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Biomedical subjects

G R Park

Publications and source records attributed to G R Park.

At least 19 recordsLinked to original sources
PubMed2003

Sexual hallucinations during and after sedation and anaesthesia.

Sexual hallucinations have been reported since the introduction of chloroform. Newer agents such as midazolam and propofol appear particularly prone to producing them. Some practitioners have been the victims of allegations resulting from the hallucinogenic effects of these drugs. Other individuals, including doctors, have used the amnesic effects of midazolam and other drugs to sexually assault victims. Clinicians should be aware of the risks to which they may inadvertently expose themselves if these drugs are not used carefully.

Adolescent↗
PubMed2001

New drugs for old.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗
PubMed2000

Reducing the demand for admission to intensive care after major abdominal surgery by a change in anaesthetic practice and the use of remifentanil.

We have used a remifentanil-based anaesthetic for patients undergoing major abdominal surgery who would normally have gone to the intensive care unit in this hospital. Avoiding intensive care unit admission was considered an advantage as a shortage of intensive care unit beds was leading to the cancellation of operations. We first used remifentanil as part of a safety and efficacy study. The aim was to see if the rapid and complete awakening obtained when using this drug would allow us to avoid the need for admission to an intensive care unit and use a high dependency unit instead. This was shown to be practicable. In comparison with a group of patients matched retrospectively for the type of operation before remifentanil was used there was a reduction in the length of time (mean+/- SD) patients' lungs were ventilated (612+/-417 vs. 9.9+/-28.9 min P< 0.0001). There was no saving in cost ( pound808.71+/- pound187.06 vs. pound795.27+/- pound253.49). When remifentanil was used routinely (after the safety and efficacy study), there were significant reductions in the time to tracheal extubation (612+/-417 vs. 4+/-10 min P < 0.0001) and costs (808.71I vs. 392.10 I P < 0.0001) compared with other patients in whom it was not used. Patients waiting for a liver transplant were also being cancelled when a donor organ became available because of the shortage of intensive care unit beds. Based on our other experience with remifentanil, we used a similar anaesthetic technique for these patients. It proved possible to extubate the trachea in 12 of 15 patients at the end of the operation. No patient needed re-intubation. The need for intensive care and therefore cancellation of surgery was reduced. In contrast, only one patient's trachea was extubated immediately after surgery in the group of patients anaesthetized before the introduction of remifentanil. A remifentanil-based technique in combination with a change in organization has therefore enabled us to avoid admission to the intensive care unit for these patients.

Abdomen↗
PubMed2000

Debate: Albumin administration should be avoided in the critically ill.

The benefit of albumin administration in the critically ill patient is unproven. Epidemiological evidence suggests that there is an increase in death among patients with burns, hypoalbuminaemia, and hypotension treated with human albumin solution (HAS). In critical illness, hypoalbuminaemia is a result of transcapillary leak, decreased synthesis, large volume body fluid losses, and dilution caused by fluid resuscitation. When treating patients with hypoalbuminaemia, efforts must be centred around correction of the underlying disorder rather than reversal of hypoalbuminaemia. Problems with using albumin arise because it is an expensive blood product, and can result in systemic changes that include cardiovascular, haematological, renal, pulmonary, and immunological effects.

Albumins↗
PubMed1999

The effect of oxygen on propofol-induced inhibition of microsomal cytochrome P450 3A4.

We have shown previously that both hypoxia and propofol may inhibit the metabolism of midazolam. We now wished to see whether there was any additive or synergistic effect when they occurred together. Microsomes were incubated with 20 microns midazolam for 60 min, and propofol 0, 50, 100 or 1000 microM was added. Incubates were further subdivided so that the environment contained 0, 10, 21 or 70% oxygen. The results confirmed our earlier study showing that propofol only had a significant inhibitory effect at a concentration greater than that seen clinically (1000 microM). Anoxia was the only environment in which significant depression of the metabolism of midazolam occurred at all concentrations of propofol. This reduced it to almost zero. Post hoc analysis of the data showed that, with the greatest concentration of propofol (1000 microM), there was increasing inhibition of metabolism of midazolam with increases of oxygen from 10 to 70%.

Anesthetics, Intravenous↗
PubMed1999

Utility of hepatocytes to model species differences in the metabolism of loxtidine and to predict pharmacokinetic parameters in rat, dog and man.

1. The metabolism of loxtidine (1-methyl-5-[3-[3-[(1-piperidinyl) methyl] phenoxy] propyl] amino-1H-1,2,4-triazole-3-methanol) was studied in freshly isolated rat, dog and human hepatocytes. Metabolism in vitro was comparable with previously available in vivo data in all three species with the marked species differences observed in vivo being reproduced in the hepatocyte model. 2. The major route for the metabolism of loxtidine by rat hepatocytes was N-dealkylation to form the propionic acid and hydroxymethyl triazole metabolites. A minor metabolic route was the oxidation of loxtidine to a carboxylic acid metabolite. The major route of metabolism for loxtidine in dog hepatocytes was glucuronidation with oxidation to the carboxylic acid metabolite being of minor importance. Incubation of loxtidine with human hepatocytes resulted in the drug remaining largely unchanged but with the carboxylic acid metabolite being produced in minor amounts. 3. In vitro studies were undertaken with rat, dog and human hepatocytes to determine the Michaelis-Menten parameters Vmax and Km for the sum of all the metabolic pathways. These kinetic parameters were used to calculate the intrinsic clearance of loxtidine. Using appropriate scaling factors, the predicted in vivo hepatic clearance was then calculated. The predicted intrinsic clearances were 51.4 +/- 12.4, 8.0 +/- 0.8 and 1.0 +/- 0.6 ml/min/kg for rat, dog and human hepatocytes respectively. These data were then used to calculate hepatic clearances of 24.5, 3.1 and 0.2 ml/min/kg for rat, dog and man respectively. 4. In vivo hepatic and intrinsic clearances for loxtidine were determined in rat, dog and human volunteers. The hepatic clearances of loxtidine were 26.6, 6.6 and 0.4 ml/min/kg in rat, dog and man respectively and intrinsic clearances were 58.5, 18.6 and 2.0 ml/min/kg in rat, dog and man respectively. 5. The present studies demonstrate that the hepatocyte model may be a valuable in vitro tool for predicting both qualitative and quantitative aspects of the metabolism of a drug in animals and man at an early stage of the drug development process.

Adult↗
PubMed1999

Sedation and analgesia.

Sedation is a process of soothing. The concept of the ideal level of sedation is controversial and has changed over the last decade. A shift from deep sedation, often enhanced by muscle relaxants that completely detaches the patient from their environment, to light sedation rendering the patient sleepy but easily arousable has been widely accepted. This change in attitude has been brought about by sophisticated modes of ventilation allowing the ventilator to synchronize with the patient's own breathing pattern. In addition, the increasingly recognised adverse effects of over-sedation have contributed to the reduction in the depth of sedation.

Analgesia↗
PubMed1998

Serum albumin and colloid osmotic pressure in survivors and nonsurvivors of prolonged critical illness.

We retrospectively compared the changes in serum albumin concentration and colloid osmotic pressure between survivors and nonsurvivors of prolonged (> or = 7 days) critical illness over a 2-year period from 1 July 1995. All patients had serum albumin measured daily, and colloid osmotic pressure measured 5 days a week, throughout their ICU admission. They received crystalloid and colloid infusions as well as parenteral or enteral feeding. Infusions of albumin were not used to treat hypoalbuminaemia. One hundred and forty-five patients were included, 66 nonsurvivors and 79 survivors. Nonsurvivors were significantly older than survivors [mean (95% CI): 58 (3.8) and 49 (4.1) years, respectively] and had a greater risk of death [mean (95% CI): 0.44 (0.06) and 0.28 (0.05); p < 0.05]. There was no significant difference in gender, APACHE II score [mean (95% CI): 22 (2.7) (nonsurvivors); 18 (2.3) (survivors)] or length of stay [median (interquartile range): 14 (9-27) days (nonsurvivors); 15 (9-26) days (survivors)]. There was no difference between the two groups in the absolute minimum serum albumin concentrations reached, the time to reach that minimum or the minimum in the first 7 days. However, nonsurvivors had a significantly lower mean serum albumin concentration: [mean (95% CI): 15.7 (5.1) g.l-1 compared with 18.3 (4.6) g.l-1 in survivors; p < 0.05]. They also had a lower recovery mean (the weighted mean after the minimum value): [mean (95% CI): 13.3 (5.1) g.l-1 (nonsurvivors) and 18.6 (5.3) g.l-1 (survivors); p < 0.01]. Analysis of colloid osmotic pressure results showed no difference between the groups in mean, minimum or recovery mean. Regression analysis of mean colloid osmotic pressure and albumin revealed that albumin only contributed 17% of the colloid osmotic pressure in these patients. The similar decrease in albumin in nonsurvivors and survivors may reflect the acute inflammatory response and/or haemodilution. However, survivors showed an ability to increase serum albumin concentrations, possibly owing to resumption of synthesis. The colloid osmotic pressure varied little between or within either group of patients, possibly because of the use of artificial colloids. There was no relationship between death and colloid osmotic pressure.

Adult↗
PubMed1998

Metabolism of remifentanil during liver transplantation.

We have investigated the pharmacokinetics of remifentanil and its less potent metabolite, GR90291, in six adult patients undergoing orthotopic liver transplantation (OLT). A single bolus infusion of remifentanil 10 micrograms kg-1 min-1 was given at the beginning of the dissection and anhepatic phases of OLT. Remifentanil and GR90291 concentrations were measured in subsequent serial arterial and mixed venous blood samples. Mean arterial clearance of remifentanil was significantly greater (P = 0.02) in the dissection phase (79.54 ml min-1 kg-1) than in the anhepatic phase (39.57 ml min-1 kg-1). Steady state volumes of distribution were not significantly different. Clearance of remifentanil during the anhepatic phase was similar to that of healthy adult patients. Mean maximum concentration (Cpmax) of GR90291 was lower in the dissection phase than in the anhepatic phase (P = 0.026). There was no significant pulmonary metabolism of remifentanil.

Adolescent↗
PubMed1998

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions.

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.

Adult↗