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ORIGINAL RESEARCH

Ketorolac Use in the National Football League

Prevalence, Efficacy, and Adverse Effects

John M. Tokish, MD; Elisha T. Powell, MD;
Theodore F. Schlegel, MD; Richard J. Hawkins, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 30 - NO. 9 - SEPTEMBER 2002


ABSTRACT

BACKGROUND: Ketorolac tromethamine is an effective NSAID for short-term relief of acute pain and can be given in oral, intravenous, and intramuscular doses. Although anecdotal reports document intramuscular ketorolac use in athletes, no study has assessed ketorolac use in a population of elite contact-sport athletes.

OBJECTIVE: This study sought to determine usage patterns, effectiveness, and possible adverse events with the use of ketorolac among National Football League (NFL) players.

METHODS: Survey forms were sent to the head team physician and head athletic trainer of each of the 31 NFL teams. Information sought included ketorolac use, logistics, effectiveness, safety, and adverse outcomes.

RESULTS: Thirty of 31 (97%) teams responded. Twenty-eight of 30 (93%) teams used ketorolac during the 2000 season. Teams that used the drug treated an average of 15 players (range, 2 to 35). The vast majority of teams (93%) used the medication on game day. Most medical staffs found that a single injection alleviated 50% to 75% of a player's pain and lasted 1 to 2 days. Most staffs (24/27, 89%) stated that they would give ketorolac up to once a week during the season. Six of 28 (21%) teams reported an adverse experience with ketorolac use. These included 4 isolated muscle injuries, 1 gastrointestinal disturbance, and 1 instance of next-day postinjection soreness. Several teams also expressed concern about psychological dependence by players. Although many medical staffs were concerned about possible bleeding complications and kidney damage, neither was reported.

CONCLUSIONS: These data suggest that ketorolac use is very common in the NFL. Most team healthcare providers believe that the drug is an effective pain reliever and are comfortable with weekly use during the season. Although isolated adverse events have been noted, most team providers feel that ketorolac is safe when the team physician directs its use.

Ketorolac tromethamine is widely used to treat acute pain and can be given in oral, intravenous (IV), and intramuscular (IM) forms. In some studies,1,2 it has shown better relief of postoperative pain than traditional narcotics. Although IM administration of ketorolac has been studied in outpatient settings,2-6 we know of no study that evaluates its use in athletes.

Use of pain relievers is common in professional sports, especially football. Although playing with pain is accepted as an occupational necessity for players, managing pain is an important role of the team physician and athletic trainer. This role has led some National Football League (NFL) team physicians to use ketorolac, an IM nonsteroidal anti-inflammatory drug (NSAID), for the treatment of acute pain. Because the drug has the potential for complications such as bleeding7 and renal damage,8 some physicians have raised concerns about its use in contact-sport athletes. We sought to survey all NFL team medical staffs to determine ketorolac use, policy, and experience.

Materials and Methods

We mailed questionnaires about ketorolac use (NFL Physicians' Society Questionnaire, table 1) to the head team physician and the head athletic trainer of each of the 31 teams in the NFL. For the few times there was disagreement between physician and trainer answers on quantitative questions, the two responses were averaged. If the medical staff had administered the drug for pain control in their players during the 2000 season, subsequent questions sought information about the logistics of administration.

TABLE 1. NFL Physicians Society Questionnaire on Ketorolac* Use

1.Have you treated any NFL player with ketorolac? ___yes ___no
2.Do you treat NFL players with ketorolac during the season? ___yes ___no
3.How many different players on your team have you treated with ketorolac during this season? __________________
4.In those players that you have treated with ketorolac, when do you give it?
(eg, day of game, day after game, 1 day before, 2 days before, etc) _______________________________________
5.What is your sense of how much relief players get with a single injection of ketorolac?
A: 0% to 25% relief; B: 26% to 50%; C: 51% to 75%; D: 76% to 100% ____________________________________
6.How long does the above benefit of a single injection last?
A: <24 hr; B: 24 to 48 hr; C: 48 to 72 hr; D: >72 hr ____________________________________________________
7.How often would you feel comfortable giving a player a ketorolac injection during the season?
A: Once a week; B: Once every 2 wk; C: Once every month;
D: Other (Please fill in) __________________________________________________________________________
8.Is there a maximum number of injections that you would give to a player during the course of a season?

____________________________________________________________________________________________

9.In your experience, are there any contraindications to using ketorolac for soreness, pain, or stiffness in players?

____________________________________________________________________________________________

10.Have you had any player experience any adverse outcome that you feel was related to the use of ketorolac?

___yes ___no

11.If you answered yes to question 10, please list the adverse outcome below.

____________________________________________________________________________________________

____________________________________________________________________________________________

12.Are there any other opinions or experiences that you have had with ketorolac that you feel are important to get to other physicians that may manage contact athletes?

____________________________________________________________________________________________

____________________________________________________________________________________________

13.There have recently been anecdotal reports of kidney failure and bleeding concerns with this drug. Have you experienced this with your team? Have these reports changed your practice with regard to the use of ketorolac?

____________________________________________________________________________________________

____________________________________________________________________________________________

*The original questionnaire used the brand name Toradol.

Other questions asked about the effectiveness of a single injection of ketorolac and about policies for repeated injections. The final questions concerned staff experience with the drug's safety, and staff members were encouraged to relate any adverse experiences associated with its use. After the initial mailing, nonresponding staffs were sent a duplicate survey to encourage participation.

Survey results were compiled and analyzed at the Steadman Hawkins Foundation in Vail, Colorado, and at the United States Air Force Academy in Colorado Springs. Responses were tallied, and percentages of responses were computed for each question.

Results

Thirty of 31 teams (97%) responded to the questionnaire, and 28 (93%) stated that they had used ketorolac during the 2000 season. The two remaining teams had strong policies against its use, citing potential complications, including renal failure and increased risk of bleeding. On teams that used the drug, an average of 15 players (range, 2 to 35) were treated. Twenty-six of 28 teams (93%) used ketorolac on game day, 1 team had a policy of no use within 48 hours of games, and 1 had a policy of no use within 12 hours of games.

Effectiveness. Respondents were asked to comment on how much relief a single injection of ketorolac provided; possible responses were in quartile percentages. Of the 26 teams that responded to this question, 11 cited relief between 26% to 50%, and 11 teams cited relief between 51% to 75%. Two teams reported that a single injection provided less than 25% relief, while 2 teams stated that relief was near complete with a single injection.

Twenty-eight teams responded to the question "How long does the above benefit of a single injection last?" Seventeen (61%) teams stated that players received between 0 to 24 hours of relief, while 9 (32%) felt players experienced 24 to 48 hours of relief. Two teams (7%) felt players received 48 to 72 hours of relief from injections. Twenty-four of 27 teams (89%) stated that they would allow a player one injection per week throughout the season. The remaining 3 teams limited injections to once every 2 weeks or once a month, or allowed use at the discretion of the treating physician.

Adverse outcomes. Several teams (6/28, 21%) each reported one adverse outcome related to ketorolac use. Four teams noted muscle injury, including strain, pull, or worsening of a contusion that the staff attributed to ketorolac. In addition, 1 team documented a case of gastrointestinal (GI) upset that resolved with cessation of ketorolac use, and 1 team reported that a player had increased generalized soreness 1 day after injection. Several teams followed up ketorolac use with serial blood workups, including coagulation and renal profiles. No team reported a renal or hematologic complication associated with ketorolac, although many were aware of this potential side effect. One team denied a player's request for the drug because he had a history of bleeding ulcers. In addition, several teams reported their concern about possible psychological addiction among certain players, and several teams now have policies about acceptable frequency of use.

Discussion

Ketorolac is effective in treating acute pain.1-3,9 IM ketorolac has an onset within 10 minutes, reaches its peak in the plasma at 50 minutes, and has a half-life of 6.5 hours in young adults.10 The drug is 99% plasma bound, metabolized in the liver, and almost entirely excreted by the kidneys. These kinetics suggest a rapid turnover, with more than 90% of the drug clearing the system within 1 day. When given intramuscularly, the recommended dose is 30 mg to 60 mg, according to individual physician preference. Contraindications include NSAID hypersensitivity, a history of bleeding ulcers, and renal or hepatic failure. Side effects include vasodilatation, headache, asthma, increased risk of bleeding, and kidney dysfunction.

Many studies have investigated the pain-relieving effectiveness of IM ketorolac in the acute postoperative period. McGuire et al2 evaluated ketorolac and the opioids meperidine and morphine. They concluded that ketorolac was as effective, and in some cases more effective, than either opioid for pain control after anterior cruciate ligament (ACL) reconstruction. In addition, they found that side effects such as nausea and vomiting were reduced and that the cost was also lower than with opioids. Barber and Gladu1 found similar results when they compared pain relief among patients taking either ketorolac or hydrocodone and acetaminophen after outpatient ACL reconstruction. Patients given ketorolac had significantly lower pain scores than those given the other drugs. In addition, ketorolac was no more likely to cause GI complaints than the narcotics, and neither treatment caused any bleeding complications. Other studies9,11 concur with these findings.

Outpatient therapy. In a double-blinded, prospective trial of ketorolac versus meperidine for severe musculoskeletal low-back pain in emergency patients, Veenema et al4 found ketorolac as effective as meperidine for pain relief. In addition, the ketorolac group showed a decreased incidence of sedation and adverse effects. In a similarly designed study, Innes et al6 compared ketorolac with acetaminophen-codeine for treating acute low-back pain in emergency-department patients from six hospitals. The authors concluded that ketorolac gave equivalent pain relief with significantly fewer adverse events than acetaminophen-codeine.

In contrast to these studies, Neighbor and Puntillo5 found that a single, 60-mg dose of IM ketorolac was no more effective than a single, 800-mg dose of oral ibuprofen for treating acute pain in urban emergency-department patients. In our study, 24 of 26 teams that responded to the question felt ketorolac was an effective pain reliever, although there was no comparison with any other pain reliever. (Effectiveness was defined as more than 25% pain relief.)

Injection effect. Anecdotally, some medical staffs felt that IM ketorolac was superior to other NSAIDs because of its route of administration. Many staffs felt that players perceived "getting a shot" as an intrinsic sign that they were receiving more powerful medicine. This perception has been addressed elsewhere with conflicting results.12 Schwartz et al12 compared the effects of a placebo saline injection resembling 60 mg of ketorolac with that of a placebo starch tablet resembling 800 mg of ibuprofen. Both placebos were administered after an initial dose of ibuprofen in patients with acute trauma pain. Patients and research nurses were blinded to the initial ibuprofen dose and the placebos. Pain was evaluated at 30-minute intervals for 120 minutes using visual analog scales. The investigators found no difference between the two protocols and concluded that an IM administration did not confer a placebo effect over an oral route. They also stated that routine use of IM-administered NSAIDs for suspected enhanced analgesia appears unwarranted. Further study of the effects of route of administration on pain relief is warranted.

Renal complications. Many authors have raised concerns regarding the safety of IM ketorolac.8,13-16 One of the most significant concerns is the rare risk of acute renal failure, in some instances with even a single dose.13 Although many authors raise the theoretical concern of renal failure with ketorolac use, most reports are of isolated cases or small series. Single case reports13,15 have been published, and Pearce et al17 and Haragsim et al8 have reported three cases of renal failure with or without hyperkalemia after ketorolac use.

Few large studies of the risk of renal failure with ketorolac use have been done. Feldman et al14 compared ketorolac with opioid use in a multicenter trial of more than 20,000 patients and found a 1.1% incidence of acute renal failure after therapy with either ketorolac or opioids. When comparing therapies based on length of treatment, there was no increased risk of acute renal failure with ketorolac as long as treatment was less than 5 days. Longer ketorolac treatment, however, showed an increased risk of renal failure compared with opioids. The authors cautioned against the longer regimen (more than 5 days).

In our study, no patient had renal failure during treatment with ketorolac. No patient was treated with a prolonged course (3 injections administered over 12 days was the maximum). It should be noted that professional football players are likely different from the nonathletic patient populations in the previous studies.

More subtle forms of renal insufficiency with ketorolac use have also been investigated. Corelli and Gericke18 performed a retrospective chart review of renal toxicity from ketorolac administration. They identified 6 patients who met their definition (renal insufficiency related to ketorolac, resolution of renal insufficiency after ketorolac use, and no other cause of renal insufficiency), 5 of whom had preexisting cardiovascular disease. Serum creatinine values increased from a mean of 1.2 ± 0.3 mg/dL to 2.9 ± 2.2 mg/dL after ketorolac use. Renal function normalized 2 days after cessation of drug use. The authors concluded that ketorolac use can be associated with reversible renal insufficiency, and they recommended caution with using the drug.

Finally, in a meta-analysis of the effects of NSAIDs (including ketorolac) on postoperative renal function, Lee et al19 found that these drugs imparted a statistically significant but clinically unimportant transient reduction in renal function. They concluded that NSAIDs should not be withheld from patients with normal renal function because of concerns about postoperative renal impairment. Our surveys did not contain any report of renal insufficiency, but few patients who received ketorolac had laboratory analyses done.

Hemorrhage. Another concern is anticoagulatory effects leading to hemorrhage, especially in the elite contact-sport athlete. Mynster and Singer20 investigated the effects of IM ketorolac on bleeding times in 20 healthy volunteers. The authors found that a single IM injection (60 mg of ketorolac) resulted in a 50% prolongation of bleeding times 4 hours after injection, but they did not speculate on whether this phenomenon is clinically significant. In another study that compared intravenous ketoprofen, ketorolac, and diclofenac on platelet function, Niemi et al21 found that all three NSAIDs caused reversible platelet dysfunction. Ketorolac had the most lasting effect, with platelet dysfunction persisting 24 hours after use.

The clinical significance of such findings are mixed. Fragen et al22 found a statistically significant but clinically unimportant reduction in hematocrit in patients undergoing total knee arthroplasty who were given ketorolac. Sharma et al23 studied the risk of postoperative hematoma in patients using ketorolac after transverse rectus abdominis musculocutaneous resection breast reconstruction. They found no increase in hematoma formation. In another study, Milne et al24 detected no increased risk of extremity ecchymosis with ketorolac use in patients after ACL reconstruction.

In contrast to these results, Garcia Rodriguez et al7 investigated the risk of hospitalization for upper-GI bleeding associated with ketorolac against that of other NSAIDs. Ketorolac users had a relative risk of 5 compared with nonusers, and use was the most significant risk factor. Other NSAID users had a relative risk of 4.4 compared with nonusers. The authors concluded that ketorolac use carried an unfavorable risk-benefit profile compared with other NSAIDs and cautioned against the drug's routine use. Strom et al25 also investigated the risk of postoperative, clinically significant bleeding with ketorolac use. These authors found an increased risk of GI and operative-site bleeding, but the risk was dose- and duration-dependent, with patients treated for more than 5 days showing the highest risk of significant bleeding.

Our study found no significant bleeding complications. This may be due to the fact that ketorolac was generally administered as a single dose and usually no more often than once a week. Nevertheless, physicians should note that bleeding times and platelet function were not routinely assessed by most teams, and therefore subclinical manifestations may have been missed. In addition, given that bleeding times are prolonged by 50% 4 hours after a single dose, ketorolac administration on game day may deserve reconsideration in contact sports.

Where We Stand

Our experience would suggest that ketorolac appears effective and safe within the current use parameters. Contrary to one study,12 the anecdotal experience of NFL medical staffs suggests a significant psychological benefit to IM administration. Studies comparing ketorolac with other NSAIDs for pain relief and complications in an athletic population are lacking, which makes recommendations regarding its use difficult. As team physicians, we urge caution against the liberal use of injectable pain relievers that might mask pain, especially in nonprofessional, active patients. We recommend further study to develop standardized guidelines for ketorolac use in athletes to protect both players and staffs from potential complications.

References

  1. Barber FA, Gladu DE: Comparison of oral ketorolac and hydrocodone for pain relief after anterior cruciate ligament reconstruction. Arthroscopy 1998;14(6):605-612
  2. McGuire DA, Sanders K, Hendricks SD: Comparison of ketorolac and opioid analgesics in postoperative ACL reconstruction outpatient pain control. Arthroscopy 1993;9(6): 653-661
  3. Larkin GL, Peacock WF 4th, Pearl SM, et al: Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. Am J Emerg Med 1999;17(1):6-10
  4. Veenema KR, Leahey N, Schneider S: Ketorolac versus meperidine: ED treatment of severe musculoskeletal low back pain. Am J Emerg Med 2000;18(4):404-407
  5. Neighbor ML, Puntillo KA: Intramuscular ketorolac vs oral ibuprofen in emergency department patients with acute pain. Acad Emerg Med 1998;5(2):118-122
  6. Innes GD, Croskerry P, Worthington J, et al: Ketorolac versus acetaminophen-codeine in the emergency department treatment of acute low back pain. J Emerg Med 1998;16(4):549-556
  7. Garcia Rodriguez LA, Cattaruzzi C, Troncon MG, et al: Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. Arch Intern Med 1998;158(1):33-39
  8. Haragsim L, Dalal R, Bagga H, et al: Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. Am J Kidney Dis 1994;24(4):578-580
  9. Eberson CP, Pacicca DM, Ehrlich MG: The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient. J Pediatr Orthop 1999;19(5):688-692
  10. Physicians' Desk Reference, ed 56. Medical Economics, Montvale, NJ, 2002, pp 3018-3022
  11. Lieh-Lai MW, Kauffman RE, Uy HG, et al: A randomized comparison of ketorolac tromethamine and morphine for postoperative analgesia in critically ill children. Crit Care Med 1999;27(12):2786-2791
  12. Schwartz NA, Turturro MA, Istvan DJ, et al: Patients' perceptions of route of nonsteroidal anti-inflammatory drug administration and its effect on analgesia. Acad Emerg Med 2000;7(8):857-861
  13. Quan DJ, Kayser SR: Ketorolac induced acute renal failure following a single dose. J Toxicol Clin Toxicol 1994;32(3):305-309
  14. Feldman HI, Kinman JL, Berlin JA, et al: Parenteral ketorolac: the risk for acute renal failure. Ann Intern Med 1997;126(3):193-199
  15. Patel NY, Landercasper J: Ketorolac-induced postoperative acute renal failure: a case report. Wis Med J 1995;94(8):445-447
  16. Perazella MA, Buller GK: NSAID nephrotoxicity revisited: acute renal failure due to parenteral ketorolac. South Med J 1993;86(12):1421-1424
  17. Pearce CJ, Gonzalez FM, Wallin JD: Renal failure and hyperkalemia associated with ketorolac tromethamine. Arch Intern Med 1993;153(8):1000-1002
  18. Corelli RL, Gericke KR: Renal insufficiency associated with intramuscular administration of ketorolac tromethamine. Ann Pharmacother 1993;27(9):1055-1057
  19. Lee A, Cooper MG, Craig JC, et al: The effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on postoperative renal function: a meta-analysis. Anaesth Intensive Care 1999;27(6):574-580
  20. Mynster CJ, Singer AJ: Effect of intramuscular ketorolac on bleeding times, abstracted. Acad Emerg Med 2001;8(5):429
  21. Niemi TT, Taxell C, Rosenberg PH: Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. Acta Anaesthesiol Scand 1997;41(10):1353-1358
  22. Fragen RJ, Stulberg SD, Wixson R, et al: Effect of ketorolac tromethamine on bleeding and on requirements for analgesia after total knee arthroplasty. J Bone Joint Surg Am 1995;77(7):998-1002
  23. Sharma S, Chang DW, Koutz C, et al: Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction. Plast Reconstr Surg 2001;107(2):352-355
  24. Milne JC, Russell JA, Woods GW, et al: Effect of ketorolac tromethamine (Toradol) on ecchymosis following anterior cruciate ligament reconstruction. Am J Knee Surg 1995;8(1):24-27
  25. Strom BL, Berlin JA, Kinman JL, et al: Parenteral ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study. JAMA 1996;275(5):376-382


The opinions or assertions presented here are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Air Force or the Department of Defense.

Dr Tokish is a major and Dr Powell is a lieutenant colonel in the United States Air Force Medical Corps at the United States Air Force Academy in Colorado Springs. Dr Schlegel is a team physician and Dr Hawkins is head team physician of the NFL's Denver Broncos at the Steadman Hawkins Foundation in Vail, Colorado. Address correspondence to Richard J. Hawkins, MD, Steadman Hawkins Sports Medicine Foundation, 181 W Meadow Dr, Suite 1000, Vail, CO 81657; e-mail to [email protected].

Disclosure information: Drs Tokish, Powell, Schlegel, and Hawkins disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.


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