Is use of these agents justified? Here are tips

Having trouble rationalizing the use of popular but off-label critical care agents? A special session at the American College of Clinical Pharmacy's annual meeting explored evidence for the use of vasopressin, Factor VIIa, intravenous proton pump inhibitors, and dexmedetomidine (Precedex, Abbott Laboratories).

The most common use for vasopressin is as rescue for septic shock patients, noted Lance Oyen, assistant pharmacy director for clinical services at the Mayo Clinic. It seems to have positive effects in multiple types of shock that involve vasodilation, he said. It should be used cautiously in patients with cardiac dysfunction. Data on vasopressin in septic shock are largely positive, he added, but all of the reported trials are retrospective and use relatively small patient numbers. The first reports from a prospective, multicenter comparison of vasopressin and norepinephrine (the VASST trial) for septic shock are due in mid-2006.

Administration of more than 0.04 units per minute is associated with myocardial ischemia, decreased cardiac output, and cardiac arrest. Vasopressin appears to be safe at the renal level, but case reports suggest potential problems with reduced sodium levels, venous thrombosis, and increased liver enzymes. "Vasopressin is a good agent to rescue patients from the jaws of death," Oyen concluded, "but you shouldn't treat patients on the floor with this therapy."

In general, MacLaren said, patients need normal levels of calcium, fibrinogen, and arterial pH and near-normal body temperature for maximum efficacy. The platelet count should be at least 27 and other clotting agents should be tried first. Consensus recommendations indicate that prophylactic use before major surgery is not appropriate. Factor VIIa is generally inappropriate unless another clotting factor therapy has been tried and has failed.

Intravenous use of proton pump inhibitors for stress ulcers and upper gastrointestinal bleeding is another touchy area. Physicians typically push hard for IV PPIs, said Jill Rebuck, clinical assistant professor of surgery at the University of Vermont College of Medicine. In reality, the utility of IV PPIs is limited. "All IV use of these agents is off-label," she noted, "like so much of what we do in the hospital. If we take the physician's word for it, every patient with GI bleeding is at high risk for a rebleed and needs an IV PPI." The reality, she said, is that IV PPIs are appropriate only for a limited number of patients for a limited time period. Endoscopic examination is appropriate for all patients with an upper GI bleed.

Low-risk ulcers, those with a clean base or a flat spot, do not need IV PPIs. High-risk bleeds, ulcers with an adherent clot, a nonbleeding visible vessel, or an active bleed may benefit from IV therapy for 24 to 72 hours.

"Pharmacists should constantly review those orders and reduce inappropriate use," Rebuck noted. "We should recommend greater than 72-hour infusion only if the patient has a new bleed. We need to get patients off IV therapy as soon as possible."

Dexmedetomidine, or dex, is emerging as a useful sedative in intensive care, surgery, and other settings. It is indicated for use for less than 24 hours in patients on mechanical ventilation in the ICU, noted Ohio State University College of Pharmacy professor Joseph Dasta. Characteristics such as quick onset and offset, lack of respiratory depression and cardiovascular effects, amnestic and analgesic properties, easy dosing, and lack of drug interactions make it just as appealing in other settings.

"The patient is sedated but is easily arousable," he explained. "Patients can respond and cooperate easily."