Use of ketorolac has become more widespread because of a demonstrable ability to improve pain scores and reduce opioid requirements, but there continues to be some concern over perioperative adverse effects related to its anti-inflammatory properties. However, as a recent literature review has shown, ketorolac has shown a favorable side effect profile with respect to bone healing, kidney function and unwanted bleeding.
According to Lawrence S. Lipana, MD, a resident physician at Yale New Haven Hospital, in Connecticut, concerns about ketorolac’s side effect profile arise from its mechanism of action, which inhibits cyclooxygenase and decreases prostaglandin production, thereby decreasing inflammation. This helps to reduce pain, but it could theoretically impair bone healing, cause unwanted bleeding and harm kidneys.
Given these opposing viewpoints, the researchers sought to review clinical studies addressing the safety of the agent, with an eye toward ultimately providing evidence-based recommendations for ketorolac’s use in the surgical setting.
Deep Literature Review
As Dr. Lipana reported at the 2016 annual meeting of the American Society of Anesthesiologists (abstract A2015), the investigators searched the literature for relevant clinical trials, retrospective studies and meta-analyses published in the last 10 years. With respect to bone healing, the analysis revealed that standard use of ketorolac has not been shown to affect fracture union. While studies have, indeed, demonstrated a negative effect on bone healing, these trials were either associated with sev eral weeks of prolonged ketorolac use or as much as four times the dose commonly used in clinical practice.
“We found that the studies that show increased nonunion rates also did not control for the types of surgery, length of use and dose,” Dr. Lipana said. “We also looked at recent animal studies—as well as soft tissue studies involving meniscal repair—and found that Toradol was safe in these situations when used below the maximum daily dose of less than 60 mg IV per day.”
The researchers also examined kidney function, concluding that patients with normal preoperative kidney function who receive nonsteroidal anti-inflammatory drugs have not been shown to develop renal failure severe enough to require dialysis, and do not experience statistically significant decreases in urine output. What’s more, long-term data show no impairment in renal function despite initial decreases in creatinine clearance and increased serum creatinine within the first month of recovery.
“Interestingly enough, studies show that even donor kidneys seem to tolerate ketorolac with no long-term impairment in renal function,” Dr. Lipana added.
The researchers found bleeding—a devastating complication of surgery—to be one of the most studied potential side effects of ketorolac use. Of interest, meta-analyses have not demonstrated an increased risk for bleeding with ketorolac use in various surgical procedures—even in high-risk procedures such as cardiac and neurologic surgery. However, patients undergoing tonsillectomies demonstrated increased risk for adverse bleeding, as did elderly individuals receiving high-dose ketorolac.
Given these findings, the researchers recommended that otherwise healthy patients can safely receive normal doses of ketorolac in the immediate postoperative period. “We recommend that before you make a decision, you look deeper into the studies that comprise current guidelines,” Dr. Lipana added.
“Hopefully I’ve convinced you that giving a 30-mg dose of Toradol at the end of a case appears to be safe in virtually all situations.” This does not mean, however, that the drug can be used indiscriminately, as certain surgical and medical situations necessitate additional caution, particularly patients with comorbid kidney, heart and liver disease.
“Just this week I had a patient who underwent a left nephrectomy,” reported Mark P. Ramirez, MD, a staff anesthesiologist at a Community Health Systems hospital in Oro Valley, Ariz. “We did not give Toradol because we were concerned about renal function in the healthy kidney. Is that reasonable in your opinion, or were we just being overly cautious?”
“Our feeling is that it’s absolutely safe,” Dr. Lipana replied.
“So even in that case you would still give Toradol?” Dr. Ramirez asked.
“Yes,” Dr. Lipana replied. “Even in fracture cases and orthopedic procedures, we found that ketorolac can reduce hospital stay by at least a day.”
Despite these findings, convincing other health practitioners to incorporate ketorolac into their practice is not always a sure thing, and requires communication and education. “The side effect that surgeons talk about most is bleeding,” Dr. Lipana said.
“It’s our job to teach the surgeons,” said Nalini Vadivelu, MBBS, DNB, associate professor of anesthesiology at Yale New Haven Hospital. “The way we see it, we are a team. So if the surgeons say they are scared because it’s their patient, we have to respect that. We did this study so we could help educate them.”
“If you look at it from their perspective,” Dr. Lipana added, “if there is a bleeding issue, the patient isn’t going to call us. They’re going to call the surgeon.”