Analgesia in Obstetrics – Long journey of gyn&obs

TOG/SIP

Correct pain management in antenatal and postpartum period is vital as inadequate pain relief may lead to
- depression and anxiety
- impact on woman’s physical and psychological well-being & ability to provide child care

Reluctance of health practitioners to prescribe analgesia → leads to ↑ use of inappropriate over-the-counter medications
Codeine → used extensively for pain relief in antenatal and postnatal period
But since 2013 → codeine is contraindicated in breast feeding women

Types of analgesics used

Non-opioid: Paracetamol, Nonsteroidal anti-inﬂammatory drugs (NSAIDs)
Opioids: Codeine, Dihydrocodeine (DHC), Tramadol, Morphine

Analgesic Mechanism of Action — Non-opioids
Paracetamol	MOA→ not fully understood Selective cycloxygenase (COX)-inhibitor & prostaglandin synthetase inhibition Widely used as first line Excellent safety profile/ few drug interactions If taken orally → effect within 40 min If taken I.V→ effect within 5 min
NSAIDs	MOA→ inhibition of COX enzyme & prostaglandin synthetase inhibition

Analgesic Mechanism of Action — Opioids
Codeine	Natural opioid with low affinity for opioid receptors Poor analgesic properties in natural form CYP2D6→ main enzyme for codeine conversion into active form i.e morphine *-10%* Caucasians → poor metablisers Ultra rapid metaboliser phenotype → due to duplications of CYP2D6 gene Prevelance varies by ethnicity Ethopians 29% Spanish 10% Caucasians 3-6% Ultra rapid metabolisers→ may have upto 50% higher plasma concentrations of active metabolite than extensive metabolisers Risk of serious toxicity even at therapeutic doses
DHC	Similar analgesic activity to codeine Effect mainly due to parent compound DHC→ to dihyromorphine (DHM) by CYP2D6 Only little DHC changes to DHM→ uneffected by individuals metabolizing capacity
Tramadol	Effective in mild to moderate pain MOA→ both opioid & monoaminergic-mediated Metabolised to active O-desmethyl by CYP2D6 Side effects: respiratory depression, constipation & psychiatric disturbance (due to ↑ O-desmethyltramadol) > 10 % general population→ do not tolerate Schedule 3 Controlled Drug
Morphine	Used for moderate to severe pain Opioid receptor agonist Active in parent form Main effect→ binding to and activating opioid receptors in CNS Primary therapeutic actions → analgesia & sedation Peak plasma levels 15-20 min after parenteral 30-90 min after oral First pass metabolism by Cytochrome P450 Oral dose→ half as potent as I.M

Antenatal Analgesia

Prior to advice→ pain should be investigated to exclude serious cause
Consider → non-pharmacological interventions as first line
All medicines→ assesses for risk vs benefits

Antenatal Analgesia
	Before 30 wks	After 30 wks
Paracetamol	Analgesic of choice in pregnancy & breastfeeding Can be both prescribed plus available over-the counter Use in ANY trimester→ does not increase risk of major birth defects Beware→ over the counter cough/cold remedies have paracetamol→ could lead to overdose	Safe throughout pregnancy
NSAIDs	Conflicting evidence for relation of increased risk of first trimester miscarriage & NSAID FDA→ avoid NSAIDs where possible during pregnancy If needed→ use lowest effective dose for shortest possible duration	FDA→ avoid NSAIDs after 30 wks because it can cause Neonatal hypertension Premature closure of ductus arteriosus ↓ fetal renal blood flow ↓ using production → ↓ amniotic fluid volume
Opioids	Short-term treatment of moderate to severe pain if paracetamol not effective Only give after assessment & by medically-qualified practitioner or midwife Avoid indiscriminate use in pregnancy Morphine→ used extensively & licensed for use in pregnancy/postnatal period	If used around delivery time→ neonatal respiratory depression Long-term use→ neonatal withdrawl symptoms & maternal dependence Use lowest effective dose for shortest possible time May exacerbate→ constipation, nausea & vomiting Risk must be weighed against severity of pain Admitted acutely to antenatal ward + severe pain + need additional analgesia→ may consider oral / I.M morphine
Gabapentin	Used in treatment of chronic pain syndromes especially neuropathic pain MOA→ poorly understood Limited evidence→ but no link with particular birth defect or increased miscarriage risk Recommended → to take high dose folic acid pre-conceptually & in 1st trimester	Very limited evidence If used around delivery time→ extra monitoring in neonatal period/ inform neonatology team

Postnatal Analgesia

Regular postnatal analgesia is important
Inadequate pain relief
- Less mobile→ ↑ VTE risk
- Shallow breathing → prone to develop pneumonia
- Impact negatively breastfeeding ability/ childcare→ depression or mental exhaustion

Unit should adopt uniform policy for postnatal analgesia, regardless of breastfeeding status (it avoids confusion for prescribing clinicians)
Mainstay of postnatal analgesia → paracetamol + NSAIDs (if not contraindicated)
Advice about Non pharmacological methods→ hold/cold compression and comfortable sitting and lying positions

Overall recommendations regarding DHC & tramdol

DHC & Tramdol→ considered in breastfeeding instead of codeine
Lowest effective doe for the shortest duration
If used >3 days → must be under close medical supervision
If needed stronger analgesia → DHC used in preference to codeine
All breastfeeding mothers (regardless of ethnicity)→ informed of potential problem and when to seek help

On discharge from hospital

Majority→ paracetamol and ibuprofen(if no contraindications)
If needed additional analgesia → discharge with limited supply of DHC (max 4 doses per day).
If intolerant to DHC→ may consider tramadol

Postnatal Analgesia
Paracetamol	Analgesia of choice for breastfeeding Very small quantity passes in milk
NSAIDs	Very limited information for use in breastfeeding Ibuprofen & diclofenac are preferred choice out of two Ibuprofen is favored NSAIDs may exacerbate asthma : 10% of patients with asthma May adversely affect renal function/ platelet function/ cause / cause gastric irritation/ulcer Contraindicated (dicolfenac and ibuprofen) → in those with known hypersensitivity Avoid in If significant Haemorrhage, hypovolemia and/or risk of ongoing haemorrhage Impaired renal function or PET Severe asthma Asthma known to be exacerbated by NSAIDs (including aspirin) H/O gastric ulcers
Opioids	Use → If more severe pain plus need for additional analgesia e.g after C/S or rotational forceps delivery Codeine Contraindicated in breastfeeding by MHRA & EMA Ultra rapid metabolisers → may have life-threatening or fatal respiratory depression or signs of over dose Adverse effects on infants bradycardia, respiratory depression, lethargy, drowsiness, poor feeding, cyanosis and infant death Reason for accumulation of potential toxic doses in breastfeeding mother → combination of maternal genotype, neonatal clearance capacity, repeated doses of codeine for > 4 days
DHC	Use lower effective dose for shortest duration All breastfed infants→ monitored regardless of maternal dose If significant adverse effects→ possibility of mother being ultra rapid metaboliser→ risks to infant ↑
Tramadol	Very limited data Tramadol & its metabolites found in breast milk even after a single dose Exclusively breastfed would receive maternal weight-adjusted doses (2% of tramadol & 0.6% of its metabolite) Current advice: can use tramadol (with caution) in breastfeeding Lowest effective dose for the shortest possible time
Morphine	In hospital → oral solution as required (e.g 10-20 mg/hr) I.M → prescribed if needed e.g if patient vomiting Clear documentation Do not give morphine by different routes simultaneously If intolerant of morphine→ consider tramdol (oral/ I.M) or DHC (oral)