Adequacy of postoperative pain control is one of the most important factors in determining when a patient can be safely discharged from a surgical facility and has a major influence on the patient’s ability to resume the normal activities of daily living.

        Adequacy of postoperative pain control is one of the most important factors in determining when a patient can be safely discharged from a surgical facility and has a major influence on the patient’s ability to resume the normal activities of daily living.³ Perioperative analgesia has traditionally been provided by opioid analgesics. However, extensive use of opioids is associated with a variety of perioperative side effects [eg, ventilatory depression, drowsiness and sedation, postoperative nausea and vomiting (PONV), pruritus, urinary retention, ileus, constipation] that can delay hospital discharge.⁴ Intraoperative use of large bolus doses or continuous infusions of potent opioid analgesics may actually increase postoperative pain as a result of their rapid elimination or the development of acute tolerance.⁵ In addition, it has been suggested by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) that excessive use of postoperative opioid analgesics leads to decreased patient satisfaction. Partial opioid agonists (eg, tramadol) are also associated with increased side effects (eg, nausea, vomiting, ileus) and patient dissatisfaction compared with those reported for both opioid⁶ and nonopioid^7,8 analgesics.

Clinical Pearl

        Therefore, in order to minimize the adverse effects of analgesic medications, anesthesiologists and surgeons are increasingly turning to nonopioid analgesic techniques as adjuvants for managing pain during the perioperative period. Multimodal, or “balanced,” analgesic techniques involving the use of smaller doses of opioids in combination with nonopioid analgesic drugs [eg, local anesthetics, ketamine, acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs) ] are becoming increasingly popular approaches to preventing pain after surgery (Table 77–1).^9–11 This review will discuss recent evidence supporting the use of nonopioid analgesic drugs and techniques for facilitating the recovery process during the perioperative period.

        LOCAL ANESTHETIC TECHNIQUES

The routine use of peripheral nerve blocks and wound infiltration with long-acting local anesthetics as an adjuvant to local, regional, and general anesthetic techniques can improve postoperative pain management after a wide variety of surgical procedures (Table 77–2).⁴ When administered before surgery, these simple techniques can also decrease anesthetic and analgesic requirements during surgery, as well as reduce the need for opioid-containing analgesics postoperatively. More effective pain relief in the early postoperative period, as a result of the residual sensory block produced by local anesthetics, facilitates recovery by enabling earlier ambulation and discharge home (ie, “fast-track” recovery).^12–14

^a Routes of administration: PO = oral, PR = per rectum, SQ = subcutaneous/tissue, IM = intramuscular, IV = intravenous.

In addition, use of local anesthetic-based techniques for preventing pain can decrease the incidence of PONV because of their opioid-sparing effects. However, these techniques are most effective for superficial procedures, and the duration of analgesia is only 6–8 h.

Clinical Pearl

        Blockade of the ilioinguinal and iliohypogastric nerves significantly decreases opioid analgesic requirements in both children and adults undergoing inguinal herniorrhaphy by providing 6–8 h of postoperative pain relief.^15–16 Similarly, a subcutaneous ring block of the penis provides effective perioperative analgesia for circumcision.¹⁷ Local anesthetic infiltration of the mesosalpinx significantly decreases pain and cramping after laparoscopic tubal ligation.¹⁸ Simple instillation of local anesthetic after removal of the gallbladder also reduced right upper quadrant and shoulder pain.^10,19 Pain after arthroscopic shoulder surgery was decreased significantly by a suprascapular nerve block,²⁰ and pain after knee surgery was minimized with a femoral nerve block.²¹ However, more complete perioperative analgesia for painful shoulder and knee procedures requires use of interscalene brachial plexus,²² and combined femoral, obturator, lateral femoral cutaneous, and sciatic nerve²³ blocks, respectively. Although additional preparation time maybe required when major peripheral nerve blocks are performed before surgery, these techniques can offer significant advantages over general and spinal anesthesia with respect to pain control in the postoperative period.^12,13,22,23

        It has been suggested that performing neural blockade with local anesthetics before surgical incision prevents the nociceptive input from altering excitability of the central nervous system by preemptively blocking the N-methyl- D-asparate- (NMDA) induced “wind up” phenomena and subsequent release of inflammatory mediators.²⁴ The concept of preemptive analgesia, or treating postoperative pain by preventing establishment of central sensitization, seems intuitively logical. However, the clinical relevance of preemptive analgesia has been questioned. Only a small number of well-controlled clinical studies have demonstrated any benefit of pre- vs postincisional analgesic administration.^25,26 A quantitative systematic review by Møiniche and colleagues²⁷ stated that evidence is still lacking to support the claim that the timing of single-dose or continuous postoperative pain treatment is critically important in the management of postsurgical pain. These investigators concluded that there was no convincing evidence that preemptive treatment with centrally or peripherally administered local anesthetics, NSAIDs, opioid analgesics, or ketamine offers any advantage with respect to postoperative pain relief when compared with a similar analgesic regimen administered after the surgical incision.²⁷ Nevertheless, preincisional local anesthetic administration offers an obvious advantage over infiltration at the end of surgery because it can provide supplemental intraoperative analgesia as well as effective analgesia in the early postoperative period after emergence from anesthesia.

Clinical Pearls

        Preincisional infiltration of the surgical wound site with local anesthetics, combined with general anesthesia, is clearly superior to general or spinal anesthesia alone in reducing postoperative pain.^28,29 For example, preincisional infiltration of the tonsillar bed with bupivacaine decreased the intensity of both constant pain and pain on swallowing fluids for up to 5 days after tonsillectomy procedures.²⁹ Paracervical block with 0.5% bupivacaine also reduced pain and the need for opioid analgesics after vaginal hysterectomy under general anesthesia.³⁰ Preincisional ilioinguinal-iliohypogastric nerve block not only improves perioperative pain control for inguinal hernia repair, but reduces the need for oral opioid- containing analgesics in the postdischarge period.¹⁶ Although local infiltration can reduce incisional pain after laparoscopic cholecystectomy,^31–34 some investigators have actually reported that infiltration of the trocar sites at the end of surgery provided better pain relief than when the local anesthetic was given before incision.³² The overall analgesic efficacy of trocar wound infiltration after laparoscopic surgery remains controversial.³⁵

        Although preincisional infiltration of the operative site with local anesthetics remains popular for reducing the perioperative opioid analgesic requirement, other simpler local anesthetic delivery systems (eg, topical applications) have been described.^36–40 Topical analgesia with a lidocaine aerosol was effective in decreasing both pain and the opioid analgesic requirement after inguinal herniorrhaphy in adults,³⁶ and instillation of 0.25% bupivacaine before surgical closure compared favorably with an ilioinguinal-iliohypogastric nerve block in children undergoing hernia repair.³⁷ Furthermore, the simple application of topical lidocaine jelly or ointment, as well as eutectic mixture of local anesthesia (EMLA) cream, have been shown to be as effective as peripheral nerve blocks or parenteral opioids in providing pain relief after outpatient circumcision.^38–40 Use of a 5% lidocaine patch has also been reported to be effective in providing peripheral analgesia.⁴¹ However, further studies are needed to define the role (if any) of this analgesic device in the postoperative period.

        Intracavitary instillation of local anesthetics is another simple, yet effective, technique for providing pain relief during the early postoperative period after laparoscopic and arthroscopic procedures. For example, when 80 mL of lidocaine 0.5% or bupivacaine 0.125% was administered intraperitoneally at the start of the laparoscopic procedure, it significantly reduced postoperative scapular pain and the need for opioid analgesic during the first 48 h after surgery.⁴² Compared with a control group receiving saline, use of intraperitoneal bupivacaine 0.5% ( 15–30 mL) also led to a larger percentage of patients going home on the day of surgery (79% vs 43%).⁴³ However, other studies involving intraperitoneal administration of local anesthetics during laparoscopy report inconsistent effects on postoperative pain and the need for opioid analgesics.^44–54 Some investigators have suggested that the beneficial effects of intraperitoneal bupivacaine are transient and have little effect on patient recovery.⁴⁹ Furthermore, when bupivacaine was injected at the preperitoneal fascial plane during extraperitoneal laparoscopic hernia repair, it also failed to reduce postoperative pain.⁵⁵ Subfacial infiltration with bupivacaine 0.5% at the trochar and incision sites reduced pain and the length of stay after laparoscopic nephrectomy procedures.⁵⁶ Yndgaard and coworkers⁵⁷ demonstrated that subfascially administered lidocaine was significantly more effective than subcutaneous injection in reducing pain after inguinal herniotomy. It is obvious that the location, volume, and timing of the local anesthetic administration are key factors in determining efficacy of intraperitoneal instillation in preventing pain after both superficial and laparoscopic surgery.^19,43,53

        Analogous to intraperitoneal administration, intrapleural instillation of local anesthetic solutions has been reported to improve pain control after laparoscopic surgery.^58–66 Some investigators report that interpleural bupivacaine produced more effective analgesia than intraperitoneal bupivacaine⁶⁶ and compared favorably with epidural bupivacaine⁵⁸ after laparoscopic cholecystectomy. Compared with standard opioid analgesics, intrapleural bupivacaine achieved better pain relief and greater improvement in postoperative pulmonary function.^59,64 In contrast, Oxorn and Whatley⁶⁵ reported that postoperative pulmonary mechanics were worsened after intrapleural bupivacaine. Adverse effects on pulmonary function (due to muscle weakness) and the risk of systemic local anesthetic toxicity (due to rapid systemic absorption) are the major concerns with this technique.^66,67 Although intercostal nerve blocks can also improve pain relief after cholecystectomy procedures, this does not necessarily lead to improved pulmonary function.⁶⁸

        Local anesthetics are also commonly injected into joint spaces to provide analgesia during and after arthroscopic procedures.^69,70 In a placebo-controlled study, intraarticular instillation of 30 mL of 0.5% bupivacaine reduced opioid requirements and facilitated early mobilization and discharge after knee arthroscopy.⁷⁰ In a follow-up study, a combination of intraarticular bupivacaine and systemic ketorolac (60 mg) further decreased pain in the early postoperative recovery period.⁷¹ In addition to the local anesthetics, a wide variety of other adjuvants (eg, morphine, ketorolac, triamcinolone, and clonidine) have also been injected into the intraarticular space to decrease postarthroscopic pain.^72–77 Small-dose intraarticular morphine (0.5–1 mg), combined with bupivacaine, appears to provide the longest lasting and most cost- effective analgesia after knee arthroscopy.^76,77 Although administering intraarticular morphine before knee surgery was reported to provide a longer duration of analgesia and greater opioid-sparing effects than when it was given at the end of surgery,⁷⁷ the clinical advantage of preemptive intraarticular local anesthetic administration remains controversial.²⁷

Clinical Pearls

        Although local anesthetic supplementation decreases the severity of incisional pain in the early postoperative period, many patients still experience significant pain when the local anesthetic effect wears off. Therefore, continuous^78,79 or intermittent perfusion^80,81 of the surgical wound (or peripheral nerve) with local anesthetic solutions has been reintroduced as a way of extending local anesthetic-induced incisional pain relief into the postoperative period. In a recent study by White and associates⁸² infusion of 0.5% bupivacaine (4 mL/h) at the median sternotomy site reduced postoperative pain and opioid analgesic requirement after cardiac surgery. As a result of the opioid-sparing effect, these patients recovered bowel and bladder function more rapidly. Similarly, wound instillation with 0.2% ropivacaine (5 mL/h) improved pain control after spine fusion surgery.⁸³ These continuous local anesthetic infusion techniques can be modified to allow for patient-controlled local anesthetic administration after surgery.^84,85

        Investigators have failed to find consistent improvement in pain scores or opioid-sparing effects when the local anesthetic was infused at the incision site after abdominal surgery.^57–86–88 Efficacy of local anesthetic infusion systems is enhanced when the catheter is placed at the sub facial level or near a peripheral nerve. For example, a continuous poplitealsciatic nerve block provides improved postoperative analgesia, decreased opioid use, and enhanced patient satisfaction after painful foot and ankle surgery.^89,90 Similarly, a continuous infraclavicular brachial plexus block provides highly effective pain control after discharge in patients undergoing shoulder surgery.⁹¹ Although continuous local anesthetic infusions with concomitant IVPCA capability appears to be superior to a continuous infusion alone for prolonging nerve blocks,^92,93 many patients elect not to use the IVPCA function on their electronic pumps.⁹¹

        When using a continuous local anesthetic infusion, analgesic efficacy is influenced by a wide variety of factors in addition to location to the catheter system, including the concentration and volume of the local anesthetic solution,⁸² as well as the accuracy and consistency of the pumps.⁹⁴ The use of a disposable, nonelectronic infusion system may offer advantages over the electronic pump because its simplicity minimizes the need for trouble shooting.⁹⁵ However, accuracy of the infusion rate of the nonelectronic pumps can change over time.⁹⁴ Temperature changes also influence the infusion rate of elastomeric pumps, and battery life is a limiting factor for the electronic pumps.⁹⁴ With these catheter delivery systems, the risk of infection appears to be small. However, bacterial colonization of the catheter is a common occurrence.⁹⁶ Patient satisfaction and comfort when using these delivery systems outside the hospital is high, and over 90% of the patients are comfortable removing the catheter at home.⁹⁷ Finally, combining local anesthetic infusion techniques with other analgesic modalities as part of multimodal analgesic therapy further improves pain control throughout the perioperative period.⁹⁸

        Peripheral nerve block techniques are simple, safe, and highly effective approaches to providing perioperative analgesia. Use of long-acting local anesthetics for neural blockade techniques involving the upper (eg, interscalene brachial plexus block) and lower (eg, femoral-sciatic nerve block) extremities can facilitate an earlier discharge after major shoulder and knee reconstructive procedures, respectively.^99,100 Availability of long-acting local anesthetics that claim less toxicity and greater selectivity with respect to sensory and motor blockade (eg, ropivacaine) may further enhance the benefits of local anesthetic supplementation after both major and minor surgery.

        Although ropivacaine 0.2% provides better pain relief with less motor impairment than lidocaine 1% for continuous interscalene brachial plexus block,¹⁰¹ its clinical advantages relative to equipotent concentrations of bupivacaine are less well established. Addition of adjuvants (eg, epinephrine, clonidine) that can prolong postoperative analgesia and facilitate recovery when using central and peripheral nerve blocks may be of greater clinical importance.^102,103 Interestingly, a more recent study¹⁰⁴ found that clonidine’s use as an adjunct to ropivacaine as part of a continuous perineural infusion technique failed to reduce postoperative pain and oral analgesic usage or improve the patient’s quality of sleep after upper extremity surgery when compared with the local anesthetic alone. Although pain control can be improved after orthopedic procedures by continuously infusing local anesthetic solutions,^{89,90 105–107} availability of longer acting local anesthetic suspensions and “delayed release” formulations containing liposomes or polymer microspheres may minimize the need for continuous infusion catheter delivery system in the future.

         NSAIDS

Oral NSAIDs have long been used for treating nonsurgical pain syndromes because of their well known antiinflammatory, antipyretic, and analgesic properties. When parenteral preparations of NSAIDs (eg, ketorolac, ketoprofen, diclofenac) became available, these drugs were more widely used in the management of acute perioperative pain. NSAIDs block the synthesis of prostaglandins by inhibiting cyclooxygenase (COX) types I and II, thereby reducing production of mediators of the acute inflammatory response. By decreasing the inflammatory response to surgical trauma, NSAIDs have been alleged to reduce peripheral nociception. Studies also suggest that the central response to painful stimuli is modulated by NSAID-induced inhibition of prostaglandin synthesis in the spinal cord.²⁷

Clinical Pearl

        Early reports suggested that parenteral NSAIDs possessed analgesic properties comparable to those for traditional opioid analgesics^108–110 without opioid-related side effects.^111,112 Compared with the partial opioid agonist tramadol, diclofenac produced better postoperative pain relief with fewer side effects after cardiac surgery.⁸ When administered as an adjuvant during outpatient anesthesia, ketorolac was associated with improved postoperative analgesia and patient comfort compared with fentanyl and the partial opioid agonist, dezocine.”^112,113 Other investigators reported that ketorolac provided postoperative pain relief similar to that of fentanyl, but was associated with less nausea and somnolence, as well as an earlier return of bowel function.¹¹⁴ In most studies, use of ketorolac has been associated with a less frequent incidence of PONV than the opioid analgesics. As a result, patients tolerate oral fluids and are fit for discharge earlier than those receiving only opioid analgesics during the perioperative period. Of interest, ketorolac (30 mg q6h) was superior to a dilute local anesthetic infusion (bupivacaine 0.125%) in supplementing epidural IVPCA hydromorphone in patients undergoing thoracotomy procedures.¹¹⁵ Furthermore, it has been found that the injection of ketorolac (30 mg) at the incision site in combination with local anesthesia resulted in significantly less postoperative pain, a better quality of recovery, and earlier discharge compared with local anesthesia alone.¹¹⁶ In fact, evidence exists for both a peripheral and central analgesic action of NSAIDs.¹¹⁷ However, when ketorolac was substituted for, or combined with, fentanyl during minor gynecologic and laparoscopic procedures, beneficial effects of the NSAID were reduced.^118,119

        Using shock wave lithotripsy to evaluate the effect of NSAIDs on visceral pain, diclofenac produced only a marginal opioid-sparing effect.¹²⁰ However, when diclofenac (1 mg/kg IV) was administered before arthroscopic surgery, it was associated with similar pain scores to fentanyl ( 1 mcg/kg IV).¹²¹ Preoperative diclofenac (50 mg) also decreased pain and the opioid analgesic requirements for 24 h after laparoscopic surgery.¹²² Similarly, preoperative administration of ketorolac to patients undergoing laparoscopic cholecystectomy¹¹⁹ decreased postoperative opioid requirements and improved some ventilatory variables during the early postoperative period. A perioperative ketorolac infusion (2 mg/h) also improved the quality of postoperative pain relief after abdominal surgery.¹²³ Ketorolac (30 mg IV) produced comparable analgesia to tramadol (100 mg IV), but with a 68% decreased incidence of PONV after maxillofacial surgery.¹²⁴ Of interest, diclofenac ( 1 mg/kg) is alleged to be a more cost-effective alternative to ketorolac (0.5 mg/kg).^125,126

        When diclofenac was administered preoperatively to pediatric patients, the incidence of both restlessness and crying, as well as the postoperative opioid requirements, were less than in patients treated with acetaminophen.¹²⁷ Similarly, oral ketorolac (1 mg/kg) was superior to small-dose acetaminophen (10 mg/kg) for pain in children undergoing bilateral myringotomy procedures.¹²⁸ In children undergoing inguinal hernia repair,¹²⁹ ketorolac (1 mg/kg IV) compared favorably with caudal bupivacaine 0.2% with respect to pain control and postoperative side effects. In addition, ketorolac- treated children had an improved recovery profile, including less vomiting, shorter times to voiding and ambulation, and earlier discharge home. Intraoperative administration of ketorolac as an adjuvant to general anesthesia in pediatric patients provided postoperative analgesia comparable to morphine with less PONV.¹³⁰ When ketorolac or morphine is administered for pain control in pediatric patients, ketorolac-induced analgesia develops more slowly but lasts longer.¹³¹

        Oral or rectal administration of NSAIDs is also effective and less costly in the prophylactic management of surgical pain.¹³² For example, when oral naproxen was administered before laparoscopic surgery, postoperative pain scores, opioid requirements, and time to discharge were significantly reduced.¹³³ Furthermore, premedication with oral ibuprofen (800 mg) was associated with superior postoperative analgesia and less nausea than with fentanyl (75 meg IV) after laparoscopic surgery.¹³⁴ However, the more important role for oral NSAIDs may be in the postdischarge period. Ibuprofen liquigel (400 mg PO) was significantly more effective than celecoxib (200 mg PO) in treating pain after oral surgery.¹³⁵ Ibuprofen (5 mg/kg PO) compared favorably with rofecoxib (0.625 mg/kg PO) for minimizing postoperative pain when used in combination with acetaminophen (20 mg/kg) prior to tonsillectomy procedures.¹³⁶ When used as part of a multimodal analgesic technique consisting of alfentanil, lidocaine, and ketorolac,¹³⁷ oral ibuprofen (800 mg q8h) was equianalgesic to paracetamol 800 mg in combination with codeine 60 mg (q8h) during the first 72 h after discharge and resulted in better global patient satisfaction and less constipation than opioid-containing oral analgesics. Ibuprofen (400 or 600 mg PO) appears to produce comparable analgesia to the combination tramadol (75–112.5 mg) and acetaminophen (650 or 975 mg) for acute postoperative pain relief.¹³⁸ To achieve the optimal benefit of using NSAIDs in the perioperative period, these compounds should be continued during the postdischarge period as part of a preventative pain management strategy.⁹⁸

        Despite the obvious benefits of using NSAIDs in the perioperative period, controversy still exists regarding their use because of the potential for gastrointestinal mucosal damage and renal tubular and platelet dysfunction.¹³⁹ Although some studies have found increased blood loss and risk of reoperation when ketorolac was administered to children undergoing tonsillectomy procedures,^140,141 a recent systematic review of the literature suggested that the evidence supporting an increase of bleeding was equivocal at best.¹⁴²

        COX-2 INHIBITORS

In an effort to minimize the potential for operative site bleeding complications, as well as gastrointestinal damage, associated with the classic nonselective NSAIDs such as ketorolac and diclofenac, the more highly selective COX-2 inhibitors are increasingly being used as nonopioid adjuvants for minimizing pain during the perioperative period (Table 77–3).¹⁴³ Early clinical studies in surgical patients evaluated the use of celecoxib, rofecoxib, and valdecoxib as preventative analgesics when administered for oral premedication.^144–148 Rofecoxib (50 mg PO) produced more effective and sustained analgesia than celecoxib (200 mg PO) after spinal surgery.¹⁴⁴ Celecoxib (200 mg PO) was equivalent to acetaminophen (2 g PO) when administered before otolaryngologic operations.¹⁴⁵ However, the analgesic efficacy of celecoxib is dose-related, and 400 mg is the currently recommended dose for prevention of acute pain.¹⁴⁶ Rofecoxib (50 mg PO) produced significantly more effective analgesia than acetaminophen (2 g PO), and the pain relief was more sustained in the postdischarge period.¹⁴⁷ Premedication with rofecoxib also facilitated recovery by reducing postoperative pain and improving the quality of recovery from the patient’s perspective.¹⁴⁸ It has also been suggested that the long-acting rofecoxib is more cost-effective than celecoxib in the perioperative period.¹⁴⁹ In a recent study,¹⁴³ a single preoperative dose of rofecoxib (25–50 mg PO) produced a 44–59% reduction in the PCA morphine requirement after major abdominal surgery.¹⁵⁰ However, clinical studies suggest a more sustained benefit can be achieved when the drug is administered both before and after surgery.^148,151 The recent withdrawal of rofecoxib from the market by its manufacturer because of an increased risk of cardiovascular side effects following prolonged use (>16 months) has led investigators to begin reevaluating other COX-2 inhibitors in the perioperative period.

Related posts:

Regional Anesthesia in the Patient with Preexisting Neurologic Disease. The History of Local Anesthesia. Stimulating Catheters. Ultrasound-Assisted Nerve Blocks in Adults. Histology of Peripheral Nerves. Supraclavicular Brachial Plexus Block.

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