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The Role of Non-Opioid Analgesic Techniques in theManagement of Pain After Ambulatory Surgery Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas In describing how patients feel after surgery, adelayeddischargefromtheday-surgeryfacilityorto Armitage (1) stated that “slapping the patient on the unanticipated hospital admissions. The intraoperative face and telling him or her that it’s all over is a use of large bolus doses or continuous infusions of complete inversion of the truth” because as far as the potent short-acting opioid analgesics (e.g., alfentanil patient is concerned, “it is often just the beginning.” and remifentanil) may actually increase postoperative Although the current armamentarium of analgesic drugs pain as a result of their rapid elimination and the and techniques is impressive, effective management of development of acute tolerance (4). Therefore, anes- postoperative pain still poses some unique challenges in thesiologists practicing in the ambulatory environ- the ambulatory setting. The increasing number and com- ment are increasingly using non-opioid analgesics as plexity of operations being performed on an outpatient adjuvants during the perioperative period (Table 1).
basis has presented anesthesia practitioners with new To minimize the adverse effects of analgesic medi- challenges with respect to acute pain management. Out- cations, “balanced” analgesic techniques involving the patients undergoing day-care procedures require a peri- use of smaller doses of opioids in combination with operative analgesic technique that is effective, has mini- non-opioid analgesic drugs (e.g., local anesthetics and mal side effects, is intrinsically safe, and can be easily nonsteroidal antiinflammatory drugs [NSAIDs]) are managed away from the hospital or surgery center.
becoming increasingly popular approaches during The adequacy of postoperative pain control is one of and after ambulatory surgery (5,6). The rationale for the most important factors in determining when a pa- the perioperative use of non-opioid analgesic drugs tient can be safely discharged from the outpatient facility and techniques in the ambulatory setting will be re- (2). Because inadequately treated pain is a major cause of prolonged stays or unanticipated hospital admissionsafter ambulatory surgery, the ability to provide effectivepain relief by simple methods that are readily available to an outpatient in his or her home environment will beone of the major challenges for providers of ambulatory Peripheral nerve blocks and wound infiltration with anesthesia in the future (3). Unfortunately, there are very local anesthetics are commonly used adjuvants to both few well controlled studies that have carefully examined monitored anesthesia care (MAC) and general anes- the optimal approaches to managing postdischarge pain thetic techniques because they can provide intra- and postoperative analgesia (Table 2). As a result, these Perioperative analgesia has traditionally been pro- techniques can decrease the anesthetic and analgesic vided by opioid analgesics. However, the use of large requirements during surgery and reduce the need for doses of opioids during ambulatory surgery can be opioid analgesics in the postoperative period. More associated with an increased incidence of postopera- effective pain relief in the early postoperative period tive complications (e.g., ventilatory depression, seda- from the residual sensory block provided by local tion, postoperative nausea and vomiting, pruritus, dif- anesthesia can facilitate the recovery process, enabling ficulty voiding, and ileus), which in turn contribute to earlier ambulation and discharge home (i.e., fast-tracking). The use of local anesthetic techniques alsodecreases the incidence of postoperative nausea and Supported by the White Mountain Institute, Los Altos, CA (Paul vomiting and thereby decreases the incidence of pro- Accepted for publication November 7, 2001.
longed recovery stays and unanticipated hospital ad- Address correspondence to Paul F. White, PhD, MD, Department missions related to intractable emetic symptoms.
of Anesthesiology and Pain Management, UT Southwestern Medi- Although additional clinical studies are needed to cal Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9068. Address identify the most cost-effective anesthetic techniques e-mail to No reprints will beavailable.
for ambulatory surgery, it would seem that peripheral 2002 by the International Anesthesia Research Society0003-2999/02 NON-OPIOID ANALGESICS AND POSTOPERATIVE PAIN Table 1. Commonly Used Non-Opioid Drugs and
Table 2. Commonly Used Techniques for Administering
Nonpharmacologic Techniques for Minimizing Pain After Local Anesthesia During Ambulatory Surgery Ilioinguinal/hypogastric (e.g., herniorrhaphy) Paracervical (e.g., dilation/curettage, cone biopsy) Peroneal/femoral/saphenous/tibial/sural (e.g., Femoral/obturator/lateral femoral cutaneous/sciatic Brachial plexus/axillary/ulnar/median/radial (e.g., arm Peribulbar/retrobulbar (e.g., ophthalmologic Mandibular/maxillary (e.g., oral surgery) IV regional (Bier block) (e.g., arms, legs) Tissue infiltration and wound instillation Cosmetic and wound procedures (e.g., blepharoplasty, Excision of masses and biopsies (e.g., breast, axilla, Field blocks or “splash” technique (e.g., hernia repair, Transcutaneous electrical nerve stimulation Transcutaneous acupoint electrical stimulation Laparoscopic procedures (e.g., cholecystectomy, tubal Acupuncture-like transcutaneous electrical nerve Arthroscopic procedures (e.g., knees, shoulders) PO ϭ oral; PR ϭ per rectum; SC ϭ subcutaneous/tissue.
Eutectic mixture of local anesthetics (e.g., skin lesions)Lidocaine spray (e.g., bronchoscopy, endoscopy, hernia nerve blocks with sedation (i.e., MAC techniques) of- Lidocaine gel or cream (e.g., circumcision or urologic or fer significant advantages over central neuraxis block- ade and general anesthesia in the ambulatory setting Cocaine paste (e.g., nasal or endosinus surgery) (7–9). In outpatients undergoing saphenous vein-stripping surgery, use of a femoral/genitofemoralnerve block significantly improved patient satisfaction It has been suggested that performing neural blockade with the anesthetic experience (7). Blockade of the with local anesthetics before the surgical incision may ilioinguinal and iliohypogastric nerves can signifi- prevent the nociceptive input from altering the excitabil-ity of the central nervous system (e.g., preemptively cantly decrease the anesthetic and analgesic require- blocking the N-methyl-d-aspartate-induced “wind up” ments in both children and adults undergoing ingui- phenomena and release of inflammatory mediators) (18).
nal herniorrhaphy, providing 6 – 8 h of postoperative The concept of preemptive analgesia (or treating post- analgesia (10,11). Similarly, subcutaneous ring block operative pain by preventing the establishment of cen- of the penis provides effective perioperative analgesia tral sensitization) seems very logical (18); however, its for circumcision procedures (12). Local anesthetic in- clinical relevance has been questioned. Only one well filtration of the mesosalpinx significantly decreases controlled study has demonstrated any benefits of pre- the pain and cramping after laparoscopic tubal liga- versus postincisional local anesthetic administration in tion procedures (13). Pain after arthroscopic shoulder the ambulatory setting (19). A recent qualitative and surgery was decreased significantly by a simple su- quantitative review by Møiniche et al. (20) suggested prascapular nerve block (14), and pain after knee sur- that evidence is still lacking that the timing of single- gery was minimized with a femoral nerve block (15).
dose or continuous postoperative pain treatment is im- However, more complete perioperative analgesia for portant in the management of postsurgical pain. These shoulder and knee surgery requires the use of an investigators concluded that there is no convincing evi- interscalene brachial plexus block (16) and combined dence that preemptive treatment with centrally or pe- femoral, obturator, lateral femoral cutaneous, and sci- ripherally administered local anesthetics, NSAIDs, opi- atic nerve (17) blocks, respectively. Although addi- oid analgesics, or ketamine offers any advantage with tional preparation time may be required when these respect to postoperative pain relief compared with a major peripheral nerve blocks are performed before similar postsurgical analgesic regimen. Nevertheless, surgery, these block techniques can offer advantages preincisional administration offers advantages over in- in the postoperative period compared with general or filtration at the end of surgery with respect to intraop- NON-OPIOID ANALGESICS AND POSTOPERATIVE PAIN Preincisional infiltration with local anesthetics in duration of analgesia and greater opioid-sparing ef- combination with general anesthesia is clearly supe- fects than when it was given at the end of surgery (37), rior to general (or spinal) anesthesia alone in relieving the clinical advantages of preemptive analgesia re- postoperative pain (21,22). In fact, preincisional infil- tration of the tonsillar bed with bupivacaine decreased Local anesthetic supplementation clearly decreases both constant pain and pain on swallowing for up to the severity of incisional pain in the early postopera- 5 days after tonsillectomy procedures in children (22).
tive period. However, outpatients may still experience Preincisional ilioinguinal hypogastric nerve block not significant pain after they have been discharged home only improves intraoperative pain control during in- because of difficulty in anticipating the degree of pain guinal hernia repair, but also reduces the need for oral when the local anesthetic effect wears off. Continuous opioid-containing analgesics after discharge (23). Al- (38,39) or intermittent perfusion (40) of the surgical though preincisional infiltration of the operative site wound with local anesthetic solutions is an old- with local anesthetics remains a popular technique for fashioned but highly effective technique for extending reducing the perioperative opioid analgesic require- incisional pain relief into the postdischarge period.
ment, other more simplified local anesthetic delivery Recently, this technique has been modified to allow systems (e.g., topical applications) have also been de- for patient-controlled local anesthetic administration scribed in the anesthesia literature (24,25). Topical an- after discharge home (41). However, some investiga- algesia with lidocaine aerosol was found to be highly tors have failed to find significant differences in pain effective in decreasing pain, as well as the opioid scores or opioid analgesic requirements when the local analgesic requirement, after inguinal herniorrhaphy in anesthetic was instilled or injected at the incision site adults (24), and instillation of 0.25% bupivacaine be- (42,43). The response to local analgesia appears to be fore surgical closure provided comparable postopera- influenced by the location, concentration, and volume tive pain relief to an ilioinguinal/iliohypogastric of the injected local anesthetic solution. For example, nerve block in children undergoing hernia repair (25).
Yndgaard et al. (44) demonstrated that subfascially Furthermore, the simple application of topical lido- administered lidocaine was significantly more effec- caine jelly or ointment is as effective as peripheral tive in reducing pain compared with subcutaneous nerve blocks or parenteral opioids in providing pain injection after inguinal herniotomy. Finally, combin- relief after outpatient circumcision (26).
ing local anesthetic techniques with other analgesic Intracavitary instillation of local anesthetics is an- modalities as part of multimodal (or “balanced”) an- other simple, yet effective, technique for providing algesic therapy can improve pain control throughout pain relief during the early postoperative period after the perioperative period (45). The concept of balanced laparoscopic and arthroscopic procedures. Intraperito- analgesia consists of administering several different neal administration of local anesthetics during lapa- analgesic drugs to alter the pathophysiologic pro- roscopy was found to be an efficient method of reduc- cesses involved in nociception, thereby producing ing the intensity of postoperative scapular pain (27).
more effective perioperative analgesia with fewer side However, when bupivacaine was injected at the pre- peritoneal fascial plane during extraperitoneal laparo- In summary, local anesthetic wound infiltration and scopic hernia repair, it did not reduce postoperative peripheral nerve block techniques are simple, safe, pain (28). Local anesthetics can also be injected into and effective approaches to providing perioperative joint spaces to provide analgesia during and after analgesia in the ambulatory setting. Use of major neu- arthroscopic surgery (29). In a placebo-controlled ral blockade techniques involving the upper (e.g., in- study, intraarticular instillation of 30 mL of 0.5% bu- terscalene brachial plexus block) and lower (e.g., fem- pivacaine reduced the opioid requirements and facil- oral nerve block) extremities can facilitate an earlier itated early mobilization and discharge after knee ar- discharge after major shoulder and knee reconstruc- throscopy (30). A follow-up study (31) involving a tive procedures, respectively (46,47). The availability combination of intraarticular bupivacaine and sys- of newer local anesthetic drugs that are alleged to be temic ketorolac (60 mg IV or IM) further decreased associated with less toxicity and greater selectivity pain in the early postoperative recovery period. A with respect to sensory and motor blockade (e.g., ropi- wide variety of adjuvants has also been injected into vacaine and levobupivacaine) may further enhance the intraarticular space to decrease postarthroscopic the benefits of local anesthetic supplementation after pain, including morphine, ketorolac, triamcinolone, ambulatory surgery. The addition of adjuvants (e.g., and clonidine (32–35). Small-dose intraarticular mor- clonidine) can prolong the postoperative analgesia phine 1–3 mg, in combination with bupivacaine, produced by peripheral nerve blocks (48). Recent seems to provide the longest lasting and most cost- studies by Klein et al. (49,50) suggest that improved effective analgesia after knee arthroscopy (36,37). Al- pain control could also be achieved after major shoul- though administering the intraarticular morphine be- der and knee procedures by using a disposable, non- fore knee surgery was reported to provide a longer electronic catheter system for continuously infusing NON-OPIOID ANALGESICS AND POSTOPERATIVE PAIN local anesthetic solutions. However, additional studies be associated with similar visual analog pain scores to are needed to document the alleged advantages of fentanyl (1 ␮g/kg IV) (62). After gynecologic laparos- these newer local anesthetic drugs and techniques.
copy surgery (63), diclofenac decreased pain and an- Future studies are also needed to determine the opti- algesic requirements for 24 h postoperatively but had mal local anesthetic concentrations and infusion rates little effect on the recovery profile. Similarly, the ad- ministration of ketorolac during the perioperative pe-riod in outpatients undergoing laparoscopic cholecys-tectomy procedures (59) decreased postoperativeopioid requirements, but this contributed to only a marginal improvement in ventilatory function at 4 hr NSAIDs have long been used for treating nonsurgical pain syndromes because of their well known antiin- When diclofenac was administered preoperatively to flammatory, antipyretic, and analgesic properties.
pediatric patients, both the incidence of restlessness and However, with the introduction of parenteral prepa- crying and the postoperative opioid requirements were rations of NSAIDs (e.g., ketorolac and diclofenac), lower in the diclofenac-treated (versus acetaminophen- these drugs have become more popular in the man- treated) patients (64). Oral ketorolac (1 mg/kg) com- agement of pain associated with ambulatory surgery.
pared favorably to small-dose acetaminophen (10 mg/ NSAIDs block the synthesis of prostaglandins by in- kg) for bilateral myringotomy procedures in children, hibiting the enzyme cyclooxygenase (COX), thereby with the ketorolac-treated patients recording lower pain reducing the production of mediators of the acute scores and requiring less analgesic medication in the inflammatory response. By decreasing the inflamma- early postoperative period (65). In children undergoing tory response to surgical trauma, NSAIDs have been inguinal hernia repair (66), ketorolac (1 mg/kg IV) com- alleged to reduce peripheral nociception. However, pared favorably to caudal bupivacaine 0.2% with respect more recent studies also suggest that the central re- to pain control and postoperative side effects. In fact, the sponse to painful stimuli may be modulated by ketorolac-treated patients had an improved recovery NSAID-induced inhibition of prostaglandin synthesis profile, including less vomiting, shorter times to voiding and ambulation, and earlier discharge home. Further- Early reports suggested that NSAIDs possessed an- more, the intraoperative administration of ketorolac as algesic properties comparable to those of opioid anal- an adjuvant to general anesthesia in pediatric patients gesics (51–53) without opioid-related side effects provided postoperative analgesia comparable to mor- (54,55). When ketorolac was administered as an adju- phine (67). As expected, the ketorolac-treated patients vant to propofol/nitrous oxide anesthesia, its use was experienced less postoperative nausea and vomiting.
associated with improved postoperative analgesia and When ketorolac or morphine are administered for pain patient comfort, which compared favorably to fenta- control in pediatric patients, ketorolac-induced analgesia nyl (55). Moreover, ketorolac was associated with a develops more slowly but is longer lasting compared decreased incidence of postoperative nausea and vomiting, and patients tolerated oral fluids and were Oral or rectal administration of NSAIDs can also be judged fit for discharge earlier than those receiving highly effective in the prophylactic management of opioid compounds. Other investigators have also re- pain after ambulatory surgery. For example, when ported that ketorolac provided similar postoperative oral naproxen was administered before laparoscopic pain relief to that of fentanyl but was associated with surgery, postoperative pain scores, opioid require- less nausea and somnolence and an earlier return of ments, and time to discharge were significantly re- bowel function after ambulatory surgery (56). Further- duced (69). Furthermore, premedication with oral ibu- more, it was recently reported that the administration profen (800 mg) was associated with superior of ketorolac (30 mg) at the incision site to supplement postoperative analgesia and less nausea compared local anesthesia resulted in significantly less postop- with fentanyl (75 ␮g IV) (70). However, the more erative pain, a better quality of recovery, and earlier important role for oral NSAIDs is in the postdischarge discharge compared with local anesthesia alone (57).
period. In a recent outpatient study involving the use However, when ketorolac was substituted for or com- of a multimodal analgesic technique consisting of al- bined with fentanyl during outpatient gynecologic fentanil, lidocaine, ketorolac, and paracetamol (71), and laparoscopic surgical procedures, the beneficial oral ibuprofen (800 mg every 8 h) was equianalgesic to effects of the NSAID were more variable (58 – 60).
paracetamol 800 mg plus codeine 60 mg (every 8 h) Use of shock-wave lithotripsy to evaluate the effect when administered during the first 72 h after dis- of NSAIDs on visceral pain, diclofenac produced only charge, and it resulted in better global patient satis- a marginal opioid-sparing effect (61). Furthermore, faction and less constipation than the opioid- when diclofenac (1 mg/kg IV) was administered be- containing oral analgesic. To achieve the optimal fore outpatient arthroscopic surgery, it was found to benefit of using NSAIDs in the perioperative period, NON-OPIOID ANALGESICS AND POSTOPERATIVE PAIN these compounds should be continued as prophylactic Korpela et al. (78) demonstrated that the opioid- analgesics for preventive pain management in the sparing effect of acetaminophen was strictly dose re- lated. The optimal dosing regimen for acetaminophenin children consists of a preoperative initial loadingdose of 40 mg/kg followed by a maintenance dose of 20 mg/kg every 6 – 8 h during the early postoperative In an effort to minimize the potential for operative-site bleeding complications, as well as gastrointestinal and An IV formulation of acetaminophen, known as renal damage, associated with the classical NSAIDs, propacetamol, has been administered to adults as an the more specific COX-2 inhibitors are being increas- alternative to ketorolac in the perioperative period ingly used as non-opioid adjuvants for minimizing (80,81). Propacetamol is a prodrug that is rapidly and pain during the perioperative period (Table 3). Early completely hydrolyzed by nonspecific plasma ester- studies evaluated the use of celecoxib and rofecoxib ases to form acetaminophen (also known as paraceta- for preventative analgesia when administered for oral mol). Although the future role of this non-opioid par- premedication (72–74). Rofecoxib (50 mg orally [PO]) enteral analgesic during the perioperative period is seems to produce more effective and sustained anal- yet to be determined, rectal acetaminophen (1.3 g) has gesia compared with celecoxib (200 mg PO) after sur- been successfully used as an adjuvant to NSAIDs and gery (72). Preliminary data suggest that celecoxib local anesthetics in adult outpatients as part of a mul- (200 mg PO) is equivalent to acetaminophen (2 g PO) timodal fast-tracking protocol (82).
when administered before outpatient otorhinolaryn-gology surgery (73). However, rofecoxib (50 mg PO) produced significantly more effective analgesia thanacetaminophen (2 g PO), and the pain relief was more Ketamine is a unique anesthetic with analgesic-like sustained in the postdischarge period (74). Premedi- properties which has been used for both the induction cation with rofecoxib also facilitated the recovery pro- and maintenance of anesthesia and as an analgesic cess by reducing postoperative pain and improving adjuvant during MAC (83). As a result of its well the quality of recovery from the patient’s perspective.
known side-effect profile (Table 4), ketamine fell into More recently, a parenterally active COX-2 inhibi- disfavor in the anesthesia community in the early tor, parecoxib (20 – 40 mg IV), has been investigated as 1980s. However, the use of so-called small-dose ket- an alternative to ketorolac and diclofenac (75,76). Pare- amine (0.1– 0.2 mg/kg IV) techniques seems to be coxib is a prodrug with an active metabolite (valde- associated with a much less frequent incidence of coxib) and is similar both pharmacokinetically and adverse events and with greater patient and physician pharmacodynamically to celecoxib. Both preoperative acceptance (84). Recent studies have described the use (75) and postoperative (76) administration of this in- of ketamine in combination with propofol for MAC vestigational COX-2 drug seems to exert significant (85,86) and IV anesthesia (87). The administration of opioid-sparing effects, and these preliminary studies ketamine 4 –18 ␮g · kgϪ1 · minϪ1 in combination with suggest that it can improve the quality of recovery and propofol 30 –90 ␮g · kgϪ1 · minϪ1 can obviate the re- patient satisfaction with postoperative pain manage- spiratory depression produced by propofol/opioid ment. However, further comparative clinical studies combinations while producing positive mood effects are needed to define the optimal role of COX-2 inhib- after surgery, and it may even provide for an earlier recovery of cognitive function (85,86). In addition, asingle bolus dose of ketamine 0.1– 0.15 mg/kg duringsurgery has been reported to produce significant opioid-sparing effects after painful ambulatory sur- Of the nonopioid analgesics, acetaminophen is poten- gery procedures (88,89). However, the clinical signifi- tially one of the most useful, yet it is vastly underused cance of ketamine’s preemptive analgesic effects re- in the ambulatory setting. When administered in an appropriate oral or rectal dose, acetaminophen can bea very useful adjuvant during the perioperative period and compares favorably to the NSAIDs in children(77). Although Watcha et al. (65) reported minimal Nonpharmacologic “electroanalgesic” techniques (e.g., analgesic-sparing effects after a 10 mg/kg dose of transcutaneous electrical nerve stimulation [TENS], acetaminophen, Rusy et al. (77) found that a larger acupuncture-like TENS, and percutaneous neuromodu- dose (35 mg/kg per rectum) was as effective as ke- lation therapy) can also be used as adjuvants in the torolac 1 mg/kg IV in reducing pain after tonsillec- treatment of both acute and chronic pain in the ambula- tomy procedures and was associated with less post- tory setting (92). Given the inherent side effects pro- operative bleeding than the NSAID. More recently, duced by both opioid and non-opioid analgesics (Table NON-OPIOID ANALGESICS AND POSTOPERATIVE PAIN Table 3. Dosage Recommendations and Duration of Action of COX-2 Inhibitors
COX-2 ϭ cyclooxygenase-2; PO ϭ orally.
a Data on file with Pharmacia (Skokie, IL) and Merck (West Point, PA).
b IV prodrug of valdecoxib (the active analgesic compound).
results regarding the effect of TENS on the require- Table 4. Potential Side Effects of Opioid and Non-Opioid
ment for opioid analgesic medication and the quality of postoperative pain relief. Several studies suggest that the location, intensity, and frequency of electrical Respiratory and cardiovascular depression stimulation are all important factors influencing the efficacy of TENS (and acupuncture-like TENS) thera- pies (96 –98). Moreover, the clinical efficacy of electro- Pruritus and skin rashSedation and dizziness analgesic techniques remains controversial because of the potential sources of bias and difficulty in quanti- fying the inherent placebo effect of the therapy. Other nonpharmacologic approaches that have also been evaluated as potentially useful analgesic adjuvants in the perioperative period include cryoanalgesia, ultra- sound, laser, and even hypnosis (99 –101). However, Sympathomimetic effects (due to vasoconstrictors) additional well controlled clinical studies are needed to establish the benefits of these nonpharmacologic modalities on patient outcome after ambulatory Allergic reactions and bronchospasmHypertensionPedal edema As more extensive and painful surgical procedures (e.g., laparoscopic cholecystectomy, adrenalectomy, and nephrectomy, as well as prostatectomy, laminec- tomy, shoulder and knee reconstructions, and hyster- ectomy) are performed on an outpatient or short-stay basis, the use of multimodal perioperative analgesic regimens containing non-opioid analgesic therapies will probably assume an increasingly important role in facilitating the recovery process and improving pa- tient satisfaction (3). Optimizing pain management is necessary to maximize the benefits of ambulatory sur- gery for both patients and health care providers. Ad-ditional outcome studies are needed to validate the 4), it is possible that nonpharmacologic approaches will beneficial effects of these newer therapeutic ap- assume a more prominent role in the management of proaches with respect to important recovery variables pain after ambulatory surgery in the future.
(e.g., resumption of normal activities and return to Most studies suggest that TENS produces a 15%– work). Although many factors other than pain per se 30% decrease in the postoperative opioid requirement must be controlled to minimize postoperative morbid- (93). In addition to reporting that TENS reduces pain ity and facilitate the recovery process after ambulatory and the need for oral analgesics, Jensen et al. (94) surgery, pain remains a major concern of all patients reported a more rapid recovery of joint mobility after undergoing surgical procedures (102).
outpatient arthroscopic surgery. In reviewing the It is clear that the anesthetic technique can influence medical literature, Carroll et al. (95) found conflicting the analgesic requirement in the early postoperative NON-OPIOID ANALGESICS AND POSTOPERATIVE PAIN period. Although opioid analgesics will continue to 9. Li S, Coloma M, White PF, et al. Comparison of the costs and play an important role in the management of moder- recovery profiles of three anesthetic techniques for ambulatoryanorectal surgery. Anesthesiology 2000;93:1225–30.
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Nicotine & Tobacco Research Nicotine & Tobacco Research Advance Access published July 9, 2010 Original Investigation The use of snus for quitting smoking compared with medicinal products Karl Erik Lund, Ph.D., 1 Ann McNeill, Ph.D., 2 & Janne Scheffels, Ph.D. 1 1 Norwegian Institute for Alcohol and Drug Research, Oslo, Norway 2 UK Centre for Tobacco Control Studies

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