34. Muscle relaxants • Atracurium: peculiar drug that is metabolised by Hoffman degradation which is independent of the hepatic and renal systems. • Dose 0.3-0.6 mg/kg, • Onset 2-3 minutes compared with suxamethonium which is 20-30 secs • Duration of action 20 minutes better recovery profile • Histamine release, thus hypotension • Isomer Cisatracurium devoid of [H] release • Useful for day cases who need controlled ventilation

35. Inhalational Agents • Nitrous Oxide • Entonox • Labour analgesia • ??? effective

36. Inhalational Agents • Halothane: arrhythmogenic • Enflurane • Isoflurane: Less uterine muscle relaxation • They deepen anaesthesia and thereby prevent awareness during C/S.

37. Local Anaesthetic agents • Definition: Agents that reversibly block neuronal transmission • Lidocaine and bupivacaine • Both are amides • Lidocaine is the agent against which all other agents are compared • It is rapid acting by all routes 5 minutes c/f 15 bupivacaine • Duration is short 1 hour for local infiltration without adrenaline extra 30 minutes if + adrenaline

38. LALidocaine • Lidocaine has been used for all types of local techniques and include treatment of arrhythmias • Dose with adr 5-7 mg/kg bd wt ( avoid such preparation in areas with end arteries e.g. digits penis) • Plain lidocaine dose 3mg/kg bd wt for non neuraxial anaesthesia • Read up on toxicity of LA and the management

39. LABupivacaine • Prolonged analgesia • Useful for epidural analgesia in labour • Duration of action precludes the addition of adrenaline unless for surgical vasoconstriction • Toxic effects on the heart severe with the development of arrhythmias that are difficult to treat • Strict adherence to prevention of inadvertent intravascular injection • Levo bupivacaine safer • Dose 2mg/kg bd wt