A comparison of patient-controlled and fixed schedule analgesia after orthognathic surgery

J Oral Maxillofac 5533.39, 1997

Surg

A Comparison of Patient-Con trolled and Fixed Schedule Analgesia After Orthogna thic Surgery DAVID S. PRECIOUS, DDS, MSc, FRCD(C),* JOE MULTARI, DDS, MS, FRCD(C),t G. ALLEN FINLEY, MD, FRCP(C),* AND PATRICK McGRATH, PHD§ Purpose: The purpose of this prospective study was to compare the effectiveness of patient-controlled intravenous (IV) opioid analgesic administration (PCA) with fixed schedule and dosage oral/rectal administration of naproxen, and opioid analgesics intramuscularly/orally as needed (IM/po prn) for postoperative analgesia over a period of 48 to 56 hours after surgery. Patients and &fethocfs: There were 75 orthognathic patients aged 25.73 ? 8.01 years, subdivided into three study groups of 25: codeine group (8 males, 17 females); naproxen group (5 males, 20 females) and PCA group (8 male, 17 females). The degree of analgesia was assessed every 4 hours from 8:00 AM to 8:00 PM hours on days 1 and 2 postsurgery using a visual analog scale (VAS). Mean daily and mean overall VAS scores were treated as parametric data and were analyzed accordingly. Mean daily VAS scores also were categorized as comfort days when mean scores were less than 3.0 cm, and as discomfort days when mean scores were equal to or greater than 3.0 cm. ANOVA were used to analyze patient demographics, pain scores, surgical time, fentanyl used during general anaesthesia, analgesic morphine equivalents, and vital signs. Chi-square tests were used to analyze sex, comfort (discomfort) days, and nausea and vomiting. Mean VAS ratings were analyzed using independent t-tests. Results: The three groups were matched in demographics, surgical time, fentanyl used, and sex. The PCA group used less than half the amount of morphine equivalent as the codeine group (P = .OOOl). Both the naproxen and the PCA groups were significantly more comfortable than the codeine group during day 1 and day 2 postsurgery. The codeine group had significantly more episodes of nausea than either the naproxen or the PCA groups. Conclusion: In patients undergoing orthognathic surgery, the naproxen and PCA regimens provided better analgesia than the codeine regimen. Postoperative pain is a new experience for most patients undergoing orthognathic surgery. They may feel intimidated and vulnerable in the hospital setting and, hence, conceal their feelings when suffering pain. Moreover, maxillomandibular fixation and facial edema limit their ability to communicate the presence and location of pain, thus portraying a false impression of comfort. Traditionally, postoperative analgesia for surgical patients has consisted of parenteral/oral opioid analgesics as needed (pro re nata; pm).lm3 An opioid analgesic pm order is usually written by the surgeon with a standard dosage and time interval. As outlined by Park-

* Professor and Chair, Department of Oral and Maxillofacial Sciences, Dalhousie University, Halifax, NS, Canada. f Former Senior Resident, Oral and Maxillofacial Surgery, Victoria General Hospital, Halifax, Canada. $ Department of Anesthesia and Director of Pain/Palliative Care Program, IWK-Grace Health Centre, Halifax, Canada. 0 Professor, Clinical Psychology PhD Program, Department of Psychology, Dalhousie University, Halifax, Canada. Address correspondence and reprint requests to Dr Precious: Department of Oral and Maxillofacial Surgery, Dalhousie University, 5981 University Ave, Halifax, N.S., B3H 355, Canada. 0 1997 American

Association

of Oral and Maxillofacial

Surgeons

0278-2391/97/5501-0005$3.00/O

33

34 house et aI: this practice is unequivocally outdated. Patient analgesia requirements differ widely after the same operation5 and a fixed schedule can sentence the patient to recurring cycles of pain and either inadequate analgesia or sedation.6 Additionally, there is individual variability with regard to blood concentrations obtained after intramuscular (&I) injection. Austin et al7 found that the blood concentration after IM administration of meperidine was in excess of the minimum analgesic concentration for only 35% of each 4-hour dosing interval. Both Marks and Sacha? and Cohen’ found a return of significant pain in more than 60% before the next analgesia dose was due. The administration of an opioid analgesic pm order rests solely with the nursing staff. They must communicate with the patient, assess the patient’s pain, make a decision on an analgesic and its dose, select a route of administration, and decide when to administer the dose. Unfortunately, some nurses wait until a patient is in severe pain before using an opioid analgesic,” or conversely, many patients wait until they have severe pain before asking for an analgesic. Worse yet, some patients may not even be aware that an analgesic is available and suffer in silence. ‘i-l3 In orthognathic surgery patients this scenario can be further compounded by maxillomandibular fixation, which limits their ability to communicate. Although pm regimens should theoretically provide for individualization of pain management requirements, optimum treatment rarely occurs, and postoperative analgesia is generally poor.4,6,9,‘3-21 Patient-controlled analgesia (PCA) improves on traditional parenteral/oral pm analgesia by providing better titration of analgesic drugs, thereby addressing individual pharmacokinetic and pharmacodynamic variation.” The concept of PCA was first described in 1968 by Sechzer.23 The earliest descriptions of actual self-administered PCA machines were by Forrest et al,24 Sechzer,25 and Keeri-Szanto.26 PCA allows patients to self-administer intravenous (IV) analgesics by means of a microprocessor-controlled pump that delivers the preprogrammed dose on demand. Advantages of this system over traditional opioid analgesics pm include: high-quality analgesia with superior pain relief, autonomy and increased psychologic satisfaction, individualized analgesia, less sedation because of drug titration, elimination of delay in the decision to medicate for pain, decreased staff time for patient care, elimination of painful IM injections, and rapid onset of analgesia.27~28PCA has been shown to provide more effective and better accepted postoperative analgesia when compared with morphine IM pm in patients undergoing orthopedic surgery,29 gastric bypass surgery,30 hysterectomy,31 abdominal surgery, 32 and cesarean section.33 Another effective alternative to the use of traditional opioid analgesics pm is the use of a nonsteroidal antiin-

ANALGESIA

AFTER

ORTHOGNATHIC

SURGERY

flammatory drug (NSAID), such as naproxen, on a fixed schedule and dose. After oral (PO) or rectal (pr) administration, naproxen is completely and rapidly absorbed from the gastrointestinal tract,34 with essentially equal bioavailability.35*36 The oral suspension is well tolerated37 and has similar bioavailability to the tablet form.38 Given orally, naproxen has been shown to be more effective than oral meperidine,39 oral codeine,40‘43 oral pentazocine,” and oral propoxyphene45 in the treatment of patients with postoperative pain. It also has been shown to be as effective as 10 mg morphine IM in patients undergoing orthopedic surgery, general surgery, and gynecologic surgery.46 Naproxen suppositories have been shown to be more effective than placebo in pain relief after herniotomy.47 The purpose of this study was to compare the effectiveness of patient-controlled IV opioid analgesic administration with fixed schedule and dosage po/pr administration of an NSAID, and the use of traditional opioid analgesics IM/po pm for postoperative analgesia over a period of 48 to 56 hours after orthognathic surgery. Patients

and Methods

Seventy-five patients aged 16 to 48 years (mean age, 25.73 2 8.01 yrs) participated in the study. All underwent orthognathic surgery for the correction of dentoskeletal deformities. Before inclusion in the study, all prospective patients were screened for the ability to understand and use a visual analog scale (VAS). Patients also were screened for the ability to comprehend and use a PCA machine. They were excluded from the study if they had a history of chronic opioid, alcohol, or other drug abuse; had a history of allergy/hypersensitivity or adverse reaction to morphine, codeine, aspirin, naproxen, or any other NSATD; had concurrent or recent history of hepatic, renal, cardiovascular, hematopoietic, endocrine, respiratory, neurologic, or psychiatric disease; had active peptic ulcer disease, gastrointestinal bleeding, or gastric dysfunction that could interfere with drug absorption; had a cleft lip/cleft palate or previous surgery for the correction of a cleft lip/cleft palate; were pregnant or lactating; or were receiving highly protein-bound drugs. All patients in this study were classified as ASA I according to the American Society of Anesthesiologists Physical Status Classification System.48 PREOPERATIVE PROCEDURE The patients were seen on the day before their orthognathic surgery, and the nature and purpose of the study was explained and any concerns or questions were addressed. The use of a lo-cm VAS, with “no pain” and “severe pain” at the 0- and lo-cm anchors, respectively, was explained to the patients in a standardized

PRECIOUS ET AL

35

fashion, and their understanding of its use was confirmed. After informed consent was obtained, subjects were randomly assignedto one of three study groups by the use of random numbers tables. There were 25 patients (8 male, 17 female) in the codeine group, 25 patients (5 male, 20 female) in the naproxen group, and 25 patients (8 male, 17 female) in the PCA group. The patients were informed of their group assignment after procurement of consent. PERIOPERATIVE

MANAGEMENT

A standardized protocol was used to produce hypotension general anesthetia to minimize any residual analgesic effects from the general anesthetic. Premedication consisted of a benzodiazepine only. Induction was achieved with either thiopental and droperidol or propofol. The choice of neuromuscular blockade agent, as well as the volatile agent and reversal agents, was left to the discretion of the anesthesiologist.Anesthesia was maintained with a nitrous oxide-oxygen combination and a volatile agent. Hypotension was maintained with labetalol or propanolol. The only opioid allowed during the general anesthetic was fentanyl, which was used in a dosage of 0.0 to 11.4 pg/kg (mean = 4.6 + 2.2 pg/kg). No other opioids or analgesics were administered intraoperatively. All of the surgical procedures were performed by four staff oral and maxillofacial surgeons. The operations consisted of Le Fort I osteotomies, bilateral sagittal split osteotomies, functional genioplasties, and the removal of third molar teeth. All patients were placed in maxillomandibular fixation after surgery. In the postanesthetic care unit (PACU), patients in the codeine and the PCA groups received IV morphine sulfate pm at the discretion of the anesthesiologist. Patients in the naproxen group received a 500-mg naproxen rectal suppository shortly after induction and just before surgery while in the operating room. These patients were then given naproxen 250 mg either pr or po every 6 hours until termination of the study. POSTOPERATIVE

ANALGESIA

Once on the nursing ward, patients in the naproxen group continued with the aforementioned regimen. If pain control was deemed inadequate for these patients, rescue analgesia in the form of codeine phosphate 30 to 60 mg IM/po every 4 hours pm was permitted. Patients in the codeine group received codeine phosphate 30 to 60 mg IM/po every 4 hours pm and morphine sulfate 0.1 to 0.2 mg/kg IM every 4 hours pm for severe pain. For patients in the PCA group, the machines were connected and activated once the patients arrived on the nursing ward. Before initiation of the study, in-

service training of the nursing staff on the use of PCA was conducted. The Abbott Lifecare 4100 PCA Infuser System (Abbott Laboratories, North Chicago, IL) was used. This system consists of a microprocessor-controlled syringe connected to the patient’s IV tubing by a special Y tube that has a one-way valve to prevent reflux of the injected drug. The patient activates the machine by depressing a button similar to a nurse call button on a cord extending from the machine. Morphine sulfate in premade 30-mL vials, with a concentration of 1.0 mg/mL, was loaded into the machine before patient use. The machines were programmed to deliver 1 mg morphine sulfate for each dose, with a lockout interval of 10 minutes, during which time further activation of the machine would not deliver a dose. The machine was able to record the total amount of morphine administered, the number of both injected and unsuccessful demands,as well as the exact time that demandswere made and delivered. In this way, it was possible to assessthe individual patient’s analgesianeeds. For the 25 patients in this study, no alteration in the delivery program was required. Because of the possible inconvenience of the IV catheter and tubing, patients had the option of having the PCA device discontinued anytime after the end of day 1 postsurgery and subsequently being placed on the codeine regimen for the remainder of the study. Seven patients discontinued PCA at the end of day 1 postsurgery, 15 patients terminated PCA during day 2 postsurgery, and three patients maintained PCA until the end of the study. ASSESSMENT

OF PAIN

Postoperative analgesiawas assessedevery 4 hours from 800 AM to 8:00 PM on day 1 and day 2 postsurgery with the use of a VAS. Patients were asked to mark the point on the scalecorresponding to the severity of their pain with a vertical line. VAS ratings were measured directly from the zero end of the scale in centimeters. No assessmentwas performed on the day of surgery becauseof the unpredictable drowsinessand associated mental and physical impairment after the general anesthetic, because this would negatively affect the patient’s ability to accurately use the VAS.49 Nursing records for the relevant periods were used to record any incidents of nausea, vomiting, or other adverse effects. The samerecords were used to record temperature (axillary), pulse, respiratory rate, and blood pressurepreoperatively, on the day of surgery, and on the subsequent 2 days postsurgery. Time and dosage of all medication administered were also recorded. The study was terminated at X:00 PM on day 2 postsurgery for all patients. At the end of the study, patients

36 Table

ANALGESIA

1.

Demographics

Comparison

of Study

Groups

Naproxen Age (yrs t SD) Height (cm f SD) Weight (kg i_ SD) Surgical time (min ? SD) Fentanyl used (mcg/kg F SD) Morphine equivalent use (mg 2 SD)

25.5 166.5 62.5 207.0 5.0 3.5

t + +i I r

9.0 8.8 11.2 61.2 2.6 6.5

were asked to rate their postoperative analgesia as very comfortable, comfortable, uncomfortable, or very uncomfortable. Patients were also asked to comment on their postoperative analgesia. DATA ANALYSIS

Data from the VAS ratings were analyzed in two ways. The mean daily and mean overall scores (in centimeters) were treated as parametric data and were analyzed accordingly. In the second method, the mean daily scores were categorized as comfort days when the mean scores were less than 3.0 cm and as discomfort days when the mean scores were greater than or equal to 3.0 cm. The data then were analyzed categorically using chi-squared tests. To standardize the amount of analgesia used in the codeine and the PCA groups, all opioid analgesics were converted to milligrams morphine as follows; 10 mg morphine IM = 130 mg codeine IM = 200 mg codeine ~0.~’ The following conversion was also used: 10 mg morphine IM = 10 mg morphine IV, because IM morphine is very rapidly absorbed51 and Berkowitz et a152 have shown that peak morphine serum levels after either IM or IV injection of 10 mg/70 kg are comparable. One-way analyses of variance (ANOVA) were used for patient demographics, pain scores, surgical time, fentanyl used, morphine equivalents, and vital signs preoperatively, on the surgical day, and on the two subsequent days. Post hoc testing of ANOVA was performed with Duncan’s Multiple Range Test. Chisquared tests were used to analyze sex, comfort days/ discomfort days, and nausea and vomiting. Patient ratings of postoperative analgesia were collapsed from four to two categories (comfortable and uncomfortable) because of the small sample size in some of the categories and to facilitate statistical analysis. Comparisons of the mean VAS ratings for the categories were then made using independent t-tests. For all tests, P 5 .05 was considered to be statistically significant. Results

All three groups were matched in demographics, surgical time, fentanyl used, and sex (Table 1). With

AFTER

ORTHOGNATHIC

SURGERY

(means) Codeine 26.4 168.3 70.1 230.8 4.8 34.0

2 i? + ? L

One-Way ANOVA (P Value)

PCA

8.6 11.7 18.3 49.1 1.9 23.4

25.3 167.9 67.6 216.0 4.1 15.7

I & 5 L +2

6.6 9.6 13.8 50.3 2.0 11.9

.88 .80 .18 .29 .30 .OOOl

respect to morphine equivalent use (Table I), the PCA group used less than half the amount used by the codeine group, and this was statistically significant (P = .OOOl). This reduction in the amount of analgesic required for relief of postsurgical pain using PCA was in agreement with studies performed by Lange et a1,53 Albert and Talbott,54 Hecker and Albert,55 and Sechzer.25 Together with the increased comfort experienced by these patients (Table 2), this emphasized the ability of these patients to titrate the drug required to effect. Comparison of the pain scores (Table 2) showed that both the naproxen and PCA groups were comfortable (scores < 3.0 cm) and that there were no statistically significant differences between them on day I, day 2, and over the 2-day postsurgery period. Both groups were significantly more comfortable than the codeine group on day 1 (P = .002), day 2 (P = .004), and over the 2-day postsurgery period (P = .OOl). Within the codeine group, the mean pain scores were greater than 3.0 cm on all measures, indicating a greater degree of postsurgical discomfort. No patients in the naproxen group required rescue medication in the PACU, but 7 of 25 patients subsequently required such medication. With regard to the ratio of comfort/discomfort days (Fig l), once again the naproxen and PCA groups provided equally effective postsurgical analgesia, whereas the codeine group had significantly inferior analgesia postsurgically (P = .004). This superiority of both the naproxen and PCA groups over the codeine group was also indicated by the patients’ rating of postoperative analgesia (Tables 3, 4).

Table Study

2. Mean Groups

Pain

Naproxen Day (” Day (” Day (2

1 cm SD) 2 cm SD) 1 + 2 cm SD)

Scores

Comparison

Codeine

of

PCA

One-Way ANOVA (P Value)

1.5

3.5 + 1.6

2.3 ~?r 1.5

.002

2.0 I! 1.8

3.3 t 1.8

1.9 ? 1.3

,004

2.0 t 1.6

3.4 i- 1.6

2.1 XL 1.3

,001

2.0 i

PRECIOUS

37

ET AL

Comfort 60

Days vs Discomfort

q n

50

Comfort Days

Days p = 0.004

Comfortable

37-

Ii 13

Naproxen

Codeine

FIGURE 1. Comparison for total number of comfort after orthognathic surgery.

PCA

Discussion

There is a paucity of literature on postoperative analgesia after orthognathic surgery. In a study involving elective procedures in otorhinolaryngology, general surgery, plastic surgery, oral and maxillofacial surgery, urology, and orthopedic surgery, Bush et alI7 demonstrated that the perceived postsurgery morbidity associated with orthognathic surgery was comparable to that of other significant surgical procedures. In 1976, Evans et a156evaluated 45 orthognathic surgery patients and concluded that postoperative pain is generally not severe enough to justify the use of strong narcotic analgesics. Unfortunately, these researchers did not objectively evaluate postoperative pain, and they incorrectly assumedthat a patient not asking for analgesicswas, in fact, comfortable. Additional prospective studies on postoperative analgesia in the orthognathic surgery literature are lacking. A number of retrospective studies clearly indicate

Rating

Naproxen Codeine PCA

8 2 3

scores

20 1.83 i 1.56

5 2.52 i- 1.58

.39

scores

10 2.65 t 1.59

15 3.91 + 1.39

.05

scores

16 1.57 F 1.08

3.08 i

9 1.01

,003

12 8 13

Table 5. Groups

Side

Effects

Uncomfortable 5 11 8

Comparison

of Study

Nausea*

V-Y Comfortable

that postoperative pain after orthognathic surgery is not sufficiently controlled with traditional methods of analgesia.57-59 It appears that in our quest to achieve technical and surgical excellence we have overlooked one of our patients’ greatest preoperative concerns and postoperative realities.60Z61 The analgesia regimens used in this study differ in many ways (drugs, pharmacologic mechanismsof action, route of administration, dose, and schedule), which makes it very difficult to rationalize the effectiveness/ineffectiveness of a particular regimen. The intent of this prospective, randomized clinical study was to investigate alternative regimens of postoperative analgesia so that more effective postoperative analgesia could be provided for patients undergoing orthognathic surgery. The ideal pain study would best be conducted in a double-blind, standardized fashion with all patients receiving either the regimen drug or placebo by all routes of administration for the regimens with their appropriate schedule. Obviously this is not appropriate in terms of both quality of care and ethics. The VAS is a valid and reliable tool with which to assesspain. It is accurate, sensitive, cost-effective, and easy to use.63-66 It is more sensitive than either categorical or descriptive pain scales,and it is able to discriminate between small changesin pain intensity.64,67.68 The VAS used in this study was selected, constructed, and

of Postoperative

VW Comfortable

Naproxen n Mean Codeine n Mean PCA n Mean

Uncomfortable

of Naproxin, Codeine, and PCA groups and discomfort days in the 2-day-period

The incidence of nausea and vomiting in all groups is summarized in Table 5. The codeine group had significantly more episodes of nausea than the naproxen and PCA groups (P = .OOl). The PCA group had fewer episodes of vomiting than the codeine or naproxen groups; however, this difference was not statistically significant.

Patient

Independent t-test (P Value)

Discomfort Days

d---38

Table 3. Analgesia

Table 4. Comparison of Patient Rating of Postoperative Analgesia With Pain Scores

Uncomfortable 0 4 1

Naproxen Codeine PCA * Chi-square 7 Chi-square

Vomiting

Yes

No

Yes

No

4 15 4

21 10 21

6 6 2

19 19 23

test, P = .OOl. test, P = .25.

38 presented to patients according to the criteria extablished by Scott and Huskisson69 in 1976. On the lo-cm VAS, pain was considered to be of moderate intensity and more than likely to require analgesia when the score was 3.0 cm or greater from the 0 anchor.29,70 It is recognized that because of the subjective nature of pain not all patients will meet this criterion; however, most patients will conform to this model. This conclusion is supported by the comparison of patients’ rating of postoperative analgesia with their pain scores (Table 4). Patients in all groups who rated their overall postoperative analgesia as comfortable had average pain scores that were less than 3.0 cm. With the exception of the naproxen group, which had only five patients in the uncomfortable subgroup, all patients who rated their overall postoperative analgesia as uncomfortable had average pain scores of 3.0 cm or greater. The results of this study clearly indicate that in patients undergoing orthognathic surgery the naproxen and PCA regimens provide significantly better analgesia than does the traditional codeine regimen. The PCA and naproxen regimens provide good postoperative analgesia of relatively equal effectiveness, whereas the traditional codeine regimen provides inferior postoperative analgesia. The naproxen regimen was very well received by the patients. Both the suspension and suppositories were well tolerated, with only one patient complaining about the taste of the suspension. This patient refused her final two doses. However, in retrospect, she acknowledged that the regimen certainly helped her pain. No patient had naproxen discontinued because of adverse effects. Two patients commented that they enjoyed being on a regular schedule and not feeling like they were “bothering the nurses.” Many of the adolescent patients were grateful for the lack of “needles” required in the postoperative period. Two patients thought that the naproxen reduced the amount of opioid they would normally have used after surgery, and this enabled them to function more comfortably without undue sedation. The PCA regimen was also well received. No patients had this regimen discontinued because of untoward effects. Two patients commented on the positive psychologic advantage of having self-control and not having to rely on the nursing staff. One patient commented on the disadvantage of having an IV and its limitation vis-a-vis mobility. Two other patients voiced displeasure with stinging in the arm whenever morphine was injected. In fact, these patients thought that this unpleasant sensation discouraged them from using the device. The PCA group had fewer overall side effects when compared with the other groups (Table 5). This appears to be a direct result of the fact that, unlike naproxen and codeine, PCA allows titration of optimal plasma

ANALGESIA

AFTER

ORTHOGNATHIC

SURGERY

analgesia concentrations while avoiding excessive dosage that would produce undesirable side effects and sedation.54’7’ Respiratory depression is a concern with any opioid analgesic. In this study, a review of the vital signs showed that no patient in either of the opioid analgesic groups had a respiratory rate of less than 12 breaths/ min, and there were no charted events of respiratory depression. Acknowledgment The clincial

authors thank Dr R.H. care of patients.

Goodday

for

his assistance

in the

References 1. Hegtvedt AK: Intraoperative and postoperative patient care. Oral Maxillofac Surg Clin North Am 2:857, 1990 2. Bell WH, Proffitt WR, White RP Jr: Surgical Correction of Dentofacial Deformities. Philadelphia, PA, Saunders, 1980 3. Schwartz SI: Principles of Surgery. New York, NY, McGrawHill, 1989 4. Parkhouse J, Lambrechts W, Simpson BRJ: The incidence of postoperative pain, Br J Anaesth 33:345, 1961 5. Cartwright PD: Pain control after surgery: A survey of current practice. Ann R Co11 Surg Engl 67:13, 1985 6. Oden RV: Acute postoperative pain: Incidence severity and the etiology of inadequate treatment. Anesthesiol Clin North Am 7:1, 1989 I. Austin KL, Stapleton JV, Mather LE: Multiple intramuscular injections: A major source of variability in analgesic response to meperidine. Pain 8:47, 1980 8. Marks RM, Sachar EJ: Undertreatment of medical inpatients with narcotic analgesics. Ann Intern Med 78:173, 1973 9. Cohen FL: Postsurgical pain relief: Patients’ status and nurses’ medication choices. Pain 9:265, 1980 10. Chapman PJ, Ganendran A, Scott RJ, et al: Attitudes and knowledge of nursing staff in relation to management of postoperative Rain. Aust N Z J Sum 57:447. 1987 11. Owen H, Kluger MT, Plummer JL: ‘Variables of patient-controlled analgesia 4: The relevance of bolus dose size to supplement a background infusion. Anaesthesia 45:619, 1990 12. Smith JM, Utting JE: Postoperative pain. Br Med J 6040:875, 1976 13. Sriwatanakul K, Otto FW, Alloza JL, et al: Analysis of narcotic analgesic usage in the treatment of postoperative pain. JAMA 250:926, 1983 14. Ross RS, Bush JP, Crummette BD: Factors affecting nurses’ decisions to administer PRN analgesic medication to children after surgery: An analog investigation. J Pediatr Psycho1 16:151, 1991 15. Carr ECJ: Postoperative pain: Patients’ expectations and experiences. J Adv Nurs 15:89, 1990 16. Berde CB: Pediatric postoperative pain management. Pediatr Clin North Am 36:921, 1989 17. Bush JP, Holmbeck GN, Cockrell JL: Patterns of PRN analgesic drug administration in children following elective surgery. J Pediatr Psvchol 14:433, 1989 18. Donovan M, billon P, McGuire L: Incidence and characteristics of pain in a sample of medical-surgical inpatients, Pain 30:69, 1987 19. Mather L, Mackie J: The incidence of postoperative pain in children. Pain 15:271, 1983 20. Nayman J: Measurement and control of postoperative pain. Ann R Co11 Surg Engl 61:419, 1979 21. Keeri-Szanto M, Heaman S: Postoperative demand analgesia. Surg Gynecol Obstet 134:647, 1972 22. White PF: Use of patient-controlled analgesia for management of acute pain. JAMA 259:243, 1988

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23. Sechzer PH: Objective measurement of pain. Anesthesiology 29:209, 1968 24. Forrest WH, Smethurst PWR, Kienitz M: Self-administration of intravenous analgesics. Anesthesiology 33:363, 1970 25. Sechzer PH: Studies in pain with the analgesic demand system. Anesth Analg 50:1, 1971 26. Keeri-Szanto M: Apparatus for demand analgesia. Canadian Anaesthetists’ Society Journal 18:581, 1971 27. Miller RD: Anesthesia. New York, NY, Churchill Livingstone, 1990 28. Ma CSJ, Lin D: Patient controlled analgesia: Drug options infusion schedules and other considerations. Hospital Formulary 26:198, 1991 29. Berde CB, Beate ML, Sethna NF, et al: Patient-controlled analgesia in children and adolescents: A randomized prospective comparison with intramuscular administration of morphine for postoperative analgesia. J Pediatr 118:460, I991 30. Bennett RL, Batenhorst RL, Bivins BA, et al: Patient-controlled analgesia: A new concept of postoperative pain relief. Ann Surg 195:700, 1982 3 1. Wasylak TJ, English MJM, Abbott FV, et al: Reduction of postoperative morbidity following patient-controlled morphine. Can J Anaesth 37:726, 1990 32. Bollish SJ, Collins CL, Kit-king DM, et al: Efficacy of patientcontrolled versus conventional analgesia for postoperative pain. Clin Pharm 4:48, 1985 33. Eisenach JC, Grice SC, Dewan DM: Patient-controlled analgesia following cesarean section: A comparison with epidural and intramuscular narcotics. Anesthesiology 68:444, 1988 34. Todd PA, Clissold SP: Naproxen: A reappraisal of its pharmacology and therapeutic use in rheumatic diseases and pain states. Drugs 40:91, 1990 35. Desager JP, Vanderbist M, Harvengt C: Naproxen plasma levels in volunteers after single-dose administration by oral and rectal routes. J Clin Pharmacol 16: 189, 1976 36. Gamst ON, Vewje AK, Aarbakke J: Bioavailability of naproxen sodium suppositories. Int J Clin Pharmacol Ther Toxic01 22:99, 1984 37. Laxer RM, Silverman ED, St Cyr C, et al: A six-month open safety assessment of a naproxen suspension formulation in the therapy of juvenile rheumatoid arthritis. Clin Ther 10:381, 1988 38. CPS-Compendium of Pharmaceuticals and Specialties. Ottawa, Canadian Pharmaceutical Association, 1992 39. Stetson JB, Robinson K, Wardell WM, et al: Analgesic activity of oral naproxen in patients with postoperative pain. Stand J Rheumatol Suppl 2:50, 1973 40. Galasko CSB, Courtney P, Jayne M, et al: Comparison of the efficacy of naproxen sodium and dihydrocodeine tartrate in the treatment of post-operative pain, Curr Med Res Opin 10:656, 1988 41. Forbes JA, Keller CK, Smith JW, et al: Analgesic effect of naproxen sodium codeine, a naproxen-codeine combination, and aspirin on the postoperative pain of oral surgery. Pharmacotherapy 6:211, 1986 42. Bloomfield SS, Barden TP, Mitchell J: Naproxen aspirin and codeine in postpartum uterine pain. Clin Pharmacol Ther 21:414, 1977 43. Ruedy J: A comparison of the analgesic efficacy of naproxen and acetylsalicylic acid-codeine in patients with pain after dental surgery. Stand J Rheumatol Suppl 2:60: 1973 44. Filtzer HS: A double-blind randomized comparison of naproxen sodium acetaminophen and pentazocine in postoperative pain. Curr Ther Res 27:293, 1980 45. Ruedy J, McCullough W: A comparison of the analgesic efficacy of naproxen and propoxyphene in patients with pain after orthopedic surgery. Stand J Rheumatol Suppl 2:56, 1973 46. Brown CR, Sevelius H, Wild V: A comparison of single doses

47.

48. 49.

50.

51.

52.

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56. 57. 58.

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60.

61. 62.

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65. 66. 67. 68.

69. 70.

71.

A