The drug-abusing parturient

1. Mike Paech Professor and Chair of Obstetric Anaesthesia School of Medicine and Pharmacology, The University of Western Australia Dept. of Anaesthesia & Pain Medicine, King Edward Memorial Hospital for Women & Royal Perth Hospital The drug-abusing parturient

2. No disclosures or conflicts of interest

5. Western Australia

7. Disclosures & Definitions I am on a Clinical Advisory Panel for MSD Substance misuse (abuse) is the harmful use of drugs for non-medical purposes.

8. Please consider this patient You are called to the assessment area of your maternity unit by the obstetric team, who want you to review and help manage a 23 year old woman at 32 weeks gestation in her first pregnancy. The patient is accompanied by a male friend. • No antenatal care • Presents with severe abdominal pain • Pink breathing air, HR 130, BP 165/95 mmHg, temp 37.6 C • Sweating, restless, poorly cooperative, appears dehydrated • Has a tense, moderately tender uterus. Fetal tachycardia of 165 bpm • History of smoking, alcohol abuse and illicit drug use (heroin and amphetamines) • Claims is ‘clean’ and on methadone program, 60 mg/day

9. Case history • Ultrasonography shows a small retroplacental clot • Venous blood required for antenatal screening tests, including full viral status; and for blood picture, cross-match, coagulation tests, electrolytes, renal and liver function. Veins are thrombosed • You find it difficult to get a coherent and comprehensive history from the patient but she tells you – hepatitis C positive; no medical disease; no surgery; allergic to anti-inflammatory drugs and tramadol • On examination she is underweight, has very poor venous access, eroded teeth, a soft systolic murmur and bi-basal crepitations

10.  Her friend approaches you outside the room and reveals that the patient has not been taking her methadone regularly over recent weeks. She has been intermittently using heroin, although a few hours previously, prior to the onset of the abdominal pain, she had injected ‘ice’ (methamphetamine).

11. Quiz – match the picture to a drug • Marihuana (marijuana) • Heroin • G- hydroxybutyrate • Nitrous oxide • Methamphetamine • Cocaine • Hallucinogenic drugs

12. Quiz – match the picture to a drug Marihuana (marijuana) Cocaine G-hydroxybutyrate Nitrous oxide Methamphetamine Heroin Hallucinogenic drugs

13. Commonly abused depressant drugs ‘Street names’ Main action • Ethanol (alcohol) Modulator GABAA R grog; booze; brew; Antagonist NMDA R hooch; etc   2. Marihuana/marijuana (cannabis) weed; grass; pot; ganja; Agonist cannabinoid R dope; hash; mary jane; etc 3. Benzodiazepines Bind GABAA R Valium (Vs); downers tranks; benzos; etc

14. 4. Opioids skag; horse; shit; junk; Agonist opioid R Harry boy; white nurse; brown sugar; cotton; kicker; oxies; etc 5. Gamma-hydroxy butyrate Agonist GABAB R GHB; gamma-OH; Agonist GHB R fantasy; liquid E; grievous bodily harm; juice; G; etc. 6. Inhaled solvents (benzene; toluene; acetone; nitrites; etc) glue; gas; sniff; poppers; bulbs; air blast; nangs; bolt; etc. Modulate GABA R Inhibit DNA synthesis

15. Commonly abused stimulatory drugs 1. Nicotine - Nicotinic ACh R agonist 2. Methamphetamine and derivatives speed; uppers; ice; crystal; Increase release, block re- fet; powder; dexies; ecstasy; uptake or inhibit metabolism of excitatory neurotransmitters (norepinephrine, dopamine, serotonin) 3. Cocaine crack; coke; candy; snow; Serotonin-norepinephrine- flake; gold dust; line; etc. dopamine reuptake inhibitor Na-channel block 4. Ketamine & designer drugs Special K; K; cat Valium; purple; Antagonist NMDA R super C; bump Binds multiple others

16. The extent of drug abuse Legal drugs Life-time prevalence of drug abuse or addiction is 10-15% in the community and that includes doctors (and anesthesiologists!)….but only 1% of doctors receive therapy Illegal (illicit) drugs Most people have used an illicit drug at some time but most are not drug abusers (drug abuse estimated 8% pop. in USA) …..and many drug abusers maintain normal function And some are cult heroes…… In Australia 5% of the population use cannabis regularly

17. Drug abuse during pregnancy In the USA 10-16% pregnant women use alcohol or smoke tobacco. Reported rates of illicit drug use during pregnancy are 4-7% - but 16% among those aged 15-17 years.

18. The extent of the problem Many illicit drug users deny use! The stereotype obstetric intravenous drug user: • A smoker with personal and social issues; anxiety, depression or other psychiatric conditions; and poor health and nutrition. • History of a lack of antenatal care and previous premature labor. • Medical problems such as anemia, hepatitis, sexually transmitted disease and urinary tract infection These women create extra work Up to 10% of hospitalized pregnant substance abusers suffer a life-threatening crisis

19. So what are the major substances of abuse?No. 1 A legal drug – ethanol (ethyl alcohol) Acute intoxication increases aspiration risk (give pharmacological prophylaxis and protect airway) Chronic use is associated with: Cardiac or liver failure • appropriate anesthetic drugs & doses? • regional anesthesia contraindicated by coagulopathy or infection? Maternal withdrawal syndrome Fetal alcohol syndrome (estimated 1 in 100 in USA)

21. No. 2 Nicotine & marihuana Nicotine Adverse obstetric outcomes Bronchospasm, secretions, postop respiratory morbidity • use regional anesthesia whenever possible • arrange appropriate postoperative respiratory care • advise abstinence > 48 hours prior to anesthesia Hepatic enzyme induction • titrate intravenous anesthetics Marihuana Oropharyngitis, uvular oedema (assess airway) Altered conscious state (agitation or sedation) Increased propofol requirements for airway instrumentation

22. No. 3 Stimulants - Methamphetamine Methamphetamine is probably the most abused illicit drug (in Australia 3% vs 1% heroin; cocaine (1%) predominates in USA) Obstetric implications • increased rates of premature delivery, low birth weight, stillbirth, neonatal death & low IQ • obstetric hemorrhage, esp. placental abruption (10% among regular cocaine users)

23. Issues for anesthesia Acute intoxication Hypertension, myocardial ischemia, arrhythmias • caution with sympathomimetics and use less arrhythmogenic anesthetic drugs Seizures - exclude eclampsia Fetal distress and placental abruption Serotonergic syndrome / sudden death Regular users have decreased anesthetic dose requirements but need more in acute intoxication • no cross-tolerance with opioids / benzos so easy to overdose • regional block depends on level of cooperation & risk of coagulation defects

25. Cocaine Hypertension, seizures • exclude eclampsia • treat with midazolam, alpha2-agonists, hydralazine, glyceryl trinitrate or nifedipine (possibly labetolol but avoid beta-blockers). • obtund the intubation response (GTN, magnesium sulphate, esmolol, high-dose opioid e.g. remifentanil) Myocardial ischemia, infarction, arrhythmias, local vascular comps • use alpha2-agonists (clonidine, dexmedetomidine) to aid BP control • use less arrhythmogenic anesthetic drugs

26. Cocaine Thrombocytopenia • decide if regional anesthesia is contraindicated Poorer response to opioid • titrate doses to effect Cholinesterase depletion • reduce dose of & monitor succinylcholine (suxamethonium)

27. Ketamine & hallucinogens Seizures - distinguish from eclampsia Caution with sympathomimetic drugs Autonomic dysregulation • control labile blood pressure and tachycardia to prevent cardiomyopathy, coronary and cerebral vasospasm Reduced plasma cholinesterase activity • reduce dose & monitor succinylcholine

28. No. 4 Opioids In USA dependency or abuse in pregnancy is increasing – 0.4% (1 in 200) in 2011 Prescription opioid abuse is up greatly in USA [Maeda A et al Anesthesiol 2014; n=113,000 in 57 mil delivery admissions]

29. Opioids & pregnancy Obstetric implications • prematurity, IUGR, stillbirth, neonatal mortality • maternal abruption, C-section, increased length of stay • maternal death during hospitalization (OR 4.6) • neonatal abstinence syndrome Maintenance when pregnant • increase methadonedose (> 40 mg/day) or continue buprenorphine dose as necessary to prevent heroin use • provide partial substitution of maintenance opioid dose perioperatively

30. Anesthesia-relevant problems Acute opioid intoxication Titrate anesthetic drugs (reduced requirements?) Chronic use IF IV opioid, difficult intravenous access • use ultrasound guidance and consider neck veins Infection risk, chronic hepatitis, malnutrition • check liver function Titrate anesthetic drug (increased requirement?) Opioid-induced hyperalgesia / tolerance

31. Opioids Beware maternal withdrawal syndrome (24-48 h) • During labour substitute usual dose with an equivalent dose of oral or parenteral opioid ….or use epidural opioid plus current oral prescription • Postop or postpartum recommence usual opioid dose immediately as well as providing additional regional or systemic analgesia • Avoid methadone for acute pain if on maintenance • Avoid opioid antagonists • Treat withdrawal with clonidine or dexmedetomidine; midazolam; doxepin and diphenhydramine; loperamide; beta-blockers

32. No. 5 Benzodiazepines & GHB Acute intoxication - provide supportive therapy Chronic use Titrate anesthetic drugs (increased requirement?) Risk of withdrawal syndromes (delirium, seizures, hyperthermia, autonomic instability)

33. No. 6 Other substances Solvents Sensory/motor deficits • perform neurological examination prior to regional Tramadol Seizures - distinguish from eclampsia Withdrawal syndrome • provide supportive therapy Remember multidrug (polydrug) abuse is common

34. Back to our patient… You are called to the assessment area of your maternity unit by the obstetric team, who want you to review and help manage a 23 year old woman at 32 weeks gestation in her first pregnancy. The patient is accompanied by a male friend. • No antenatal care • Likely abruption and current use of IV heroin & metamphetamine • In pain, agitated, hypertensive, dehydrated • Difficult veins You are going to have to look after her now and for C-section!

35. In addition to usual preoperative assessment, what are the main initial management considerations? • Obtain her cooperation (give analgesics & possibly drugs to reduce agitation) • Get venous access to allow blood testing, rehydration and IV drug administration • Confirm ongoing obstetric surveillance to exclude significant maternal blood loss and observe fetal status • Review blood gases, blood counts and coagulation tests to exclude contraindications to regional anesthesia and to correct existing abnormalities

37. What are the priorities for herpreoperative medical management and planning? • Assessment of her intravascular volume status and correction of hypovolemia • Treat hypertension with titrated vasodilators or labetolol • Review her history and blood tests to exclude severe preeclampsia & other abnormalities • Performing a sepsis and drug screen • Consult with the operating room team and HDU staff to inform them of her need for surgery and well-monitored postoperative care

38. Which are the likelyanesthetic challenges ? • Difficulty deciding whether she is likely to tolerate surgery when awake under regional block, or whether general anesthesia is advisable • Intraoperative pain control during surgery if under spinal anesthesia • An increased risk to staff of cross-infection • Achieving good quality pain relief – likely difficult due tolerance and hypersensitivity unless regional analgesic techniques are used The analgesia plan should include an agreement with her about the duration of perioperative opioid administration & post-discharge referral to a community or hospital opioid-management program

39. Options for satisfactory postoperative analgesia are - • Low thoracic epidural infusion of low concentration local anesthetic and lipophilic opioid, possibly also with clonidine, for up to 48 hours • Bilateral TAP blocks or continuous wound infiltration followed by patient-controlled intravenous tramadol or fentanyl & adjuncts • Intrathecal morphine 250 mcg or more followed by patient-controlled intravenous analgesia • Epidural morphine 5 mg boluses plus adjuncts Analgesic adjuncts • IV ketamine infusion starting at 0.1 mg/kg/h • gabapentin or pregabalin (150 mg bd) • tapentadol SR (100 mg bd)

40. Back to the patient………….. You talk to the obstetricians, who arrange a cat 3 C-section after investigations and stabilization over the next hour or two (the fetal condition remains OK). You - • give her oral clonidine, insert an IV cannula under ultrasound guidance and do ‘labs’. • titrate IV fentanyl & midazolam until she is more comfortable and cooperative. • give IV fluid and correct her hypertension with oral nifedipine • obtain her consent for regional anesthesia (a CSE) and/or general anesthesia (plan B) – with final decision later, based on blood results and her mental state. • obtain her agreement about a plan for postop analgesia.

41. Her hemodynamic status improves & she is much more cooperative. You perform a double segment CSE anesthetic (low lumbar IT bupivacaine, morphine and clonidine; low thoracic epidural catheter) The C-section is uneventful apart from mild intraoperative pain managed with pelvic LA; nitrous oxide. The neonate is in good condition but goes to special care nursery for observation. She is nursed in the high-dependency unit, under the care of pain specialists & obstetricians; and observed for signs of opioid and alcohol withdrawal. Oral methadone is recommenced immediately postop and a low dose of oral clonidine continued.

42. Thromboprophylaxis with low molecular weight heparin is commenced. She gets excellent pain relief with her thoracic PCEA for 2 days; and then adequate relief with oral acetaminophen (paracetamol), celecoxib, tapentadol, pregabalin. She is investigated for cardiac or pulmonary pathology (SBE? sepsis?). Post-discharge Community Drug and Alcohol unit follow-up is organized by obstetricians.

43. Key points • Drug abuse during pregnancy is not uncommon but may be difficult to detect and is frequently denied • The most commonly abused drugs are alcohol, tobacco and cannabis; amphetamines, cocaine and opioids • Adverse maternal outcomes include morbidity from acute intoxication or withdrawal (esp. alcohol, opioids, stimulants) and obstetric morbidity such as placental abruption (stimulants, opioids)

44. Key points • Adverse fetal and neonatal outcomes include impaired placental function and premature delivery (stimulants, opioids), neonatal withdrawal syndromes (opioids, benzodiazepines, tramadol) or developmental abnormalities (neonatal alcohol syndrome) • Medical, obstetric and other disease or pathology (pre-eclampsia / eclampsia, infection, hepatic disease, anemia) should be excluded before assuming acute drug intoxication is the sole cause of presenting symptoms and signs

45. Key points • The acutely intoxicated woman poses challenges due to lack of cooperation, difficult venous access, physiological derangements (coma and respiratory depression from opioids, excessive sympathetic activity from stimulants) and the need for urgent delivery • Substance abusing women are more likely to require additional analgesic and anesthetic services and pain management may be very difficult (opioids)

46. Key points • Regional anesthetic challenges include psychological suitability; relative contraindications such as infection or coagulopathy; and poorer or greater responses to vasopressors (use direct-acting). CSE techniques are advantageous. • GA challenges include altered drug requirements & exaggerated response to intubation.

47. References • Scott K, Lust K. Illicit substance use in pregnancy – a review. Obstet Med 2010;3:94-100 • Wendell AD. Overview and epidemiology of substance abuse in pregnancy. ClinObstetGynecol 2013;56:91-96 • Bell J, Harvey-Dodds L. Pregnancy and injecting drug use. BMJ 2008;336:1303-1305 4. French E. Substance abuse in pregnancy: compassionate and competent care for the patient in labor. ClinObstetGynecol 2013;56:173-177 5. Hall AP, Henry JA. Illicit drugs and surgery. Int J Surg 2007;5:365-370 7. Slamberova R. Drugs in pregnancy: the effects on mother and her progeny. Physiol Res 2012;61 (S1):S123-135

49. THANKS!