Chapter 15 Marini Pharmacotherapy

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SECTION I • Techniques and Methods in Critical Care

returns in order to reduce cost as well as prevent bac- terial resistance. A classic example of this is stopping vancomycin or linezolid when there are no gram-pos- itive bacteria on cultures. Stop dates on antibiotics should be placed when ordering antibiotics; almost every non-necrotizing pneumonia can be treated with 7 days of therapy (as long as the patient clinically improves early in therapy), and most intra-abdominal infections are now treated with 4 to 5 days of therapy. Placing appropriate stop dates at time of order entry will prevent continuation of antibiotic treatment for days or even weeks longer than what is needed. Often, medication profile review reveals con- tinuation of outpatient medications of questionable or no value during hospitalization. Most patients do not need vitamins or antihistamines, for example, during critical illness. It is generally recommended that oral hypoglycemic agents be held in critical ill- ness (opting to use insulin instead) because of fluc- tuating oral intake. Similarly, alpha-blockers (e.g., tamsulosin) can be held for those patients with uri- nary catheters in place. In general, at least initially, it is probably most appropriate to hold outpatient medications and reevaluate restarting them on a day-to-day basis. Shortening of ICU or Hospital Stay The choice of a more expensive drug may result in net cost savings by reducing the length of hospital stay. For patients needing therapeutic anticoagulation (e.g., for VTE or pulmonary embolism), LMWH or UFH are both options. LMWHs are generally more expensive, but because they may be given via subcuta- neous injections in an outpatient setting (vs. intrave- nous UFH and oral warfarin), it may be the best cost saving option, and patients may be able to discharge days sooner. Another example is in choice of seda- tives. Both propofol and dexmedetomidine are more expensive sedation options than either midazolam or lorazepam (both benzodiazepines). However, because propofol and dexmedetomidine are both shorter act- ing and may be more easily titrated off, they may lead to fewer ventilator and ICU days, thereby making them the more cost-effective choices. PHARMACOKINETICS Patients in the ICU are often given 10 or more med- ications simultaneously. As the number of medica- tions, severity of illness, and patient age increase, so does the risk of an adverse drug reaction. Although few physicians have enthusiasm for studying

pharmacokinetics (the sum of the processes the body is conducting on the drug, including absorp- tion, distribution, metabolism, and excretion) or pharmacodynamics (the physiologic and biochemi- cal effects of the drug on the body), understanding the basic concepts is essential to providing quality care. The critical care physician must develop a healthy respect for medications with narrow thera- peutic margins and serious side effects. Intensivists must also learn how pharmacokinetics and phar- macodynamics differ between critically ill and ambulatory patients. Five major concepts are key to understanding appropriate drug dosing: absorp- tion, distribution, and protein binding, metabolism, elimination, and half-life. Absorption Absorption is the ability of a drug to move from the site of administration into the bloodstream. The extent of absorption is typically measured in terms of bioavailability (the fraction of an administered dose that reaches systemic circulation). All drugs, other than those given by the intravenous route, are affected by absorption, but few studies have evalu- ated the affect that specific critical illnesses have on this process. Many factors may affect absorption including, gastric pH, gastrointestinal (GI) motility, bowel wall edema, splanchnic perfusion, first-pass metabolism, and enteral feeding interactions. In states of decreased perfusion, the body’s physiologic response is to shunt blood toward vital organs and away from the GI tract, which may decrease enteral absorption. In patients requir- ing vasopressor therapy, it is well documented that there are differing degrees of alterations in splanch- nic perfusion. Bowel edema is a common cause of inefficient absorption. There are many reasons for decreased gastric motility, including abdominal surgery, medications (e.g., opioids), ileus, immobility, traumatic brain injury, and electrolyte abnormalities (especially cal- cium or potassium). Absorption from the GI tract is favored when the drug is nonionized and lipophilic because absorption occurs by passive diffusion. The rate of absorption in the intestine will be greater than that in the stomach, even if the drug is pre- dominately ionized in the intestine or largely non- ionized in the stomach. Any factor that accelerates gastric emptying such as right-sided positioning or use of motility agents (e.g., erythromycin, metoclo- pramide) will be likely to increase the rate of drug