سيف ناصر القلعة Pharmacology Critically ill adult patients often receive multiple medications during their admissions to an intensive care unit. These patients may be at risk for increased adverse effects from their medi cations because of altered metabolism and elimination that is commonly seen in the critically ill patient. Organ dysfunc tion or drug interactions may produce increased serum drug or active metabolite concentrations, resulting in enhanced or adverse pharmacologic effects. Therefore, it is important to be familiar with each patient’s medications, including the drug’s metabolic profile, drug interactions, and adverse effect profile. This chapter reviews medications commonly used in intensive care units and discusses mechanisms of action, indications for use, common adverse effects, contraindications, and usual doses. A summary of intravenous (IV) medication informa tion is provided in Chapter 23, Pharmacology Tables. MEDICATION SAFETY In the care of the critically ill, the medication use process is particularly complex. Each step in the process is fraught with the potential for breakdowns in medication safety (ie, adverse drug events [ADEs], medication errors). Improve ment in medication safety requires interdisciplinary focus and attention. The Institute for Safe Medication Practices (ISMP) has highlighted the following key elements which must be optimized in order to maintain patient safety in the medication use process: • Patient information: Having essential patient infor mation at the time of medication prescribing, dis pensing, and administration will result in a significant decrease in preventable ADEs. • Drug information: Providing accurate and usable drug information to all health-care practitioners involved in the medication-use process reduces the amount of preventable ADEs. • Communication of drug information: Miscommunica tion between physicians, pharmacists, and nurses is a common cause of medication errors. To minimize medication errors caused by miscommunication, it is important to always verify drug information and eliminate communication barriers. • Drug labeling, packaging, and nomenclature: Drug names that look alike or sound alike, as well as prod ucts that have confusing drug labeling and non distinct drug packaging significantly contribute to medication errors. The incidence of medication errors is reduced with the use of proper labeling and the use of unit dose systems within hospitals. • Drug storage, stock, standardization, and distribution: Standardizing drug administration times, drug con centrations, and limiting the dose concentration of drugs available in patient care areas will reduce the risk of medication errors or minimize their conse quences should an error occur. • Drug device acquisition, use, and monitoring: Appro priate safety assessment of drug delivery devices should be made both prior to their purchase and dur ing their use. Also, a system of independent double checks should be used within the institution to pre vent device-related errors such as, selecting the wrong drug or drug concentration, setting the rate improp erly, or mixing the infusion line up with another. • Environmental factors: Having a well-designed system offers the best chance of preventing errors; however, sometimes the ICU environment may contribute to medication errors. Environmental factors that can often contribute to medications errors include poor lighting, noise, interruptions, and a significant workload. • Staff competency and education: Staff education should focus on priority topics, such as new medi cations being used in the hospital, high-alert medi cations, medication errors that have occurred both internally and externally, protocols, policies, and procedures related to medication use. Staff education can be an important error-prevention strategy when combined with the other key elements for medication safety. • Patient education: Patients must receive ongoing edu cation from physicians, pharmacists, and the nursing staff about the brand and generic names of medica tions they are receiving, their indications, usual and actual doses, expected and possible adverse effects, drug or food interactions, and how to protect them selves from errors. Patients can play a vital role in pre venting medication errors when they are encouraged to ask questions and seek answers about their medi cations before drugs are dispensed at a pharmacy or administered in a hospital. 1 • Quality processes and risk management: The way to prevent errors is to redesign the systems and pro cesses that lead to errors rather than focus on correcting the individuals who make errors. Effective strategies for reducing errors include making it difficult for staff to make an error and promoting the detection and correction of errors before they reach a patient and cause harm. MEDICATION ADMINISTRATION METHODS Intravenous Intravenous (IV) administration is the preferred route for medications in critically ill patients because it permits com plete and reliable delivery. Depending on the indication and the therapy, medications may be administered by IV push, intermittent infusion, or continuous infusion. Typically, IV push refers to administration of a drug over 3 to 5 minutes; intermittent infusion refers to 15-minute to 2-hour drug administration several times per day, and continuous infu sion administration occurs over a prolonged period of time. Intramuscular or Subcutaneous Intramuscular (IM) or subcutaneous (SC) administration of medications should rarely be used in critically ill patients. This is due to a number of factors including delayed onset of action, unreliable absorption because of decreased periph eral perfusion (particularly in patients who are hypotensive or hypovolemic), or inadequate muscle or decreased SC fat tissue. Furthermore, SC/IM administration may result in incomplete, unpredictable, or erratic drug absorption. If medication is not absorbed from the injection site, a depot of medication can develop. If this occurs, once perfusion is restored, absorption can potentially lead to supratherapeutic or toxic effects. Additionally, patients with thrombocytope nia or who are receiving thrombolytic agents or anticoagu lants may develop hematomas and bleeding complications due to SC or IM administration. Finally, administering fre quent IM injections may also be inconvenient and painful for patients. Oral Oral (PO) administration of medication in the critically ill patient can also result in incomplete, unpredictable, or erratic absorption. This may be caused by a number of factors including the presence of an ileus impairing drug absorp tion, or to diarrhea decreasing gastrointestinal (GI) tract transit time and time for drug absorption. Diarrhea may have a pronounced effect on the absorption of sustained release preparations such as theophylline, procainamide, or calcium channel–blocking agents, resulting in a suboptimal serum drug concentration or clinical response. Several medi cations such as fluconazole and the fluoroquinolones have been shown to exhibit excellent bioavailability when orally administered to critically ill patients. The availability of an oral suspension for some of these agents makes oral admin istration a reliable and cost-effective alternative for patients with limited IV access. In patients unable to swallow, tablets are often crushed and capsules opened for administration through nasogastric or orogastric tubes. This practice is time consuming and can result in blockage of the tube, necessitating removal of the clogged tube and insertion of a new tube. If enteral nutri tion is being administered through the tube, it often has to be stopped for medication administration, resulting in inad equate nutrition for patients. Also, several medications (eg, phenytoin, carbamazepine, and warfarin) have been shown to compete, or interact, with enteral nutrition solutions. This interaction results in decreased absorption of these agents, or complex formation with the nutrition solution leading to precipitation and clogging of the feeding tube. Liquid medications may circumvent the need to crush tablets or open capsules, but have their own limitations. An example is ciprofloxacin (Cipro) oral solution which is an oil-based preparation that should not be given via feeding tube because of the high probability of clogs. Many liquid dosage forms contain sorbitol as a flavoring agent or as the primary delivery vehicle. Sorbitol’s hyperosmolarity is a fre quent cause of diarrhea in critically ill patients, especially in patients receiving enteral nutrition. Potassium chloride elixir is extremely hyperosmolar and requires dilution with 120 to 160 mL of water before administration. Administer ing undiluted potassium chloride elixir can result in osmotic diarrhea. Lastly, sustained-release or enteric-coated prepara tions are difficult to administer to critically ill patients. When sustained-release products are crushed, the patient absorbs the entire dose immediately as opposed to gradually over a period of 6, 8, 12, or 24 hours. This results in supratherapeu tic or potentially toxic effects soon after the administration of the medication, with subtherapeutic effects at the end of the dosing interval. Sustained-release preparations must be con verted to equivalent daily doses of immediate-release dosing forms and administered at more frequent dosing intervals. Enteric-coated dosage 2 forms that are crushed may be inac tivated by gastric juices or may cause stomach irritation. Enteric-coated tablets are specifically formulated to pass through the stomach intact so that they can enter the small intestine before they begin to dissolve. Sublingual Because of the high degree of vascularity of the sublingual mucosa, sublingual administration of medication often pro duces serum concentrations of medication that parallel IV administration, and an onset of action that is often faster than orally administered medications. Traditionally, nitroglycerin has been one of the few medications administered sublingually (SL) to critically ill patients. Several oral and IV medications, however, have been shown to produce therapeutic effects after sublingual administration. Captopril has been shown to reliably and predictably lower blood pressure in patients with hyperten sive urgency. Oral lorazepam tablets have been administered SL to treat patients in status epilepticus; preparations of oral triazolam and IV midazolam have been shown to produce sedation after sublingual administration. Intranasal Intranasal administration is a way to effectively administer sedative and analgesic agents. The high degree of vascularity of the nasal mucosa results in rapid and complete absorption of medication. Agents that have been administered success fully intranasally include meperidine, fentanyl, sufentanil, butorphanol, ketamine, and midazolam. Transdermal Transdermal administration of medication is of limited value in critically ill patients. Although nitroglycerin oint ment is extremely effective as a temporizing measure before IV access is established in the acute management of patients with angina, heart failure (HF), pulmonary edema, or hyper tension, nitroglycerin transdermal patches are of limited benefit. Transdermal patches are limited by their slow onset of activity and their inability for dose titration. Also, patients with decreased peripheral perfusion may not sufficiently absorb transdermally administered medications to produce the desired therapeutic effect. Transdermal preparations of clonidine, nitroglycerin, or fentanyl may be beneficial in patients who have been stabilized on IV or oral doses, but require chronic administration of these agents. Chronic use of nitroglycerin transdermal patches is further complicated by the development of tolerance. However, the development of tolerance can be avoided by removing the patch at bed time, allowing for an 8- to 10-hour “nitrate-free” period. A eutectic mixture of local anesthetic (EMLA) is a com bination of lidocaine and prilocaine. This local anesthetic mixture can be used to anesthetize the skin before insertion of IV catheters or the injection of local anesthetics that may be required to produce deeper levels of topical anesthesia. Although transdermal administration of medications is an infrequent method of drug administration in critically ill patients, its use should not be overlooked as a potential cause of adverse effects in this patient population. Exten sive application to burned, abraded, or denuded skin can result in significant systemic absorption of topically applied medications. Excessive use of viscous lidocaine products or mouthwashes containing lidocaine to provide local anesthe sia for mucositis or esophagitis also can result in significant systemic absorption of lidocaine. Lidocaine administered topically to the oral mucosa has resulted in serum concentra tions capable of producing seizures. The diffuse application of topical glucocorticosteroid preparations also can lead to absorption capable of producing adrenal suppression. This is especially true with the high-potency fluorinated steroid preparations such as betamethasone dipropionate, clobetasol propionate, desoximetasone, or fluocinonide 3
