Postoperative Analgesia for Outpatient Arthroscopic Knee Surgery with Intraarticular Bupivacaine and Ketorolac

Abstract

Intraarticular (IA) local anesthetics are often used for the management and prevention of pain after arthroscopic knee surgery.Systemic ketorolac is also useful in the management of these patients. Ketorolac, a nonsteroidal antiinflammatory drug (NSAID), alters the sensitivity of peripheral nociceptors by reducing the local concentration of allogenic chemicals which are activated by peripheral tissue injury. It is interesting to speculate that placing a NSAID at the site of injury might result in more profound pain relief. However, IA ketorolac has not been evaluated in arthroscopic patients. This study thus was designed to determine which regimen would result in the most effective analgesic benefit. The four groups evaluated received ketorolac (either via the parenteral or IA route) or saline placebo with or without IA bupivacaine, as follows: Group 1 received IA bupivacaine; Group 2, intravenous ketorolac and IA bupivacaine; Group 3, IA bupivacaine with ketorolac; and Group 4, IA ketorolac. The results of this study revealed a significant difference in analgesia from the IA administration of ketorolac. The group who received a combination of IA bupivacaine and IA ketorolac had decreased postoperative pain, a decreased need for postoperative analgesics, and an increased analgesic duration. We conclude that the use of IA ketorolac improved comfort in patients undergoing knee arthroscopy.

(Anesth Analg 1995;80:1154-7)

A variety of analgesic techniques has been used to manage postoperative pain after arthroscopic knee surgery. Although reports have shown varying degrees of success, intraarticular (IA) injections of local anesthetics and/or opioid analgesics are currently being used for postoperative analgesia after ambulatory arthroscopic knee surgery. Systemic ketorolac has been used effectively to manage postarthroscopic knee pain ^[1]. We hypothesized that ketorolac given IA would provide more significant analgesia than when administered systemically.

Methods

After institutional review board approval, informed written consent was obtained from 80 patients scheduled to undergo elective arthroscopic meniscal surgery by a single surgeon. Patients were eligible for participation if they spoke English, if they were more than 18 yr of age, and if they were ASA physical status I or II. Patients were excluded if they were being medicated with narcotics preoperatively or if they had a contraindication to the use of nonsteroidal antiinflammatory drugs (NSAIDs).

Patients were assigned to one of four treatment groups in a double-blind randomized manner: Group 1 [B(IA)] received intravenous (IV) saline (S) (2 mL) and (IA) 0.25% bupivacaine (B) (30 mL); Group 2 [K(IV)B(IA)] received IV ketorolac (K) (60 mg, 2 mL) and IA 0.25% bupivacaine (30 mL); Group 3 [K(IA)B(IA)] received IV S (2 mL) and IA 0.25% bupivacaine (28 mL) with ketorolac (60 mg, 2 mL); and Group 4 [K(IA)] received IV S (2 mL) and IA ketorolac (60 mg, 2 mL) with S (28 mL).

After placement of routine monitors, patients received a similar general anesthetic. Induction of anesthesia was achieved with propofol 2 mg/kg and fentanyl 2 micro gram/kg. Endotracheal intubation was facilitated with succinylcholine 1 mg/kg. Anesthesia was maintained with nitrous oxide (67%) in oxygen and isoflurane (1.0%-2.0% inspired concentration).

When the surgical procedure was completed, the study drug was injected in the patient's knee joint through the arthroscope. In addition, either 2 mL of saline or ketorolac (60 mg) was administered IV at this time according to the study protocol.

Pain scores were recorded by a blinded observer in the postanesthesia care unit (PACU) at 1 and 2 h after injection of the study drug. Patients were at rest when they were evaluated. A 10-cm linear visual analog scale was used for this measurement with 0 cm corresponding to no pain and 10 cm the worst imaginable pain at 1 and 2 h after injection of the study drug.

Patients received IV fentanyl (25 micro gram every 5 min as needed) in the PACU if they experienced pain.

Upon discharge from the hospital, patients were instructed to take one Tylenol No. 3 Registered Trademark (acetaminophen 300 mg/codeine 30 mg; McNeil Pharmaceuticals, Don Mills, Ontario) every 3 h as needed for pain. The first time they required additional opioid analgesia (either IV fentanyl or oral analgesics) and the total analgesic requirement during the initial 24 h after surgery were documented. (Patients were contacted by telephone the following day.)

Analgesic duration was considered as the time from IA injection of the study drug to the first requirement of supplemental opioid analgesics (either IV fentanyl in the PACU or oral analgesics at home).

Patients were discharged when they were oriented to time and place, were able to void, had stable vital signs, and could ambulate with the assistance of crutches. Discharge time was classified as the time from the end of surgery until the patients were able to meet the discharge criteria.

Demographic data were analyzed with analysis of variance. Times (duration of procedure, time to discharge, and analgesic duration), pain scores, and amount of postoperative analgesics were analyzed by the Kruskal-Wallis test. If a significant result was obtained, the Wilcoxon signed rank test was performed to determine between which groups there was significance; a Bonferroni adjustment was made for multiple comparisons. The use of fentanyl in the PACU was evaluated with Fisher's exact test. Significance was determined at the P < 0.05 level.

Results

There were no significant differences among the four treatment groups with respect to age, height, weight, duration of surgery, or the time to discharge Table 1.

Table 1: Comparison of the Four Treatment Groups with Respect to Age, Height, Weight, Duration of Surgery, and Time to Discharge

There was significance with respect to the pain scores at 1 (P < 0.001; Figure 1) and 2 h (P < 0.0001; Figure 2) postoperatively. The K(IA)B(IA) group had lower 1- and 2-h pain scores (0.6 +/- 0.4; 0.9 +/- 0.6) than the B(IA) group (1.8 +/- 1.8, P < 0.005; 2.2 +/- 1.2; P < 0.02), and the K(IA) group (1.9 +/- 1.2, P < 0.001; 1.8 +/- 0.7; P < 0.001). The K(IA)B(IA) group had lower 2-h pain scores than the K(IV)B(IA) group (2.0 +/- 1.0; P < 0.001). The K(IA)B(IA) group did not have significantly lower 1-h pain scores than the K(IV)B(IA) group (2.0 +/- 2.1; P = not significant).

Figure 1: The pain scores at 1 h postoperatively in the four groups. Group B(IA) received intraarticular (IA) bupivacaine; Group K(IV)B(IA) received intravenous (IV) ketorolac and IA bupivacaine; Group K(IA)B(IA) received IA bupivacaine with ketorolac; and Group K(IA) received IA ketorolac. The box represents the 25th-75th percentiles and the median is represented by the solid line. Outliers, shown by the circles, are defined as values between 1.5 and 3 box lengths. Lines are drawn from the end of the box to the largest and smallest observed values that are not outliers. VAS = visual analog scale.

Figure 2: The pain scores at 2 h postoperatively in the four groups. Group B(IA) received intraarticular (IA) bupivacaine; Group K(IV)B(IA) received intravenous (IV) ketorolac and IA bupivacaine; Group K(IA)B(IA) received IA bupivacaine with ketorolac; and Group K(IA) received IA ketorolac. The box represents the 25th-75th percentiles and the median is represented by the solid line. Lines are drawn from the end of the box to the largest and smallest observed values. VAS = visual analog scale.

There was a significant difference with respect to the duration of analgesia among the groups (P < 0.0008). The K(IA)B(IA) group had a significantly longer time to first analgesic request (892 +/- 399) than the K(IV)B(IA) group (390 +/- 354, P < 0.001), the B(IA) group (442 +/- 461, P < 0.012), and the K(IA) group (402 +/- 295, P < 0.001).

The 24-h consumption of Tylenol No. 3 Registered Trademark was significantly different among the groups (P < 0.0001). The K(IA)B(IA) group had significantly fewer tablets consumed (1.2 +/- 1.0) than the K(IV)B(IA) group (3.5 +/- 2.0, P < 0.0004), the B(IA) group (2.9 +/- 2.3, P < 0.008), and the K(IA) group (3.3 +/- 1.3, P < 0.0001).

The number of patients in each group who received IV fentanyl in the PACU were as follows: K(IA)B(IA) group, 0/20; K(IV)B(IA) group, 4/20; B(IA) group, 5/20; and the K(IA) group, 2/20. There was no statistical difference among any of these groups.

Discussion

In an attempt to improve the recovery from arthroscopic knee surgery, research has been directed toward new techniques for postoperative analgesia. Previous studies have investigated IA local anesthetics, IA opioids, and systemic NSAIDs.

Although most local anesthetics probably would provide for effective analgesia when administered IA, bupivacaine frequently is chosen because of its long duration of action. Although most studies reveal a benefit from IA local anesthetic administration ^[2-6], some studies have failed to demonstrate any significant decrease in postoperative pain ^[7,8]. Because opioid receptors have been isolated in inflamed synovial tissue, research has been undertaken to mediate peripheral analgesia through the use of low-dose IA morphine (1-5 mg). Although investigational human studies have revealed effective analgesia up to 48 h from the administration of IA morphine ^[4,9-11], this still remains controversial since other studies have not demonstrated any significant clinical effect ^[3,5,7]. NSAIDs have proven useful in relieving postoperative pain after arthroscopy ^[1]; this may result from their ability to mediate pain and inflammation at the surgical site. Pain scores were similar when either systemic ketorolac or IA bupivacaine was administered after arthroscopic knee surgery ^[1]. We postulated that the administration of IA ketorolac (although it is not approved for this use by the Food and Drug Administration) might further reduce inflammation on the surface of the knee joint, and thus improve analgesia.

Several recent studies have demonstrated a significant central action of NSAIDs ^[12,13]. Intrathecal ketorolac has been shown to exert a direct spinal action by blocking hyperalgesia induced by the activation of spinal glutamate and substance P receptors ^[13]. The results of the present study provide some evidence that NSAIDs exhibit a significant portion of their effect at the periphery rather than through a central mechanism. Increasing the concentration of NSAID at the site of the noxious stimuli may be responsible for the benefit in the present study.

Ketorolac is costly. At our institution, the acquisition cost is $6.27 and the patient charge is $25.08. Although this is expensive, savings could be realized due to a reduced need for postoperative analgesics in the patients who received the combination of bupivacaine and ketorolac IA. The pharmacy acquisition cost and patient charge for the fentanyl administered in the PACU are $0.30 and $1.20, respectively. The costs associated with the oral analgesics vary between pharmacies, but the average cost is approximately $0.50 per pill.

In conclusion, we have shown that ketorolac, when administered along with bupivacaine through the IA route, results in a significant improvement in analgesia. There was decreased patient discomfort, an increased time to first analgesic request, and a decreased need for postoperative analgesics.