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The Effect of Morphine-Lidocaine-Ketamine

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The Effect of Morphine-Lidocaine-Ketamine THE EFFECT OF MORPHINE-LIDOCAINE-KETAMINE- DEXMEDETOMIDINE CO-INFUSION ON MINIMUM ALVEOLAR CONCENTRATION OF ISOFLURANE IN DOGS Thesis Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Graduate School of The Ohio State University By Lisa Michelle Sams, D.V.M. Graduate Program in Comparative and Veterinary Medicine The Ohio State University 2011 Thesis Committee: Dr. Phillip Lerche, Advisor Dr. Richard M. Bednarski Dr. John A.E. Hubbell Copyright by Lisa Michelle Sams 2011 ABSTRACT The purpose of this study was to determine the effects of an infusion of dexmedetomidine, a co-infusion of morphine-lidocaine-ketamine (MLK), and a co- infusion of dexmedetomidine-morphine-lidocaine-ketamine (alpha-MLK) on minimum alveolar concentration (MAC) of isoflurane in dogs. The MAC of an inhalant anesthetic required to prohibit purposeful movement is a measure of anesthetic potency (Eger et al 1965). Isoflurane is the most commonly used inhalant anesthetic in veterinary practice (Lozano et al 2009), but has potent vasodilatory effects and causes a dose-dependent decrease in mean arterial pressure in anesthetized dogs (Steffey and Howland 1977). Additional drugs are used during anesthesia to decrease the inhalant anesthetic requirement, a concept referred to as balanced anesthesia. Each of the drugs we infused has a different central nervous system receptor mechanism of action. Co-infusion of MLK, as well as the infusion of each drug separately, has been shown to reduce MAC in isoflurane-anesthetized dogs (Muir et al 2003). Dexmedetomidine, an alpha-2 agonist, has been shown to reduce isoflurane MAC in dogs (Pascoe et al 2006). Dexmedetomidine is a commonly used sedative with analgesic and muscle relaxant properties. The effect of a co-infusion of alpha-MLK on isoflurane anesthesia has not been critically evaluated in the dog. Our hypothesis was that infusion of alpha-MLK would significantly decrease isoflurane MAC (MAC-Iso) compared to dexmedetomidine or MLK infusions. ii For this study, six dogs were anesthetized to determine MAC-Iso (baseline). Following MAC-Iso determination, each dog was anesthetized on three separate occasions with isoflurane, with a minimum of 7 days between anesthetic episodes. On each occasion, and in random order, dexmedetomidine, MLK, or alpha-MLK infusions were administered, and MAC was determined. Additionally, hemodynamic and metabolic parameters as well as bispectral index (BIS) were measured during each experiment. The investigator was blinded to the infusion given. Data were analyzed using ANOVA for repeated measures. Dunnett and Tukey posttests were performed to identify differences within and among groups, respectively, when differences were detected. The MAC-Iso was 1.3 ± 0.15%. Dexmedetomidine, MLK, and alpha-MLK significantly lowered MAC-Iso by 30, 55, and 90%, respectively. Heart rate was significantly decreased from baseline in all infusion groups. Heart rate did not differ significantly between dexmedetomidine and alpha-MLK infusion groups. Mean arterial pressure for alpha-MLK increased significantly from baseline. Systemic vascular resistance was significantly increased for the dexmedetomidine and alpha-MLK infusion groups. The BIS values increased significantly compared to baseline for the MLK and alpha-MLK infusion groups. There was no significant difference for time to extubation and sternal recumbency among groups. Infusions of dexmedetomidine, MLK, and alpha-MLK reduced MAC-Iso in dogs. Changes in cardiovascular parameters were within clinically acceptable ranges for iii healthy dogs. BIS can be an effective monitoring tool for measuring the depth of anesthesia. iv ACKNOWLEDGEMENTS I would like to thank my advisor, Dr. Phillip Lerche, for his guidance and support. I would also like to thank Dr. Richard Bednarski, Dr. John Hubbell, Dr. Turi Aarnes, and the remainder of the Anesthesia Section, including the technical support staff, for all their help during my residency program. I would like to thank Tim Vojt for his creativity in producing the medical illustrations. This research was supported by an intramural grant from the Canine Research Fund. Finally, I would like to thank my six research dogs - Delilah, Poppy, Hank, Pedro, Cletus, and Rosie - for being excellent subjects and I want to thank the people that gave them a new home and a new life. v Vita 1998………………………………………....West Henderson High School 2002…………………………………………B.S. Animal Science, University of Georgia 2006…………………………………………D.V.M., University of Georgia 2007…………………………………………Anesthesia Internship, University of Georgia 2008…………………………………………Internship in Small Animal Internal and Emergency Medicine, Greenbrier Veterinary Referral Center 2008 to present……………………………...Anesthesia Residency, The Ohio State University Publications Sams L, Braun C, Allman D, Hofmeister E. A comparison of the effects of propofol and etomidate on the induction of anesthesia and on cardiopulmonary parameters in dogs. Vet Anaesth Analg 2008; 35(6): 488-94. Hofmeister EH, Brainard BM, Sams LM, Allman DA, Cruse AM. Evaluation of induction characteristics and hypnotic potency of isoflurane and sevoflurane in healthy dogs. Am J Vet Res. 2008; 69 (4): 451-6. Sams L, Hofmeister E. Vet Med Today: Anesthesia Case of the Month. J Am Vet Med Assoc 2008; 232 (2): 206-209. Fields of Study Major Field: Comparative and Veterinary Medicine vi Table of Contents Page Abstract………………………………………………………………………………..…..ii Acknowledgements…………………………………………………………………….…v Vita……………………………………………………………………………………......vi List of Tables……………………………………………………………………..….….viii List of Figures………………………………………………………………………...…..ix List of Abbreviations…………………………………………………………………......xi Chapter 1: Introduction………………………………………………………………...…1 Chapter 2: Review of the Literature………………………………………………………7 Chapter 3: Materials and Methods…………………………………………………….....29 Chapter 4: Results………………………………………………………………………..45 Chapter 5: Discussion……………………………………………………………………60 Chapter 6: Conclusion……………………………………………………………………77 Footnotes…………………………………………………………………………………78 References………………………………………………………………………………..80 Appendix: Sedation Scoring System for Pilot Study……….……………………………91 vii List of Tables Table 4.1 Variables recorded in dogs anesthetized with isoflurane and given infusions of dexmedetomidine, morphine-lidocaine-ketamine, and dexmedetomidine- morphine-lidocaine-ketamine on separate occasions……………………………………………………………………………57 Table 4.2 Metabolic variables recorded from arterial blood gas samples in dogs anesthetized with isoflurane and given infusions of dexmedetomidine, morphine-lidocaine-ketamine, and dexmedetomidine- morphine-lidocaine -ketamine on separate occasions…………………………………………….…58 viii List of Figures Figure 1.1 Multi-modal analgesia at receptor level……………………………......6 Figure 2.1 Sensory nervous system process of pain perception…………….……15 Figure 2.2 The mechanism of nociception……………………………………….16 Figure 2.3 Peripheral sensitization…………………………………………….…17 Figure 2.4 Central sensitization…………………………………………………..18 Figure 3.1 Bifrontal configuration of the EEG leads for BIS monitoring……......34 Figure 3.2 BIS monitor taking EEG measurements on a dog…………………....34 Figure 3.3 LiDCOplus cardiac output monitor……………………………….….35 Figure 3.4 Set-up for the LiDCO sensor…………………………………………35 Figure 3.5 Final instrumentation setup in the laboratory…………………….…..36 Figure 3.6 Timeline for isoflurane MAC determination………………………….39 Figure 3.7 Timeline for MAC determination for the treatments…………………40 Figure 4.1 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on isoflurane MAC concentration in dogs…………………………47 ix Figure 4.2 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on mean arterial pressure in dogs…………………………………….48 Figure 4.3 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on heart rate in dogs…………………………………………………..49 Figure 4.4 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on cardiac output in dogs……………………………………………..50 Figure 4.5 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on cardiac index in dogs…………………………………………..…51 Figure 4.6 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on stroke volume in dogs…………………………………………….52 Figure 4.7 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on systemic vascular resistance in dogs………………………………53 Figure 4.8 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on BIS value in dogs…………………………………………………..54 Figure 4.9 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on time to extubation from the end of isoflurane anesthesia in dogs…………………………………………………………………..55 Figure 4.10 The effect of infusions of dexmedetomidine, MLK, and alpha-MLK on time to sternal recumbency in dogs……………………………..…56 x LIST OF ABBREVIATIONS α2-agonist alpha2 adrenergic receptor agonist alpha-MLK dexmedetomidine-morphine-lidocaine-ketamine ANOVA analysis of variance BDNF brain-derived neurotrophic factor BIS bispectral index CaO2 oxygen content of arterial blood CI cardiac index CNS central nervous system CO cardiac output CRI continuous rate infusion DAP diastolic arterial pressure DO2 oxygen delivery to tissue ECG electrocardiogram EEG electroencephalogram EMG electromyography ETCO2 end tidal carbon dioxide ET-Iso end tidal isoflurane HR heart rate IV intravenous LiCl lithium chloride xi LiDCO lithium dilution cardiac output LRS lactated Ringer‟s solution MAC minimum alveolar concentration MAC-Iso minimum alveolar concentration of isoflurane MAP mean arterial pressure
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