INTRODUCTION — Management of postoperative pain relieves suffering and leads to earlier mobilization, shortened hospital stay, reduced hospital costs, and increased patient satisfaction [1-3]. Pain control regimens should not be standardized; rather, they are tailored to the needs of the individual patient, taking into account medical, psychological, and physical condition; age; level of fear or anxiety; surgical procedure; personal preference; and response to agents given.
The major goal in the management of postoperative pain is minimizing the dose of medications to lessen side effects while still providing adequate analgesia. This goal is best accomplished with multimodal and preemptive analgesia [4].
A multidisciplinary team approach (eg, acute pain service) is useful for formulating a plan for pain relief, particularly in complicated patients, such as those who have undergone extensive surgery, chronically use narcotics, or have medical comorbidities that could increase their risk of analgesia-related complications or side effects.
This topic discusses the management of acute surgical pain. The management of chronic pain is discussed 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 transaction, 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 anti-inflammatory 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).
Synergism between medications decreases the dosages 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 meta-analysis 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 ibuprofen 800 mg (orally), ketorolac 30 mg (intravenously), or gabapentin 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 gabapentin is 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 preoperative gabapentin administration 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 of gabapentin for preemptive analgesia [23]. In a double-blinded, placebo-controlled trial, preemptive gabapentin was not effective in reducing postoperative pain and morphine requirements 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 as morphine, 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 patient-controlled) opioids found no significant difference in the incidence of respiratory depression [39].
Intrathecal injection — Small intrathecal doses of morphine (0.1 to 0.2 mg) or fentanyl (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 intrathecal morphine 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 or morphine 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 of morphine 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.
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 [43-45]. Commonly used combinations include bupivacaine (0.125 percent) or ropivacaine (0.2 percent) plus fentanyl (2 mcg/mL) or hydromorphone (20 mcg/mL) [46-51]. 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 [52].
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) 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 4 mL/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 bupivacaine and 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 [53,54].
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 hydromorphone) (20 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 [55-60].
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 physician 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 physician approval. In addition, the pain service physician and covering team physicians should be notified promptly if analgesia is inadequate, respiratory rate is less than 8 breaths/minute, systolic blood pressure is less than 80 mmHg, sedation or motor block increases, or temperature is greater than 101.5 degrees F on two occasions within eight hours.
Peripheral nerve blocks — Local anesthetics can also be administered, in a selective manner, perineurally. The monitoring protocols for regional blocks are similar to those described for neuraxial anesthesia [61-63]. (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% ropivacaine, can be used for surgical anesthesia. For postoperative pain relief, a continuous infusion of 0.2% ropivacaine at a rate of 10 mL/hour is most commonly used [64-69]. (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 are morphine, hydromorphone, and fentanyl [70-73].
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 [74]. 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 [74].
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: for morphine the loading dose is 0.1 to 0.3 mg/kg and for hydromorphone 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 physician. 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 morphine administration 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 that methylnaltrexone, a polar opiate antagonist which 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".)
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 morphine are 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 blood-brain 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, intravenous fentanyl 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 — Sufentanil and 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 thus decreasing opioid side effects [75]. NSAIDS also play an important role as adjuncts to other agents, such as epidural analgesia, and intravenous administration of ketorolac can be given for preemptive analgesia. (See 'Preemptive analgesia' above and 'Oral nonsteroidal anti-inflammatory drugs' below.)
Administration of ketorolac reduces narcotic consumption by 25 to 45 percent and indirectly lowers opioid side effects such as ileus, nausea, and vomiting [14,15,76-80]. 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 — COX-2 inhibitors are another option for single dose preoperative administration. (See 'Preemptive analgesia' above.)
Two meta-analyses of randomized, placebo-controlled trials evaluating the efficacy of parecoxib (seven studies) and etoricoxib (five studies) found that single-dose treatments of these medications (parecoxib 20 or 40 mg and etoricoxib 120 mg) provided significantly more effective analgesia than placebo and was well tolerated [81,82]. Significantly fewer participants receiving these COX-2 inhibitors required rescue medications over the study period.
Several studies found that single-dose COX-2 inhibitors have greater analgesic efficacy and tolerability than opioid-containing analgesics, but were similar to nonselective NSAIDs in postoperative pain management [76,78,80,83-86]. However, unlike nonselective NSAIDS, COX-2 inhibitors carry a "black-box" warning regarding cardiovascular risk, although this risk appears to be more relevant for long-term use. (See "Overview of selective COX-2 inhibitors" and "COX-2 selective inhibitors: Adverse cardiovascular effects".)
Ketamine — Ketamine is a noncompetitive inhibitor of the N-methyl-D-aspartate (NMDA) receptor. Ketamine reduces hyperalgesia and prevents opioid tolerance, therefore lowering morphine consumption and its side effects [87]. It also acts as a bronchodilator. The clinical use of ketamine is limited due to its potential to cause hallucinations and a dissociative mental state. For this reason, experienced anesthesia personnel should be involved in managing the drug [88]. We suggest an infusion dose starting at 0.1 mg/kg/hr up to 0.3 mg/kg/hr [87].
Systematic reviews of randomized trials evaluating the adjunctive use of ketamine with morphine PCA consistently find significantly lower PCA morphine consumption [58,89-92]. However, results are variable with respect to measurement of qualitative pain control, with some trials showing significantly improved postoperative pain scores while others show no benefit.
Ketamine can be particularly useful as an adjunct when used in patients taking chronic opioids or methadone whose pain is poorly controlled in spite of high dose opioid therapy. (See 'Patients using opioids chronically' below and 'Patients on methadone' below.)
Intravenous lidocaine — Intravenous lidocaine can be administered by infusion intraoperatively and/or postoperatively for the management of pain. An initial bolus (1.5 to 2 mg/kg) can be used with an intraoperative infusion dosage ranging between 1.5 to 3 mg/kg/hour. The infusion can be continued postoperatively but is usually at a lower dosage. 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 [93]. There appears to be a trend toward a reduction in the length of stay; however, variability exists in the reported data [93,94].
The side effects of intravenous lidocaine are discussed in detail elsewhere. (See "Major side effects of intravenous lidocaine".)
Intravenous acetaminophen — Oral acetaminophen is one of the most widely used agents for acute pain relief, but historically, poor solubility and stability of this agent in aqueous solution prevented its use in an intravenous form. Stable formulations of intravenous acetaminophen (ie, propacetamol, paracetamol) have been developed and are commercially available (eg, Ofirmev™).
Propacetamol is a prodrug that is hydrolyzed by plasma esterases to paracetamol within minutes of administration [95]. The disadvantages of propacetamol are that it requires reconstitution, and may cause contact dermatitis and pain at the site of injection. In contrast, paracetamol is a ready-to-use solution without these adverse reactions.
Paracetamol acts at both central and peripheral points of the pain pathway, including stimulation of nitric oxide by direct inhibition of n-methyl-D-aspartate (NMDA) receptors and inhibition of the cyclo-oxygenase 2 pathway [96].
In adults, paracetamol is administered as a 1 g/100 mL intravenous infusion over 15 minutes with a maximum dose of 4 g daily. Paracetamol is metabolized in the liver and excreted in the urine, and caution is advised when using this agent in patients with hepatic or renal insufficiency. Overdose can occur and is treated with acetylcysteine. The treatment of paracetamol overdose is reviewed elsewhere. (See "Acetaminophen (paracetamol) poisoning in adults: Treatment".)
A systematic review identified 21 studies that compared the use of paracetamol alone or in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) [97]. Paracetamol combined with NSAIDs was more effective than paracetamol alone or NSAID alone in 85 and 64 percent, respectively, of the studies evaluated. The administration of intravenous acetaminophen has opioid-sparing effects [98,99]. The role of intravenous acetaminophen in preemptive analgesia is currently unclear and further study is needed [100,101].
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 [102]. (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 [103]. Compared with conventional parenteral analgesia, PCA provided better pain control, led to greater opioid use, 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 and hydromorphone, 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 [104,105].
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 usual methadone dose orally as soon as possible and covering postoperative analgesic requirements with additional opioids as needed via PCA pump. These patients may require high doses, which are usually safe for this population because of tolerance to serious side effects, such as respiratory depression. We suggest consultation with pain physicians. Conversion tables for the commonly used opioids can also be useful (table 2 and figure 6). (See "Treatment of opioid use and dependence".)
POSTOPERATIVE ORAL ANALGESICS — There is a wide range of oral pain medications to choose from, including acetaminophen (325 to 1000 mg orally or rectally every four to six hours, to a maximum dose of 4 g/day), ibuprofen (300 to 800 mg 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) or a combination of these, such as Percocet (combinations of 325 to 650 mg acetaminophen, 2.5 to 10 mg oxycodone, one or two tablets every four to six hours), Percodan (325 mg aspirin, 4.5 mg oxycodone, one or two tablets every four to six hours), Tylenol #2 (300 mg acetaminophen, 15 mg codeine, one to two tablets every four to six hours), Tylenol #3 (300 mg acetaminophen, 30 mg codeine, one to two tablets 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.
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 [15,76,83,106-108]. (See 'Preemptive analgesia' above.)
Commonly used oral NSAIDS that can be used for postoperative pain are ibuprofen, 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, or morphine. 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 4). As an example, a patient taking 40 mg of intravenous morphine over 24 hours would be given 20 mg of oxycodone every four hours or 5 mg of hydromorphone every 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 [109].
Alpha-2 agonists also reduce the undesirable physiological and psychological effects of opioid withdrawal [110]. Studies indicate that alpha-2 agonists such as clonidine and dexmedetomidine exert a potent analgesic response, and that their potency is increased by concomitant opioid therapy [111,112].
Oral clonidine at doses of 150 to 200 micrograms preoperatively has been shown to provide perioperative hemodynamic stability and reduce the requirement of postoperative analgesics [113-115].
Anticonvulsants — Anticonvulsant agents such as gabapentin (Neurontin®) and pregabalin (Lyrica®) are effective in the management of chronic neuropathic pain conditions. These agents are gamma-aminobutyric acid (GABA) analogues; GABA is an inhibitory neurotransmitter that is widely distributed throughout the central nervous system. (See 'Surgical pain mechanism' above.)
Gabapentin and pregabalin exert analgesic and opioid sparing effects, and as a result, decrease opioid-related side-effects [116-121]. A disadvantage to these agents is a dose-dependent sedation [118,121]. Several systematic reviews support an adjunctive role for these agents in the management of postoperative pain [118,120-122].
PERSISTENT POSTOPERATIVE PAIN — Normally, incisional pain gradually resolves over a period of days to weeks. Increasing pain or pain that persists for months warrants consideration of other etiologies, including local scar formation, infection, dehiscence/hernia, foreign body reaction, conditions unrelated to the surgery (endometriosis, pelvic mass, malignancy, spinal radiculopathy), and incisional neuroma. Investigation of these patients should include a thorough history and physical examination with attention to the surgical site. Appropriate laboratory and imaging studies are ordered based on clinical findings. (See "Abdominal surgical incisions: Prevention and treatment of complications".)
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 and gabapentin 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 as codeine, acetaminophen/codeine combinations, 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 as morphine or hydromorphone for postoperative analgesia (Grade 2C). Addition of nonsteroidal anti-inflammatory drugs, if not contraindicated, may lower the narcotic requirement and improve 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 (spinal or epidural anesthesia) in addition to general anesthesia (Grade 2C). In addition to preemptive analgesia, the neuraxial approach provides postoperative analgesia. We use intrathecal or epidural morphine (Duramorph 0.2 mg for spinal, 3 mg for epidural route) 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 neuraxial morphine, 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 on methadone, 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.)
- 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.)
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