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The Implications of the Opioid Epidemic

for the Treatment of Perioperative Pain

Nan Xiang, Denise Courtney, Shivana Ramsingh, Rebecca Donald,

and Sudheer Potru

Abstract The opioid epidemic in the United States and around the world has signiﬁ-

cant implications for the use of opioids in the management of acute and chronic pain.

The perioperative period is often the initial exposure to opioids for many patients and

may be an inﬂection point for particularly vulnerable patients. Adjusting expecta-

tions and consistent messaging from the surgical, anesthesiology, nursing, and other

teams when appropriate is likely to result in the best outcomes for the patient.

Keywords Opioid crisis

· Opioid epidemic · Fentanyl · Substance use disorder ·

Addiction · Overdose

1 Introduction

The opioid epidemic, declared a U.S. public health emergency in 2017, refers to a

modern crisis involving substantially increased rates of misuse, abuse, and overdose

deaths attributed to the opioid class of drugs. Since 1999, the United States has

experienced an estimated one million deaths from drug overdoses, the majority of

which involve opioids and, more recently, s peciﬁcally fentanyl [1]. With over 10,0000

N. Xiang · S. Potru (

)

Department of Anesthesiology, Emory University, Atlanta, GA, USA

e-mail: sudheer.potru@emory.edu; sudheer.potru@emory.edu

N. Xiang

e-mail: nan.xiang@emory.edu

D. Courtney

Atlanta VA Healthcare System, Decatur, GA, USA

e-mail: denise.courtney@va.gov

S. Ramsingh

University of West Indies, St. Augustine, Trinidad and Tobago

R. Donald

Department of Anesthesiology, Vanderbilt University, Nashville, TN, USA

e-mail: rebecca.donald@vumc.org

A. Abd-Elsayed and K. Schroeder (eds.), Perioperative Pain Management,

https://doi.org/10.1007/978-3-031-67648-2_4

https://t.me/med1917

54 N. Xiang et al.

deaths annually, drug overdose is now the number one cause of unintentional death

in the U.S. and has contributed to an unprecedented decline in life expectancy [2–

4]. In addition to the impact on mortality, consequences of the opioid epidemic

include (1) rising rates of human immunodeﬁciency virus (HIV) and hepatitis C

virus (HCV) infections; (2) escalating rates of perinatal morbidity and mortality;

and (3) an estimated one trillion dollars in ﬁnancial burden to the U.S. economy

[5–9].

In this chapter, we seek to explain the origins of the opioid epidemic in the United

States, review the evolution of the epidemic itself, discuss mitigation strategies, and

describe perioperative evidence-based patient management in the current prescribing

environment.

Background of the Opioid Epidemic

While the opioid epidemic clearly has numerous causes, the origin story for this crisis

can largely be traced back to a series of events beginning in the 1990s. In 1996, Purdue

Pharma utilized already-existing extended-release medication technology to bring to

market a high-dose oxycodone product known as OxyContin. Although oxycodone

was an old drug, the approval of this new formulation was based on the Food and

Drug Administration’s assessment that OxyContin’s delayed absorption reduced the

potential for eventual opioid abuse. Upon approval, Purdue began an aggressive

marketing campaign that resulted in billions of dollars in revenue for the company

and a ﬂood of prescription opioids into communities [10]. Citing narrowly focused

medical literature to increase drug sales, Purdue claimed that OxyContin was safe

and effective for chronic pain, with little addiction potential [10]. Purdue’s assertion

that OxyContin was largely nonaddictive was based on a New England Journal of

Medicine letter to the editor published in 1980 by physicians from Boston University

Medical Center; this brief letter summarized ﬁndings of a non-peer-reviewed, retro-

spective study evaluating 1,1882 hospitalized patients that received at least one dose

of an opioid medication while admitted [10, 11]. The review found that only four

patients who received an opioid became addicted, leading the authors to conclude

that ‘the development of addiction is rare in medical patients with no history of addic-

tion” [11]. Similarly, Purdue’s signiﬁcant push to expand opioid use for chronic non-

malignant pain was based on a retrospective review of just 38 patients that concluded

opioid therapy to be a “safe, salutary, and more humane” option for treating chronic

pain [12]. Purdue later pled guilty to felony misbranding and violating federal anti-

kickback laws for making false claims related to OxyContin and paying physicians

to write more and higher-dose OxyContin prescriptions [13].

Until the early 2000s, opioids were primarily being used to treat acute pain, but

rates of opioid prescribing for chronic noncancer pain began to increase substantially;

in 2012, the national opioid dispensing rate peaked at 255 million prescriptions [14,

15]. Aggressive pharmaceutical marketing and increased focus on the treatment of

uncontrolled pain in the medical community (including the pain as the “ﬁfth vital

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The Implications of the Opioid Epidemic for the Treatment … 55

sign” initiative) resulted in widespread acceptance for the use of opioids for non-

cancer pain [10, 16]. Lack of standardization of curriculum and training for physicians

in the areas of pain management and substance use disorders (SUDs) may have

contributed to expanded opioid prescribing.

However, the opioid epidemic is certainly a result of a multisystem failure.

Many rural and socioeconomically disadvantaged communities experienced chal-

lenges with access to specialty pain management care, as well as poverty and mental

health comorbidities, making them particularly vulnerable to opioid use. Prescrip-

tion opioids often entered these communities at unprecedented rates through “pill

mills” run by unscrupulous clinicians and entrepreneurs as well as true illicit drug

dealers. Clinicians at these facilities across the country prescribed and dispensed

hundreds of thousands of opioid tablets without standard workup or physical exam,

and sometimes without even having seen the patient at all [17]. Although law enforce-

ment became increasingly aware of the contributors to opioid abuse and diversion,

physicians practicing medicine and writing prescriptions was considered outside of

the purview of traditional law enforcement [18]. In recent years, the pharmaceutical

distributors that shipped millions of opioid pills to pill mills have faced lawsuits for

failure to monitor and report suspicious orders [19].

Characteristics of the United States health care system played a role in the rise of

the opioid crisis as healthcare facilities commonly rely on volume-based care rather

than value-based care for revenue. Furthermore, prescription opioids are often more

ﬁnancially accessible than other pain treatments like physical therapy, interventional

procedures, or other non-medication-based treatment modalities [20]. Many prescrip-

tion drug plans cover common opioids but either provide limited coverage or require

prior authorization for less addictive pain medications, interventional procedures, or

medications used to treat opioid use disorder [20, 21]. Also exacerbating the ongoing

crisis was pharmaceutical industry inﬂuence on lawmakers, federal regulatory bodies,

professional medical organizations, and patients through direct-to-consumer adver-

tising, as well as American socioeconomic and cultural factors, including the so-

called “pill for every ill” mentality [22]. Now, with over two million Americans

currently diagnosed with opioid use disorder, the opioid epidemic is ongoing and

continues to evolve [23].

Evolution of the Opioid Epidemic

The opioid epidemic has emerged in waves distinguished by the types of opioids

contributing to overdose deaths. The ﬁrst wave, which began around 1996, was

dominated by prescription opioids. The abundance of prescription opioids facilitated

their illegal distribution and non-medical use; between 1992 and 2003 the number

of people misusing prescription drugs increased by 90% [24, 25]. Opioid-related

deaths paralleled this increase in both medical and nonmedical use of prescribed

opioids; in 2007, commonly prescribed opioids were involved in 78% of opioid

overdose deaths [26]. As previously noted, the total number of opioid prescriptions

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56 N. Xiang et al.

dispensed peaked at more than 260 million in 2012, but from 2012 to 2021, the rates

of opioid prescribing decreased in all 50 states with a national decrease of 46.4%

during this time period [27]. Despite this decrease, prescription opioids still played

a prominent role in opioid overdose deaths, but the percentage of deaths involving

only prescription opioids gradually fell with increasing rates of heroin and fentanyl

use [26].

The second wave of the opioid epidemic was marked by the transition to heroin,

an illicitly produced semisynthetic opioid derived from the opium poppy, beginning

roughly around 2010. As deaths attributable to opioids began to rise in the early 2000s,

state and federal laws were passed with the intention of reducing supply, demand, and

harm of prescribed opioids [25]. The National All Schedules Prescription Electronic

Reporting (NASPER) Act was passed in 2005, which provided for the establishment

of prescription drug monitoring programs (PDMPs) in each state [24]. PDMPs led

to greater vigilance about possible opioid misuse, doctor shopping, or prescription

opioid diversion and further curbed opioid prescribing. According to a study by

Dowell et al., the combination of more restrictive prescribing laws and increasing

use of PDMPs led to the reduction in opioid prescriptions by 8% and prescription

overdose deaths by 12% from 2006 to 2013 [28].

In addition to the development of PDMPs and the passage of legislation creating

greater restrictions and scrutiny related to opioid prescribing, other measures were

taken to bring greater attention to the dangers of prescription opioids. In 2011, the

Centers for Disease Control (CDC) declared deaths from prescription opioids an

“epidemic.” This was followed in 2012 with the development of a new “Policy

Academy” by the American Medical Association to address the growing problem of

prescription opioids [27]. Finally, in 2016, the initial CDC Guideline for Prescribing

Opioids for Chronic Pain was published. The stated goal of these guidelines was to

provide guidance about responsible opioid prescribing for primary care providers

who may not have had formal training in pain management or addiction medicine. In

the wake of this publication, however, many states passed additional laws to limit the

supply of opioids. In addition, limitations on opioid prescriptions by pharmacies and

insurers have created additional pressure on clinicians to stop or avoid prescribing

opioids [20]. While there was likely a beneﬁt realized from reducing the number

of opioid pills in circulation, many patients treated with opioids for years and/or

decades were (and have been) left searching for other clinicians to prescribe their

medications.

Unfortunately, the ongoing demand for and reduced availability of prescription

opioids coincided with the inﬂux of heroin into the United States from international

markets. Heroin also saw a dramatic decrease in price during this time, making it

easier to access and cheaper to obtain than other illicit prescription opioids [25].

The increasing ease of access to a more potent yet cheaper opioid prompted many

users of prescription opioids to transition to heroin as their drug of choice [20].

A study by Cerdá and colleagues found that those with a history of prescription

opioid misuse were 13 times more likely to start using heroin than those who had

no history of prescription opioid misuse [29]. As heroin began to dominate the illicit

opioid market, deaths involving heroin also began to rise; from 2010 to 2017, deaths

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The Implications of the Opioid Epidemic for the Treatment … 57

involvingheroin increased ﬁvefold.The percentage of opioid deaths involving heroin

peaked at 41% in 2015, but even while the percentage of deaths involving heroin

decreased, the overall number of deaths involving heroin continued to increase. It

was only after 2017 that deaths involving heroin ﬁnally began to decline [26].

The United States entered the third and most deadly wave of the opioid epidemic

around 2013, when synthetic opioids began to dominate the illicit drug market. As

previously discussed, synthetic opioids, particularly fentanyl, began to gradually

supplant heroin as the predominant illicit opioid for several reasons. First, fentanyl

can be produced inexpensively in a lab from chemicals that are both easy to obtain and

not tightly regulated abroad; Mexico remains the primary source of illicit fentanyl

with many of the requisite chemicals being purchased from China. Second, since

fentanyl is 50 to 100 times as potent as heroin, smaller quantities can be transported,

so the drug is more easily smuggled and distributed [25]. In addition, there is a large

online market for illicit drugs, facilitating the purchase of unregulated opioids [30]

(Fig. 1).

The increased potency of fentanyl and its related compounds has undoubtedly

contributed to the dramatic rise in opioid overdose deaths during the opioid epidemic.

With the ever-changing landscape of the illicit opioid market, the content and potency

of illicit drugs have become unpredictable, making it at times impossible for users

to know what they are consuming. According to the 2021 DEA Fentanyl Proﬁling

Programming Report, the purity of the 666 fentanyl powder samples (representing

more than 778 kg of drug) analyzed ranged from 0.1 to 75.6% with an average purity

of 14.4%. The fentanyl content of the pressed pills (commonly marketed by drug

dealers as oxycodone, OxyContin, or Percocet) also varies signiﬁcantly, with the

average amount of fentanyl increasing from 1.3 mg/tablet in 2017 to 2.2 mg/tablet

in 2022 [31]. Finally, opioid deaths are being increasingly attributed to synthetic

fentanyl analogs whose chemical structure can easily be manipulated to evade detec-

tion by law enforcement. The potency of these compounds varies signiﬁcantly. From

Fig. 1 The Waves of the Opioid Epidemic. https://www.cbo.gov/publication/58532

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58 N. Xiang et al.

2019 to 2020, deaths involving synthetic opioids increased by over 56% and in 2020,

synthetic opioids were involved in over 82% of opioid-involved deaths. This repre-

sents an 18-fold increase from the number of deaths involving synthetic opioids

in 2013; users are caught unaware of fentanyl’s potency and many have suffered

unintentional overdoses [1].

A fourth wave of the opioid epidemic appears to be emerging at the time of this

writing, as synthetic opioids are increasingly used in combination with psychos-

timulants such as methamphetamines or cocaine as well as other CNS depressants

such as xylazine, an alpha-2-agonist utilized primarily as a tranquilizer in animals

[32]. Some individuals intentionally combine opioids with stimulants to not only

enhance the euphoria from the opioids but also to counteract what some perceive as

the unpleasant effects of opioids [32]. Other users unwittingly consume combination

drugs, as synthetic opioids and stimulants are increasingly combined by drug dealers

or suppliers [25]. Not only do deaths due to psychostimulants in combination with

synthetic opioids continue to rise, but deaths attributable to stimulants alone have

also been steadily rising; overdose deaths due to psychostimulants alone increased

2.3-fold from 2015 to 2020 [33].

The Impact of COVID-19 on the Opioid Epidemic

The death rate during the third wave of the opioid epidemic saw an inﬂection

point in the spring of 2020 coinciding with the start of the COVID-19 pandemic.

From December 2019 to December 2020, more than 9,3000 Americans died of

drug overdoses, which was an increase of 29.4% from the prior 12 months [34].

First, the increased stress and isolation from the pandemic led to an increase in

substance use, both in quantity and frequency of use. According to the CDC, by

June 2020, 13% of Americans reported starting or increasing substance use as a

way to cope with the stress of the pandemic [35]. Escalating use in isolation due to

social distancing, the increased potency of illicit opioids, and reduced access to harm

reduction (including safe injection sites, medical practitioners, and medications for

OUD) likely contributed to the escalation in opioid overdose deaths.

For patients with opioid use disorder (OUD) who were already in treatment,

disruptions in care, particularly access to FDA-approved medications for OUD

(methadone, buprenorphine, and naltrexone) and mental health services contributed

to risk of relapse and overdose deaths for this vulnerable and marginalized patient

population. Additionally, for this patient population that relies heavily on social

support for recovery, the isolation from the pandemic proved particularly detrimental

[36].

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The Implications of the Opioid Epidemic for the Treatment … 59

While the COVID-19 pandemic compounded the challenges of the opioid

epidemic, it also led to implementation of several policies that positively impacted the

trajectory of OUD care. This included easier access to care and initiation of MOUD

treatment with buprenorphine via telehealth without the requirement of performing an

in-person visit. Additionally, many Opioid Treatment Programs (OTPs, also known

as methadone clinics), which usually require daily visits for methadone dispensing,

allowed patients on a stable treatment regimen to obtain 14–28 days of medication

at a time and several have continued this practice for stable patients. Finally, the

increasing use of virtual meetings by groups such as Alcoholics Anonymous and

Narcotics Anonymous provided social and emotional support for those who rely on

community social support for recovery [36].

Measures to Mitigate the Opioid Crisis

On October 26th, 2017, the Department of Health and Human Services (HHS), noting

the escalating numbers of overdose deaths, declared the opioid crisis a national public

health emergency (NPHE) in the United States of America; this was later extended

several times and is ongoing [37]. Legislation related to the opioid crisis includes

the Comprehensive Addiction and Recovery Act (CARA, 2016), the 21st Century

CURES Act (2016), the Substance Use-Disorder Prevention that Promotes Opioid

Recovery and Treatment (SUPPORT) for Patients and Communities Act (2018), the

Opioid Crisis Response Act (2018), the more recent State Opioid Response Grant

Authorization Act (2022), and the Medication Access and Training Expansion Act

(MATE, 2022).

While addressing the speciﬁcs of each law would make this chapter excessively

long and is likely out of the scope of this text, these statutes effectively are attempting

to do the following [38–41]:

1. Provide improved education to teenagers and parents regarding the dangers of

opioids (and other drugs) by expanding prevention programs.

2. Improve social and educational programs to support reduction of stigma related

to SUDs and SUD care as well as promote recovery programs and strategies.

3. Increase access to harm reduction strategies such as syringe exchange programs

and safe injection sites.

4. Improve access to MOUD treatment, including requiring Medicaid coverage of

methadone, buprenorphine, and naltrexone. The CARA and SUPPORT statutes

also initially expanded of the scope of practice of multiple practitioners to

prescribe buprenorphine; however, the MATE Act ultimately resulted in elimi-

nation of the so-called “X-waiver”, removing patient caps and limitations from

buprenorphine to improve access as well.

5. Strengthen state prescription drug monitoring programs to include more

substances as well as to link to other states’ PDMP programs to provide

comprehensive prescribing information.

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60 N. Xiang et al.

6. Expand access to naloxone, which is now over-the-counter as of early 2023(43).

7. Educate health care practitioners about the care of patients with SUDs.

8. Increase funding for trial and state opioid response efforts.

9. Increase funding to law enforcement agencies to provide more robust resources

to stop the ﬂow of illicit drugs across the U.S. borders.

10. Improve criminal justice reform, including expansion of drug courts, to reduce

penalties and promote recovery for SUDs.

Perioperative Consequences of the Opioid Epidemic

It behooves the anesthesiologist and pain physician to understand the consequences

of opioid use, including opioid-induced constipation, nausea and vomiting, depres-

sion, worsening of sleep apnea, decreased cognitive function, and development of

tolerance and physical dependence [43]. Chronic use can also lead to the develop-

ment of opioid use disorder (OUD), the desire to obtain and take opioids (either

prescribed or illicit) without regard to personal, social, or professional consequences

[44]. According to the CDC, an estimated quarter of all patients receiving long-term

opioid therapy in a primary care setting suffer from OUD [45].

Chronic opioid use also impacts the post-operative period. Multiple studies have

shown an association between preoperative chronic opioid use and increased postop-

erative complications, increased healthcare utilization such as length of hospital stay

or discharge to a rehabilitation facility, and delayed recovery and wound healing;

these associations occurred in various surgical specialties, including but not limited

to elective abdominal surgery, foot and ankle surgery, total knee and hip arthroplasty,

and posterior lumbar fusion for degenerative spine disease [46–49]. In fact, in a retro-

spective study by Santosa 2020, patients who had been classiﬁed with “medium”

and “high” preoperative opioid use –which was based on oral morphine equivalents

and duration of ongoing opioid therapy –were found to have increased postoperative

mortality compared to the opioid naïve control group [50]. Nadarajah et al. found that

patients undergoing shoulder surgery with preoperative opioid prescriptions appear

to experience higher levels of postoperative pain, decreased function, and decreased

satisfaction [51]. Waljee et al. found that chronic opioid use was associated with

longer hospital length of stay, hospital readmission, and increased ﬁnancial costs for

care [46].

While preoperative opioid use appears to be associated with negative outcomes in

the postoperative period, one must also consider how undergoing a surgical procedure

can potentially contribute to chronic opioid use. The impetus to completely eliminate

postoperativepain due to both social and marketing determinants may have resulted in

the exposure of many opioid-naïve patients to high opioid regimens postoperatively.

Compounding the situation is the lack of an established workﬂow for guiding patients

from acute perioperative pain management to outpatient chronic pain management.

In a landmark study, Brummett et. al examined over 3,6000 opioid-naïve patients

who had undergone “major” and “minor” surgeries between 2012 and 2015 and

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The Implications of the Opioid Epidemic for the Treatment … 61

found that 6.5% of the major surgery patients and 5.9% of the minor surgery patients

were still ﬁlling opioid prescriptions between 90 and 180 days postoperatively [52].

There was not a statistical difference between the major and minor surgery groups;

patient risk factors for persistent postoperative opioid use included tobacco use,

alcohol and other SUDs, anxiety, depression, and preoperative pain disorders such

as back pain and centralized pain. Notably, the number of oral morphine equivalents

prescribed, was also associated with an increased rate of persistent postoperative

opioid use, though the authors note the overall effect size was small. This and other

studies support the existence of modiﬁable patient factors that seem to predominantly

contribute to the risk of persistent postoperative opioid use, while the predicted or

actual magnitude of surgical pain does not appear to be a major differentiator [52, 53].

Other retrospective cohort studies have shown similar ﬁndings. Clarke et. al found

that approximately 3.1% of a total of 3,9000 opioid-naïve patients in Canada from

2003 to 2010 were still receiving opioid medications more than 90 days following

surgery [54]. Alam’s 2012 retrospective cohort study in Canada demonstrated that

opioid-naïve patients undergoing short-stay surgery were 44% more likely to become

long-term opioid users within 1 year if they received an opioid prescription within

7 days after surgery [55]. Not surprisingly, preoperative opioid use is associated with

longer duration of postoperative opioid use, with studies reporting 64–77% of chronic

opioid users continuing to ﬁll opioid prescriptions several months after surgery [53].

More than 20% of patients arriving for elective surgery are already taking opioids, a

sizable portion of the surgical patient population [53].

In summary, opioid-naïve patients are at risk of developing persistent postop-

erative opioid use while individuals already on chronic opioids are also unable to

consistently wean from their opioid regimens following surgery, even if these surg-

eries may be improving their underlying pain generators. This suggests that the

surgical procedure is often an inﬂection point adding to the population of patients

on chronic opioids. A combination of patient risk factors (some modiﬁable), peri-

operative management, and postoperative opioid prescribing practices may play a

signiﬁcant role in this process.

Preoperative

The ﬁrst “intervention” point is at the time of surgical procedure scheduling, with

identiﬁcation of patients who may be at increased risk for persistent postoperative

opioid use. As previously noted, there are multiple patient characteristics that increase

such risk, and established questionnaires such as the Opioid Risk Tool (ORT) aim to

use self-reported data to predict the risk of opioid misuse. However, recent studies

suggest that revisions to the ORT may be needed to maintain their validity and its

applicability to the postoperative period is unclear [56–58].

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62 N. Xiang et al.

2 Opioid Risk Tool—OUD (ORT–OUD) [58]

This tool should be administered to patients upon an initial visit prior to beginning

or continuing opioid therapy for pain management. A score of 2 or lower indicates

low risk for future opioid use disorder; a score of >/= 3 indicates high risk for opioid

use disorder.

Revised Opioid Risk Tool

Category Yes No

Personal history of illicit drug use [1]

Personal history of alcohol misuse [1]

Personal history of prescription drug misuse [1]

Family history of illicit drug use [1]

Family history of alcohol misuse [1]

Family history of prescription drug misuse [1]

Age between 16 and 45 years old [1]

History of depression [1]

History of ADHD, OCD, bipolar disorder, schizophrenia [1]

Tota l

Adapted from Cheatle et al. [58].

For patients at increased risk for persistent opioid use (and those for whom

increased or chronic opioid use could potentially be harmful), it is important to

provide appropriate expectations for severity of postoperative pain, as Waljee et al.

have shown that appropriate analgesic expectations correlated with lower reported

postoperative pain [59]. Additionally, a discussion about non-opioid therapies for

analgesia as well as the expected course for postoperative recovery can be beneﬁcial.

Furthermore, in patients with a history of chronic pain and on chronic opioid therapy,

care coordination with their prescribing physician is essential. A clear roadmap for

timely follow-up with the surgeon to assess appropriate recovery as well as a return

visit for the patient’s prescribing physician can provide clarity and reassurance. For

at-risk patients without a chronic pain practitioner, discussion of a possible postop-

erative consultation with a pain specialist may be appropriate. While addressed in

other areas of this text, a similar approach can be taken with patients suffering from

substance use disorders. For SUD patients, close collaboration between the surgical,

anesthesia, and SUD treatment teams is likely to improve the rate of follow-up as

well as outcomes [60].

In patients on chronic opioids, a discussion should be held regarding potential

tapering of the regimen prior to surgery. While tapering strategies vary, one study

recommends a reduction 10% per week over multiple weeks with collaboration

between the surgical, anesthesia, and primary care or pain management services [61].

A small study evaluating the effects of preoperative reduction of opioids on patients

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