1. Cuddy, Paul G. PharmD

Article Content

Critically ill patients receive many drugs during their hospitalization; some function as primary therapeutic interventions and others serve a supportive role enabling patients to sustain themselves until their underlying problems resolve. This issue of Critical Care Nursing Quarterly (22:4) is devoted to drug therapy topics and addresses not only new drugs administered as primary therapeutic interventions but also older medications that support patients recovering from their primary insluts. The important and increasingly well-recognized issue of drug interactions is reviewed; nutritional support and drug therapy monitoring are also discussed.


Recently several important cardiovascular medications have been introduced that fall into one of two therapeutic classes-low molecular weight heparins and GPIIb/IIIa inhibitors. These drugs represent significant therapeutic advances that are finding increasingly broader indicatons for their use. DiDomenico summarizes these new classes of medications by describing their mechanism of action, pharmacokinetics, therapeutic use, toxicity profiles, and costs; appropriate comparisons to unfractionated heparin are introduced where apt. A brief discussion of the recently marketed direct thrombin inhibitor, lepirudin, is also provided and its place in therapy identified.


Historically antiarrhythmic drugs were prescribed widely based upon evidence accumulated from studies that used a variety of surrogate endopints. The publication of the CAST trials challenged that practice and has restricted use of these potentially lethal drugs. 1,2. Wooten reviews the important cardiac and noncardiac toxicities of this drug class and provides information useful in the construction of monitoring parameters for efficacy and toxicity. Specific attention is devoted to the proarrhythmic effects of antiarrhythmic drugs presently available.


Numerous drug therapies have been administered over the years to mechanically ventilated patients to minimize their discomfort. Yagan et al. discusses these therapeutic approaches by initially describing the causes of distress in the mechanically ventilated patient and the overall goals of ICU care. After presenting this background information, nonpharmacologic and pharmacologic interventions are discussed with emphasis directed to opioids, neuromuscular blocking agents, benzodiazepines and the different anesthetic induction agents. Historically, the patient receiving mechanical ventilation has been identified as being at significant risk for stress ulceration. Although stress ulcer prophylaxis therapy is still widespread, recent literature has challenged this practice in many critically ill patients. Foxworth reviews this controversial topic employing an evidence-based approach and contrasts the experience gained in the 1970s with the results of trials published in the 1990s. Foxworth concludes that the practice of providing stress ulcer prophylaxis to ICU patients is too ubiquitous and yields a small benefit to patient outcome.


Since the critically ill patient routinely receives two or more drugs, the likelihood that one of these medications will alter the effect of other coadministered agents is great. In fact, it is quite likely that many drugs interact with other medications, but the degree of this interaction is of such a mild nature that these interactions go unrecognized. At the other extreme, some important interactions, eg., mibefradil and terfenadine, are worrisome enough that drugs have actually been withdrawn from market. A deeper understanding of the metabolic basis of these drug interactions has evolved recently, particularly in cytochrome P450 drug-metabolizing enzymes, which helps elucidate the topic for clinicians. Streetman describes the mechanism by which drugs are normally metabolized and identifies factors that can lead to alterations in drug metabolism thereby helping practitioners predict and prevent potentially serious interactions.


Delirium is a common and serious problem that potentially affects all hospitalized patients, and it certainly occurs in the critically ill population since these patients present with predisposing conditions and are recipients of hospital-related insults, eg., medications. Geehan et al. describe a case of delirium that complicated a patient's hospital course, and the authors use this experience as the focal point for their discussion of delirium in the ICU. Although many of the therapeutic agents that are used in the ICU can precipitate delirium, patients may also experience delirium as part of their underlying medical conditions. For example, withdrawal syndromes, delirium tremens in particular, are known to cause delirium. Using a combination of appropriate selection of medications and an awareness of delirium as a side effect, the authors show how a patient in the ICU may be treated in a manner to minimize the clouding of consciousness.


Providing nutrition support in the critically ill patient has become routine in most ICU settings despite an absence of well-controlled studies demonstrating a clear mortality benefit. Case et al, provide a concise overview of nutritional support in the ICU focusing upon indications for enteral and parenteral feedings, caloric and protein requirements, complications, and metabolic monitoring. Important adjunctive therapies that are used to achieve nutritional goals, eg., insulin infusions to control serum glucose and prokinetic agents to improve gastric emptying, are also discussed.


A common thread running through this drug therapy issue is that a clear need exists to monitor all therapeutic interventions for intended as well as unintended consequences. Cuddy provides a conceptual framework to drug monitoring and emphasizes the need to routinely identify monitoring parameters for efficacy and toxicity for all drugs prescribed. Specific guidelines are presented to help identify these monitoring parameters as well as assist in their interpretation. The role of therapeutic drug monitoring is identified and guidelines provided for interpreting therapeutic drug concentrations.


I am pleased to have this opportunity to present important issues in drug therapy to critical care practitioners. Each author has addressed an issue they confront daily and the quality of the publication reflects their expertise in these areas.




1. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators: Preliminary report: effect of encainide and flecanide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989; 321:406-412. [Context Link]


2. The Cardiac Arrhythmia Suppression Trial II Investigators. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. N Engl J Med 1992; 327:227-233. [Context Link]