Safety Evaluation of IVIB
All NSAIDs contain label warnings and precautions regarding the risk of gastrointestinal bleeding or ulceration, cardiovascular risks, renal and hepatic injury, and bleeding related to platelet dysfunction (67, 68). Nevertheless, these AEs are predominantly connected to long-term drug use, whereas acute perioperative use of NSAIDs is considered relatively safe. Overall, IVIB had not demonstrated increased risk of SAEs, including hematological and renal system, in pain and fever management according to our analyses. It showed a decreased risk of nausea or vomiting, probably owing to the lower cumulative consumption of opioid medication in multimodal analgesia management (69). Furthermore, the elderly patients who received IVIB also experienced far fewer AEs overall (59%) than did those receiving placebo (94%) (50 ). In pediatric population, the majority of AEs were mild to moderate, and there was no significant difference between IVIB and intravenous acetaminophen (70, 71).
It is worth mentioning that several studies have investigated the safety of single and multiple doses of IVIB administered over 5 to 10 minutes other than 30 minutes recommended for the treatment of postoperative pain in health adults. They found that 22%~29% of patients experienced AEs, and the most common AE was infusion site pain (11%~15%). No deaths or IVIB-related SAEs were reported (72, 73). Also, studies assessed the safety and acceptability of 5- to 10-minute infusion of IVIB and found that it appeared a faster efficacy in reducing fever compared to acetaminophen administered at a regular pace (41, 66). IVIB rapid infusion was therefore proved be well tolerated and proved additional benefits in the perioperative period and emergent situations.