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7 Elective Surgery forPatients withSubstance Use Disorder or Recent Substance Misuse
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Management Strategies
For chronic marijuana users, regardless of the route of ingestion, use within 72h of
elective surgery should be discouraged [43]. Patients who cannot or will not abstain
prior to surgery should be counseled as to the risks involved with continued use during the perioperative period. For the patient who presents with recent use, informed
consent should be obtained at least 2h after the last ingestion and in the absence of
signs of impairment.
Inhalants
Nitrous Oxide
Inhalants represent a very small portion of the commonly misused drugs worldwide,
but deserve mention as they are most often used by the younger, healthier patients
who would seem, without knowing this history, to fall into the very-low risk category for elective surgery. Nitrous oxide (N2O) or laughing gas specically has long
been established as a very commonly misused drug, especially in the United
Kingdom (UK), the United States (US), and Australia (38.6% and 29.4% lifetime
prevalence) [50]. In this study, the eighth most commonly misused substance was
N2O. Intoxication with this substance is achieved through inhalation of the gas,
often in the absence of supplemental oxygen, which generates auditory and visual
hallucinations, euphoria, and total body insensitivity to pain. As a result of this
inability to feel pain, accidental injury sometimes severe is not uncommon. Misuse
of N2O represents a signicant problem because of the difculty involved with identication, as we will see below, and the toxicity associated with chronic misuse [51].
Paint Solvents
So called hufng or the inhalation of the volatile agents present in paints (particularly spray paints), paint thinner, and industrial solvents, induce a state of euphoria,
similar to that which is achieved by the inhalation of N2O.Unlike N2O, however, the
effects are longer lasting and are more likely to be associated with dependence,
tolerance, irritability, anxiety, and cravings. Commonly available household items
including air freshener, nail polish remover, and model glue have documented misuse potential [52]. Due to the low cost and high availability of these agents these are
most commonly misused by adolescents, including those of low income countries [53].

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Anesthetic Gases
The misuse of the volatile hydrocarbon anesthetics, most commonly sevourane,
has also been reported, especially among people with access to these agents such as
physicians, nurses, and even hospital employees as these drugs are not controlled in
the same way that opioids and other scheduled drugs are.
Identication
With the exception of the patient who presents for elective surgery with a history of
neurological complications related to chronic N2O misuse or who admits to this
misuse in the preoperative interview, identication of chronic use is difcult. The
effects of the drug are transient and, while there is the potential for addiction, the
stigmata of N2O misuse, even in the most severe cases, is often absent. Nitrous
oxide misuse is not detected by any available screening tools due to its short halflife and rapid elimination through the lungs [54]. Intoxication lasts for a brief period,
measured in seconds or minutes, and there is no evidence that even chronic N2O use
has any residual effects on the sensorium. Absent laboratory conrmation, the interview is the best opportunity to elicit this information.
Identication of the patient who chronically misuses commercially available
industrial solvents is difcult. On routine pre-op laboratory examination, the presence of anemia or leukopenia may indicate chronic misuse and should be further
evaluated [55]. Physical signs include the residue of paint or adhesive around the
oropharynx, commonly associated with the practice of “bagging” whereby the agent
is placed in a paper bag and ingested via hyperventilation, or by the neurologic decits associated with chronic misuse. There are currently no commercially available
laboratory tests which can identify the chronic user, so an increased index of suspicion is essential during the preoperative interview. The misuse of the volatile anesthetic agents is even more difcult to identify, as chronic use of these agents is much
less likely to result in neurologic sequelae.
Implications forSurgery
Chronic exposure to N2O is thought to put the user at risk for the development of a
hypercoagulable state, increasing the risk for deep venous thrombosis (DVT) and
potential pulmonary embolism (PE) during elective surgery. Several case reports of
thromboembolisms, especially in young, otherwise healthy individuals, point to the
increased risk when these patients opt to undergo elective surgery in this setting
[56–58].
The effects of chronic N
chemical structure, and depend primarily on the degree to which the agent has been
used, including length of use and total dose. During use, peripheral vasodilation
O and volatile agent misuse are similar regardless of
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occurs, resulting in compensatory tachycardia, but decreased myocardial contractility often causes orthostatic hypotension. It is unclear if these physiological phenomena occur in the chronic user who presents for elective surgery while not under the
inuence, but this should be a concern, as tachycardia combined with decreased
myocardial contractility resulting in hypotension have been reported. With acute
intoxication, bradycardia, decreased cardiac output, and “sudden sniff death syndrome” may occur, most likely related to the development of a malignant dysrhythmia [59].
Management Strategies
Patients with chronic inhalation misuse are at increased risk for nausea and vomiting, which can lead to aspiration, and reactive airway disease, even in the absence
of asthma, which increases the risk for bronchospasm and laryngospasm. These
volatile agents are known hepatotoxins and chronic users are also at risk for undiagnosed liver disease, which has the potential to affect many of the anesthetic agents
used during elective surgery. Renal injury, specically chronic renal tubular acidosis, has also been reported and should be evaluated prior to elective surgery. Chronic
use can also lead to vitamin B12 deciency, commonly manifesting as peripheral
neuropathy [60].
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CNS Depressants
Opioids
Opioids are a broad class of drugs that interact with opioid receptors and cause pain
relief and euphoria. The term “opioid” includes all drugs in this class. The term
“opiate” refers to natural opioid compounds such as heroin, morphine, and codeine.
Semi-synthetic and synthetic opioids are commonly prescribed for postoperative
pain management and include the popular fentanyl and its derivatives.
It has been well-established that opioid misuse is a pressing public health issue.
Over the past few decades, there has been a dramatic increase in opioid prescriptions with a parallel increase in opioid misuse, abuse, and overdose. The opioid
crisis has become so severe that it has been declared a public health emergency by
the U.S. government, with the CDC citing 44 deaths daily from opioid overdose
[61]. 3.7% of the United States population has misused opioids in the past year, the
most common substance being prescription pain relievers [62]. Approximately 25%
of preoperative patients will be using opioids [63].
It is important to note that not all patients who chronically use opioids are misusing them or have opioid use disorder (OUD). Some patients may present for surgery
who are using prescribed opioids appropriately for chronic pain conditions. After a

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few weeks of consistent opioid use however, patients will become “dependent,”
meaning they will experience withdrawal symptoms if they stop taking the medication. Physical dependence can exist without addiction or a use disorder. If a patient
is addicted to opioids or has OUD, there is physical dependence as well as cravings
and inability to control drug use.
Identication
Opioids can be taken by a variety of routes, including oral, inhaled, and injected. In
those who inject, marks may be seen on the skin. Signs of acute opioid intoxication
include slowed respiratory rate, pinpoint pupils, nausea and vomiting, and confusion or delirium. The usual urine drug screen is able to detect heroin, but is not
sensitive for synthetic opioids such as oxycodone, hydrocodone, methadone, or fentanyl. These drugs can be tested with specic immunoassay panels [39].
Implications forSurgery
Those who chronically use opioids will have a higher tolerance for the drug class,
which can make pain management intraoperatively and postoperatively challenging. Patients may be admitted to the hospital for pain management who would have
otherwise been able to be discharged from the PACU.Studies across surgical elds
have found that having OUD is associated with longer hospital stay by approximately 2days [64, 65]. In orthopedic surgery, OUD was associated with increased
mortality and morbidity such as respiratory failure, myocardial infarction, and surgical site infection [66]. Patients who use opioids intravenously, such as heroin,
have even more risk. Due to the route of administration, they are at risk for endocarditis, pulmonary infection, infected deep venous thrombosis, and sepsis [67].
Management Strategies
Preoperatively, it is important to distinguish if the patient has an OUD or uses opioids chronically for pain. Those with OUD should be referred to appropriate
resources where they can be weaned from opioids safely before surgery takes place
[4]. In contrast, those who use prescribed opioids for pain conditions should continue their medications. They should take their usual pain medication the morning
of surgery, especially if they take any long-acting opioids such as methadone [68].
Pain may be difcult to control in patients who have a tolerance to opioids. There
are no formal guidelines for pain management, but most recommend a multimodal
approach [69]. Instead of higher doses of a single medication type, lower doses of a
variety of medications with different mechanisms of action are used [70].
Acetaminophen, ketorolac, and lidocaine patches are mainstays of treatment.
Regional anesthesia can be useful, including nerve blocks, peripheral nerve

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catheters, and epidural catheters. In patients with refractory pain, ketamine infusion
can be considered [71]. Patient-controlled analgesia (PCA) pumps administering
opioids are a great tool for hospitalized patients [72].
Opioid maintenance therapy is used for patients with OUD and includes three
main medication options: buprenorphine, methadone, and naltrexone [73].
Buprenorphine is a partial mu agonist and full kappa antagonist with weak analgesic effect. Importantly, it has a ceiling effect on respiratory depression which makes
overdose less likely [74]. Because it blocks the binding of any additional opioids to
pain receptors, it can make the treatment of pain difcult [75]. A multimodal pain
approach is recommended, and additional buprenorphine can be given [76]. As
acute cessation can precipitate withdrawal symptoms, it is recommended to continue through surgery [77]. Methadone is a full mu agonist with more analgesic
effect than buprenorphine. It is long acting with a biphasic elimination. It can also
be taken preoperatively including the day of surgery. Those who take methadone
may need higher doses of opioid medications to adequately treat pain. The QTc can
be prolonged by methadone and should be monitored. These two drugs are not interchangeable; in patients treated with methadone, treating with a partial agonist such
as buprenorphine will precipitate withdrawal [78]. Naltrexone is an opioid antagonist that prevents the binding of opioids to pain receptors [79]. It follows that
patients taking naltrexone can have postoperative pain that is extremely difcult to
control, and that naltrexone should be discontinued preoperatively. Oral naltrexone
should be discontinued for 2–3days and injectable naltrexone for 28days before
elective surgery [80]. Because chronic naltrexone use leads to an upregulation of
opioid receptors, patients are at an increased risk of overdose once naltrexone is
discontinued (Table7.1) [81].
All opioid-dependent patients who are admitted to the hospital postoperatively
are at risk for withdrawal. Acute withdrawal can cause central excitability such as
insomnia and anxiety, and autonomic hyperactivity such as tachycardia, hypertension, sweating, and hyperthermia [4]. Other classic signs include piloerection, lacrimation, nausea and vomiting, and pupillary dilation. Withdrawal can be
Table 7.1 Perioperative opioid maintenance therapy
Drug Type
Buprenorphine Partial mu agonist,
Methadone Full mu agonist Continue, take day
Naltrexone Competitive mu
full kappa antagonist
antagonist, partial
kappa agonist
Preoperative
management Postoperative considerations
Continue, take day
of surgery
of surgery
PO: Stop 2–3days
preoperatively
IM: Stop 28days
preoperatively
• Inhibits additional opioids from
binding to receptors, making them
less effective at treating pain
• Multimodal pain approach is
benecial
• Those taking methadone may
require higher doses of opioids
• Can prolong QTc
• Patients are more sensitive to
opioids, increased risk of
overdose

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life-threatening, and so any patients who present with opioid use preoperatively
should be carefully monitored in the postoperative period.
CNS Stimulants
Cocaine andMethamphetamines
In the United States in the past year, 1.7% of the population has used cocaine [82].
Cocaine is involved in one in ve overdose deaths. The rate of patients who present
for elective surgery and are found to be positive for cocaine on drug testing likely
varies regionally, though one center reports a rate of 1% [83]. Cocaine can be used as
a powder which is inhaled nasally, used orally, or dissolved and injected intravenously. Crack cocaine is a form with a quicker euphoric effect that is smoked.
Recently, there has been a rise in cocaine contaminated with fentanyl and fentanyl
analogues, which should be kept in mind with any reported history of cocaine use [84].
Identication
Signs of acute cocaine intoxication include tachycardia, hypertension, pupillary
dilation, diaphoresis, tremor, restlessness, and agitation. Chronic misuse can cause
seizure, stroke, and cognitive impairment [85, 86]. Physical exam ndings concern-
ing for cocaine misuse include nasal/septal/palatal defects, gingivitis, and pulmonary symptoms in crack cocaine users. A urine drug screen is positive after acute
use for 2–3days and for several weeks with chronic use [39].
The signs of acute intoxication with methamphetamines are similar to acute
cocaine intoxication and include akathisia, hypervigilance, volatile or violent
behavior, psychosis, dilated and minimally reactive pupils, tachycardia, hypertension, hyperthermia, and diaphoresis [87]. Chronic misuse is evident in most users
by the presence of so-called meth mouth which is characterized by severe tooth
decay and loss caused by associated corrosive chemicals, xerostomia, impaired gingival and tooth perfusion, and poor diet. There may be the odor of ammonia on the
breath, and the presence of ‘meth mites’ or ‘meth bugs’ caused by intense localized
pruritus which chronic users commonly scratch until open wounds are created [39].
Of note, while methamphetamines are commonly included in most urine toxicology drug screens, false positive results have been reported in those taking brompheniramine (an antihistamine), phenylpropanolamine (a nasal decongestant),
bupropion and trazodone (common antidepressants), chlorpromazine and promethazine (common antipsychotics), and ranitidine (an H
blocker) [41].
2

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Implications forSurgery
Cocaine has been shown to induce thrombocytopenia [88]. This may cause some
anesthesiologists to not perform neuraxial techniques or regional blocks due to risk
of hematoma in nerve spaces. Surgically, this can increase risk of operative bleeding. Cocaine use can also cause pseudovasculitis and may impair wound healing [39].
There are concerns about the deleterious effects of cocaine use on organ systems
during general anesthesia. Cocaine use is a known risk factor for cardiovascular
events including severe hypertension, dysrhythmias, MI, and aortic dissection [49].
Case reports have reported severe cardiac events in chronic cocaine users in the
absence of acute intoxication [89]. Cocaine use can also cause spontaneous pneumothorax [90].
The risks for the patient who chronically misuses methamphetamines are similar
and include uncontrolled hypertension, perioperative MI, and coronary artery
spasm. Chronic users may have developed cardiomyopathy and pulmonary hypertension and are at risk for aortic dissection [91]. In one study, patients who tested
positive for methamphetamines within 24h of surgery were 31.4% more likely to
experience hemodynamic instability during the rst hour of general anesthesia as
compared to 26.1% who tested positive between 2–7days prior to surgery and only
6.3% of controls [92].
Management Strategies
Elective surgery in a patient who is acutely intoxicated should be postponed. There
is debate about the best management strategy for a patient who is not acutely intoxicated, but presents for elective surgery with a positive drug screen. The conservative approach is to wait 1week after cessation or for a negative drug screen [89].
Cancelation of cases leads to increased cost, and some studies suggest that general
anesthesia is safe in a non-acutely intoxicated patient [83, 93]. For these reasons, it
may also be appropriate to observe the patient for 8h (the time it would take for any
active cocaine to be metabolized), and if asymptomatic, proceed with surgery [94].
Overall, the decision to proceed with elective surgery should take into consideration the patient history, acuity of the surgery, discussion between the surgeon and
anesthesiologist, and discussion between the surgical team and the patient.
Postponing surgery up to 7 days somewhat decreases the risks associated with
methamphetamine use, but not to the levels of patients who do not use methamphetamines [92].

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Hallucinogens
Lysergic Acid Diethylamide (LSD), Psilocybin,
andPhencyclidine
First synthesized by Swiss Chemist Albert Hofmann from ergot derivatives in an
attempt to nd a drug capable of reducing postpartum hemorrhage, lysergic acid
diethylamide (LSD) has recently seen a resurgence in use as a treatment for
anxiety, depression, psychosomatic disorders and addiction [95]. While its use
today remains primarily as a recreational hallucinogen, LSD has a long history
of medical application, particularly within the psychiatric community, as a
means to facilitate remission of psychiatric symptoms. With the recent move
toward decriminalization and legalization of psychoactive drugs, LSD should be
considered, along with other hallucinogens, as a potential agent which will
complicate the perioperative management of the patient presenting for elective
surgery.
Identication
LSD, as with other “classical hallucinogens” such as psilocybin and dimethyltryptamine, alters perception and creates an altered state of consciousness. Alterations
include distortions in the perception of time, depth, the size and shape of objects,
movement, color, sounds, touch and are associated with delusions which have led to
unintentional self-harm or harm to others [96]. When acutely intoxicated, patients
may appear to be psychotic, exhibiting symptoms of anxiety, dysphoria and confusion. Increases in heart rate and blood pressure are often accompanied by mydriasis,
almost to the point of elimination of the iris, mild hyper or hypothermia, piloerection, and hyperglycemia. Use is not associated with physical dependence nor is
there a withdrawal syndrome, though tolerance for the effects of LSD has been
reported [97].
Implications forSurgery
It is likely that LSD works as an agonist at the serotonin 2A receptor (5-HT2A),
and there is evidence that HT2A antagonists can attenuate and perhaps reverse the
main effects of these substances [98]. If a patient presents for elective surgery
under the inuence of LSD, the procedure should be rescheduled. Recent use does
not preclude elective surgery, though use of other recreational pharmaceuticals
should be investigated through discussion prior to proceeding.

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Management Strategies
Patients who present for elective surgery not currently under the inuence of LSD
do not require any specic management strategies directly related to recent use. It
should be noted, however, that recent or chronic use has been associated with “ashbacks”, in which the individual experiences the effects of the hallucinogen even
though they are no longer under its inuence [99]. These events can be triggered by
the stress of surgery, fatigue, or by the concomitant administration of other medications during the perioperative period, and should the patient experience symptoms
as described above, this should be considered as part of the differential diagnosis.
Supportive care is indicated and the patient may benet from anxiolytics and, in
extreme cases, psychiatric consultation.
Conclusion
Surgery should take into consideration the recency and extent of use, the surgical
and anesthetic risks, and the necessity of the surgery. Programmed discussion of
substance misuse with surgical candidates is fundamental as it allows time to refrain
from the substance preoperatively, but also may provide a motivation to quit that did
not exist earlier.
There are always new drugs with misuse potential being synthesized, and it
would behoove the surgeon to stay up-to-date with novel substances that may be
prevalent in their community. For example, xylazine (“Tranq”) has recently become
epidemic to certain cities in the USA, with overdose deaths increasing 1127% from
2020 to 2021in the South [100]. Patients may not disclose drug use if not specically asked, so by knowing the common names of drugs of misuse a more accurate
history may be obtained (Table7.2).
Table 7.2 Implications for surgery and preoperative management for commonly misused
substances
Substance Implications for surgery Preoperative management
Alcohol
Tobacco
• Increased risk of cardiopulmonary
events, bleeding, and infection
• Increased length of hospital stay
and cost
• Increased risk of pulmonary
complications (laryngospasm,
bronchospasm, reintubation), ICU
admission, infection, cardiac
events
• Poor wound healing
• Ideally abstain for 1month
preoperatively
• Can proceed if not acutely
intoxicated
• Ideally abstain for 6–8weeks
preoperatively
• For patients with coronary disease:
At a minimum abstain for 12h
preoperatively, if not may postpone
• If recent use, may discuss risks
with patient and obtain informed
consent
(continued)

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Table 7.2 (continued)
Substance Implications for surgery Preoperative management
Marijuana
Nitrous oxide
Opioids
Cocaine
Methamphetamine
Lysergic acid
diethylamide
(LSD)
• Increased risk of MI, ectopy,
airway obstruction, laryngospasm,
bronchospasm, awareness under
anesthesia
• Increased risk of DVT, PE,
tachycardia and hypotension,
dysrhythmia, aspiration,
laryngospasm, bronchospasm
• Challenging pain management
• Increased risk of respiratory
failure, MI, surgical site infection
• Increased risk of
thrombocytopenia, cardiovascular
event (aortic dissection, MI,
hypertension, dysrhythmias),
spontaneous pneumothorax
• Increased risk of coronary artery
spasm, aortic dissection, MI,
hypertension
• HT2A antagonists (ex. trazodone)
can attenuate and perhaps reverse
the main effects of the drug
• Ideally abstain for 72h
preoperatively
• If recent use, may discuss risks
with patient and obtain informed
consent at least 2h after ingestion
in absence of signs of impairment
• In chronic users evaluate for
reactive airway disease, hepatic
and renal disease, vitamin B12
deciency
• If not acutely intoxicated, no
contraindication to proceeding
with surgery
• OUD: Wean off opioids before
elective surgery
• maintenance therapy: See Table7.1
• Chronic pain: Continue regimen up
to day of surgery
• Postpone for 7days after last use
• If case is more urgent, can observe
for 8h and proceed if
asymptomatic
• Postpone for 7days after last use
• If not acutely intoxicated, no
contraindication to proceeding
with surgery
T. Scott and E. O. Bryson
References
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