Chapter 15 Marini Pharmacotherapy

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CHAPTER 15 • Pharmacotherapy

to toxic or subtherapeutic levels. In an attempt to avoid these fluctuations, many drugs in the ICU are given as a continuous or titratable infusion (vaso- pressors, sedatives, analgesics). Other drugs (espe- cially antibiotics) may avoid these fluctuations in peak and trough levels and achieve goal therapeu- tic ranges by extended infusion. Instead of infusing in over 1 hour, they may be infused over 8 hours. Highly lipid-soluble drugs, drugs with long half- lives, and those with a large volume of distribution may progressively accumulate for long periods of time before toxic side effects emerge. Deterioration of renal or hepatic function may impair drug excre- tion. The addition of new drugs to an established regimen may also alter metabolism, compete for protein binding or alter absorption. Inhalation Use of inhaled drugs offers the advantage of rapid absorption across a rather large surface area with minimal adverse effects. Targeting the drug to the target organ generally allows for a lower dose than is needed with systemic delivery, with fewer and less severe adverse effects. There are distinct disadvan- tages to this delivery method, however, including need for ancillary equipment (e.g., spacer), incon- sistent dosing technique, low efficiency of lung deposition, contamination of ambient air, and loss of drug. There are three types of devices to deliver aero- solized drugs, and all can be clinically effective if used correctly; these include the metered-dose inhaler (MDI), the dry powder inhaler (DPI), and nebulizer. Although lung deposition efficacy has increased with newer-generation devices, it remains in the 40% to 50% range. Use of inhaled drugs in the ICU is appealing to reduce the number of drugs given parenterally, but this method of drug delivery is complicated by depo- sition of the aerosol particles in the ventilator circuit and the endotracheal tube. Both inhaled beta-adren- ergic (albuterol) and anticholinergic (ipratropium) agents have proven efficacy in mechanically ven- tilated patients. Efficacy of drug delivery depends on several factors, including type of nebulizer used, proximity to the airway opening, actuation of an MDI into an in-line chamber spacer, midinspira- tory timing of MDI actuation, ventilator mode, tidal volume, circuit humidification, and ventilator duty cycle. With proper technique, it has been shown

that four (4) puffs of an MDI will produce signifi- cant and near-maximal therapeutic effects that are comparable to those obtained with 6 to 12 times the same dose given by a nebulizer. Apart from its labor saving, quicker delivery and lower cost advantages, many practitioners consider MDIs more efficacious to prescribe during mechanical ventilation. Endotracheal Instillation The endotracheal route of administration utilizes the absorptive capacity of the lung. A drug solution is introduced through the endotracheal tube and allowed to migrate into the lower respiratory tree. Delivery to the distal site of absorption is facilitated by insufflation using a manual ventilator (or similar device such as an artificial manual breathing unit). The proposed site of circulatory absorption is the alveolar capillary circulation. Only certain drugs are safe and effective when given this way. There are several considerations when using the endotracheal route of drug administration. First, the proper technique must be employed. Patients must be tilted (avoid a fully upright position) to allow the drug to filter into the lower respiratory tree. Adequate ventilation also plays an important role in distribution. Most reports suggest manual ventilation at least 5 to 10 times afterward to assure maximal distribution. Drugs should be diluted in 0.25 mL (for pediatric patients) to 10 mL (for adults) of 0.9% saline or sterile water. Somewhat arbitrary recommendations for endotracheal dos- ing are 2 to 3 times the usual intravenous doses for nearly all candidate drugs. Endotracheal drug administration has typically been reserved for cardiopulmonary resuscitation in which no intravenous access is available. Drugs typ- ically given in this situation can be remembered by the mnemonic NAVEL (naloxone, atropine, vaso- pressin, epinephrine, and lidocaine). Epinephrine, atropine, and naloxone are reported to be effective and appear to have no added adverse effects when given via the endotracheal route. There are risks with other drugs, however. Sodium bicarbonate may inactivate lung surfactant, isoproterenol and cal- cium chloride are reported to cause tissue necrosis, and bretylium is poorly absorbed and does not result in adequate blood levels. When the more reliable intraosseous (IO) access can be quickly attained and immediately accomplished, endotracheal dos- ing is seldom used (see below).