Antibiotic Stewardship

Definition and Goals

1. Optimize clinical outcomes - cure infection, minimize toxicity and adverse events
2. Preserve antimicrobials - curb the development of resistance within patient populations by limiting selection pressure that drives resistant strains
3. Reduce harm - decrease adverse effects such as C. difficile infection, drug toxicity, and drug-drug interactions
4. Control costs - reduce hospital antimicrobial expenditure and length of stay

• Harrison's Principles of Internal Medicine 22E, p. 1222; Goldman-Cecil Medicine, p. 261

The CDC Core Elements Framework

For Hospitals (7 Core Elements)

For Outpatient Settings (4 Core Elements, CDC 2016)

1. Commitment to improving antibiotic prescribing
2. Action - implement at least one policy/practice to improve prescribing and assess its effectiveness
3. Tracking and Reporting - monitor prescribing and feed data back to clinicians
4. Education and Expertise - provide clinician education and access to stewardship experts

• Red Book 2021 (AAP), p. 1328; CDC Core Elements

Key Stewardship Strategies

1. Prospective Audit with Feedback

2. Formulary Restriction and Preauthorization

• Formulary restriction: limits indiscriminate use of selected antimicrobials absent demonstrated benefit; controls costs
• Preauthorization: clinicians must obtain approval before using certain agents (broad-spectrum, highly toxic, or expensive drugs). This is one of the most commonly used and most effective strategies.

3. De-escalation

• Selects the narrowest effective agent based on susceptibility data and PK/PD properties
• Is guided by inflammatory biomarkers - procalcitonin (PCT) has been validated in randomized trials and meta-analyses as an effective adjunct for safe de-escalation, reducing antibiotic days without adverse effects on mortality
• Has been shown safe and may improve survival outcomes in sepsis and VAP
• Murray & Nadel's Respiratory Medicine, p. 1133; Fishman's Pulmonary Diseases, p. 3159

4. Duration Optimization

5. IV-to-Oral (IV-to-PO) Conversion

6. Clinical Decision Support (CDS)

7. Education and Communication Training

• Making a clear diagnosis and communicating it to the patient
• Focusing on positive actions patients can take to feel better
• Reviewing the expected course of illness
• Describing red-flag symptoms warranting return to care

Ambulatory Antibiotic Stewardship

• Peer comparison - showing clinicians their prescribing rates vs. peers
• Accountable justification - requiring prescribers to document reasoning for antibiotic use
• Precommitment - asking clinicians to commit in advance to evidence-based prescribing
• Patient education materials explaining when antibiotics are and are not needed
• Telemedicine (phone, video, or electronic messaging) - potential to improve convenience and reduce inappropriate prescribing

• Delayed prescribing (giving a prescription and asking patients not to fill it unless symptoms don't improve) is conceptually flawed, ignores the natural history of self-limited respiratory infections (5-14 days), shifts clinical decision-making to patients, and sends a mixed message about antibiotic appropriateness.
• Procalcitonin and CRP testing remain unproven or non-durable for outpatient antibiotic reduction.
• Harrison's Principles of Internal Medicine 22E, p. 296

Choosing Wisely: AAP/PIDS Recommendations

1. Always obtain blood, urine, or appropriate cultures before initiating empiric antibiotic therapy for suspected invasive bacterial infection (except in exceptional cases)
2. Do not use broad-spectrum agents for perioperative prophylaxis, and do not continue prophylaxis after incision closure for clean/clean-contaminated procedures
3. Do not treat uncomplicated CAP in otherwise healthy, immunized hospitalized patients with therapy broader than ampicillin
4. Avoid treating asymptomatic bacteriuria (except in pregnancy or pre-urologic procedure)
5. Do not use antibiotics for uncomplicated acute otitis media in children ≥2 years with mild disease

• Red Book 2021, p. 1329

Outcomes of Stewardship Programs

• Significant reductions in total antimicrobial use
• Reduced rates of antimicrobial resistance among healthcare-associated pathogens
• Reduced C. difficile infection incidence
• Improved clinical outcomes
• Significant cost savings in hospital antimicrobial expenditure

Recent Developments (2025-2026)

• AI-driven stewardship: A 2025 systematic review (PMID: 39955846) examined artificial intelligence approaches in antibiotic stewardship programs, showing promise for optimizing prescription practices through decision support algorithms.
• CDC 2026 Outpatient Core Elements Update: The CDC is updating outpatient Core Elements in 2026 to focus specifically on the role of health system leadership in supporting and expanding outpatient ASP programs across networks, standardizing implementation for more consistent quality of care. (CDC 2025 Stewardship Report)
• Dental stewardship: A 2025 systematic review (PMID: 39400429) specifically examined dental antibiotic stewardship interventions, reflecting the growing recognition that dentistry is a major contributor to outpatient antibiotic use.

Stewardship Team Composition

• Infectious disease physician (program leader)
• Clinical pharmacist with ID training (co-leader)
• Clinical microbiologist
• Hospital epidemiologist / infection preventionist
• Information systems / informatics specialist

Opioid-Free Anaesthesia (OFA)

Based on Miller's Anesthesia, 10th Edition (2-Volume Set)

1. Concept and Rationale

• The opioid crisis and risks of prescription opioid misuse and dependence
• Postoperative nausea and vomiting (PONV) - a major cause of unplanned hospital admission after ambulatory surgery
• Opioid-induced hyperalgesia (OIH) - paradoxical increased pain sensitivity with opioid use
• Respiratory depression - particularly dangerous in obese patients, OSA, elderly
• Postoperative delirium and neurocognitive dysfunction
• Immunosuppression - opioids may suppress natural killer cell activity and affect cancer recurrence

• Obese patients and those with obstructive sleep apnea (OSA)
• Patients at high risk for PONV
• Patients with chronic pain or opioid use disorder
• Patients undergoing ambulatory/day-case surgery
• Bariatric surgery

"OFA seems not to be the solution but, by using a multimodal pharmacologic and technical approach, the anesthesiologist can still make important contributions to ameliorate the prescription opioid crisis."

• Miller's Anesthesia 10e, p. 6868

2. The Multimodal Analgesic Foundation

"Multimodal analgesia relies on the additive or synergistic combination of drugs acting at various points on the pain pathway. Typical combinations include local anesthetic wound infiltration or regional techniques and routine NSAIDs."

• Miller's Anesthesia 10e, p. 10023

3. Pharmacological Pillars of OFA

A. Ketamine (NMDA Receptor Antagonist)

• Antagonises the NMDA (N-methyl-D-aspartate) receptor - the excitatory glutamatergic receptor central to central sensitisation and hyperalgesia
• Inhibits nociceptive central hypersensitisation
• Reduces the release of pronociceptive transmitters from the dorsal horn
• Also occupies mu-opioid receptors in brain and spinal cord - contributing to some of its analgesic effect
• Has antidepressant properties

• Plasma level ≥0.1 mcg/mL elevates pain thresholds (subanesthetic analgesic dose)
• Short duration due to rapid redistribution from brain to tissues
• Prevents opioid-induced hyperalgesia (OIH) - the NMDA receptor mediates both hyperalgesia and antinociceptive tolerance induced by opioids; preventive ketamine blocks this
• S(+) enantiomer (esketamine) offers 10% faster hepatic biotransformation and quicker recovery

• Low-dose boluses (0.1-0.5 mg/kg IV) intraoperatively
• Infusion continued postoperatively: common postoperative infusion doses are 0.1-0.2 mg/kg/hr
• Analgesic, opioid-sparing, and antidepressant effects
• Does NOT cause or prevent postoperative delirium (large multicenter trial)
• Particular value in thoracotomy - used as part of multimodal therapy combining regional analgesia and anti-inflammatories

B. Dexmedetomidine (Selective α2-Agonist)

• Highly selective α2A/α2C-adrenoceptor agonist (α2:α1 selectivity ratio 1620:1 vs. clonidine's 220:1)
• Analgesic mechanism: Stimulates α2C- and α2A-receptors in the dorsal horn, directly suppressing pain transmission by:
  • Reducing release of substance P and glutamate
  • Hyperpolarising inhibitory interneurons
• Sedation mechanism: Activates locus coeruleus → releases inhibition of VLPO → VLPO releases GABA onto TMN → inhibits histamine release → induces NREM-like sleep
• Provides sedation without significant respiratory depression (key advantage)

• Systemic infusion provides significant opioid-sparing effect intraoperatively and postoperatively
• In the ICU/postoperative setting: reduces narcotic requirements by ~50% compared with placebo
• When used as part of an anaesthetic regimen: reduces MAC of inhaled anaesthetics
• Useful in OSA patients - minimal effects on pharyngeal tone unlike opioids and benzodiazepines
• Also used as adjuvant to regional blocks: prolongs sensory block duration (e.g., 1 mcg/kg added to bupivacaine) by prolonged hyperpolarisation of unmyelinated C-fibres

C. NSAIDs and COX-2 Inhibitors

• Non-selective NSAIDs (naproxen, ibuprofen, diclofenac, ketorolac): inhibit both COX-1 and COX-2
• Selective COX-2 inhibitors (celecoxib): spare platelet COX-1, lower GI bleeding risk
• Can be given orally, rectally, intramuscularly, or intravenously
• IV diclofenac and ketorolac: well-evidenced for acute postoperative pain

D. Paracetamol (Acetaminophen)

• Often underestimated - has equivalent and sustained analgesic effects compared with other perioperative analgesics
• Routes: oral, rectal, or IV
• Opioid-sparing effect is inconsistent in the literature - some RCTs and meta-analyses show reduction in opioid consumption; others do not
• Given its high safety profile, its use as a routine analgesic adjuvant is considered reasonable
• Best given preoperatively or at the start of surgery for preemptive effect

E. IV Lidocaine Infusion (Systemic Local Anaesthetic)

• Reduces postoperative pain, opioid consumption, and accelerates return of bowel function (particularly in abdominal surgery)
• Typical dose: 1.5 mg/kg bolus → 1.5-2 mg/kg/hr infusion intraoperatively
• Can be continued into the postoperative period

F. Dexamethasone

• Used in higher doses than antiemetic doses as part of multimodal analgesia
• Onset of action: 1-2 hours → administer BEFORE surgical trauma
• Meta-analyses show: less postoperative pain, fewer opioids required, shorter PACU stays
• Most effective at intermediate doses (6.4-10 mg IV); given preoperatively
• A large RCT confirmed 8 mg intraoperative dexamethasone does NOT increase surgical site infection rates

G. Gabapentinoids (Gabapentin, Pregabalin)

• Initially anticonvulsants, gained popularity for acute perioperative pain
• However, routine use is NOT justified per current evidence:
  • No clinically significant difference in acute or chronic postoperative pain at multiple time points
  • Lower PONV risk (benefit)
  • BUT: increased length of stay, increased dizziness and visual disturbance
  • Risk of neurological and respiratory adverse reactions, especially in ambulatory patients where they delay discharge

4. Regional and Neuraxial Techniques

• Neuraxial analgesia (epidural, spinal): local anaesthetic-based regimen; intrathecal local anaesthetics provide potent, long-lasting analgesia at subanesthetic doses
• Peripheral nerve blocks: brachial plexus, femoral, sciatic, TAP blocks, paravertebral blocks
• Local infiltration analgesia (LIA): wound infiltration with local anaesthetic
• Topical local anaesthetics: lidocaine patches and glyceryl trinitrate patches have been found effective for some ambulatory procedures

5. OFA vs. Opioid-Sparing Anaesthesia (OSA)

6. Limitations and Cautions of OFA

• Haemodynamic instability: Studies on OFA showed increased demand for vasopressors, hypotensive and bradycardic phases
• Postoperative sedation and falls reported
• Safety concerns: A large proof-of-concept study had to be terminated prematurely due to high incidences of hypoxia and bradycardia
• OFA is not universally applicable - patients with severe uncontrolled pain, those on chronic opioids, and those with opioid use disorder still require individualised management
• Chronic pain patients on long-term opioids must have their preoperative analgesics continued to prevent withdrawal
• The "delayed prescription" strategy (give a prescription but ask the patient not to fill it) is conceptually flawed and should be avoided

7. Special Populations Where OFA is Particularly Valuable

Obese Patients and OSA

• Avoiding respiratory depressants (opioids, benzodiazepines) is paramount
• Full OFA/opioid-sparing with NSAIDs, ketamine, dexmedetomidine, clonidine, epidural LA, peripheral nerve blocks minimises postoperative respiratory arrest risk
• Benzodiazepines actually have a greater effect on pharyngeal tone than opioids and should be avoided in OSA patients

Bariatric Surgery

• High PONV risk
• Respiratory vulnerability due to morbid obesity
• 2025 RCT (PMID: 40269993) confirmed OFA feasibility and benefits in bariatric surgery

Elderly/Cognitive Impairment

• Opioids (especially meperidine and normeperidine), benzodiazepines, and gabapentinoids are associated with delirium
• Ketamine, acetaminophen, NSAIDs, and COX-2 inhibitors may reduce postoperative cognitive dysfunction through opioid-sparing effects
• Processed EEG (bispectral index) guides titration of inhalational agents to age-adjusted MAC

8. Practical OFA Protocol (Miller's Synthesis)

9. Recent Evidence (2023-2025)

• A 2023 systematic review and meta-analysis (PMID: 37515877, J Clin Anesth) on OFA: reduced PONV, but with trade-offs including haemodynamic effects - consistent with Miller's cautionary statements
• A 2025 network meta-analysis (PMID: 38578868, Anesth Analg) in bariatric surgery: OFA superior to conventional analgesia for PONV prevention; opioid-sparing and OFA had comparable analgesic outcomes
• A 2025 RCT in bariatric surgery (PMID: 40269993): OFA was safe and effective, with better PONV profile

Key Take-Home Messages from Miller's

1. OFA is not "the solution" - it is part of a broader multimodal strategy, not a universal replacement for opioids
2. The evidence base is still evolving - some well-designed trials have been terminated early due to haemodynamic complications
3. Dexmedetomidine is the cornerstone α2-agonist - provides sedation without respiratory compromise, reduces MAC, and cuts opioid requirements by ~50%
4. Ketamine is essential - its NMDA antagonism directly blocks central sensitisation and prevents OIH
5. Regional techniques are non-negotiable - OFA without reliable regional anaesthesia is not safe for most surgical procedures
6. Patient selection matters - OFA is particularly valuable in OSA, bariatric, ambulatory, and high-PONV-risk patients

Tumescent Anaesthesia

From Miller's Anesthesia, 10th Edition (2-Volume Set)

1. Definition and Overview

"An additional method of local anesthetic injection, tumescent anesthesia, is included because it is widely used in office-based plastic surgery."

• Miller's Anesthesia 10e, Chapter 25, p. 3589

2. Tumescent Solution Composition

3. The Critical Pharmacological Principle: Why Such High Doses Are Safe

Standard Maximum Dose of Lidocaine (Conventional Teaching):

• Without epinephrine: 3-4 mg/kg
• With epinephrine: 7 mg/kg

Tumescent Lidocaine Dose:

• Up to 45 mg/kg have been reported to produce safe plasma concentrations (around or below 5 μg/mL)

A. The Role of Epinephrine - Slowing Systemic Absorption

"Vasoconstrictors, usually epinephrine, are frequently included in local anesthetic solutions to decrease the rate of vascular absorption, thereby allowing more anesthetic molecules to reach the nerve membrane and thus improve the depth and duration of anesthesia."

• Miller's Anesthesia 10e, p. 3583

• Dramatically slows absorption of lidocaine into the systemic circulation
• Reduces bleeding to near zero (nearly bloodless field)
• Extends duration of anaesthesia

B. Slow, Sustained Release from Fat

• Subcutaneous fat is poorly vascularised
• Lidocaine distributes into fat and is released very slowly
• This creates a depot effect - the drug trickles into circulation over many hours

C. The Delayed Peak Plasma Concentration

"...total doses of lidocaine up to 45 mg/kg have been reported to produce safe plasma concentrations around or below 5 μg/mL, but notably, these may only peak up to 20 hours after infusion, depending on the site of infiltration."

• Miller's Anesthesia 10e, p. 3598

4. Mechanisms of Action and Benefits

5. Technique - How It Is Performed

1. Solution preparation: Dissolve 500-1000 mg lidocaine + 1 mg epinephrine (+ NaHCO₃ ± triamcinolone) in 1 litre normal saline
2. Infusion pump: A peristaltic pump (tumescent pump) delivers the solution through a blunt multi-hole infusion cannula
3. Subcutaneous injection: Solution is infiltrated throughout the subcutaneous fat compartment of the planned liposuction area
4. Wait period: A minimum wait of 15-30 minutes (often longer) is recommended after infiltration before commencing liposuction - to allow full vasoconstriction and anaesthetic penetration
5. Liposuction: Standard suction-assisted or power-assisted lipectomy proceeds in a nearly bloodless field

Settings Where It Is Used:

• Purely tumescent technique: Procedure performed under tumescent anaesthesia alone, with patient awake or minimally sedated
• Combined with IV sedation / general anaesthesia: Tumescent fluid provides local anaesthesia and haemostasis; systemic anaesthesia provides unconsciousness and anxiolysis
• Burn surgery: Tumescent local anaesthesia is injected into donor skin harvest sites to provide analgesia and reduce blood loss

6. Safety Profile

Published Evidence:

"Despite these seemingly huge doses, very good safety outcomes have been reported in several case series."

Fatal Outcomes:

"Conversely, there have been several case series of cardiac arrest and death during plastic surgical procedures in patients with multiple risk factors. Here high local anesthetic concentrations and concomitant use of sedatives may have contributed to the patients' instability and deterioration."

• Miller's Anesthesia 10e, p. 3598

7. Local Anaesthetic Systemic Toxicity (LAST)

LAST in Liposuction Context:

• 11% followed subcutaneous infiltration (the same route as tumescent)
• Cases also reported from liposuction specifically
• Only 2% of providers outside anaesthesiology were aware that lipid emulsion is the treatment for LAST - a critical knowledge gap when tumescent is performed by surgeons and dermatologists without anaesthesia staff

LAST Plasma Threshold:

• Lidocaine >5 μg/mL - CNS toxicity (perioral paraesthesia, tinnitus, metallic taste, seizures)
• Lidocaine >8 μg/mL - Cardiac toxicity (ventricular arrhythmia, cardiac arrest)

LAST Treatment (from Miller's):

1. Stop injection immediately
2. Call for help; call cardiac arrest team
3. Airway management - 100% O₂, secure airway if necessary
4. Lipid emulsion (Intralipid 20%) IV - the specific antidote
   • Bolus: 1.5 mL/kg IV over 1 minute, can repeat up to 3 times
   • Infusion: 0.25 mL/kg/min
5. Basic and Advanced Cardiac Life Support (ACLS)
   • Avoid vasopressin, calcium channel blockers, beta-blockers
   • Prefer epinephrine in reduced doses for ACLS
6. Have a checklist - ASRA LAST checklist is recommended

"Lipid emulsion rescue therapy improves success of resuscitation from cardiac arrest due to local anesthetic toxicity if given immediately after a local anesthetic overdose."

• Miller's Anesthesia 10e, p. 6232

8. Role of Epinephrine in the Tumescent Solution - In Depth

1. Slows systemic absorption - reduces peak plasma lidocaine levels
2. Haemostasis - dramatically reduces intraoperative blood loss; the surgical field remains nearly bloodless
3. Prolongs anaesthetic duration - most pronounced with lidocaine
4. Intravascular injection marker - if accidentally injected intravascularly, produces a transient tachycardia, alerting the injector (though false negatives and positives can occur, especially in patients under general anaesthesia or on beta-blockers)

"Postoperative tachycardia and hypertension may be seen if tumescent fluid containing epinephrine or other adrenoceptor agonists was administered in large quantities during the surgery."

• Miller's Anesthesia 10e, p. 12390 (Burns chapter)

9. Special Situations

Tumescent in Burns Surgery

"In its simplest form, regional anesthesia may be tumescent local anesthesia injected into a donor site prior to harvesting..."

"Injection of tumescent fluid into the burn or donor site should be minimized in the very young as gradual absorption of the tumescent fluid several hours later can lead to pulmonary oedema."

• Miller's Anesthesia 10e, Burns chapter

Alkalinisation of the Solution (Sodium Bicarbonate)

1. Reduces pain on injection - the acidic nature of standard lidocaine solutions is partly responsible for burning pain on subcutaneous infiltration
2. May improve onset - alkalinisation shifts lidocaine toward the non-ionised (free base) form which penetrates nerve membranes more readily

"Alkalinization of lidocaine solutions by the addition of sodium bicarbonate immediately before injection reduces pain on skin infiltration and may improve onset."

• Miller's Anesthesia 10e, p. 3590

10. Factors Governing Safety - Key Variables

11. Summary Table - Tumescent vs. Standard Infiltration

Key Take-Home Points from Miller's

1. Large volumes + dilute concentration = the defining characteristic of tumescent anaesthesia
2. Epinephrine is not optional - it is the primary safety mechanism enabling high lidocaine doses
3. The delayed peak (up to 20 hours) is the most clinically dangerous feature - patients can deteriorate after leaving the operating room or office
4. Concomitant IV sedation with tumescent is the most hazardous combination and requires anaesthesia team presence
5. LAST can occur even from subcutaneous infiltration - lipid emulsion must always be immediately available
6. In paediatric patients and burns: minimise tumescent volumes to avoid delayed pulmonary oedema from fluid redistribution
7. Alkalinise with NaHCO₃ to reduce injection pain and improve onset
8. Miller's concludes: "Factors governing uptake and clearance from this method of local anesthetic delivery deserve further study" - acknowledging that the pharmacokinetics are still not fully understood

Labor Analgesia: Non-Neuraxial and Neuraxial Techniques

From Miller's Anesthesia, 10th Edition (2-Volume Set), Chapter 57

1. The Pain of Labor - Background

• Some patients experience severe pain only in the second stage
• Others report severe pain from the very first contraction
• A pain-free labor is rare

• Parity
• Maternal pelvic size and shape
• Fetal size and presentation
• Maternal anxiety, pain tolerance, and psychological state
• Quality of social support during labor (doula, partner)
• Whether labor is induced or contractions are augmented
• Genetic factors - one study found Asian women reported more pain; an association was found with a SNP in the β2-adrenergic gene

"For most pregnant patients, labor is intensely painful. However, the time course of pain intensity is highly variable, dynamic, and unpredictable."

• Miller's Anesthesia 10e, p. 8839

Anatomy of Labor Pain

• First stage: Pain from uterine contractions and cervical dilation is carried by visceral afferents through T10-L1 nerve roots
• Second stage (descent and delivery): Somatic pain from perineal distension and stretching is conveyed through the pudendal nerve (S2-S4)

Part I: NON-NEURAXIAL TECHNIQUES

2. Non-Pharmacologic Methods

"Although many nonpharmacologic techniques seem to reduce the perception of labor pain, most published studies lack the rigorous scientific methodology for useful comparison of these techniques to pharmacologic methods."

3. Systemic Pharmacologic Drugs

A. Opioids

Meperidine (Pethidine)

• Once the most widely used opioid in obstetrics - now rarely used
• Dose: 50 mg IV / 50-100 mg IM
• Problems:
  • Maternal half-life 2.5-3 hours
  • Active metabolite normeperidine half-life: 13-23 hours in mother; up to 3x longer in fetus/newborn
  • Normeperidine is neurotoxic and accumulates with repeated doses
  • Risk to neonate increases with higher doses and shorter dose-to-delivery intervals: lower Apgar scores, prolonged time to sustained neonatal respiration

Morphine

• Rarely used for labor pain
• Active metabolite (morphine-6-glucuronide) has a longer neonatal half-life
• Produces significant maternal sedation
• IM morphine used occasionally by obstetricians for analgesia, sedation, and rest in latent labor - onset 10-20 minutes
• Side effects: respiratory depression, histamine release (pruritus, rash)

Mixed Agonist-Antagonist Opioids: Nalbuphine and Butorphanol

• Nalbuphine: Analgesic potency similar to morphine; 10-20 mg IV/IM/SC every 4-6 hours; generally well tolerated
• Butorphanol: 5x as potent as morphine, 40x more potent than meperidine; 1-2 mg IV/IM; generally well tolerated

Fentanyl (IV/PCA)

• Highly lipid-soluble; rapid onset (2-4 min); short duration (30-45 min); no active metabolites
• IV infusion: 50-100 mcg/h - no significant difference in neonatal Apgar scores and respiratory effort vs. control at these doses
• Fentanyl PCA: bolus 10-25 mcg; lockout 5-12 minutes
• Multicenter RCT comparing fentanyl PCA vs. neuraxial analgesia: PCA group required more antiemetics, had more sedation, higher pain scores, and neonates were more likely to require resuscitation and naloxone
• High doses immediately prior to birth cause neonatal depression

Remifentanil (IV PCA) - The Preferred Systemic Opioid

• Rapid onset (2 min); very short context-sensitive half-life (~3 min) due to non-specific plasma esterase metabolism
• Offers superior pain relief and lesser fetal effects compared to other IV opioids (due to rapid fetal metabolism after delivery)
• Analgesic effects still inferior to neuraxial analgesia
• Requires careful maternal oxygenation and ventilation monitoring - maternal apnoea and desaturation are the main risks
• Typical PCA: 0.2-0.8 mcg/kg bolus; lockout 2-3 minutes

B. Inhaled Analgesia

Nitrous Oxide (N₂O) - Entonox (50% N₂O / 50% O₂)

• Self-administered via facemask or mouthpiece, inhaled with each contraction
• Provides partial but not complete pain relief
• Does not cause neonatal depression at analgesic doses
• Advantages: rapid onset and offset, patient-controlled, no IV access needed
• Used extensively in the UK and Europe; growing use in the US

Volatile Anaesthetics (Methoxyflurane)

• Used in some countries; generally not mainstream for labor

C. Other Systemic Agents

Ketamine (IV, Subanesthetic Doses)

• Doses <0.25 mg/kg IV can be used as a profound analgesic
• Often causes unwanted hallucinations - can be reduced by co-administering benzodiazepines
• At induction doses (1-1.5 mg/kg): cardiovascular stimulant; ideal for the haemodynamically compromised bleeding patient
• Larger doses: increase uterine tone, reduce uterine arterial perfusion, lower maternal seizure threshold
• Risk: repeated subanesthetic dosing may cause loss of consciousness with an unprotected airway - aspiration risk
• No neonatal depression at standard induction dosing

Part II: NEURAXIAL TECHNIQUES

4. General Principles of Neuraxial Labor Analgesia

Pre-Procedure Assessment

• A preprocedural anaesthesia assessment should be performed for any candidate for neuraxial labor analgesia
• Clinical assessment recommended for all patients admitted to labor and delivery - not just those requesting analgesia - to detect comorbidities that may complicate labor, obstetric procedures, or anaesthesia
• In otherwise healthy pregnant patients, laboratory testing is NOT required during a routine preprocedural obstetric assessment

Oral Intake During Labor

• ASA recommends: moderate amounts of clear liquids are allowed throughout labor with neuraxial analgesia
• A period of abstention from solids before neuraxial placement is not required
• However: solid food ingestion should be avoided in laboring patients (aspiration risk for potential emergency caesarean)

Timing of Neuraxial Placement

"If a parturient chooses neuraxial analgesia, there is no point during the first stage of labor that is 'too early' to initiate epidural analgesia."

• 2011 meta-analysis (prospective RCTs, n=15,399 parturients): placing epidural at ≤3 cm dilation vs. active labor showed no increase in cesarean delivery rate and no prolongation of the first stage
• Current ASA guidelines: Maternal request for labor pain relief is sufficient justification for epidural initiation; timing should NOT depend on arbitrary cervical dilation

5. Neuraxial Analgesic Drugs

Local Anaesthetics

• Any preservative-free local anaesthetic may be used
• Goal: excellent analgesia without motor blockade, maternal hypotension, or fetal effects
• Low concentrations are used to maximise sensory block and minimise motor block

• Meta-analysis of RCTs: Low concentrations (≤0.1% bupivacaine or ≤0.17% ropivacaine) vs. high concentrations = shorter second stage, less motor block, lower incidence of assisted vaginal delivery
• This evidence has driven routine use of dilute solutions for labor epidural analgesia

Opioid Additives

• Lipid-soluble opioids added to reduce total local anaesthetic dose while maintaining analgesia
• Fentanyl 1-3 mcg/mL - most commonly used
• Sufentanil 0.1-0.5 mcg/mL - also used
• These reduce motor blockade while preserving analgesia and enhancing maternal satisfaction
• Opioid-only epidural regimens do NOT provide adequate analgesia without unacceptable side effects
• Main dose-limiting side effect: pruritus

Other Adjuvants

6. Specific Neuraxial Techniques for Labor

A. Epidural Analgesia

• Catheter placed in the epidural space between L2-3 and L4-5
• Combination of low-concentration local anaesthetic + opioid delivered continuously
• Versatile - block density can be increased for operative delivery (vacuum, forceps, or emergency caesarean section)

• Decreased maternal catecholamines (reduces stress response)
• Effective pain relief
• Increased patient satisfaction
• Ability to rapidly achieve surgical anaesthesia for emergency caesarean delivery (by topping up the catheter)

• Dosing through the needle within the epidural space is NOT recommended (risk of intravascular or intrathecal bolus)
• Most providers give a test dose after catheter placement to check for intravascular or intrathecal placement
• Standard test dose: small LA dose that would cause dizziness/tinnitus/lip numbness if intravascular; motor block if intrathecal - but NOT total spinal
• Many include 15 mcg epinephrine - intravascular injection would produce a transient tachycardia/hypertension
• Mitigation of undetected misplacement: dose slowly; aspirate intermittently; watch for CSF or blood in catheter; monitor for unexpected vital sign changes, CNS symptoms, or motor block throughout dosing

• Continuous epidural infusion (CEI)
• Patient-Controlled Epidural Analgesia (PCEA) - allows the patient to self-administer boluses
• Programmed Intermittent Epidural Bolus (PIEB): Automatic boluses at set intervals (discussed below)

Programmed Intermittent Epidural Bolus (PIEB)

• Delivers epidural solution as intermittent boluses rather than a continuous infusion
• The higher injection pressure with boluses achieves better spread of the solution in the epidural space
• A meta-analysis found PIEB provided improved pain control, enhanced maternal satisfaction, decreased motor block, and reduced consumption of local anaesthetic compared to CEI
• Now widely regarded as the superior delivery mode for labor epidural analgesia

B. Spinal Analgesia (Intrathecal)

• Single injection of opioid ± small dose of local anaesthetic into the subarachnoid space
• Quick to perform; rapid onset; limited duration
• Best suited for:
  • Multiparous parturients with advanced dilation where delivery is imminent
  • Second stage of labor
  • Patients who cannot hold still for epidural catheter placement
  • The first component of a CSE technique

• Fentanyl 15-25 mcg alone or with small-dose bupivacaine
• Sufentanil 5-10 mcg ± bupivacaine 0.5-2.5 mg

C. Combined Spinal-Epidural (CSE) Analgesia

1. Epidural needle placed in the epidural space
2. A long spinal needle (pencil-point) passed through the epidural needle into the subarachnoid space
3. Intrathecal dose injected
4. Spinal needle withdrawn; epidural catheter threaded
5. Subsequent doses via epidural catheter

• Rapid onset (intrathecal component) - superior initial analgesia vs. epidural alone
• Prolonged duration (epidural catheter for maintenance and operative delivery)
• Lower dose of local anaesthetic for initiation
• Excellent for the patient in advanced labor needing fast pain relief

• Faster and better initial analgesia
• Patients may ambulate more easily ("walking epidural") due to minimal early motor block from dilute intrathecal doses
• Potential disadvantage: epidural catheter placement and function cannot be verified until the spinal wears off

D. Dural Puncture Epidural (DPE) Technique

1. Epidural space identified
2. A spinal needle punctures the dura (as in CSE)
3. But NO intrathecal drug is injected - only epidural dosing follows

• Better sacral spread (important for second-stage pain)
• More consistent analgesia
• Reduced risk of unilateral block
• Less breakthrough pain

• Does not carry the risk of intrathecal drug injection complications (post-dural puncture headache from CSE is rare with pencil-point needles, but intrathecal drug side effects are avoided with DPE)
• Slower onset than CSE but faster than plain epidural

E. Neuraxial Analgesia and Progress of Labor

"If a parturient chooses neuraxial analgesia, there is no point during the first stage of labor that is 'too early' to initiate epidural analgesia. Current ASA guidelines note that maternal request for labor pain relief is sufficient justification for epidural initiation and the timing should not depend on an arbitrary cervical dilation."

• Meta-analysis (2011, n=15,399): early epidural (≤3 cm dilation) vs. active labor: no increase in caesarean delivery, no prolongation of first stage
• Current evidence does not support withholding neuraxial analgesia to preserve labor progress

7. Other Regional Nerve Blocks (Non-Neuraxial)

A. Paracervical Block

• Performed by obstetricians
• Local anaesthetic injected lateral to cervix at 4 o'clock and 10 o'clock
• Controls first stage pain (cervical dilation)
• More effective than placebo or IM meperidine
• No difference vs. IV fentanyl PCA for pain relief

• Transient fetal bradycardia (most common)
• Maternal local anaesthetic toxicity
• Risk of injection into the presenting fetal head - potentially devastating
• Therefore: for viable fetuses, obstetricians in the US largely avoid this block
• Still used for: intrauterine fetal demise labor, D&C, and dilation and evacuation

B. Pudendal Nerve Block

• Derived from sacral roots S2-S4
• Transvaginal or transperitoneal approach
• Treats pain during second stage of labor and episiotomy repair
• Not as effective as intrathecal fentanyl + bupivacaine - very rarely utilized now
• Disadvantage: May impede the urge to push during second stage

• High rate of block failure
• Systemic local anaesthetic toxicity
• Ischiorectal or vaginal haematoma
• Rarely: fetal injection of local anaesthetic

8. Contraindications to Neuraxial Anaesthesia

"The decision to place neuraxial anesthesia should be individualized for the patient and the risks and benefits should be considered."

9. Analgesia for Operative Vaginal Delivery

• Epidural top-up: 5-10 mL of 1-2% lidocaine or 2-3% 2-chloroprocaine through the indwelling catheter
• Pudendal nerve block can be considered as an adjunct
• If no epidural catheter is in place: CSE approach is preferred over a single-injection spinal - so that the epidural catheter is available to dose up for emergency caesarean if operative vaginal delivery fails

10. Summary Comparison: Neuraxial Techniques for Labor

Key Take-Home Points from Miller's

1. Maternal request is sufficient justification - there is no "too early" for neuraxial analgesia based on cervical dilation
2. Dilute local anaesthetic + opioid is the gold standard neuraxial combination - maximises analgesia, minimises motor block
3. Epidural analgesia is the mainstay - versatile, convertible to surgical anaesthesia for emergency caesarean
4. PIEB delivers better analgesia than continuous infusion - better spread, less motor block, less drug consumption
5. Remifentanil PCA is the best systemic opioid option where neuraxial is not feasible - but requires continuous pulse oximetry and vigilant monitoring for maternal apnoea
6. Meperidine should be abandoned - its active metabolite normeperidine accumulates and is neurotoxic with prolonged neonatal half-life
7. Paracervical block is largely avoided for viable fetuses due to fetal bradycardia risk
8. DPE is an emerging technique offering improved sacral spread over standard epidural without the intrathecal drug risks of CSE