Medication errors, including infusions, are one of the most common preventable causes of harm to patients in health care agencies. Such errors account for approximately 33 percent of incident reports electronically submitted, and are the seventh leading cause of Sentinel Events reported to the Joint Commission.^1,2 Reducing the risks of drug administration is a requirement for all areas of clinical practice. Data from reporting systems, published case reports, and surveys of more than 770 health care practitioners, were recently evaluated by the Institute for Safe Medication Practices, resulting in a published list of high-alert medications (Table 6-1). Medications on the list are more likely to cause significant patient harm when compared with other groups of medications and have more reported administration errors.³ Frequently, medications on the high-alert list are administered to high-risk and critically ill pregnant women. Therefore, in order to promote patient safety, a medication’s mechanism of action, correct dose, recognized drug interactions, and precautions regarding administration should be known. Safe-practice strategies to decrease the inherent risk when prescribing, dispensing, and administering these medications should also be developed in clinical agencies.

In the critically ill gravida, fetal and newborn outcomes are usually dependent upon timely maternal stabilization. Many of the medications administered for the purpose of maternal stabilization have a direct effect on uterine blood flow or uterine activity. Some cross the placental barrier and have varying effects on the fetal heart rate (FHR). Potential effects include baseline FHR changes, suppression or exaggeration of decelerations, frequency and amplitude of accelerations, and degree of variability.⁴ Therefore, as a result, it is difficult for the health care provider to determine whether changes in fetal status are a result of a specific medication that has been administered, physiologic variation, or both. For example, if maternal oxygen delivery is impaired and leads to a decrease in uterine perfusion and fetal oxygenation, the electronic fetal monitor (EFM) may no longer show signs of fetal well-being. Although there are no predictive or diagnostic EFM tracings for fetal hypoxia, assessment parameters that have been associated with fetal stress include the combination of fetal tachycardia, absent or minimal baseline variability, and recurrent late decelerations. Specific information related to FHR assessment may be found in the Guidelines for Fetal Heart Rate Monitoring, which includes a description of the three-tiered classification system used to collectively interpret assessment findings. Sustained
decreases in uterine perfusion may lead to further decreases in fetal oxygenation, a shift to anaerobic metabolism, accumulation of lactic acid, and metabolic acidosis. Specific EFM signs that indicate the possibility of fetal metabolic acidemia include absent baseline variability, absence of accelerations, an abnormal baseline rate (tachycardia and/or bradycardia), and recurrent late and/or prolonged decelerations.⁴

Early in pregnancy, teratogenic exposure is a concern with medication administration. A teratogen is any chemical, substance, or exposure that may cause birth defects, permanent abnormality of structure or function, in a developing fetus. Women may be reluctant to take any medication during pregnancy due to the possibility or perceived possibility of fetal effects. In an attempt to prevent harmful medications from reaching the market, clinical drug trials to determine safety and efficacy are required for new drugs marketed and sold in the United States (U.S.) by the Food and Drug Administration (FDA). The FDA places medications into risk categories regarding use during pregnancy and potential effects on the developing fetus (Table 6-2). However, because medications are not tested on pregnant women, and animal studies do not always predict effects in humans, approximately 80 percent of marketed medications have unknown teratogenic risk in
pregnancy.⁵ Box 6-1 lists the drugs or substances suspected or proven to be human teratogens.⁶

Many drugs present in the bloodstream will be excreted in breast milk. The drug concentration in milk depends on many factors, such as the amount of drug in the maternal serum, the transfer of the drug across the placental barrier, its lipid solubility, its degree of ionization, its molecular size, and the extent to which it is excreted. Fetal accumulation of a drug that is transmitted in breast milk is contingent upon a variety of factors. Variations in the amount of milk formed in the breast may be altered due to decreased blood flow to breast tissue. Alterations in milk pH and composition also affect the concentrations of drugs found in breast milk.⁷

Drug exposure to the breast-feeding newborn is greatest when feeding or pumping occurs immediately following medication administration to the mother.⁷ An effective strategy to decrease the drug concentration in breast milk is to pump or feed the infant when the maternal serum levels begin to decline. Women who desire to breast-feed their infants should be encouraged not to abandon this desire due to critical illness and current medications. Nurses and lactation consultants can assist the breast-feeding woman with pumping to promote breast milk production and to relieve engorgement. Discarding the milk is advised if drug toxicity and adverse pharmacologic actions of the drug are known, or if the drug transfer is unknown.⁷

Neurotransmitters in the peripheral nervous system—epinephrine and norepinephrine—are synthesized and primarily stored in nerve terminals until released by a nerve impulse. Medications that mimic the actions of epinephrine and norepinephrine are called adrenomimetic drugs. Receptors for epinephrine and norepinephrine (adrenoceptors) are selective for their respective agonists and antagonists (medications that enhance or block epinephrine and/or norepinephrine at adrenoreceptors).⁷

Autonomic receptors include those for acetylcholine (cholinergic) and those for catecholamines (adrenergic). The actions of catecholamines are determined by their ability to bind to three major classes of receptors: alpha (α), beta (β), and dopaminergic (Δ) (Table 6-3). Alpha receptors mediate excitation of the effector cells, whereas beta receptors provoke relaxation.⁷ A woman’s neurohormonal response has an important effect on the pharmacodynamics of medications used during critical illness. Heart rate, contractility, peripheral vascular tone, and metabolic changes are regulated by these endogenous changes. Also, certain diseases causing critical illness can change the receptor density, alter affinity, and change the response to agents (Table 6-4). Therefore, the pharmacologic effect is not necessarily equivalent to plasma drug concentrations, and may lead to substantial variation.⁸

A thorough discussion of concepts related to hemodynamic function including oxygen transport physiology is found in Chapter 4. Review of these concepts may be helpful as the reader considers select pharmacologic agents in context with the patient’s complete physiologic condition.