Analgesic%20and%20anaesthetic%20drugs%20in%20Obstetrics%20and%20Gynaecology

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Analgesic and anaesthetic drugs in Obstetrics and
Gynaecology

• Sim-Daisy Amanor-Boadu
• Dept of Anaesthesia, COMUI,
• UI, Ibadan

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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

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Objectives

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

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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

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?Perioperative medicine

• Anaesthetic management commences from the
  preoperativegtgtgtgtintraoperativegtgtgtpostoperative
  period
• Management of each period usually entails use of
  specific agents e.g. antacids, anxiolytics,
  analgesics inhalational agents etc

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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

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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.

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Preoperative period BDZ

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

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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

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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

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Induction Agents

• Barbiturates
• Phenols
• Phencyclidines
• BDZ
• Opioids

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Induction agents

• 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 hrsgtgtgtgthang over effect
• Not analgesic
• Cumulative in repeated doses
• Cardio-respiratory depressant
• Dose 3.5- 5mg/kg bd wt
• Uses OG

• 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

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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

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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

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Phencyclidine

• Ketamine
• CNS Neuro protective??? ?ICP intense analgesia
• Hallucinations
• GIT NV
• Musculoskeletal Purposeless movements
• Roving eyes, nystagmus

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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)

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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

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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

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Morphine

• 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

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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

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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 gtgtgt delayed respiratory
  depression which may be seen as late as 6-12hrs
  post admin

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Complications of opioid Analgesics

• Sedation
• Respiratory depression
• Nausea and vomiting
• Constipation
• Pruritus
• Tolerance and dependence

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ComplicationsSedation

• 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

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ComplicationsSedation

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

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ComplicationsRespiratory 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 lt 10 and patient sedated observe more
  frequently and monitor oxygen saturation

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ComplicationsRespiratory Depression

• If RR 8 or lt 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

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Complications.Nausea Vomiting

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

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Complications.Nausea Vomiting

• Evidence based effectiveness of prophylactic
  anti-emetic on NV
• 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.

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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.

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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.

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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

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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

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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

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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

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Inhalational Agents

• Nitrous Oxide
• Entonox
• Labour analgesia
• ??? effective

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Inhalational Agents

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

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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

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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

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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