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1240 PART 11: Special Problems in Critical Care

reaction in the ICU when elimination of an agent, which they have 4. Hansten PD, Horn JR: Drug Interactions Analysis and Management.
received chronically prior to hospitalization, is subject to a drug-disease Applied Therapeutics, Inc (updated quarterly).
interaction (eg, theophylline toxicity precipitated by development of 5. Tatro DS (ed.): Drug Interaction Facts. St Louis: Lippincott (updated
congestive heart failure), or drug-drug interaction (eg, theophylline quarterly).
toxicity caused by concurrent ciprofloxacin administration). In the
absence of another convincing etiology, discontinuation or dose reduc- 6. medicine.iupui.edu/flockhart/ (updated periodically).
tion of the suspected drug is indicated. Subsequent improvement in 7. Stockley’s Drug Interactions, Pharmaceutical Press. Tenth Edition 2013.
signs or symptoms is presumptive evidence of an ADR; of note, ADRs
precipitated by agents with long half-lives may require a longer period Drug Interaction Software Subscription Services: Most institutions utilize
for resolution. The degree of certainty in ADR diagnosis increases if one or more computer software programs available by subscription,
rechallenge with the suspected drug leads to reappearance of the pre- such as Epocrates Rx Pro, to help identify drug interactions. These
sumed ADR; however, readministration of drug for this purpose is not programs are continuously in development, and to date no system has
recommended unless the information is crucial for subsequent patient been demonstrated to be superior to an experienced clinician in iden-
management and alternative drugs are not available. If an idiosyncratic tifying drug interactions. Barriers to the development of drug-drug
or allergic type reaction is suspected, drug readministration may be interaction (DDI) detection software for widespread use include dif-
hazardous. Prior to considering rechallenge, appropriate consultation ficulty of portability and integration into existing hospital computer
is suggested, to evaluate viable alternative therapies, the potential for systems, development and maintenance of the knowledge base, and
challenge-induced anaphylaxis, possible desensitization procedures establishment of formal methodology of evaluation of these systems.
(if any), and formulation of a comprehensive treatment protocol to Nonetheless, existing available software are a good initial step toward
manage any adverse sequelae of reexposure to the agent. decreasing ADRs due to drug-drug interactions.
Identifying the culprit drug in patients receiving multiple medica-
tions can be challenging. The most likely offender should be either dose Dedicated ICU Intensivists and Pharmacists: Many studies have investi-
gated the benefits of a dedicated team of professionals in the ICU, with
reduced or discontinued (as appropriate based on the suspicion of a
dose-dependent vs an idiosyncratic/allergic phenomenon), while less the team led by a physician with specialized training in critical care
medicine.
This advantage is theorized to be a result of specialized
106,107
likely candidate drugs are continued. If the suspected reaction does not
improve, remaining drugs may be discontinued sequentially, beginning training in particular issues that arise in critically ill patients, a broader
perspective of issues that pertain to critically ill patients, and improved
with the most likely candidate. In a patient suffering a severe reaction,
all medications should be stopped if possible. A common example in continuity of care. In fact, the Leapfrog Initiative—a coalition of some
of the nation’s largest employers, such as General Electric and General
the ICU is the patient who develops thrombocytopenia while receiving
prophylactic therapy with an H blocker and subcutaneous heparin. In Motors—has identified this as one of the three changes that they
believe would most improve safety. This same rationalization can be
108
2
this situation, thrombocytopenia frequently represents a manifestation
of disease, particularly if hemodynamic instability is present, and not an used to justify the role of a dedicated ICU pharmacist. The traditional
role of a pharmacist to accept and clarify orders and dispense medica-
ADR. Nevertheless, in the presence of severe or progressive thrombo-
cytopenia, an ADR should be considered and medication adjustments tions is antiquated. Having a pharmacist who participates in clinical
rounds as a full member of the patient care team in the ICU can sig-
made. Heparin use correlates most firmly with drug-induced throm-
104
bocytopenia, and this agent should be discontinued first. H blockers nificantly decrease ADRs and decrease costs of hospitalization as com-
The benefits may be explained
pared to pharmacist review alone.
109,110
2
(and indeed most other drugs used in the ICU) are not responsible for
the majority of cases of thrombocytopenia and may be continued if by improved communication between the health care professionals,
optimization of therapy, and improved monitoring and management of
clinically important. In patients with critical thrombocytopenia,
104
however, risk-benefit analysis supports discontinuation of both drugs adverse drug events. For example, for the treatment of an infection in
a critically ill patient, the ICU pharmacist may contribute specialized
pending further evaluation, which may include assay for antiplatelet
antibodies (drug-specific tests are possible). knowledge in selecting the narrowest-spectrum antibiotic, in select-
ing an appropriate drug to minimize antibiotic resistance based on
Numerous published tables list drugs associated with ADRs. 98,105 These
lists are merely suggestive that a sign or symptom may be drug related. patterns of organism resistance in the hospital, in minimizing potential
adverse drug reactions, and in selecting the most cost-effective agent.
They include both well-documented and poorly documented drug
reactions and are clearly not all inclusive. The absence of a drug from Barriers to implementing the dedicated ICU pharmacist model include
the initial investment of money and time to create a new staff position,
a particular category does not exclude the possibility of drug reaction,
since there is always a first identified or reported reaction, especially but these initial costs are likely to be easily overcome by savings in drug
costs and prevention of adverse drug events.
during the initial period of postmarketing surveillance following approval
and release of a new drug for widespread use. In the absence of a simple, Computerized Order Screening Systems: Computerized screening of
dedicated, and exhaustive source of information about ADRs specific medication orders at the time of prescription data entry is performed
to critical care, most clinicians rely on their institution’s hospital drug in many acute care practice settings. Such programs allow for real-time
information service, and various library and internet resources. It is checks for potential drug interactions with the patient, disease states,
105
important to become familiar with these resources and to utilize govern- or other drugs. Physician order entry (POE) systems also obviate
ment and pharmaceutical industry information services to aid in evalu- potential medical errors due to illegible handwriting or transcrip-
ating potential ADRs. Appropriate information resources include the tion errors. Common problems with these programs include a lack
following: of primary literature referencing, routine detection of insignificant
General Drug Information References interactions, and a significant lag time between introduction of a
1. Physicians’ Desk Reference. Medical Economics Company, Inc new drug and interaction data updates. Physicians with minimal
(annual editions). technological expertise may also be hesitant to use such technol-
ogy. Nonetheless, POE systems are another change that the Leapfrog
2. American Hospital Formulary Service Drug Information. Bethesda, Initiative has identified that may contribute to significant reduction
MD: American Society of Health-Systems Pharmacists, Inc (annual in ADRs. Introduction of computerized physician order entry systems
editions). clearly reduces medication prescription errors and ADRs; however,
3. Drug Facts and Comparisons. Philadelphia: Lippincott. Phone: the quality of the implementation process could be a decisive factor
1-800-232-0554 for product information (updated monthly). determining overall success or failure. 111
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