Chapter 15 Marini Pharmacotherapy

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SECTION I • Techniques and Methods in Critical Care

Intraosseous (IO) Intraosseous infusion is a rapid and safe method for obtaining parenteral access in patients with difficult venous access. Infusion of fluids and drugs into the bone marrow space has been researched since the 1920s, and it has since been verified that fluids and drugs administered through the IO space reach the central circulation as quickly as those given via a central venous catheter and faster than those given via a peripheral catheter. Mean IO pressures are close to the mean systemic pressure—much closer to central venous than to arterial values. IO can also be used for drawing blood samples. Although sometimes used when establishing urgent venous access proves difficult, the most frequent clinical situations in which IO is utilized remain cardiopul- monary resuscitation and trauma. A wide variety of drugs are delivered safely through IO access including adenosine, amio- darone, atropine, epinephrine, insulin, morphine, propofol, and many others. Theoretically, any medi- cation that can be given intravenously can be given via IO access. Each drug should be flushed with 10 mL of fluid to keep it from dwelling in the med- ullary cavity. In the arrest setting, blood concentrations of drugs will vary by IO injection site. For instance, peak blood concentrations are achieved faster for sternal IO than for tibial IO. In addition to slower peak concentrations, the peak concentration achieved by the tibial route may be only two thirds of that delivered via the sternum. Sternal IO time to peak blood concentrations and total delivered dose appear similar to central venous administration. Risks to using the IO route include osteomyelitis, bacteremia, soft tissue infection, and extravasation. Intravenous Injection The intravenous (IV) route is the most reliable route of drug administration and avoids problems of bio- availability and delays associated with absorption. Unfortunately, the IV route can result in danger- ously high peak drug concentrations, especially when a drug is infused rapidly through a central venous catheter. Cardiac toxicity can occur with phenytoin (hypotension) or potassium (dysrhyth- mias) during rapid IV infusions of these medica- tions. IV infusions allow the administration of drugs that would otherwise be too caustic, unstable, or

poorly absorbed to dose via other routes. At steady state, continuous infusions will sustain drug levels, limit peaks and troughs, and avoid the associated problems of subtherapeutic levels and toxicity. It must be kept in mind, however, that if the patient develops renal or hepatic dysfunction, continuous infusion rates should be adjusted to avoid excessive drug accumulation. Continuous IV infusion is the most costly method of drug administration and often is not necessary. For example, intermittent dosing of pain medications and sedatives is often just as effective and often shortens ICU length of stay. High costs arise from two sources: IV drugs are typically the most expensive formulations and substantial costs are also incurred in securing and maintaining IV access. The incremental costs of inserting an IV line are often overlooked and are increased even more if complications (e.g., hemothorax, pneumo- thorax, or catheter-related sepsis) occur. IV dosing can be avoided for many medications that achieve similar blood concentrations when given orally. Bioavailability for some orally given medications approaches 100% (e.g., fluoroquinolones, flucon- azole, metronidazole). Subcutaneous Injections Subcutaneous (SQ) injections may be appropriate if the drug is non-irritating and administered in a small volume (approx. 1 mL or less). Advantages of SQ administration include relatively rapid onset in nonshock states, reasonably uniform absorption (in normal patients), and avoidance of first-pass metabolism. Disadvantages of SQ administration include localized pain, abscess formation, infection, expensive cost, nerve damage, and local hemato- mas. Typical drugs that are given via this route in the ICU include insulin and anticoagulants (e.g., UFH and LMWHs). Critical illness can affect SQ absorption, mak- ing this route of administration less desirable in this population. During circulatory shock, blood is shunted to vital organs, depriving the subcu- taneous tissue of normal perfusion. One study evaluating the use of enoxaparin in patients receiving vasopressors found that the anti–factor Xa levels were significantly lower and not within the recommended therapeutic range. Profound edema (>10 kg of fluid weight gain) also impedes absorption. Morbid obesity may also make true