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Postoperative Pain Management
Yusuke Mazda, MD PhD
1
, Sandra Jadin, MD
2
, James S. Khan, MD MSc FRCPC
3
1
Division of Obstetric Anesthesia, Department of Anesthesiology, Saitama Medical Center, Saitama Medical University, Kawagoe,
Japan;
2
Department of Anesthesiology and Perioperative Medicine, Queen’s University, Kingston, Canada;
3
Department of Anesthesia
and Pain Medicine, University of Toronto, Toronto, Canada
Corresponding Author: Dr. James S. Khan, MD MSc FRCPC: James.khan@medportal.ca
Submitted: November 6 2020. Accepted: January 18, 2021. Published: March 16, 2021. DOI: 1022374/cjgim.v16iSP1.529
Copyright: Yusuke Mazda et al.
License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons
.org/licenses/by/4.0
ABSTRACT
After surgery, over 80% of people experience moderate-to-severe acute pain. Poorly controlled
postoperative pain limits recovery and is associated with detrimental short- and long-term
morbidity. While surgeons have traditionally been responsible for postoperative pain management,
all clinicians providing care for surgical patients have a basic understanding of common
pharmacologic and interventional pain management strategies. In this review, we discuss the
consequences of acute pain, approaches to pain assessment, and an overview of commonly used
therapies to manage postoperative pain.
RÉSUMÉ
Après une opération, plus de 80% des gens ressentent des douleurs aiguës modérées à intenses.
Une douleur postopératoire mal maîtrisée limite le rétablissement et est associée à une morbidité
défavorable à court et à long terme. Bien que les chirurgiens soient habituellement responsables
du traitement de la douleur postopératoire, il est impératif que tous les cliniciens qui soignent des
patients ayant subi une intervention chirurgicale aient une connaissance de base des stratégies
pharmacologiques et interventionnelles courantes relatives au traitement de la douleur. Dans cette
revue, nous abordons les conséquences de la douleur aiguë, les approches de l’évaluation de la
douleur et un aperçu des traitements couramment utilisés pour traiter la douleur postopératoire.
Key Points
• Acute pain is common after surgery and many patients will suffer from moderate-to-severe
postoperative pain.
• Postoperative pain is associated with poor clinical outcomes, patient dissatisfaction, and long-
term morbidities such as chronic post-surgical pain.
• Comprehensive pain assessments are needed to plan for the use of analgesic therapies
preoperatively, intraoperatively, and postoperatively.
• Multimodal analgesia is the optimal treatment strategy and includes the use of several
different therapies to achieve adequate pain control.
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Introduction
Postoperative pain is one of the most significant concerns for
patients when undergoing surgery
1
and is a strong predictor
of whether patients are satisfied with their perioperative care.
2
Unfortunately, approximately 88% of patients report moderate-to-
severe acute pain after surgery.
3
Unmanaged postoperative pain
has consequences which include deleterious physiological effects,
increased healthcare utilization, and poor clinical outcomes,
such as acute pain predisposing to the development of chronic
post-surgical pain (CPSP).
4,5
While our understanding and
tools to manage pain have improved, inadequately controlled
postoperative pain continues to be an unresolved global health-care
problem. Furthermore, the recent and ongoing opioid epidemic
has increased pressure to reduce opioids during and after surgery
as a strategy to mitigate the rates of persistent opioid use.
4
As
such, there is increasing interest to provide multimodal analgesia
and identify novel interventions to improve postoperative pain
management and reduce persistent post-surgical opioid use.
While postoperative pain has traditionally been the
primary responsibility of surgeons, successful management of
postoperative pain requires a multidisciplinary approach that
involves anesthesiologists, internists, perioperative physicians,
and family physicians.
6
An understanding of postoperative pain
and commonly used interventions are required for effective
management of patients undergoing surgery. This article aims
to provide a basic overview of the principles, approaches, and
strategies to manage acute postoperative pain.
Physiology of Acute Postoperative Pain
Postoperative pain refers to pain immediately after surgery and
can persist for weeks and months. The International Association
for the Study of Pain proposes that the normal healing time
following surgery is approximately 3 months, and any pain
after this period (that did not exist prior to surgery), should be
considered pathologic (i.e., CPSP).
7
Acute surgical pain is described as nociceptive pain that is
well-localized and characterized as sharp, aching, or throbbing.
It is triggered by the activation of local peripheral nociceptive
fibers, specifically the lightly myelinated A-delta and slow-
conducting unmyelinated C fibers.
8
These fibers are activated
via thermal, mechanical, and chemical-induced tissue injury.
9
Surgery results in direct activation of these nociceptive fibers
through mechanical trauma from a surgical incision, manual
handling of tissues, and surgical retraction. As such, acute pain
is influenced by the location of surgery, its extent, and degree
of tissue and neuronal traumatization.
10
These mechanical
injuries initiate an inflammatory cascade of events that result
in an outpouring of mediators including potassium, adenosine-
triphosphate, sodium, nerve growth factor (NGF), tumor necrosis
factor-alpha (TNF-α), prostaglandins, bradykinins, histamines,
and interleukins
11,12
that result in further chemical-induced
activation of local nociceptive fibers.
Nociceptive input from A-delta and C fibers enters the
spinal cord via the dorsal horn and synapses with second-
order neurons at A-delta at Laminae II and V, C and Laminae
II. From here, pain signals cross to ascending spinothalamic
and spinoreticular pathways to ultimately reach higher brain
centers. Spinothalamic tract neurons synapse with third-order
neurons in the thalamus, relaying the signal to the cortex, and
spinoreticular tract neurons synapse in the brainstem with
projections to the thalamus, hypothalamus, and cortex, and
are involved in the emotional and psychological experience of
pain. Given the multiple triggers involved in postoperative pain,
effective pain management strategies aim to address specific
nociceptive triggers (i.e., inflammation from the surgical incision,
neuropathic pain from local nerve injury) and sites (e.g., dorsal
horn where opioids act) along the pain pathways.
Clinical Consequences of Acute Pain
There are several physiological and clinical consequences of
postoperative pain (Table 1).
4
Pain contributes to increased
heart rate, hypertension, increased myocardial contractility,
and potentially myocardial ischemia.
13
Pain also alters normal
respiratory function via splinting of the abdominal muscle,
diaphragmatic dysfunction, reduced vital capacity, and inability to
cough, especially for surgeries that require an abdominal incision.
Other physiological effects of postoperative pain include reduced
intestinal motility, altered renal physiology, impaired immune
and coagulation function, muscle weakness, sleep disruption,
and psychological distress.
13
Furthermore, from a healthcare
resource perspective, acute postoperative pain also results in
prolonged recovery room stay, delayed hospital discharge, and
unanticipated admissions or readmissions after surgery.
14–16
Table 1. Consequences of Inadequate Postoperative Pain
Patient
• Reduce QoL
• Impaired sleep
• Impaired physical activities, which may delay recovery
• Impaired mental status
• Develop chronic pain
Hospital
• Increase postoperative readmission
• Increase ED visit for refilling pain medications
Society
• Increase cost of care
• Long-term opioid use
QoL = Quality of Life; ED = Emergency Department.
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Poorly controlled acute pain after surgery has an impact
on a patient’s well-being long after the immediate postoperative
period. Patients with moderate-to-severe pain (≥4 on a 0–10 scale)
within 4 days after surgery were at increased risk of functional
limitations, poor recovery, and decreased quality of life 6-months
after surgery.
17
Furthermore, greater acute pain is a predictor of
the development of CPSP.
18
CPSP has recently been designated
as a separate pain disorder by the International Classification
of Diseases,
7
and is associated with reduced physical function,
psychological and emotional distress, and poor quality of life.
19
Assessment of Pain
An accurate assessment of pain is critical to effective pain
management. Pain is a subjective experience and is influenced
by the patient’s genetics, emotions, mood, and other ongoing
medical issues. It is important that the patient’s pain is assessed
using validated pain intensity instruments. Pain intensity scales
are often used and include the Numeric Rating Scale (0 to 10 scale
where 0 represents no pain and 10 represents worst imaginable
pain), Verbal Rating Scale (comprises a list of adjectives used
to denote increasing pain intensities), and the Visual Analog
Scale (a 10-cm line anchored by verbal descriptors of “no pain”
and “worst imaginable pain” and the patient is asked to mark a
line to indicate pain intensity).
6
There is insufficient evidence
to recommend a specific pain assessment tool over another in
the postoperative period, although the numerical rating scale
(NRS) is the most commonly used, with satisfactory analgesia
commonly occurring with ≤3 out of 10, and an estimated minimally
important difference of 2 points.
20
Additionally, the Brief Pain
Inventory (BPI) is a simple and easy tool for assessing pain and
is useful in chronic or cancer pain; however, it is not clinically
feasible to assess acute surgical pain due to pain dynamics
and high frequency for assessments by nurses. Assessing pain
in older adults or those with cognitive impairments presents
greater challenges. Observation scales, such as the Abbey pain
scale, use observed behavior and physiological parameters to
give a numerical pain assessment.
21
It is imperative that pain is not only evaluated at rest but
also in movement. Movement-evoked pain is often neglected;
however, it is estimated to be 95–226% more intense than pain at
rest and more directly affects post-surgical functional recovery.
22
A surrogate measure of pain intensity in the postoperative
period is opioid consumption. If opioids are available on an “as
needed” basis and patients have increased pain, their opioid
usage will increase. Some have argued that a composite score of
pain intensities and opioid consumption should be considered
for a more valid assessment of pain.
23
Additional elements
of a postoperative pain assessment should include the onset
and pattern of pain, location, quality of pain, aggravating and
alleviating factors, previous effective or ineffective therapies, and
effect of pain on sleep, mood, emotions, and physical function.
24
Overview of Acute Pain Management
Professional association guidelines (American Pain Society
[APS], the American Society of Regional Anesthesia and Pain
Medicine [ASRA], and the American Society of Anesthesiologists
[ASA]) have provided general recommendations for optimal
postoperative pain management.
24
These recommendations
include preoperative education, accurate pain assessment,
multimodal analgesia, and transitional management (Table 2).
They particularly emphasize the importance of patient education
and reducing opioids after surgery. Of note, positive and goal-
directed patient expectation enhances early recovery from
surgery, and postoperative opioid tapering should be planned by
both hospital specialists and family physicians. Adequate pain
management promotes patient recovery and rehabilitation and
might reduce postoperative adverse events, even healthcare costs
as well.
25
The goal of postoperative pain management should
be not to eliminate pain (i.e., achieving zero pain). Aiming for
complete pain relief may prove challenging and can lead to
overuse of pain medications. Clinicians should aim to balance
the efficacy and side-effects of pain therapies.
The optimal management of postoperative pain first
begins preoperatively. Identifying those at high risk of acute
postoperative pain allows for early consideration of preventative
analgesics (i.e., preoperative and intraoperative medications
or interventions) (Table 2). Preoperative pain, chronic opioid
use, pain catastrophizing, and type of surgery, specifically
orthopedics, urologic, general surgery, and plastic surgery, are
all risk factors for increased postoperative pain.
26–29
Further,
younger age, females, preoperative pain, and opioid use, increased
postoperative pain, and psychological factors (i.e., depression,
anxiety, and catastrophizing), appear to be risk factors for CPSP.
30
Multimodal analgesia is the desired method for postoperative
pain management. This includes combining different analgesic
therapies to provide analgesia while minimizing the side-effect
of each medication.
31
This approach is recommended both for
patients with prolonged hospital stays postoperatively or day cases
that go home immediately after surgery. Utilizing agents that
target different mechanisms along the pain pathway will allow
for improved analgesia.
31
In the following section, we outline
commonly used analgesic therapies in the perioperative period. It
is recommended that these options are used in combination and
tailored to the specific patient characteristics such as coexisting
medical conditions as well as institutional resources. Of note,
patients with chronic pain on analgesic medications should
continue the basal analgesia throughout the surgical period
and will require interdisciplinary care (e.g., anesthesiologists
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or acute pain service) to modify the basal therapy in addition
to adding patient-specific analgesic regimens.
Pharmacological Therapies
Acetaminophen
Acetaminophen is considered one of the cornerstones of
multimodal pain management. It was first discovered in the
19th century,
32
and since then it has become the most widely
used drug in the world.
33
While its mechanism of the analgesic
action is not clear, it is believed to exert its action via central
and peripheral cyclooxygenase inhibition, modulation of spinal
serotonin, endocannabinoid activity, and inhibition of nitric
oxide.
34
A recent study concluded that scheduled administration
of Acetaminophen had a statistically significant decrease in
pain scores at all time intervals.
35,36
It is available in oral, rectal,
and intravenous (IV) forms, with the analgesic effects of rectal
acetaminophen lasting longer.
37–39
The oral and rectal routes have
been preferred over IV due to lack of pain during administration.
The IV formulation was approved in Europe in 2002, the United
States in 2011, and in Canada in 2018.
37
Currently, there is limited
evidence to suggest one formulation is superior to another.
40–42
It is important to note that absorption of rectal acetaminophen
can vary with absorption from lipophilic-based suppositories
being more rapid than from water-based formulations.
Table 2. Perioperative Pain Management Considerations and Recommendations
Preoperative
Preoperative evaluation
Identification of risk factors
Consider referral to Acute Pain Service or Transitional Pain Service
Intraoperative
Consider regional anesthetic technique (single-shot or continuous catheter) for patients/procedures at high-risk of postoperative pain
Consider neuraxial technique, with possible intrathecal opioids
Intraoperative lidocaine or ketamine infusions
Postoperative
Comprehensive daily pain assessments
Mild pain/Minor surgical procedure
Acetaminophen 500–1000 mg PO every 6 h for 3–5 days
and one of the following
Celecoxib 100–200 PO BID for 3–5 days
Ibuprofen 200–800 mg PO BID every 4 h for 3–5 days
Naproxen 250–500 mg PO BID for 3–5 days
(If cannot take oral medications)
Acetaminophen 1000 mg IV every 6 h (if available) for 3–5 days
Ketorolac 15 mg IV every 8 h for 3 days
In addition to one of the following:
Oxycodone 5–10 mg PO every 4 h as needed
Hydromorphone 1–2 mg PO every 4 h as needed
Morphine 5–15 mg PO every 4 h as needed
Moderate pain/Invasive surgical procedure
Options in order of increasing difficulty in managing pain
1. Standing Acetaminophen and NSAIDs (if possible)
2. Consider Patient Controlled Analgesia
3. Consider postoperative regional anesthetic technique
4. Consider Ketamine infusion
5. Consider Lidocaine infusion
6. Consider Cannabinoids
7. Consider Gabapentinoids
BID = twice a day; NSAID = Nonsteroidal anti-inflammatory drug; PO = oral route.
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The efficacy of perioperative acetaminophen is well-studied.
A Cochrane review reported that with a single oral analgesic
dose of 975 mg to 1 g, the number needed to treat (NNT) to
experience a 50% pain relief over 4 to 6 h after administration
is 3.6 (95% CI 3.4 to 4.0).
43
Given its high tolerability and low
side-effect potential,
44
acetaminophen is often used as a first-
line agent. However, the role of acetaminophen as an opioid-
sparing agent is unclear. A recent systemic review of the use of
acetaminophen in patients after major surgery who were also
using patient-controlled analgesia (PCA) indicated a reduction
in morphine consumption of 8.7 mg (95% CI −11.4 to −5.9),
after adjusting for baseline opioid consumption.
45
Joint practice
guidelines from the APS, ASRA, and ASA recommend the
routine use of acetaminophen postoperatively.
24
While they
are not clear on whether acetaminophen should be prescribed
as a standing dose versus as-needed dose, many institutional
practices prescribe standing doses during the in-hospital stay
after surgery.
The main concern with acetaminophen is hepatotoxicity
mediated through the accumulation of a highly reactive metabolite
(N-acetyl-p-benzoquinoneimine [NAPQI]); fortunately, it is rare
when given at therapeutic doses (below 4 g/day).
46
Identifying
patients at increased risk for toxicity is important to reduce
the dose or avoid acetaminophen all together (e.g., those with
cirrhosis, alcohol use, or on P450 inducers such as carbamazepine,
phenytoin, rifampin).
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Nonsteroidal anti-inflammatory drugs act by inhibiting the
cyclooxygenase (COX) enzyme, which is responsible for the
formation of prostaglandins from arachidonic acid and is involved
in acute inflammatory pain.
47
COX is found in two isoforms:
COX-1 and COX-2. COX-1 is constantly expressed and plays
an essential role in the maintenance of gastrointestinal mucosa,
platelet function, and renal perfusion, whereas COX-2 is induced
by inflammation.
44,47
All NSAIDs bind to both COX enzymes,
with non-selective NSAIDs (i.e., ibuprofen, naproxen, ketorolac)
having a greater affinity for the COX-1 enzyme, whereas COX-2
selective NSAIDs (i.e., celecoxib, rofecoxib) have greater affinities
for the COX-2 enzyme (5- to 50-fold greater).
48
Oral NSAIDs have been shown to be effective in managing
acute postoperative pain. The NNT for a single oral dose of
common NSAIDs (to produce at least 50% maximum pain
relief over 4–6 h) are quite low (i.e., ibuprofen 200 mg: NNT 2.1,
diclofenac 50 mg: NNT 2.1).
44
Both perioperative NSAIDs and
COX-2 inhibitors appear to reduce IV morphine consumption
by 10 mg of morphine.
45
Perioperative NSAIDs have also been
shown to reduce postoperative nausea, vomiting, sedation,
and improve patient satisfaction.
49,50
Further, there is ample
data to suggest that NSAIDs are more effective analgesics than
acetaminophen,
51,52
and that combination is more effective than
a single agent alone.
53
There is inconclusive evidence with regard to clinically
significant side effects of perioperative use of NSAIDs.
45
In addition to well-known side-effects of gastric bleeding,
thromboembolic events, and renal dysfunction, two specific
adverse effects exist within the perioperative period, anastomotic
leaks after gastrointestinal surgeries and impaired bone healing
after orthopedic surgeries. A meta-analysis (16 studies, 15,242
fractures) evaluating the latter complication demonstrated an
increased risk (OR 2.07, 95% CI 1.19 to 3.61) of prolonged
or impaired bone healing with NSAIDs use after orthopedic
procedures (adult and pediatric).
54
However, the effect was
not identified for low-dose NSAIDs (diclofenac <125 mg/
day, ketorolac 120 mg/day) taken for less than 2 weeks, which
has been confirmed in additional studies.
55–57
Nonetheless,
spine surgeons have erred on the side of caution and prefer to
avoid NSAIDs postoperatively.
58
Additionally, within patients
undergoing colorectal surgery, a meta-analysis (24 studies, n
= 31,877) showed an increased risk for anastomotic leaks (OR
1.73, 95% CI 1.31 to 2.29) with the use of NSAIDs.
59
While
there are conflicting data to definitively demonstrate an effect
on anastomotic leaks, NSAIDs after gastrointestinal surgeries
have been shown to improve the return of bowel function and
feeding.
60
Joint guidelines from the APS, ASRA, and ASA state
that there is insufficient evidence to recommend against the
use of NSAIDs in orthopedic surgeries, spinal fusions, and
colorectal surgery.
24
Nonsteroidal anti-inflammatory drugs are a useful adjunct to
acute pain management after surgery and should be considered
for all patients after surgery, except for patient populations at
high risk of adverse events (e.g., elderly, renal dysfunction,
gastric ulcers, significant bleeding). COX-2 selective inhibitors
have significantly lower upper gastrointestinal complications,
no antiplatelet effects, and possibly lower risk of renal effects,
allowing it to be considered particularly in elderly patients.
61–63
Generally, if NSAIDs and COX-2 inhibitors are used, they should
be given in their lowest effective dose for only a brief period
after surgery (3–7 days).
57,64
Gabapentinoids
Gabapentinoids, such as pregabalin and gabapentin, are anti-
convulsants that are also a class of analgesic medications. The
primary mode of action is inhibition of voltage-gated α2δ
calcium channels leading to inhibition of neurotransmitter
release.
31
While prior reviews have suggested that gabapentinoids
reduce postoperative pain and opioid consumption,
65
a recently
published meta-analysis (281 trials, n = 24,682) showed no
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clinically significant effect on postoperative pain control.
65
While gabapentinoids were associated with lower pain on
a 100-point scale, the difference was not large enough to be
considered clinically significant. Further, it is important to
consider the increased risk of adverse events compared to the
minimal opioid-sparing effects.
66–68
Given an increased number
of reported side effects such as visual disturbances and dizziness,
the usefulness of these agents in the perioperative setting has
been recently questioned.
69
Ketamine
Ketamine is a dissociative anesthetic and is often used during
general anesthesia and for procedural sedation. It produces rapid
sedation and analgesia that is mediated through antagonism of the
N-methyl-D-aspartate receptors (NMDA).
70
A 2020 systematic
review of randomized controlled trials (RCT) indicated that
when ketamine was given as an adjuvant to general anesthesia,
there were significant reductions in pain intensity up to 24 h
after surgery and reduced opioid consumption for up to 12 h
postoperatively.
71
These findings were generally consistent with
a prior 2018 Cochrane review, except that the opioid reduction
effect was seen up to 48 h.
72
Ketamine has been demonstrated to be an effective agent
for postoperative pain after a number of surgical procedures
including abdominal surgery, orthopedic, spinal, otolaryngologic,
and gynecological procedures.
73
Ketamine reduces postoperative
pain scores at rest up to 72 h after surgery (weighted mean
difference [WMD] −1.3, 95% CI −2.4 to −0.2).
74
Further, ketamine
infusions reduced postoperative opioid consumption up to 48
h after surgery (WMD [cumulative morphine consumption]
−12.7 mg, 95% CI −18.9 to −6.6) and reduced postoperative
nausea and vomiting, which may be related to its opioid-reducing
effect.
73,75–78
Additionally, intravenous ketamine infusions can
assist in reducing postoperative pain in opioid-tolerant patients
79
and those with chronic pain undergoing surgery.
80
In a prior
systematic review, ketamine has been shown to reduce CPSP
at the 3rd month.
81
However, ketamine can alter blood pressure, heart rate, and
mental status, so administration should be done carefully when
performed outside a monitored setting (e.g., surgical ward).
82
Ketamine is associated with psychotomimetic effects (e.g.,
hallucinations, nightmares), however, when given intraoperatively,
there was no significant increase in these side-effects, particularly
if a benzodiazepine is administered.
71
Typical infusion regimens
range from 0.02 to 0.1 mg/kg/h (any dosage below <0.25 mg/kg/h
is considered sub-anesthetic), and at these dosages, side-effects
are uncommon.
83,84
Longer infusions (24–72 h) are safe and
show increased benefit over shorter infusions. Infusions should
be typically administered in collaboration with the hospital Pain
Service or Anesthesia colleagues and should be considered in
patients with challenging to manage postoperative pain refractory
to opioid management, after major noncardiac surgery (i.e.,
spine, thoracotomies), and those with a history of chronic pain
or opioid tolerance. Ketamine may not be appropriate for day
surgical cases and small procedures not associated with intense
postoperative pain. More studies will certainly be required to
clearly define the role of ketamine for postoperative analgesia.
85
Intravenous Lidocaine Infusions
Lidocaine is an amide local anesthetic that provides analgesia
through antagonism of voltage-gated sodium channels and appears
to have anti-inflammatory and anti-hyperalgesic properties.
86,87
While lidocaine is most often used for local or regional anesthesia,
there has been increasing use of intravenous lidocaine in recent
years. It has been used to treat chronic pain disorders in an
outpatient setting for decades.
88,89
Enhanced Recovery After Surgery
(ERAS) guidelines adopted intraoperative intravenous lidocaine
in bowel surgery given data that it improves postoperative pain,
opioid consumption, the return of bowel function, and length
of hospital stay (current level of recommendation: strong).
90
A
recent Cochrane review of RCTs confirmed an effect on reducing
pain scores up to 24 h after surgery as well as a significant
reduction in risk of ileus, time to first defecation, postoperative
nausea, and opioid consumption (mean difference [MD] 4.52
mg morphine equivalents, 95% CI −6.25 to −2.79).
91
Lidocaine
infusions typically start intraoperatively and many centers have
migrated to using postoperative infusions for acute pain.
92
Despite the widespread use of lidocaine infusions in clinical
practice, during and after surgery, there is little guidance on
specific indications, ideal infusion regimen (dose and duration),
and what monitoring should be performed. Most benefit has been
documented within gastrointestinal surgeries—however, most
studies have been within this surgical population. In breast cancer
surgery, an intraoperative lidocaine infusion appears to reduce
the development of CPSP.
93,94
Postoperative lidocaine infusions
should be considered in patients with refractory acute pain not
responsive to opioid therapy, abdominal surgeries, and history of
chronic pain. Typical lidocaine infusion dosages include a bolus
of 1–1.5 mg/kg followed by a 1–3 mg/kg/h infusion; bolus dose
can be omitted if the infusion is expected to continue for hours to
days.
91
Monitoring for possible local anesthetic toxicity should be
performed, however, at the specified infusion regimens, toxicity
is rare.
95
Toxicity ranges from mild-to-severe adverse effects in
a dose-dependent relationship. Mild symptoms include perioral
paraesthesia, visual disturbances, tinnitus, sedation, with severe
toxicity resulting in cardiovascular collapse and seizures. Thus,
monitoring for mild symptoms with cessation of an infusion
can prevent progression to severe toxicity. Some institutions
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measure plasma lidocaine concentrations (toxicity occurring
above 5 µg/mL),
86
as an extra safety mechanism, although this
is not done routinely.
96
Toxicity is treated with lipid emulsion
(e.g., Intralipid
®
). The use of Intralipid (lipid emulsion) as a
treatment of local anesthetic toxicity (LAST) has become a
standard of care. It is a lipid emulsion that acts as a lipid sink to
draw the hydrophobic local anesthetics out of the tissues. The
American Society of Regional Anesthesia has published specific
recommendations and a checklist for the treatment of LAST.
Cannabinoids
Cannabinoids are substances that act on the cannabinoid CB1
and CB2 receptors. CB1 receptors are found predominately in the
brain and spinal cord (along the pain pathways), whereas CB2
receptors are primarily found on immune cells.
97
Two categories
of cannabinoids exist, cannabis-derived pharmaceuticals (i.e.,
dronabinol and nabilone) and botanical-derived extracts. Analgesic
efficacy of cannabinoids has been primarily demonstrated in
chronic pain patients,
98–101
with little literature on perioperative
use. A recent systematic review of RCTs (924 patients) and
observational studies (4259 patients) on the use of cannabinoids
for acute pain in the perioperative period indicated no significant
reduction in opioid consumption but a significant increase in
pain at 12 h after surgery and increased odds of hypotension.
102
Considering the current evidence base, there are no strong
indications to use cannabis in the perioperative period.
Opioids
Opioids are considered as a central component of postoperative
pain management (Figure 1). Opioids exert their action by
binding to opioid receptors (e.g., mu, delta, and kappa), which
are located on the central and peripheral nervous system. The mu
receptor is primarily involved in providing analgesia; however,
mu receptors are also expressed on the gastrointestinal tract and
Figure 1. Opioids as a central component of postoperative pain management.
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may be involved in causing opioid-induced nausea, vomiting,
and constipation. Opioids can be administered via oral, rectal,
sublingual, transdermal, subcutaneous, intramuscular, intravenous,
or neuraxial routes. The most commonly used drugs after
surgery for in-patient acute pain are oxycodone, morphine, and
hydromorphone in Canada,
103,104
although the most frequently
prescribed opioids in the US was oxycodone with acetaminophen
and hydrocodone with acetaminophen, and those in the UK was
morphine and codeine with acetaminophen.
105
After a major
surgery, opioids are typically delivered via patient-controlled
analgesia (IV PCA), which allows patients to control their opioid
administration while reducing the risk of overdose and can
also reduce nursing workloads,
106
facilitate early ambulation,
reduce respiratory complications, and provide higher patient
satisfaction.
107
Although opioids have a diverse range of side-effects (Table3),
life-threatening adverse events, such as respiratory depression,
are rare and typically happen within 24 h after surgery under
intravenous patient-controlled or neuraxial analgesia.
108
A
systematic review of observational studies reported the incidence
of postoperative opioid-induced respiratory depression of 5 in
1000.
109
Also, those with pre-existing cardiac disease, pulmonary
disease, and obstructive sleep apnea are at increased risk of
opioid-induced respiratory depression.
Surgery is a period where opioid-naïve patients become
exposed to opioids. Unfortunately, up to 6.5% of patients after
minor and major surgery develop new persistent opioid use.
110
Tobacco use, alcohol and substance abuse disorders, mood
disorders, anxiety, and preoperative pain are risk factors for
persistent use. Opioid prescribing after surgery, and particularly
at discharge appears to be an important factor—45% of patients
who do not take opioids on their last day in the hospital after
surgery are prescribed opioids upon discharge.
111
Further,
patients only used 27% of the opioids prescribed to them
after surgery and prescription size was the strongest predictor
of long-term opioid use.
112
A multidisciplinary expert panel
(composed of surgeons, pain specialists, pharmacists, patients)
at John Hopkins provided consensus recommendations on the
appropriate opioid prescribing after different surgical procedures.
Recommendations for prescribing for most surgeries include
0 to 15 tablets of oxycodone 5 mg, with only certain surgeries
(thoracic, orthopedic, open gynecological surgeries) allowing up to
20 tablets. A Canadian consensus statement on recommendations
for opioid prescribing after surgery has also been published and
includes a number of recommendations including (in part)
patient education about appropriate expectations and non-
opioid analgesia use, identification of risk factors, basing opioid
prescription on functional recovery after surgery, prescription
having an expiry date of 30 days from discharge, and if a refill
is needed, only providing a 14-day refill.
57
Interventional Pain Procedures
Regional anesthesia involves using local anesthetics to produce a
conduction block at specific neuronal tissues. Patients may receive
a regional anesthetic as their primary form of anesthesia during
surgery or to assist with postoperative pain. These procedures
are typically performed under ultrasound-guidance, which may
reduce complications compared to traditional landmark-based
approaches.
113
Literature on the efficacy of regional anesthesia
after surgery varies on the type of procedure and specific
technique, but overall, these procedures have been shown to
result in improved postoperative analgesia and reduced opioid
consumption.
114–116
A large number of regional techniques are
used perioperatively and include epidural anesthesia/analgesia
(cesarean sections and midline laparotomies), brachial plexus
blocks (i.e., interscalene, supraclavicular, infraclavicular, axillary
brachial plexus blocks for upper extremity procedures), fascial
iliac plane block (for hip surgery), adductor canal block (used
in knee surgeries), and erector spinae block (for mastectomy or
truncal surgeries).
117
The length of the effect depends on the type
of local anesthetic and whether the procedure is a “single-shot”
(12 to 24 h) or includes placement of a catheter, which allows
for continuous infusion of local anesthesia (several days after
surgery).
118,119
Further, the combination of multiple regional
blocks appears to provide superior analgesia compared to
Table 3. Common Opioid-Related Side-Effects
Common Occasional Rare
Gastrointestinal
• Nausea
• Vomiting
• Constipation
• Delayed gastric
emptying
• Biliary colic
Neurological
• Sedation
• Drowsiness
• Cognitive
dysfunction
• Hallucination
• Mood disturbance
• Anxiety
• Myoclonus
• Delirium
• Seizure
• Addiction
Respiratory
• Cough reflex
inhibition
• Dry mouth
• Bronchospasm
• Respiratory depression
• Noncardiac pulmonary
edema
Others
• Miosis • Pruritis
• Muscle rigidity
• Hyperalgesia
• Allodynia
• Tolerance
• Physical dependence
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single-injection techniques.
120
Furthermore, for certain surgical
populations, such as hip fracture patients, early regional techniques
should be considered as they will typically be in pain prior to
their surgical procedure. A study in patients admitted with hip
fractures indicated that a preoperative fascia iliaca nerve block
resulted in lower preoperative opioid consumption, lower pain
intensities, and earlier discharge.
121
Several factors discourage the use of regional anesthesia,
such as lack of clinical experiences or resources and, access to
an ultrasound machine which is considered standard-of-care
in performing regional anesthesia. Of note, regional anesthesia
technique and timing (i.e., when to perform, if a catheter can
be placed, when to remove catheter) is also dependent if the
patient is on anticoagulation or antiplatelet therapy or has a
bleeding disorder.
122
In general, peripheral nerve blocks may be
considered in patients with anticoagulation/antiplatelet therapy,
whereas neuraxial techniques are contraindicated (i.e., due to
risk of epidural hematomas causing spinal cord or nerve root
compression).
Patients with Chronic Pain Presenting for Surgery
Patients with a history of chronic pain are more likely to experience
moderate-to-severe pain after surgery.
123
These patients may
also be maintained on chronic opioids which presents further
challenges within the perioperative period. These patients are
not only at higher risk of more severe pain and greater opioid use
after surgery, but epidemiological studies also indicate that they
are at higher risk of poor postoperative outcomes—in a cohort
of 200,005 patients undergoing elective surgery, preoperative
opioid use was associated with a longer hospital stay, higher
rate of readmission, and increased healthcare expenditures.
124
Multidisciplinary perioperative care models such as the
Transitional Pain Service have been developed to manage
these high-risk patients. These programs typically evaluate
patients prior to surgery, mitigate exacerbating factors, provide
interdisciplinary care including behavioral management strategies,
and support care after discharge.
125,126
In general, patients on
long-term non-opioid analgesics should have their medications
continued in the perioperative period, with some exceptions
such as NSAIDs in surgery at high-risk of bleeding. Further,
patients on chronic opioids should be continued on their home
doses in the perioperative period, while anticipating greater
opioid consumption after surgery (up to three times greater)
compared to opioid-naïve patients.
127
Long-acting opioid
formulations such as buprenorphine should also be continued
perioperatively, as suggested by Canadian expert consensus.
128
Opioid-tolerant patients should be maximized on non-opioid
adjuncts, interventional regional techniques, and particularly
ketamine infusions, which has been shown to reduce pain
intensities and opioid consumption in those with chronic opioid
use.
79,129
In challenging cases, opioid rotation (changing from one
opioid to another) can potentially be helpful in the postoperative
period, which takes advantage of the incomplete cross-tolerance
of opioids.
130
High-risk patients such as those with a preoperative
history of chronic pain and those maintained on chronic opioids
should likely be followed after hospital discharge for titration
back to baseline analgesic and opioid dosages.
Conclusions
Postoperative pain is an important consideration in a patient’s
perioperative care. Unmanaged pain may contribute to poor
postoperative clinical outcomes, including CPSP which is
analogous to a functional disability associated with increased
healthcare expenditures. Optimal management of postoperative
pain includes multimodal and interdisciplinary approaches
with the utilization of effective therapies in the preoperative,
intraoperative, and postoperative periods.
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