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Indian Journal of Pharmacology, Vol. 38, No. 6, November-December, 2006, pp. 435-437 Correspondence Teaching undergraduate students appropriate dose calculations in relation to intravenous infusion Parmar DM, Jadav SP Department of Pharmacology, M.P. Shah Medical college, Jamnagar-361008 Code Number: ph06125 Medical emergencies such as cerebral malaria, diabetic coma, cardiogenic shock and many more require immediate treatment with parenteral drug administration. Intravenous (i.v.) infusion is one of the commonly preferred routes for this purpose. As one of the goals of undergraduate training is to train students in managing patients,[1] it is mandatory that the students acquire a sound knowledge of certain basic steps of intravenous drug infusion. These include dose calculation ( viz., based on body weight and body surface area) and clinical skills ( viz. , proper collection of drugs from ampoule/vial, introduction of drug into suitable diluting fluid, i.v. drip setting, etc.). One of the ways to achieve such a goal is by including many exercises on calculation of infusion rates in the undergraduate pharmacology practicals curriculum. As dose calculation is an important initial step in such clinical procedures, we have emphasized it in relation to different aspects such as the following: Total dose: The infusion rate will not differ in case of total dose administration (e.g., infusion rate of quinine will remain the same for a 30, 50 or a 70 kg patient since it is given in the dose of 10 mg/kg in 500 ml of 10% dextrose solution which is to be administered over 4 h). In contrast to this, the infusion rate will differ when drugs are to be given at the specified rates (e.g., infusion rate of aminophylline will differ for a 30, 50 or a 70 kg patient since it is to be given in the dose of 1 mg/kg/hr in 500 ml of normal saline). Weight (mg/kg): The weight-based dose calculation (mg/kg) is more popular despite certain disadvantages, viz., one needs to know the different doses according to body weight (mg/kg) as well as according to the age of the patient.[2] Body surface area: Body surface area (BSA) is another method which is considered as a more accurate basis for dose calculation since total body water, extracellular fluid volume and metabolic activity are better paralleled by it. The BSA of an individual can be calculated from the formula of Dubois [BSA (m 2) = Body weight (kg) 0.425 X Height (cm) 0.725 X 0.007184] or obtained from chart-form/slide-rule nomograms based on body weight and height. Dose recommendations in terms of BSA are available only for a limited number of drugs (e.g., anticancer drugs) as this method is more cumbersome in clinical practice.[3]
Time: The dose of some drugs is calculated per minute and per hour (e.g., dopamine 5 mcg/kg/min and insulin 0.1 U/kg/h). The infusion rates differ for different time duration in case of anticancer drugs like paclitaxel (see below). Average adult body weight: The dose can also be calculated by using the average adult body weight (60-70 kg) basis from the formula: [Individual dose = Body weight (kg)/70 x average adult dose].[3] Diluting fluid: Selection of a suitable diluting fluid is necessary for i.v., infusion. For example, 10% dextrose solution is being used for quinine infusion, which prevents hypoglycemia due to hyperinsulinemia caused by the powerful stimulatory effect of quinine on pancreatic beta cells,[4] whereas dopamine infusion is given with 5% dextrose (acidic pH) solution for its compatibility and stability with the latter (i.e., 5% dextrose).[5] Some problems that may be encountered during dose calculation are listed below. 1. Following the same steps of dose calculation for different drugs To calculate the rate of quinine infusion is simple since quinine is to be given in 500 ml of 10% dextrose solution, to be administered over 4 h (i.e., we have to administer 500 ml of 10% dextrose solution with the required dose of quinine over 4 h). But students can make mistakes if they follow this step of rate calculation for calculating the infusion rate of other drugs that are to be administered by their specified infusion rates (e.g., aminophylline: 1 mg/kg/h). Therefore, the students should be taught these aspects as well since many drugs come under this category (e.g., dopamine, insulin and oxytocin). [Please refer comparison given on page 1] Thus, it is obvious that such an infusion rate for aminophylline (133-167 drops/min) is not practically feasible. The correct calculation for the rate of aminophylline infusion is given below. Exercise: You have decided to give i.v. infusion of aminophylline for a child (10 years old, 30 kg) suffering from acute bronchial asthma (Dose: 1 mg/kg/hr). Set an i.v. drip for this patient. Answer: A. Calculate the required dose of Inj. aminophylline: B. Selection of fluid: C. Aminophylline is available as 2.5% W/V in 10 ml ampoule, i.e. 250 mg/10 ml. Now we have 250 mg in 500 ml of normal saline solution, i.e. 30 mg will be present in 30/250 x 500 = 60 ml, which is to be administered in 1 h. So, the desired rate of administration will be: Thus, in 1 min, 1 ml is to be given OR Introduce all 10 ml of Inj. aminophylline into 500 ml of normal saline solution. i.e. 500 ml of normal saline solution contains 250 mg of aminophylline So, 1 ml will have 1/500 x 200 = 0.5 mg of aminophylline. So, 30 mg will be present in 30/0.5 x 1 = 60 ml, which is to be administered in 1 h. 2. Dose calculation by different methods Problem: Calculate the required dose for aminophylline infusion for a child suffering from acute bronchial asthma (12 years old, 37 kg, BSA 1.25 m 2 Dose: 1 mg/kg/h). Solution: A. mg/kg basis: B. Average adult body weight (60-70 kg) basis: C. BSA-based rule:
According to this, (37 + 30) percentage of the adult dose of a drug This shows that there is no difference in doses calculated by mg/kg and average adult body weight-based rules, but there is a definite difference when both are compared with the BSA-based rule. The dose calculated by the Salisbury rule is closer to the BSA-based value. Metabolism of theophylline (aminophylline) is often faster in children, after the first year of life,than in adults; and there is a marked interindividual variation in the rate of its elimination (average half-life is about 3.5 h in young children as compared to 8-9 h in adults).[3],[4] Considering these pharmacokinetic parameters as well as the narrow safety margin of aminophylline, the more accurate BSA-based rule may be preferred for dose calculation, keeping in mind its limited application in a clinical set-up. 3. Dose calculation in relation to time duration Paclitaxel (an anticancer drug) is to be given in different schedules [ Schedule 1: 175 mg/m 2 over 3 h (infusion rate: 58 mg/m 2 per hour, plasma clearance: 212 ml/min per m 2) and Schedule 2: 175 mg/m 2 over 24 hours (infusion rate: 7 mg/m 2 per hour, plasma clearance: 393 ml/min per m 2)].[4] A practical problem may arise if one calculates the dose of paclitaxel for schedule 2 from schedule 1. The dose and infusion rate will become 1400 mg/m 2 and 58 mg/m 2 respectively, which appear very different from the actual schedule 2 for 24 h. As clearance of paclitaxel is saturable and decreases with an increasing dose or dose rate,[4] such probable mistakes will definitely affect the clinical response. To conclude, during undergraduate pharmacology practicals, different aspects, such as total dose, weight (mg/kg and average adult body weight basis), BSA, time duration and diluting solution, as well as likely practical problems that may arise during dose calculation, should be highlighted by demonstrating different exercises on the calculation of infusion rates. References
Copyright 2006 - Indian Journal of Pharmacology |
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