CONTENTS. Page_. Solutions to the Exercises Unit Conversions Exercise: Fill in the missing information PART 1 Exercises: 1 18 PART 2 Exercises: 1 8

Transcription

1 CONTENTS Page_ Introduction Unit Conversions: Exercise: Fill in the missing information PART 1: Exercises: Calculate an Intermittent Dose Calculate an Intermittent Dose of a Solid Formulation Calculate an Intermittent Dose of a Liquid Formulation Calculate an Intermittent Dose Adjusted to the Patient s Body Weight PART 2: Exercises: Calculate a Continuous Dose (administered by intravenous infusion) Calculate the Corresponding Infusion Rate for a Prescribed Dose Solutions to the Exercises Unit Conversions Exercise: Fill in the missing information PART 1 Exercises: 1 18 PART 2 Exercises: 1 8 Appendix: Medication Errors

2 INTRODUCTION You are being offered this Medication Calculation Module because clinical instructors are concerned that students are struggling to translate the amount of drug prescribed, into the corresponding amount of an available formulation of that drug that should be administered to the patient. A medication error is perhaps the most frequent, swift and subtle act of negligence by which nurses pose harm to patients. Medication errors are widely recognized as a big complicated patient safety problem that can t be solved with a calculator alone (read some of the background material included as an appendix if you re interested). Only a fraction of medication errors stem directly from mathematical errors. Giving the wrong drug has nothing to do with math, but giving the wrong dose might. A drug dose calculation is a principled procedure. Proficiency in mathematics does not ensure proficiency in calculating a drug dose, but there is a link. When you become familiar with the concepts that link a mathematical calculation with giving a correct dose, your patients and career will be better for it. There are two kinds of dose calculations, depending on whether a drug is delivered in intermittent doses or administered continuously: 1. Most drugs are administered in discrete doses at intermittent times (i.e., once-daily, twice-daily, every six hours ). The time between each dose is called a dose interval. Most drugs come in solid or liquid forms. Sometimes a drug that will be given in liquid form is supplied as a solid, and thus needs to be reconstituted (ie, dissolved or suspended in a diluent). Directions for reconstitution will always be found in the package insert. We will begin with exercises on how to deliver a correct intermittent dose of a solid or liquid formulation. 2. Some drugs are administered continuously, often by intravenous infusion of a drug in solution. Accordingly, there will be a second set of exercises on how to initiate and adjust a continuously administered drug. 2

3 UNIT CONVERSIONS WARNING!!! Analogies help some to relate a new concept with familiar concepts, but for others, analogies conversely add confusion. The same is true for background trivia: for some it inspires interest, for others it s too much information! Don t read the green stuff if it will only confuse you. Concept: Money is a currency we re familiar with. Money is expressed in units such as dollars {$(Canadian, US, Australian)}, Pounds { }, Yen { }, or Euros { }. Money can be issued as bank notes or coins of various denominations (i.e., a fifty dollar bill or a hundred dollar bill). A $50 bank note is about the same size and weight as a $100 bank note. Dose is a currency. It is almost always expressed as mass units (e.g., grams {g}, milligrams {mg}, micrograms {μg}). A few older drugs such as penicillin, heparin and insulin are still prescribed in conventional units. Both kinds of units represent an amount of drug. The recommended dose range ties an amount of drug to its expected biological effects. Instead of bank notes or coins, drugs are issued in solid or liquid formulations such as tablets, capsules or vials. Instead of denominations, solid drug formulations are issued in various strengths such as a 50 mg tablet or a 100 mg tablet. Liquid drug formulations may be issued or reconstituted in various concentrations such as 50 mg per ml or 100 mg per ml. Whereas solid formulations are issued as units per capsule or units per tablet, liquid formulation units have a volume of liquid as a denominator that defines concentration. The math is simply to purchase the prescribed dose using available formulations as currency, but first ensure that the prescription and the formulation on hand are converted to the same units. You wouldn t want to pay $50 for something that costs 50 cents, because that s a hundred times too much! You shouldn t give 50 milligrams of drug to a patient that was prescribed 50 micrograms; that s a thousand times too much! Try filling in the? s in the tables below. If you are having trouble with metric conversions and symbols, you ought to make yourself a pocket card and carry it with you for reference until you ve caught on to the system / a thousand kilo 0.1 1/ one tenth deci / one hundredth centi / one thousandth milli / one millionth micro Fill in the missing information: kilogram (kg) =? grams ? 10-9? gram (g) = 1000?? kg 10 6? milligram (mg) = 0.001? 1000? 10-6? microgram (μg) = ? 0.001? 10-6? Fill in the missing information: one litre (L) =? ml ? 75 milliliters (ml) =? L 75000? 500 microlitres (μl) = ?? ml The "insulin unit" dates back to when preparations of the hormone extracted from porcine or bovine pancreas were impure and it was necessary to standardize batches so that one unit of insulin was the amount required to reduce blood glucose in a fasting rabbit to 45 mg/dl (2.5 mmol/l). In most countries, human insulin is supplied in solution or suspension of 100 U/mL, which is about 3.6 mg/ml, which is between 25 and 30 U/mg. The biological activity of heparin varies slightly between commercial preparations, but is around 150 USP units/mg. One USP unit of heparin is the amount that prevents 1.0 ml of citrated sheep plasma from clotting for 1 hour after the addition of 0.2 ml of 1% calcium chloride. 3

4 Part 1: How to deliver a correct intermittent dose of a solid or liquid formulation: Try these exercises on how to deliver a correct intermittent dose of a solid or liquid formulation, starting with solid formulations that have been prescribed in the same units as the strengths of the formulation on hand: 1. Warfarin tablets are scored so they can be split in half. Supplies of both 4 mg tablets and 5 mg tablets have been issued to treat your patient who has chronic atrial fibrillation. He is initially prescribed warfarin 10 mg p.o. once-daily. How will you administer that dose? [HINT: an item priced at $10 can be purchased with two $5 bills, but drug calculations require exact change, meaning that you can t give the patient three 4 s and expect him to spit out 2 mg.] His target INR is 2.5, but after 48 hrs on 10 mg/day his INR is actually 4.5. In response, the prescription is to skip the next dose, then resume warfarin at 7 mg p.o. once-daily. From a supply of 4 mg and 5 mg tablets, how will you administer a 7 mg oral dose? Within 36 hours of adjusting the dose, his INR is now 1.8, so his dose is increased to 9 mg daily. From a supply of 4 mg and 5 mg tablets, how will you administer a 9 mg oral dose? [Warfarin is the principal oral anticoagulant prescribed for most patients at substantial risk for arterial and venous thromboembolic complications, but it has a narrow therapeutic index: a little too much warfarin will put the patient at excess risk of non compressible hæmorrhage (e.g., intracranial or GI bleed), but not enough warfarin leaves the patient at risk of a thromboembolic catastrophe such as an ischemic stroke. Warfarin is inconvenient because it interacts with numerous foods and drugs, thus requires dose adjustments in relation to close laboratory monitoring of fluctuations in a patient s prothrombin times (PT, now most often standardized as international normalized ratio {INR}).] 2. Digoxin mg p.o. is prescribed to a patient with a fast ventricular response to atrial flutter. You have digoxin 0.25 mg tablets on hand. How many tablet(s) should you give to the patient? 3. Diazepam 25 mg p.o. is prescribed. You have diazepam 10 mg tablets on hand. How many tablet(s) should you give to the patient? [If you don t know why diazepam is being prescribed (e.g., manage anxiety, pre-anaesthetic, raise convulsive threshold, skeletal muscle relaxant, and mitigate ethanol withdrawal symptoms) you won t know how to assess the response. It will likely make the patient drowsy, and sometimes that s the desired effect. If not, it is an expected side-effect.] Be careful with this next question. The units in which the drug is prescribed are not the same units as the formulation on hand is labeled. 4. An woman with bacterial otitis media is prescribed sulfisoxazole 1 g p.o. You have 500 mg tablets on hand. How many tablet(s) should you give to the patient? 4

5 Now try calculating a liquid dose: 5. A fellow with intractable hiccups is prescribed chlorpromazine 25 mg IM. You have an unopened 10 ml vial of solution for injection labeled 25 mg/ml. What amount of chlorpromazine solution should you prepare to inject? 6. An ampoule of Drug A is labeled, 100 mg/10 ml. The patient is to receive a 15 mg dose. What volume should you administer? 7. Drug B is supplied in 2 ml ampoules labeled 100 mg/ml IM STAT. If your patient is to receive a 200 mg dose, what volume should you inject? 8. A casualty officer orders Gravol 30 mg IM STAT for an 8 year old that is puking in the ER. The department doesn t stock that brand. On hand are Novo-Dimenate (dimenhydrinate) 50 mg/2ml and PMS-Diphenhydramine (diphenhydramine) 50 mg/ml. Which drug should you give, and what volume of that drug should you inject? Regarding the use of brand names in general: The names of drugs are a problem. Each and every drug has a single generic name that is common to USA, Canada, the EU and Japan. Generic drug nomenclature is somewhat systematic in relation to drug class: (e.g., -statins, -glitazones, -triptans, -prils, -olols ). But most drugs eventually acquire multiple brand names that vary internationally, and are catchy sounding but sometimes confusingly similar sounding. Solution: educational material should emphasize generic names and de-emphasize brand names. Examples: Generic Name: amoxacillin Brand Names: CANADA: Amoxil, Apo-Amoxi, Gen-Amoxicillin, Novamoxin, Nu-Amoxi, plus combinations; ELSEWHERE: Agram, Alfamox, Almodan, Amodex, Amoxidal, Amoxidin, Amoxillat, Amoxypen, Ardine, AX250, Clamoxyl, Cuxacillin, Dura AX, Flemoxin, Hiconcil, Ibiamox, Larocin, Larotid, Moxal, Moxaline, Neamoxyl, Polymox, Raylina, Robamox, Sigamopen, Silamox, Trimox, Uro-Clamoxyl, Ultimox, Zamocillin; Generic Name: metoprolol Brand Names: CANADA: Lopressor, Betaloc, Dom-Metoprolol, Apo-Metoprolol, Novo- Metoprolol, Nu-metop, PMS-metoprolol, Gen-metoprolol Health professionals should avoid behaviours that reflect or might be construed to reflect conflicts of interest. Reference to brand names raises suspicion that treatment decisions may be unduly influenced by marketing forces rather than unbiased clinical scientific evidence and sound clinical judgment. 9. Morphine and atropine are compatible in the same syringe and may be given together as a single injection. A physician orders morphine 4 mg IV and atropine 0.6 mg IV to be given together to a man with symptomatic bradycardia. In stock, morphine sulphate is available in ampoules containing 5 mg/ml, 10 mg/ml and 15 mg/ml. Atropine sulfate is available in ampoules of 0.4 mg/ml or 0.6 mg/ml. Select the most appropriate size syringe: 1 ml, 3 ml or 5 ml. Which stock concentration of morphine do you choose? What volume of that concentration yields a 4 mg dose? Which stock concentration of atropine do you choose? What volume of that concentration yields a 4 mg dose? What is the total volume (i.e., both drugs) for injection? What size of syringe would be appropriate for that volume? 5

6 10. A preoperative medication order reads: Give morphine 12 mg IM, atropine 0.4 mg IM and prochlorperazine 7.5 mg IM one hour prior to induction. In stock, morphine sulphate is available in ampoules containing 5 mg/ml, 10 mg/ml and 15 mg/ml. Atropine sulfate is available in ampoules of 0.4 mg/ml or 0.6 mg/ml. Prochlorperazine is available in 10 mg/2 ml ampoules. Select the most appropriate size syringe: 1 ml, 3 ml or 5 ml. Which stock concentration of morphine do you choose? What volume of that concentration yields a 4 mg dose? Which stock concentration of atropine do you choose? What volume of that concentration yields a 4 mg dose? What volume of prochlorperazine 10 mg/2 ml yields a 4 mg dose? What is the total volume (i.e., both drugs) for injection? What size of syringe would be appropriate for that volume? It may be of interest that the American Society of Anesthesiologists Task Force Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective Procedures do not recommend routine use of gastric acid reducing agents, antiemetics or antimuscarinic drugs intended to minimize the risk of pulmonary aspiration, because there is insufficient evidence that these medications actually have any effect on the incidence or severity of pulmonary aspiration. 11. You are caring for a woman with threatened premature delivery at 31 weeks gestation. An order is given to administer betamethasone 12 mg IM STAT, and repeat in 24 hours. Betamethasone is available in 1 ml vials containing 4 mg/ml. How many vials will you need to open to administer the prescribed dose? What volume of that solution will you prepare to inject? 12. The physician orders 5 International Units (IU) of oxytocin administered with the delivery of the anterior shoulder. The vial contains 1 ml of solution containing 10 IU of oxytocin. What volume of oxytocin solution will you draw up? 13. Following birth, the physician orders Vitamin K 1 mg I.M. for the infant. Vitamin K is supplied in 1 ml vials containing 10 mg/ml. What volume of that solution will you prepare to administer by intramuscular injection? What size of syringe (0.5 ml, 1 ml, 3 ml) would be least appropriate for this injection? 6

7 14. A woman in early labor is prescribed Demerol 150 mg with Gravol 25 mg IM. You have the following concentrations of these drugs available to you: Demerol 50 mg/ml in a 1 ml vial Demerol 75 mg/ml in a 1 ml vial Demerol 100 mg/ml in a 1 ml vial Gravol 50 mg/ml in a 1 ml vial Which stock concentration of Demerol do you choose? Explain. What volume of that concentration yields a 150 mg dose? What volume of the Gravol concentration yields a 25 mg dose? What is the total volume (i.e., both drugs) for injection? Is that an appropriate volume for IM injection? Regarding the use of meperidine (aka, pethidine) [Demerol ] as an example: Although it is still used frequently on many labor units, there may be better alternatives. The choice is controversial. The American Society for Gastrointestinal Endoscopy suggested that meperidine might be preferred over morphine, on the basis of evidence that morphine crosses the fetal blood-brain barrier more rapidly. However, both drugs readily enter the fetal brain and there is no evidence cited in the guideline that a differential rate of fetal CNS penetration after maternal administration of either meperidine or morphine is of any clinical importance. Other jurisdictions continue to describe meperidine as a choice for early labor analgesia. Mander R. Analgesia and anaesthesia in childbirth: obscurantism and obfuscation. J Advanced Nursing 1998;28: Faucher MA and Brucker MC. Intrapartum Pain: Pharmacologic Management. JOGNN 2000;29: ISMP Canada Safety Bulletin. Meperidine (Demerol) Medication Safety Issues. Spring accessed online Hale TW. Drug therapy and breastfeeding: antibiotics, analgesics, and other medications. NeoReviews. 2005;6(6):e233-e240. NSW-TAG. Use of pethidien for pain management in the emergency department. August 2004 ASGE. Guidelines for endoscopy in pregnant and lactating women. 2005;61(3): Nova Scotia Perinatal Program: 7

8 What if the dose is to be adjusted to the size of the patient? To get the most benefit with the least side effects, it may be useful to normalize (i.e., tailor) the dose of a drug to the volume of the body compartment into which the drug distributes, which often corresponds well enough with the patient s total body weight (or perhaps lean body weight, estimated bone mass or body surface area). The general idea is to give bigger people bigger doses, and smaller people proportionally smaller doses, so they all achieve the same tissue levels following a dose that is the right size for them. It is especially common to adjust pædiatric doses according to a child s weight. In that case, the prescription might read, Drug-C syrup 2 mg/kg p.o. q4h. It means, first determine how much the child weighs, then give 2 milligrams of Drug-C for every kilogram of body weight. If the child weighs 14 kg, the dose would be 14 2 mg = 28 mg. Try to determine the correct volume of a drug formulation that you should prepare to give to a patient who has been prescribed these weight-adjusted doses: 15. A 5 year old asthma patient is prescribed theophylline elixir 3 mg per kg body weight p.o. q6h. She weighs 15 kg. What dose of theophylline elixir does that work out to? How much theophylline would she get per day? Theophylline elixir comes in a 480 ml bottle containing 80 mg/15 ml. What volume of elixir will provide the prescribed dose? 16. A 4 year old child has oxacillin 50 mg/kg/day in divided doses infuse IV at 6 hour intervals; not to exceed 1.5 g/day. Oxacillin comes pre-mixed in vials of two different sizes containing either 1 g or 2 g of oxacillin in 50 ml of iso-osmotic dextrose solution. This child weighs 12.5 kg. How much oxacillin should this child receive on a daily basis? Does that exceed the prescribed daily limit? Dividing the total daily dose into equal doses, how many milligrams should be given every 6 hours? If you choose to draw a dose from the 1g/50 ml concentration, what is the smallest syringe you could use to draw up the dose: will you need a 1 ml, 3 ml, 5 ml, or a 10 ml syringe? 17. A 4 month old child is prescribed cefpodoxime oral suspension 4 mg/kg p.o. q12h. The child weighs 25 kg. The bottle is reconstituted to a 50 mg/ml concentration of lemon crème flavored cefpodoxime suspension. How much of that suspension should you give for each dose? 18. Remember the woman that was prescribed Demerol 150 mg during early labor in question #14? Following birth three hours later, her 3500 g infant has respiratory 8

9 depression. The resuscitation team calls for naloxone hydrochloride [Narcan ] 0.1 mg/kg IV. Naloxone hydrochloride comes in 1 ml vials that contain 0.4 mg/ml. What is the correct dose in mg? How many millilitres of the 0.4 mg/ml solution corresponds to that dose? Part 2: exercises on how to initiate and adjust a continuously administered drug: 1. Your patient is receiving a continuous heparin infusion. The intravenous solution contains units of heparin in 500 ml of 5% dextrose (D5W). The patient is to receive 1800 units of heparin per hour. What volume of the heparin solution must infuse to provide that dose of heparin in one hour? The infusion pump rate has to be programmed in ml/hr, so what rate will you select? At that rate, how long will a 500 ml bag of heparin in D5W last? 2. A patient s daily fluid balance is being supplemented by constant intravenous infusion of 1500 ml/24 hours of 5% dextrose in 0.9% sodium chloride solution (D5S), using a 60 drops = 1 ml infusion set. At how many drops per minute should you regulate the iv to deliver 1500 ml/24 hrs? 3. The patient you are caring for is a type 1 diabetic in active labor. She has a continuous insulin infusion prescribed according to a sliding scale (i.e., you adjust the infusion rate, and thus titrate her insulin dose according to her capillary blood glucose response). The intravenous solution contains Humulin R 50 units/500 ml of 0.9% sodium chloride (normal saline): Blood glucose (mmol/l) Humulin R (units/hour) < 4 mmol/l Hold insulin < 6 mmol/l 1 unit/hr < 8 mmol/l 2 units/hr 8 mmol/l 3 units/hr You obtain a capillary blood glucose reading of 6.9 mmol/l. What rate in ml/hr will you program the pump to deliver the corresponding insulin dose rate? [Insulin is a critical dose hormone that has been associated with a high rate of serious adverse events worldwide. Several patient safety advocates recommend that institutions institute policy to establish 1 unit/ml as the standard concentration of insulin for continuous infusion, and exceptions should be clearly flagged. Thus, an exception is represented in the above example: 0.1 unit/ml rather than 1 unit/ml However, 1 unit/ml is a rather high concentration, and safe delivery implies use of infusion equipment designed to accurately deliver small hourly volumes. If an empty bag of the more dilute 0.1 unit/ml concentration was replaced with a new bag of 1 unit/ml and proceeded to run at the same rate, the woman would receive 20 units per hour rather than 2 units per hour. Her mental and physical status would deteriorate and she might seizure.] This next question will challenge your skill with very potent drugs that are administered in doses measured in uncommonly small units. 4. You are caring for a woman who will undergo an attempt to induce labor with IV oxytocin. You initiate a primary IV line of normal saline, and are now preparing the 9

10 oxytocin solution to run as a secondary piggyback infusion. Oxytocin is supplied in vials containing 10 international units (IU)/mL. One ml of oxytocin 10 IU/mL is added to a 500 ml bag of normal saline (assume a final concentration of 10 IU/500mL [rather than 10 IU/501 ml]). What is the resulting oxytocin concentration expressed in milliunits/ml? If that concentration of oxytocin is infused at a rate of 1 ml/hour, how many milliunits/minute would be infused? If the infusion is to be initiated at 0.66 milliunits/minute, at what rate in ml/hour should you program the infusion pump? If the induction protocol is to increase the oxytocin infusion rate by 3 milliunits every 30 minutes, what will be the incremental change in ml/hour pump rate will you make every 30 minutes? 5. Imagine that you begin a shift on a hospital inpatient unit. One of the patients has an insulin drip that according to the last capillary blood glucose reading should be running at 5.5 insulin units per hour. The reservoir is labeled, Humulin R 10 units in 100 ml of 0.9% saline. The infusion pump is set at 45 ml/hr. Assuming that the labeled concentration is correct, what rate should the infusion pump be set at to infuse 5.5 units per hour? [If you patient appears stable, the very next thing you ll probably want to do is another capillary blood glucose reading, right?] 6. If you are to infuse ranitidine 50 mg in 10 ml IV over 15 minutes, at what rate should the ranitidine solution be infused if the infusion pump must be programmed in milliliters per hour? 7. A patient with acute coronary syndrome weighs 67 kg. Following a 180 μg bolus, she is receiving eptifibatide [Integrilin ] by continuous infusion of 2 μg/kg/min. If the eptifibatide concentration for infusion is 75 mg in 100 ml of 0.9% sodium chloride solution, what rate should the drug solution be infused if the infusion pump must be programmed in milliliters per hour? 8. You are to start an intravenous infusion of 0.9% sodium chloride containing potassium chloride 20 meq/l, and maintain the infusion at 125 ml/hr. If you use a macrodrip infusion set (15 gtts/ml), at how many drops per minute should this infusion be maintained? If you use a microdrip infusion set (60 gtts/ml), at how many drops per minute should this infusion be maintained? What dose of KCl will the patient be getting: each hour? each day? 10

11 Solutions to the problems: Unit Conversion Exercise Fill in the missing information: kilogram (kg) = _1000_grams mg 10-9 μg gram (g) = 1000 mg kg 10 6 μg milligram (mg) = g 1000 μg 10-6 kg microgram (μg) = g 0.001mg 10-6 g Fill in the missing information: one litre (L) = 1000 ml μl 75 milliliters (ml) = L μl 500 microlitres (μl) = L 0.5 ml Part 1: Exercises on how to deliver a correct intermittent dose of a solid or liquid formulation. Important math skill set up and rearrange a cross-multiply equation: 1. Warfarin tablets are scored so they can be split in half. Supplies of both 4 mg tablets and 5 mg tablets have been issued to treat your patient who has chronic atrial fibrillation. He is initially prescribed warfarin 10 mg p.o. once-daily. How will you administer that dose? The prescribed dose is 10 mg. Here s the math: (1) 10 mg dose = 4 mg formulation or (2) 10 mg dose = 5 mg formulation? tablets 1 tablet? tablets 1 tablet {this is where you rearrange the equation by cross-multipication: the top number (numerator) on one side of the equal sign times the bottom number (denominator) on the other} 4? = ? = 10 1 {rearrange according to another rule: if a number is multiplied on one side of the equal sign, it is the same as dividing the other side of the equal sign by that number}? = _10_? = _10_ 4 5? = 2.5 of the 4 mg tablets? = 2 of the 5 mg tablets So, there are two reasonable answers: (1) 10 mg dose divided by 4 mg tablets (i.e., 10/4) equals 2.5 tablets. (2) 10 mg dose divided by 5 mg tablets (i.e., 10/5) equals 2 tablets The solution that avoids splitting tablets and represents the lowest pill burden administer two of the 5 mg tablets. is to 11

12 (Part 1, question #1 continued): His target INR is 2.5x, but after 48 hrs on 10 mg/day his INR is actually 4.5x. In response, the prescription is to skip the next dose, then resume warfarin at 7 mg p.o. once-daily. From a supply of 4 mg and 5 mg tablets, how will you administer a 7 mg oral dose? The prescribed dose is 7 mg. Let s solve this one like a building set (e.g., tinker toy) in which you have 4 types of pieces, and you can use as many of each as you need to build a dose. Desired Dose Combinations of Tablets 2 mg Half of a 4 mg tablet 2.5 mg Half of a 5 mg tablet 4 mg One 4 mg tablet 4.5 mg Half of a 4 mg tablet + Half of a 5 mg tablet 5 mg One 5 mg tablet 5.5 mg One 4 mg tablet + Half of a 5 mg tablet 6 mg One 4 mg tablet + Half of a 4 mg tablet 6.5 mg One 4 mg tablet + Half of a 5 mg tablet 7 mg One 5 mg tablet + Half of a 4 mg tablet 7.5 mg One 5 mg tablet + Half of a 5 mg tablet 8 mg Two 4 mg tablets 8.5 mg One 4 mg tablet + Half of a 5 mg tablet + Half of a 4 mg tablet 9 mg One 5 mg tablet + One 4 mg tablet 9.5 mg One 5 mg tablet + Half of a 5 mg tablet + Half of a 4 mg tablet 10 mg Two 5 mg tablets 10.5 mg Two 4 mg tablets + Half of a 5 mg tablet 11 mg One 5 mg tablet + One 4 mg tablet + Half of a 4 mg tablet 11.5 mg One 5 mg tablet + One 4 mg tablet + Half of a 5 mg tablet 12 mg Three 4 mg tablets or Two 5 mg tablets + Half of a 4 mg tablet 12.5 mg Two 5 mg tablets + Half of a 5 mg tablet 14 mg Two 5 mg tablets + One 4 mg tablet 15 mg Three 5 mg tablets The only reasonable way to build a 7 mg dose from the formulations on hand, is to give one 5 mg tablet plus half of a 4 mg tablet (i.e., 5 mg + 2 mg = 7 mg). Within 36 hours of adjusting the dose, his INR is now 1.8x, so his dose is increased to 9 mg daily. From a supply of 4 mg and 5 mg tablets, how will you administer a 9 mg oral dose? Give one 5 mg tablet + one 4 mg tablet (5 mg + 4 mg = 9 mg). [Some will recognize that this is a permutation problem. If you have calculus, you don t need to construct the table, and probably don t need this module.] [Warfarin is the principal oral anticoagulant prescribed for most patients at substantial risk for arterial and venous thromboembolic complications, but it has a narrow therapeutic index: a little too much warfarin will put the patient at excess risk of non compressible hæmorrhage (e.g., intracranial or GI bleed), but not enough warfarin leaves the patient at risk of a thromboembolic catastrophe such as an ischemic stroke. Warfarin is inconvenient because it interacts with numerous foods and drugs, thus requires dose adjustments in relation to close laboratory monitoring of fluctuations in a patient s prothrombin times (PT, now most often standardized as international normalized ratio {INR}).] 12

13 2. Digoxin mg p.o. is prescribed to a patient with a fast ventricular response to atrial flutter. You have digoxin 0.25 mg tablets on hand. How many tablet(s) should you give to the patient? Prescribed dose is mg, and we know there s 0.25 mg of digoxin in one tablet mg = mg 1 tablet(s)? tablet(s) 0.25? = ? = = 0.5 tablet(s) 0.25 So a mg dose will be half of a 0.25 mg tablet 3. Diazepam 25 mg p.o. is prescribed. You have diazepam 10 mg tablets on hand. How many tablet(s) should you give to the patient? The prescribed dose is 25 mg, and we know there s 10 mg of diazepam in one tablet. 10 mg = 25 mg 1 tablet(s)? tablet(s) 10? = 25 1? = 25 = 2.5 tablet(s) 10 So a 25 mg dose will be administered as two and a half 10 mg tablets [If you don t know why diazepam is being prescribed (e.g., manage anxiety, pre-anaesthetic, raise convulsive threshold, skeletal muscle relaxant, and mitigate ethanol withdrawal symptoms) you won t know how to assess the response. It will likely make the patient drowsy, and sometimes that s the desired effect. If not, it is an expected side-effect.] 13

14 Be careful with this next question. The units in which the drug is prescribed are not the same units as the formulation on hand is labeled. 4. An woman with bacterial otitis media is prescribed sulfisoxazole 1 g p.o. You have 500 mg tablets on hand. How many tablet(s) should you give to the patient? The prescribed dose is 1 gram (i.e., 1000 mg), and we know there s 500 mg (i.e., 0.5 g) of sulfisoxazole in one tablet. Decide which units you want to work with (both are used in the following example): Here s the math: (1) 1000 mg dose = 500 mg or (2) 1 g dose = 0.5 g? tablets 1 tablet? tablets 1 tablet {this is where you rearrange the equation by cross-multipication: the top number (numerator) on one side of the equal sign times the bottom number (denominator) on the other} 500? = ? = 1 1 {rearrange according to another rule: if a number is multiplied on one side of the equal sign, it is the same as dividing the other side of the equal sign by that number}? = _1000_? = _1_ ? = 2 of the 500 mg tablets? = 2 of the 0.5 g tablets The supply is labeled 500 mg, so if you chose to work the equation in grams, you have to conclude that 0.5 g = 500 mg. 14

15 Now try calculating a liquid dose: 5. A fellow with intractable hiccups is prescribed chlorpromazine 25 mg IM. You have an unopened 10 ml vial of solution for injection labeled 25 mg/ml. What amount of chlorpromazine solution should you prepare to inject? The prescribed dose is 25 mg, and we know there s 25 mg of chlorpromazine in one ml of solution. 25 mg = 25 mg 1 ml? ml 25? = 25 1? = 25 = 1 ml 25 So a 25 mg dose will be administered as a 1 ml injection of a 25 mg/ml solution. 6. An ampoule of Drug A is labeled, 100 mg/10 ml. The patient is to receive a 15 mg dose. What volume should you administer? The prescribed dose is 15 mg, and we know there s 100 mg of Drug A in 10 ml of solution. 100 mg = 15 mg 10 ml? ml 100? = 15 10? = 150 = 1.5 ml 100 So a 15 mg dose will be administered as a 1.5 ml injection of a 100 mg/10 ml solution. 7. Drug B is supplied in 2 ml ampoules labeled 100 mg/ml IM STAT. If your patient is to receive a 200 mg dose, what volume should you inject? The prescribed dose is 200 mg, and we know there s 100 mg of Drug B in 1 ml of solution. 100 mg = 200 mg 1 ml? ml 100? = 200 1? = 200 = 2 ml 100 So a 200 mg dose will be administered as a 2 ml injection of a 100 mg/ml solution. 15

16 8. A casualty officer orders Gravol 30 mg IM STAT for an 8 year old that is puking in the ER. The department doesn t stock that brand. On hand are Novo-Dimenate (dimenhydrinate) 50 mg/2ml and PMS-Diphenhydramine (diphenhydramine) 50 mg/ml. Which drug should you give, and what volume of that drug should you inject? The prescribed dose is 30 mg, and we know there s 50 mg of dimenhydrinate [Gravol ] in 2 ml of solution. 50 mg = 30 mg 2 ml? ml 50? = 30 2? = 60 = 1.2 ml 50 So a 30 mg dose will be administered as a 1.2 ml injection of a 50 mg/2 ml solution. Regarding the use of brand names in general: The names of drugs are a problem. Each and every drug has a single generic name that is common to USA, Canada, the EU and Japan. Generic drug nomenclature is somewhat systematic in relation to drug class: (e.g., -statins, -glitazones, -triptans, -prils, -olols ). But most drugs eventually acquire multiple brand names that vary internationally, and are catchy sounding but sometimes confusingly similar sounding. Solution: educational material should emphasize generic names and de-emphasize brand names. Examples: Generic Name: amoxacillin Brand Names: CANADA: Amoxil, Apo-Amoxi, Gen-Amoxicillin, Novamoxin, Nu-Amoxi, plus combinations; ELSEWHERE: Agram, Alfamox, Almodan, Amodex, Amoxidal, Amoxidin, Amoxillat, Amoxypen, Ardine, AX250, Clamoxyl, Cuxacillin, Dura AX, Flemoxin, Hiconcil, Ibiamox, Larocin, Larotid, Moxal, Moxaline, Neamoxyl, Polymox, Raylina, Robamox, Sigamopen, Silamox, Trimox, Uro-Clamoxyl, Ultimox, Zamocillin; Generic Name: metoprolol Brand Names: CANADA: Lopressor, Betaloc, Dom-Metoprolol, Apo-Metoprolol, Novo- Metoprolol, Nu-metop, PMS-metoprolol, Gen-metoprolol Health professionals should avoid behaviours that reflect or might be construed to reflect conflicts of interest. Reference to brand names raises suspicion that treatment decisions may be unduly influenced by marketing forces rather than unbiased clinical scientific evidence and sound clinical judgment. 16

17 9. Morphine and atropine are compatible in the same syringe and may be given together as a single injection. A physician orders morphine 4 mg IV and atropine 0.6 mg IV to be given together to a man with symptomatic bradycardia. In stock, morphine sulphate is available in ampoules containing 5 mg/ml, 10 mg/ml and 15 mg/ml. Atropine sulfate is available in ampoules of 0.4 mg/ml or 0.6 mg/ml. Select the most appropriate size syringe: 1 ml, 3 ml or 5 ml. Which stock concentration of morphine do you choose? Should we try to minimize the volume for injection? The upper limit of acceptable volume that may be injected into various tissue sites will be supported by opinions and policies at the least, but it would be interesting to review the quality of evidence available to define clinically important limits. On a pharmacological basis, it stands to reason that the optimal volume could vary with the nature of the solution as well as the physical size and health of the muscular injection site. Let s choose the middle one: morphine 10 mg/ml. What volume of that concentration yields a 4 mg dose? The prescribed dose is 4 mg, and we know there s 10 mg of morphine in 1 ml of solution. 10 mg = 4 mg 1 ml? ml 10? = 4 1? = _4_ = 0.4 ml 10 So a 4 mg dose of morphine will be administered as a 0.4 ml injection of a 10 mg/ml solution. Which stock concentration of atropine do you choose? Let s use the 0.6 mg/ml solution. What volume of that concentration yields a 4 mg dose? The prescribed dose is 0.6 mg, and we know there s 0.6 mg of atropine in 1 ml of solution. 0.6 mg = 0.6 mg 1 ml? ml 0.6? = 0.6 1? = _0.6_ = 1 ml 0.6 So a 0.6 mg dose of atropine will be administered as a 1 ml injection of a 0.6 mg/ml solution. What is the total volume (i.e., both drugs) for injection? 0.4 ml + 1 ml = 1.4 ml What size of syringe would be appropriate for that volume? A 3 ml syringe would work. 17

18 10. A preoperative medication order reads: Give morphine 12 mg IM, atropine 0.4 mg IM and prochlorperazine 7.5 mg IM one hour prior to induction. In stock, morphine sulphate is available in ampoules containing 5 mg/ml, 10 mg/ml and 15 mg/ml. Atropine sulfate is available in ampoules of 0.4 mg/ml or 0.6 mg/ml. Prochlorperazine is available in 10 mg/2 ml ampoules. Select the most appropriate size syringe: 1 ml, 3 ml or 5 ml. Which stock concentration of morphine do you choose? Let s work out what the dose would be for both the 10 and 15 mg/ml solutions. What volume of that concentration yields a 12 mg dose? (1) 15 mg = 12 mg or (2) 10 mg = 12 mg 1 ml? ml 1 ml? ml {this is where you rearrange the equation by cross-multipication: the top number (numerator) on one side of the equal sign times the bottom number (denominator) on the other} 15? = ? = 12 1 {rearrange according to another rule: if a number is multiplied on one side of the equal sign, it is the same as dividing the other side of the equal sign by that number}? = _12_? = _12_ 15 10? = 0.8 ml of the 15 mg/ml sol n or? = 1.2 ml of the 10 mg/ml sol n. Which stock concentration of atropine do you choose? Let s work out what the dose would be for both the 0.4 and 0.6 mg/ml solutions. What volume of that concentration yields a 4 mg dose? (1) 0.4 mg = 0.4 mg or (2) 0.6 mg = _0.4 mg 1 ml? ml 1 ml? ml {this is where you rearrange the equation by cross-multipication: the top number (numerator) on one side of the equal sign times the bottom number (denominator) on the other} 0.4? = ? = {rearrange according to another rule: if a number is multiplied on one side of the equal sign, it is the same as dividing the other side of the equal sign by that number}? = _0.4_? = _0.4_ ? = 1 ml of the 0.4 mg/ml sol n or? = 0.66 ml of the 0.6 mg/ml sol n. What volume of prochlorperazine 10 mg/2 ml yields a 7.5 mg dose? The prescribed dose is 7.5 mg, and we know there s 10 mg of prochlorperazine in 2 ml of solution. 10 mg = 7.5 mg 2 ml? ml 10? = 7.5 2? = _14_ = 1.4 ml 10 So a 7.5 mg dose of prochlorperazine will be administered as a 1.4 ml injection of a 10 mg/2 ml solution. 18

19 What is the total volume (i.e., all 3 drugs) for injection? (1.4 ml of prochlorperazine) + (0.8 ml or 1.2 ml of morphine) + (0.66 or 1 ml of atropine) = from 2.86 to 3.6 ml, depending on which concentration of each drug you selected. What size of syringe would be appropriate for that volume? A 3 ml syringe would work if you chose the highest concentrations of morphine and atropine, otherwise you will need a 5 ml syringe. Some institutions might have policies against injecting more than 3 ml at a single IM site, others won t. It may be of interest that the American Society of Anesthesiologists Task Force Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective Procedures do not recommend routine use of gastric acid reducing agents, antiemetics or antimuscarinic drugs intended to minimize the risk of pulmonary aspiration, because there is insufficient evidence that these medications actually have any effect on the incidence or severity of pulmonary aspiration. 11. You are caring for a woman with threatened premature delivery at 31 weeks gestation. An order is given to administer betamethasone 12 mg IM STAT, and repeat in 24 hours. Betamethasone is available in 1 ml vials containing 4 mg/ml. What volume of that solution will you prepare to inject? The prescribed dose is 12 mg, and we know there s 4 mg of betamethasone in 1 ml of solution. 4 mg = 12 mg 1 ml? ml 4? = 12 1? = _12_ = 3 ml 4 So a 12 mg dose of betamethasone will be administered as a 3 ml injection of a 4 mg/ml solution. How many vials will you need to open to administer the prescribed dose? In other words: How many 1 ml vials will it take to make 3 ml? The math:? 1 ml vials = 3 ml; rearrange to:? = 3/1 = 3 The 3 ml injection will be drawn from 3 1 ml vials. 19

20 12. The obstetrician orders 5 International Units (IU) of oxytocin administered with the delivery of the anterior shoulder. The vial contains 1 ml of solution containing 10 IU of oxytocin. What volume of oxytocin solution will you draw up? The prescribed dose is 5 IU, and we know there s 10 IU of oxytocin in 1 ml of solution. 10 IU = 5 IU 1 ml? ml 10? = 5 1? = _5_ = 0.5 ml 10 So a 5 IU dose of oxytocin will be administered as a 0.5 ml injection of a 10 IU/mL solution. 13. Following birth, the physician orders Vitamin K 1 mg I.M. for the infant. Vitamin K is supplied in 1 ml vials containing 10 mg/ml. What volume of that solution will you prepare to administer by intramuscular injection? The prescribed dose is 1 mg, and we know there s 10 mg of vitamin K in 1 ml of solution. 10 mg = 1 mg 1 ml? ml 10? = 1 1? = _1_ = 0.1 ml 10 So a 1 mg dose of vitamin K will be administered as a 0.1 ml injection of a 10 mg/ml solution. What size of syringe (0.5 ml, 1 ml, 3 ml) would be least appropriate for this injection? You need higher precision syringes to administer small volumes of potent drugs acurately. If the 0.5 ml and 1 ml syringes have the same precision, either will do. 20

21 14. A woman in early labor is prescribed Demerol 150 mg with Gravol 25 mg IM. You have the following concentrations of these drugs available to you: Demerol 50 mg/ml in a 1 ml vial Demerol 75 mg/ml in a 1 ml vial Demerol 100 mg/ml in a 1 ml vial Gravol 50 mg/ml in a 1 ml vial Which stock concentration of Demerol do you choose? Explain. Choosing the highest concentration will allow the lowest volume for injection. The highest concentration of Demerol available in this case is the 100 mg/ml concentration. What volume of that concentration yields a 150 mg dose? The prescribed dose is 150 mg, and we know there s 100 mg of Demerol in 1 ml of solution. 100 mg = 150 mg 1 ml? ml 100? = 150 1? = _150_ = 1.5 ml 100 So a 150 mg dose of Demerol will be administered as a 1.5 ml injection of a 100 mg/ml solution. What volume of the Gravol concentration yields a 25 mg dose? The prescribed dose is 25 mg, and we know there s 50 mg of Gravol in 1 ml of solution. 50 mg = 25 mg 1 ml? ml 50? = 25 1? = _25_ = 0.5 ml 50 So a 25 mg dose of Gravol will be administered as a 0.5 ml injection of a 50 mg/ml solution. What is the total volume (i.e., both drugs) for injection? 1.5 ml of Demerol ml of Gravol = 2 ml for injection Is that an appropriate volume for IM injection? Usually? Regarding the use of meperidine (aka, pethidine) [Demerol ] as an example: Although it is still used frequently on many labor units, there may be better alternatives. The choice is controversial. The American Society for Gastrointestinal Endoscopy suggested that meperidine might be preferred over morphine, on the basis of evidence that morphine crosses the fetal blood-brain barrier more rapidly. However, both drugs readily enter the fetal brain and there is no evidence cited in the guideline that a differential rate of fetal CNS penetration after maternal administration of either meperidine or morphine is of any clinical importance. Other jurisdictions continue to describe meperidine as a choice for early labor analgesia. Mander R. Analgesia and anaesthesia in childbirth: obscurantism and obfuscation. J Advanced Nursing 1998;28: Faucher MA and Brucker MC. Intrapartum Pain: Pharmacologic Management. JOGNN 2000;29: ISMP Canada Safety Bulletin. Meperidine (Demerol) Medication Safety Issues. Spring accessed online Hale TW. Drug therapy and breastfeeding: antibiotics, analgesics, and other medications. NeoReviews. 2005;6(6):e233-e240. NSW-TAG. Use of pethidien for pain management in the emergency department. August 2004 ASGE. Guidelines for endoscopy in pregnant and lactating women. 2005;61(3): Nova Scotia Perinatal Program: 21

22 What if the dose is to be adjusted to the size of the patient? To get the most benefit with the least side effects, it may be useful to normalize (i.e., tailor) the dose of a drug to the volume of the body compartment into which the drug distributes, which often corresponds well enough with the patient s total body weight (or perhaps lean body weight, estimated bone mass or body surface area). The general idea is to give bigger people bigger doses, and smaller people proportionally smaller doses, so they all achieve the same tissue levels following a dose that is the right size for them. It is especially common to adjust pædiatric doses according to a child s weight. In that case, the prescription might read, Drug-C syrup 2 mg/kg p.o. q4h. It means, first determine how much the child weighs, then give 2 milligrams of Drug-C for every kilogram of body weight. If the child weighs 14 kg, the dose would be 14 2 mg = 28 mg. Try to determine the correct volume of a drug formulation that you should prepare to give to a patient who has been prescribed these weight-adjusted doses: 15. A 5 year old asthma patient is prescribed theophylline elixir 3 mg per kg body weight p.o. q6h. She weighs 15 kg. What dose of theophylline elixir does that work out to? Dose = 3 mg/kg 15 kg = 45 mg of theophylline every 6 hours. How much theophylline would she get per day? 24 hours/day divided into 6 hour intervals = 24/6 = 4 doses. 4 doses/day 45 mg/dose = 180 mg/day Theophylline elixir comes in a 480 ml bottle containing 80 mg/15 ml. What volume of elixir will provide the prescribed dose? The prescribed dose is 45 mg, and we know there s 80 mg of theophylline in 15 ml of solution. 80 mg = 45 mg 15 ml? ml 80? = 45 15? = _675_ = 8.44 ml 80 So a 45 mg dose of theophylline will be administered as 8.44 ml of a 80 mg/ 15mL solution. 22

23 16. A 4 year old child has oxacillin 50 mg/kg/day in divided doses infuse IV at 6 hour intervals; not to exceed 1.5 g/day. Oxacillin comes pre-mixed in vials of two different sizes containing either 1 g or 2 g of oxacillin in 50 ml of iso-osmotic dextrose solution. This child weighs 12.5 kg. How much oxacillin should this child receive on a daily basis? Dose/day = 50 mg/kg 12.5 kg = 625 mg/day. Does that exceed the prescribed daily limit? No. 625 mg/day < 1500 mg/day limit Dividing the total daily dose into equal doses, how many milligrams should be given every 6 hours? 24 hours/day divided into 6 hour intervals = 24/6 = 4 doses. 625 mg/day divided into 4 doses/day = 625/4 = mg/dose If you choose to draw a dose from the 1g/50 ml concentration, what is the smallest syringe you could use to draw up the dose: will you need a 1 ml, 3 ml, 5 ml, or a 10 ml syringe? The prescribed dose is 156 mg, and we know there s 1000 mg of oxacillin in 50 ml of solution mg = 156 mg 50 ml? ml 1000? = ? = _7812.5_ = 7.8 ml 1000 So a 156 mg dose of oxacillin will be administered as 7.8 ml of a 1 g/ 50 ml solution. You ll need a 10 ml syringe. 17. A 4 month old child is prescribed cefpodoxime oral suspension 4 mg/kg p.o. q12h. The child weighs 25 kg. The bottle is reconstituted to a 50 mg/ml concentration of lemon crème flavored cefpodoxime suspension. How much of that suspension should you give for each dose? The prescribed dose is 4 mg/kg 25 kg = 100 mg, and we know there s 50 mg of cefpodoxime in 1 ml of suspension. 50 mg = 100 mg 1 ml? ml 50? = 100 1? = _100_ = 2 ml 50 So a 100 mg dose of cefpodoxime will be administered as 2 ml of a 50 mg/ml oral suspension.. 23

24 18. Remember the woman that was prescribed Demerol 150 mg during early labor in question #14? Following birth three hours later, her 3500 g infant has respiratory depression. The resuscitation team calls for naloxone hydrochloride [Narcan ] 0.1 mg/kg IV. Naloxone hydrochloride comes in 1 ml vials that contain 0.4 mg/ml. What is the correct dose in mg? The dose is 0.1 mg/kg 3.5 kg = 0.35 mg How many millilitres of the 0.4 mg/ml solution corresponds to that dose? The prescribed dose is 0.35 mg, and we know there s 0.4 mg of naloxone in 1 ml of solution. 0.4 mg = 0.35 mg 1 ml? ml 0.4? = ? = _0.35_ = ml 0.4 So a 0.35 mg dose of naloxone will be administered as ml of a 0.4 mg/ml solution. You ll need a 1 ml syringe. Part 2: exercises on how to initiate and adjust a continuously administered drug: 1. Your patient is receiving a continuous heparin infusion. The intravenous solution contains units of heparin in 500 ml of 5% dextrose (D5W). The patient is to receive 1800 units of heparin per hour. What volume of the heparin solution must infuse to provide that dose of heparin in one hour? The prescribed dose is 1800 units/hr, and we know there s units of heparin in 500 ml of solution = ml? ml 10000? = ? = _900000_ = 90 ml So a 1800 unit/hr dose of heparin will be administered by infusing 90 ml of a unit/500 ml solution. The infusion pump rate has to be programmed in ml/hr, so what rate will you select? To run at 90 ml/hour, program the pump to infuse 90 ml/hour. At that rate, how long will a 500 ml bag of heparin in D5W last? 500 ml = 5.56 hours; i.e., not quite 6 hours. 90 ml 24

25 2. A patient s daily fluid balance is being supplemented by constant intravenous infusion of 1500 ml/24 hours of 5% dextrose in 0.9% sodium chloride solution (D5S), using a 60 drops = 1 ml infusion set. At how many drops per minute should you regulate the iv to deliver 1500 ml/24 hrs? Let s work this out in ml/minute, then multiply ml/min 60 gtts/ml. There are 24hrs/day 60 min/hrs = 1440 minutes/day. Set up and rearrange a cross-multiply equation: 1500 ml =? ml 1440 min 1 min 1440? = ? = _1500 = about 1 ml/min, 1440 and using a 60 drops = 1 ml infusion set, we should run 1 ml/min 60 gtts/ml = 60 gtts/min (about 1 drop/second). 3. The patient you are caring for is a type 1 diabetic in active labor. She has a continuous insulin infusion prescribed according to a sliding scale (i.e., you adjust the infusion rate, and thus titrate her insulin dose according to her capillary blood glucose response). The intravenous solution contains Humulin R 50 units/500 ml of 0.9% sodium chloride (normal saline): Blood glucose (mmol/l) Humulin R (units/hour) < 4 mmol/l Hold insulin < 6 mmol/l 1 unit/hr 8.9 is < 8 mmol/l 2 units/hr 8 mmol/l 3 units/hr You obtain a capillary blood glucose reading of 6.9 mmol/l. What rate in ml/hr will you program the pump to deliver the corresponding insulin dose rate? Set up and rearrange a cross-multiply equation: 50 units = 2 units 500 ml? ml 50? = 500 2? = _1000 = 20 ml/hr, 50 [Insulin is a critical dose hormone that has been associated with a high rate of serious adverse events worldwide. Several patient safety advocates recommend that institutions institute policy to establish 1 unit/ml as the standard concentration of insulin for continuous infusion, and exceptions should be clearly flagged. Thus, an exception is represented in the above example: 0.1 unit/ml rather than 1 unit/ml However, 1 unit/ml is a rather high concentration, and safe delivery implies use of infusion equipment designed to accurately deliver small hourly volumes. If an empty bag of the more dilute 0.1 unit/ml concentration was replaced with a new bag of 1 unit/ml and proceeded to run at the same rate, the woman would receive 20 units per hour rather than 2 units per hour. Her mental and physical status would deteriorate and she might seizure.] 25