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CASE AND COMMENTARY: Milliliters vs. Milligrams

Posted Dec 10 2010 7:00am

Milliliters vs. Milligrams


A 32-year-old man was admitted to the hospital after a vehicle collision and multiple traumatic injuries. His evaluation showed acute cerebral edema. An order for intravenous dexamethasone was written, with the dosing schedule specified as "10 mg IV stat, then 8 mg q 6 hrs x 2 doses, then 4 mg q 6 hrs x 2 doses, then 4 mg q 6 hrs for 2 doses, then 2 mg q 6 hrs x 2 doses." The pharmacist processed the order, dispensing a multidose 4 mg/mL 5 mL vial to the unit. The vial, containing a total of 20 mg dexamethasone, was anticipated to furnish the stat 10 mg dose and the second 8 mg dose to be given 6 hours later. The pharmacist labeled the vial, instructing the nurse regarding the necessary volume (mL) to be drawn from the vial to provide the appropriate dose (mg). After 1 hour, the nurse called the pharmacist requesting more dexamethasone, stating there was no medication available for the second dose. After questioning the nurse, the pharmacist determined that the patient was given the entire vial (20 mg) as the initial (stat) dose, a twofold overdose. The attending physician was contacted and informed of the error. Since the patient was given only one dose, no harm was expected. Subsequent dexamethasone doses were given as ordered, with close monitoring for adverse effects.



by Robert L. Poole, PharmD; Tessa Dixon, PharmD


Prescribing and administration errors are the most commonly reported errors in the medication use process. The frequency and severity of such errors have been well documented in both professional and lay publications. Consequently, additional safeguards, such as computerized prescriber order entry (CPOE) with real-time clinical decision support, medication barcoding, and patient-specific dose individualization, have been introduced. Despite the fact that these advancements are aimed at reducing system failures, lapses in performance are important sources for errors.

The errors described in this case may have resulted from both system failures and errors in personal performance. Management of an acute trauma patient can be chaotic and confusing, adding additional stress to the system. The cascading dexamethasone order may have confused both the nurse and pharmacist as the "4 mg q 6 hrs x 2 doses" is repeated, rather than written as a continuous tapering of the dose. Emergency situations result in a sense of urgency, which may lead health care professionals to bypass important safeguards, such as reviewing the order prior to sending it to the pharmacy, verifying the ordered dose, or reading medication labeling. In such situations, a pharmacist verifying an emergent order, rushing to make the medication available, may inadvertently dispense a product without important labeling.

The second error in this case occurred when the nurse administered the entire contents of the 20-mg multidose vial of dexamethasone instead of the 10-mg ordered dose. Fortunately, dexamethasone has a wide therapeutic index associated with a single dose, and the patient most likely suffered no ill effects. While this error may have occurred because the printed instructions were not followed by the nurse, it is also possible that the pharmacist did not provide prominent, legible, or unambiguous instructions regarding the appropriate volume and dose. The Institute for Safe Medication Practices recommends that nurses read the label three times ("RL3X") to ensure it is the right drug, in the right dose, by the right route, for the right patient, at the right time (also known as the "5 Rights").( 1 )

Pharmacy should have standard dispensing procedures when a medication is available in several different sizes and/or concentrations or from several different manufacturers. In this case, the pharmacist could have prevented the error by providing the initial dose in the ordered patient-specific dose in a ready-to-administer form. Multidose or bulk vials are best utilized within the pharmacy to prepare patient-specific doses, rather than sending these vials to the floor, which forces the nurse to prepare the individualized dose.

Dose individualization—the pharmacy preparation of patient-specific, weight-based unit doses—has become the standard of care, particularly in pediatric hospitals. Each dose is prepared by pharmacy personnel in a ready-to-administer dose and dosage form and labeled with the patient's name, location, drug name, expiration date, and medical record number or account number. A medication safety goal should be the preparation of patient-specific doses for all patients: infants, children, and adults. Making doses available in unit of use has been highly effective in reducing medication errors.( 2-4 ) In one study, the frequency of medication errors was reduced by 82% by changing to unit of use.( 3 )

Most drugs are available from pharmaceutical manufacturers in a unit of use dose form, in which one tablet, one capsule, one vial, etc., can be administered as an individualized dose for an adult patient. Some drug doses must be individualized for adults in either mg/kg or mg/m2 (e.g., most cancer chemotherapy). High-risk medications, such as insulin or heparin, are commonly prescribed using protocols or order sets, which include individualization of dose along with appropriate monitoring parameters.

These issues are even more challenging in pediatrics. Drug dosing in children is affected by the limited pediatric FDA-labeled indications for use, large variability in patient sizes and weights, and a paucity of clinical trials to establish safe and effective doses. Most pediatric patients are unable to swallow medications in solid oral dosage forms and require liquid dosage forms to be compounded into solutions or suspensions. Children's hospital pharmacies are challenged daily with the task of preparing medications for patients ranging in weights from 400 g to 120 kg, resulting in the potential of up to a 300-fold dosing error.( 5 ) Prescribing dosing errors are the leading source of medication order errors (82%) in children.( 6 ) Kaushal, Bates, and colleagues reported that the most common errors in the medication use process in children occurred during physician prescribing (74%) and nurse administration (13%) followed by pharmacy dispensing (1%).( 7 ) Additional risk for error is possible when pharmacies stock medications in multiple strengths and concentrations as they strive to meet the needs of pediatric patients.

Whether the patient is a child or an adult, patient-specific dose individualization can be a significant source of cost savings as one vial, capsule, or tablet may be used to prepare several doses. However, savings on drug costs can be offset by the need for additional pharmacy personnel to repackage or compound doses. An approach to minimize both labor and drug cost and maximize patient safety can be adopted. In such an approach, certain medications—high-alert, narrow therapeutic index, and highly toxic drugs—are individualized for patients ( Table ). Similarly, expensive drugs can be prepared in patient-specific doses by extracting multiple doses from a single vial to minimize drug waste and pharmaceutical costs. While less optimal, some drugs can be dispensed in the manufacturer's packaging along with instructions to the nurse regarding dosage preparation. Examples of medications not requiring pharmacy individualization might include inexpensive drugs with a low toxicity profile, drugs with short stability after reconstitution or after opening (e.g., ampicillin), and drugs accessed by nurses from automated dispensing machines within the patient care units (e.g., antihistamines). Independent of whether the drug is delivered to the nurse in individualized form, the nurse is expected to carefully read the label and review the product dispensed from pharmacy according to the principle of 5 Rights.

The preparation of patient-specific doses is a labor-intensive process that can result in increased cost. Dose individualization is less of an issue for adult patients, because most medications are already supplied in unit-dose form by the manufacturer. Any cost–benefit analysis should include an evaluation of the cost of pharmaceuticals, personnel costs, capital costs for repackaging and compounding equipment, as well as facility costs required to build the necessary space for such processes. These costs must be balanced by the associated improvements in patient safety.

Other Solutions

Physician understanding of available product formulation, often aided by computerized decision support embedded in a CPOE system, may result in rounding of an ordered dose to the nearest whole unit of a product, thus minimizing nursing calculations or the need for pharmacy individualization of the patient dose. Medications with wide therapeutic indices and low toxicity profiles are particularly good candidates for this dose standardization. Minimizing the number of product strengths and concentrations in the pharmacy inventory can also reduce dispensing errors. Finally, clearly defined standards of practice in medication dispensing procedures should be in place to avoid errors. Additional information toward prevention of medication errors and improving medication system safety is available from several well-respected organizations.( 8-13 )

Take-Home Points

  • Recognize that both system failures and human failures contribute to medication administration errors.
  • Patient dose individualization is a safe and effective method for delivering medications to patients.
  • Careful nurse review of all medications to ensure the 5 Rights is essential.
  • Patient dose individualization can save drug costs, especially in pediatrics where multiple orders can be filled from a single adult dosage unit.
  • Individualization requires the pharmacy to have sufficient personnel to address workload and turnaround time requirements based on patient acuity and other services provided.
  • If all doses cannot be provided to patients in individualized units of use, give highest priority to pediatric patients and to high-risk, high-alert medications.

Robert L. Poole, PharmD
Director of Pharmacy, Lucile Packard Children's Hospital at Stanford

Clinical Professor of Pharmacy, University of California, San Francisco

Tessa Dixon, PharmD
Pharmacy Resident, Lucile Packard Children's Hospital at Stanford



1. Institute for Safe Medication Practices (ISMP) Web site. Horsham, PA. [Available at]

2. Schultz SM, White SJ, Latiolais CJ. Medication errors reduced by unit-dose. Hospitals. 1973;47:106-112. [go to PubMed]

3. Simborg DW, Derewicz HJ. A highly automated hospital medication system. Five years' experience and evaluation. Ann Intern Med. 1975;83:342-346. [go to PubMed]

4. ASHP statement on unit dose drug distribution. In: Best Practices for Health-System Pharmacy. Hawkins B (ed). Bethesda, MD: American Society of Health-System Pharmacists; 2003:90. ISBN: 9781585280551.

5. Poole RL, Benitz WE, Reich JD, et al. Medication errors in children [letter]. JAMA. 2001;286:915-916. [go to PubMed]

6. Folli HL, Poole RL, Benitz WE, Russo JC. Medication error prevention by clinical pharmacists in two children's hospitals. Pediatrics. 1987;79:718-722. [go to PubMed]

7. Kaushal R, Bates DW, Landrigan C, et al. Medication errors and adverse drug events in pediatric inpatients. JAMA. 2001;285:2114-2120. [go to PubMed]

8. Patient Safety. Bethesda, MD: American Society of Health-System Pharmacists Web site. [Available at]

9. Levine SR, Cohen MR, Blanchard NR, et al. Guidelines for preventing medication errors in pediatrics. J Pediatr Pharmacol Ther. 2001;6:427-443.

10. Reports. Washington, DC: Institute of Medicine of the National Academies Web site. [Available at]

11. Joint Commission 2010 Medication Management Standards. Oak Brook, IL: The Joint Commission; 2010.

12. Bates DW, Leape LL, Cullen DJ, et al. Effect of computerized physician order entry and a team intervention on prevention of serious medication errors. JAMA. 1998;280:1311-1316. [go to PubMed]

13. How to Improve. Cambridge, MA: The Institute for Healthcare Improvement Web site. [Available at]


 


Table. Examples of High-Alert Drug Classes.

(Go to table citation in commentary)

Adrenergic agonists (epinephrine, phenylephrine, norepinephrine)
Adrenergic antagonists (beta-blockers)
Anesthetic agents (propofol, ketamine)
Antiarrhythmics (amiodarone, lidocaine)
Antithrombotic agents (heparin, warfarin)
Chemotherapy (parenteral and oral)
Concentrated electrolytes (IV potassium, sodium, magnesium)
Dextrose (hypertonic)
Epidural or intrathecal medication
Hypoglycemic agents (insulin, oral agents)
Inotropic drugs (digoxin, milrinone)
Moderate sedation agents (midazolam, chloral hydrate)
Narcotics/opiates (IV, transdermal, and oral)
Neuromuscular blockers (succinylcholine, rocuronium, vecuronium)


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