Management of Postoperative Pain
Content
9/14/2014
Management of postoperative pain
Management of postoperative pain
Authors Section Deputy
Bhavani- Editor Editor
Shankar Ellen WK Nancy A
Kodali, Rosenquist,
Nussmeier,
MD
MD
MD,
Jasmeet
FAHA
S Oberoi,
MD
Disclosures: BhavaniShankar Kodali, MDNothing
to disclose.Jasm eet S
Oberoi, MDNothing to
disclose. Ellen WK
All
topics areMDNothing
updated as
Rosenquist,
to new evidence becomes available and our peer review process is complete.
Literature
review
current through: Aug 2014. | This topic last updated: May 12, 2014.
disclose. Nancy
A
Nussm eier, MD,
INTRODUCTION
— Management of postoperative pain relieves suffering and leads to earlier mobilization, shortened
FAHAEmployee of UpToDate,
Inc.
hospital
stay, reduced hospital costs, and increased patient satisfaction [1-3]. Pain control regimens should not be
Contributor disclosures
standardized;
rather, are
they are tailored to the needs of the individual patient, taking into account medical,
review ed for conflicts of
psychological,
and
physical
condition; age; level of fear or anxiety; surgical procedure; personal preference; and
interest by the editorial
group. When
response
to found,
agentsthese
given.
are addressed by vetting
through
a multi-level
review
The
major
goal in the
management of postoperative pain is minimizing the dose of medications to lessen side effects
process, and through
while
still
providing
adequate
analgesia. This goal is best accomplished with multimodal and preemptive analgesia [4].
requirements for references
to be provided to support the
Acontent.
multidisciplinary
Appropriatelyteam approach (eg, acute pain service) is useful for formulating a plan for pain relief, particularly in
referenced content
is
complicated
patients,
such as those who have undergone extensive surgery, chronically use narcotics, or have
required of all authors and
medical
comorbidities
must conform
to UpToDatethat could increase their risk of analgesia-related complications or side effects.
standards of evidence.
This
topicofdiscusses
the management of acute surgical pain. The management of chronic pain is discussed
Conflict
interest policy
elsewhere. (See "Evaluation of chronic pain in adults" and "Overview of the treatment of chronic pain".)
SURGICAL PAIN MECHANISM — Surgical pain is due to inflammation from tissue trauma (ie, surgical incision,
dissection, burns) or direct nerve injury (ie, nerve transection, stretching, or compression) (figure 1) [5]. The patient
senses pain through the afferent pain pathway (figure 2), which can be altered by various pharmacologic agents.
Tissue trauma releases local inflammatory mediators that can produce augmented sensitivity to stimuli in the area
surrounding an injury (hyperalgesia) or misperception of pain to non-noxious stimuli (allodynia) (figure 3). Other
mechanisms contributing to hyperalgesia and allodynia include sensitization of the peripheral pain receptors (primary
hyperalgesia) and increased excitability of central nervous system neurons (secondary hyperalgesia) [5-7].
Analgesic therapy has traditionally targeted central mechanisms involved in the perception of pain using opioids
(figure 4); however, it has become clear that a better approach uses several agents, each acting at different sites of
the pain pathway. This approach lessens the dependence on a given medication and mechanism.
Pain receptor activity can be directly blocked (eg,lidocaine) or anti-inflammatory agents (eg,aspirin, nonsteroidal antiinflammatory agents) can be used to diminish the local hormonal response to injury, thus indirectly decreasing pain
receptor activation.
Some analgesic agents target the activity of neurotransmitters by inhibiting or augmenting their activity
(eg, ketamine,clonidine, paracetamol,gabapentin, pregabalin) (figure 5). Neurotransmitters are responsible for carrying
electrical signals across the gap junctions between neurons. To produce analgesia, the activity of several
neurotransmitters is targeted, including substance P, calcitonin gene-related peptide, aspartate, glutamate, and
gamma-aminobutyric acid (GABA).
http://www.uptodate.com/contents/management-of-postoperative-pain
1/12
9/14/2014
Management of postoperative pain
Synergism between medications decreases the doses needed and helps avoid the unwanted effects associated with
the higher doses that would be required if only a single agent was used.
PREEMPTIVE ANALGESIA — Preemptive analgesia is the administration of analgesics prior to onset of noxious
stimuli. Preemptive analgesia modifies peripheral and central nervous system processing of noxious stimuli, thereby
reducing hyperalgesia and allodynia [5-7]. Preemptive analgesia reduces postoperative opioid use and opioid side
effects.
Effective preemptive analgesic techniques use multiple pharmacological agents to reduce nociceptor (pain receptor)
activation by blocking or decreasing receptor activation, and inhibiting the production or activity of pain
neurotransmitters.
Local — Local anesthetic can be injected prior to surgical incision and may promote preemptive analgesia. A metaanalysis of randomized trials found significantly decreased analgesic consumption and increased time to first rescue
analgesic request, but no significant differences in postoperative pain scores in patients who had preemptive local
anesthetic wound infiltration [8]. Some randomized trials have shown that local anesthetic injection around small
incision sites reduces postoperative somatic pain, but is inadequate for visceral pain [8-12].
Systemic — For preemptive analgesia, we use ibuprofen800 mg (orally), ketorolac 30 mg (intravenously),
orgabapentin 600 mg (orally). COX-2 inhibitors are also gaining acceptance for preemptive analgesia but have
precautions for their use. (See 'Oral nonsteroidal anti-inflammatory drugs'below and 'COX-2 inhibitors'below.)
Trials with clonidine,ketorolac, and ibuprofen [13-15] have demonstrated decreased postoperative narcotic
requirements.
The effect of preemptive analgesia using gabapentinis more variable. In multiple randomized trials, gabapentin
(also pregabalin) in doses ranging from 300 to 1200 mg orally one hour before surgery reduced postoperative opioid
usage [4,16-22]; however, two trials reported it was not useful in spinal surgery [23,24]:
● Six of seven randomized trials reported preoperativegabapentinadministration decreased analgesic requirements
by at least one-third during the first 24 postoperative hours. The remaining trial found the analgesic requirement
significantly reduced for postoperative days 2 through 10 [4,16-22].
● Two other randomized trials of patients undergoing spinal surgery did not find a benefit. Patients undergoing
lumbar discectomy showed no additional postoperative benefit from using more than 600 mg ofgabapentin for
preemptive analgesia [23]. In a double-blinded, placebo-controlled trial, preemptive gabapentin was not effective
in reducing postoperative pain and morphinerequirements in patients undergoing lumbar laminectomy [24].
NEURAXIAL (REGIONAL) ANALGESIA
Intraoperative epidural or intrathecal opioid injection — Intraoperative administration of epidural or intrathecal
opioids reduces the need for systemic opioids postoperatively [25-37]. For major abdominal surgeries with extensive
incisions, epidural infusions with local anesthetic provide superior pain relief as compared with conventional parenteral
narcotics. With less extensive surgery, however, intrathecal narcotics alone can be used for postoperative analgesia.
A single dose of intrathecally (spinal) administered narcotic can provide substantial pain relief up to 18 to 24 hours
postoperatively. Neuraxial analgesia is also suitable for those patients who are chronically dependent on narcotics for
pain relief.
Delayed respiratory depression due to rostral spread of opioids to the respiratory center in the medulla is a concern
with epidural or intrathecal administration of opioids. Respiratory depression may occur up to 18 hours after a
hydrophilic agent, such asmorphine, is injected. The incidence is approximately 0.1 percent at a dose of 0.2 mg
morphine and occurs almost exclusively in obese patients [38].
Observational studies report the incidence of respiratory depression in patients given single-injection neuraxial opioids
is in the range of 0.01 to 3 percent. A metaanalysis of randomized and observational trials comparing single-injection
or continuous neuraxial opioids compared with parenteral (ie, intravenous, intramuscular, or intravenous patienthttp://www.uptodate.com/contents/management-of-postoperative-pain
2/12
9/14/2014
Management of postoperative pain
controlled) opioids found no significant difference in the incidence of respiratory depression [39].
Intrathecal injection — Small intrathecal doses ofmorphine (0.1 to 0.2 mg) orfentanyl (10 to 20 mcg) are
administered during the placement of a spinal anesthetic. The onset of analgesia and its duration depend upon
whether the drug is lipophilic or hydrophilic and how it is transported within the cerebrospinal fluid.
Opioids administered in the subarachnoid space appear to act principally on mu receptors in the substantia
gelatinosa of the dorsal horn of the spinal cord by suppressing excitatory neuropeptide release from nerve fibers (type
C). The degree of uptake from the cerebrospinal fluid by the dorsal horn is determined primarily by the
physicochemical properties of the drug and, in particular, lipid solubility. Lipid-soluble compounds enjoy greater direct
diffusion into neural tissue as well as greater delivery to the dorsal horn by spinal segmental arteries.
Morphine is highly ionized and hydrophilic and does not penetrate lipid-rich tissues as well as fentanyl. Morphine
reaches maximum effect in about 45 minutes and lasts for 18 to 24 hours when administered by the spinal route. By
comparison, fentanyl, which is lipophilic (lipid soluble) and penetrates into the lipid rich dorsal horn, acts more
quickly, but its duration of action is shorter [38].
Uncommonly, a patient has severe pain postoperatively in spite of intrathecalmorphine administration. We usually
supplement these patients with intravenous narcotics. Typically, fentanyl(50 to 100 mcg intravenously) or morphine (3
mg intravenously) produces immediate pain relief. Once the initial pain is controlled, the intrathecal morphine that
was administered at placement of the spinal block often provides adequate ongoing pain relief.
In the rare circumstance when these measures fail, patient controlled analgesia (PCA) with fentanyl ormorphine can
be initiated. (See 'Patient controlled analgesia' below.)
The combination of PCA and intrathecal opioids does not increase the risk of respiratory depression over that with
either modality alone [40-42].
Epidural injection — The dose ofmorphine by the epidural route is about 5 to 10 times that of the intrathecal
route. We use 3 mg of epidural morphine for lumbar and low thoracic epidurals; however, for less painful surgery or
high-risk patients, lower doses can provide adequate analgesia with fewer side effects. For example, epidural
morphine 1.5 mg was as effective as 3 mg for post-cesarean delivery pain and was associated with a 60 percent
reduction in pruritus [43].
Postoperative epidural analgesia with local anesthetics and opioids — Local anesthetics and opioids can be
intermittently injected via an epidural catheter to provide analgesia postoperatively [34]. This approach is particularly
useful in patients who already have an epidural catheter located at the lumbar or low thoracic level for surgical
anesthesia; however, an epidural catheter can be placed postoperatively for this purpose. Typically, epidural
analgesia is continued until the patient is able to tolerate oral medications.
A combination of a local anesthetic and opioid is administered via a patient-controlled epidural pump (PCEA). This
combination lowers the dose requirements for each drug, as well as lowers the frequency of side effects [44-46].
Commonly used combinations includebupivacaine (0.125 percent) or ropivacaine (0.2 percent)
plus fentanyl (2 mcg/mL) orhydromorphone (20 mcg/mL)[47-52]. Sufentanil has also been used, but is costly without
providing any anesthetic or analgesic advantage.
A metaanalysis of randomized trials comparing the efficacy of epidural with local anesthetic alone versus epidural
with local anesthetic and opioid concluded that combination therapy was associated with a significant reduction in
visual analog scale pain scores on the first postoperative day [53].
Occasionally, analgesia is not satisfactory due to extensive surgery or patchy coverage of the epidural block. In these
situations, we suggest administering a local anesthetic (eg,bupivacaine 0.125 percent) via PCEA and opioid via
intravenous PCA. We suggest postoperative epidural analgesia combined with opioids via PCA for reoperations,
extensive resections, and opioid-dependent patients.
We use a standard regimen of 6 mL/hour basal rate of epidural bupivacaine (0.125 percent)
http://www.uptodate.com/contents/management-of-postoperative-pain
3/12
9/14/2014
Management of postoperative pain
with hydromorphone(20 mcg/mL), allowing the patient to self bolus 2 mL of this combination of drugs, with a bolus
lockout of 20 minutes and four-hour limit of 34 mL. For the mid and higher thoracic epidurals we use a mix of
bupivacaine 0.0625 percent with hydromorphone (20 mcg/mL)and a basal rate of 4mL/hour, keeping the remaining
settings the same.
Similar to earlier reports in obstetric patients and after different types of surgery, patient-controlled epidural analgesia
with bupivacaineand fentanyl provided as good postoperative analgesia as continuous epidural infusion of bupivacaine
and fentanyl after total knee arthroplasty. PCEA provided as good analgesia as continuous epidural analgesia with a
significantly smaller amount of bupivacaine-fentanyl solution [54,55].
Epidural infusions have to be fine-tuned to the patient's requirements. Usually, the epidural infusions are started prior
to completion of the surgery to obtain pain relief at the conclusion of surgery. Occasionally, boluses of 4 to 8
mL bupivacaine mix (0.125 percent with hydromorphone20 mcg/mL) are given if the patient is uncomfortable due to
pain upon emergence from anesthesia. Postoperative blood pressure and fluid requirements must be carefully
monitored while providing such boluses. Usually two boluses are enough to provide pain relief if the epidural catheter
is sited correctly. Once initial comfort is obtained, the PCEA epidural is continued as stated above. Occasionally, if
the patient requires additional boluses over and above the normal PCEA set doses as described above, to maintain
comfort, we usually either increase the basal rate to 8 to 10 mL with four-hour limit increased to a maximum of 64
mL. Increasing the continuous basal infusion avoids fluctuations in the level of analgesia, which occur with
intermittent administration.
Less commonly, epidurally administered alpha-2 agonists (eg, clonidine), NMDA receptor antagonists (eg, ketamine),
and cholinesterase inhibitors (eg,neostigmine) are used. They are opioid sparing and provide preemptive analgesia
that improves postoperative analgesia for these patients without increasing the incidence of adverse effects [56-61].
Morbid obesity — For morbidly obese patients, it is beneficial to provide postoperative analgesia via the epidural
route, particularly in those with a history of sleep apnea. Neuraxial analgesia is beneficial in obese patients, as they
are susceptible to sleep apnea and respiratory depression that may be exacerbated by parenteral narcotics. Patients
with sleep apnea and obesity are at increased risk for respiratory depression, and consideration must be given to
using local anesthetic alone for the epidural infusions. Patient controlled analgesia is an alternative in the absence of
epidural analgesia; however, the patients need to be closely monitored during the postoperative period. (See'Patient
controlled analgesia'below.)
Monitoring — It is important to carefully monitor patients receiving neuraxial analgesics for side effects, which
can be life-threatening. All patients with epidurals should be examined by a clinician at least daily to assess the
following: adequacy of pain relief; level of activity tolerated; whether there is any motor blockade from the epidural
medication; presence of side effects such as nausea and pruritus; and whether there are signs suggestive of infection
(erythema, tenderness, swelling, discharge) at the site of epidural catheter placement. Hypotension is not uncommon
after major abdominal surgery, so a careful assessment of fluid balance and other potential causes of hypotension
are warranted before implicating the epidural infusion as the source. Nausea or severe pruritus may warrant removing
the opioid from the infusion mix. Management of intrathecal morphine-induced pruritus is discussed separately.
(See "Pruritus: Overview of management".)
Parenteral or oral nonsteroidal anti-inflammatory agents can be used to supplement analgesia if narcotics are
removed from the epidural infusions.
Nursing protocols for patients with intrathecal opioids and epidural infusions should include monitoring respiratory rate
at least every two hours, maintaining intravenous access, keeping ephedrine and naloxone readily available, and not
administering parenteral or oral narcotics or sedatives without pain service clinician approval. In addition, the pain
service clinician and covering team clinicians should be notified promptly if analgesia is inadequate, respiratory rate is
less than eightbreaths/minute, systolic blood pressure is less than 80 mmHg, sedation or motor block increases, or
temperature is greater than 101.5°F on two occasions within eight hours.
Peripheral nerve blocks — Local anesthetics can also be administered, in a selective manner, perineurally. The
http://www.uptodate.com/contents/management-of-postoperative-pain
4/12
9/14/2014
Management of postoperative pain
monitoring protocols for regional blocks are similar to those described for neuraxial anesthesia [62-64]. (See"Overview
of peripheral nerve blocks".)
Commonly used perineural blocks include the brachial plexus block to manage upper extremity pain, and femoral or
popliteal nerve block for lower extremity pain. These neural structures can be localized using ultrasound guidance or
nerve stimulation techniques, and either a single shot of anesthetic injected or a perineural catheter placed to initiate
continuous infusions. A loading bolus, usually of 20 to 30 mL of 0.5 percentropivacaine, can be used for surgical
anesthesia. For postoperative pain relief, a continuous infusion of 0.2 percent ropivacaine at a rate of 10 mL/hour is
most commonly used [65-70]. (See "Peripheral nerve block: Techniques", section on 'Upper extremity' and"Peripheral
nerve block: Techniques", section on 'Lower extremity'.)
For postoperative chest wall and abdominal pain, a paravertebral technique can be utilized. This approach delivers
local anesthetic in the vicinity of the spinal nerves after their exit from the neural foramen. Usually, multiple spinal
levels need to be blocked individually to provide effective pain relief. (See "Peripheral nerve block: Techniques",
section on 'Paravertebral nerve block'.)
POSTOPERATIVE INTRAVENOUS MEDICATIONS
Parenteral opioids — Opiates provide swift and potent analgesia when administered parenterally. The most
commonly used intravenous opioids for treatment of postoperative pain aremorphine, hydromorphone,
and fentanyl [71-74].
Meperidine is not recommended for postoperative pain relief because it lowers seizure threshold, has a dysphoric
effect, and is not as efficacious as other drugs available [75]. Additionally, it has a slower rate of metabolism in the
elderly and in patients with hepatic and renal impairment, which leads to accumulation of meperidine and its active
metabolite normeperidine [75].
Intravenous opiates can be delivered in three different modes:
● Bolus intravenous injections are often used for moderate pain, with doses titrated to analgesic requirements and
the avoidance of respiratory depression and hemodynamic instability. Opioids given by intermittent injection
generally are not able to maintain steady analgesic plasma levels for two to four hours. Therefore, it is important
to give a loading dose: formorphine the loading dose is 0.1 to 0.3mg/kg and forhydromorphone it is 0.01 to
0.03 mg/kg to achieve adequate basal plasma levels. Ideally, this loading dose is given intraoperatively to allow
a smooth transition of pain control when the patient becomes awake and alert.
● Continuous intravenous infusions of opiates are used for moderate to severe pain which is poorly controlled with
repeated bolus injections. After an initial bolus dose, a low continuous infusion rate is set with subsequent
adjustment for adequate analgesia.
● Patient-controlled analgesia is useful in conscious patients (see below). This technique allows self-dosing with
opiates up to a predetermined limit set by the clinician. A low-dose continuous infusion may be added to
establish a basal level of analgesia. (See'Patient controlled analgesia' below.)
All opiates share common side effects. These include somnolence, depression of brainstem control of respiratory
drive, hypotension (more common in hypovolemic patients and following rapid injection), urinary retention, and emesis
due to direct stimulation of the chemoreceptor trigger zone. Histamine release often follows morphineadministration
and may produce flushing, tachycardia, hypotension, pruritus, and bronchospasm. Gastrointestinal transit slows with
prolonged administration, resulting in constipation and ileus in many patients; this effect is thought to reflect binding
to local opiate receptors in the gut. Some data suggest thatmethylnaltrexone, a polar opiate antagonist that does not
cross the blood-brain barrier, may diminish the peripherally-mediated side effects of opiates while maintaining central
analgesic effects. (See "Pain control in the critically ill adult patient".)
Use of acetaminophen or an NSAID with opioids reduces narcotic requirements [76]. This is particularly useful in
patients with high narcotic needs (opioid tolerance or chronic use) and may decrease narcotic-related side effects.
http://www.uptodate.com/contents/management-of-postoperative-pain
5/12
9/14/2014
Management of postoperative pain
When pain is less severe and the patient is able to take an oral diet, oral pain relievers can be initiated and continued
after discharge, as needed. (See 'Oral opioids'below.)
Morphine — Morphine is the prototype opiate and remains widely used. The onset of analgesia is rapid, with the
peak effect occurring in one to two hours and an elimination half-life of three to five hours.
● Bolus intravenous injections of morphineare initiated with a 2 mg dose, administered slowly over four to five
minutes, and titrated upward in 1 to 2 mg increments every one to three hours.
● For continuous infusions, a bolus dose of 2 to 5 mg is followed by 1 mg per hour; subsequent dose adjustments
in the hourly infusion rate are titrated to the desired level of analgesia. Continuous infusions may be of use in
opioid-tolerant patients such as those on chronic opiate therapy who need parenteral administration.
● Intramuscular injection: 5 to 10 mg every three to four hours as needed. Subcutaneous injection is possible but
not recommended, as repeated subcutaneous administration causes local tissue irritation, pain, and induration.
Fentanyl — A synthetic derivative of morphine,fentanyl is approximately 100 times more potent. It is also more
lipid-soluble than morphine, which results in a more rapid onset of action, due to improved penetration of the bloodbrain barrier, and a shorter half-life of two to three hours. Fentanyl usually is administered as a continuous
intravenous infusion, mainly in an intensive care unit setting. Fentanyl is virtually devoid of histamine-releasing
properties, and may therefore be preferred in the presence of hemodynamic instability or bronchospasm. (See "Pain
control in the critically ill adult patient".)
Intravenous boluses every one to two hours may, however, be given for moderate postoperative pain.
● For moderate analgesia after outpatient surgery, intravenousfentanyl is initiated with a 25 mcg to 100 mcg bolus
administered over one to two minutes; additional boluses can be given every one to two hours as needed until
oral medications can be instituted prior to discharge.
● For moderate to severe pain, a loading dose of 50 to 200 mcg is followed by a continuous intravenous infusion of
25 to 50 mcg per hour, with titration to adequate analgesia.
Administration of fentanyl for more than five days is associated with deposition of the drug in adipose tissue. These
stores are mobilized following the cessation of drug and may result in prolonged sedation.
Hydromorphone — Hydromorphone (Dilaudid) is a semisynthetic opiate agonist which, like fentanyl, has a more
rapid onset of analgesia (within 30 minutes) and a shorter half-life (2.4 hours) than morphine. For control of moderate
to severe pain, 0.2 to 0.6 mg of hydromorphone is administered as an intravenous bolus every two to three hours.
Sufentanil, alfentanil, and remifentanil — Sufentaniland Alfentanil are derivatives of fentanyl. Sufentanil is 10
times more potent than fentanyl, whereas alfentanil has about 1/5 to 1/10 the potency of fentanyl. Due to their rapid
onset of action (within two to three minutes of an injection) and short elimination half-lives (approximately 90
minutes), these agents are nearly always used as adjuncts to anesthesia and for immediate postoperative analgesia.
Sufentanil appears to cause less hemodynamic instability, respiratory depression, and chest-wall rigidity than
fentanyl or alfentanil. However, the high cost of sufentanil precludes its routine use for perioperative analgesia.
Remifentanil, another derivative of fentanyl, is an ultra short-acting agent with a context-sensitive half-life remaining at
four minutes after a four-hour infusion due to its rapid hydrolysis by nonspecific tissue and plasma esterases. It has
an analgesic potency approximately equal to fentanyl.
For patients with renal compromise, the dose of these medications has to be decreased depending on the degree of
renal insufficiency.Remifentanil is the opioid agent least subject to alterations in bioavailability associated with
hepatic insufficiency; however, its potency has other inherent dangers. It is advisable to refer to a drug formulary
before prescribing these agents in patients with renal or hepatic insufficiency.
Ketorolac — Nonsteroidal anti-inflammatory agents (NSAIDS) are useful in reducing the amount of opiates requested
by the patient and decreasing opioid side effects [76]. NSAIDS also play an important role as adjuncts to other
http://www.uptodate.com/contents/management-of-postoperative-pain
6/12
9/14/2014
Management of postoperative pain
agents, such as epidural analgesia, and intravenous administration ofketorolac can be given for preemptive analgesia.
(See'Preemptive analgesia' above and 'Oral nonsteroidal anti-inflammatory drugs' below.)
Administration of ketorolacreduces narcotic consumption by 25 to 45 percent and indirectly lowers opioid side effects
such as ileus, nausea, and vomiting [14,15,77-81]. The usual dose of ketorolac in our practice is 30 mg given
intravenously. NSAIDs are discussed in more detail separately. (See "NSAIDs: Therapeutic use and variability of
response in adults" and "Nonselective NSAIDs: Overview of adverse effects".)
COX-2 inhibitors — Single doses of COX-2 inhibitors may be used to decrease the need for opioids postoperatively.
In Cochrane reviews of placebo-controlled randomized trials of postoperative pain control, use of celecoxib (200 or 400
mg oral), etoricoxib (120 mg oral), or parecoxib (20 or 40 mg intravenous or intramuscular) delayed and decreased the
need for rescue analgesics without significant side effects [82-84].
In several trials, single-dose COX-2 inhibitors had greater analgesic efficacy and tolerability than opioids, but were
similar to nonselective NSAIDs for postoperative pain management [77,81,85-87]. In the United States, COX-2
inhibitors carry a "black-box" warning regarding cardiovascular risk, although this risk appears to be related to longterm use. (See "Overview of selective COX-2 inhibitors" and "COX-2 selective inhibitors: Adverse cardiovascular
effects".)
COX-2 inhibitors may also be used for single dose preoperative administration. (See 'Preemptive analgesia'above.)
Ketamine — Ketamine is a noncompetitive inhibitor of the N-methyl-D-aspartate (NMDA) receptor. Ketamine
reduces hyperalgesia and opioid tolerance, thereby decreasing postoperative opioid requirements and possibly
chronic post-surgical pain [88]. It may be used in subanesthetic doses in the perioperative period, generally for
patients whose pain might be difficult to manage with opioids alone. The clinical use of ketamine is limited due to its
potential to cause hallucinations and a dissociative mental state.
In a 2011 systematic review and metaanalysis of trials of perioperative intravenous (IV)ketamine, there was a
reduction in total opioid consumption and an increase in the time to first analgesic [89]. Patients having the most
painful surgical procedures, including thoracic, upper abdominal, and major orthopedic operations, had improvement
in pain scores despite a decrease in opioid consumption. Ketamine was not effective for patients having surgery
associated with mild pain, such as tonsillectomy, dental, or head and neck surgery.
There is great variability in doses of ketamine used for postoperative analgesia; typical single IV doses range from
150 to 1000 mcg/kg,and IV continuous infusions range from 120 to 600mcg/kg per hour [88].
The benefit of addingketamine to patient controlled analgesia (PCA) with opioids is less clear. In a 2010 systematic
review, the addition of ketamine to opioid PCA reduced pain score, opioid consumption, and postoperative
desaturation after thoracic surgery; however, there was no benefit for orthopedic or abdominal surgery [90]. Doses of
ketamine in these studies varied from 0.75 to 5 mg ketamine for each milligram of morphine.
Ketamine can be particularly useful as an adjunct when used in patients taking chronic opioids ormethadone whose
pain is poorly controlled in spite of high-dose opioid therapy.
There may be a role forketamine in prevention of postoperative chronic pain syndromes [91].
Intravenous lidocaine — Intravenouslidocaine can be administered by infusion intraoperatively and/orpostoperatively
for the management of pain. An initial bolus (1.5 to 2 mg/kg)can be used with an intraoperative infusion dose ranging
between 1.5 to 3mg/kg/hour. The infusion can be continued postoperatively but is usually at a lower dose. The
duration of postoperative therapy needed is poorly defined.
The most significant benefit of lidocaine infusion is seen following major abdominal surgery, with significantly
improved pain scores in the immediate postoperative period, and reduced incidence of postoperative ileus compared
with placebo [92]. There appears to be a trend toward a reduction in the length of stay; however, variability exists in
the reported data [92,93].
http://www.uptodate.com/contents/management-of-postoperative-pain
7/12
9/14/2014
Management of postoperative pain
The side effects of intravenous lidocaine are discussed in detail elsewhere. (See "Major side effects of class I
antiarrhythmic drugs".)
Magnesium — Magnesium is an antagonist of the NMDA receptor. Intravenous (IV) magnesium has been found
effective as an adjuvant treatment to reduce opioid requirements; it may be useful in opioid-tolerant patients, or when
there are medical concerns related to opioid dose.
In two 2013 meta-analyses of trials of intraoperative IVmagnesium sulfatecompared with placebo or no treatment in
over 1200 patients, peri-operative IV magnesium reduced opioid consumption and pain scores in the first 24 hours
postoperatively, without serious adverse effects [94,95]. In one of the analyses, 24-hour morphineconsumption
decreased by 24.4 percent (7.6 mg [95% CI 5.8-9.5 mg]); pain scores at 24 hours after surgery were reduced on a
100 point scale by 4.2 (95% CI 2.1-6.3) at rest and 9.2 (95% CI 2.3-16.1) on movement [94]. Both bolus and
continuous infusion regimens were effective. Total peri-operative doses ranged from 1.03 g to 23.5 g, without
correlation between dose and reduction in morphine consumption; the optimum regimen could not be determined.
Magnesium may provide benefit when used in patients who are also receivingketamine. In a trial of 50 patients having
scoliosis surgery, the addition of IV magnesium to an intraoperative ketamine regimen decreased
postoperative morphineconsumption by 30 percent, with improved sleep and satisfaction scores, but no change in
pain scores [96].
Intravenous acetaminophen — Intravenous acetaminophen may be used in patients in whom oral or rectal
administration is not an option. Intravenously administered acetaminophen has a more rapid and predictable onset of
effect (5 to 10 minutes) and time to peak concentration (15 minutes) in most patients compared with rectal or oral
administration (onset 10 to 60 minutes or more). In a meta-analysis of randomized trials, the addition of
acetaminophen (intravenous or oral) tomorphine following major surgery resulted in a small, but statistically
significant, decrease in morphine use postoperatively [76].
The addition ofacetaminophen to nonsteroidal anti-inflammatory drugs (NSAID) regimens can improve pain control. A
systematic review that compared the use of acetaminophen alone or in combination with NSAIDs for postoperative
pain showed the combination to be more effective than NSAIDs alone in 64 percent of the studies [97].
A reduced dose is suggested for low weight adults and adolescents (body weight 33 to 50 kg) and in patients with
mild or moderate hepatic insufficiency, chronic alcoholism, malnutrition, or dehydration. Patients with severe renal
insufficiency (CrCl ≤30 mL/min) may receive a usual dose, but not more often than once every six
hours. Acetaminophen is contraindicated in patients having severe hepatic insufficiency or severe active liver disease.
PATIENT CONTROLLED ANALGESIA — The patient controlled analgesia (PCA) pump is the preferred mode of
administering opioids for moderate to severe postoperative pain. The benefits include easier patient access to pain
medication, reduced chance of medication error, and ready titration (table 1). A meta-analysis of analgesia after
intraabdominal surgery found that continuous epidural analgesia significantly improved control of postoperative pain
compared with opioid PCA, but was associated with a higher incidence of pruritus [98]. (See 'Neuraxial (regional)
analgesia' above.)
Morphine, hydromorphone, and fentanyl can be administered via PCA pump. The pump is discontinued when the
patient is able to tolerate oral analgesics. A systematic review of randomized trials comparing PCA versus
conventional administration of opioids evaluated 55 trials [99]. Compared with conventional parenteral analgesia, PCA
use was associated with higher opioid consumption, provided better pain control, and resulted in greater patient
satisfaction in spite of a higher incidence of pruritus. There is insufficient evidence to draw comparisons about the
other advantages and disadvantages of these two methods of pain relief. The incidence of other side effects was
similar between the groups, with no differences observed in the length of hospital stay.
A fentanyl PCA may be used for patients with allergies or intolerances to morphine andhydromorphone, but is less
desirable in most patients because of its short duration of action. Fentanyl may be easier to titrate in patients with
renal and hepatic insufficiency. Alternatively, hydromorphone can be used in patients with renal insufficiency
http://www.uptodate.com/contents/management-of-postoperative-pain
8/12
9/14/2014
Management of postoperative pain
[100,101].
Issues related to opioid administration via PCA pump in specific subpopulations are described below:
Patients using opioids chronically — Patients who are using opioids chronically should be monitored closely. The
postoperative analgesic needs of these patients, which may already be high, will typically exceed their daily doses.
Several options are available to meet the acute pain management requirements of these patients. A continuous PCA
basal infusion may be needed to control pain effectively since routine dosing schedules may not be sufficient.
Another method for providing a basal opioid level for opioid-tolerant patients is the addition of long acting opiates via a
transdermal route (eg, fentanyl patch), with titration of shorter-acting agents for acute postoperative pain. Transdermal
routes should not be used for the control of postoperative pain in nonopioid tolerant patients due to their slow onset of
action (peak levels achieved 24 to 48 hours after patch placement), and potential harmful side effects, particularly
respiratory depression.
Patients on methadone — For patients on methadone maintenance for drug dependency or for chronic pain, we
suggest restarting their methadone as soon as possible; this may be administered orally with the usual dose or
intravenously with half the usual dose. Postoperative analgesic requirements may be covered with additional opioids
as needed via PCA pump. Although these patients require high opioid doses, they are generally tolerant to serious
side effects, such as respiratory depression. Consultation with a pain specialist may be helpful. Conversion tables for
commonly-used opioids can also be useful (figure 6 andtable 2). (See "Treatment of opioid use disorder".)
POSTOPERATIVE ORAL ANALGESICS — A wide variety of oral pain medications are available for the treatment of
acute pain.
Choices include:
● Acetaminophen (325 to 1000 mg orally [or rectally] every four to six hours, to a maximum dose of 4g/day)
● Ibuprofen (300 to 800 mg orally three or four times per day)
● Narcotics
• Codeine 15 to 60 mg orally every four to six hours
• Oxycodone 5 to 30 mg orally every four to six hours
• Combination therapies such as Percocet (combinations of 325 to 650 mgacetaminophen/2.5to 10
mgoxycodone, one or two tablets orally every four to six hours), Percodan (325 mg aspirin/4.5 mg
oxycodone, one or two tablets orally every four to six hours), Tylenol #2 (300
mgacetaminophen/15mg codeine, one to two tablets orally every four to six hours), Tylenol #3 (300
mgacetaminophen/30mg codeine, one to two tablets orally every four to six hours)
Depending upon the severity of the pain, prior allergies, prior patient experience and tolerance of these medications
(nausea, gastrointestinal upset, bleeding disorders), any of these oral medications can be prescribed and tailored to
the needs of the individual.
A Cochrane review analyzed the data for single dose oral analgesics from 35 prior Cochrane Reviews treating about
45,000 participants for acute postoperative pain [102]. No drug was found to produce high levels of pain relief in all
participants. In patients with acute moderate to severe pain, 70 percent achieved good pain relief with the best drugs
and pain relief for the worst drugs occurred in about 30 percent of the patients. The percentage of patients treated
with placebo who achieved at least 50 percent maximum pain relief over four to six hours ranged from 5 to 15 percent.
The period over which pain was relieved varied from two hours to 20 hours. Drug/dosecombinations with good (low)
numbers needed to treat (NNT) for at least 50 percent maximum pain relief over four to six hours relative to placebo
included [102]:
● Ibuprofen 400 mg (NNT 2.5, 95% CI 2.4-2.6)
http://www.uptodate.com/contents/management-of-postoperative-pain
9/12
9/14/2014
Management of postoperative pain
● Diclofenac 50 mg (NNT 2.7, 95% CI 2.4-3.0)
● Etoricoxib 120 mg (NNT 1.9, 95% CI 1.7-2.1)
● Codeine 60 mg + paracetamol 1000 mg (NNT 2.2, 95% CI 1.8-2.9)
● Celecoxib 400 mg (NNT 2.5, 95% CI 2.2-2.9)
● Naproxen 500/550 mg (NNT 2.7; 95% CI 2.3-3.3)
A long duration of action (>8 hours) was noted for:
● Etoricoxib 120 mg
● Diflunisal 500 mg
● Naproxen 500/550 mg
● Celecoxib 400 mg
● Oxycodone 10 mg plus paracetamol 650 mg
Oral nonsteroidal anti-inflammatory drugs — We suggest that pharmacological management of mild to moderate
postoperative pain begin with a nonsteroidal anti-inflammatory drug (NSAID), unless there is a contraindication to
these agents. Preoperative administration of oral NSAIDS prior to elective minor surgery reduces postoperative pain
[15,77,103-106]. (See'Preemptive analgesia'above.)
Commonly used oral NSAIDS that can be used for postoperative pain areibuprofen, diclofenac,ketoprofen, and
paracetamol. If oral medication is not tolerated, rectal administration is an alternative route.
NSAIDs are discussed in more detail separately. (See"NSAIDs: Therapeutic use and variability of response in
adults" and "Nonselective NSAIDs: Overview of adverse effects".)
Oral opioids — When the patient is tolerating an oral diet, the opioid regimen for patients with moderate to severe
pain can be switched from intravenous to oral opioids such as oxycodone,hydromorphone, ormorphine. General
opioid dosing guidelines are provided in the table (table 3). (See 'Postoperative intravenous medications'above.)
Ideally, the dose should be calculated on the basis of the 24-hour PCA dose and appropriate conversion calculated
(figure 6 and table 2). As an example, a patient taking 40 mg of intravenousmorphine over 24 hours would be given 20
mg ofoxycodone every four hours or 5 mg of hydromorphoneevery four hours. Patients with mild to moderate pain can
be switched to NSAIDS or acetaminophen.
Alpha-2 receptor agonists — The exact mechanism by which alpha-2 agonists produce analgesia remains
unknown; it is postulated that release of acetylcholine may play a role [107].
Alpha-2 agonists also reduce the undesirable physiological and psychological effects of opioid withdrawal [108].
Studies indicate that alpha-2 agonists such as clonidineand dexmedetomidine exert a potent analgesic response,
and that their potency is increased by concomitant opioid therapy [109,110].
Oral clonidine at doses of 150 to 200 mcg preoperatively has been shown to provide perioperative hemodynamic
stability and reduce the requirement of postoperative analgesics [111-113].
Anticonvulsants — Anticonvulsant agents such asgabapentin and pregabalinare effective in the management of
chronic neuropathic pain conditions.
Perioperative gabapentin andpregabalin exert analgesic and opioid sparing effects and, as a result, decrease opioidrelated side-effects [114-119]. A disadvantage to these agents is a dose-dependent sedation [116,119]. Several
systematic reviews support an adjunctive role for these agents in the management of postoperative pain [116,118120].
PERSISTENT POSTOPERATIVE PAIN — Normally, incisional pain gradually resolves over a period of days to
weeks. Increasing pain or pain that persists for months may be due to surgical complications (eg, local scar
formation, infection,dehiscence/hernia, foreign body reaction, and incisional neuroma), or to conditions unrelated to
http://www.uptodate.com/contents/management-of-postoperative-pain
10/12
9/14/2014
Management of postoperative pain
the surgery (eg, endometriosis, pelvic mass, malignancy, spinal radiculopathy). These patients should have a
thorough history and physical examination with attention to the surgical site. (See "Complications of abdominal
surgical incisions".)
Persistent pain may develop after surgery in 10 to 50 percent of patients, depending on the type of surgery; severe
chronic pain develops in 2 to 10 percent of these patients [121]. This pain is most often neuropathic. Therapy at the
time of surgery may prevent the development or reduce the severity of postoperative chronic pain [91].
SUMMARY AND RECOMMENDATIONS
● Pain control regimens should be tailored to the needs of the individual patient, taking into account the patient's
age, medical and physical condition, level of fear/anxiety,personal preferences, type of surgical procedure, and
response. (See'Introduction' above.)
● We suggest preemptive analgesia with drugs such as ibuprofen,ketorolac, COX-2 inhibitors
andgabapentin before induction of general anesthesia (Grade 2B). These agents are particularly useful to
decrease postoperative pain scores in ambulatory surgical patients. (See'Preemptive analgesia'above.)
● Following ambulatory surgery under sedation, we suggest treatment of acute pain in the recovery room with
intravenous fentanyl, followed by oral pain relievers such ascodeine,acetaminophen/codeinecombinations, or
nonsteroidal anti-inflammatory drugs upon discharge (Grade 2C). (See'Postoperative oral analgesics' above.)
● Following open or laparoscopic surgical procedures under general anesthesia, we suggest patient controlled
analgesia using intravenous narcotics such asmorphine orhydromorphone for postoperative analgesia (Grade
2C). Addition of nonsteroidal anti-inflammatory drugs, if not contraindicated, lowers the narcotic requirement and
improves quality of analgesia. The narcotics are switched to the oral route as soon as the patient tolerates oral
fluids. (See 'Patient controlled analgesia' above and'Postoperative oral analgesics' above.)
● For patients undergoing major abdominal surgeries with extensive incisions and those who are chronically
dependent on narcotics for pain relief, we suggest neuraxial anesthesia (epidural or spinal anesthesia) in
addition to general anesthesia (Grade 2C). In addition to preemptive analgesia, the neuraxial approach provides
postoperative analgesia. (See'Preemptive analgesia'above and'Intraoperative epidural or intrathecal opioid
injection' above.)
● For neuraxial anesthesia, epidural or intrathecal morphine(up to morphine 3 mg for epidural, Duramorph 0.2 mg
for spinal) can be used to provide postoperative pain relief for about 18 to 24 hours; this can be supplemented
with nonsteroidal anti-inflammatory drugs without increasing the risk of postoperative respiratory compromise. If
the pain relief is not satisfactory with this combination, additional intravenous narcotics (patient controlled
analgesia [PCA]) are provided and monitored by the pain service personnel.Ketamine can be used as an
adjunct, as well, especially in opioid-dependent patients and in situations where neuraxial anesthesia is
contraindicated. (See'Preemptive analgesia'above and'Intraoperative epidural or intrathecal opioid injection' above
and'Patient controlled analgesia' above.)
● For those patients in whom the pain relief is required for a longer duration than can be provided by a single dose
of neuraxialmorphine, we suggest postoperative patient controlled epidural analgesia (PCEA) as long as
needed, via a lumbar or low thoracic epidural catheter placed preoperatively (Grade 2B). Postoperative epidural
infusions are monitored by the postoperative pain service personnel. (See 'Postoperative epidural analgesia with
local anesthetics and opioids' above.)
● For patients onmethadone, we suggest restarting their usual dose of methadone if the situation permits (Grade
2C); however, opioid-dependent patients often require dosing over and above their baseline dose. We suggest
postoperative epidural catheter analgesia, even if the surgery is expected to result in average pain levels,
because it lowers opioid requirements (Grade 2C). A continuous infusion of narcotics is also acceptable; this
decision has to be individualized depending on the surgery and patient. (See 'Patients on methadone' above.)
http://www.uptodate.com/contents/management-of-postoperative-pain
11/12
9/14/2014
Management of postoperative pain
● For morbidly obese patients, we suggest postoperative analgesia via the epidural route to reduce the risk of
respiratory depression (Grade 2C). The use of only epidurally administered local anesthetics is an option.
(See 'Morbid obesity' above.)
http://www.uptodate.com/contents/management-of-postoperative-pain
12/12
Management of postoperative pain
Management of postoperative pain
Authors Section Deputy
Bhavani- Editor Editor
Shankar Ellen WK Nancy A
Kodali, Rosenquist,
Nussmeier,
MD
MD
MD,
Jasmeet
FAHA
S Oberoi,
MD
Disclosures: BhavaniShankar Kodali, MDNothing
to disclose.Jasm eet S
Oberoi, MDNothing to
disclose. Ellen WK
All
topics areMDNothing
updated as
Rosenquist,
to new evidence becomes available and our peer review process is complete.
Literature
review
current through: Aug 2014. | This topic last updated: May 12, 2014.
disclose. Nancy
A
Nussm eier, MD,
INTRODUCTION
— Management of postoperative pain relieves suffering and leads to earlier mobilization, shortened
FAHAEmployee of UpToDate,
Inc.
hospital
stay, reduced hospital costs, and increased patient satisfaction [1-3]. Pain control regimens should not be
Contributor disclosures
standardized;
rather, are
they are tailored to the needs of the individual patient, taking into account medical,
review ed for conflicts of
psychological,
and
physical
condition; age; level of fear or anxiety; surgical procedure; personal preference; and
interest by the editorial
group. When
response
to found,
agentsthese
given.
are addressed by vetting
through
a multi-level
review
The
major
goal in the
management of postoperative pain is minimizing the dose of medications to lessen side effects
process, and through
while
still
providing
adequate
analgesia. This goal is best accomplished with multimodal and preemptive analgesia [4].
requirements for references
to be provided to support the
Acontent.
multidisciplinary
Appropriatelyteam approach (eg, acute pain service) is useful for formulating a plan for pain relief, particularly in
referenced content
is
complicated
patients,
such as those who have undergone extensive surgery, chronically use narcotics, or have
required of all authors and
medical
comorbidities
must conform
to UpToDatethat could increase their risk of analgesia-related complications or side effects.
standards of evidence.
This
topicofdiscusses
the management of acute surgical pain. The management of chronic pain is discussed
Conflict
interest policy
elsewhere. (See "Evaluation of chronic pain in adults" and "Overview of the treatment of chronic pain".)
SURGICAL PAIN MECHANISM — Surgical pain is due to inflammation from tissue trauma (ie, surgical incision,
dissection, burns) or direct nerve injury (ie, nerve transection, stretching, or compression) (figure 1) [5]. The patient
senses pain through the afferent pain pathway (figure 2), which can be altered by various pharmacologic agents.
Tissue trauma releases local inflammatory mediators that can produce augmented sensitivity to stimuli in the area
surrounding an injury (hyperalgesia) or misperception of pain to non-noxious stimuli (allodynia) (figure 3). Other
mechanisms contributing to hyperalgesia and allodynia include sensitization of the peripheral pain receptors (primary
hyperalgesia) and increased excitability of central nervous system neurons (secondary hyperalgesia) [5-7].
Analgesic therapy has traditionally targeted central mechanisms involved in the perception of pain using opioids
(figure 4); however, it has become clear that a better approach uses several agents, each acting at different sites of
the pain pathway. This approach lessens the dependence on a given medication and mechanism.
Pain receptor activity can be directly blocked (eg,lidocaine) or anti-inflammatory agents (eg,aspirin, nonsteroidal antiinflammatory agents) can be used to diminish the local hormonal response to injury, thus indirectly decreasing pain
receptor activation.
Some analgesic agents target the activity of neurotransmitters by inhibiting or augmenting their activity
(eg, ketamine,clonidine, paracetamol,gabapentin, pregabalin) (figure 5). Neurotransmitters are responsible for carrying
electrical signals across the gap junctions between neurons. To produce analgesia, the activity of several
neurotransmitters is targeted, including substance P, calcitonin gene-related peptide, aspartate, glutamate, and
gamma-aminobutyric acid (GABA).
http://www.uptodate.com/contents/management-of-postoperative-pain
1/12
9/14/2014
Management of postoperative pain
Synergism between medications decreases the doses needed and helps avoid the unwanted effects associated with
the higher doses that would be required if only a single agent was used.
PREEMPTIVE ANALGESIA — Preemptive analgesia is the administration of analgesics prior to onset of noxious
stimuli. Preemptive analgesia modifies peripheral and central nervous system processing of noxious stimuli, thereby
reducing hyperalgesia and allodynia [5-7]. Preemptive analgesia reduces postoperative opioid use and opioid side
effects.
Effective preemptive analgesic techniques use multiple pharmacological agents to reduce nociceptor (pain receptor)
activation by blocking or decreasing receptor activation, and inhibiting the production or activity of pain
neurotransmitters.
Local — Local anesthetic can be injected prior to surgical incision and may promote preemptive analgesia. A metaanalysis of randomized trials found significantly decreased analgesic consumption and increased time to first rescue
analgesic request, but no significant differences in postoperative pain scores in patients who had preemptive local
anesthetic wound infiltration [8]. Some randomized trials have shown that local anesthetic injection around small
incision sites reduces postoperative somatic pain, but is inadequate for visceral pain [8-12].
Systemic — For preemptive analgesia, we use ibuprofen800 mg (orally), ketorolac 30 mg (intravenously),
orgabapentin 600 mg (orally). COX-2 inhibitors are also gaining acceptance for preemptive analgesia but have
precautions for their use. (See 'Oral nonsteroidal anti-inflammatory drugs'below and 'COX-2 inhibitors'below.)
Trials with clonidine,ketorolac, and ibuprofen [13-15] have demonstrated decreased postoperative narcotic
requirements.
The effect of preemptive analgesia using gabapentinis more variable. In multiple randomized trials, gabapentin
(also pregabalin) in doses ranging from 300 to 1200 mg orally one hour before surgery reduced postoperative opioid
usage [4,16-22]; however, two trials reported it was not useful in spinal surgery [23,24]:
● Six of seven randomized trials reported preoperativegabapentinadministration decreased analgesic requirements
by at least one-third during the first 24 postoperative hours. The remaining trial found the analgesic requirement
significantly reduced for postoperative days 2 through 10 [4,16-22].
● Two other randomized trials of patients undergoing spinal surgery did not find a benefit. Patients undergoing
lumbar discectomy showed no additional postoperative benefit from using more than 600 mg ofgabapentin for
preemptive analgesia [23]. In a double-blinded, placebo-controlled trial, preemptive gabapentin was not effective
in reducing postoperative pain and morphinerequirements in patients undergoing lumbar laminectomy [24].
NEURAXIAL (REGIONAL) ANALGESIA
Intraoperative epidural or intrathecal opioid injection — Intraoperative administration of epidural or intrathecal
opioids reduces the need for systemic opioids postoperatively [25-37]. For major abdominal surgeries with extensive
incisions, epidural infusions with local anesthetic provide superior pain relief as compared with conventional parenteral
narcotics. With less extensive surgery, however, intrathecal narcotics alone can be used for postoperative analgesia.
A single dose of intrathecally (spinal) administered narcotic can provide substantial pain relief up to 18 to 24 hours
postoperatively. Neuraxial analgesia is also suitable for those patients who are chronically dependent on narcotics for
pain relief.
Delayed respiratory depression due to rostral spread of opioids to the respiratory center in the medulla is a concern
with epidural or intrathecal administration of opioids. Respiratory depression may occur up to 18 hours after a
hydrophilic agent, such asmorphine, is injected. The incidence is approximately 0.1 percent at a dose of 0.2 mg
morphine and occurs almost exclusively in obese patients [38].
Observational studies report the incidence of respiratory depression in patients given single-injection neuraxial opioids
is in the range of 0.01 to 3 percent. A metaanalysis of randomized and observational trials comparing single-injection
or continuous neuraxial opioids compared with parenteral (ie, intravenous, intramuscular, or intravenous patienthttp://www.uptodate.com/contents/management-of-postoperative-pain
2/12
9/14/2014
Management of postoperative pain
controlled) opioids found no significant difference in the incidence of respiratory depression [39].
Intrathecal injection — Small intrathecal doses ofmorphine (0.1 to 0.2 mg) orfentanyl (10 to 20 mcg) are
administered during the placement of a spinal anesthetic. The onset of analgesia and its duration depend upon
whether the drug is lipophilic or hydrophilic and how it is transported within the cerebrospinal fluid.
Opioids administered in the subarachnoid space appear to act principally on mu receptors in the substantia
gelatinosa of the dorsal horn of the spinal cord by suppressing excitatory neuropeptide release from nerve fibers (type
C). The degree of uptake from the cerebrospinal fluid by the dorsal horn is determined primarily by the
physicochemical properties of the drug and, in particular, lipid solubility. Lipid-soluble compounds enjoy greater direct
diffusion into neural tissue as well as greater delivery to the dorsal horn by spinal segmental arteries.
Morphine is highly ionized and hydrophilic and does not penetrate lipid-rich tissues as well as fentanyl. Morphine
reaches maximum effect in about 45 minutes and lasts for 18 to 24 hours when administered by the spinal route. By
comparison, fentanyl, which is lipophilic (lipid soluble) and penetrates into the lipid rich dorsal horn, acts more
quickly, but its duration of action is shorter [38].
Uncommonly, a patient has severe pain postoperatively in spite of intrathecalmorphine administration. We usually
supplement these patients with intravenous narcotics. Typically, fentanyl(50 to 100 mcg intravenously) or morphine (3
mg intravenously) produces immediate pain relief. Once the initial pain is controlled, the intrathecal morphine that
was administered at placement of the spinal block often provides adequate ongoing pain relief.
In the rare circumstance when these measures fail, patient controlled analgesia (PCA) with fentanyl ormorphine can
be initiated. (See 'Patient controlled analgesia' below.)
The combination of PCA and intrathecal opioids does not increase the risk of respiratory depression over that with
either modality alone [40-42].
Epidural injection — The dose ofmorphine by the epidural route is about 5 to 10 times that of the intrathecal
route. We use 3 mg of epidural morphine for lumbar and low thoracic epidurals; however, for less painful surgery or
high-risk patients, lower doses can provide adequate analgesia with fewer side effects. For example, epidural
morphine 1.5 mg was as effective as 3 mg for post-cesarean delivery pain and was associated with a 60 percent
reduction in pruritus [43].
Postoperative epidural analgesia with local anesthetics and opioids — Local anesthetics and opioids can be
intermittently injected via an epidural catheter to provide analgesia postoperatively [34]. This approach is particularly
useful in patients who already have an epidural catheter located at the lumbar or low thoracic level for surgical
anesthesia; however, an epidural catheter can be placed postoperatively for this purpose. Typically, epidural
analgesia is continued until the patient is able to tolerate oral medications.
A combination of a local anesthetic and opioid is administered via a patient-controlled epidural pump (PCEA). This
combination lowers the dose requirements for each drug, as well as lowers the frequency of side effects [44-46].
Commonly used combinations includebupivacaine (0.125 percent) or ropivacaine (0.2 percent)
plus fentanyl (2 mcg/mL) orhydromorphone (20 mcg/mL)[47-52]. Sufentanil has also been used, but is costly without
providing any anesthetic or analgesic advantage.
A metaanalysis of randomized trials comparing the efficacy of epidural with local anesthetic alone versus epidural
with local anesthetic and opioid concluded that combination therapy was associated with a significant reduction in
visual analog scale pain scores on the first postoperative day [53].
Occasionally, analgesia is not satisfactory due to extensive surgery or patchy coverage of the epidural block. In these
situations, we suggest administering a local anesthetic (eg,bupivacaine 0.125 percent) via PCEA and opioid via
intravenous PCA. We suggest postoperative epidural analgesia combined with opioids via PCA for reoperations,
extensive resections, and opioid-dependent patients.
We use a standard regimen of 6 mL/hour basal rate of epidural bupivacaine (0.125 percent)
http://www.uptodate.com/contents/management-of-postoperative-pain
3/12
9/14/2014
Management of postoperative pain
with hydromorphone(20 mcg/mL), allowing the patient to self bolus 2 mL of this combination of drugs, with a bolus
lockout of 20 minutes and four-hour limit of 34 mL. For the mid and higher thoracic epidurals we use a mix of
bupivacaine 0.0625 percent with hydromorphone (20 mcg/mL)and a basal rate of 4mL/hour, keeping the remaining
settings the same.
Similar to earlier reports in obstetric patients and after different types of surgery, patient-controlled epidural analgesia
with bupivacaineand fentanyl provided as good postoperative analgesia as continuous epidural infusion of bupivacaine
and fentanyl after total knee arthroplasty. PCEA provided as good analgesia as continuous epidural analgesia with a
significantly smaller amount of bupivacaine-fentanyl solution [54,55].
Epidural infusions have to be fine-tuned to the patient's requirements. Usually, the epidural infusions are started prior
to completion of the surgery to obtain pain relief at the conclusion of surgery. Occasionally, boluses of 4 to 8
mL bupivacaine mix (0.125 percent with hydromorphone20 mcg/mL) are given if the patient is uncomfortable due to
pain upon emergence from anesthesia. Postoperative blood pressure and fluid requirements must be carefully
monitored while providing such boluses. Usually two boluses are enough to provide pain relief if the epidural catheter
is sited correctly. Once initial comfort is obtained, the PCEA epidural is continued as stated above. Occasionally, if
the patient requires additional boluses over and above the normal PCEA set doses as described above, to maintain
comfort, we usually either increase the basal rate to 8 to 10 mL with four-hour limit increased to a maximum of 64
mL. Increasing the continuous basal infusion avoids fluctuations in the level of analgesia, which occur with
intermittent administration.
Less commonly, epidurally administered alpha-2 agonists (eg, clonidine), NMDA receptor antagonists (eg, ketamine),
and cholinesterase inhibitors (eg,neostigmine) are used. They are opioid sparing and provide preemptive analgesia
that improves postoperative analgesia for these patients without increasing the incidence of adverse effects [56-61].
Morbid obesity — For morbidly obese patients, it is beneficial to provide postoperative analgesia via the epidural
route, particularly in those with a history of sleep apnea. Neuraxial analgesia is beneficial in obese patients, as they
are susceptible to sleep apnea and respiratory depression that may be exacerbated by parenteral narcotics. Patients
with sleep apnea and obesity are at increased risk for respiratory depression, and consideration must be given to
using local anesthetic alone for the epidural infusions. Patient controlled analgesia is an alternative in the absence of
epidural analgesia; however, the patients need to be closely monitored during the postoperative period. (See'Patient
controlled analgesia'below.)
Monitoring — It is important to carefully monitor patients receiving neuraxial analgesics for side effects, which
can be life-threatening. All patients with epidurals should be examined by a clinician at least daily to assess the
following: adequacy of pain relief; level of activity tolerated; whether there is any motor blockade from the epidural
medication; presence of side effects such as nausea and pruritus; and whether there are signs suggestive of infection
(erythema, tenderness, swelling, discharge) at the site of epidural catheter placement. Hypotension is not uncommon
after major abdominal surgery, so a careful assessment of fluid balance and other potential causes of hypotension
are warranted before implicating the epidural infusion as the source. Nausea or severe pruritus may warrant removing
the opioid from the infusion mix. Management of intrathecal morphine-induced pruritus is discussed separately.
(See "Pruritus: Overview of management".)
Parenteral or oral nonsteroidal anti-inflammatory agents can be used to supplement analgesia if narcotics are
removed from the epidural infusions.
Nursing protocols for patients with intrathecal opioids and epidural infusions should include monitoring respiratory rate
at least every two hours, maintaining intravenous access, keeping ephedrine and naloxone readily available, and not
administering parenteral or oral narcotics or sedatives without pain service clinician approval. In addition, the pain
service clinician and covering team clinicians should be notified promptly if analgesia is inadequate, respiratory rate is
less than eightbreaths/minute, systolic blood pressure is less than 80 mmHg, sedation or motor block increases, or
temperature is greater than 101.5°F on two occasions within eight hours.
Peripheral nerve blocks — Local anesthetics can also be administered, in a selective manner, perineurally. The
http://www.uptodate.com/contents/management-of-postoperative-pain
4/12
9/14/2014
Management of postoperative pain
monitoring protocols for regional blocks are similar to those described for neuraxial anesthesia [62-64]. (See"Overview
of peripheral nerve blocks".)
Commonly used perineural blocks include the brachial plexus block to manage upper extremity pain, and femoral or
popliteal nerve block for lower extremity pain. These neural structures can be localized using ultrasound guidance or
nerve stimulation techniques, and either a single shot of anesthetic injected or a perineural catheter placed to initiate
continuous infusions. A loading bolus, usually of 20 to 30 mL of 0.5 percentropivacaine, can be used for surgical
anesthesia. For postoperative pain relief, a continuous infusion of 0.2 percent ropivacaine at a rate of 10 mL/hour is
most commonly used [65-70]. (See "Peripheral nerve block: Techniques", section on 'Upper extremity' and"Peripheral
nerve block: Techniques", section on 'Lower extremity'.)
For postoperative chest wall and abdominal pain, a paravertebral technique can be utilized. This approach delivers
local anesthetic in the vicinity of the spinal nerves after their exit from the neural foramen. Usually, multiple spinal
levels need to be blocked individually to provide effective pain relief. (See "Peripheral nerve block: Techniques",
section on 'Paravertebral nerve block'.)
POSTOPERATIVE INTRAVENOUS MEDICATIONS
Parenteral opioids — Opiates provide swift and potent analgesia when administered parenterally. The most
commonly used intravenous opioids for treatment of postoperative pain aremorphine, hydromorphone,
and fentanyl [71-74].
Meperidine is not recommended for postoperative pain relief because it lowers seizure threshold, has a dysphoric
effect, and is not as efficacious as other drugs available [75]. Additionally, it has a slower rate of metabolism in the
elderly and in patients with hepatic and renal impairment, which leads to accumulation of meperidine and its active
metabolite normeperidine [75].
Intravenous opiates can be delivered in three different modes:
● Bolus intravenous injections are often used for moderate pain, with doses titrated to analgesic requirements and
the avoidance of respiratory depression and hemodynamic instability. Opioids given by intermittent injection
generally are not able to maintain steady analgesic plasma levels for two to four hours. Therefore, it is important
to give a loading dose: formorphine the loading dose is 0.1 to 0.3mg/kg and forhydromorphone it is 0.01 to
0.03 mg/kg to achieve adequate basal plasma levels. Ideally, this loading dose is given intraoperatively to allow
a smooth transition of pain control when the patient becomes awake and alert.
● Continuous intravenous infusions of opiates are used for moderate to severe pain which is poorly controlled with
repeated bolus injections. After an initial bolus dose, a low continuous infusion rate is set with subsequent
adjustment for adequate analgesia.
● Patient-controlled analgesia is useful in conscious patients (see below). This technique allows self-dosing with
opiates up to a predetermined limit set by the clinician. A low-dose continuous infusion may be added to
establish a basal level of analgesia. (See'Patient controlled analgesia' below.)
All opiates share common side effects. These include somnolence, depression of brainstem control of respiratory
drive, hypotension (more common in hypovolemic patients and following rapid injection), urinary retention, and emesis
due to direct stimulation of the chemoreceptor trigger zone. Histamine release often follows morphineadministration
and may produce flushing, tachycardia, hypotension, pruritus, and bronchospasm. Gastrointestinal transit slows with
prolonged administration, resulting in constipation and ileus in many patients; this effect is thought to reflect binding
to local opiate receptors in the gut. Some data suggest thatmethylnaltrexone, a polar opiate antagonist that does not
cross the blood-brain barrier, may diminish the peripherally-mediated side effects of opiates while maintaining central
analgesic effects. (See "Pain control in the critically ill adult patient".)
Use of acetaminophen or an NSAID with opioids reduces narcotic requirements [76]. This is particularly useful in
patients with high narcotic needs (opioid tolerance or chronic use) and may decrease narcotic-related side effects.
http://www.uptodate.com/contents/management-of-postoperative-pain
5/12
9/14/2014
Management of postoperative pain
When pain is less severe and the patient is able to take an oral diet, oral pain relievers can be initiated and continued
after discharge, as needed. (See 'Oral opioids'below.)
Morphine — Morphine is the prototype opiate and remains widely used. The onset of analgesia is rapid, with the
peak effect occurring in one to two hours and an elimination half-life of three to five hours.
● Bolus intravenous injections of morphineare initiated with a 2 mg dose, administered slowly over four to five
minutes, and titrated upward in 1 to 2 mg increments every one to three hours.
● For continuous infusions, a bolus dose of 2 to 5 mg is followed by 1 mg per hour; subsequent dose adjustments
in the hourly infusion rate are titrated to the desired level of analgesia. Continuous infusions may be of use in
opioid-tolerant patients such as those on chronic opiate therapy who need parenteral administration.
● Intramuscular injection: 5 to 10 mg every three to four hours as needed. Subcutaneous injection is possible but
not recommended, as repeated subcutaneous administration causes local tissue irritation, pain, and induration.
Fentanyl — A synthetic derivative of morphine,fentanyl is approximately 100 times more potent. It is also more
lipid-soluble than morphine, which results in a more rapid onset of action, due to improved penetration of the bloodbrain barrier, and a shorter half-life of two to three hours. Fentanyl usually is administered as a continuous
intravenous infusion, mainly in an intensive care unit setting. Fentanyl is virtually devoid of histamine-releasing
properties, and may therefore be preferred in the presence of hemodynamic instability or bronchospasm. (See "Pain
control in the critically ill adult patient".)
Intravenous boluses every one to two hours may, however, be given for moderate postoperative pain.
● For moderate analgesia after outpatient surgery, intravenousfentanyl is initiated with a 25 mcg to 100 mcg bolus
administered over one to two minutes; additional boluses can be given every one to two hours as needed until
oral medications can be instituted prior to discharge.
● For moderate to severe pain, a loading dose of 50 to 200 mcg is followed by a continuous intravenous infusion of
25 to 50 mcg per hour, with titration to adequate analgesia.
Administration of fentanyl for more than five days is associated with deposition of the drug in adipose tissue. These
stores are mobilized following the cessation of drug and may result in prolonged sedation.
Hydromorphone — Hydromorphone (Dilaudid) is a semisynthetic opiate agonist which, like fentanyl, has a more
rapid onset of analgesia (within 30 minutes) and a shorter half-life (2.4 hours) than morphine. For control of moderate
to severe pain, 0.2 to 0.6 mg of hydromorphone is administered as an intravenous bolus every two to three hours.
Sufentanil, alfentanil, and remifentanil — Sufentaniland Alfentanil are derivatives of fentanyl. Sufentanil is 10
times more potent than fentanyl, whereas alfentanil has about 1/5 to 1/10 the potency of fentanyl. Due to their rapid
onset of action (within two to three minutes of an injection) and short elimination half-lives (approximately 90
minutes), these agents are nearly always used as adjuncts to anesthesia and for immediate postoperative analgesia.
Sufentanil appears to cause less hemodynamic instability, respiratory depression, and chest-wall rigidity than
fentanyl or alfentanil. However, the high cost of sufentanil precludes its routine use for perioperative analgesia.
Remifentanil, another derivative of fentanyl, is an ultra short-acting agent with a context-sensitive half-life remaining at
four minutes after a four-hour infusion due to its rapid hydrolysis by nonspecific tissue and plasma esterases. It has
an analgesic potency approximately equal to fentanyl.
For patients with renal compromise, the dose of these medications has to be decreased depending on the degree of
renal insufficiency.Remifentanil is the opioid agent least subject to alterations in bioavailability associated with
hepatic insufficiency; however, its potency has other inherent dangers. It is advisable to refer to a drug formulary
before prescribing these agents in patients with renal or hepatic insufficiency.
Ketorolac — Nonsteroidal anti-inflammatory agents (NSAIDS) are useful in reducing the amount of opiates requested
by the patient and decreasing opioid side effects [76]. NSAIDS also play an important role as adjuncts to other
http://www.uptodate.com/contents/management-of-postoperative-pain
6/12
9/14/2014
Management of postoperative pain
agents, such as epidural analgesia, and intravenous administration ofketorolac can be given for preemptive analgesia.
(See'Preemptive analgesia' above and 'Oral nonsteroidal anti-inflammatory drugs' below.)
Administration of ketorolacreduces narcotic consumption by 25 to 45 percent and indirectly lowers opioid side effects
such as ileus, nausea, and vomiting [14,15,77-81]. The usual dose of ketorolac in our practice is 30 mg given
intravenously. NSAIDs are discussed in more detail separately. (See "NSAIDs: Therapeutic use and variability of
response in adults" and "Nonselective NSAIDs: Overview of adverse effects".)
COX-2 inhibitors — Single doses of COX-2 inhibitors may be used to decrease the need for opioids postoperatively.
In Cochrane reviews of placebo-controlled randomized trials of postoperative pain control, use of celecoxib (200 or 400
mg oral), etoricoxib (120 mg oral), or parecoxib (20 or 40 mg intravenous or intramuscular) delayed and decreased the
need for rescue analgesics without significant side effects [82-84].
In several trials, single-dose COX-2 inhibitors had greater analgesic efficacy and tolerability than opioids, but were
similar to nonselective NSAIDs for postoperative pain management [77,81,85-87]. In the United States, COX-2
inhibitors carry a "black-box" warning regarding cardiovascular risk, although this risk appears to be related to longterm use. (See "Overview of selective COX-2 inhibitors" and "COX-2 selective inhibitors: Adverse cardiovascular
effects".)
COX-2 inhibitors may also be used for single dose preoperative administration. (See 'Preemptive analgesia'above.)
Ketamine — Ketamine is a noncompetitive inhibitor of the N-methyl-D-aspartate (NMDA) receptor. Ketamine
reduces hyperalgesia and opioid tolerance, thereby decreasing postoperative opioid requirements and possibly
chronic post-surgical pain [88]. It may be used in subanesthetic doses in the perioperative period, generally for
patients whose pain might be difficult to manage with opioids alone. The clinical use of ketamine is limited due to its
potential to cause hallucinations and a dissociative mental state.
In a 2011 systematic review and metaanalysis of trials of perioperative intravenous (IV)ketamine, there was a
reduction in total opioid consumption and an increase in the time to first analgesic [89]. Patients having the most
painful surgical procedures, including thoracic, upper abdominal, and major orthopedic operations, had improvement
in pain scores despite a decrease in opioid consumption. Ketamine was not effective for patients having surgery
associated with mild pain, such as tonsillectomy, dental, or head and neck surgery.
There is great variability in doses of ketamine used for postoperative analgesia; typical single IV doses range from
150 to 1000 mcg/kg,and IV continuous infusions range from 120 to 600mcg/kg per hour [88].
The benefit of addingketamine to patient controlled analgesia (PCA) with opioids is less clear. In a 2010 systematic
review, the addition of ketamine to opioid PCA reduced pain score, opioid consumption, and postoperative
desaturation after thoracic surgery; however, there was no benefit for orthopedic or abdominal surgery [90]. Doses of
ketamine in these studies varied from 0.75 to 5 mg ketamine for each milligram of morphine.
Ketamine can be particularly useful as an adjunct when used in patients taking chronic opioids ormethadone whose
pain is poorly controlled in spite of high-dose opioid therapy.
There may be a role forketamine in prevention of postoperative chronic pain syndromes [91].
Intravenous lidocaine — Intravenouslidocaine can be administered by infusion intraoperatively and/orpostoperatively
for the management of pain. An initial bolus (1.5 to 2 mg/kg)can be used with an intraoperative infusion dose ranging
between 1.5 to 3mg/kg/hour. The infusion can be continued postoperatively but is usually at a lower dose. The
duration of postoperative therapy needed is poorly defined.
The most significant benefit of lidocaine infusion is seen following major abdominal surgery, with significantly
improved pain scores in the immediate postoperative period, and reduced incidence of postoperative ileus compared
with placebo [92]. There appears to be a trend toward a reduction in the length of stay; however, variability exists in
the reported data [92,93].
http://www.uptodate.com/contents/management-of-postoperative-pain
7/12
9/14/2014
Management of postoperative pain
The side effects of intravenous lidocaine are discussed in detail elsewhere. (See "Major side effects of class I
antiarrhythmic drugs".)
Magnesium — Magnesium is an antagonist of the NMDA receptor. Intravenous (IV) magnesium has been found
effective as an adjuvant treatment to reduce opioid requirements; it may be useful in opioid-tolerant patients, or when
there are medical concerns related to opioid dose.
In two 2013 meta-analyses of trials of intraoperative IVmagnesium sulfatecompared with placebo or no treatment in
over 1200 patients, peri-operative IV magnesium reduced opioid consumption and pain scores in the first 24 hours
postoperatively, without serious adverse effects [94,95]. In one of the analyses, 24-hour morphineconsumption
decreased by 24.4 percent (7.6 mg [95% CI 5.8-9.5 mg]); pain scores at 24 hours after surgery were reduced on a
100 point scale by 4.2 (95% CI 2.1-6.3) at rest and 9.2 (95% CI 2.3-16.1) on movement [94]. Both bolus and
continuous infusion regimens were effective. Total peri-operative doses ranged from 1.03 g to 23.5 g, without
correlation between dose and reduction in morphine consumption; the optimum regimen could not be determined.
Magnesium may provide benefit when used in patients who are also receivingketamine. In a trial of 50 patients having
scoliosis surgery, the addition of IV magnesium to an intraoperative ketamine regimen decreased
postoperative morphineconsumption by 30 percent, with improved sleep and satisfaction scores, but no change in
pain scores [96].
Intravenous acetaminophen — Intravenous acetaminophen may be used in patients in whom oral or rectal
administration is not an option. Intravenously administered acetaminophen has a more rapid and predictable onset of
effect (5 to 10 minutes) and time to peak concentration (15 minutes) in most patients compared with rectal or oral
administration (onset 10 to 60 minutes or more). In a meta-analysis of randomized trials, the addition of
acetaminophen (intravenous or oral) tomorphine following major surgery resulted in a small, but statistically
significant, decrease in morphine use postoperatively [76].
The addition ofacetaminophen to nonsteroidal anti-inflammatory drugs (NSAID) regimens can improve pain control. A
systematic review that compared the use of acetaminophen alone or in combination with NSAIDs for postoperative
pain showed the combination to be more effective than NSAIDs alone in 64 percent of the studies [97].
A reduced dose is suggested for low weight adults and adolescents (body weight 33 to 50 kg) and in patients with
mild or moderate hepatic insufficiency, chronic alcoholism, malnutrition, or dehydration. Patients with severe renal
insufficiency (CrCl ≤30 mL/min) may receive a usual dose, but not more often than once every six
hours. Acetaminophen is contraindicated in patients having severe hepatic insufficiency or severe active liver disease.
PATIENT CONTROLLED ANALGESIA — The patient controlled analgesia (PCA) pump is the preferred mode of
administering opioids for moderate to severe postoperative pain. The benefits include easier patient access to pain
medication, reduced chance of medication error, and ready titration (table 1). A meta-analysis of analgesia after
intraabdominal surgery found that continuous epidural analgesia significantly improved control of postoperative pain
compared with opioid PCA, but was associated with a higher incidence of pruritus [98]. (See 'Neuraxial (regional)
analgesia' above.)
Morphine, hydromorphone, and fentanyl can be administered via PCA pump. The pump is discontinued when the
patient is able to tolerate oral analgesics. A systematic review of randomized trials comparing PCA versus
conventional administration of opioids evaluated 55 trials [99]. Compared with conventional parenteral analgesia, PCA
use was associated with higher opioid consumption, provided better pain control, and resulted in greater patient
satisfaction in spite of a higher incidence of pruritus. There is insufficient evidence to draw comparisons about the
other advantages and disadvantages of these two methods of pain relief. The incidence of other side effects was
similar between the groups, with no differences observed in the length of hospital stay.
A fentanyl PCA may be used for patients with allergies or intolerances to morphine andhydromorphone, but is less
desirable in most patients because of its short duration of action. Fentanyl may be easier to titrate in patients with
renal and hepatic insufficiency. Alternatively, hydromorphone can be used in patients with renal insufficiency
http://www.uptodate.com/contents/management-of-postoperative-pain
8/12
9/14/2014
Management of postoperative pain
[100,101].
Issues related to opioid administration via PCA pump in specific subpopulations are described below:
Patients using opioids chronically — Patients who are using opioids chronically should be monitored closely. The
postoperative analgesic needs of these patients, which may already be high, will typically exceed their daily doses.
Several options are available to meet the acute pain management requirements of these patients. A continuous PCA
basal infusion may be needed to control pain effectively since routine dosing schedules may not be sufficient.
Another method for providing a basal opioid level for opioid-tolerant patients is the addition of long acting opiates via a
transdermal route (eg, fentanyl patch), with titration of shorter-acting agents for acute postoperative pain. Transdermal
routes should not be used for the control of postoperative pain in nonopioid tolerant patients due to their slow onset of
action (peak levels achieved 24 to 48 hours after patch placement), and potential harmful side effects, particularly
respiratory depression.
Patients on methadone — For patients on methadone maintenance for drug dependency or for chronic pain, we
suggest restarting their methadone as soon as possible; this may be administered orally with the usual dose or
intravenously with half the usual dose. Postoperative analgesic requirements may be covered with additional opioids
as needed via PCA pump. Although these patients require high opioid doses, they are generally tolerant to serious
side effects, such as respiratory depression. Consultation with a pain specialist may be helpful. Conversion tables for
commonly-used opioids can also be useful (figure 6 andtable 2). (See "Treatment of opioid use disorder".)
POSTOPERATIVE ORAL ANALGESICS — A wide variety of oral pain medications are available for the treatment of
acute pain.
Choices include:
● Acetaminophen (325 to 1000 mg orally [or rectally] every four to six hours, to a maximum dose of 4g/day)
● Ibuprofen (300 to 800 mg orally three or four times per day)
● Narcotics
• Codeine 15 to 60 mg orally every four to six hours
• Oxycodone 5 to 30 mg orally every four to six hours
• Combination therapies such as Percocet (combinations of 325 to 650 mgacetaminophen/2.5to 10
mgoxycodone, one or two tablets orally every four to six hours), Percodan (325 mg aspirin/4.5 mg
oxycodone, one or two tablets orally every four to six hours), Tylenol #2 (300
mgacetaminophen/15mg codeine, one to two tablets orally every four to six hours), Tylenol #3 (300
mgacetaminophen/30mg codeine, one to two tablets orally every four to six hours)
Depending upon the severity of the pain, prior allergies, prior patient experience and tolerance of these medications
(nausea, gastrointestinal upset, bleeding disorders), any of these oral medications can be prescribed and tailored to
the needs of the individual.
A Cochrane review analyzed the data for single dose oral analgesics from 35 prior Cochrane Reviews treating about
45,000 participants for acute postoperative pain [102]. No drug was found to produce high levels of pain relief in all
participants. In patients with acute moderate to severe pain, 70 percent achieved good pain relief with the best drugs
and pain relief for the worst drugs occurred in about 30 percent of the patients. The percentage of patients treated
with placebo who achieved at least 50 percent maximum pain relief over four to six hours ranged from 5 to 15 percent.
The period over which pain was relieved varied from two hours to 20 hours. Drug/dosecombinations with good (low)
numbers needed to treat (NNT) for at least 50 percent maximum pain relief over four to six hours relative to placebo
included [102]:
● Ibuprofen 400 mg (NNT 2.5, 95% CI 2.4-2.6)
http://www.uptodate.com/contents/management-of-postoperative-pain
9/12
9/14/2014
Management of postoperative pain
● Diclofenac 50 mg (NNT 2.7, 95% CI 2.4-3.0)
● Etoricoxib 120 mg (NNT 1.9, 95% CI 1.7-2.1)
● Codeine 60 mg + paracetamol 1000 mg (NNT 2.2, 95% CI 1.8-2.9)
● Celecoxib 400 mg (NNT 2.5, 95% CI 2.2-2.9)
● Naproxen 500/550 mg (NNT 2.7; 95% CI 2.3-3.3)
A long duration of action (>8 hours) was noted for:
● Etoricoxib 120 mg
● Diflunisal 500 mg
● Naproxen 500/550 mg
● Celecoxib 400 mg
● Oxycodone 10 mg plus paracetamol 650 mg
Oral nonsteroidal anti-inflammatory drugs — We suggest that pharmacological management of mild to moderate
postoperative pain begin with a nonsteroidal anti-inflammatory drug (NSAID), unless there is a contraindication to
these agents. Preoperative administration of oral NSAIDS prior to elective minor surgery reduces postoperative pain
[15,77,103-106]. (See'Preemptive analgesia'above.)
Commonly used oral NSAIDS that can be used for postoperative pain areibuprofen, diclofenac,ketoprofen, and
paracetamol. If oral medication is not tolerated, rectal administration is an alternative route.
NSAIDs are discussed in more detail separately. (See"NSAIDs: Therapeutic use and variability of response in
adults" and "Nonselective NSAIDs: Overview of adverse effects".)
Oral opioids — When the patient is tolerating an oral diet, the opioid regimen for patients with moderate to severe
pain can be switched from intravenous to oral opioids such as oxycodone,hydromorphone, ormorphine. General
opioid dosing guidelines are provided in the table (table 3). (See 'Postoperative intravenous medications'above.)
Ideally, the dose should be calculated on the basis of the 24-hour PCA dose and appropriate conversion calculated
(figure 6 and table 2). As an example, a patient taking 40 mg of intravenousmorphine over 24 hours would be given 20
mg ofoxycodone every four hours or 5 mg of hydromorphoneevery four hours. Patients with mild to moderate pain can
be switched to NSAIDS or acetaminophen.
Alpha-2 receptor agonists — The exact mechanism by which alpha-2 agonists produce analgesia remains
unknown; it is postulated that release of acetylcholine may play a role [107].
Alpha-2 agonists also reduce the undesirable physiological and psychological effects of opioid withdrawal [108].
Studies indicate that alpha-2 agonists such as clonidineand dexmedetomidine exert a potent analgesic response,
and that their potency is increased by concomitant opioid therapy [109,110].
Oral clonidine at doses of 150 to 200 mcg preoperatively has been shown to provide perioperative hemodynamic
stability and reduce the requirement of postoperative analgesics [111-113].
Anticonvulsants — Anticonvulsant agents such asgabapentin and pregabalinare effective in the management of
chronic neuropathic pain conditions.
Perioperative gabapentin andpregabalin exert analgesic and opioid sparing effects and, as a result, decrease opioidrelated side-effects [114-119]. A disadvantage to these agents is a dose-dependent sedation [116,119]. Several
systematic reviews support an adjunctive role for these agents in the management of postoperative pain [116,118120].
PERSISTENT POSTOPERATIVE PAIN — Normally, incisional pain gradually resolves over a period of days to
weeks. Increasing pain or pain that persists for months may be due to surgical complications (eg, local scar
formation, infection,dehiscence/hernia, foreign body reaction, and incisional neuroma), or to conditions unrelated to
http://www.uptodate.com/contents/management-of-postoperative-pain
10/12
9/14/2014
Management of postoperative pain
the surgery (eg, endometriosis, pelvic mass, malignancy, spinal radiculopathy). These patients should have a
thorough history and physical examination with attention to the surgical site. (See "Complications of abdominal
surgical incisions".)
Persistent pain may develop after surgery in 10 to 50 percent of patients, depending on the type of surgery; severe
chronic pain develops in 2 to 10 percent of these patients [121]. This pain is most often neuropathic. Therapy at the
time of surgery may prevent the development or reduce the severity of postoperative chronic pain [91].
SUMMARY AND RECOMMENDATIONS
● Pain control regimens should be tailored to the needs of the individual patient, taking into account the patient's
age, medical and physical condition, level of fear/anxiety,personal preferences, type of surgical procedure, and
response. (See'Introduction' above.)
● We suggest preemptive analgesia with drugs such as ibuprofen,ketorolac, COX-2 inhibitors
andgabapentin before induction of general anesthesia (Grade 2B). These agents are particularly useful to
decrease postoperative pain scores in ambulatory surgical patients. (See'Preemptive analgesia'above.)
● Following ambulatory surgery under sedation, we suggest treatment of acute pain in the recovery room with
intravenous fentanyl, followed by oral pain relievers such ascodeine,acetaminophen/codeinecombinations, or
nonsteroidal anti-inflammatory drugs upon discharge (Grade 2C). (See'Postoperative oral analgesics' above.)
● Following open or laparoscopic surgical procedures under general anesthesia, we suggest patient controlled
analgesia using intravenous narcotics such asmorphine orhydromorphone for postoperative analgesia (Grade
2C). Addition of nonsteroidal anti-inflammatory drugs, if not contraindicated, lowers the narcotic requirement and
improves quality of analgesia. The narcotics are switched to the oral route as soon as the patient tolerates oral
fluids. (See 'Patient controlled analgesia' above and'Postoperative oral analgesics' above.)
● For patients undergoing major abdominal surgeries with extensive incisions and those who are chronically
dependent on narcotics for pain relief, we suggest neuraxial anesthesia (epidural or spinal anesthesia) in
addition to general anesthesia (Grade 2C). In addition to preemptive analgesia, the neuraxial approach provides
postoperative analgesia. (See'Preemptive analgesia'above and'Intraoperative epidural or intrathecal opioid
injection' above.)
● For neuraxial anesthesia, epidural or intrathecal morphine(up to morphine 3 mg for epidural, Duramorph 0.2 mg
for spinal) can be used to provide postoperative pain relief for about 18 to 24 hours; this can be supplemented
with nonsteroidal anti-inflammatory drugs without increasing the risk of postoperative respiratory compromise. If
the pain relief is not satisfactory with this combination, additional intravenous narcotics (patient controlled
analgesia [PCA]) are provided and monitored by the pain service personnel.Ketamine can be used as an
adjunct, as well, especially in opioid-dependent patients and in situations where neuraxial anesthesia is
contraindicated. (See'Preemptive analgesia'above and'Intraoperative epidural or intrathecal opioid injection' above
and'Patient controlled analgesia' above.)
● For those patients in whom the pain relief is required for a longer duration than can be provided by a single dose
of neuraxialmorphine, we suggest postoperative patient controlled epidural analgesia (PCEA) as long as
needed, via a lumbar or low thoracic epidural catheter placed preoperatively (Grade 2B). Postoperative epidural
infusions are monitored by the postoperative pain service personnel. (See 'Postoperative epidural analgesia with
local anesthetics and opioids' above.)
● For patients onmethadone, we suggest restarting their usual dose of methadone if the situation permits (Grade
2C); however, opioid-dependent patients often require dosing over and above their baseline dose. We suggest
postoperative epidural catheter analgesia, even if the surgery is expected to result in average pain levels,
because it lowers opioid requirements (Grade 2C). A continuous infusion of narcotics is also acceptable; this
decision has to be individualized depending on the surgery and patient. (See 'Patients on methadone' above.)
http://www.uptodate.com/contents/management-of-postoperative-pain
11/12
9/14/2014
Management of postoperative pain
● For morbidly obese patients, we suggest postoperative analgesia via the epidural route to reduce the risk of
respiratory depression (Grade 2C). The use of only epidurally administered local anesthetics is an option.
(See 'Morbid obesity' above.)
http://www.uptodate.com/contents/management-of-postoperative-pain
12/12
