Comparison of required induction dose, induction and recovery characteristics, and cardiorespiratory effects of co-administration of ketofol with diazepam and midazolam in healthy dogs

Document Type: Infectious agents- Diseases- Surgery

Authors

1 Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

2 Student of Veterinary Medicine,Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran

Abstract

Background: Co-administration of anesthetics has been employed to decrease potential unpleasant effects associated with single drug. OBJECTIVES: This study was designed to evaluate the effects of co-administration of ketofol with diazepam or midazolam in healthy dogs. METHODS: Six adult mix-breed male dogs were used. After sedation with acepromazine (0.1 mg/kg), anesthesia was induced with keteofol (KF; 1 ml contained 5 mg ketamine and 5 mg propofol), ketofol-diazepam (KFD), or ketofol-midazolam (KFM) (1 ml contained 5 mg KF and 2.5 mg diazepam or midazolam) randomly. All the dogs received the three treatments with at least one week interval. RESULTS: The total dose of ketofol used for induction of anesthesia in KF (4.2±0.44 mg/kg) was significantly higher than KFD (2.27±0.6 mg/kg) and KFM (1.68±0.25 mg/kg). The total dose of diazepam and midazolam used in KFD and KFM was 1.00±0.25 and 0.73±0.10 mg/kg, respectively (p>0.05). The time needed for sternal recumbency, standing position and normal walking was longer in KFD and KFM compared to KF (p<0.05). Heart rate (HR) showed significant increase in KF at several time points (p<0.05). Respiratory rate (fr) in KF showed a significant decrease during the anesthesia period compared to the base (p<0.05). HR and fr were more stable in KFD and KFM. Induction and recovery quality in the three treatments were acceptable. CONCLUSIONS: Co-administration of ketofol with diazepam and midazolam reduced the required induction dose and prolonged recovery in dogs. Diazepam and midazolam could attenuate the unfavorable effects of ketofol in some cardiorespiratory variables.
 

Keywords


Article Title [Persian]

مقایسه دوز مورد نیاز القا، خصوصیات القا و برگشت از بیهوشی و تأثیرات قلبی-تنفسی تجویز همزمان کتوفول با دیازپام و میدازولام در سگهای سالم

Authors [Persian]

  • هادی ایمانی 1
  • علی بنی آدم 1
  • بهمن مصلی نژاد 1
  • شهرزاد شعبانی 2
1 گروه علوم درمانگاهی، دانشکده دامپزشکی دانشگاه شهید چمران اهواز، اهواز، ایران
2 گروه علوم درمانگاهی، دانشکده دامپزشکی دانشگاه شهید چمران اهواز، اهواز، ایران
Abstract [Persian]

زمینه مطالعه:  تجویز همزمان داروهای بیهوشی به منظور کاهش اثرات ناخواسته هر یک از این داروها انجام می‌شود. هدف: این مطالعه به منظور بررسی اثرات تجویز همزمان کتوفول با دیازپام و میدازولام در سگ‌های سالم طراحی شد. روش کار: تعداد شش قلاده سگ بالغ نژاد مخلوط مورد استفاده قرار گرفتند. پس از آرام‌بخشی با داروی آسپرومازین (mg/kg 1/0)، بیهوشی با یکی از سه درمان کتوفول (KF، هر میلی‌لیتر شامل mg‌5 کتامین و mg‌5 پروپوفول)، کتوفول-دیازپام (KFD) و کتوفول-میدازولام (KFM) (هر  میلی‌لیتر شامل mg‌5 کتوفول و mg‌5/2 دیازپام یا میدازولام) به صورت تصادفی القا شد. همه سگ‌ها هر سه درمان را به فاصله حداقل یک هفته دریافت نمودند. نتایج: دوز مورد نیاز برای القای بیهوشی در KFر(mg/kg 44/0±2/4) بالاتر از KFDر(mg/kg 6/0±27/2) و KFMر(mg/kg 25/0±68/1) تعیین شد (05/0>p). دوز نهایی دیازپام و میدازولام در KFD و KFM به ترتیب mg/kg 25/0±00/1 و mg/kg 10/0±73/0 بود (05/0<p). زمان مورد نیاز برای نشستن روی جناغ، ایستادن و راه رفتن طبیعی در گروه KFD و KFM طولانی‌تر از KF بود (05/0>p). تعداد ضربان قلب در KF در چندین نقطه زمانی افزایش یافت (05/0>p). تعداد تنفس در KF یک کاهش معنی‌داری را در زمان بیهوشی در مقایسه با زمان پایه نشان داد. ضربان قلب و تعداد تنفس در KFD و KFM ثبات بیشتری را نشان داد. کیفیت القا و برگشت از بیهوشی در هر سه درمان قابل قبول بود. نتیجه‌گیری نهایی: تجویز همزمان کتوفول با دیازپام و کتامین مقدار داروی مورد نیاز برای القا را کاهش داد و برگشت از بیهوشی را طولانی ساخت. دیازپام و میدازولام توانستند برخی اثرات جانبی قلبی-تنفسی کتوفول را کاهش دهند.

Keywords [Persian]

  • تجویز همزمان
  • کتوفول
  • دیازپام
  • میدازولام
  • سگ
 

Abbasivash, R., Aghdashi, M.M., Sinaei, B., Kheradmand, F. (2014) The effects of propofol-midazolam-ketamine co-induction on hemodynamic changes and catecholamine response. J Clin Anesth. 26: 628-633.

Andolfatto, G., Willman, E. (2010) A prospective case series of pediatric procedural sedation and analgesia in the emergency department using single‐syringe ketamine-propofol combination (Ketofol). Acad Emerg Med. 17: 194-201.

Braun, C., Hofmeister, E.H., Lockwood, A.A., Parfitt, S.L. (2007) Effects of diazepam or lidocaine premedication on propofol induction and cardiovascular parameters in dogs. J Am Anim Hosp Assoc. 43: 8-12.

Brock, N., Hildebrand, S. (1990) A comparison of xylazine-diazepam-ketamine and xylazine-guaifenesin-ketamine in equine anesthesia. Vet Surg. 19: 468-474.

Butera, T., Moore, J., Garner, H., Amend, J., Clarke, L., Hatfield, D. (1978) Diazepam/xylazine/ketamine combination for short-term anesthesia in the horse. Vet Med Small Anim Clin. 73: 490,495-496,499.

Chai, C., Wang, S. (1966) Cardiovascular actions of diazepam in the cat. J Pharmacol Exp Ther. 154: 271-280.

Covey‐Crump, G.L., Murison, P.J. (2008) Fentanyl or midazolam for co‐induction of anaesthesia with propofol in dogs. Vet Anesth Analg. 35: 463-472.

Erdogan, M.A., Begec, Z., Aydogan, M.S., Ozgul, U., Yucel, A., Colak, C., Durmus, M. (2013) Comparison of effects of propofol and ketamine-propofol mixture (ketofol) on laryngeal mask airway insertion conditions and hemodynamics in elderly patients: a randomized, prospective, double-blind trial. J Anesth. 27: 12-17.

Fayyaz, S., Kerr, C.L., Dyson, D.H., Mirakhur, K.K. (2009) The cardiopulmonary effects of anesthetic induction with isoflurane, ketamine‐diazepam or propofol‐diazepam in the hypovolemic dog. Vet Anesth Analg. 36: 110-123.

Haskins, S., Farver, T., Patz, J. (1986) Cardiovascular changes in dogs given diazepam and diazepam-ketamine. Am J Vet Res. 47: 795-798.

Haskins, S., Pascoe, P.J., Ilkiw, J.E., Fudge, J., Hopper, K., Aldrich, J. (2005) Reference cardiopulmonary values in normal dogs. Comp Med. 55: 156-161.

Haskins, S.C. (2015) Monitoring Anesthetized Patients, In: Veterinary Anesthesia and Analgesia. The Fifth Edition of Lumb and Jones. Grimm, K.A., Lamont, L.A., Tranquilli, W.J., Greene, S.A., Robertson, S.A. (eds.). John Wiley & Sons, Pondicherry, India, p. 86-113.

Haskins, S.C., Farver, T.B., Patz, J.D. (1985) Ketamine in dogs. Am J Vet Res. 46: 1855-1860.

Henao-Guerrero, N., Riccó, C.H. (2014) Comparison of the cardiorespiratory effects of a combination of ketamine and propofol, propofol alone, or a combination of ketamine and diazepam before and after induction of anesthesia in dogs sedated with acepromazine and oxymorphone. Am J Vet Res. 75: 231-239.

Hopkins, A., Giuffrida, M., Larenza, M.P. (2014) Midazolam, as a co‐induction agent, has propofol sparing effects but also decreases systolic blood pressure in healthy dogs. Vet Anesth Analg. 41: 64-72.

Ilkiw, J., Suter, C., McNeal, D., Farver, T., Steffey, E. (1996) The effect of intravenous administration of variable‐dose midazolam after fixed‐dose ketamine in healthy awake cats. J Vet Pharmacol Ther. 19: 217-224.

Kennedy, M.J., Smith, L.J. (2014) A comparison of cardiopulmonary function, recovery quality, and total dosages required for induction and total intravenous anesthesia with propofol versus a propofol-ketamine combination in healthy Beagle dogs. Vet Anesth Analg. 42: 350-359.

Ko, J.C., Payton, M.E., White, A.G., Galloway, D.S., Inoue, T. (2006) Effects of intravenous diazepam or microdose medetomidine on propofol-induced sedation in dogs. J Am Anim Hosp Assoc. 42: 18-27.

Lerche, P., Nolan, A., Reid, J. (2000) Comparative study of propofol or propofol. Vet Rec. 146: 571-574.

Mair, A.R., Pawson, P., Courcier, E., Flaherty, D. (2009). A comparison of the effects of two different doses of ketamine used for co‐induction of anaesthesia with a target‐controlled infusion of propofol in dogs. Vet Anesth Analg. 36: 532-538.

Mannarino, R., Luna, S.P., Monteiro, E.R., Beier, S.L., Castro, V.B. (2012) Minimum infusion rate and hemodynamic effects of propofol, propofol‐lidocaine and propofol‐lidocaine‐ketamine in dogs. Vet Anesth Analg. 39: 160-173.

Martinez-Taboada, F., Leece, E.A. (2014) Comparison of propofol with ketofol, a propofol-ketamine admixture, for induction of anaesthesia in healthy dogs. Vet Anesth Analg. 41: 575-582.

Muir, W., Gadawski, J. (1998) Respiratory depression and apnea induced by propofol in dogs. Am J Vet Res. 59: 157-161.

Rankin, D.C. (2015) Sedatives and Tranquilizers, In: Veterinary Anesthesia and Analgesia. The Fifth Edition of Lumb and Jones. Grimm, K.A., Lamont, L.A., Tranquilli, W.J., Greene, S.A., Robertson, S.A. (eds.). John Wiley & Sons, Pondicherry, India, p. 196-207.

Riccó, C.H., Henao-Guerrero, N. (2014) Cardiovascular effects of orotracheal intubation following anesthetic induction with propofol, ketamine-propofol, or ketamine-diazepam in premedicated dogs. J Am Vet Med Assoc. 244: 934-939.

Seliskar, A., Nemec, A., Roskar, T., Butinar, J. (2007) Total intravenous anaesthesia with propofol or propofol/ketamine in spontaneously breathing dogs premedicated with medetomidine. Vet Rec. 160: 85-91.

Smith, I., White, P.F., Nathanson, M., Gouldson, R. (1994) Propofol. An update on its clinical use. Anesthesiology. 81: 1005.

Smith, J., Gaynor, J., Bednarski, R., Muir, W. (1993) Adverse effects of administration of propofol with various preanesthetic regimens in dogs. J Am Vet Med Assoc. 202: 1111-1115.

Tweed, W., Minuck, M., Mymin, D. (1972) Circulatory responses to ketamine anesthesia. Anesthesiology, 37: 613-619.

Watkins, S., Hall, L., Clarke, K. (1987) Propofol as an intravenous anaesthetic agent in dogs. Vet Rec. 120: 326-329.

White, K.L., Shelton, K., Taylor, P.M. (2001) Comparison of diazepam-ketamine and thiopentone for induction of anaesthesia in healthy dogs. Vet Anesth Analg. 28: 42-48.

Wong, D.H., Jenkins, L.C. (1974) An experimental study of the mechanism of action of ketamine on the central nervous system. Can Anesth Soc J. 21: 57-67.