Pain management in the postoperative care setting is of utmost importance for patients who underwent CABG. Therefore, pharmacological and interventional approaches have been developed for postoperative analgesia. Currently, there is an increase in the mean age of the patients, and in the number of comorbidities in patients undergoing CABG. Overall, a method of postoperative analgesia which is cost-effective and comfortable for the patient with minimum complication rates and side effects which also shortens the duration of postoperative stay should be chosen. However, postoperative pain managing is often incomplete by the side effects of opioids; especially when used alone in large doses for an extensive period, opioids can lead to acute tolerance and, more seriously, respiratory depression and hypotension. For these reasons, multimodal approaches that add non-opioid agents to opioid-based regimens are favorable. This study aimed to compare the effects of Ketorolac and Paracetamol on postoperative pain management. The main finding in the present study was confirmation of the beneficial analgesic effect of ketorolac and Paracetamol, which alleviated pain in all of the patients. Such effects seem to be less marked with Paracetamol, possibly because of the low dose selected.
NSAIDs block the synthesis of prostaglandins through the inhibition of COX-1 and COX-2, thus lowering the production of acute inflammatory response mediators. By decreasing the inflammatory response to surgical trauma, NSAIDs reduce peripheral nociception. NSAIDs also appear to have a central analgesic mechanism, possibly through the inhibition of prostaglandin synthesis within the spinal cord. In general, NSAIDs have a low side-effect profile when administered for the short-term purpose of perioperative analgesia after cardiac surgery (20, 21).
Ketorolac is effective at reducing pain, and several studies have reported its safety and efficacy in the perioperative period. In many reports, the use of ketorolac as an adjuvant to a PCA opioid resulted in an opioid-sparing effect ranging from 16–33% (22). The hypothesis by which ketorolac exerts these possible beneficial effects is proposed to be related to its COX-1 selectivity and minimal inhibition of COX-2 (23). As previously discussed, the boxed warning for NSAIDs arose from specific data for the COX-2 selective NSAID, valecoxib (24) COX-2 inhibitors selectively reduce prostacyclin synthesis with no effect on thromboxane A2. Prostacyclin is a potent inhibitor of platelet aggregation; its selective blockade by COX-2 inhibitors may upset thrombosis homeostasis and cause adverse cardiovascular events. Ketorolac, on the other hand, potently blocks platelet aggregation through thromboxane A2 inhibition (23, 25). This may be beneficial in patients with aspirin resistance to prevent CABG graft failure. The duration of this antiplatelet effect can last up to 24 hours after a single dose. Additionally, antiplatelet effects of ketorolac may offset the risk of hemorrhage in postoperative patients who may be hypercoagulable following exactly off-pump CABG surgery (17).
The authors previously reported the results of a randomized trial that found that oral naproxen is effective as an adjunct for the optimization of pain control and lung recovery after CABG, without increasing the risk of postoperative complications. In contrast to naproxen, intravenous ketorolac can be provided earlier in the postoperative period before the resumption of oral intake. Ketorolac provides an analgesic effect similar to that of fentanyl, but with a lower incidence of postoperative nausea and somnolence, and leads to an earlier return of bowel function.(15)With these advantages over opioids, ketorolac administration ultimately may shorten hospital length of stay.
Paracetamol has been studied in many surgical settings such as functional endoscopic sinus surgery, cholecystectomy, hysterectomy, and orthopedic surgeries with variable favorable results (26, 27). Direction of acetaminophen via a nasogastric tube or rectally after surgery is insufficient to accomplish an antipyretic plasma concentration (10 mg/ml); this was probably mainly because of late gastric emptying after anesthesia and surgery (13, 28) In a study conducted by Cattabriga et al., they found that, in patients undertaking cardiac surgery, intravenous paracetamol in combination with tramadol delivers effective pain control(29) (30).
Paracetamol have resulted in hypotension in critically ill patients although this effect could be explained as an allergic phenomenon (31). The remaining prostaglandin inhibitors seem to exert less marked cardiac depressant effect; in fact, the haemodynamic safety of other NSAIDs such as diclofenac and ketorolac used at antipyretic doses and analgesic doses has been reported in several studies (29).
The hemodynamic effects of NSAIDs used for postoperative pain control in patients undergoing major vascular surgery have been reported in a few studies (32, 33) .Although exogenous administration of prostaglandins has marked hemodynamic repercussions, exogenous inhibition of prostaglandin synthesis has little hemodynamic effect. This could reflect a balance between the reduction in synthesis of prostaglandins with vasodilator and vasoconstrictor actions, with a neutral overall effect. However, NSAIDs must be used cautiously in clinical situations in which prostaglandins have been shown to have advantageous therapeutic effects, such as circulatory insufficiency, shock, myocardial ischemia, coronary spasm and systemic and pulmonary hypertension; in addition, NSAIDs may antagonize the effect of antihypertensive medication. In the present study, such patients were excluded and therefore no evaluation of hemodynamic stability when the drugs were present were made.
Our study found no association between use of 0.5 mg/kg ketorolac and mortality, MI, or clinically important hemorrhage. These results, however, are limited by unexpected differences in the baseline characteristics of number of on-pump CABG patients and STS risk scores. On-pump CABG means a patient placed on cardiopulmonary bypass throughout surgery (34). The STS risk score is intended for all patients who undergo CABG surgery and helps as a prognosticator of post-operative mortality.(35)
Limitations
This study has several limitations. First; sample size was small second; this study was single-centered. We recommended future trial with large sample size, multi-center and long duration of follow-up.