While our understanding of the clinical impact of steroid-immunosuppressant interactions is limited, it remains a fact that corticosteroids have complex induction and inhibition interactions with common metabolic and transport pathways. Given the complex interaction of corticosteroids on crucial metabolic enzymes and transporter proteins, monitoring of immunosuppressive agents during steroid withdrawal is warranted to ensure optimal treatment outcomes.

The role of allopurinol in the prevention of ischemia-reperfusion injury was assessed in a model of heart-lung transplantation. Fourteen swine were divided into two groups (seven donors and seven recipients). All heart and lung blocks were placed in hypothermic storage after perfusion with cold iso-osmolar cardioplegic solution and modified Collins solution, respectively (t = 8-10 degrees C for heart and t = 16-18 degrees C for lungs). The total ischemic time including the orthotopic transplantation was 6 h. Animals (donors and recipients) were pretreated with allopurinol given orally at a dosage of 50 mg/kg for 4 days. Animals were assessed by monitoring heart and lung function, including extravascular lung water at three time intervals, which included pretransplantation (donor), and 30 min and 2 h posttransplantation (recipient). Erythrocyte peroxidation susceptibility was assessed for 3 days, and surgery was performed on day 4. The malondialdehyde levels determined from erythrocyte exposure to in vitro peroxidative challenge classified three paired donor and recipient animals as responders and four paired donor and recipient animals as nonresponders to the allopurinol pretreatment. A persistent deterioration of lung function was observed over time in nonresponders (p less than .05) (increase of lung water, decrease of partial pressure of oxygen, increase in alveolar-arterial gradient, and decrease in arterial-alveolar tension ratio). Responders showed no significant alterations in lung function. This study in swine, a species devoid of myocardial xanthine oxidase activity, indicates that allopurinol may have a mechanism of action other than xanthine oxidase inhibition in the prevention of ischemia-reperfusion injury. The parallelism between protection of lung function and of red blood cells suggests the involvement of a generalized increase in tissue antioxidant capacity.

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Thiopental has been used for decades in the treatment of refractory intracranial hypertension in patients with traumatic and nontraumatic head injuries. Commonly reported adverse effects include hypotension, hypokalemia, respiratory complications, and hepatic dysfunction. Neutropenia has rarely been reported as an adverse effect of thiopental. We witnessed probable thiopental-induced neutropenia in two patients with traumatic brain injuries who developed increased intracranial hypertension that was refractory to standard therapy. Based on a MEDLINE search of published case reports and literature, we propose two mechanisms by which thiopental-related neutropenia might be explained. The first is inhibition of inflammatory mediator nuclear factor-kappa B (NF-kappa B), leading to granulocyte apoptosis. The second mechanism involves inhibition of calcineurin. Although the precise link between these two mechanisms has not been elucidated, calcineurin is known to regulate NF-kappa B activity. Development of neutropenia does not appear to be correlated with time but may correlate with plasma concentrations of thiopental. The optimum management of drug-induced neutropenia is unclear. The decision to discontinue thiopental in patients who develop neutropenia should be made by weighing the risks versus benefits. Broad-spectrum antibiotics may be required in the presence of fever. The role of hematopoietic growth factors such as granulocyte colony-stimulating factor is not yet defined. Given the adverse infectious consequences of neutropenia, it is essential to closely monitor neutrophil counts in patients receiving thiopental.

Background: Clinicians commonly rely on tertiary drug information references to guide drug dosages for patients who are receiving continuous renal replacement therapy (CRRT). It is unknown whether the dosage recommendations in these frequently used references reflect the most current evidence.