.

d
CME

Contemporary Approaches to Postoperative

Pain Management
Amanda M. Murphy, M.D.
Learning Objectives: After reading this article, the participant should be able
Siba Haykal, M.D., Ph.D.
to: 1. Describe the fundamental concepts of multimodal analgesia techniques
Downloaded from https://journals.lww.com/plasreconsurg by UzfDro27B/DcD4/G11DEe5zW78IdedZT2NhfkOjOWuThFARJl0+pFc2nCSfqHZiWY7VoBwRsXhd5v3+cFUY35urPoEGvFY1aEl6TotqdqUC7jLoCNIETzWXbD9obRc6uXi6C5dIuXwU= on 03/23/2020

Donald H. Lalonde, M.D.

Toni Zhong, M.D.
Toronto, Ontario; and Saint John,
New Brunswick, Canada
and how they target pain pathophysiology. 2. Effectively educate patients on
postoperative pain and safe opioid use. 3. Develop and implement a multi-
modal postoperative analgesia regimen.
Summary: For many years, opioids were the cornerstone of postoperative
pain control, contributing to what has become a significant public health
concern. This article discusses contemporary approaches to multimodal, opi-
oid-sparing postoperative pain management in the plastic surgical patient. 
(Plast. Reconstr. Surg. 144: 1080e, 2019.)

E
ffective treatment of postoperative pain is
an essential component of every operation.
Research has shown that inadequate postop-
erative pain management is associated with worse
outcomes and increased risk of chronic post-
surgical pain.1 Although the efficacy of periop-
erative multimodal, opioid-sparing analgesia was
established over 20 years ago, it is only recently
emerging as the standard of care amid the current
opioid epidemic. In addition, increased adop-
tion of enhanced recovery after surgery pathways
represents a paradigm shift in surgical care. Mul-
timodal analgesia is a central component of all
enhanced recovery after surgery pathways. Rou-
tine use of multiple nonopioid analgesic modali-
ties is not only easy to implement, it conclusively
decreases perioperative opioid use and opioid-
related adverse effects.2 This has been shown to
expedite recovery from surgery, improve out-
comes, and decrease costs.3–5
Optimal postoperative pain management
requires an understanding of the pathophysiol-
ogy of pain, available analgesic modalities, inva-
siveness of the procedure, and patient factors
associated with increased pain. In this article,
we review these fundamental concepts, discuss
advances in postoperative pain management,
identify current knowledge gaps, and address
areas of controversy.
Enhanced Recovery after Surgery
Originally pioneered in colorectal surgery in
2001, enhanced recovery after surgery combines
evidence-based care elements into comprehensive
protocols that span the entire perioperative period,
resulting in expedited postoperative recovery,
improved surgical outcomes, and reduced costs.6,7
In plastic surgery, enhanced recovery after surgery
protocols have been developed for microsurgical
and breast reconstruction.3,5,8 A number of retro-
spective studies examining initiation of enhanced
recovery after surgery protocols in patients under-
going abdominally based breast reconstruction have
reported significant reduction in postoperative opi-
oid consumption and decreased hospital length of
Disclosure: Dr. Zhong has received funds from the
Canadian Institutes for Health Research, for the
Foundation Scheme & New Investigator awards
(2015 to 2020); the Canadian Breast Cancer Foun-
dation; the Canadian Cancer Society, for the MC-
CAT multicenter clinical trial; and from the PEGI
single-center randomized controlled trial. The re-
maining authors have no financial interest to declare
in relation to the content of this article.
Related digital media are available in the full-text
version of the article on www.PRSJournal.com.

From the Departments of Surgery and Surgical Oncology,
University of Toronto.
Received for publication January 15, 2019; accepted May 1,
2019.
Copyright © 2019 by the American Society of Plastic Surgeons
DOI: 10.1097/PRS.0000000000006268
By reading this article, you are entitled to claim
one (1) hour of Category 2 Patient Safety
Credit. ASPS members can claim this credit by
logging in to PlasticSurgery.org Dashboard, click-
ing “Submit CME,” and completing the form.

1080e www.PRSJournal.com
Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 144, Number 6 • Postoperative Pain Management

stay in enhanced recovery after surgery cohorts when
compared with traditional care after surgery.9–12
Although procedure-specific variations exist,
the core enhanced recovery after surgery ele-
ments can be applied to almost all plastic surgical
procedures. These are reviewed in Figure 1.
Preoperative Expectation Management
The preoperative visit is an opportunity to set
expectations and to screen for factors that can
identify patients who may have increased postop-
erative analgesia needs. Preoperative pain, anxi-
ety/depression, young age, obesity, type of surgery
(abdominal, orthopedic, and thoracic surgery),
and long duration have been identified as predic-
tors of increased postoperative pain.13,14
A key part of perioperative patient education
is setting expectations for pain control. The abil-
ity of preoperative counseling to mitigate post-
operative pain was initially reported in the New

Fig. 1. Enhanced Recovery After Surgery Society guideline adapted for plastic
surgery.

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Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Plastic and Reconstructive Surgery • December 2019
England Journal of Medicine in 1964.15 Subsequent
research has confirmed that patients engaged in
collaborative care and shared decision-making
with their providers experience better health out-
comes.14,16,17 Patients and families should be coun-
seled that the goal of postoperative analgesia is
not zero pain, but rather a tolerable level of pain
that allows optimal physical and emotional func-
tion. The degree and duration of expected pain
should be discussed, in addition to how to tailor
their activity level to minimize pain.
Counseling patients to maximize nonnarcotic
analgesics has been shown to mitigate postopera-
tive opioid use in multiple plastic surgical proce-
dures.17–19 There is strong evidence to support that
all patients with normal kidney and liver function
should be advised to take both acetaminophen and
a nonsteroidal antiinflammatory drug, such as ibu-
profen, around the clock for the first 48 to 96 hours
postoperatively.20 In fact, results of several prospec-
tive randomized trials indicate that the addition of
an opioid is not necessary for effective postoperative
pain control following many soft-tissue procedures,
including bilateral breast reduction, ganglion
excision, carpal tunnel release, and trigger finger
release.21–24 A detailed example of patient counsel-
ing and expectation management of postoperative
analgesia is presented. [See Video (online), which
details setting patient expectation for zero narcotic
breast reduction/mastopexy. Dr. Don Lalonde
explains to the patient at the time of surgery how
to take postoperative pain medication and modify
activity for a pleasant experience without narcotic.]
In cases where the surgeon feels postoperative
opioids are indicated, patients should be educated
on associated adverse effects, including significant
risk of postoperative nausea and vomiting, seda-
tion, respiratory depression, constipation, and
risk of dependence and addiction. In addition,
if opioids are to be prescribed, patients must be
counseled on proper disposal of excess tablets.
In a recent study, only 5.3 percent of over 1000
ambulatory surgical patients received any disposal
information for excess opioids from their physi-
cian, nurses, or pharmacists.22 Because proper
disposal of excess tablets is key in minimizing
diversion, the U.S. Food and Drug Administration
and Health Canada recommend that all patients
prescribed opioids are counseled on proper dis-
posal of excess tablets.25,26
Perioperative Multimodal Analgesia
Multimodal analgesia is the concurrent use
of multiple classes of analgesic medications and/
or techniques, to improve analgesia and decrease
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Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
opioid-related adverse effects. A summary of
multimodal target areas is outlined in Figure 2.
Although an endless permutation of analgesic
combinations exist, multimodal analgesia tradi-
tionally combines an opioid with one or more
nonopioid medication (acetaminophen and/or
nonsteroidal antiinflammatory drug) and local
or regional block.1 A number of randomized tri-
als and meta-analyses support that using multiple
analgesics to target different areas of pain process-
ing provides more effective postoperative analge-
sia and decreased opioid use.27
Given the breadth and variation of proce-
dures inherent in plastic surgery, selection of
multimodal therapies can be challenging. Apart
from acetaminophen and nonsteroidal antiin-
flammatory drugs, relatively few of the available
nonopioid adjuvant medications (Table 1) have
been rigorously studied as part of a multimodal
regimen. The most promising and novel therapies
are discussed in detail below.
Acetaminophen and Nonsteroidal
Antiinflammatory Drugs
Use of acetaminophen or nonsteroidal antiin-
flammatory drugs postoperatively has been over-
whelmingly shown to reduce opioid consumption
and result in less pain than opioids alone.28–31 In
addition, because nonsteroidal antiinflammatory
drugs and acetaminophen have different mecha-
nisms of action, studies indicate that combining
the two is better in terms of pain control compared
with either drug on its own.32,33 In other surgical
specialties, several prospective, randomized trials
looking at postoperative pain control in ambulatory
procedures have demonstrated equal or better post-
operative pain control using nonsteroidal antiin-
flammatory drugs with or without acetaminophen,
compared with opioid-containing regimens.34–36
Outpatient procedures examined include mastecto-
mies, hernia repair, laparoscopic cholecystectomies,
anterior cruciate ligament repair, and arthroscopic
procedures. In addition, patients taking acetamin-
ophen plus nonsteroidal antiinflammatory drug
experienced fewer medication side effects and were
more satisfied with their pain control compared
with patients on an opioid-containing regimen.35
In the plastic surgical literature, several
reports have found that use of acetaminophen
plus nonsteroidal antiinflammatory drugs with-
out the addition of opioids provides appropriate
postoperative analgesia.23,24,37 Weinheimer et al.
published a prospective, randomized, double-
blind controlled trial of 60 patients undergoing
similar soft-tissue hand procedures randomized
 Volume 144, Number 6 • Postoperative Pain Management

Fig. 2. Schematic representation of nociceptive processing and target areas of analgesic modalities. NSAIDs, nonsteroidal antiin-
flammatory drugs; CCK, cholecystokinin; NO, nitric oxide; NMDA, N-methyl-d-aspartate.

to either acetaminophen/hydrocodone or acet- nonselective cyclooxygenase inhibition. The

aminophen/ibuprofen.23 The study found no sig-
nificant difference in pain severity or time until
patients reported they were pain free between
groups. In addition, there were significantly more
side effects reported in the opioid group. Simi-
lar findings have been reported following breast
reductions and aesthetic breast surgery.24,37
Nonsteroidal antiinflammatory drugs exert
their analgesic and antiinflammatory effects
through inhibition of the enzyme cyclooxygen-
ase, which is required for the formation of pros-
taglandins and thromboxane from arachidonic
acid.38 There are several isozymes of cyclooxy-
genase. The cyclooxygenase-1 isozyme is consti-
tutively expressed and plays an important role in
gastric mucous production and platelet activa-
tion. Alternatively, cyclooxygenase-2 is induced
by inflammatory stimuli, resulting in the produc-
tion of prostaglandins that contribute to pain and
inflammation.39
Traditional nonsteroidal antiinflammatory
drugs such as ibuprofen and ketorolac act by
impairment of cyclooxygenase-1 function by these
medications is associated with increased risk of
gastric ulceration and bleeding.40 Celecoxib is a
cyclooxygenase-2 selective nonsteroidal antiin-
flammatory drug, reportedly providing superior
analgesia without the detrimental effects of cyclo-
oxygenase-1 inhibition.40 Celecoxib has not been
found to be superior to over-the-counter ibupro-
fen in terms of opioid-sparing effects or patient
satisfaction with pain management in randomized
trials of ambulatory surgery.41,42
In addition to increased risk of gastrointes-
tinal bleeding, nonsteroidal antiinflammatory
drugs are associated with increased risk of renal
dysfunction and cardiovascular events and should
be avoided in patients with comorbid renal and
cardiac disease.20,43,44 A meta-analysis published in
The Lancet found that for 1000 patients at moder-
ate risk of heart disease, 1 year of high-dose non-
steroidal antiinflammatory drug use would result
in three major vascular events. For 1000 patients
at moderate risk of gastrointestinal complications,

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 Plastic and Reconstructive Surgery • December 2019

Table 1.  Summary of Analgesic Modalities and Recommendations for Use in Multimodal Therapy
Adjunct Advantages Disadvantages
Preoperative counseling Less pain; opioid sparing; improved patient
satisfaction
Local anesthesia Fast; minimal risk Analgesia limited by duration of action; potential
LA toxicity
Liposomal bupivacaine Reported 72-hr analgesia Serious interactions with other LAs; current evi-
dence does not indicate superiority to bupivacaine
hydrochloride; expensive
Regional anesthesia
  • PVB Less pain; opioid sparing Technique failure; multilevel injections required;
pneumothorax; vascular/pleural puncture
  • TAP Less pain; opioid sparing Technique failure; LA toxicity; peritoneal puncture
  •  Pecs II Less pain; opioid sparing; less invasive than Technique failure; LA toxicity
PVB; may improve immediate postoperative
shoulder ROM following mastectomy
  •  Brachial plexus Less pain; opioid sparing See Table 3
 (see Table 3)
Acetaminophen Less pain; opioid sparing Hepatotoxicity
NSAIDs Less pain; opioid sparing Platelet dysfunction, GI bleeding/ulceration,
  • Ibuprofen cardiovascular events, and renal dysfunction
  • Naproxen (GI risks and platelet dysfunction less with COX-2
  • Ketorolac selective NSAIDs)
  • Celecoxib
  • Meloxicam
Gabapentinoids Less pain; opioid sparing Dizziness; sedation; peripheral edema; renal
 • Gabapentin excretion
 • Pregabalin
NMDA receptor Less pain; opioid sparing; may inhibit Ketamine: hallucinations, hypertension, tachycardia
antagonists chronic pain; consider in patients with
  • Ketamine opioid tolerance
  • Dextromethorphan
α2-Adrenoreceptors Less pain; opioid sparing; insufficient Hypotension, bradycardia
  • Clonidine evidence to recommend routine use
  • Dexmedetomidine
Antidepressant Definite benefit in chronic pain; insufficient TCA: antihistaminic, anticholinergic, and anti–α-
medications evidence to recommend routine use adrenergic side effects
  •  Amitriptyline (TCAs)
  •  Duloxetine (SNRI)
TENS Less pain; may be opioid sparing; low risk May limit mobility; not enough evidence to
of harm recommend specific regimen
LA, local anesthetic; PVB, paravertebral block; TAP, transversus abdominis plane; ROM, range of motion; NSAIDs, nonsteroidal antiinflamma-
tory drugs; GI, gastrointestinal; COX-2, cyclooxygenase-2; TCAs, tricyclic antidepressants; SNRI, serotonin-norepinephrine reuptake inhibitor;
TENS, transcutaneous electrical nerve stimulation.

1 year of high-dose nonsteroidal antiinflamma- drugs.20 Unlike nonsteroidal antiinflammatory

tory drugs would result in 16 gastrointestinal
complications. Because the report is based on 1
year of high-dose nonsteroidal antiinflammatory
drug use, the implications for perioperative risk
are unclear; however, several meta-analyses of ran-
domized trials have failed to identify increased
postoperative or gastrointestinal bleeding risk with
perioperative use of ketorolac or ibuprofen.20,45,46
The mechanism of action of acetaminophen
is less well understood. In vitro, acetaminophen
weakly inhibits both cyclooxygenase-1 and cycloox-
ygenase-2, but does not reduce synthesis of gastric
mucosal prostaglandins or thromboxane in vivo,
leading researchers to theorize that an uniden-
tified form of cyclooxygenase is inhibited.39,47
It is a potent analgesic, antipyretic agent that
demonstrates synergistic analgesic effects when
combined with nonsteroidal antiinflammatory
drugs, acetaminophen is safe for use in patients
with peptic ulcer disease and renal dysfunction.
Because it is hepatically cleared, it should be
avoided in patients with liver dysfunction.39,47
Some confusion exists over the maximum
daily dose of acetaminophen. In 2011, McNeil
Consumer Healthcare (Fort Washington, Pa.), the
manufacturer of the Tylenol brand of acetamino-
phen, decreased the recommended maximum
daily dose from 4 g/day to 3 g/day in the United
States (see https://www.tylenol.com/safety-dos-
ing/usage/dosage-for- adults). This decision was
based on a 2009 U.S. Food and Drug Adminis-
tration advisory committee recommendation to
decrease the maximum daily dose as a way to miti-
gate accidental acetaminophen overdoses.48 This
recommendation was not evidence based, and
most generic manufacturers of acetaminophen in

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 Volume 144, Number 6 • Postoperative Pain Management
the United States and Canada, including the Cana-
dian manufacturer of Tylenol, have maintained
the 4 g/day maximum. Although large-scale trials
are lacking, a handful of prospective studies indi-
cate that a maximum dose of 4000 mg acetamino-
phen for acute postoperative pain is well within
safe therapeutic limits.49,50 In a prospective multi-
center, double-blind, randomized, placebo-con-
trolled clinical trial of high-dose acetaminophen
in patients with acute stroke, 697 patients were
administered 6000 mg of acetaminophen for 3
consecutive days. None of these patients had alter-
ations in liver enzymes.49 In addition, given that
the elimination half-life of acetaminophen is 2 to
3 hours, lengthening the dosing to 1000 mg every
8 hours postoperatively may result in therapeutic
failure in the latter part of their dosing regimen.
To summarize, there is strong evidence that
combined use of acetaminophen and a nonste-
roidal antiinflammatory drug provides superior
analgesia and decreased opioid consumption
postoperatively.20,34,35,37 Several authors have in
fact demonstrated that scheduled administration
of high-dose acetaminophen plus a nonsteroidal
antiinflammatory drug in the early postoperative
period is associated with lower pain scores, fewer
adverse events, and improved patient satisfaction
than an opioid-containing regimen.35,43,46
Gabapentinoids
Initially developed as anticonvulsants, gaba-
pentinoids—like pregabalin and gabapentin—
are structural analogues of the neurotransmitter
gamma-aminobutyric acid and bind with high affin-
ity to voltage-gated calcium channels in the nervous
system. Although the exact nature of how these
medications exert therapeutic effects is incom-
pletely understood, the interaction of these drugs
with voltage-gated calcium channels in the central
nervous system causes a reduction in depolariza-
tion-induced influx of calcium required for release
of excitatory neurotransmitters including gluta-
mate, noradrenaline, dopamine, and serotonin.51
Gabapentinoids have a wide safety profile
and are generally well tolerated. Common side
effects include sedation, dizziness, and visual
disturbances.52 Both gabapentin and pregabalin
have been proven to be effective adjuncts in the
management of chronic neuropathic pain.53,54
Although large-scale randomized trials support-
ing routine use of gabapentinoids in the perioper-
ative setting are lacking, contemporary evidence
indicates that the perioperative administration
of gabapentin is associated with a significant
decrease in postoperative opioid use.55–58 Similar
Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
effects have been reported with perioperative
pregabalin,51,59 which has been promoted as pref-
erable to gabapentin given a more predictable
pharmacokinetic profile in that oral absorption
is both extensive and proportional to dose.51,60 In
addition, pregabalin has been found to reduce
postoperative nausea and vomiting when admin-
istered preoperatively, a finding that has not been
associated with gabapentin.59
The evidence surrounding optimal periopera-
tive dosing for gabapentinoids remains unclear.
Studies comparing outcomes of a single preopera-
tive dose with repeated postoperative dosing are
lacking. Interestingly, a meta-analysis of 55 random-
ized controlled trials involving 4155 patients found
that all dosing regimens of pregabalin provided
a significant reduction in pain scores and opioid
consumption at 24 hours compared with placebo.52
In addition, there were no significant differences in
acute pain outcomes when comparing regimens of
a single preoperative administration of pregabalin
(75 to 150 mg) to repeated postoperative dosing.
Antidepressant Agents
Tricyclic antidepressants inhibit the reuptake
of serotonin and norepinephrine in the central
nervous system.61 Both amitriptyline (tricyclic
antidepressant) and duloxetine, a serotonin-nor-
epinephrine reuptake inhibitor, have proven to
be effective adjuncts in chronic pain conditions.62
Their analgesic effects are attributed to modula-
tion of the descending inhibitory pain pathways
in the brain and spinal cord, resulting in suppres-
sion of central pain sensitization.62
To date, the existing evidence surrounding
the use of these agents in acute postoperative pain
management is limited and conflicting. Although
a handful of studies pertaining to postoperative
pain suggest an opioid-sparing effect of dulox-
etine, they failed to demonstrate a difference
in postoperative pain scores when compared to
placebo.63–66 In addition, because tricyclic antide-
pressants also block histaminic, cholinergic, and
α-adrenergic receptors, they have a significant
side-effect profile that must be taken into consid-
eration.61 In summary, the evidence does not cur-
rently support use of tricyclic antidepressants for
acute postoperative pain.
N-Methyl-d-Aspartate Antagonists
The N-methyl-d-aspartate glutamate receptors
are involved in nociceptive procession and play an
important role in the development of chronic and
neuropathic pain. In chronic pain states, up-regu-
lation of the N-methyl-d-aspartate receptor results
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 Plastic and Reconstructive Surgery • December 2019
in increased central sensitization and hyperalge-
sia.67 Perioperative inhibition of N-methyl-d-aspar-
tate receptors has been proposed as a desirable
adjunct with potential preventative effects on the
development of chronic postsurgical pain.67,68
Clinically available N-methyl-d-aspartate recep-
tor antagonists include ketamine, amantadine, mag-
nesium sulfate, dextromethorphan (an antitussive
used in cough syrup), and methadone. With the
exception of methadone, meta-analyses of random-
ized trials demonstrate that use of these medications
intraoperatively or in the immediate postoperative
period results in decreased postoperative opioid
use and an improvement in postoperative pain
scores.68–70 Most studies have focused on ketamine
and recommend reserving this agent for major
operations or in patients who are highly opioid tol-
erant.20,68 Common side effects of ketamine must be
taken into consideration, including severe halluci-
nations, hypertension, tachycardia, and salivation.71
α2-Adrenoreceptor Agonists
Activation of the α2-adrenoreceptors in the
spinal cord inhibits nociceptive neurotrans-
mission. Clonidine and dexmedetomidine are
α2-adrenoreceptor agonists that have sedative,
analgesic, and antisympathetic effects and are
most commonly used for patient sedation in the
intensive care unit setting and some procedural
sedation. In a meta-analysis of prospective ran-
domized trials, both clonidine and dexmedetomi-
dine were found to provide opioid-sparing effects
when administered perioperatively.72 Most stud-
ies have focused on abdominal surgery; however,
orthopedic73 and neurosurgical74 procedures have
also shown benefit. Their use in ambulatory and
plastic surgical procedures is less well defined.
Although the available evidence supports the
use gabapentinoids, N-methyl-d-aspartate recep-
tor antagonists, and α2-adrenoreceptor agonists
individually as nonopioid adjuvants for the man-
agement of postoperative pain, further trials are
needed to elucidate the optimal combinations of
these adjuvants. The vast majority of studies of the
latter two are based on data from inpatient popu-
lations following general surgical procedures, and
further studies are required to determine efficacy
in the plastic surgical population.
LOCAL AND REGIONAL ANESTHESIA
Local Anesthesia
Local and regional anesthetics are integral
components of most multimodal pain protocols,
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Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
particularly in plastic surgery. Local anesthet-
ics act by binding of voltage-gated sodium chan-
nels and blocking of the excitation threshold of
nociceptive afferent neurons, thereby preventing
transmission of pain signals.75
As plastic surgeons, we are well trained in
safe and effective delivery of local anesthesia.76–79
Using the “wide-awake” approach, tumescent local
anesthesia can be injected with minimal pain.
This technique has been well described in previ-
ous reports, and effectively eliminates intraop-
erative opioid use and postoperative nausea and
vomiting by avoiding the need for sedation.80–82
Although originally pioneered in hand surgery,
this technique has been extended to include a
multitude of cosmetic and reconstructive proce-
dures, including abdominoplasty, face lift, breast
reduction, and augmentation.37,76,77,82 Combining
a rapid-onset agent such as lidocaine with a lon-
ger acting local anesthetic such as bupivacaine
provides dual benefit of painless injection with
prolonged postoperative analgesia.83,84
Intravenous administration of lidocaine intra-
operatively has been shown to decrease post-
operative pain scores and opioid consumption
in patients undergoing open and laparoscopic
abdominal surgery.85 In patients undergoing
breast surgery, however, multiple studies have
found that there is no difference in postopera-
tive pain scores or opioid consumption in patients
administered intravenous lidocaine versus pla-
cebo.85–87 Despite this lack of short-term benefit,
a randomized controlled trial of 36 mastectomy
patients found that intraoperative intravenous
lidocaine infusion was associated with significant
reduction in postmastectomy pain (11.8 percent
versus 47.4 percent) at 3 months postoperatively.88
Although encouraging, this finding has yet to be
corroborated in large-scale trials.87
Exparel (Bupivacaine Liposome Injectable
Suspension; Pacira Pharmaceuticals Inc., San
Diego, Calif.) is a novel formulation of bupiva-
caine encapsulated in multivesicular liposomes.
Liposomal bupivacaine has been approved by the
U.S. Food and Drug Administration for single-
dose wound infiltration or administration as a
depo-local anesthetic. The encapsulation within
liposomes allows for slow release of bupivacaine,
with reported analgesic effects lasting up to 72
hours.89
Although appealing, at present, the evidence
surrounding perioperative liposomal bupiva-
caine is conflicting. In plastic surgery, a system-
atic review of eight studies investigating liposomal
bupivacaine for postoperative pain management
 Volume 144, Number 6 • Postoperative Pain Management
concluded that liposomal bupivacaine was safe
and provided equal or superior postoperative
pain control compared with traditional pain man-
agement.90 Given that the included studies were
either not comparative or underpowered, the
modest benefit reported should be further vali-
dated in large-scale comparative trials. A subse-
quent retrospective study reported significantly
shorter hospital length of stay in patients admin-
istered single transversus abdominis plane injec-
tions of Exparel, when compared with patients
administered continuous bupivacaine by means
of catheter or placebo. Because a single injection
of bupivacaine was not used for comparison, it is
difficult to infer superiority of liposomal bupiva-
caine from this report.
A 2017 Cochrane review identified nine ran-
domized, double-blind, controlled trials comparing
infiltration of liposomal bupivacaine with placebo
or nonliposomal anesthetic into the surgical site of
1377 patients. The quality of evidence was assessed
using Grading of Recommendations, Assessment,
Development and Evaluations and ranged from
moderate to very low. The authors concluded that
Exparel at the surgical site does appear to reduce
postoperative pain compared with placebo, but
Fig. 3. Illustration of the four types of brachial plexus blocks used for regional anesthesia in the upper extremity.
Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
was not found to be superior to traditional bupiva-
caine based on current evidence.91
Important safety concerns associated with
use of Exparel have been published in the peer-
reviewed literature.89,92 Liposomal bupivacaine has
clinically meaningful interactions with other local
anesthetics and, according to the manufacturer,
must not be injected within 20 minutes of admin-
istering another nonliposomal local anesthetic, as
this may cause a rapid release of bupivacaine mol-
ecules. At the recommended dose of 266 mg of
bupivacaine, this represents potential for serious
local anesthetic systemic toxicity.92
In summary, although liposomal bupivacaine
offers significant promise for sustained postopera-
tive local anesthesia, the limited evidence available
fails to show superiority to bupivacaine hydrochlo-
ride. Additional studies are required to establish
whether there is a cost-effective role for liposomal
bupivacaine in the routine management of post-
operative pain.
Regional Anesthesia
Compared with general anesthesia, the use
of regional blocks is associated with improved
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 Plastic and Reconstructive Surgery • December 2019

Table 2.  Description of Brachial Plexus Blocks*

Block Extent of Surgical Anesthesia Advantages Disadvantages
Interscalene •  Shoulder and radial arm and •  Uncomplicated tech- •  Does not anesthetize hand
forearm nique •  Transient vocal hoarseness, Horner
•  Interscalene groove at level of C6/ •  Minimal risk pneumo- syndrome, and hemidiaphragmatic
cricoid cartilage thorax paresis caused by temporary blockade
•  Spares ulnar aspect of arm forearm of recurrent laryngeal, stellate gan-
and hand glion, and phrenic nerves
Supraclavicular •  Targets trunks • Reliable •  Highest risk of pneumothorax among
•  Complete upper limb anesthesia •  Procedure of choice for BP block techniques
•  1 cm superior to mid clavicle, just procedures requiring •  Transient vocal hoarseness, Horner
lateral to external jugular vein upper limb tourniquet syndrome, and hemidiaphragmatic
paresis caused by temporary blockade
of recurrent laryngeal, stellate gan-
glion, and phrenic nerves
Infraclavicular •  Targets BP cords •  Good if continuous UE •  Risk of axillary artery puncture and
•  3 cm inferomedial to coracoid anesthesia is required, as intravascular injection because of
•  Anesthesia distal to mid humerus regional anatomy allows proximity of cords to axillary artery
•  Procedures of hand, forearm up to for safe placement of •  Transient vocal hoarseness, Horner
and including elbow catheter syndrome, and hemidiaphragmatic
•  Lower risk of pneumo- paresis caused by temporary blockade
thorax of recurrent laryngeal, stellate gan-
glion, and phrenic nerves
Axillary •  Targets terminal nerves of BP except •  Avoids complication •  Often misses musculocutaneous nerve
axillary (median, radial, and ulnar, associated with other BP [i.e., radial aspect of forearm not anes-
with or without musculocutaneous) blocks in the neck/chest thetized (LABC nerve)]
•  Anesthesia of forearm wrist and hand (e.g., pneumothorax,
Horner syndrome)
BP, brachial plexus; UE, upper extremity; LABC, lateral antebrachial cutaneous.
*Wu CL, Raja SN. Treatment of acute postoperative pain. Lancet 2011;377:2215–2225.

perioperative analgesia and decreased opioid use,
both intraoperatively and in the immediate post-
operative period.93,94 Anesthesia is achieved using
local anesthetics or opioids administered either by
means of a single injection or continuous catheter
infusion by means of neuraxial and peripheral
blocks. Neuraxial techniques include epidural and
spinal/intrathecal anesthesia. Peripheral tech-
niques are more commonly used in plastic surgi-
cal procedures, particularly brachial plexus blocks
as adjuncts for upper extremity surgery (Fig. 3).
A detailed description of the four brachial plexus
block techniques is outlined in Table 4. In addi-
tion to these, other regional modalities relevant to

Fig. 4. Illustration of bilateral transversus abdominis plane block catheter placement using a 3-cm
incision, followed by blunt dissection through external and internal oblique muscles.

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Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
 Volume 144, Number 6 • Postoperative Pain Management
Table 3.  Comparison of Local Anesthetic Pharmacokinetic Properties
Local Anesthetic Onset
Lidocaine 1–3
Ropivacaine 10–15
Bupivacaine 10–15
Liposomal bupivacaine 15–20
plastic surgery include paravertebral and transver-
sus abdominis plane blocks.
Paravertebral Blocks
Paravertebral blocks have been promoted as
part of a multimodal regimen to decrease postop-
erative pain and reduce opioid consumption fol-
lowing breast surgery.95 The goal of paravertebral
blocks for breast surgery is to isolate and anesthe-
tize all or some of the T1 to T6 nerve roots as they
exit out of the intervertebral foramen, producing
motor, sensory, and sympathetic blockade. This is
typically accomplished using multilevel injections
of 0.5% ropivacaine with 1:400,000 epinephrine,
or bupivacaine 0.25 to 0.5% with 1:400,000 epi-
nephrine.96,97 Many anesthesiologists prefer ropi-
vacaine because of a lower cardiotoxicity profile.98
In addition, ropivacaine has a higher maximal safe
dose (5 mg/kg for ropivacaine versus 3 mg/kg for
bupivacaine), allowing for larger volumes neces-
sary for multilevel injection. Although rare, com-
plications associated with paravertebral blocks are
serious and include pleural puncture/pneumo-
thorax, significant vascular injury, and epidural or
intrathecal injection.
A number of studies have found that paraver-
tebral blocks reduce postoperative pain scores and
opioid use in patients undergoing immediate autol-
ogous and alloplastic breast reconstruction.95–97
However, variations in anesthetic agent, number of
thoracic nerve roots blocked, and use of multimodal
pain regimens varies greatly across studies. As such,
the optimum use of paravertebral blocks in breast
surgery has not been unequivocally determined.
In recent years, less invasive peripheral nerve
blocks have been increasingly applied as multi-
modal adjuncts in breast surgery.99 The Pecs II
Table 4.  Dosing Regimen for Commonly Used Adjunct Medications
Medication Recommended Preoperative Dose (mg)
Acetaminophen 1000
Ibuprofen Not enough evidence to recommend
Celecoxib 200–400
Gabapentin 600–1200
Pregabalin 150–300
PO, oral; BID, twice daily; TID; three times daily.
Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Duration (min) Dose (mg/kg)/with Epinephrine
60–120 (120–180 with epinephrine) 4.5/7
180–360 (240–420 with epinephrine ) 3/4
120–240 (180–420 with epinephrine ) 2.5/3
24–72 hr 266-mg bolus dose
block is a novel technique that targets the pecto-
ral, intercostobrachial, and long thoracic nerves
to provide anesthesia to the anterolateral chest
wall and axilla. Early studies indicate a significant
reduction in postoperative opioid consumption
and superior postoperative analgesia in patients
undergoing immediate breast reconstruction with
a latissimus dorsi flap and implant.100
One of the most debated areas of research over
the past decade has been the impact of anesthetic
technique on breast cancer recurrence following con-
troversial reports of survival benefit in mastectomy
patients who had received paravertebral blocks.101
Although subsequent clinical investigations have
not been able to reproduce these findings,102 in vitro
and animal studies have found that local anesthetic
agents may reduce the incidence of cancer recur-
rence through systemic antiinflammatory action in
addition to direct effects on the proliferation and
migration of cancer cells.103,104 The ultimate clinical
implications have yet to be determined and are cur-
rently being explored in large multicenter trials.
Transversus Abdominis Plane Blocks
The goal of transversus abdominis plane
blocks is to anesthetize the anterior abdominal
wall by administration of local anesthetic into the
plane between the internal oblique and transver-
sus abdominis muscles. This can be performed by
anesthesia under ultrasound guidance or under
direct vision by the surgical team before closure.
A number of meta-analyses have demonstrated
that use of transversus abdominis plane blocks
provides superior pain relief and decreases opioid
consumption following open and laparoscopic
abdominal surgery in the immediate postopera-
tive period.105,106 Similar results were reported in
Recommended Postoperative Dose
1000 mg every 6 hr scheduled for 48–72 hr then as needed
400–800 mg every 8 hr scheduled for 48–72 hr then as needed
200 mg PO BID for 3–5 days
100–300 mg PO TID for 7 days
50–100 mg PO TID for 7days
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 Plastic and Reconstructive Surgery • December 2019

a double-blind, placebo-controlled, randomized approach to postoperative pain varies consid-

trial following abdominally based microsurgi-
cal breast reconstruction.107 In this study, bilat-
eral transversus abdominis plane catheters were
inserted by the surgical team under direct vision
(Fig. 4). Doses of 0.2 mg/ml 0.25% bupivacaine
were administered at 8-hour intervals until the
catheters were removed on postoperative day 3.
Use of transversus abdominis plane blocks was
associated with a significant decrease in morphine
consumption postoperatively.
Physical Modalities
Contemporary physical modalities with pro-
posed benefit for postoperative pain include
transcutaneous electrical nerve stimulation, acu-
puncture, massage, and cold therapy. In general,
these modalities are considered safe, but evi-
dence to support efficacy as part of a multimodal
erably. With the exception of transcutaneous
electrical nerve stimulation, there is currently
insufficient evidence to support or discourage use
of acupuncture, massage, and cold therapies as
adjuncts for postoperative pain management.
Transcutaneous electrical nerve stimulation
delivers low-voltage electrical currents using a small,
portable device and is thought to activate endog-
enous descending inhibitory pathways.20 There is
moderate-quality evidence reported in a systematic
review of 20 randomized trials that transcutaneous
electrical nerve stimulation decreases postopera-
tive analgesia requirements by 20 percent.108 The
American Pain Society recommends consideration
of transcutaneous electrical nerve stimulation as an
adjunct to other postoperative pain treatments20;
however, there is currently insufficient evidence
regarding which specific transcutaneous electrical
nerve stimulation regimen is most effective.

Fig. 5. Multimodal analgesia strategy. PO, oral; Q12H, every 12 hours; PRN, as needed; Q6H, every
6 hours; Q8H, every 8 hours.

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 Volume 144, Number 6 • Postoperative Pain Management
Prescribing Guidelines for Plastic Surgeons
Current evidence supports implementation
of multimodal anesthesia to reduce perioperative
opioid consumption. There is strong evidence
that a combination of preoperative counsel-
ing, use of long-acting local/regional anesthe-
sia, combined with 48 to 72 hours of scheduled
acetaminophen and ibuprofen can eliminate the
need for postoperative narcotics in ambulatory
soft-tissue procedures in opioid-naive patients.
The anatomical location and type of surgery
impact the degree of expected postoperative pain.
In general, procedures and injuries that involve
bones and joints are more painful than those that
involve soft tissue.22,109,110 Although a number of
studies have examined the degree of pain and/or
the quantity of opioid required for pain relief after
specific ambulatory surgical procedures,110–113 most
do not report the use of multimodal adjunct medi-
cations. Furthermore, because the majority are
single-institution studies, the applicability to other
institutions and patient populations is unclear.
In general, opioids should be considered as part
of a multimodal regimen in cases involving bone or
joint manipulation, trauma, or major flap surgery.
The majority of evidence demonstrates that intra-
venous administration of opioids is not superior to
oral administration in terms of postoperative anal-
gesia. In addition, opioids should not be dosed in
a scheduled fashion but rather prescribed on an
as-needed basis. The only exception to this rule is
in the opioid-tolerant patient who requires regular
opioids to prevent withdrawal. In situations where
patients demonstrate potential for increased post-
operative analgesia, preoperative consultation with
the pain service can aid in decision-making.
CONCLUSIONS
In summary, based on the evidence, we rec-
ommend the following approach to perioperative
pain management (Fig. 5):
• Many soft-tissue procedures in plastic sur-
gery do not require opioids for effective
pain management.
• If opioids are necessary for postoperative
pain management, they should not be used
as the sole modality.
• There is good evidence to support the fol-
lowing multimodal regimen in all patients
without contraindications:
◦ 
Structured preoperative education and
expectation management.
Copyright © 2019 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
◦ Preoperative nonsteroidal antiinflamma-
tory drug plus acetaminophen.
◦ Intraoperative local anesthesia.
◦ Postoperative scheduled dosing of non-
steroidal antiinflammatory drug plus
acetaminophen for 48 to 96 hours.
• If opioids are to be prescribed, we recom-
mend adding a single preoperative dose of
pregabalin followed by 2 to 5 days’ postop-
erative administration in addition to the
above modalities.
• In opioid-naive patients, consider a limited
course (1 to 3 days) of short-acting, oral
opioids in patients following bony manipu-
lation, major flap surgery, and trauma.
Toni Zhong, M.D.
Division of Plastic Surgery
University Health Network
200 Elizabeth Street, 8N-871
Toronto, Ontario M5G 2C4, Canada
toni.zhong@uhn.ca
@drtonizhong
‍ACKNOWLEDGMENT
Dr. Zhong is the inaugural Belinda Stronach Chair
in Breast Cancer Reconstruction chair holder (2017 to
2022) at the University Health Network and the Univer-
sity of Toronto.
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