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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 51 (1996), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 51 (1996), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Liver samples were obtained at hepatectomy from patients with end stage alcoholic liver disease (n = 5), primary biliary cirrhosis (n = 5) and chronic rejection needing retransplantation (n = 5). Normal liver material was also obtained from five organ donors. From these samples microsomes were made containing cytochrome P450 3A. The amount of this enzyme was measured by Western immunoblotting and its function assessed by measuring the rate of production of two metabolites of midazolam, 1-hydroxy midazolam and 4-hydroxy midazolam. There was a wide range in all groups for both the expression and function of this enzyme. Liver tissue affected by cirrhotic disease showed greater preservation of enzyme function than that affected by hepatocellulur disease. There was a good correlation between the expression of the enzyme and production of the 1-hydroxy metabolite, but a poor correlation between production of the 4-hydroxy metabolite and expression. This poor correlation may reflect the failure to measure the specific enzyme responsible for producing 4-hydroxy midazolam.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The metabolism of many drugs is abnormal in the critically ill patient. The causes of this are unknown, and investigation in patients is difficult. We therefore used isolated, cultured human hepatocytes to study the effects of hypoxia and induction on cytochrome P450 3 A, the cytochrome responsible for the metabolism of many drugs. When hepatocytes were exposed to 5% oxygen, the amount of 3 A produced, after induction with rifampicin, was five to 10 times less than the amount produced in 21% oxygen. In another study, we exposed isolated hepatocytes for 4 days to serum from five critically ill patients or from volunteers. At the end of this time, the functional ability of the hepatocytes to glucuronidate 14C progesterone was measured. Four of the five patients had a substance in their plasma that reduced the ability of the hepatocytes to glucuronidate progesterone. The nature of this substance and the reason that the serum from the fifth patient did not affect metabolism are unknown. This model is able to simulate the abnormalities which occur in critically ill patients. Further studies are needed to explain our observations and to identify the substances in the serum from critically ill patients that alter drug metabolism.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 46 (1991), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The efficacy of low-dose dopamine as a renal protective agent was compared with that of dopexamine in patients who underwent orthotopic liver transplantation. Twelve patients who received a continuous infusion of dopexamine (1–3 μg/kg/minute) were matched for age, diagnosis, pre-operative creatinine clearance and blood loss with 12 patients who received a low-dose infusion of dopamine (2 μg/kg/minute). The catecholamine infusion was started after induction of anaesthesia and continued for 48 hours after surgery. Patients in the dopexamine group had less evidence of renal impairment and failure than those in the dopamine group during 7 days after the operation, although the differences between groups did not achieve statistical significance. Similarly there were no significant differences between the two groups in peri-operative urine output, urine/plasma osmolality ratio or creatinine clearance. Dopexamine is at least as effective as dopamine for renal protection in patients who undergo liver transplantation.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 44 (1989), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The postoperative course of 335 adult patients who underwent orthotopic liver transplantation from 1968–1987 was reviewed retrospectively to identify patients who died in the intensive care unit and the causes of death. Forty-four percent of all deaths occurred in the intensive care unit. The mortality rate in the intensive care unit peaked in 1984 (48%), but decreased to 11% in 1987. The main causes for death in the intensive care unit were infection (55%) and haemorrhage (19%). The patients who died spent more time in the intensive care unit, had a longer period of tracheal intubation and received a larger intra-operative blood transfusion than patients who died in other locations.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 44 (1989), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 43 (1988), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The pharmacokinetics of oral controlled release morphine were studied in 10 patients to investigate the effect of two different anaesthetic techniques on its absorption and metabolism. Five patients received general anaesthesia with neuromuscular blockade; the remainder received lumbar epidural analgesia with general anaesthesia but without neuromuscular blocking agents. Blood samples were collected throughout the peri-operative period for estimation of plasma morphine concentration using two radio immunoassay techniques, one specific for morphine, the other less specific and crossreacting with morphine glucuronides. Plasma morphine concentrations with the specific method were similar for the two groups of patients but there was a statistically significant difference between the two groups with the less specific method at 30 and 45 minutes after induction of anaesthesia. This difference was because of the varying concentrations of morphine metabolites and may reflect the change in splanchnic blood flow produced by lumbar epidural analgesia.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 43 (1988), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A 22-year-old male was involved in a road traffic accident and sustained multiple injuries. He received an infusion of midazolam to sedate him during a period of artificial ventilation. His conscious level remained depressed 36 hours after the infusion was discontinued but the sedation was completely reversed with flumazenil. An infusion was started because of the short duration of action of flumazenil, and continued for 8 days. The infusion was slopped seven times during this period and on each occasion except the last, his conscious level deteriorated but returned to normal when flumazenil was administered again. Plasma concentrations of midazolam and α-hydroxymidazolam were measured and found to be low during this period. Possible explanations for this finding are discussed.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 42 (1987), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The pharmacokinetics of midazolam and its metabolite, 1-OH midazolam, were studied in six critically ill patients during and after a continuous intravenous infusion of midazolam. Four patients had an increased elimination half-life of midazolam; two were associated with a reduction in plasma clearance with low plasma concentrations of the metabolite, and two with normal metabolite levels and increased volume of distribution. The two patients with reduced clearance suffered from septic shock and were studied over a longer period. Their altered clearance was due to a reduced capability to form the 1-OH metabolite. As their condition improved, plasma concentrations of 1-OH midazolam increased and midazolam clearance returned towards normal. The impaired ability of critically ill patients with septic shock to metabolise midazolam, may be due to reduced organ perfusion and may lead to cumulation of midazolam in these patients.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Administration of low dose dopamine (2.0 μg/kg/minute) begun before surgery in patients undergoing liver transplantation decreases the incidence of postoperative renal impairment. Thirty-four consecutive patients in the Cambridge/King's College Hospital liver transplantation series were studied. Nineteen patients (21 transplant operations) received prophylactic low dose dopamine throughout the operative and early postoperative period, while 15 patients (15 transplant operations) received dopamine only when clinically indicated for incipient renal failure or as an inotropic agent. In the prophylactic dopamine group, only two transplant operations (9.5%) were complicated by renal impairment, whereas in the other group, 10 patients (67%) developed renal impairment (p = 0.001); of these, four developed acute renal failure (27%). Comparison of seven pairs of patients, matched for age, sex, diagnosis, operative blood loss and operative hypotension (one group receiving dopamine, the other not), revealed a significantly higher urine output in the first 24 hours and creatinine clearance 24—48 hours after surgery (p 〈 0.05) in those treated prophylactically. In view of these findings, we would recommend that consideration be given to the prophylactic use of dopamine in patients undergoing orthotopic liver transplantation.
    Type of Medium: Electronic Resource
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