Local Infiltration of Analgesics at Surgical Wound to Reduce Postoperative Pain After Laparotomy in Rats.
There is an increasing use of local infiltration analgesia (LIA) to reduce postoperative pain. Despite widespread use of LIA, wide variations in drug combinations and concomitant use of systemic analgesics have made it difficult to determine the optimal drug combinations for LIA. Using a previously validated rat laparotomy model, the optimal LIA combination of medications to reduce postoperative pain was determined.



Laparotomy was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, and dexamethasone were injected over the sutured muscle wound before skin closing, and compared to saline (placebo). The same medications were injected systemically as controls. Postoperative pain was assessed by measuring spontaneous rearing activity.



A high-dose 3-drug LIA combination (50 μL of bupivacaine 0.75%, ketorolac 6.0 mg/mL, and dexamethasone 2.0 mg/mL) increased rearing (decreased pain) at 2 hours (P = 0.0032) postsurgery compared to saline. However, the same 3 drugs injected systemically had a similar analgesic effect (P = 0.0002). Bupivacaine 0.75% alone was not effective for LIA. When low-dose (9-fold reduction) 3-drug LIA combination was used, LIA increased rearing (P = 0.0034) whereas the same 3 drugs injected systemically had no effect. Low-dose LIA ketorolac/dexamethasone (2-drug combination) also increased rearing (P = 0.0393).



Our animal study suggests that clinical trials with low-dose LIA combinations of local anesthetic, nonsteroidal anti-inflammatory drug, and corticosteroid may be useful for reducing postoperative pain after laparotomy.
From the Department of Anesthesiology, Rush University Medical Center, Chicago, IL.
Jeffrey S
JS
Kroin
Jinyuan
J
Li
Mario
M
Moric
Brian W
BW
Birmingham
Kenneth J
KJ
Tuman
Asokumar
A
Buvanendran
D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal; D002045:Bupivacaine / Q000008:administration & dosage*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005938:Glucocorticoids / Q000008:administration & dosage*; D007267:Injections; D020910:Ketorolac / Q000008:administration & dosage*; D007813:Laparotomy; D008297:Male; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D058106:Wound Closure Techniques
D000779:Anesthetics, Local; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D005938:Glucocorticoids; D003907:Dexamethasone; D002045:Bupivacaine; D020910:Ketorolac