Ketorolac for pain management after abdominal surgical procedures in infants.

ABSTRACT

Background. While the use of intravenous ketorolac in infants less than 6 months old has not been previously reported, ketorolac may reduce opioid use and prevent opioid-associated side effects that are frequent in this age group. We reviewed our experience with ketorolac in infants to develop recommendations for using it after abdominal surgery.

Methods. We reviewed the records of 10 infants less than 6 months old who received ketorolac supplemented with morphine and 8 infants who received morphine alone for pain after abdominal surgery.

Results. Infants receiving ketorolac required less morphine than infants receiving morphine alone in the first 48 hours after surgery. Four patients receiving ketorolac did not require any supplemental morphine.

Conclusions. Ketorolac reduces the amount of morphine required after abdominal surgery in infants less than 6 months old. The use of ketorolac deserves further study as a method of reducing opioid-associated adverse effects in this patient group.

KETOROLAC TROMETHAMINE (Toradol, Roche Pharmaceuticals), a nonsteroidal anti-inflammatory agent, has been shown to be effective in relieving moderate postoperative pain in children. (1-4) Because ketorolac can reduce opioid requirements after surgical procedures, it may prevent undesirable opioid-related effects on respiratory, cardiovascular, central nervous system, genitourinary, and gastrointestinal function. (5) Pain control in infants less than 6 months old is often difficult in particular because of concerns of respiratory depression after the administration of opioids. In this study, we report the use of intravenous ketorolac in infants less than 6 months old having abdominal surgical procedures. On the basis of this initial experience, we have developed recommendations for the effective use of ketorolac in this patient population.

METHODS

This study was approved by the Institutional Review Board at the University of Missouri- Columbia Hospitals and Clinics. The medical records of 10 consecutive extubated infants less than 6 months old who received ketorolac supplemented with intermittent intravenous boluses of morphine sulfate for pain management after abdominal surgery from December 1998 to December 1999 were retrospectively reviewed. A group of 8 infants who received intermittent intravenous boluses of morphine sulfate alone for pain management after abdominal procedures over a similar period served as a control group. All patients were operated on and were under the care of the same surgeon. In both groups, morphine sulfate was given at a dose of 0.1 mg/kg every 2 to 3 hours, according to a pain scoring system. (6) No patient received local anesthesia in the wound or caudal medications. Data recorded included age, postconceptual age, weight, operative procedure, amount of either ketorolac or morphine administered, urine output, episodes of vomiting, and time of first bowel movement (resolution of postoperative ileus). Using the CRIES score (6) prospectively, the bedside nurse assessed pain at least every 4 hours. CRIES is a pain scoring system based on physiologic and behavioral variables associated. with postoperative neonatal pain. This pain scale was developed at our institution and is used for all infants in the postoperative period. The validity and reliability of this score in infants up to 6 months old has been previously reported. (6) Charts were reviewed for potential complications associated with ketorolac administration, including bleeding (hematemesis, melena, wound hematoma, or postoperative transfusion), renal insufficiency, thrombocytopenia, purpura, and skin rash. Parametric data were expressed as mean [+ or -] SD and were analyzed using the unpaired, two-tailed Student's t test. The maximum CRIES scores for each 12-hour period were compared using the Mann-Whitney U test with significance defined at P<.05.

RESULTS

A comparison of patients receiving ketorolac plus morphine sulfate and those receiving morphine sulfate alone is shown in the Table. Age, postconceptual age, weight, procedures done, and length of stay were similar in each group. CRIES scores were not different between the two groups. Infants receiving ketorolac required less morphine sulfate than infants receiving morphine sulfate alone (0.04 [+ or -] 0.05 versus 0.15 [+ or -] 0.06 mg/kg/day, P< .01, Table) during the first 48 hours after surgery. Four patients who received ketorolac required no supplementation with morphine sulfate. Patients received 1.1 [+ or -] 0.4 mg/kg/day (range, 1.0 to 1.5 mg/kg/day) of ketorolac for up to 48 hours postoperatively. Ketorolac was administered intravenously at 0.5 mg/kg every 8 hours in 8 patients and every 12 hours in 2 patients on a fixed schedule. Two patients receiving ketorolac plus morphine sulfate and two patients receiving morphine sulfate alone had transient episodes of apnea within the first 12 hours after sur gery. Postoperative bleeding, renal insufficiency, or skin change was not observed in either group. Vomiting was observed in one patient receiving morphine sulfate alone. No difference in time to first bowel movement (resolution of postoperative ileus) was observed (Table).

DISCUSSION

Ketorolac is a nonsteroid anti-inflammatory medication that has been shown to be effective for the management of mild to moderate postoperative pain. (1-4) The efficacy of this medication in older children after major surgical procedures has been shown previously. In a report by Bean-Lijewski and Hunt, (1) children receiving ketorolac after general, orthopedic, or genitourinary procedures required less meperidine postoperatively. No differences in length of stay or in opioid-associated effects were seen in children treated with meperidine alone or ketorolac plus meperidine in this study. Gonzalez and Smith (3) found that ketorolac reduced length of stay while providing adequate postoperative analgesia after uretero-neocystostomy in children as young as 10 weeks old. Eberson et al (4) described the use of ketorolac after orthopedic procedures in patients aged 6 months to 18 years and found that ketorolac significantly decreased opioid-related complications and postoperative length of stay. On the basis of thes e favorable findings, we sought to determine whether these observations could be extended to infants less than 6 months old having elective and emergency abdominal procedures.

In this study, we focused on the efficacy of ketorolac in the first 48 hours postoperatively because (1) infants frequently do not require intravenous analgesics more than 48 hours after laparotomy, and (2) ketorolac was given for no more than 48 hours after surgery. Our data show that the use of ketorolac can significantly reduce opioid requirements after abdominal surgical procedures in infants while providing equivalent analgesia. In four patients, ketorolac was the only analgesic required, further demonstrating the efficacy of this medication for pain management after laparotomy. Although the number of patients in each group was not large enough to compare opioid-associated side effects, previous studies have shown that a reduction in opioid administration may significantly reduce or eliminate adverse effects. (5)

Because ketorolac can significantly prolong bleeding time, we have avoided ketorolac use in any infant at risk for bleeding complications. (1) Premature infants (postconceptual age less than 37 weeks) who are at risk for intra-ventricular hemorrhage, infants with preoperative evidence of upper or lower gastrointestinal bleeding, and infants with peritonitis or other uncontrolled sites of serious infection that may be associated with coagulopathy did not receive ketorolac. The susceptibility of premature infants to renal injury from nonsteroidal anti-inflammatory medications also suggests that ketorolac should be avoided in this group. (7) To further reduce the risk of adverse effects, the duration of ketorolac use should be limited to only 24 to 72 hours postoperatively. Although previous studies of ketorolac use in children have reported using doses as high as 0.5 mg/kg every 6 hours, the maximum dose of ketorolac used in the current study was 0.5 mg/kg every 8 hours. (1-5) Based on our initial experience, we recommend dosing ketorolac at 0.5 mg/kg every 8 hours for up to 1 or 2 days after surgery.

In summary, ketorolac significantly reduced morphine sulfate requirements in infants less than 6 months old having laparotomy. The use of ketorolac deserves further study as a method to reduce opioid-associated adverse effects in this patient group.

TABLE

Comparison of infants Receiving Ketorolace Plus Morphine Sulfate or
Morphine Sulfate Alone After Major Abdominal Surgical Procedures

                            Ketorolac and
                             Morphine (*)

No, of patients                  10
Age (weeks)                    3 [+ or -] 4 (range 0-11)
Postconceptual age (weeks)    40 [+ or -] 3 (range 37-49)
Weight (kg)                  3.2 [+ or -] 0.9
Amount of morphine          0.04 [+ or -] 0.05
 given in 48 hours
 (mg/kg/day)
Time of first bowel
 movement (days)             1.4 [+ or -] 0.6

                            Morphine                       P Value
                             Alone (+)

No, of patients                  8
Age (weeks)                    7 [+ or -] 7 (range 1-19)     NS
Postconceptual age (weeks)    44 [+ or -] 6 (range 37-54)    NS
Weight (kg)                  3.7 [+ or -] 1.2                NS
Amount of morphine          0.15 [+ or -] 0.06             <.001
 given in 48 hours
 (mg/kg/day)
Time of first bowel
 movement (days)             1.7 [+ or -] 1.1                NS

(*)Operations done: stoma formation (5), repair of intestinal atresia,
(1), Nissen fundoplication (1).

(+)Operations done: stoma formation (2), intestinal resection and
anastamosis (2), portoenterostomy (1), pyloroplasty (1), exploratory
laparotomy (1).

NS = Not significant.

References

(1.) Bean-Lijewski JD, Hunt RD: Effect of ketorolac on bleeding time and postoperative pain in children: a double-blind, placebo-controlled comparison with meperidine. J Clin Anesth 1996; 8:25-30

(2.) Purday JP, Reichert CC, Merrick PM: comparative effects of three doses of intravenous ketorolac or morphine on emesis and analgesia for restorative dental surgery in children. Can J Anaesth 1996; 43:221-225

(3.) Gozalez A, Smith DP: Minimizing hospital length of stay in children undergoing ureteroneocystostomy. Urology 1998; 52:501-504

(4.) Eberson GP, Pacicca DM, Ehrlich MG: The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patients. J Pediatr Orthop 1999; 19:688-692

(5.) Romsing J, Walther-Larsen S: Peri-operative use of nonsteroidal anti-inflammatory drugs in children: analgesic efficacy and bleeding. Anaesthesia 1997; 52:673-683

(6.) Krechel SW, Bildner J: CRIES: a new neonatal postoperative pain measurement score. initial testing of validity and reliability. Paediatr Annesth 1995; 5:53-61

(7.) van Bel F, Guit GL, Schipper J, et al: Indomethacin-induced changes in renal blood flow velocity waveform in premature infants investigated with color Doppler imaging. J Pediatr 1991; 118:621-626

RELATED ARTICLE: KEY POINTS

* Ketorolac can significantly reduce opioid requirements after abdominal surgical procedures in infants less than 6 months old.

* Initial observations suggest that ketorolac should be dosed at 0.5 mg/kg intravenously every 8 hours for up to 1 or 2 days after surgery.

* It is recommended that ketorolac not be used in infants who are premature, with active surgical site bleeding or with known or suspected coagulopathy.

From the Departments of Surgery, Anesthesiology, and Child Health, Children's Hospital at University of Missouri Hospitals and Clinics, Columbia.

Reprint requests to Randall S. Burd, MD, PhD, Robert wood Johnson Medical School, Pediatric Surgery, MEB 4th Floor, One Robert wood Johnson P1, New Brunswick, NJ 08903.