Liver transplant recipients administered gelatin (GEL) rather than human albumin solution (HAS) can become profoundly hypoalbuminemic in the early postoperative period and often have hepatic dysfunction at this time. The combined effect of these two abnormalities could be an increase in the unbound (active) concentration of lowextraction highly albumin-bound drugs, such as tacrolimus (TAC). This may increase the efficacy and/or toxicity of such drugs. We prospectively compared the clinical outcome of 69 de novo liver transplant recipients randomized primarily to TAC or cyclosporine (CYA) and secondarily to HAS or GEL therapy during the first 14 days after liver transplantation. Antipyrine clearance on the 7th postoperative day was used as a measure of liver metabolic function. Serum albumin levels were significantly lower in both GEL arms than HAS arms during the first 14 days (P < .001). Although antipyrine clearance was similar in all four trial arms, it was intermediate between that found in historic healthy controls and patients with cirrhosis (P < .0001). Serum creatinine concentrations were significantly greater in the TAC plus GEL arm than the other three arms (P < .001). The linearized treated acute rejection rate was significantly greater in the TAC plus HAS arm than the other three arms (relative risk, 2.02; 95% confidence interval, 1.07 to 3.78; P ؍ .03). These data indicate that excess nephrotoxicity can occur with TAC in liver transplant recipients with impaired hepatic metabolism who are administered GEL. In addition, supplementary albumin may reduce the efficacy of TAC in liver transplant recipients at a time when the risk for rejection is greatest. (Liver Transpl 2002;8:224-232.)
Summary
We performed a postal survey to assess the ability of intensive care unit directors and Her Majesty's Coroners to recognise deaths that should be reported to the local coroner. The survey questionnaire consisted of 12 hypothetical case scenarios. Coroners were significantly better at identifying reportable deaths than intensive care unit directors (median correct recognition scores of 11 (interquartile range 9.25–11) vs. 8 (interquartile range 7–10), respectively, p < 0.01). Deaths associated with an accident, medical treatments, industrial disease, neglect and substance abuse were significantly under‐reported by intensive care unit directors (p < 0.01). Results show that significant numbers of deaths on intensive care units in England and Wales may not be being referred for further investigation, and that wide variation in local coroners' practices exists. Improvements in postgraduate medicolegal education about deaths reportable to a coroner are required. National regulations need to be more detailed and standardised so that regional variation is eliminated.
In this hospital the number of potential and actual organ donors has fallen in 11 yr. This is a combination of decreasing numbers of patients becoming brain dead and increased relative refusal rate. It has only been partially offset by a more liberal attitude of the coroner and non-heart beating donors.
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