Chapter 15 Marini Pharmacotherapy

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SECTION I • Techniques and Methods in Critical Care

Continuous infusion is the most costly method of administration because a dedicated line, infusion pump, specialized cassettes, and tubing (all of which are expensive) are required. Also, each infusion site increases the risk of infection, and the mere pres- ence of an intravenous catheter in a patient with fever is likely to prompt an expensive evaluation as well as empiric antibiotics. Furthermore, if a central venous catheter must be inserted for access (e.g., for vasopressor therapy), the danger of infection persists and the risks of arterial puncture and pneu- mothorax are added. Sometimes switching from continuous infusion to intermittent intravenous dosing (e.g., benzodiazepines) or from continuous infusion to extended-duration infusion (e.g., antibi- otics) may provide cost savings with additional ben- efits or at least minimized harm. Intermittent dosing of longer-acting agents can free up an intravenous line for administration of other required medica- tions and blood products and in the process may avoid insertion of other catheters. Examples of this include using intermittent lorazepam (longer acting) in substitution of a continuous midazolam infusion or intermittent intravenous metoprolol (every 4 to 6 hours) in place of esmolol, which must be given as a continuous infusion. The belief is often wrong that giving a medi- cation by continuous infusion is mandated by the pharmacokinetics of the drug or confers more accurate control over its effects. Exact titration of a plasma drug level is rarely necessary or achievable, and drug levels often do not correlate with effects. Critically ill patients commonly have such altered pharmacodynamics that short-acting drugs can often have prolonged actions, many of which relate to the pH of the drug (basic vs. acidic) and whether it is hydrophilic versus lipophilic, both of which will be discussed later in this chapter. In addition, con- tinuous infusions may obscure signs that the drug is no longer necessary. Continuously infused sedatives should undergo a daily reduction or holiday for this reason and doing so may help prevent ventilator-

and vancomycin are inexpensive to purchase, their costs are increased by the need for frequent peak and trough levels (currently, each vancomycin level costs in excess of $50), along with frequently moni- tored creatinine levels. Another example is the use of UFH versus LMWH for therapeutic anticoagula- tion. Although LMWHs carry a higher acquisition cost, because of ease of administration and lack of drug level monitoring, they often end up costing less overall. UFH, when being used for therapeu- tic anticoagulation, is usually given as a continuous infusion and is therefore associated with the need for an intravenous line and all of its associated prob- lems and costs, as described previously. In addition, continuously infused UFH requires frequent moni- toring of coagulation status, which implies costs of testing as well as associated nursing efforts to evalu- ate labs and make infusion adjustments. Avoiding Competing Therapies It makes no sense to provide one drug that negates or counteracts the effect of another. Yet, it happens frequently when pharmacists are not monitoring the medication profile. One example is the use of two agents that directly compete for the same sub- strates (e.g., use of nonsteroidal anti-inflammatory drugs [NSAIDs] and aspirin in acute myocardial infarction, or use of buprenorphine or other par- tial antagonists with opioids). One medication may also bind with another, making it less effective (e.g., simultaneous use of calcium carbonate antacids that chelate fluoroquinolone antibiotics). Finally, it is important to think about situations in which side effects of certain medications may counteract those of another (e.g., giving propofol, which is well known to cause hypotension, to a patient receiving a vasopressor). We often want to maintain or restart outpatient medications soon after admission, but careful thought must be given to whether or not it is appropriate to do so. It may be best, for example, to hold bupropion (which can lower seizure threshold) in a patient admitted for a traumatic brain hemor- rhage or antihypertensive agents (e.g., ACE inhibi- tors or diuretics) in a patient admitted for septic shock on vasopressors. Optimizing Dosing One of the most important areas for safety improvement, which also often reduces drug cost, is careful attention to dosing as organ function changes. Most medications should be dosed less

associated pneumonias. Drug Monitoring Costs

A hidden cost of drug use is the coincident need to monitor drug levels and indices of organ func- tion (e.g., serum creatinine for potentially neph- rotoxic drugs, liver function tests for potentially hepatotoxic drugs, creatine kinase for daptomycin or platelets for linezolid). Although aminoglycosides