Peripartum Analgesia (Preston day 3) Flashcards
What is the IV dose for fentanyl in labour?
0.5-1 mcg/kg dosing repeated to max 4 mcg/kg
What is the Maximum safe local anesthetic doses with/without epinephrine for lidocaine 1% and bupivacaine 0.25%. ?
Lidocaine 4-5 mg/kg plain, 7 mg/kg with epi
Bupivicaine 175 mg plain or 335 mg with epi
What is the early labour morphine dose?
IM 5-15 mg
SC 5-10 mg (most common)
IV 2-5 mg
PO 15-60 mg
How are prostaglandins formed?
By arachidonic acid - that forms COX 1 and COX2
Which NSAIDs are in the proproinic acid category (4)?
ibuprofen, naproxen, diclofenac, ketoprofen
What are examples of prostaglandin inhibitors?
NSAIDS ex asprin and ibuprofen - COX 1 and COX 2
COX 2 inhibtors (just COX 2)
What does COX 1 do (2)?
Constitutional
* 1) Protects gastric mucosa
2) Aids in making platelets sticky
What does COX 2 do?
Inducible
* Recruit inflammatory cells
* Sensitize skin to pain receptors
Regulate hypothalamic temperature control
Why does NO work well for contraction pain?
Fast on, fast off - reaches height concentration level in 3 mins
What is nitrous oxide?
A weak inhalational anesthetic agent with very poor solubility (doesn’t distribute to all other tissues but builds to a good concentration in lungs and gets into blood and effects brain)
What is Entonox?
- 50:50 mixture of N2O used labour LAUGHING GAS
- Used by 35% birthers in Canada (higher where epidural not available)
- Very weak, maybe no benefit over air, but many ppl obtain relief (psychosocial benefit likely real - focus on breathing technique)
Breathing at start of contraction to maximize N2O [ ] at peak of contraction - avoid hyperventilation because it shifts maternal oxyhemoglobin dissociation curve to left and reduced fetal O2 uptake
What is MOA of NO?
CNS depressant thought to alter main perception through descending spinal cord pathway
How is NO used with labouring person?
Quick uptake - fast on fast off (poor lipid solubility and low potency) makes it good for contraction pain
What are the safety measures w/Nos in labour (6)?
- Scavenging system - exhale into device and sent outside (to prevent exposure to HCP in room)
- Demand valve (only flows when inhales)
- Regular maintenance
- Greenhouse gas (limit use in other contexts)
- Patient ONLY administered
- Mouthpiece better than mask
Benefits of NO (6)?
- Safe for fetus/neonate as poor lipid solubility therefore transfer low and onset of spontaneous respirations at birth quickly eliminates residual N2O (only goes lung->blood->brain->back again) [breathing gets rid of the NO]
- No effect on uterine tone
- Inexpensive
- Minimal toxicity, minimal cardiac depression
- No known effect on breastfeeding
i.e. relatively benign
Side effectes of NO?
- Side effects dizziness, nausea, sedation, hypoventilation (breath less often)
- Loss of consciousness from OD - rare but happens 0.4 % with the 50:50 mixture
Possible sedation with prior parental opioid use (morphine/fentanyl)
What are the sedatives (2)?
Benzodiazepines and Phenothiazines
What did ‘twilight sleep’ have?
Benzos and opioids :(
What are benzodiazepines?
- Most commonly used for sedation and anxiolysis (sedated but awake)
- Useful to reduce excessive anxiety peri-procedure:
- Anxiety is linked to increased pain
- Anxiety is linked to increased nausea/vomiting
What are possible effects of benzos on dyad?
May affect neonatal neurobehavioral scores if used regularly in pregnancy
- Pregnancy Class D:
- 1st trimester – cleft lip/palate (valium specifically)
3rd trimester – neonatal benzodiazpine withdrawal syndrome
- 1st trimester – cleft lip/palate (valium specifically)
What receptor does benzos act on?
indirect GABA A – enhance effects of GABA
What are the traits of benzos?
- Hepatic metabolism
- Highly protein bound
What are the effects of Benzodiazepines (7)?
- Sedation
- Hypnosis
- Anxiolysis
- Anti-convulsant
- Amnesia (bigger doses)
- Muscle relaxant
Co-analgesic
What are the side-effects of benzos (8)?
- Drowsiness
- Amnesia
- Depression
- Balance impairment
- Dependence
- Cognitive impairment
- Paradoxical reactions
Respiratory Depression (insignificant in healthy adult if sole agent; enhances respiratory depressant effects of co-administered opioid)
What are GABA (A) receptors (3)?
- GABA is the primary inhibitory neurotransmitter in the CNS
- GABA-receptor allows Cl- to cross into the cell, hyperpolarizing the membrane and inhibiting neural transmission
Benzodiazepines INCREASE frequency of channel opening - inhibits anxiety
What are 2 sedative drug that may be used in pregnancy?
Midazolam (rapid onset, short acting, potent but you can titrate to small doses, effective for elective cesarean and anxiety
Lorazepam (longer duration of action, sublingually, prolonged effects)
What are the general mechanisms of nausea and vomiting?
triggered centrally in the brain - the chemoreceptor trigger zone (CTZ)
**peripherally **- the GI tract
Vomiting controlled by the vomiting centre (VC)
What do the general mechanisms of nausea and vomiting suggest about management with drug classification?
- Multiple different drug classes interact with receptors in the CRTZ and VC
- Some drugs are better for nausea, others for vomiting
- Some drugs work well both as prophylaxis and treatment, others for only one action
- Nausea/vomiting during pregnancy, labour/delivery, postpartum is common and distressing
Try what is known to be the most efficacious drug first, and then go to the next one. If someone has a history of nausea and vomiting we use drugs to prevent nausea and vomiting
What should we use for nausea in peripartum?
1) Start ondansetron (acute)
2) If n/v is common - use dexamethasone ongoing/preventativley postpartum
3) Other options dimenhydrinate, metocloprmaide, prochlorperazine (not if bf)
Standard recs for n/v in pregnancy?
(1) prental vits 3 months before pregnancy
(2) B6 plus doyxlyamine (safe and effective)
(3) less evidence - ginger
Where are vomiting triggers (3)?
GI tract, Chemoreceptor Trigger Zone, Vomiting Centre
What is a drug from each major classification that is effective in preventing/treating nausea and vomiting peripartum (5-6)?
- 5-HT3 antagonists - best Ondansetron (used in Canada) Dolasetron
- NK1 blockers - best Aprepitant
- Corticosteroids - Dexamethasone
- Dopamine antagonists - metoclopramide
- Antihistamines/Anticholinergics - Dimenhydrinate (gravol)
(B6)
What should you know about Ondansetron?
Ondansetron doesn’t add additional risks for 1st trimester fetal malformations.
What should you know about Ondansetron?
Ondansetron doesn’t add additional risks for 1st trimester fetal malformations.
What are opioid antagonists (2) ?
Naloxone and flumazenil
Why are opioid antagonists used w pregnant people?
- 30% of women of reproductive age fill opioid prescriptions each year
- Antepartum maternal opioid use has increased by at least 5 times since 2000
Neonatal abstinence syndrome (NAS) or Neonatal Opioid Withdrawal Symptoms (NOWS) has at least doubled
What should you know if your client is using opioids?
- Referral to perinatal addiction specialist is needed
- Rooming in and breastfeeding are recommended
- Suboxone (buprenorphine/naloxone combination) has recently been approved for use during pregnancy
- Intrapartum analgesia IS an issue: please ensure anesthesia consultation occurs antepartum
- If operative birth is required, postpartum analgesia often challenging and requires a stay in a High Acuity Unit for 24-48h
What are the ‘adjuncts’ (3)?
- Non-opioid analgesics that may be used peripartum
Acetaminophen, NSAIDs, Tramadol
What is NSAID?
Non-steroidal Anti-inflammatory Drug, includes aspirin, ibuprofen, naproxen, diclofenac, indoclid, celecoxib
What do NSAIDs do (3)?
Analgesic, antipyretic (anti-fever), and anti-inflammatory agents
What is NSAIDs MOA?
They work by inhibiting cyclooxygenase enzymes, which prevents downstream synthesis of prostaglandins
Why are NSAIDs so good at blocking pain and inflammation?
They block Prostaglandin E2 - primary mediator of inflammation and activation/up regulation of nociceptors (COX 2 mechanism)
Unintended effects of inhibiting prostaglandins with NSAIDs?
- Prostaglandins make platelets sticky and protect the lining of your stomach therefore NSAIDs (COX 1 Mechanism)
Decrease platelet aggregation and increase gastric irritation
What does COX 1 and COX 2 do?
- Cox 1 - prostaglandins protect gastric mucosa and aid platelet aggregation
Cox 2 - Prostaglandin E 2 - inflammation and up regulation of pain
What are the properties of NSAIDs (5)?
- Well absorbed from GI tract with minimal 1st pass effect
- Small volumes of distribution: don’t saturate fat stores
- Do cross the blood-brain barrier
- Hepatic metabolism, predominantly CYP450
- All non-selective and COX-2 have ceiling effect – exceeding that dose only increases side-effects
Inhibition of COX-1 responsible for majority of drug toxicity
What are the chemical classifications of NSAIDs?
- Carboxylic acids - aspirin
- Acetic acids - indomethacin
* Propionic acids - ibuprofen, naproxen, diclofenac, ketoprofen most common
Pyyrolopyrrol - keyorolac
What is the most common class of NSAID used?
Propionic acids
What the most commonly uses in NSAIDs in parturient?
- NSAIDS used before 30-32 weeks to stop premature labour
- Considered safe in second trimester
Not teratogenic but associated with excess risk of miscarriage when used prior to 18 weeks
What are the doses of the commonly used in NSAIDS in parturient?
- Ibuprofen (Advil)
- Dose: 200-400 mg oral
- Onset: 30 mins
- Duration: 4-6 hours
- Maximum daily dose: 1600 mg
- Least GI irritant and less potent than naproxen
Naproxen (Aleve)
* Dose: 250 mg oral/500 mg rectal
* Onset: 45-60 mins
* Duration: 4-10 hours
* Maximum daily dose: 1500 mg
Longest elimination half life
What is COX 2 drug?
- Celecoxib - less GI and no platelet effects
For birther treated with low molecular weight heparin thromboprophylaxis post cesarean
What is acetaminophen?
TYLENOL Analgesic and antipyretic (fever) agent (neither OPIOID or NSAID)
What is acetaminophen’s MOA?
- Cyclo-oxygenase (COX)-3 (inhibits COX same as NSAIDS but a different enzyme)inhibition with central inhibition of PGE2 production (inflamation and pain)
Hepatic metabolism 90% to glucuronide and sulfate conjugates that are renally excreted
Acetaminophen’s side effects?
Fulminant hepatic necrosis (DEATH OF LIVER CELLS) if exceed maximum daily dose for several days if susceptible: alcohol, malnutrition, fasting, pre-eclampsia
Acetaminophen’s benefits (6)?
- Opioid sparing - you can reduce opioids administered by 10-20%
- Synergistic w opioids 1+1=3
- Additive effect with NSAIDs
- Better for somatic pain
- Good side-effect profile
Can effect smaller women more *standard doses don’t work
What is the commonly prescribed dose of acetaminophen?
- Dose: 975-1000 mg oral/ 975 mg rectal
- Dose every 4-6 hours
- Oral onset time: 30 mins
- Lasts for 3-4 hours for acute pain
Maximum 24 hour dose: 4000 mg or (for smaller ppl) 75 mg/kg
What is Tramadol?
- Atypical weak mu-receptor agonist that has GABA, serotonergic and noradrenergic receptor effects
- Potency 1/10th of morphine, onset 10 minutes IM, duration 2 hours, T½ 6 h
- Fetal: maternal concentration 0.97
- Prolonged T½ in neonate
- Hepatic metabolism: CYPD26 - therefore genetic hypermetabolizers
- Active metabolite: O-desmethyltramadol (not a clean drug)
- Better labour analgesia than meperidine, more nausea
- Only available in oral formulation in Canada, no data on safety for breastfeeding
Increasing use as alternative to codeine or more potent opioids for post-delivery pain
How is Tramadol different from NSAIDS and acetaminophen?
It has different receptors effects, it’s NOT an opioid but has some weak effects on mew receptors. It also effects the GABBA receptors. It attracts serotonergic effects, which can help with depression. Not a clean drug.
It’s weird?
What are commonly prescribed benzos?
Midazolam and Lorazepam
Dose and side effects of Midazolam?
IV 0.15 mcg/kg
Neoanatal hypotonia, potent amnestic, safe at elective c-sections
Loraxepam dose and side effects?
1-2 mg sublingual
Effective co-anlegesic early labour, but potent prolonged amnestic
Ondansetron dose and side effects?
IV 4 mg prophalaxis, 2-4 mg rx
Headache and palpitations
What is dose and side effects of dexamethasone?
4-8 mg IV
Fluid retention, hyperglycemia, sterioid psychosis
What is first line for n/v in pregnancy?
Diclectin - antihistimine doxylamine and b6
What is dose and side effects of diclectin?
10 mg doxylamine + 10 mg pyridoxine (B6)
Not intended to treat active nausea
2 tabs at night (1 tab in morning 1 tab mid-day) for 24 hour control
Drowsiness, irritability, insominia, urinary retention, dry mouth
