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Biomedical subjects

R McGory

Publications and source records attributed to R McGory.

10 recordsLinked to original sources
PubMed2000

Hepatitis B immune globulin: the US experience.

The increasingly aggressive use of hepatitis B immune globulin (HBIg) in liver transplantation for hepatitis B infected patients has led to a great improvement in this procedure by lowering the incidence of allograft infection. In this article, major US studies on the use of HBIg are reviewed, including clinical results, clinical failures and problems, and the remaining information still needed for optimal therapy. Several major clinical findings have resulted from these studies. (1) With a high dose of HBIg and continuous use of this agent, it is possible to prevent recurrence in hepatitis B virus DNA-positive patients. (2) It is difficult to predict the required post-transplant dose of HBIg or the recurrence of hepatitis B in allografts. (3) While passive immunization of HBIg can help achieve successful transplants of patients suffering from hepatitis B cirrhosis, there are two typical patterns of failure: allograft infection with wild-type hepatitis B virus in the early perioperative period and with a mutant virus more than 6 months post-transplantation. These problems appear to arise only in patients with pre-transplant viral replication. (4) Combination therapy of HBIg and lamivudine seems promising for further improvement of liver transplantation. (5) There are still unanswered questions concerning the combination strategy: optimal timing, patient selection, duration of therapy, and the risk of viral mutations and adverse events. In addition, the role of changing immunosuppression protocols in improving transplantation of hepatitis B infected patients has not been determined.

Antiviral Agents↗
PubMed2000

Pharmacoeconomic analysis of HBV liver transplant therapies.

The outcome of liver transplantation for patients infected with the hepatitis B virus (HBV) has greatly improved over the last several years. The rate of allograft infection has decreased from 85 to 25%, while the post-transplant mortality rate due to HBV has decreased from 50% at 18 months to nearly nonexistent. For the most part, this result has been due to the increased dose and extended use of hepatitis B immunoglobulin (HBIg). Current lack of knowledge of the amount of HBIg monotherapy that is necessary to suppress residual virus has led to an expensive therapy. In our early experience, no alternative existed at the time of transplant for this group of recipients. Administration of HBIg was directed toward patient safety and optimal outcome rather than cost containment. The significance of the economic impact of this decision is discussed in this article. Analysis of institutional expenses revealed that the cost of HBIg to establish viral control was fairly consistent over time, despite the increased purchase price of the drug. Individualized dosing of HBIg was more expensive in the first year after transplantation compared to typical monthly administration protocols, but was substantially less expensive after 12 months due to decreased dosage needs. In addition to HBIg acquisition price, factors that affect expenditure for HBIg maintenance include time intervals between doses, purchase contracts, overhead of drug administration, and methods employed in determining charge structures. Combination therapies with nucleoside analogues may have a beneficial effect on future costs. Controlled trials to identify the optimum and most cost-effective therapy need to be performed.

Antiviral Agents↗
PubMed1999

Pharmacokinetic considerations.

Limited studies of the pharmacokinetics of pain medication suggest altered serum elimination when the liver is hypoperfused or affected by severe cirrhosis. Drugs that are eliminated by Phase I oxidation reactions are sensitive to changes in hepatic blood flow, while drugs eliminated by Phase II glucuronidation are more affected by diseased hepatocytes. Additionally, alterations in renal function decrease elimination of both parent drugs and metabolites, resulting in toxicity for selected opioids such as meperidine and morphine. Caution is suggested in drawing general conclusions from pharmacokinetic patterns of opioid elimination discussed in this review. Practitioners should be aware that drugs with short duration of action may have long half-lives and accumulate in end-stage liver and renal disease. While pharmacokinetic differences have been described in various populations, the clinical effects and adverse outcomes are greatly influenced by numerous independent physiologic alterations seen in critical care patients. Patients with severe alterations in liver and renal function should be administered pain medications judiciously because these patients are predisposed to metabolic disarrays. These patients should not be denied pain care, but they may benefit from smaller, less frequently administered doses, rather than continuous infusion of opioid drugs. Titration of doses to clinical effects with careful patient assessment for adverse effects is crucial for achieving desired therapeutic outcomes with analgesic agents in the ICU.

Absorption↗
PubMed1998

Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function.

BACKGROUND: An oral formulation of ganciclovir (GCV) was recently approved for the prevention of cytomegalovirus disease in solid organ transplant recipients. This study was designed to determine the bioavailability of GCV and to test a dosing algorithm in transplant and dialysis patients with different levels of renal function. METHODS: Pharmacokinetic studies were carried out in 23 patients who were either a recipient of an organ transplant or on hemodialysis. Drug dosing was established by the following algorithm based on calculated creatinine clearance (CrCl): CrCl = [(140-age) x body weight]/(72 x Cr) x 0.85 for women that is, CrCl >50 ml/min, 1000 mg every 8 hr; CrCl of 25-50 ml/min, 1000 mg every 24 hr; CrCl of 10-24 ml/ min, 500 mg every day; CrCl < 10 ml/min (or on dialysis), 500 mg every other day after dialysis. GCV was taken within 30 min after a meal. The patients received oral GCV for between 12 days and 14 weeks. Serum specimens (or plasma from patients on hemodialysis) obtained at steady state were analyzed for GCV concentrations by high-performance liquid chromatography. In nine of the transplant recipients, absolute bioavailability was determined by comparing GCV levels after single oral and intravenous doses of GCV. RESULTS: The following GCV concentrations (mean +/-SD) were determined: with CrCl of > or =70 ml/min, the minimum steady-state concentration (Cmin) and maximum concentration (Cmax) were 0.78+/-0.46 microg/ml and 1.42+/-0.37 microg/ml, respectively, with a 24-hr area under the concentration time curve (AUC0-24) of 24.7+/-7.8 microg x hr/ml; with CrCl of 50-69 ml/min, the Cmin and Cmax were 1.93+/-0.48 and 2.57+/-0.39 microg/ml, respectively, with an AUC0-24 of 52.1+/-10.1 microg x hr/ml; with CrCl of 25-50 ml/min, the Cmin and Cmax were 0.41+/-0.27 and 1.17+/-0.32 microg/ml, respectively, with an AUC0-24 of 14.6+/-7.4 microg x hr/ml. For one patient with a CrCl of 23.8 ml/min, the Cmin and Cmax were 0.32 and 0.7 microg/ml, respectively, with an AUC0-24 of 10.7 microg x hr/ml. With CrCl of <10 ml/min, the mean Cmin and Cmax were 0.75+/-0.42 and 1.59+/-0.55 microg/ml, respectively, with a mean AUC0-24 of 64.6+/-18.8 microg x hr/ml. Absolute bioavailability, for the nine patients so analyzed, was 7.2+/-2.4%. For those patients with end-stage renal failure, GCV concentrations fell during dialysis from a mean of 1.47+/-0.48 microg/ml before dialysis to 0.69+/-0.38 microg/ml after dialysis. CONCLUSIONS: The bioavailability of oral GCV in transplant patients was similar to that observed in human immunodeficiency virus-infected patients. However, levels between 0.5 and 1 microg/ml (within the IC50 of most cytomegalovirus isolates) could be achieved with tolerable oral doses. The proposed dosing algorithm resulted in adequate levels for patients with CrCl greater than 50 ml/min and for patients on dialysis. For patients with CrCl between 10 and 50 ml/min, the levels achieved were low and these patients would likely benefit from increased doses.

Administration, Oral↗
PubMed1997

Retransplantation of patients with severe posttransplant hepatitis B in the first allograft.

BACKGROUND: The outcome of orthotopic liver transplantation (OLTX) in patients retransplanted for severe hepatitis B virus (HBV) in the first allograft has been poor due to high rates of HBV reinfection and even more aggressive disease in the second graft. Recent data suggest that hepatitis B immunoglobulin (HBIg) given after transplantation can be successful in delaying or preventing HBV reinfection in patients transplanted for chronic hepatitis B cirrhosis. We report the successful retransplantation of patients who developed recurrent or de novo hepatitis B after OLTXY. METHODS: Using similar HBIg regimens, two centers retransplanted seven patients after they developed recurrent or de novo hepatitis B in the first allograft. At retransplantation all seven patients were HBs antigen (Ag) positive; four patients were positive for HBeAg and HBV DNA by immunoblot assay, two patients were negative for HBeAg and HBV DNA, and one patient was positive for HBV DNA and negative for HBeAg. All patients were either HDV Ag or anti-HDV negative. One patient was anti-HCV positive. All patients received HBIg infusions after retransplantation to maintain serum anti-HBs levels >500 IU/L indefinitely. RESULTS: After retransplantation, six of seven patients are alive (86%): all are without evidence of HBV recurrence with serum negative for HBsAg, HBeAg, and HBV DNA by immunoblot assay. Liver biopsies are normal on routine studies with immunohistochemical stains for HBcAg and HBsAg also being negative. Mean follow-up of these six patients is 40.1 months (range 21-63 months). One patient (14%) developed HBV reinfection 7 months after his second transplant, in spite of maintaining target anti-HBs levels. He maintained stable liver function with minimal evidence of clinical hepatitis B, but died 8 months later from an unrelated stroke. CONCLUSIONS: We conclude that patients with recurrent or de novo hepatitis B after OLTX can be successfully retransplanted using aggressive immunoprophylaxis to prevent HBV reinfection. The failure of HBIg therapy in one patient underscores the need for other effective adjunctive anti-HBV modalities.

Adult↗
PubMed1996

Prostaglandin E1 administration following orthotopic liver transplantation: a randomized prospective multicenter trial.

BACKGROUND & AIMS: Prostaglandin E1 (PGE1) has been used after orthotopic liver transplantation (OLT) based on limited clinical data suggesting PGE1 infusion improves immediate hepatic allograft function. The aim of this study was to conduct a randomized double-blinded multicenter trial to evaluate the effect of PGE1 on early hepatic and renal function in patients undergoing OLT. METHODS: One hundred eighteen patients were randomized to receive either PGE1 or crystalloid placebo intravenously after allograft revascularization. Primary end points were incidence of primary allograft nonfunction (PNF) or severe renal dysfunction. RESULTS: The incidence of PNF was 6.7% (4 of 60) and 6.9% (4 of 58) in the control and PGE1 groups, respectively. PGE1 infusion was, however, associated with improved early renal function (mean peak creatinine level of 1.4 +/- 1.0 and 2.0 +/- 1.0 in patients treated with PGE1 and placebo, respectively; P < 0.001). Severe renal dysfunction occurred more frequently in the placebo group (26.7%) than in the PGE1 group (13.8%; P = 0.65). Additionally, dialysis treatments were more frequent in the placebo group (0.7 +/- 2.0 per patient) than in the PGE1 group (0.2 +/- 1.0 per patient; P = 0.10). Initial intensive care unit stay was shorter in patients treated with PGE1 (4.0 +/- 3.6 days) compared with controls (10.5 +/- 17.1 days) (P < 0.01). CONCLUSIONS: PGE1 administration after OLT resulted in improved renal function and decreased initial postoperative intensive care unit stay but did not affect the incidence of PNF.

Adult↗
PubMed1996

Magnesium repletion and its effect on potassium homeostasis in critically ill adults: results of a double-blind, randomized, controlled trial.

OBJECTIVES: The aims of this study were to evaluate the safety and efficacy of magnesium replacement therapy and to determine its effect on potassium retention in hypokalemic, critically ill patients. DESIGN: A prospective, double-blind, randomized, placebo-controlled trial. SETTING: A surgical intensive care unit (ICU). PATIENTS: A total of 32 adult surgical ICU patients were admitted to the study on the basis of documented hypokalemia (potassium of < 3.5 mmol/L) within the 24-hr period before entering the study. Patients were randomized to receive either placebo (n = 15) or magnesium sulfate (n = 17). One patient from each group was excluded from the study due to failure to complete the full series of doses. INTERVENTIONS: Patients received a "test dose" of either magnesium sulfate (2 g, 8 mmol) or placebo (5% dextrose in water) infused over 30 mins every 6 hrs for eight doses. The next schedule test dose was held if hypermagnesemia (magnesium of > 2.8 mg/dL [> 1.15 mmol/L]) was documented at any time during the study. Routine replacements of potassium and magnesium continued during the duration of the study, when clinically indicated, for serum potassium concentrations of 3.5 mmol/L or serum magnesium concentrations of < 1.8 mg/dL (< 0.74 mmol/L). MEASUREMENTS AND MAIN RESULTS: Age, weight, and Acute Physiology and Chronic Health Evaluation II scores were recorded on entry into the study. Just before administration of each test dose, blood was drawn for magnesium and potassium, bicarbonate, pH, and glucose determinations, and an aliquot of the preceding 6 hrs urine collection was sent for magnesium and potassium determinations. Serum calcium, phosphate, urea nitrogen, and creatinine concentrations were measured daily. The amounts of magnesium and potassium administered via parenteral nutrition, tube feeding, and replacement infusions were calculated for each 6-hr interval. The amounts of magnesium and potassium excreted in the urine were similarly assessed. The groups showed no differences with regard to age, weight, Acute Physiology and Chronic Health Evaluation II scores, or initial serum magnesium concentration. Initial potassium, bicarbonate, pH, calcium, phosphate, glucose, blood urea nitrogen, and creatinine values were not different between groups. Patients receiving magnesium sulfate showed a statistically significant increase in serum magnesium concentration at 6 hrs when compared with placebo, as well as with itself at time 0 (p < .0001), a difference maintained throughout the study. Compared with the placebo group, the total amount of elemental magnesium administered was significantly greater in the treatment group (1603 +/- 124 vs. 752 +/- 215 mg [65.7 +/- 5.8 vs. 30.8 +/- 8.8 mmol], p < .0001), as was urine magnesium excretion (1000 +/- 156 vs. 541 +/- 68 mg [41.0 +/- 6.4 vs. 22.2 +/- 2.8 mmol] p < .0001). However, the net magnesium balance (total magnesium in - total urine magnesium) was significantly more positive in the treatment group (612 +/- 180 vs. 216 +/- 217 mg [25.1 +/- 7.4 vs. 8.9 +/- 8.9 mmol], p < .005). The treatment and control groups had the same serum potassium concentrations and did not receive different amounts of potassium (245 +/- 39 vs. 344 +/- 45 mmol, respectively, p = .06), although the treatment group required less potassium replacement/6 hrs by 30 hrs compared with itself at time 0 (p < .05). Despite the same serum potassium values, the net potassium balance for 48 hrs was positive in the treatment group (+ 72 +/- 32 mmol) and negative in the control group (-74 +/- 95 mmol, p < .05). There were no complications associated with the magnesium sulfate administration. CONCLUSIONS: Magnesium sulfate administered according to the above regimen safety and significantly increases the circulating magnesium concentration. Despite greater urine magnesium losses in the treatment group, this group exhibited significantly better magnesium retention.

Critical Illness↗