FRCA Notes

Substance Misuse

The curriculum asks for knowledge of the "implications of lifestyle factors such as... substance abuse on patient outcomes" and the impact on "the conduct of anaesthesia and perioperative care... of substance abuse".

A CRQ on opioid tolerance (September 2025) saw marks dropped on: risk factors for opioid tolerance and the definition of opioid-induced hyperalgesia.

A CRQ on opioid stewardship (February 2024) was marred by poor knowledge of opioid equivalence and the perioperative management of fentanyl patches.

Resources

  • Problem drug use affects around 1 in 100 people aged 15 - 64 in the UK; for intravenous drug use it is around 1 in 300
  • Users may be reluctant to disclose their habit and the first sign may be withdrawal symptoms
  • Polysubstance use is common; identifying one substance should prompt questions about others
  • Avoid using slang terms to identify drugs; these evolve rapidly and vary by region
  • Tobacco, cannabis and alcohol are covered on their own pages: smoking and alcohol abuse


Term Definition
Substance use disorder Diagnosed using the 11 DSM-5 criteria across four domains: impaired control, social impairment, risky use and pharmacological effects (tolerance and withdrawal)
2 - 3 criteria: mild | 4 - 5: moderate | ≥6: severe
Tolerance Predictable and physiological
An increased dose is required to achieve the same effect
Physical dependence Predictable and physiological
Stopping, reducing or reversing the drug causes a withdrawal syndrome
Addiction An unpredictable effect of the drug; a disease
Aberrant drug-seeking and drug-taking behaviour despite physical, social and psychological harm
Pseudoaddiction Drug-seeking behaviour due to under-treatment of pain, which resolves once analgesia is adequate
Opioid-induced hyperalgesia A state of nociceptive sensitisation secondary to opioid exposure; pain is often more diffuse and widespread
Cross-tolerance Tolerance to one drug results in tolerance to structurally similar drugs of the same class; this is often incomplete between opioids

Tolerance vs. opioid-induced hyperalgesia

  • Both present as inadequate analgesia despite opioid use, and can be difficult to distinguish from each other and from progression of the underlying disease
  • Tolerance: analgesia improves with an increased dose or opioid rotation
  • Opioid-induced hyperalgesia: pain does not respond to an increased dose; treatment paradoxically requires an opioid dose reduction
    • Mechanism likely involves NMDA receptor activation, glial cell activation and altered opioid intracellular signalling
    • First described in patients on methadone maintenance; may also occur with short-term use of high-potency opioids such as remifentanil, although evidence is conflicting

Risk factors for tolerance and harm

  • The key factors are dose and duration of opioid use
  • Two-thirds of patients taking >120mg/day oral morphine equivalent, or treated for >3 months, will continue their opioids for years
  • Compared with <20mg/day, doses of >50mg/day and >100mg/day carry a 3.7x and 8.9x greater risk of overdose respectively


Pharmacology

  • Alkaloid from the coca plant; snorted, smoked (crack cocaine) or injected
  • Inhibits central reuptake of catecholamines and serotonin, causing euphoria and intense sympathetic stimulation
  • Sodium channel blockade (its local anaesthetic action) predisposes to broad complex arrhythmias
  • Metabolised by plasma cholinesterase and the liver
  • Street cocaine is often cut with other local anaesthetics such as lidocaine, some of which can cause methaemoglobinaemia

Clinical effects

Cardiovascular Neurological Serotonin syndrome
Tachycardia Anxiety Hyperpyrexia
Hypertension Paranoid ± psychosis Multi-organ failure
Arrhythmias Mydriasis
Myocardial ischaemia/infarction Headache
Coronary vasospasm SAH
Dissection Stroke
Accelerated atheroma production Seizures and coma

Management of acute toxicity

  • Benzodiazepines are first-line for agitation, seizures and hypertension
  • Persistent hypertension: nitrates, then calcium channel blockers
  • Central sympatholysis with dexmedetomidine or clonidine provides anxiolysis and blood pressure control with a single agent
  • Broad complex tachycardia: sodium bicarbonate
  • β-blockers are controversial due to the risk of unopposed α-mediated vasoconstriction and paradoxical hypertension:
    • If used, it may be prudent to achieve α-blockade first with phentolamine
    • Labetalol has not been shown to abolish coronary vasospasm
    • More recent guidance (AHA 2023) suggests β-blockers are probably safe

Pharmacology

  • Includes MDMA ('ecstasy'), methamphetamine, mephedrone and prescribed ADHD medications
  • Indirect sympathomimetics, causing release and inhibiting reuptake of catecholamines
  • MDMA is profoundly serotonergic and can precipitate serotonin syndrome even without other serotonergic drugs
  • Newer agents such as mephedrone have amphetamine-like effects, and should be managed as for MDMA

Clinical effects

  • Sympathetic stimulation including risk of arrhythmia and myocardial ischaemia
  • Hyperthermia and rhabdomyolysis (worsened by exertional dehydration) carry a high risk of death; manage with cooling, resuscitation, neuromuscular blockade and dantrolene
  • Sudden death is rare; possibly due to arrhythmias from sympathetic stimulation or QT prolongation
  • Chronic use: dependence, paranoia, psychosis and cardiomyopathy

Acute yponatraemia

  • Caused by excessive water intake to combat dry mouth or fear of dehydration combined with SIADH; can cause cerebral oedema and death

Effect on anaesthetic requirements

  • Acute use increases MAC and causes exaggerated responses to indirect sympathomimetics
  • Chronic use depletes catecholamine stores, decreasing MAC and causing hypotension which may be refractory to ephedrine
  • Direct-acting vasopressors (e.g. phenylephrine, noradrenaline) give a more predictable response

Overdose

  • Reduced consciousness, pinpoint pupils, bradypnoea and bradycardia should prompt a trial of naloxone
    • IV, or IM whilst access is obtained; initial dose 0.4 - 2mg, repeated after 2mins if no response
    • Up to 4mg may be required, followed by an infusion of 60% of the initial dose per hour
    • Avoid boluses in suspected ischaemic heart disease; the sudden sympathetic surge may cause myocardial ischaemia
  • Rhabdomyolysis and compartment syndrome may occur even without a history of unconsciousness
    • Treat hyperkalaemia conventionally, including sodium bicarbonate
    • Avoid calcium infusions for the associated hypocalcaemia (unless ECG changes of hyperkalaemia), as hypercalcaemia and tissue calcium deposition occur during recovery

Withdrawal

  • Dysphoria, rhinorrhoea, lacrimation, myalgia, piloerection, diarrhoea and abdominal cramps; established 24 - 48hrs after abstinence
  • Re-establish maintenance therapy quickly by liaising with the patient's prescriber; methadone 10 - 40mg can be used in the interim
  • Adjuncts: diazepam, clonidine, loperamide and β-blockers for tachycardia

Substitution and maintenance therapy

  • Aims to reduce harm from drug use, provide stability, prevent withdrawal and reduce craving

Methadone Buprenorphine Naltrexone
Mechanism μ agonist
NMDA antagonist
Monoamine reuptake inhibitor		 Partial μ agonist
κ and δ antagonist
High affinity with slow dissociation		 Long-acting competitive opioid antagonist (48 - 72hrs)
Use Specialist initiation at 10 - 40mg; maintenance 60 - 120mg/day Sublingual; maintenance 12 - 24mg/day (max 32mg)
Suppresses withdrawal and craving for 24 - 48hrs; less sedating and euphoric		 Highly motivated patients maintaining abstinence from opioids or alcohol
Key issues Metabolised by CYP3A4 to inactive metabolites
Dose-dependent QTc prolongation		 Theoretically antagonises full agonists, risking analgesic failure or withdrawal Chronic use doubles brain μ and δ receptor numbers, causing marked opioid sensitivity once stopped (returns to baseline ~6 days)
Perioperative management Continue usual dose; add IR opioids for acute pain
If nil by mouth, rotate to IV fentanyl or morphine PCA		 Continue usual dose; maximise opioid-sparing techniques; use full agonists for acute pain
Opioid doses may be very high, so consider HDU		 Stop 72hrs before surgery
Maximise opioid-sparing analgesia and consider HDU post-operatively

  • Buprenorphine patches (up to 70mcg/hr) are unlikely to interfere with full agonists and should be continued
  • Alternative strategies for high-dose sublingual buprenorphine include supplementary buprenorphine doses, or rotating to a full agonist (e.g. methadone) before surgery


  • Equianalgesic tables are based on small, single-dose studies in healthy opioid-naïve volunteers, so should be used with caution
  • Because of incomplete cross-tolerance, reduce the calculated dose by 30 - 50% when rotating opioids, with IR opioid available for breakthrough pain

Opioid Conversion to oral morphine
IV morphine × 2 - 3
Oral oxycodone × 1.5 - 2
Oral methadone × 2 - 3 (non-linear; seek specialist advice)
Oral tapentadol ÷ 2.5 - 3
Oral tramadol ÷ 5 - 10
Oral codeine ÷ 10
Transdermal fentanyl 12mcg/hr ≈ 30mg oral morphine per 24hrs
Transdermal buprenorphine 10mcg/hr ≈ 24mg oral morphine per 24hrs

  • Ratios vary between sources; always check local guidance

GHB (gamma hydroxybutyrate)

  • A GABA metabolite acting at GABA and GHB receptors; metabolised to CO2 and water
  • Large doses cause brief euphoria followed by coma, with rapid recovery within 2 - 3hrs
  • Myoclonus may be mistaken for seizures, but miosis is present
  • Bradycardia responds to antimuscarinics; agitation and delirium can complicate emergence, and self-extubation is common due to the rapid recovery

GHB withdrawal

  • Unexpected and severe: autonomic instability, aggressive delirium, psychosis, seizures, hyperthermia and rhabdomyolysis
  • Requires massive doses of diazepam, with phenobarbital or a propofol infusion if needed; cooling and bicarbonate to reduce the risk of rhabdomyolysis
  • Avoid neuroleptics as they lower the seizure threshold

Benzodiazepines

  • Tolerance and cross-tolerance increase anaesthetic requirements
  • Abrupt cessation causes withdrawal (anxiety, tremor, hallucinations and seizures), so doses should be tapered rather than stopped
  • Flumazenil may precipitate seizures in chronic users and is rarely indicated

Anabolic steroids

  • Used by bodybuilders, amateur athletes and some occupational groups
  • Suspect in muscular patients with acne, striae, gynaecomastia or needle marks (or hirsutism in women)
  • Effects:
    • Psychological and endocrine effects are most common
    • Cardiovascular: hypertension, thrombosis and LVH; focal myocardial fibrosis may provide a substrate for malignant arrhythmias and sudden death
    • Hepatic: raised transaminases, cholestasis and hepatocellular carcinoma with long-term use
  • Pre-operatively, add LFTs to routine bloods; ECG and echocardiogram are mandatory
  • Increased muscle mass reduces chest wall compliance and increases oxygen consumption, CO2 production and work of breathing; a tracheal tube is preferred over an LMA for most procedures
  • Resistance to non-depolarising NMBAs (increased nicotinic receptors); suxamethonium is not contraindicated but causes more vigorous fasciculations

Ketamine

  • Recreational users may be tolerant to its anaesthetic and analgesic effects
  • Chronic use causes ketamine uropathy (ulcerative cystitis with a small, contracted bladder)

Hallucinogens

  • LSD, psilocybin and salvinorin A rarely cause serious problems in isolation; symptomatic treatment is usually sufficient

Respiratory

  • Reactive airways with smoked substances
  • Respiratory depression and aspiration with opioid and sedative overdose
  • Pulmonary hypertension from injected cutting agents such as talc, causing V/Q mismatch
  • Septic pulmonary emboli, abscesses and tuberculosis

Cardiovascular

  • Stimulants: hypertension, arrhythmias, coronary vasospasm, MI, dissection and accelerated atheroma
  • Methadone: QTc prolongation
  • Anabolic steroids: LVH, myocardial fibrosis and arrhythmias
  • IV drug use: infective endocarditis, usually right-sided, and venous thrombosis

Neurological

  • Stroke, SAH and seizures with stimulants
  • Serotonin syndrome and hyperthermia
  • High rates of psychiatric comorbidity and suicide
  • Altered pain processing: tolerance and opioid-induced hyperalgesia

Renal

  • AKI from rhabdomyolysis
  • Ketamine uropathy
  • Hyponatraemia with MDMA

Gastrointestinal

  • Chronic liver disease from hepatitis B and C
  • Hepatotoxicity and cholestasis with anabolic steroids
  • Delayed gastric emptying with acute intoxication and opioids

Nutritional and metabolic

  • Malnutrition is common; assess nutritional status, consider vitamin supplementation and the risk of refeeding syndrome

Haematological

  • Blood-borne viruses: HIV, hepatitis B and hepatitis C
  • DIC with hyperthermia
  • Methaemoglobinaemia from local anaesthetic cutting agents in cocaine

Endocrine

  • Chronic opioid use suppresses the HPA axis and gonadal function
  • Anabolic steroids cause gonadal suppression and gynaecomastia

MSK

  • Rhabdomyolysis and compartment syndrome
  • Injection site abscesses, cellulitis, osteomyelitis and septic arthritis

Perioperative management of the patient with a substance use disorder


  • The aims are to prevent withdrawal, provide effective analgesia and ensure continuity of care after discharge
  • Early identification of complex patients allows time for multidisciplinary planning with the patient (anaesthetists, pain specialists, GP, psychology, physiotherapy)

History and examination

  • A non-judgemental approach encourages an accurate history
  • Establish:
    • Substances used; prescribed, illicit and over-the-counter
    • Quantity, frequency, route and time of last use
    • Any maintenance therapy: drug, dose, prescriber and dispensing pharmacy
    • Previous withdrawal and current engagement with addiction services
  • Determine whether the patient is acutely intoxicated, tolerant or dependent, as this alters their physiology and pharmacology
  • Look for complications of use (see organ systems above), particularly cardiovascular disease, infection and venous access difficulty

Investigations

  • FBC, U&E, LFTs, bone profile, glucose, CK and clotting
  • ECG: ischaemia and arrhythmias with stimulants; QTc with methadone
  • Echocardiogram if cardiomyopathy or endocarditis is suspected, and in all anabolic steroid users
  • Blood-borne virus screening and urine drug screening only with the patient's consent

Optimisation

  • Postpone elective surgery in the acutely intoxicated patient
  • Continue maintenance therapy (methadone, buprenorphine) and baseline opioids, including transdermal patches
  • Stop naltrexone 72hrs before elective surgery
  • Long-term opioid use before surgery is associated with worse outcomes (longer stay, readmission, infection and persistent opioid use); supervised tapering before elective surgery may be considered where appropriate
  • Plan post-operative care in a monitored setting where high opioid doses are anticipated

Monitoring and access

  • Venous thrombosis is common in IV drug users so prepare for needing ultrasound and in some cases central venous access
  • Remove central lines as soon as the patient is ambulant or unsupervised, to reduce the risk of air embolism, infection or misuse of the line
  • Temperature monitoring, particularly with stimulants
  • Consider depth of anaesthesia monitoring given unpredictable requirements

Anaesthetic technique

  • Sedating substances reduce MAC; stimulants increase it
  • Acute intoxication increases aspiration risk; consider an RSI
  • Transdermal opioid patches should be continued, but avoid direct heat (e.g. warming devices) over the patch, which increases absorption; poorly perfused or cold skin reduces absorption

Analgesia

  • Continue the baseline opioid and treat acute pain with additional immediate-release opioid; doses required may be very large
  • Maximise opioid-sparing techniques:
    • Regular paracetamol and NSAIDs unless contraindicated
    • Wound infiltration, regional and neuraxial techniques, with catheters to extend benefit into the post-operative period
    • Ketamine: an NMDA antagonist which attenuates both tolerance and opioid-induced hyperalgesia; consider low-dose infusion (e.g. 100 - 200mg/24hrs) for 1 - 3 days
    • Clonidine or dexmedetomidine
    • IV lidocaine infusion

Drugs to avoid

  • Indirectly acting sympathomimetics (ephedrine) and ketamine with acute stimulant use or serotonin syndrome; use direct-acting agents such as phenylephrine
  • Mixed agonist/antagonist opioids (e.g. nalbuphine) and naloxone in patients on maintenance therapy, which may precipitate withdrawal; reserve naloxone for clinically significant respiratory depression

Analgesia

  • Involve local pain services to help continue robust analgesia into the post-operative period
  • Opioid-tolerant patients report higher rest and dynamic pain scores and use 2 - 3x more opioid via PCA
  • Staff may be apprehensive about giving large doses; under-treatment can lead to drug-seeking behaviour which is misperceived as manipulative
  • Assess overall effectiveness of analgesia, not just pain scores: side-effects, signs of withdrawal, expectations, mood and function (e.g. ability to cough, deep breathe and mobilise)
  • PCA bolus size can be based on the patient's usual 24hr opioid requirement (see opioid conversions)
  • PRN oral immediate release opioid: traditionally 1/6 of the total 24hr dose 4-hourly, though starting with standard doses and titrating is reasonable
  • Gabapentinoids are not routinely recommended, but may have a role where pain remains poorly controlled despite maximising other techniques (e.g. gabapentin 100 - 300mg tds, pregabalin 50 - 75mg bd); be aware of their abuse potential
  • Patients on high-dose buprenorphine or after stopping naltrexone may need HDU-level monitoring

Withdrawal

  • Withdrawal is a risk factor for delirium and increased length of stay; anticipate it rather than manage an agitated, tachycardic and hypertensive patient
  • Use validated scoring tools (e.g. COWS for opioids, CIWA for alcohol)
  • Opioids: re-establish maintenance therapy; symptomatic treatment with clonidine
  • Benzodiazepines and GHB: benzodiazepine cover, with anticipation of seizures

Complications

  • Inadequate analgesia and withdrawal
  • Respiratory depression and oversedation, particularly with polysubstance use
  • Delirium
  • Wound and line infection
  • Overdose after discharge if tolerance has fallen

Discharge planning

  • Communicate a clear onward plan to the GP, addiction services and pharmacist, emphasising reduction and cessation of any new opioids that are no longer required
  • Provide a limited supply of additional analgesia, and consider take-home naloxone

  • Up to 10% of pregnant women are affected by SUD; alcohol, tobacco, cannabis, opioids and cocaine are the most commonly used substances, and polysubstance use is common
  • Cravings typically fall with each trimester (partly due to progesterone), so continued use in pregnancy is likely to reflect addiction requiring treatment
  • Substance use in pregnancy is associated with acute cardiovascular events and maternal mortality, and pregnant and postpartum women are at increased risk of fatal overdose

Approach

  • These women are more likely to present late, receive inadequate antenatal care and experience stigma from healthcare providers
  • A non-judgemental approach, early antenatal anaesthetic review and multidisciplinary planning (obstetrics, midwifery, addiction services, neonatology and social care) are key
  • Drug testing should only be performed with consent; a positive result should not be a barrier to care or the sole factor in decisions regarding family separation

Specific substances

  • Cocaine and amphetamines:
    • Associated with placental abruption, preterm birth and PPROM
    • Acute intoxication can mimic pre-eclampsia and eclampsia (severe hypertension, headache, proteinuria and seizures)
    • Treat spinal-induced hypotension with phenylephrine or noradrenaline
    • Prescribed ADHD stimulant treatment does not need to be stopped in pregnancy
  • Cannabis: cannabinoid hyperemesis syndrome may be mistaken for hyperemesis gravidarum
  • Tobacco: smokers may have a slower onset and shorter duration of motor block following spinal anaesthesia
  • Benzodiazepines: should be tapered rather than stopped; in utero exposure may cause 'floppy infant syndrome' (hypotonia, hypothermia, lethargy, apnoea and poor feeding)

Opioid use disorder

  • Treatment with methadone or buprenorphine is key to preventing overdose, maternal and fetal death; continue it throughout the peripartum period
  • Both are metabolised more rapidly as pregnancy progresses (increased CYP3A4 activity), so dose adjustments and more frequent dosing are often needed
  • The analgesic duration of methadone (4 - 8hrs) is much shorter than its suppression of withdrawal (24 - 48hrs); splitting the daily dose every 6 - 8hrs around delivery may improve analgesia
  • Labour pain may be experienced with greater intensity, and analgesic requirements are higher

Labour analgesia

  • Early neuraxial analgesia is preferred, using standard low-concentration local anaesthetic with a lipophilic opioid
  • Breakthrough pain should be assessed and treated as for any other parturient to avoid bias and undertreatment
  • Clonidine or dexmedetomidine may be added if standard epidural top-ups fail

Caesarean delivery

  • Neuraxial anaesthesia is recommended over GA where possible, including neuraxial fentanyl and morphine
  • Consider continuing epidural analgesia for 12 - 48hrs, or abdominal wall blocks
  • Regular paracetamol and NSAIDs unless contraindicated; low-dose ketamine has limited supporting evidence, and routine gabapentin is not recommended
  • In patients on buprenorphine, do not treat neuraxial opioid side-effects such as pruritus with nalbuphine or naloxone as this may precipitate withdrawal
  • Life-threatening respiratory depression from buprenorphine may require high-dose naloxone, e.g. 2 - 3mg bolus followed by an infusion of 4mg/hr

Fetal and neonatal effects


Substance Effects
Opioids Neonatal opioid withdrawal syndrome
Cocaine / amphetamines Abruption, preterm birth, perinatal death
Cannabis Low birth weight, preterm birth, stillbirth, impaired neurodevelopment
Benzodiazepines Preterm birth, low birth weight, floppy infant syndrome
Alcohol Fetal alcohol spectrum disorder, growth restriction, miscarriage
Tobacco Low birth weight, preterm birth, abruption, sudden infant death syndrome

  • Neonates exposed in utero should be monitored for withdrawal
  • Epidural fentanyl during labour can be detected in neonatal meconium; anaesthetists should be aware of this to avoid incorrect assumptions of illicit use