DRUG DOSAGES & CONTINUOUS RATE INFUSION PROTOCOLS FOR CARDIOVASCULAR RESEARCH IN SWINE M. Michael Swindle, DVM, Diplomate ACLAM & ECLAM, swinetech@hotmail.com INTRODUCTION Swine are prone to arrhythmias associated with manipulation of the heart and creation of heart failure models. It is better to prevent them by selection of appropriate anesthetic protocols and usage of adjunct agents for prevention of the arrhythmias. Discussion of the use of these agents is included in Swindle and Smith, 2015. Table 1 includes dosages of commonly used agents in cardiovascular surgery, interventional catheter protocols and heart failure models. The drugs and dosages in Table 1 are based upon a combination of published literature and practical experience in the laboratory. As a general rule, when using a new drug without a known dosage in swine, I start with the human pediatric dosage. Reviews and recommendations on the continuous rate infusion protocols (CRI) can be found online. 2, 3 It is imperative that anesthetists understand that cardioactive drugs are given to effect and careful monitoring the pig s various cardiopulmonary parameters is essential. This is especially true in CRI protocols used to treat or prevent cardiopulmonary emergencies. Calculation of a CRI dosage can be complicated. Many of the infusion rates are administered as µg/kg/min while the concentration of the drug is usually supplied by the pharmaceutical company in. Generally the various CRI drugs are loaded into a 250 ml bag of 0.9% Saline or Dextrose 5% in water. The concentration of the drug in the iv bag is dependent upon the weight of the animal and the anticipated duration of drug delivery. Human pediatric bag concentrations can be used as a starting point. 3 The preferred method of delivery of the CRI is via an infusion pump in which the rate is set in ml/hr. Lactated Ringer s Solution is the conventional iv fluid used for maintenance during surgery at a dosage of 5-15 ml/kg/hr. If a bag with a drip rate is used instead of an infusion pump then the number of drops it takes to reach 1 ml of solution must be determined. Different types of iv systems for drop delivery can confuse this calculation. Some useful conversions to be considered are: 1 mg = 1000 µg 1 µg = 0.001 mg Mg % solution = gm/100 ml which can be reduced to mg/ ml 20 % solution = 2 gm/100 ml = 2000 mg/100 ml = 20 mg/ml Mg/kg/hr is converted to µg/kg/minute by converting mg to µg and dividing by 60 to convert hours to minutes: 1 mg/ kg/hr = 1000 µg/kg/hr = 1000/60 = 16.6 µg/kg/min Concentration of the drug in the iv bag is used to calculate how many ml/hr are needed to be set in the iv infusion pump for a desired CRI. Example: For 4 mg/ml concentration in the iv bag, the calculated administration rate for a 20 kg pig and a dose of 2 /hr is: 2 /hr X 20 kg = 40 mg total/hr divided by 4 mg/ml = 10 ml/hr The same volume of the drug to be placed into the iv bag is removed prior to injecting the drug. Example: If 4 ml of the drug is to be injected into the bag, then 4 ml of the iv fluid is removed first. CARDIOPULMORY EMERGENCIES Monitoring of the pig requires that you have an EKG, pulse oximetry, end tidal CO2, rectal or esophageal temperature, and direct observation as a minimum for complex cases. In the case of cardiopulmonary emergency the flow chart in Table 2 provides a list of drugs to be administered according the particular situation. This type of resource along with an emergency kit containing the main cardiac drugs (listed in the table) and their dosages should be present in the operating room. A defibrillator also should be present. In pigs in ventricular fibrillation a 10 joule countershock can be delivered with paddles directly on the heart. In a closed chest situation a 200 joule countershock will be required. Table 3 contains the physiologic effects of the various cardioactive drugs used in swine. REFERENCES 1. Swindle MM, Smith AC, 2015. Swine in the Laboratory: Surgery, Anesthesia, Imaging and Experimental Techniques, Taylor and Francis (CRC Press): Boca Raton, FL. 2. Macintire DK, Tefend M, 2004. Constant Rate Infusions: Practical Use, VC, http:// www.veterinaryteambrief.com/sites/default/ files/sites/cliniciansbrief.com/files/0404_ procedurepro.pdf 3. Larsen GY, Parker HB, Cash J, O Connell M, Grant MJC, 2005. Standard Drug Concentrations and Smart-Pump Technology Reduce Continuous- Medication-Infusion Errors in Pediatric Patients, Pediatrics 116(1): http://pediatrics. aappublications.org/content/116/1/e21.full
TABLE 1. DRUGS USED IN CARDIOVASCULAR RESEARCH (IV DOSAGES) 0.2-0.6 1.0 mg/ml 0.2-0.6 /hr Bronchodilation 5-10 50 mg/ml 0.5-3.5 /hr Class I & II antiarrhythmic to prevent fatal arrhythmias 0.001 0.5 mg/ml 0.4 /hr Paralytic agent 0.01-0.03 0.4 mg/ml 0.04 /hr Increase heart rate & treat heart block 5.0-7.0 infused slowly over 5-15 minutes Increase contractility, treat Ca channel blocker overdose 0.01-0.04 Treat supraventricular arrhythmias, decrease conduction, increase contractility 0.2 1 mg/ml 2-10 μg/kg/hr Ca channel blocker, Class IV antiarrhythmic, prevent supraventricular arrhythmias 4 mg/ml 2-10 μg/kg/hr Increase heart rate & improve contractility 40 mg/ml 2-10 /hr 2-20 μg/kg/min Increase heart rate & blood pressure, improve contractility 0.02-0.05 2.4 mg/ml 3 /hr 0.025-0.3 μg/kg/min Treat ventricular fibrillation, increase cardiac output & perfusion, vasoconstriction 0.1 2 mg/mlb 0.2 /min Short term Anesthetic used in pigs with cardiovascular compromise/induction only 200-500 IU/kg 100 IU/ml 18 IU/kg/hr Anticoagulation 8 μg/ml 0.01 μg/kg/min Treat bradycardia & heart block 2-4 4 mg/ml 4 /hr 20-80 μg/kg/min Prevent vasospasm, treat ventricular arrhythmias 0.15-0.3 meq/kg 0.75-1 meq/kg/day Treat intractable ventricular fibrillation 0.25-1.0 1 mg/ml 3 /hr Intraoperative analgesic, reduce preload & oxygen consumption, vasodilation. Not recommended for survival procedures 200 μg diluted in 2 slow infusion to effect 0.2 mg/ml 1-20 μg/kg/min Coronary vasodilation 5-20 μg/kg 100 μg/ml 0.1-0.5 μg/kg/min Increase blood pressure by vasoconstriction 6.0-8.0 8 mg/ml 10-20 /hr 10-40 μg/kg/min Ventricular antiarrhythmic 0.04-0.06 1 mg/ml 1 /min Treat tachycardia 1-1.5 1 mg/ml 2-2.5 /hr Paralytic agent 1-2 mev/kg 1 meq/ml 0.3-0.5 mev/kg/hr Must monitor blood gas Treat acidosis in cardiopulmonary resuscitation 0.2 mg/ml 0.5-0.8 μg/kg/min Reduce blood pressure, vasodilation 0.05 μg/kg 10 μg/ml 10-30 μg/kg/hr Used in high dose opioid anesthetic protocols 0.1 0.1 mg/ml 0.01-0.05 /hr Paralytic agent 0.05-0.15 2.5 mg/ml 2-10 μg/kg/min Treat supraventricular arrhythmias, Ca channel blocker, Class IV antiarrhythmic
CARDIOPULMORY ARREST