The Effect of Ketorolac on Recovery After Anorectal Surgery: Intravenous Versus Local Administration

Abstract

The role of ketorolac in facilitating the recovery process after ambulatory surgery is controversial. Ketorolac, a nonsteroid antiinflammatory drug (NSAID), produces pain relief with less respiratory depression, nausea, and vomiting than opioid analgesics (1). When used as an alternative to fentanyl in outpatients undergoing laparoscopy (2), ketorolac was associated with comparable postoperative analgesia and shorter discharge times. Additionally, the combination of ketorolac and local anesthesia provided superior postoperative analgesia than either drug alone in patients undergoing knee arthroscopy procedures (3,4). Although IV ketorolac has well known opioid-sparing properties (2–4) and even possible anesthetic-sparing qualities (5), the injection of ketorolac at the surgical site has been reported to possess varying degrees of analgesic activity (6–8). When ketorolac was administered “locally” to patients undergoing hemorrhoidectomy (6) and inguinal hernia repair (7), it decreased the postoperative pain scores and enhanced patient comfort compared with systemic morphine and IV ketorolac, respectively. However, in patients undergoing breast surgery (8), the analgesic effect of ketorolac administered at the surgical site was no more effective than IV ketorolac. We hypothesized that the administration of ketorolac at the surgical site (local) would provide more effective postoperative analgesia than IV administration during surgery performed under local anesthesia with sedation as part of a monitored anesthesia care technique. Specifically, this study was designed to determine if a single dose of ketorolac could facilitate the recovery process after anorectal surgical procedures. Methods After obtaining institutional review board approval, 105 consenting, ASA physical status I and II outpatients scheduled for minor anorectal surgical procedures were randomly assigned to one of three study groups according to a double-blinded protocol. The three study groups consisted of Control (saline), IV ketorolac, and local ketorolac. Patients with a history of sensitivity to NSAIDs, gastrointestinal bleeding, or renal impairment were excluded. On arrival in the operating room (OR), patients were administered diazepam emulsion, 5–10 mg IV, and then positioned in either the prone or lithotomy position. Standard monitors were placed, and oxygen (2 L/min) was administered through nasal cannulae with a CO2 sampling port. Before the start of surgery, patients received: 1) Control group: 2 mL saline IV and 2 mL of saline mixed with the local anesthetic solution, 2) IV ketorolac group: 2 mL (60 mg) ketorolac IV and 2 mL saline mixed with the local anesthetic solution, and 3) Local ketorolac group: 2 mL saline IV and 2 mL of ketorolac (60 mg) mixed with the anesthetic solution. Propofol, 50–100 μg · kg−1 · min−1 IV, was administered to maintain an Observer’s Assessment of Alertness/Sedation score (9) of 2 or 3 (with 5 = awake/alert to 1 = asleep). Lidocaine gel 2% was then topically applied to the anodermal area with a large cotton applicator. Fentanyl, 25 μg IV, was administered 3–5 min before infiltrating the surgical field with 35 mL of a mixture containing lidocaine 1% and bupivacaine 0.25% with epinephrine 1/200,000 and sodium bicarbonate 4.2% (3 mL). Patient discomfort during the surgical procedure was treated with boluses of fentanyl, 25 μg IV At the end of the surgical procedure, the propofol infusion was discontinued. If the patient achieved a fast-track score of 12 or more (i.e., awake, alert, oriented, able to purposely move extremities, with stable vital signs and minimal pain, and without intractable symptoms of nausea or vomiting) (10) on leaving the OR, they were transported directly to the day-surgery (Phase II) recovery area. The degree of postoperative pain was assessed on arrival in the recovery unit by using a descriptive scale (0=none to 3=severe) and a 10-cm linear visual analog scale (VAS), with 0 = no pain to 10 = worst pain imaginable. The postoperative analgesic requirement was assessed before discharge home. Recovery times were recorded from discontinuation of the propofol infusion until the patient was able to tolerate oral fluids, walk unassisted (ambulation time), and be discharged home. Discharge criteria required that the patient be awake, alert, with stable vital signs on sitting and standing, and be able to walk without assistance. Voiding was not a prerequisite for discharge home. A predischarge questionnaire was completed by each patient to assess their quality of recovery (QoR) score (11). Additionally, a global QoR score (11) was also obtained from each patient before discharge home by using a 10-cm linear VAS, with 0 = poor recovery and 10 = excellent recovery. Oral hydrocodone (2.5 mg) with acetaminophen (500 mg) was prescribed for pain control after discharge. Finally, a follow-up evaluation was performed via telephone at 24 h and in the Proctology Clinic 10 days after surgery. Data analysis consisted of Number Cruncher Statistical Systems (NCSS, Kaysville, UT) version 6.0, one-way analysis of variance for all continuous variables. When significant differences were noted, the Newman-Keuls test was performed for post hoc intergroup comparisons. The VAS scores were analyzed by using the Kruskal-Wallis test, and if a significant result was obtained, Wilcoxon’s ranked sum test was performed. Categorical (discrete) variables were analyzed by using the χ2 test. Data were presented as mean values ± sd, numbers, or percentages, with P values < 0.05 considered statistically significant. Results The three study groups were comparable with respect to age, weight, height, sex, ASA physical status, and HIV status (Table 1). The types of surgical procedures (e.g., hemorrhoidectomy, pilonidal cyst excision, fistulotomy, anal condyloma fulguration, and sphincterotomy) were evenly distributed among the three study groups. There were also no differences in the durations of surgery and anesthesia, the intraoperative fentanyl and propofol dosage requirements, or in the volume of intraoperative IV fluids (Table 2).Table 1: Demographic Data for the Three Study GroupsTable 2: Surgery and Anesthesia Duration, Intraoperative Anesthetic, Analgesic, and IV Fluids RequirementsAll patients achieved an Observer’s Assessment of Alertness/Sedation score of 5 and a fast-track score of 12 or more before leaving the OR. The Local ketorolac group had lower VAS pain scores than the Control group on arrival in the Phase II recovery unit (Table 3). There were no episodes of postoperative nausea and vomiting in any of the treatment groups. Compared with the Control group, fewer patients in the IV and Local ketorolac groups experienced pain (37% vs 6% and 6%, respectively) and required oral analgesics (20% vs 3% and 0%, respectively) before discharge home. No antiemetic medication or supplemental oxygen was required after surgery. Although the time required for oral intake and ambulation were comparable (Table 3), the time to discharge home was significantly shorter when ketorolac was infiltrated locally at the surgical site compared with the Control group (Table 3). Of importance, the patients in the Control group also had significantly lower QoR scores than the IV and Local ketorolac groups (Table 3).Table 3: Postoperative Pain and Recovery Scores, Recovery and Discharge Times, Analgesic Requirements, and Postdischarge Side EffectsCompared with the Control group, fewer patients in the two ketorolac groups required oral analgesic medication during the first 24 h after discharge (Table 3). However, the incidence of wound infections was similar in the three study groups at the 10-day follow-up visit. In addition, the incidences of hematoma formation, bleeding with bowel movements, and urinary difficulty were similar in all groups (Table 3). Discussion Some colorectal surgeons have been reluctant to embrace the concept of day surgery for anorectal procedures because of the perceived difficulty in providing adequate postoperative pain relief (12). Although ketorolac decreases the need for postoperative opioid analgesic medication after ambulatory surgery (2–4), some investigators have been unable to demonstrate an improvement in clinically meaningful outcome variables [e.g., time to discharge home and QoR (13,14)]. This study provides evidence to support the concept that the use of even a single dose of ketorolac during surgery can improve the recovery profile after anorectal procedures in the ambulatory setting. The controversy regarding the optimal route of administration of ketorolac resulted, in part, because of the differential effects of the drug on the central (spinal cord) and peripheral nervous systems (15). Reuben and Connelly (4), Reuben et al. (16), Reuben and Duprat (17), and Connelly et al. (7) have suggested that the effectiveness of ketorolac is enhanced when injected at the site of the surgical incision. For example, these investigators have reported that injecting ketorolac (60 mg) directly at the surgical site in patients undergoing inguinal hernia repair produces superior analgesia compared with the parenteral (IV) route of administration (7). Although no randomized, placebo-controlled studies using locally administered ketorolac during anorectal surgery have been published, our results suggest that injection of ketorolac at the surgical site may produce a slight advantage over systemic administration with respect to discharge time. Perhaps the slower absorption after local injection produces a more sustained analgesic effect in the postoperative period. When administered systemically during outpatient gynecologic surgery, ketorolac was not associated with an increase in side effects and facilitated an earlier discharge compared with opioid and partial opioid agonist drugs (2). This placebo-controlled, double-blinded study demonstrated a significant reduction in postoperative pain when ketorolac 60 mg was administered either IV or locally before anorectal surgery. However, with respect to the postoperative VAS pain scores and discharge times, the only statistically significant differences compared with the Control group were in the Local ketorolac group. The differences may have been minimized because all three study groups received local anesthesia at the surgical site. Although all patients achieved fast-track criteria (18) in the OR, the ketorolac-treated patients required significantly less oral analgesic medication both before and after discharge home. More importantly, ketorolac improved the QoR from the perspective of the patient without producing side effects or postdischarge complications. In conclusion, ketorolac (60 mg) administered either IV or locally as part of the local anesthetic mixture, improved postoperative pain control and the QoR after outpatient anorectal surgery.