Veterinary Anaesthesia and Analgesia, 2016, 43, 86 90 doi:10.1111/vaa.12273 SHORT COMMUNICATION Comparison of anesthesia with a morphine lidocaine ketamine infusion or a morphine lidocaine epidural on time to extubation in dogs Erin Wendt-Hornickle & Lindsey BC Snyder Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin Madison, Madison, WI, USA Correspondence: Erin Wendt-Hornickle, Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA. E-mail: ewendtho@umn.edu Abstract Objective To evaluate and compare the time to extubation in two commonly used methods of analgesia in dogs undergoing elective pelvic limb orthopedic procedures. Study design Prospective, randomized, doubleblinded clinical study. Animals Twenty-five adult, client-owned, healthy dogs aged 4.4 1.6 years and weighing 38.5 3.5 kg. Methods All dogs were premedicated with dexmedetomidine (5 10 lg kg 1 ) intramuscularly (IM) and anesthesia was induced with propofol (2 6mgkg 1 ) intravenously (IV). Atipamazole (0.05 0.1 mg kg 1 ) was administered IM after instrumentation. Anesthesia was maintained with isoflurane in oxygen. Dogs were randomly assigned to one of two groups. In one group, morphine (0.1 mg kg 1 ) and lidocaine (2% lidocaine added to a total volume of 0.2 ml kg 1 ) were administered epidurally and a saline placebo constant rate infusion (CRI) was administered IV (group EPI). In the other group (group MLK), morphine (4 lg kg 1 minute 1 ), lidocaine (50 lg kg 1 minute 1 ) and ketamine (10 lg kg 1 minute 1 ) were administered as an IV CRI and a saline placebo was administered by epidural injection. Temperature at the discontinuation of isoflurane, temperature at extubation, time to extubation, duration of inhalation anesthesia and duration of surgery were recorded. Results No significant differences between the groups were found in time to extubation, temperature at the end of surgery, temperature at extubation and total surgical time. Total anesthesia time was significantly longer in group EPI. Conclusions and clinical relevance Administration of MLK at the doses reported in this study did not prolong the time to extubation in comparison with a morphine lidocaine epidural nerve block. The results indicate that concern over prolonging the time to extubation is not a reason to avoid the administration of MLK. Keywords analgesia, constant rate infusion, epidural, MLK. Introduction Drug administration before and during inhalation anesthesia can have a significant impact on the return to consciousness and the return of reflex activity, such as the swallowing reflex observed at extubation (Sinclair & Faleiro 2006). In humans, delayed extubation is most commonly reported with reference to patients being weaned from cardiac bypass machines (Wong et al. 1999), a context that is distinct 86
from that of any other anesthetic procedure. Therefore, in human and veterinary patients, there is no set standard for a delayed extubation or return to consciousness in the literature. The veterinary literature has previously focused on the respective influences of the surgical procedure (Burns et al. 2014), the anesthetic induction agent (Maney et al. 2013) and intraoperative hypothermia (Redondo et al. 2012) on time to extubation. The combination of morphine, lidocaine and ketamine (MLK) as an intravenous (IV) constant rate infusion (CRI) in maintenance fluids has gained popularity as a multimodal approach to analgesia. However, anecdotal reports suggest that veterinarians perceive that MLK administered during anesthesia results in a delay to extubation. Consequently, MLK may not be chosen, may be used at a decreased dose rate or may be stopped before the end of surgery. In such cases, the MLK infusion is not being used as previously described (Muir et al. 2003). The purpose of this study was to evaluate the time to extubation in dogs administered an MLK CRI for cruciate ligament repair and to compare this with that in an established analgesia protocol, a morphine lidocaine epidural. The hypothesis was that MLK would not prolong the time to extubation. Materials and methods The Institutional Animal Care and Use Committee at the University of Wisconsin approved the study prior to its beginning. Animals Twenty-five client-owned, healthy adult dogs, with American Society of Anesthesiologists (ASA) class I or II status, scheduled for tibial plateau leveling osteotomy (TPLO) or tibial tuberosity advancement (TTA) for cranial cruciate ligament injury were eligible for inclusion in the study. Additional information was obtained for another study, which required the exclusion of dogs undergoing additional surgical procedures, or with an ASA status of greater than class II or a body condition score of >7 out of 10, and northern breed dogs. Owner consent, obtained after the delivery of thorough descriptions of the treatments, was obtained before dogs entered the study. Anesthetic management Food, but not water, was withheld for 12 hours prior to anesthesia. Dogs were administered dexmedetomidine (5 10 lg kg 1 ; Dexdomitor; Zoetis, Inc., MI, USA) intramuscularly (IM) in the epaxial muscles for sedation and an IV catheter was placed. Anesthesia was induced with propofol IV (2 6 mgkg 1 ; PropoFlo; Abbott Animal Health, IL, USA). The dogs were orotracheally intubated and anesthesia was maintained with isoflurane (Piramal Critical Care, Inc., PA, USA) in oxygen using an out-of-circle isoflurane vaporizer and a circle system. After instrumentation for monitoring, the dexmedetomidine was antagonized with atipamezole (0.05 0.1 mg kg 1 ; Antisedan; Zoetis, Inc.) IM in the epaxial muscles (at a volume equal to that of the dexmedetomidine) to eliminate the effect of dexmedetomidine on recovery. Ventilation was spontaneous or controlled to maintain normocapnia. Routine monitoring was performed as per the standard of care for any clinical patient, and included pulse oximetry, capnography, and noninvasive blood pressure and rectal temperature measurements. Circulating warm water tabletop heating pads and forced warm air heaters were used for the duration of surgery. Isoflurane delivery was adjusted to maintain an anesthetic depth adequate for the surgical procedure. Groups Block randomization, in groups of 10 dogs, was used to randomly assign dogs to either of two groups. All anesthesia personnel involved were unaware of the assigned group. All drugs and placebos were prepared by pharmacy personnel and provided to anesthesia personnel in syringes labeled for epidural or CRI administration. All treatments were administered by the same individual (EW-H). The IV fluid infusion rate was regulated using a fluid pump (Vet/ IV 2.2; Heska Corp., CO, USA). Group MLK Dogs in the MLK group were administered a CRI of morphine (24 mg L 1 ; Hospira, Inc., IL, USA), lidocaine (300 mg L 1 ; Hospira, Inc.) and ketamine (60 mg L 1 ; Hospira, Inc.) in crystalloid fluid (PlasmaLyte A; Baxter Healthcare Corp., IL, USA) at a rate of 10 ml kg 1 hour 1 (0.17 ml kg 1 minute 1 ; morphine 4 lg kg 1 minute 1, lidocaine 50 lg kg 1 minute 1, ketamine 10 lg kg 1 minute 1 ). A placebo (0.9% NaCl; 0.2 ml kg 1 total 87 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 86 90
volume) was administered by epidural injection to each dog. Group EPI Dogs in this group were administered a preservativefree (PF) morphine (0.1 mg kg 1 ; APP Pharmaceuticals LLC, IL, USA) and PF lidocaine (2% lidocaine added to the morphine to a total volume of 0.2 ml kg 1 ; APP Pharmaceuticals LLC) lumbosacral epidural injection using a previously described method (Torske & Dyson 2000). The hanging drop techniquewasusedtoconfirmcorrectepiduralplacement of the needle (22 gauge, 2.5 cm or 3.5 cm spinal needle; Becton Dickinson & Co., NJ, USA). Immediately following epidural administration, three syringes containing 0.9% NaCl in volumes equivalent to those of the MLK infusion were injected into the perioperative fluid bag and infused at 10 ml kg 1 hour 1. Recovery The isoflurane and IV fluid infusion were discontinued at the removal of the surgical drapes. Bladder care was performed just prior to the discontinuation of isoflurane. Following postoperative radiography, dogs were moved to a recovery cage and positioned with the surgical limb up. Dogs were allowed to recover quietly with no deliberate stimulation. Extubation was performed by the anesthetist once laryngeal reflexes were regained and vigorous swallowing resumed. Time to extubation was the time from discontinuation of inhalation anesthesia and crystalloid fluid administration (with MLK or placebo) to removal of the endotracheal tube. Statistical analysis Time to extubation, temperature at the end of surgery, temperature at the time of extubation, total surgical time and total anesthesia time were all individually compared between groups MLK and EPI using unpaired t-tests. All statistical analyses were conducted in QuickCalcs (GraphPad Software, Inc., CA, USA). Results are reported as the mean standard deviation (SD); p-values of <0.05 are considered to indicate statistical significance. Results Total anesthesia time differed significantly between the groups (p = 0.03), whereas the duration of surgery did not (p = 0.11) (Table 1). There was no significant difference between the groups in temperature at the end of surgery (p = 0.32) or temperature at extubation (p = 0.32). Mean SD times to extubation following discontinuation of isoflurane in groups MLK and EPI were 26 18 minutes and 21 19 minutes, respectively, and were not significantly different (p = 0.49) (Table 1). All epidural injections were performed by the same individual (EW-H) and all were completed within 5 minutes. No adverse events were observed in any dog during recovery from anesthesia. Discussion The results of this study support the hypothesis that administration of an MLK CRI is not associated with a delay to extubation in healthy canine patients undergoing either TPLO or TTA in comparison with dogs administered a morphine lidocaine epidural nerve block. Delayed extubation is difficult to define in veterinary medicine because the perception of prolonged recovery is subjective as a result of multiple factors that influence the nature of recovery. In veterinary patients, caseload, support staff availability, duration of procedure, specialty training and perceived patient risk influence the perception that an extubation is delayed. Morphine, lidocaine and ketamine provide analgesia by varying mechanisms. When administered as a CRI, the combination can reduce the minimum alveolar concentration of isoflurane in dogs by 45% (Muir et al. 2003). The fact that little technical skill is needed to add drugs to an existing fluid bag may explain the increase in popularity in veterinary medicine of the IV MLK infusion as a pain management technique. A potential limitation to this study was the sample size.asthenatureofthestudywasclinical,samplesize was dependent upon caseload. The MLK and EPI groups, despite similar mean times to extubation, included several outliers to the data. In four of 13 dogs (30.8%) in the MLK group and two of 12 dogs (16.7%) intheepigroup, timetoextubationwas>30 minutes. Undoubtedly, a time to extubation of 60 minutes would be considered by many to represent a prolonged recovery inadog ofasaclassi oriistatus. Had alarger population been evaluated, a difference between groups might have been discovered. Hypothermia can have an effect on the recovery of consciousness after anesthesia. A decrease in body 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 86 90 88
Table 1 Data collected for 25 dogs anesthetized with isoflurane for orthopedic surgery, in which either an intravenous constant rate infusion of morphine lidocaine ketamine (group MLK, n = 13) or a morphine lidocaine epidural injection (group EPI, n = 12) was administered Group Dog Total anesthesia time (minutes) Total surgery time (minutes) Temperature at end of surgery ( C) Temperature at extubation ( C) Time to extubation (minutes) MLK 2 365 210 37.2 37.7 17 MLK* 4 195 130 37.4 36.7 60 MLK 7 250 150 37.4 36.9 35 MLK 8 240 140 36.7 36.9 29 MLK 10 230 130 37.8 37.9 21 MLK 12 190 110 37.0 36.6 15 MLK 13 270 140 38.0 38.0 6 MLK* 15 345 240 38.4 38.4 17 MLK 16 255 150 37.0 36.7 13 MLK* 17 225 150 36.7 36.2 24 MLK 18 240 150 36.8 36.8 44 MLK* 23 300 170 37.8 37.8 2 MLK* 24 210 110 37.3 36.8 55 Mean SD 255 53 152 37 37.3 1.0 37.1 1.0 26 18 EPI* 1 370 200 36.6 36.5 15 EPI* 3 260 140 38.3 37.6 18 EPI* 5 345 200 36.1 36.1 7 EPI* 6 360 210 36.5 36.3 25 EPI 9 220 140 38.2 38.2 7 EPI* 11 250 115 37.8 37.8 10 EPI* 14 400 200 35.9 35.6 12 EPI* 19 345 200 36.7 36.3 19 EPI 20 330 220 38.3 37.9 6 EPI 21 270 140 35.1 35.1 60 EPI* 22 255 180 37.5 37.5 11 EPI 25 270 170 37.2 37.2 60 Mean SD 306 58 176 34 37.0 1.0 36.8 1.0 21 19 *Arthroscopy was performed before surgery; time for arthroscopy was not included in the surgery time. Preoperative radiography was performed during general anesthesia. Significantly different from group MLK. SD, standard deviation. temperature is associated with a decrease in cardiac output and secondary circulatory changes that affect pharmacokinetics (Sinclair & Faleiro 2006). In the present study, mean temperatures at extubation were 37.1 C in the MLK group and 36.8 C in the EPI group. Hypothermia in dogs has been defined as a decrease in body temperature to below 37 C, and mild hypothermia is considered to occur at 32 37 C (Armstrong et al. 2005). By this definition, the dogs in our study were at the upper end of mild hypothermia. Our results may have been different in either group if any of the dogs had been more significantly hypothermic. It is possible that the perceived delay in extubation in dogs receiving MLK CRIs is more closely related to the patient s temperature at the end of surgery. However, this was not the focus of our study and is only speculation. It is interesting that there was a statistically significant difference in total anesthesia time, but not surgical time, in the present study. In humans, increased surgical time has been implicated in delayed recovery of consciousness following anesthesia (Sinclair & Faleiro 2006). Factors that might explain the significantly greater anesthesia time in the EPI group include the time required to administer an epidural, the fact that preoperative radiography was performed in two dogs in the EPI group and none in the MLK group, and the greater number of dogs in the EPI group submitted to arthroscopy. The epidural injection was performed by the same individual in all dogs and added no more than 5 minutes to the anesthesia time. Preoperative radiography was unlikely to have contributed to the difference as only two dogs in the EPI group were involved. Arthroscopy is 89 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 86 90
the most likely cause of the difference in anesthesia time between groups. Arthroscopy was considered a procedure separate from the surgery and was recorded separately. Arthroscopy was performed in more dogs in the EPI group (eight of 12 dogs, 66.7%) than in the MLK group (five of 13 dogs, 38.5%). Thus, although time to extubation did not differ between the two groups, total anesthesia time in the MLK group was 50 minutes shorter than in the EPI group. It is possible that had the anesthetic times been more equal across the groups, a significant difference in time to extubation might have emerged. Further investigation into the impact of anesthesia time on recovery in dogs is required. In conclusion, an MLK CRI did not delay the time to extubation in clinically healthy dogs undergoing TPLO or TTA compared with dogs administered a morphine lidocaine epidural nerve block. Because the administration of an MLK CRI is relatively easy and requires minimal technical skill, this approach can be used in dogs without delaying extubation. The clinical relevance of these findings will benefit a wide variety of dogs undergoing surgical procedures that are not candidates for epidural nerve blocks. References Armstrong SR, Roberts BK, Aronsohn M (2005) Perioperative hypothermia. J Vet Emerg Crit Care 15, 32 37. Burns BR, Hofmeister EH, Brainard BM (2014) Anesthetic complication in dogs undergoing hepatic surgery: cholecystectomy versus non-cholecystectomy. Vet Anaesth Analg 41, 186 190. Maney JK, Shepard MK, Braun C et al. (2013) A comparison of cardiopulmonary and anesthetic effects of an induction dose of alfaxalone or propofol in dogs. Vet Anaesth Analg 40, 237 244. Muir WW III, Wiese AJ, March PA (2003) Effects of morphine, lidocaine, ketamine, and morphine lidocaine ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane. Am J Vet Res 64, 1155 1160. Redondo JI, Suesta P, Serra I et al. (2012) Retrospective study of the prevalence of postanesthetic hypothermia in dogs. Vet Rec 171, 374. Sinclair RCF, Faleiro RJ (2006) Delayed recovery of consciousness after anaesthesia. Contin Educ Anaesth Crit Care Pain 6, 114 118. Torske KE, Dyson DH (2000) Epidural analgesia and anesthesia. Vet Clin North Am Small Anim Pract 30, 859 874. Wong DT, Cheng DC, Kustra R et al. (1999) Risk factors of delayed extubation, prolonged length of stay in the intensive care unit, and mortality in patients undergoing coronary artery bypass graft with fast-track cardiac anesthesia: a new cardiac risk score. Anesthesiology 91, 936 944. Received 29 September 2014; accepted 17 February 2015. 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 43, 86 90 90