In more than 50 to 70% of cases, the leading cause of death due to trauma is brain damage [ 1 , 2 ]. Posttraumatic headache is a disabling secondary headache disorder often attributed to traumatic brain injury and affects millions of individuals worldwide [ 3 , 4 ]. Population-based data have shown that the lifetime prevalence of this disorder is estimated to be 4.7% in men and 2.4% in women [ 4 , 5 ]. Headache is the most common complaint in emergency departments [ 4 , 6 ].

This headache is a heterogeneous disorder, and patients may respond to different and specific treatments. The lack of evidence-based approaches has forced clinicians to choose treatment methods for primary headaches (migraines and tension headaches). A concerted effort to address these shortcomings is to conduct randomized controlled trial studies. This approach, in turn, leads to a better description of the disease and the availability of evidence-based treatment options [ 4 ].

In developing countries, morphine is mainly used in emergencies for pain relief in trauma patients despite known side effects. At the same time, acetaminophen and ketorolac intravenous (IV) are more suitable painkillers for trauma patients. However, the preference for the last two drugs is not clear. They consider that both drugs have their strengths and weaknesses [ 7 ]. Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that is used to reduce pain, fever, and inflammation; its use can be a substitute for the use of narcotic painkillers, and respiratory depression does not follow these drugs [ 8 , 9 , 10 ].

Recently, the FDA approved acetaminophen IV as an NSAID antipyretic and analgesic drug. This drug is faster and more effective than oral or rectal [ 10 , 11 ]. Studies have shown that acetaminophen IV has fewer side effects than opioids are preferred. Complications such as nausea, emesis, pruritus, hypotension, respiratory depression, constipation, and hepatotoxicity are less after the administration of this drug [ 12 , 13 ]. The results of a systematic review showed that acetaminophen IV has better pain reduction than IV morphine sulfate, especially in acute limb trauma and traumatic headache. However, more studies need to be done so that emergency medicine specialists can make better decisions about headache management in patients with head trauma [ 13 ].

A few studies have been conducted to compare the comparative efficacy of prescribing ketorolac IV vs. acetaminophen IV for headaches following head trauma. In this study, we aimed to test the application of ketorolac IV vs. acetaminophen IV for managing patients with trauma injuries to support clinicians in better understanding these technologies and choosing the better treatment choice.

Sixty eligible patients were allocated to 2 groups of 30 and entered the study. There were 18 men and 12 women in the ketorolac IV group and 16 men and 14 women in the acetaminophen IV group. The average age in the ketorolac IV group was 29.8 ± 9 and in the acetaminophen IV group was 30.4 ± 10.27. Also, the occupation of most people in the ketorolac IV group was university student and in the acetaminophen IV group was a housewife. There were no significant differences between the two groups in terms of sociodemographic characteristics, including gender, age, job, and mechanism of trauma ( P > 0.05) ( Table 1 ).

The two groups were the same regarding the baseline VAS before the treatment, and there was no statistically significant difference ( P = 0.787). Significant differences were based on VAS in the ketorolac IV vs. acetaminophen IV group 6 h after injection ( P = 0.006). Moreover, the trend of VAS score reduction was significant in preinjection times (baseline) to 2 h ( P = 0.01) and baseline to 6 h ( P = 0.001) after injection in the ketorolac IV group vs. the acetaminophen IV group. It should be noted that the comparison of VAS scores and other outcomes could not be made due to the drop of 100% and 90% 12 h after injection in the two groups of ketorolac IV and acetaminophen IV ( Table 2 ).

Effective management of headaches following head trauma by emergency physicians is critical. Using effective drugs with fewer complications improves clinical results and safety for patients complaining of headaches following head trauma [ 14 ].

The results of the present study showed that the pain score 6 h after injection in the ketorolac IV group was lower than in the acetaminophen IV group, and the pain reduction rate from baseline to 2 h and 6 h after drug administration in the ketorolac IV group was more than the acetaminophen IV group. A similar study showed significant declines in VAS scores in ketorolac IV and paracetamol throughout the time sequence ( P < 0.05). The statistical VAS score was slightly higher in the paracetamol group at most time points, except for 6 h [ 15 ]. According to a previous study, ketorolac IV and acetaminophen IV produced a similar postoperative palliative effect. However, ketorolac reduced Dilaudid usage and improved the return of bowel function compared to acetaminophen [ 16 ]. In another study, there was no significant difference between the two groups of ketorolac IV vs. acetaminophen IV in the average scores of VAS after surgery. However, ketorolac IV produced lower pain scores than acetaminophen IV in the later postoperative treatment [ 10 ]. The results of Sorri et al.’s (2021) study showed that there is no significant difference in pain reduction between the three groups treated with acetaminophen and ketorolac IV and a combination of the two drugs [ 14 ].

In examining the changes in the pain score during the study, although in the ketorolac IV vs. acetaminophen IV group, a downward trend can be seen among all measurement times; however, the type of decreasing trend in the two groups was not the same. Hence, the slope of the pain score reduction in ketorolac IV is more than in the acetaminophen IV group. Sorri et al. (2021) showed that the hill of pain reduction in the combination of ketorolac IV and acetaminophen IV was more than in either alone. It is suggested that if there are no contraindications, the combination of acetaminophen IV and ketorolac IV should be injected to reduce the pain of conscious trauma patients [ 14 ].

The frequency of pruritus, nausea and emesis, and pethidine consumption in all the hours under examination after drug administration was insignificant in the ketorolac IV vs. acetaminophen IV group. The frequency of drowsiness 2 h after drug administration was lower in the ketorolac IV vs. acetaminophen IV group. In Anand et al.’s (2013) study, the incidence of nausea in the ketorolac IV group was significantly lower compared to the acetaminophen IV [ 10 ]. In the study comparing IV ibuprofen vs. ketorolac IV for reducing renal colic pain, the most common complication was nausea and emesis, which was more in the IV ibuprofen group. However, there was no significant difference between the two drugs regarding side effects [ 17 ]. Zackova et al. (2001) also showed that the ketorolac IV group had lower side effects, such as emesis [ 18 ]. There was no significant difference in pain reduction between ketorolac and dexamethasone. However, in the dexamethasone group, the percentage of patients who needed narcotics and antiemetics was significantly lower [ 19 ]. Side effects caused by the use of narcotic drugs, such as respiratory depression, nausea, and drowsiness, do not occur with the use of ketorolac, so ketorolac is reported to be a safe and effective drug for pain control in patients after surgery and other pain cases [ 20 ]. Some studies report other side effects of ketorolac, including coagulation, gastrointestinal problems, and nephrotoxicity [ 21 ], which were not investigated in the present study. However, studies have shown that the use of ketorolac can reduce opioid injection use and its consequences [ 22 , 23 ]; moreover, the use of injectable ketorolac for pain relief of joints, its effectiveness, is good. It has few short-term side effects [ 24 ]. In the study of Javaherforooshzadeh et al. (2020), there were significant differences in morphine consumption in the two paracetamol versus ketorolac IV groups at 24 h and 48 after intubation, and the average consumption of morphine was higher in the ketorolac IV group [ 15 ].

In the present study, the comparison of the VAS score of the two groups in 2 h with the adjusted pain score preinjection and the comparison of the VAS score of the two groups in 6 h with the adjusted pethidine consumption in 2 h were significant. Based on this study’s data, ketorolac’s effect on pain control was better than the acetaminophen IV group. In Rahimzadeh et al.’s (2013) study, the number of additional painkillers used to control pain to the satisfaction of the patient was lower in the acetaminophen IV group than in the ketamine group [ 25 ].

However, in the present study, ketorolac IV vs. acetaminophen IV had better effectiveness with fewer side effects. Previous studies have reported that ketorolac IV is as effective as morphine or meperidine in relieving postoperative pain. Due to ketorolac’s good effectiveness in pain, the need to receive pethidine similar to acetaminophen IV has not decreased.

The present study showed that ketorolac IV was more effective than acetaminophen IV in reducing headaches following head trauma. The results of the current study emphasize controlling the pain associated with head trauma with non-narcotics with more efficacy and fewer side effects at a reasonable cost.