Approximately 5 million seriously ill and surgical patients annually require complex care and are admitted to an intensive care unit (ICU), coronary care unit (CCU), or post-anesthesia care unit (PACU). The clinical outcome for many critical care patients may depend on tight anti-coagulation control, acute glucose control, sedation control, acute hypertensive control, or electrolyte control (potassium replacement). Effective treatment using widely prescribed medications for these conditions may be complicated by well known shortcomings of these agents including unpredictable dose response, narrow therapeutic ranges, high potential for complications and the consequent high probability of medication errors. Challenges associated with careful management of anti-coagulation control, acute glucose control, and sedation control are highlighted in the following sections.
Clinical Challenges with Anti-coagulation Control
UF heparin, alone or in conjunction with other anticoagulants, is a standard of treatment in patients with heart attacks, stroke, unstable angina, thrombosis, pulmonary embolism and deep vein thrombosis. It has been used in hundreds of millions of patients worldwide and still commands a 40% market share of anticoagulants used in the acute care setting. UF heparin is administered intravenously (IV) and its effects are well understood. It has a rapid onset of action, can be accurately measured with the use of a standard test, activated partial thromboplastin time (aPTT) measured in seconds, and can be rapidly reversed by administering aprotinin if needed.
However, the anticoagulation effects of UF heparin vary widely from patient to patient and clinicians experience significant difficulty in achieving and maintaining patients within the desired therapeutic range. The need to achieve a therapeutic aPTT range and the effect of being out of that range on clinical outcomes has been well established in numerous clinical trials. In spite of this, more clinical studies have reported wide patient variability in the dose of UF heparin required to maintain patients within the therapeutic range and one major study recently published in Circulation determined that patients were within the therapeutic range only 33% of the time.
This represents a major problem for clinicians and hospitals because of a significant increase in the incidence of bleeding in patients over dosed with UF heparin, and increased ischemic events, (e.g., heart attack, strokes) for patients who are under dosed with UF heparin. This problem has been estimated to cost hospitals over $1 billion per year in the U.S. alone.
The problem is serious enough that the Joint Commission of the American Hospital Association, which accredits hospitals, established National Patient Safety Goals in 2008 requiring improvements in medication safety. One goal specifically called for a reduction in the likelihood of patient harm associated with the use of anticoagulant therapy involving heparin, LMWH, warfarin, and direct thrombin inhibitors, and included recommendations to:
- Format anticoagulation orders and flow sheet to follow patient through from transition from hospital to skilled care to home.
- Use anticoagulation dosing services
- Report lab results to someone who can take action
- Develop and implement standardized protocols and dosing for all agents
- Establish guidelines for holding heparin and administering a reversal agent
Further, Medicare will no longer reimburse hospitals for situations involving medication errors resulting from incorrect administration of anticoagulants.
Drug delivery systems are a proven method for improving the therapeutic index of drugs, including older drugs like UF heparin. Numerous clinical studies have shown that more effective delivery of UF heparin could significantly improve clinical outcomes. Automedics’ first products, HepGuide DSS and the AutoHep System, are designed to dramatically improve the control and delivery of UF heparin to attain and maintain patients within the therapeutic range.
Clinical Challenges with Sedation Control
Sedation is an integral part of critical care for PACU patients and ICU patients requiring mechanical ventilation. Typically administered either by intermittent bolus dosing or by continuous infusion, sedatives reduce the stress response, provide anxiolysis, improve tolerance of ventilatory support, and facilitate nursing care. Unfortunately, oversedation has adverse effects, including the potential to prolong mechanical ventilation and increased ICU stay, organ failure, and reintubation rates (Kollef).1
Clinicians experience significant challenges with determining the adequacy of sedation because 1) of the subjective nature of assessments, particularly where constant communication with the patient is not possible; 2) many clinical parameters such as changes in vital signs may be unreliable indicators of the presence of pain; 3) critically ill patients frequently exhibit unpredictable alterations in their pharmacodynanamic profiles; and 4) concern with drug accumulation.2. Sedation of critically ill patients would be optimized if strategies that attended to pharmacokinetic and pharmacodynamic profiles commonly observed in such patients were well described, and in turn provided specific guidance for drug administration.
Clinical Challenges with Glucose Control
Hyperglycemia and insulin resistance are common in critical care patients, even if they have not previously had diabetes. There has been concern that hyperglycemia or relative insulin deficiency (or both) during critical illness may directly or indirectly confer a predisposition to complications, such as severe infections, polyneuropathy, multiple-organ failure, and death3. For these reasons, an increasing number of critical care patients are treated using an intense insulin therapy (IIT) protocol to achieve tight glucose control. IIT requires frequent blood glucose tests in order to achieve this control. Currently, these tests are performed using conventional finger-stick blood glucose tests, which are painful, time consuming, and increase risk of infection.