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Multimodal Pain Management Strategies for Office-Based and Ambulatory Procedures

Multimodal Pain Management Strategies for Office-Based and Ambulatory Procedures Office-based surgical procedures account for up to 25% of all elective surgical procedures performed in the United States.1 Ambulatory surgical procedures now make up 70% of the total volume of hospital-based elective surgical procedures.2 More major surgical procedures are being performed on an ambulatory or 23-hour hospital stay basis including intra-abdominal, intrathoracic, and major orthopedic procedures. Postoperative pain, nausea, and vomiting are the most common factors leading to delays in outpatient discharge and admissions to the hospital following ambulatory surgery.3,4 An understanding of the pharmacologic concepts and pain management techniques for those office-based procedures performed within the scope of a primary care practice, and for patients undergoing hospital-based ambulatory (outpatient) surgical procedures, is a crucial component in the continuing education of the primary care physician. Opioid analgesics are the historical choice of primary analgesic medications for postoperative pain. It has been well documented that opioid analgesics are commonly associated with nausea, vomiting, sedation, dysphoria, pruritus, constipation, urinary hesitancy, and respiratory depression.5 Multimodal analgesia, or balanced analgesia, refers to the use of more than one medication or class of medication, or the use of more than one analgesic technique to produce analgesia through multiple mechanisms.6 Multimodal analgesic strategies for postoperative pain management, including the use of combinations of local anesthetic neural blockade techniques and nonopioid analgesic medications supplemented with opioid analgesics, have been shown to improve postoperative analgesia and reduce postoperative opioid requirements and opioid-related adverse effects.7-9 Multimodal postoperative pain management is applicable and equally important to both the pediatric and adult patient populations. Patient Education and Preoperative Considerations A multimodal strategy for postoperative analgesia should begin prior to the surgical procedure because patient preparation and education may improve postoperative outcome.10 Patients should be educated on the importance and rationale for using the multimodal approach, including local anesthetic neural blockade and adjuvant analgesics, in addition to opioid analgesics. Patients may also benefit from an explanation of how much and what type of pain can be expected following their procedure. Patients should receive instruction on the importance of coughing, deep breathing, ambulation, and postoperative rehabilitation. Patient information on acute postoperative pain management is available from a number of public sources.10,11 Preemptive analgesia refers to the concept that an analgesic medication or intervention administered prior to surgical tissue injury may produce a greater effect than the same medication or intervention administered following surgical tissue injury.12 This preemptive analgesic effect has been demonstrated for several different medications in animal models, but collecting definitive clinical data in postoperative patients has been more challenging.13,14 The theoretical basis for preemptive analgesia relates the phenomenon of wind-up or hyperalgesia (increased pain response to subsequent stimulation) in response to acute tissue injury.12 Prevention or reduction of this wind-up or hyperalgesic response by administration of analgesics prior to the tissue injury may reduce the overall pain response. Anti-inflammatory analgesic medications, local anesthetic wound infiltration or nerve block, or small doses of opioid analgesics are frequently administered prior to surgical incision to take advantage of this preemptive effect.15,16 Nonopioid Analgesics The nonopioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely used for treatment of pain after minor surgical procedures. However, it is an important consideration to use these medications as adjuvant analgesics for major surgical procedures due to their ability to produce analgesia through a nonopioid mechanism, reducing opioid analgesic requirements and opioid-related adverse effects. Clinical trials have demonstrated an improvement in analgesic efficacy and a 30% to 40% reduction in opioid analgesic requirements with the perioperative coadministration of acetaminophen or NSAIDs.17-19 Concerns about the effect of NSAIDS on platelet function leading to potential perioperative bleeding complications and the association between NSAID use and gastroduodenal erosions and ulcerations have limited the routine perioperative use of these agents. The mechanism of activity of the NSAIDs involves the inhibition of the cyclooxygenase-mediated pathways in the production of prostaglandin mediators of pain and inflammation.20 This mechanism has been demonstrated to be active at the peripheral site of tissue injury as well as centrally in the spinal cord.21 The discovery of a second isoform of the cyclooxygenase (COX) enzyme, known as COX-2, produced in most tissues only in response to tissue injury, pain, or inflammation has led to the development of the COX-2 selective inhibitors.20 These drugs have been demonstrated in multiple clinical trials to produce analgesic efficacy equal to that of the traditional nonselective NSAIDs without the COX-1 mediated adverse effects of inhibition of platelet aggregation or gastroduodenal ulceration, although there is some controversy about the latter.22-24 Potential adverse effects of the nonopioid analgesics include hepatic toxicity when high doses of acetaminophen are ingested and exacerbation of hypertension, edema, heart failure, or renal insufficiency with use of the COX-2 selective inhibitors in patients with these preexisting medical conditions or risk factors. The routine use of acetaminophen, a traditional NSAID, or one of the COX-2 selective inhibitors, celecoxib or rofecoxib, should be considered in patients without contraindications to their use, as primary or adjuvant analgesics in the management of postoperative pain. Local Anesthetic Techniques The local anesthetic agents are the most powerful class of analgesic drugs in the management of localized postoperative pain. Local anesthetics block the transmission of neural impulses through a mechanism involving membrane sodium channel blockade. Sufficient local neural membrane sodium channel blockade inhibits propagation of the neural impulse in sensory, motor, and autonomic nerve fibers. Limitations of these drugs include a limited duration of action, limitations on the distribution of analgesic effect, and the relatively narrow therapeutic index of the drugs. Lidocaine (0.5%-1.0%) or bupivacaine (0.25%) are the local anesthetic agents most commonly used for local anesthetic infiltration. The addition of epinephrine in a 1:200 000 concentration will prolong the duration of anesthetic effect.25 Lidocaine has a relatively short duration of action. Bupivacaine, which has a longer duration of effect, is nevertheless associated with profound cardiovascular (arrhythmias, cardiac arrest) and central nervous system effects (seizures, central nervous system depression) in cases of unintentional intravascular injection or overdose.25 Two new single-isomer local anesthetic agents, ropivacaine and levobupivacaine, provide moderate to long duration of action, equal to that of bupivacaine, and a much greater safety profile with respect to cardiovascular and central nervous system toxicity.26,27 These 2 local anesthetics are safer alternatives to bupivacaine for extending the duration of local anesthetic effect into the postoperative period. For small to moderate and relatively superficial surgical procedures, infiltration of the surgical wound with a long-acting local anesthetic (bupivacaine, 0.25%; ropivacaine, 0.25%-0.5%; or levobupivacaine, 0.25%) produces up to 4 hours of pain relief.25,26 This approach in combination with a nonopioid analgesic, such as acetaminophen, celecoxib, or rofecoxib, may produce adequate analgesia for minor surgical procedures and may be considered as the basal analgesic technique for all surgical procedures. For a longer duration of analgesic effect, placement of small catheters into the surgical wound or near the local innervation and continuous infusions of dilute concentrations of local anesthetic with disposable elastomeric (balloon-type) infusion devices have been described.28-30 Opioid Analgesics For patients undergoing surgical procedures who are expected to require analgesic medication beyond the effect of the nonopioid adjuvant medications, the use of intermittent doses of opioid analgesics, such as oxycodone, morphine, or hydromorphone, should be considered. Systemically administered opioid analgesics have a site of action primarily involving opioid receptor binding in the brain, whereas spinally administered opioid analgesics have activity at opioid receptors in the spinal cord dorsal horn. The single drug preparations of oxycodone (not the acetaminophen combination products), morphine, or hydromorphone may be added on an as-needed basis for moderate to severe levels of pain intensity. The morphine, hydromorphone, or plain oxycodone offer advantages over the acetaminophen–opioid analgesic combination products in that dose adjustment to analgesic effect may be made without exceeding the 4000 mg/d acetaminophen dose limit. Acetaminophen, an NSAID, or a COX-2 selective inhibitor is then dosed separately. Opioid analgesics, especially in higher doses, are likely to produce constipation. Consideration should be given to the coadministration of laxatives or stool softeners in patients receiving opioid analgesics. While currently surrounded in controversy because of illegal diversion and misuse, the sustained-release opioid analgesics, such as controlled-release oxycodone or controlled-release morphine sulfate, offer a significant prolongation of the duration of effect and a reduction in the dosing frequency for opioid analgesics in patients with higher postoperative opioid analgesic requirements. A tapering dose of these sustained-release opioid analgesics administered in combination with a nonopioid analgesic and small intermittent doses of a shorter-acting opioid analgesic has been shown to improve postoperative sleep patterns and overall analgesic efficacy as compared with only shorter-acting opioid analgesic preparations.31 Ladder of Therapy for Multimodal Postoperative Analgesia Similar to the ladder of therapy for cancer pain developed by the World Health Organization,32 the multimodal strategy for the management of postoperative pain may be presented in a stepwise structure (Figure 1). Minor superficial surgical procedures such as excisional biopsy are expected to incur less postoperative pain, while larger or more extensive procedures, including orthopedic procedures, upper abdominal, or thoracic surgical procedures, generally result in more postoperative pain. Similar to the World Health Organization ladder of therapy, treatment for each patient begins at Step 1, with medications or interventions added in subsequent steps in response to increased pain intensity. Step 1 in this structural representation includes a nonopioid analgesic (acetaminophen, NSAIDs, or COX-2 selective inhibitors) administered in a continuous, around-the-clock dosing regimen, and local anesthetic infiltration of the surgical wound for minor surgical procedures. Step 2 includes the addition of an opioid analgesic on an as-needed basis for surgical procedures with a moderate intensity of postoperative pain. Step 3 includes the addition of major peripheral neural blockade, plexus blockade, and sustained-release opioid analgesics as indicated for those patients undergoing more involved surgical procedures, patients undergoing more painful procedures, or those patients who might otherwise be expected to have a high postoperative opioid dose requirement. Alternative Nonpharmacologic Therapies A variety of nonpharmacologic therapies have been described that have been shown to either reduce postoperative pain, reduce postoperative analgesic requirements, reduce perioperative anxiety, or improve the patient's overall sense of well-being. These nonpharmacologic therapies include the application of heat or cold, massage, exercise, and transcutaneous electrical nerve stimulation.10 Some patients have also demonstrated various postoperative benefits from relaxation, imagery, hypnosis, and biofeedback techniques.10 A recent study reported a 50% reduction in postoperative morphine requirement, a 20% to 30% reduction in postoperative nausea, and a 30% to 50% reduction in plasma cortisol and epinephrine with the use of preoperative intradermal acupuncture.33 Another recent study reported the beneficial response to intraoperative music and therapeutic suggestions during general anesthesia. Patients exposed to relaxing music and soothing and encouraging therapeutic suggestion had a lower postoperative opioid dose requirement, better pain relief, and less postoperative fatigue at hospital discharge compared with patients in the control group.34 Nonpharmacologic therapies should be considered for any patient with interest or acceptance of these techniques as a component of a multimodal pain management strategy. Consultation of a Pain Management Specialist Patients with selected preprocedural indications may benefit from consultation with or evaluation and management by an anesthesiology pain management specialist. These patients may include those with a history of severe or unexpected adverse reactions to pain medications or a history of difficulty with postoperative or postprocedural pain control, those patients scheduled to undergo more extensive or painful procedures, or those patients with a preprocedural history of chronic or recent opioid use. These patients may require special analgesic dosing considerations. Patients with a history of preprocedural opioid use can be anticipated to have higher postprocedural analgesic requirements compared with patients who are opioid naive. A consultation with an anesthesiology pain management specialist may be helpful in determining appropriate specialized pain management techniques or analgesic dosing recommendations for patients with these and other preprocedural considerations, or for patients who may present unusual postprocedural pain management problems. Future Considerations There are several areas of pharmacological research that may add additional opioid and nonopioid analgesic alternatives for patients undergoing office-based and ambulatory surgical procedures. Clinical development of novel analgesic drugs, which act through nonopioid analgesic mechanisms including N-methyl-D-aspartate receptor antagonists, α2-receptor agonists, and adenosine A1-receptor agonists, may provide additional nonopioid analgesic alternatives.35 Propacetamol,36 a prodrug of acetaminophen (paracetamol), and parecoxib,37 a prodrug of a new COX-2 selective inhibitor valdecoxib, are both in clinical development for perioperative intravenous administration. Electrophoretic transdermal drug delivery systems could allow outpatient postoperative patient-controlled opioid analgesia without the requirement for intravenous access or infusion pumps.38 Continued development in local anesthetic pharmacology with liposomal encapsulation techniques may allow selective neural blockade for a period of a few days with a single injection.39 Conclusion The effectiveness of multimodal strategies for postoperative pain management has been demonstrated with a variety of medications and therapeutic interventions. Postoperative pain can delay the patient's discharge to home, impair the patient's ability to participate in early postoperative rehabilitation, and occasionally require hospital admission. The understanding that pain is more easily managed with a preventive strategy than with a reactive treatment approach suggests initiation of appropriate therapy prior to, during, and immediately following the surgical procedure. The rational use of combinations of analgesic medications, such as nonopioid analgesics, local anesthetic infiltration of the surgical wound, and opioid analgesics, in addition to other therapeutic interventions, can improve pain relief, reduce postoperative adverse effects, and improve functional postoperative recovery for patients following office-based and ambulatory surgical procedures. References 1. Laurito CE. The Society for Office-Based Anesthesia, Orlando, Florida, March 7, 1998. J Clin Anesth.1998;10:445-448.Google Scholar 2. White PF. Ambulatory anaesthesia and surgery: past, present and future. In: White PF, ed. Ambulatory Anaesthesia and Surgery. London, England: WB Saunders; 1997. 3. Chung F, Ritchie E, Su J. Postoperative pain in ambulatory surgery. Anesth Analg.1997;85:808-816.Google Scholar 4. Fortier J, Chung F, Su J. Unanticipated admission after ambulatory surgery: a prospective study. Can J Anaesth.1998;45:612-619.Google Scholar 5. Gutstein HB, Akil H. Opioid analgesics. In: Hardman JG, Limbird LE, Gilman AG, eds. The Pharmacological Basis of Therapeutics. New York, NY: McGraw-Hill; 2001:569-620. 6. Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth.1997;78:606-617.Google Scholar 7. Brodner G, Van Aken H, Hertle L. et al. Multimodal perioperative management—combining thoracic epidural analgesia, forced mobilization, and oral nutrition—reduces hormonal and metabolic stress and improves convalescence after major urologic surgery. Anesth Analg.2001;92:1594-1600.Google Scholar 8. Rosaeg OP, Krepski B, Cicutti N. et al. Effect of preemptive multimodal analgesia for arthroscopic knee ligament repair. Reg Anesth Pain Med.2001;26:125-130.Google Scholar 9. Michaloliakou C, Chung F, Sharma S. Preoperative multimodal analgesia facilitates recovery after ambulatory laparoscopic cholecystectomy. Anesth Analg.1996;82:44-51.Google Scholar 10. Acute Pain Management Guideline Panel. Acute Pain Management: Operative or Medical Procedures and Trauma: Clinical Practice Guideline. Rockville, Md: Agency for Health Care Policy and Research, Public Health Service, US Dept of Health and Human Services; 1992. 11. American Academy of Family Physicians. Pain control after surgery: pain medicines. Available at: http://www.familydoctor.org/handouts/259.html. Accessibility verified June 24, 2002. 12. Woolf CJ, Chong MS. Preemptive analgesia—treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg.1993;77:362-379.Google Scholar 13. Katz J. Pre-emptive analgesia: evidence, current status and future directions. Eur J Anaesthesiol Suppl.1995;10:8-13.Google Scholar 14. Dahl JB, Kehlet H. The value of pre-emptive analgesia in the treatment of postoperative pain. Br J Anaesth.1993;70:434-439.Google Scholar 15. Ejlersen E, Andersen HB, Eliasen K, Mogensen T. A comparison between preincisional and postincisional lidocaine infiltration and postoperative pain. Anesth Analg.1992;74:495-498.Google Scholar 16. Dahl JB, Hjortso NC, Stage JG. et al. Effects of combined perioperative epidural bupivacaine and morphine, ibuprofen, and incisional bupivacaine on postoperative pain, pulmonary, and endocrine-metabolic function after minilaparotomy cholecystectomy. Reg Anesth.1994;19:199-205.Google Scholar 17. Dahl JB, Kehlet H. Non-steroidal anti-inflammatory drugs: rationale for use in severe postoperative pain. Br J Anaesth.1991;66:703-712.Google Scholar 18. Etches RC, Warriner CB, Badner N. et al. Continuous intravenous administration of ketorolac reduces pain and morphine consumption after total hip or knee arthroplasty. Anesth Analg.1995;81:1175-1180.Google Scholar 19. Korpela R, Korvenoja P, Meretoja OA. Morphine-sparing effect of acetaminophen in pediatric day-case surgery. Anesthesiology.1999;91:442-447.Google Scholar 20. Hawkey CJ. COX-2 inhibitors. Lancet.1999;353:307-314.Google Scholar 21. Yaksh TL, Dirig DM, Conway CM. et al. The acute antihyperalgesic action of nonsteroidal, anti-inflammatory drugs and release of spinal prostaglandin E2 is mediated by the inhibition of constitutive spinal cyclooxygenase-2 (COX-2) but not COX-1. J Neurosci.2001;21:5847-5853.Google Scholar 22. Matheson AJ, Figgitt DP. Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs.2001;61:833-865.Google Scholar 23. Clemett D, Goa KL. Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. Drugs.2000;59:957-980.Google Scholar 24. Hrachovec JB, Mora M, Wright JM, Perry TL, Bassett KL, Chambers GK, Silverstein F, Simon L, Faich G. Reporting of 6-month vs 12-month data in a clinical trial of celecoxib [letters and reply]. JAMA.2001;286:2398-2400.Google Scholar 25. Covino BG, Wildsmith JAW. Clinical pharmacology of local anesthetic agents. In: Cousins MJ, Bridenbaugh PO, eds. Neural Blockade in Clincal Anesthesia and Pain Management. Philadelphia, Pa: Lippincott-Raven Publishers; 1998:97-128. 26. McClellan KJ, Spencer CM. Levobupivacaine. Drugs.1998;56:355-362.Google Scholar 27. Markham A, Faulds D. Ropivacaine: a review of its pharmacology and therapeutic use in regional anaesthesia. Drugs.1996;52:429-449.Google Scholar 28. Rawal N, Axelsson K, Hylander J. et al. Postoperative patient-controlled local anesthetic administration at home. Anesth Analg.1998;86:86-89.Google Scholar 29. Corda DM, Enneking FK. A unique approach to postoperative analgesia for ambulatory surgery. J Clin Anesth.2000;12:595-599.Google Scholar 30. Grant SA, Nielsen KC, Greengrass RA. et al. Continuous peripheral nerve block for ambulatory surgery. Reg Anesth Pain Med.2001;26:209-214.Google Scholar 31. Reuben SS, Connelly NR, Maciolek H. Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery. Anesth Analg.1999;88:1286-1291.Google Scholar 32. Ventafridda V, Tamburini M, Caraceni A. et al. A validation study of the WHO method for cancer pain relief. Cancer.1987;59:850-856.Google Scholar 33. Kotani N, Hashimoto H, Sato Y. et al. Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses. Anesthesiology.2001;95:349-356.Google Scholar 34. Nilsson U, Rawal N, Unestahl LE. et al. Improved recovery after music and therapeutic suggestions during general anaesthesia. Acta Anaesthesiol Scand.2001;45:812-817.Google Scholar 35. Dahl V, Raeder JC. Non-opioid postoperative analgesia. Acta Anaesthesiol Scand.2000;44:1191-1203.Google Scholar 36. Hernandez-Palazon J, Tortosa JA, Martinez-Lage JF, Perez-Flores D. Intravenous administration of propacetamol reduces morphine consumption after spinal fusion surgery. Anesth Analg.2001;92:1473-1476.Google Scholar 37. Cheer SM, Goa KL. Parecoxib (parecoxib sodium). Drugs.2001;61:1133-1141.Google Scholar 38. Gupta SK, Sathyan G, Phipps B. et al. Reproducible fentanyl doses delivered intermittently at different time intervals from an electrotransport system. J Pharm Sci.1999;88:835-841.Google Scholar 39. Grant GJ, Bansinath M. Liposomal delivery systems for local anesthetics. Reg Anesth Pain Med.2001;26:61-63.Google Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Multimodal Pain Management Strategies for Office-Based and Ambulatory Procedures

Crews, James C.
JAMA , Volume 288 (5) – Aug 7, 2002
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References (45)

Publisher
American Medical Association
Copyright
Copyright © 2002 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.288.5.629
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Abstract

Office-based surgical procedures account for up to 25% of all elective surgical procedures performed in the United States.1 Ambulatory surgical procedures now make up 70% of the total volume of hospital-based elective surgical procedures.2 More major surgical procedures are being performed on an ambulatory or 23-hour hospital stay basis including intra-abdominal, intrathoracic, and major orthopedic procedures. Postoperative pain, nausea, and vomiting are the most common factors leading to delays in outpatient discharge and admissions to the hospital following ambulatory surgery.3,4 An understanding of the pharmacologic concepts and pain management techniques for those office-based procedures performed within the scope of a primary care practice, and for patients undergoing hospital-based ambulatory (outpatient) surgical procedures, is a crucial component in the continuing education of the primary care physician. Opioid analgesics are the historical choice of primary analgesic medications for postoperative pain. It has been well documented that opioid analgesics are commonly associated with nausea, vomiting, sedation, dysphoria, pruritus, constipation, urinary hesitancy, and respiratory depression.5 Multimodal analgesia, or balanced analgesia, refers to the use of more than one medication or class of medication, or the use of more than one analgesic technique to produce analgesia through multiple mechanisms.6 Multimodal analgesic strategies for postoperative pain management, including the use of combinations of local anesthetic neural blockade techniques and nonopioid analgesic medications supplemented with opioid analgesics, have been shown to improve postoperative analgesia and reduce postoperative opioid requirements and opioid-related adverse effects.7-9 Multimodal postoperative pain management is applicable and equally important to both the pediatric and adult patient populations. Patient Education and Preoperative Considerations A multimodal strategy for postoperative analgesia should begin prior to the surgical procedure because patient preparation and education may improve postoperative outcome.10 Patients should be educated on the importance and rationale for using the multimodal approach, including local anesthetic neural blockade and adjuvant analgesics, in addition to opioid analgesics. Patients may also benefit from an explanation of how much and what type of pain can be expected following their procedure. Patients should receive instruction on the importance of coughing, deep breathing, ambulation, and postoperative rehabilitation. Patient information on acute postoperative pain management is available from a number of public sources.10,11 Preemptive analgesia refers to the concept that an analgesic medication or intervention administered prior to surgical tissue injury may produce a greater effect than the same medication or intervention administered following surgical tissue injury.12 This preemptive analgesic effect has been demonstrated for several different medications in animal models, but collecting definitive clinical data in postoperative patients has been more challenging.13,14 The theoretical basis for preemptive analgesia relates the phenomenon of wind-up or hyperalgesia (increased pain response to subsequent stimulation) in response to acute tissue injury.12 Prevention or reduction of this wind-up or hyperalgesic response by administration of analgesics prior to the tissue injury may reduce the overall pain response. Anti-inflammatory analgesic medications, local anesthetic wound infiltration or nerve block, or small doses of opioid analgesics are frequently administered prior to surgical incision to take advantage of this preemptive effect.15,16 Nonopioid Analgesics The nonopioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely used for treatment of pain after minor surgical procedures. However, it is an important consideration to use these medications as adjuvant analgesics for major surgical procedures due to their ability to produce analgesia through a nonopioid mechanism, reducing opioid analgesic requirements and opioid-related adverse effects. Clinical trials have demonstrated an improvement in analgesic efficacy and a 30% to 40% reduction in opioid analgesic requirements with the perioperative coadministration of acetaminophen or NSAIDs.17-19 Concerns about the effect of NSAIDS on platelet function leading to potential perioperative bleeding complications and the association between NSAID use and gastroduodenal erosions and ulcerations have limited the routine perioperative use of these agents. The mechanism of activity of the NSAIDs involves the inhibition of the cyclooxygenase-mediated pathways in the production of prostaglandin mediators of pain and inflammation.20 This mechanism has been demonstrated to be active at the peripheral site of tissue injury as well as centrally in the spinal cord.21 The discovery of a second isoform of the cyclooxygenase (COX) enzyme, known as COX-2, produced in most tissues only in response to tissue injury, pain, or inflammation has led to the development of the COX-2 selective inhibitors.20 These drugs have been demonstrated in multiple clinical trials to produce analgesic efficacy equal to that of the traditional nonselective NSAIDs without the COX-1 mediated adverse effects of inhibition of platelet aggregation or gastroduodenal ulceration, although there is some controversy about the latter.22-24 Potential adverse effects of the nonopioid analgesics include hepatic toxicity when high doses of acetaminophen are ingested and exacerbation of hypertension, edema, heart failure, or renal insufficiency with use of the COX-2 selective inhibitors in patients with these preexisting medical conditions or risk factors. The routine use of acetaminophen, a traditional NSAID, or one of the COX-2 selective inhibitors, celecoxib or rofecoxib, should be considered in patients without contraindications to their use, as primary or adjuvant analgesics in the management of postoperative pain. Local Anesthetic Techniques The local anesthetic agents are the most powerful class of analgesic drugs in the management of localized postoperative pain. Local anesthetics block the transmission of neural impulses through a mechanism involving membrane sodium channel blockade. Sufficient local neural membrane sodium channel blockade inhibits propagation of the neural impulse in sensory, motor, and autonomic nerve fibers. Limitations of these drugs include a limited duration of action, limitations on the distribution of analgesic effect, and the relatively narrow therapeutic index of the drugs. Lidocaine (0.5%-1.0%) or bupivacaine (0.25%) are the local anesthetic agents most commonly used for local anesthetic infiltration. The addition of epinephrine in a 1:200 000 concentration will prolong the duration of anesthetic effect.25 Lidocaine has a relatively short duration of action. Bupivacaine, which has a longer duration of effect, is nevertheless associated with profound cardiovascular (arrhythmias, cardiac arrest) and central nervous system effects (seizures, central nervous system depression) in cases of unintentional intravascular injection or overdose.25 Two new single-isomer local anesthetic agents, ropivacaine and levobupivacaine, provide moderate to long duration of action, equal to that of bupivacaine, and a much greater safety profile with respect to cardiovascular and central nervous system toxicity.26,27 These 2 local anesthetics are safer alternatives to bupivacaine for extending the duration of local anesthetic effect into the postoperative period. For small to moderate and relatively superficial surgical procedures, infiltration of the surgical wound with a long-acting local anesthetic (bupivacaine, 0.25%; ropivacaine, 0.25%-0.5%; or levobupivacaine, 0.25%) produces up to 4 hours of pain relief.25,26 This approach in combination with a nonopioid analgesic, such as acetaminophen, celecoxib, or rofecoxib, may produce adequate analgesia for minor surgical procedures and may be considered as the basal analgesic technique for all surgical procedures. For a longer duration of analgesic effect, placement of small catheters into the surgical wound or near the local innervation and continuous infusions of dilute concentrations of local anesthetic with disposable elastomeric (balloon-type) infusion devices have been described.28-30 Opioid Analgesics For patients undergoing surgical procedures who are expected to require analgesic medication beyond the effect of the nonopioid adjuvant medications, the use of intermittent doses of opioid analgesics, such as oxycodone, morphine, or hydromorphone, should be considered. Systemically administered opioid analgesics have a site of action primarily involving opioid receptor binding in the brain, whereas spinally administered opioid analgesics have activity at opioid receptors in the spinal cord dorsal horn. The single drug preparations of oxycodone (not the acetaminophen combination products), morphine, or hydromorphone may be added on an as-needed basis for moderate to severe levels of pain intensity. The morphine, hydromorphone, or plain oxycodone offer advantages over the acetaminophen–opioid analgesic combination products in that dose adjustment to analgesic effect may be made without exceeding the 4000 mg/d acetaminophen dose limit. Acetaminophen, an NSAID, or a COX-2 selective inhibitor is then dosed separately. Opioid analgesics, especially in higher doses, are likely to produce constipation. Consideration should be given to the coadministration of laxatives or stool softeners in patients receiving opioid analgesics. While currently surrounded in controversy because of illegal diversion and misuse, the sustained-release opioid analgesics, such as controlled-release oxycodone or controlled-release morphine sulfate, offer a significant prolongation of the duration of effect and a reduction in the dosing frequency for opioid analgesics in patients with higher postoperative opioid analgesic requirements. A tapering dose of these sustained-release opioid analgesics administered in combination with a nonopioid analgesic and small intermittent doses of a shorter-acting opioid analgesic has been shown to improve postoperative sleep patterns and overall analgesic efficacy as compared with only shorter-acting opioid analgesic preparations.31 Ladder of Therapy for Multimodal Postoperative Analgesia Similar to the ladder of therapy for cancer pain developed by the World Health Organization,32 the multimodal strategy for the management of postoperative pain may be presented in a stepwise structure (Figure 1). Minor superficial surgical procedures such as excisional biopsy are expected to incur less postoperative pain, while larger or more extensive procedures, including orthopedic procedures, upper abdominal, or thoracic surgical procedures, generally result in more postoperative pain. Similar to the World Health Organization ladder of therapy, treatment for each patient begins at Step 1, with medications or interventions added in subsequent steps in response to increased pain intensity. Step 1 in this structural representation includes a nonopioid analgesic (acetaminophen, NSAIDs, or COX-2 selective inhibitors) administered in a continuous, around-the-clock dosing regimen, and local anesthetic infiltration of the surgical wound for minor surgical procedures. Step 2 includes the addition of an opioid analgesic on an as-needed basis for surgical procedures with a moderate intensity of postoperative pain. Step 3 includes the addition of major peripheral neural blockade, plexus blockade, and sustained-release opioid analgesics as indicated for those patients undergoing more involved surgical procedures, patients undergoing more painful procedures, or those patients who might otherwise be expected to have a high postoperative opioid dose requirement. Alternative Nonpharmacologic Therapies A variety of nonpharmacologic therapies have been described that have been shown to either reduce postoperative pain, reduce postoperative analgesic requirements, reduce perioperative anxiety, or improve the patient's overall sense of well-being. These nonpharmacologic therapies include the application of heat or cold, massage, exercise, and transcutaneous electrical nerve stimulation.10 Some patients have also demonstrated various postoperative benefits from relaxation, imagery, hypnosis, and biofeedback techniques.10 A recent study reported a 50% reduction in postoperative morphine requirement, a 20% to 30% reduction in postoperative nausea, and a 30% to 50% reduction in plasma cortisol and epinephrine with the use of preoperative intradermal acupuncture.33 Another recent study reported the beneficial response to intraoperative music and therapeutic suggestions during general anesthesia. Patients exposed to relaxing music and soothing and encouraging therapeutic suggestion had a lower postoperative opioid dose requirement, better pain relief, and less postoperative fatigue at hospital discharge compared with patients in the control group.34 Nonpharmacologic therapies should be considered for any patient with interest or acceptance of these techniques as a component of a multimodal pain management strategy. Consultation of a Pain Management Specialist Patients with selected preprocedural indications may benefit from consultation with or evaluation and management by an anesthesiology pain management specialist. These patients may include those with a history of severe or unexpected adverse reactions to pain medications or a history of difficulty with postoperative or postprocedural pain control, those patients scheduled to undergo more extensive or painful procedures, or those patients with a preprocedural history of chronic or recent opioid use. These patients may require special analgesic dosing considerations. Patients with a history of preprocedural opioid use can be anticipated to have higher postprocedural analgesic requirements compared with patients who are opioid naive. A consultation with an anesthesiology pain management specialist may be helpful in determining appropriate specialized pain management techniques or analgesic dosing recommendations for patients with these and other preprocedural considerations, or for patients who may present unusual postprocedural pain management problems. Future Considerations There are several areas of pharmacological research that may add additional opioid and nonopioid analgesic alternatives for patients undergoing office-based and ambulatory surgical procedures. Clinical development of novel analgesic drugs, which act through nonopioid analgesic mechanisms including N-methyl-D-aspartate receptor antagonists, α2-receptor agonists, and adenosine A1-receptor agonists, may provide additional nonopioid analgesic alternatives.35 Propacetamol,36 a prodrug of acetaminophen (paracetamol), and parecoxib,37 a prodrug of a new COX-2 selective inhibitor valdecoxib, are both in clinical development for perioperative intravenous administration. 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Journal

JAMA – American Medical Association

Published: Aug 7, 2002

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