Systemic and anti-nociceptive effects of prolonged lidocaine, ketamine, and butorphanol infusions alone and in combination in healthy horses

Abstract

BackgroundProlonged drug infusions are used to treat horses with severe signs of pain, but can be associated with altered gastrointestinal transit. The purpose of this study was to determine the effects of prolonged constant rate infusions (CRI) of lidocaine (L), butorphanol (B), and ketamine (K) alone and in combination on gastrointestinal transit, behavior, and thermal nociceptive threshold in healthy horses.MethodsEight healthy adult horses were used in a randomized, cross-over, blinded, prospective experimental trial. Interventions were saline, L, K, B, LK, LB, BK, and LBK as an intravenous CRI for 96 hours. Drugs were mixed or diluted in saline; following a bolus, CRI rate was 0.15mL/kg/hr with drug doses as follows: L – 1.3 mg/kg then 3 mg/kg/hr; B – 0.018 mg/kg then 0.013 mg/kg/hr; K – 0.55 mg/kg then 0.5 mg/kg/hr. Two-hundred plastic beads were administered intragastrically by nasogastric tube immediately prior to the bolus. Feces were collected every 2 hours, weighed, and beads manually retrieved. Behavior was scored every 2 hours, vital parameters every 6 hours, and thermal nociceptive threshold every 12 hours for 96 hours. Drug concentrations in the LBK solution were tested every 6 hours for 72 hours.ResultsFour of 64 trials (3 LBK, 1 BK) were discontinued early due to signs of abdominal discomfort. There were no apparent differences between groups in vital parameters or thermal threshold. Transit time was delayed for LB and LBK with a corresponding decrease in fecal weight that was most severe in the final 24 hours of infusion. Significant changes in behavior scores, vital parameters, or thermal threshold were not observed. The concentration of each drug in the combined solution declined by less than 31% over the sampling period.ConclusionsDrug combinations containing butorphanol cause an apparent delay in gastrointestinal transit in healthy horses without substantially affecting somatic nociception at the doses studied. Combinations of lidocaine and ketamine may have less impact on gastrointestinal transit than infusions combined with butorphanol. Further work is needed to determine the effects of these drugs in painful or critically ill patients.

Meperidine pharmacokinetics and effects on physiologic parameters and thermal threshold following intravenous administration of three doses to horses

“…Excepting for the brief report by Steffey and Pascoe [7] there are no published studies describing the effects of meperidine on nociception in horses. However, using a model similar to that described for the currently reported study similar observations on thermal nociception have been reported following administration of a constant rate infusion of butorphanol [30] and IV administration of methadone to horses. Although, 1 mg/kg has been previously reported to be a clinically acceptable dose, there are only minimal data to support this [31].…”

Pain control in horses: What do we really know?

“…Ketamine infusion (1.2 mg/kg bwt/h for up to 96 h) was associated with a significant delay in total gastrointestinal transit time in one report . In another study, constant‐rate infusion administration of lidocaine plus butorphanol or lidocaine plus butorphanol and ketamine resulted in delayed total gastrointestinal transit time and decreased faecal output, whereas each drug given individually and all other combinations of the 3 drugs did not delay transit, relative to placebo, in healthy horses . Thus, while multimodal therapy may be necessary in horses with severe pain, one should carefully monitor faecal output and reduce or change the drugs administered on a case‐by‐case basis.…”

Occurrence, treatment protocols, and outcomes of colic in horses within Nairobi County, Kenya

“…Systemically administered lidocaine has been found to have anti-inflammatory properties such as reduction of mucosal cyclooxygenase-2 expression and neutrophil count in ischemic-injured equine intestine or amelioration of the negative effects of flunixin meglumine on the recovery of injured mucosa [ 20 ]. It has been observed that there were no effects of prolonged lidocaine (continuous rate) infusion on gastrointestinal transit, except when in combination with butorphanol [ 21 ].…”