12.1 Opioid Abuse
Jane C. Ballantyne
The dramatic increase in opioid abuse in the United States has become a public health crisis. The rate of opioid use disorder, especially of prescription opioids, has increased dramatically since 1990. Much of this increase is due to a brisk trade in prescription opioids illegally diverted from pharmacies or resold by patients, although some represents iatrogenic addiction related to excessive prescribing. Opioids are prescribed more frequently and in much greater doses for chronic non-cancer pain, with oxycodone a choice among addicts (1
). By the early 2000’s prescription opioids were the second most popular drug of abuse after cannabis. Deaths and hospitalizations from opioid overdoses spiked and became a more common cause of death among the young than motor vehicle collisions. In recent years, a series of initiatives by government and law enforcement, and changes in treatment guidelines and practice norms, have begun to reduce the availability of prescription opioids. However, there is evidence that many opioid use disorder patients have shifted to heroin or other illicit opioids instead.
Opioid addicts suffer many health complications, particularly when injecting drugs rather than smoking, snorting, or ingesting them. Numerous infectious complications include HIV
and Hepatitis C abscesses, and necrotizing soft tissue infection (NSTI
), which may require urgent surgical intervention. Hematogenous spread of bacteria is common, causing sepsis, bacterial endocarditis, and osteomyelitis. Many of these complications are related to patient’s poor nutrition, hygiene, risky sexual behaviors, prostitution, and sharing or reusing hypodermic needles. Studies of patients seeking to enter buprenorphine treatment have shown high rates of pain, depression, and anxiety (2
Opioid use disorders typically involve developing profound opioid tolerance, and pain management can be very challenging. It is difficult in this population to distinguish between the patient’s requests for opioids to treat their cravings and withdrawal, versus their requests for pain relief. High opioid requirements, preference for intravenous (IV) formulations, and reluctance to taper opioids postoperatively are common. Some patients may supplement their prescribed opioid analgesia with illicit opioids smuggled in by a friend or family member. If the patient appears intoxicated, particularly if this is shortly after a visit or a trip off ward, a urine drug screen may be helpful. This is more useful if the prescribed analgesic is different than their drug of choice—for example, a patient with a history of buying oxycodone illicitly may be prescribed hydromorphone so that illicit oxycodone use may be detected.
OPIOID PHARMACOLOGY AND ADDICTION
Most opioids are functionally very similar, as full mu-opioid receptor agonists. Heroin is diamorphine, which is rapidly converted in the blood to morphine and is clinically similar to morphine, with the distinction that there is no legal availability for heroin in the United States and limited accessibility in the United Kingdom. It is therefore not possible to treat patients for medical purposes with heroin, but other opioids may be used to replace it, with the caveat that very high doses may be required due to the extreme opioid tolerance.
It is important to use opioid-sparing adjunctive analgesia whenever possible, just as in patients on chronically high opioid doses. Regional analgesia, especially use of continuous catheter infusions such as epidural or sciatic nerve blocks are helpful to reduce nociceptive burden and opioid requirements. NSAIDs and neuropathic pain medications such as gabapentin are opioid-sparing. Low-dose ketamine infusions reverse some of the opioid tolerance in these patients and provide additional analgesia, but can worsen comorbid psychiatric illness. These interventions should be discussed with the patient and planned for during the preoperative visit.
For most opioids other than buprenorphine and codeine (which is highly constipating), there is no fixed ceiling dose and the dose can be increased as required. However, the risk of adverse effects including sedation, constipation, and respiratory suppression increase dramatically as the dose increases. There is considerable evidence that high-dose opioid administration in some patients will actually worsen pain due to the development of opioid-induced hyperalgesia. This puts a practical limit on dose escalation of opioids, and patients with tolerance require careful titration to match their baseline requirements and pain treatment without overmedication. Patient-controlled analgesia (PCA
) allows hospitalized patients to manage their own pain and determine their actual opioid requirements. PCA
can be combined with the patient’s chronic methadone prescription or chronic opioids, but otherwise should be the only mode of opioid delivery. Intermittent IV boluses of opioids are helpful to manage breakthrough pain associated with movement or dressing changes, but are highly reinforcing for patients with IV drug use histories and are prone to being overused. A basal rate of opioid infusion can be added to the PCA
regimen, but this reduces the safety factor otherwise associated with PCA
MEDICATIONS TREATING OPIOID USE DISORDERS
Many opioid use disorder patients are enrolled in methadone maintenance programs which provide daily methadone dosing. Since methadone has a long halflife, a steady state is maintained with daily dosing, which prevents withdrawal and reduces cravings. It is worth noting the analgesic effect of methadone only lasts 6 to 8 hours, so daily dosing of methadone is usually indicative of addiction treatment rather than pain treatment. Methadone is used for cancer and chronic pain. Its nonlinear potency curve means that patients on high doses of other opioids can be switched to relatively small doses of methadone. However, methadone has serious associated risks. The metabolism and half-life are variable, so it is unpredictable when steady state is reached and how much drug will accumulate.
Patients have died from opioid overdoses due to a daily fixed dose of methadone accumulating in their bodies. Methadone interacts with rifampin and prolongs the QT interval.
The dose and recent use of methadone needs to be verified with the patient and the pharmacy or maintenance program. It is not recommended to stop methadone during surgery, rather the verified dose is continued perioperatively, with the addition of a standard opioid such as PCA
morphine or hydromorphone or oral oxycodone for acute pain (3
). Postoperatively, the patient will taper off the short-acting opioids and continue the methadone.
Patients with tolerance due to illicit opioid use may also be started on methadone perioperatively to avoid withdrawal and reduce their requirements for short-acting opioids. In this case, the patient is started on fairly low doses of methadone (10 to 30 mg a day) and titrated only every few days to prevent excessive accumulation. Patients diagnosed with opioid use disorder may be referred to methadone maintenance after discharge. It is illegal to prescribe methadone for addiction to outpatients in the United States without special legal permission.
Buprenorphine is increasingly popular as a treatment of opioid use disorder since it may be prescribed in a doctor’s office and dispensed at an ordinary pharmacy. Buprenorphine is available as a pure drug (Subutex) or combined with naloxone to deter IV injection of the drug (Suboxone). The naloxone is neutralized when taken orally so does not interfere with analgesia. Buprenorphine, as a partial agonist-antagonist of the mu-opioid receptor, complicates perioperative care since it interferes with the analgesic effects of other opioids. Buprenorphine binds very tightly to the mu-opioid receptor and will block the effects of other opioids, including IV morphine and fentanyl. This is more problematic in severe acute pain situations, such as trauma.
When possible, buprenorphine is stopped 5 days before surgery, unless the surgery is expected to be minimally painful, in which case it may be manageable with acetaminophen and a temporary increase in buprenorphine dose up to the maximum dose of 32 mg/day (3
Naltrexone may be prescribed as a preventive treatment for opioid use disorder. Naltrexone prevents the patient from enjoying the reinforcing effects of opioid ingestion. This treatment will interfere with opioid analgesia, particularly if the patient received the depot formulation of naltrexone, which lasts 30 days. Surgery is delayed for 3 days for the short-acting form, or 30 days after the depot form, whenever possible.
1. Bohnert AS, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305:1315-1321.
2. Mark TL, Dilonardo J, Vandivort R, et al. Psychiatric and medical comorbidities, associated pain, and health care utilization of patients prescribed buprenorphine. J Substance Abuse Treat. 2013;44:481-487.
3. Bryson EO. The perioperative management of patients maintained on medications used to manage opioid addiction. Curr Opin Anesthesiol. 2014;27:359-364.
12.2 Cocaine or Amphetamine Abuse
Jane C. Ballantyne
Cocaine and stimulants are popular drugs of abuse, with about 1.5 million users of each estimated in the United States. Cocaine and stimulants act on dopamine in the central nervous system (CNS
) through different mechanisms, which accounts for their similar side effects and addictive properties. Long-term use results in tolerance, but also physical and behavioral adverse effects as noted below in Table 12.1
Amphetamines and methamphetamines are powerful stimulants on the CNS
, increasing alertness, suppressing appetite, and reducing the need for sleep. Stimulants are used medically to treat attention-deficit disorder and to augment antidepressants. Just as with opioids, there is considerable diversion of prescription stimulants as well as illicit stimulants. Stimulants can be ingested or injected. Methamphetamine has a particularly long half-life and users can stay up for several days at a time. Many users will use a second substance as a “parachute drug” to help them sleep after a binge; benzodiazepines, zolpidem, and quetiapine are reported favorites for this.
TABLE 12.1 Adverse Effects of Stimulant Abuse
Paranoia and psychosis
Compulsive repetitive behavior (“punding”)
Nasal septum perforation (cocaine only)
Preeclampsia (in pregnant women)
Acute amphetamine intoxication can cause hyperthermia and increased anesthetic requirements. Chronic long-term amphetamine use depletes presynaptic catecholamine stores, which reduces anesthetic requirements and makes chronic users vulnerable to hypotension, requiring direct-acting vasopressors to make up for the lack of sympathetic tone. Patients who are admitted in the aftermath of a stimulant binge may present as irritable or even acutely psychotic, only to become intensely somnolent once the drug wears off. This somnolence may be mistaken for hypoactive delirium, depression, or opioid overdose, but is benign and resolves spontaneously once the patient has rested (1
Cocaine is extracted from Erythroxylum Coca, a plant native to the Andes mountains. While the leaves of the coca plant are chewed as a fairly benign stimulant in indigenous areas, the extracted cocaine is much more potent. Cocaine typically comes in two forms, cocaine hydrochloride in powder form, and alkalinized cocaine, known as crack or rock cocaine. Cocaine can be ingested but is more typically snorted, injected, or in the alkalinized form, smoked. Cocaine has a short half-life of 0.5 to 1.5 hours and is metabolized by liver and plasma cholinesterases quickly, although metabolites such as benzylcognine may be detectable in urine for 3 to 5 days. Cocaine is a potent reuptake inhibitor of catecholamine neurotransmitters such as norepinephrine, serotonin, and dopamine. The increased dopamine activity causes euphoria, and other catecholamines contribute to increased sympathetic tone throughout the body. High blood levels of cocaine can depress ventricular function and interfere with heart rhythms through sodium channel blockade, similar to a local anesthetic. Prolonged cocaine use can produce changes in the heart including decreased vascular compliance, contraction-band necrosis, and ventricular hypertrophy. Some of these changes (see Table 12.1
) appear to persist for a long time after exposure.
A week’s abstinence is recommended at minimum before surgery, although there is no certain advantage in delaying surgery if there is no evidence of acute cocaine exposure. Cocaine withdrawal is unpleasant but not usually severe or risky. Patients who are acutely intoxicated with cocaine are at higher risk for cardiac events, arrhythmias and hypertension during surgery, which may require the use of alpha- and betaadrenergic antagonists. Cocaine use may be especially risky in neurosurgery (2
). Further assessment with ECG
, troponin levels, and if indicated stress testing, may be required in selected cases (3
1. Pulley DD. Preoperative evaluation of the patient with substance use disorder and perioperative considerations. Anesthesiol Clin. 2016;34:201-211.
2. Dwarakanath S, Cook AM, Fahy BG. Perioperative care of the cocaine-dependent neurosurgical patient. J Anesthesiol Clin Res. 2013;2:12.
3. McCord J, Jneid H, Hollander JE, et al. Management of cocaine-associated chest pain and myocardial infarction. Circulation. 2008;117(14):1897-1907.
12.3 Alcohol and Other Substance Use Disorders
Jane C. Ballantyne
Substance use disorders are common and can pose challenges to perioperative care. Alcohol use disorders are present in 14% of the US population and 7% of the population abuses other substances. These conditions are found in all ages and ethnic groups and it is important to screen for them routinely to avoid missing patients. Many providers are most familiar with patients with severe substance use disorders who may have severe legal and social consequences, such as the homeless alcoholic or imprisoned heroin addict. However, there are many patients with significant substance use disorders who are less obvious (1
Patients should be routinely asked about a history of substance use, both active and in recovery. Positive or evasive answers to screening questions trigger more detailed questions and assessments. This process is facilitated by taking a fact-oriented, nonjudgmental approach to the interview and explaining that the medical team needs accurate information to plan treatment and avoid complications. The variety of substances and their subtypes (Table 12.2
) are enormous and subject to a great deal of variability, but recognition of the type of substance abused and the severity of use guides treatment. Polysubstance use is common. Patients reporting one substance of abuse should be interviewed about others. Table 12.3
reproduces the CAGE-AID tool, a screening tool for asking about substance use. With the growing prevalence of electronic medical records that can access records within and across medical systems, providers are more likely to discover substance use disorders from chart review than before. This information can be discussed with the patient.
TABLE 12.2 Types of Substances of Abuse
Types of Substances
Primary Anesthetic Risk
Central nervous system Depressants, Sedative/Hypnotics
Benzodiazepines, barbituates, alcohol
Withdrawal and seizures
Prescription opioids, heroin
Inadequate analgesia, withdrawal
Methamphetamine, prescription stimulants, cocaine
LSD, psilocybin mushrooms
Delirium, anxiety, psychosis
Marijuana, hashish, hash oil (“dabs”)
Inhalants, bath salts
LSD, lysergic acid diethylamide
TABLE 12.3 CAGE Adapted to Include Drugs (CAGE-AID), a Screening Test for Substance Use Disorders (2)
The CAGE or CAGE-AID should be preceded by these two questions:
Do you drink alcohol?
Have you ever experimented with drugs?
If the patient has experimented with drugs, ask the CAGE-AID questions. If the patient only drinks alcohol, then ask the CAGE questions.
In the last 3 months, have you felt you should cut down or stop drinking (or using drugs)?
In the last 3 months, has anyone annoyed you or gotten on your nerves by telling you to cut down or stop drinking (or using drugs)?
In the last 3 months, have you felt guilty or bad about how much you drink (or use drugs)?
In the last 3 months, have you been waking up wanting to have an alcoholic drink (or use drugs)?
Once substance abuse has been recognized detailed documentation and specific plans are made to reduce risk. Patients with sedative/hypnotic addiction may need benzodiazepines to prevent withdrawal, while patients with opioid use disorder may need special pain management plans and the addition of methadone to prevent withdrawal. Details of the frequency and amount of use are helpful for planning. A past history of alcohol withdrawal seizures or delirium tremens (DTs
) greatly increases the risk associated with withdrawal. The specifics of these adverse effects and ways to avoid them should be detailed. The patient may be referred for treatment and, even if unable to achieve abstinence they may improve their risk by reducing the frequency and intensity of use. Elective surgeries may need to be delayed until abstinence is achieved, which can be assessed with urine drug testing. Studies have shown a greatly reduced risk of surgical complications in patients who achieve abstinence. Even if the substance use disorder is in remission, patients may be at increased risk. Patients in recovery from opioid use, for example, may have difficulty appropriately managing opioid analgesia and may have concerns about relapsing. Input from an addiction specialist can be helpful.
There are many medications used to treat addiction such as naltrexone for alcohol or opioid use disorders, and methadone and buprenorphine maintenance for
opioid use disorder which have perioperative implications. The dosage and prescriber of these medications are verified during the preoperative evaluation. While most States in the United States have online prescription monitoring programs which show controlled substance prescriptions, they usually do not contain information on noncontrolled substances, medications prescribed at Veterans Affairs facilities or at methadone maintenance clinics. The physical examination may yield clues to possible substance use issues (Table 12.4
TABLE 12.4 Common Stigmata of Substance Use Disorders
Substance Use Disorder
Decreased respiratory rate
Lethargy, pinpoint pupils
Track marks, local abscesses
IV drug abuse
IV drug abuse complicated by endocarditis
Jaundice, caput medusae, ascites
Alcohol or sedative withdrawal, or stimulant intoxication
Patients with substance use disorders are at high risk for associated health issues, such as infectious hepatitis or human immunodeficiency virus (HIV
). Many addicts are heavy smokers with unhealthy lifestyles. Medications without perioperative implications for addiction, such as gabapentin or SSRI
antidepressants, should usually be continued.
ALCOHOL USE DISORDER
Alcohol use disorder is the most common substance use disorder other than tobacco and is present in every culture worldwide. The lifetime prevalence for alcohol use disorder is estimated as 29%, which includes all levels of severity, including binge drinking. Lifetime prevalence of severe alcohol use disorder is 13.9% (3
). It can be difficult to make this diagnosis in patients whose disorder is not particularly severe, since alcohol is so commonly used. Patients usually admit to drinking but may minimize the amount and deny any problems associated with drinking. In some cases, the diagnosis is made when medical complications are noted, or from collateral information from the patient’s family or medical record. Alcohol is a potent intoxicant which affects many different organ systems, particularly with prolonged and intense use and
with poor dietary intake. Table 12.5
lists medical complications associated with prolonged alcohol use. Heavy alcohol use increases the risk of perioperative mortality (4
Laboratory abnormalities include elevated liver enzymes, decreased mean corpuscular volume (MCV
), and coagulation abnormalites. Table 12.6
lists suggested preoperative assessment.
TABLE 12.5 Medical Complications of Alcohol Use Disorder
Central Nervous System
Cerebral atrophy, cerebellar degeneration, amnestic blackouts, tremor
Dilated cardiomyopathy, dysrhythmia, peripheral arterial insufficiency, hypertension
Gastritis, esophagitis, esophageal varices, gastric ulcers, pancreatitis, hepatitis, cirrhosis
Wernicke-Korsakoff syndrome, hypoalbuminemia, hypomagnesemia, pellagra, beriberi
Microcytic anemia, coagulopathy
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