“Let us avoid making surgical patients pay with unnecessary suffering for the opioid overprescribing sins of others.”

Image: Adobe Stock.

Image: Adobe Stock.

Despite the thousands of years during which opioids have been used medicinally, the appropriate indications and usage for opioids, across medicine, remain incompletely defined. Having charged ahead with good intentions and strong opinions yet at times without strong data, practitioners are now grappling with serious missteps. The current opioid crisis is large and pervasive. The dimension—nearly 50,000 annual opioid-related deaths in the United States—is difficult to comprehend.1  The problem is no longer limited to the United States; Canada now faces similar problems, as does Europe.2  Rightly or wrongly, yet all with assumed good intent, practitioners, regulators, governments, courts, pharmacies, insurers, healthcare institutions, and others are responding. These responses are profoundly influencing medical practice in ways intended, unintended, and unexpected. One perhaps unintended consequence has been to germinate an “opioid phobia” in many quarters.

It is all too easy in the current opioid-phobic environment to lose track of the basic problem that gave rise to the opioid crisis—poorly managed pain. Pain is currently the most prevalent, disabling, and burdensome health problem in the United States, the societal costs of which exceed those of heart disease, diabetes, and cancer combined.3  Antecedent contributors to the current opioid crisis, originally intended to address the pain problem, include a prominent letter suggesting lack of addiction from opioids used medicinally, the advent of pain as the fifth vital sign, aggressive pain management standards, avaricious pharmaceutical manufacturers, and clearly inappropriate prescribing.4  Stated succinctly, “In fact the epidemic began because hundreds of thousands of well-meaning doctors overprescribed narcotic painkillers, thinking they were doing the right thing for suffering patients.”5  Nevertheless, our overall understanding of pain is limited, the tools available to treat it are insufficiently effective, and many practitioners—though well-intentioned—have been naive about the risks and benefits of craftily marketed treatments.

The field of anesthesiology finds itself variously and variably affected by, and responsive, reactive, and/or reactionary to, the opioid crisis. These actions, particularly those pertaining to perioperative opioid use, have largely been self-imposed, unlike externally imposed requirements from legislation and regulation of discharge and outpatient oral opioid prescribing. Yet postoperative pain remains poorly treated; more than 80% of patients report inadequate postoperative pain relief, and there has been little overall progress in the last 20 yr.6  This is worrisome because acute postoperative pain is a major risk factor for chronic postoperative pain,7  and avoiding our strongest analgesics, if thereby increasing acute postoperative pain, may worsen the chronicity problem.

Opioids have for decades been used throughout the perioperative process, from induction, to balanced anesthesia maintenance, to preemergence titration, to postanesthetic recovery, where they are the mainstay of moderate to severe pain management from the postanesthesia care unit through convalescence. Opioids are prized for their analgesic effectiveness and efficacy, support of cardiovascular stability, lack of neurotoxicity, and availability with a diverse range of pharmacologic profiles. More than five decades of anesthesia research on opioids have contributed greatly to better understanding of opioid pharmacology, and in turn, informed, rational opioid use has improved anesthesia care. In short, the value of opioids to anesthesia practice is unquestioned. However, we continue to struggle with basic unresolved issues such as the identification of best doses and duration of opioid therapy and the ability to tailor opioid therapy for optimal individual outcomes.

In light of these uncertainties and the opioid crisis, it is understandable and necessary that anesthesiologists and surgeons thoughtfully scrutinize perioperative opioid use and prescribing.8  Excessive postoperative oral take-home opioid prescribing has been identified as especially problematic and is being addressed.9  However, anesthesia practice has become focused on, if not obsessed with, precipitously reducing or eliminating intraoperative opioid use. But is the elimination of intraoperative opioid use a reasonable goal? We appear poised to fundamentally change anesthesia practice without having a rational basis for doing so.

“Opioid-free anesthesia” has recently become a cause célèbre. It is touted by its advocates as having potential advantages in providing superior (or at least equivalent) anesthetic outcomes and potentially reduced risks of developing chronic postoperative opioid use or even the likelihood of developing a frank opioid use disorder. Regrettably, very little information from clinical trials involving these techniques is available. While a few reports do variably suggest possible short-term reductions in postoperative opioid use or nausea and vomiting,10–12  whether these effects are generalizable, or in whom these properties might be considered sufficiently advantageous to routinely employ opioid-free techniques, has yet to be defined. More broadly, it is entirely unclear whether there are long-term detriments to intraoperative opioid administration. Moreover, if intraoperative opioids are eliminated, but patients receive equivalent postoperative postanesthesia care unit, ward, and take-home opioids, it is unclear that much would be gained. In fact, an opioid-free anesthesia protocol for colorectal surgery was observed to have minimal effect on discharge opioid prescribing.13  Importantly, a link between persistent postoperative opioid use and specific approaches to intraoperative or even early postoperative opioid administration has yet to be demonstrated.

Much enthusiasm for opioid restriction or abolition attends to Enhanced Recovery After Surgery pathways. Almost universally, these pathways call for reduced intraoperative opioid use. While Enhanced Recovery After Surgery components of minimally invasive surgical techniques, discontinuation of nasogastric tubes, and early ambulation all contribute to faster recovery, it is not clear that small amounts of opioids are detrimental components of multimodal analgesic strategies. As recently acknowledged, the anesthetic and analgesic components of Enhanced Recovery After Surgery protocols, including the use of specific anesthetic techniques, avoidance of opioids, and the substitution of adjuvants like magnesium and lidocaine infusions, presently lack compelling evidence.14  Moreover, the incorporation of regional anesthesia may improve pain control, reduce early postoperative opioid exposure, and facilitate rehabilitation, but longer-term opioid use does not appear to be lower in orthopedic patients receiving neuraxial analgesia or nerve blocks.15,16  The more appropriate goal may be to focus on postoperative pain relief and rapid recovery as the primary objectives, rather than elimination of opioids, and see where the outcome data take us. In short, while opioid-free anesthesia may be feasible, we do not know if and when it is optimal or useful. Absent well-controlled clinical investigations and evidence of benefit, practitioners should remain circumspect about opioid-free techniques.

Perhaps counterintuitively, opioids themselves can be opioid sparing. The intraoperative administration of a long-duration opioid like methadone has been shown to reduce both postoperative pain and, for some surgeries, opioid use for up to 3 months.17,18  Methadone in carefully selected doses is effective in patients undergoing both major and ambulatory surgery.19 

Anesthesiologists more than many other groups of physicians focus on carefully tailoring therapeutic regimens to the needs and circumstances of individual patients. This principle should extend to optimal drug selection without the arbitrary elimination of useful drugs. Although available information regarding perioperative opioids does not justify relegating their use to history, when and how they are most useful remains to be better established. Practitioners and patients would be helped in addressing this quandary by deciding on guiding principles for optimizing perioperative opioid management. The following is a list to be considered:

  • Approaches to the management of perioperative pain should be less arbitrary and commercially influenced and more evidence-based than the practices that caused the opioid crisis in the first place.

  • Focus on changing what we know to be problematic, e.g., excess postoperative take-home opioid prescribing, and less on what is of unclear value, e.g., eliminating every last milligram of perioperative opioid.

  • Attempt to tailor perioperative management to individual patients; avoid one size fits all.

  • Move research beyond descriptions of postoperative opioid use and pill counts; ask why the opioids are being used, address risk factors for chronic use such as psychological disease, and work to reduce or eliminate medical factors such as chronic postoperative pain.

  • Involve implementation science in the study of perioperative opioid management to facilitate education and adoption of best practices. Where multiple providers with differing priorities are involved, careful plans must be made.

The news is not all bad, and the situation is not entirely beyond our control. Indeed, it is ours to control, and to lead. Patients could benefit from better informed practices surrounding perioperative opioid use, but there are clear pitfalls of bowing to pressures that would result in expedient but ill-advised solutions. Anesthesiologists are for the moment in the enviable position of still being able to alter practices through the acquisition and rational application of data and evidence. Let us avoid making surgical patients pay with unnecessary suffering for the opioid overprescribing sins of others.

Supported by the Department of Veterans Affairs (Washington, D.C.) grant No. I01 BX000881 (to Dr. Clark) and National Institutes of Health (Bethesda, Maryland) grant No. R01 DA042985 (to Dr. Kharasch).

Dr. Kharasch is the Editor-in-Chief of Anesthesiology, and his institution receives salary support from the American Society of Anesthesiologists (Schaumburg, Illinois) for this position. Dr. Avram is the Assistant Editor-in-Chief of Anesthesiology, and his institution receives salary support from the American Society of Anesthesiologists for this position. Dr. Avram also has a financial relationship with the Department of Anesthesiology, North Shore University Evanston Hospital (Evanston, Illinois) for research consultation. Dr. Clark receives consulting fees from Teikoku Pharma (San Jose, California).

1.
Scholl
L
,
Seth
P
,
Kariisa
M
,
Wilson
N
,
Baldwin
G
:
Drug and opioid-involved overdose deaths - United States, 2013-2017.
MMWR Morb Mortal Wkly Rep
2018
;
67
:
1419
27
2.
Kalkman
GA
,
Kramers
C
,
van Dongen
RT
,
van den Brink
W
,
Schellekens
A
:
Trends in use and misuse of opioids in The Netherlands: A retrospective, multi-source database study.
Lancet Public Health
2019
;
4
:
e498
505
3.
Gaskin
DJ
,
Richard
P
:
The economic costs of pain in the United States.
J Pain
2012
;
13
:
715
24
4.
Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use
. Edited by
Phillips
JK
,
Ford
MA
,
Bonnie
RJ
.
Washington, D.C.
,
2017
5.
Quinones
S
:
Physicians get addicted too, The Atlantic.
May 2019
6.
Gan
TJ
:
Poorly controlled postoperative pain: Prevalence, consequences, and prevention.
J Pain Res
2017
;
10
:
2287
98
7.
Glare
P
,
Aubrey
KR
,
Myles
PS
:
Transition from acute to chronic pain after surgery.
Lancet
2019
;
393
:
1537
46
8.
Kharasch
ED
,
Brunt
LM
:
Perioperative opioids and public health.
Anesthesiology
2016
;
124
:
960
5
9.
Neuman
MD
,
Bateman
BT
,
Wunsch
H
:
Inappropriate opioid prescription after surgery.
Lancet
2019
;
393
:
1547
57
10.
Beloeil
H
:
Opioid-free anesthesia.
Best Pract Res Clin Anaesthesiol
2019
;
33
:
353
60
11.
Bakan
M
,
Umutoglu
T
,
Topuz
U
,
Uysal
H
,
Bayram
M
,
Kadioglu
H
,
Salihoglu
Z
:
Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: A prospective, randomized, double-blinded study.
Braz J Anesthesiol
2015
;
65
:
191
9
12.
Ziemann-Gimmel
P
,
Goldfarb
AA
,
Koppman
J
,
Marema
RT
:
Opioid-free total intravenous anaesthesia reduces postoperative nausea and vomiting in bariatric surgery beyond triple prophylaxis.
Br J Anaesth
2014
;
112
:
906
11
13.
Brandal
D
,
Keller
MS
,
Lee
C
,
Grogan
T
,
Fujimoto
Y
,
Gricourt
Y
,
Yamada
T
,
Rahman
S
,
Hofer
I
,
Kazanjian
K
,
Sack
J
,
Mahajan
A
,
Lin
A
,
Cannesson
M
:
Impact of enhanced recovery after surgery and opioid-free anesthesia on opioid prescriptions at discharge from the hospital: A historical-prospective study.
Anesth Analg
2017
;
125
:
1784
92
14.
Joshi
GP
,
Kehlet
H
:
Enhanced recovery pathways: Looking into the future.
Anesth Analg
2019
;
128
:
5
7
15.
Mueller
KG
,
Memtsoudis
SG
,
Mariano
ER
,
Baker
LC
,
Mackey
S
,
Sun
EC
:
Lack of association between the use of nerve blockade and the risk of persistent opioid use among patients undergoing shoulder arthroplasty: Evidence from the Marketscan Database.
Anesth Analg
2017
;
125
:
1014
20
16.
Sun
EC
,
Bateman
BT
,
Memtsoudis
SG
,
Neuman
MD
,
Mariano
ER
,
Baker
LC
:
Lack of association between the use of nerve blockade and the risk of postoperative chronic opioid use among patients undergoing total knee arthroplasty: Evidence from the Marketscan Database.
Anesth Analg
2017
;
125
:
999
1007
17.
Murphy
GS
,
Avram
MJ
,
Greenberg
SB
,
Shear
TD
,
Deshur
MA
,
Dickerson
D
,
Bilimoria
S
,
Benson
J
,
Maher
CE
,
Trenk
GJ
,
Teister
KJ
,
Szokol
JW
:
Postoperative pain and analgesic requirements in the first year after intraoperative methadone for complex spine and cardiac surgery.
Anesthesiology
2020
;
132
:
330
42
18.
Murphy
GS
,
Szokol
JW
:
Intraoperative methadone in surgical patients: A review of clinical investigations.
Anesthesiology
2019
;
131
:
678
92
19.
Komen
H
,
Brunt
LM
,
Deych
E
,
Blood
J
,
Kharasch
ED
:
Intraoperative methadone in same-day ambulatory surgery: A randomized, double-blinded, dose-finding pilot study.
Anesth Analg
2019
;
128
:
802
10