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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

Renal effect of dopexamine hydrochloride in patients with chronic renal dysfunction.

Dopexamine hydrochloride, a dopamine analogue, has been reported, both experimentally and clinically, to increase renal blood flow (RBF) and improve renal function in normal kidneys. The availability of computer-enhanced radionuclide scintigraphy, which provides accurate non-invasive measurement of changes in RBF, enabled us to study the renographic effects of dopexamine hydrochloride in patients with chronic renal dysfunction (CRD). Ten patients suffering from CRD and ten normal kidney donors were the study population. Renography was performed, heart rate (HR) and blood pressure (BP) measured, and hematological and biochemical tests carried out before and after intravenous infusion of dopexamine 2 micrograms kg-1 min-1 for 60 min. The patient population displayed significant increases in total cortical and medullary RBF and renographic clearance rate (CR), while in kidney donors the RBF was increased in all kidney regions with no change in CR. HR increased in both groups, while BP showed no significant changes. The hematological and biochemical changes were transient and returned to preinfusion levels after 24 h. It is concluded that dopexamine hydrochloride 2 micrograms kg-1 min-1 increases RBF and CR in patients with CRD.

Adult

An active heat and moisture exchanger.

We have carried out a laboratory evaluation of an active heat and moisture exchanging filter (aHMEF). The device consists of a conventional heat and moisture exchanging filter (HMEF) with an additional heating element and water supply. It was compared with a standard HMEF using a model lung. The aHMEF with the heating element alone, reduced 2-hourly water loss compared with the HMEF (P < 0.001); with both the heating element and additional water, this was reduced further (P < 0.001). The mean catheter mount temperature with the HMEF and heater was 32.7 (SD 1.8) degrees C and with the complete aHMEF was 34.6 (1.6) degrees C. The maximum temperature with the heating element in use was 37.7 degrees C. We conclude that the aHMEF provided effective, controllable and convenient humidification of inspired gases.

Evaluation Studies as Topic

Plasma concentrations of flumazenil during liver transplantation.

Six patients were given flumazenil (1 mg) during the anhepatic period of liver transplantation. We found higher mean plasma flumazenil concentrations during the anhepatic period than occurred in patients with hepatic cirrhosis. It was only possible to measure plasma flumazenil concentrations in four patients after revascularisation of the donor liver. Of these, elimination half-lives could be calculated in only three patients (normal in one and prolonged in two). In these two patients the elimination half-lives were prolonged to the same extent as in patients with fulminant hepatic failure. The changes during the anhepatic period occur because the liver contributes to the central volume of distribution. After revascularisation of the donor organ the prolonged half-lives indicate that transplanted livers may not recover normal metabolic functions immediately.

Blood Loss, Surgical

The use of sedative agents in critically ill patients.

The main aim of sedation in the critically ill patient is to provide relief from anxiety and pain. The current, ideal level of sedation should leave a patient who is lightly asleep but easily roused. No single regimen is suitable for all patients. The level of sedation should be monitored, and the choice of agent, the dose and the route of administration adjusted appropriately. Midazolam is often used to provide sleep and anxiolysis. Alternatives include propofol and isoflurane. Propofol is easily titrated to achieve the desired level of sedation, and its effects rapidly end when the infusion is stopped. Isoflurane also appears promising, but special equipment is needed for its administration. Morphine is the standard analgesic agent. The principal metabolites, morphine-6-glucuronide, is also a potent opioid agonist and may accumulate in renal failure. Of the newer analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent of choice in renal failure. Neuromuscular blocking agents are indicated only in specific circumstances, and used only once it is known patients are asleep and pain free. The actions of these agents are unpredictable in the critically ill patient. Alterations in drug effect and elimination may occur, especially in the patient with hepatic and renal failure. This may also apply to active metabolites of the parent drug. When planning sedation regimens, specific patient needs and staffing levels must be remembered. Attention to the environment is also important. Midazolam and morphine given by intermittent bolus or by infusion are the mainstay of most regimens. Propofol is ideal for short periods of care on the ICU, and during weaning when longer acting agents are being eliminated.

Critical Care

Propofol metabolism in man during the anhepatic and reperfusion phases of liver transplantation.

1. An i.v. dose of 14C-propofol (0.53 mg/kg) was administered to three male and three female patients during the anhepatic phase of liver transplantation, which lasted 30-56 min after dosing. Arterial and venous blood samples, bile (T-tube drainage) and urine were collected at various times afterwards and submitted to h.p.l.c. and radioassay or specific fluorescence detection for the unchanged drug. 2. Extrahepatic metabolism was apparent during the anhepatic phase, since at 30 min post-dose, unchanged propofol comprised only 42-89% of the blood radioactivity. 3. Examination of the plasma radioactivity during the anhepatic phase in two subjects showed evidence of propofol glucuronide and 4-quinol sulphate, confirming extrahepatic metabolism of the drug. Quinol glucuronides were only detected in the liver reperfusion phase. 4. There was no evidence that the lungs contribute to the extrahepatic metabolism of propofol, since drug concentrations in the arterial blood were not less than in central venous samples. 5. During the first 24 h period, urine collected from five patients contained 7-74% dose, whilst the bile contained 0.1-0.9%. In three patients with normal renal function recovery in urine was 66-74% dose. Examination of urinary radioactivity in one subject showed the main component to be propofol glucuronide during the anhepatic phase.

Adult

Prolonged action of enoximone in renal failure.

Enoximone was administered on two separate occasions to a 37-year-old woman with renal failure secondary to thrombotic thrombocytopenic purpura. Plasma concentrations of enoximone and its principal metabolite, enoximone sulphoxide, were measured over a 9-day period. As renal function improved the rate of elimination of enoximone sulphoxide increased. The duration of effect of enoximone may be prolonged in patients with renal failure.

Acute Kidney Injury

A comparison of dopexamine and dopamine to prevent renal impairment in patients undergoing orthotopic liver transplantation.

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 micrograms/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 micrograms/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 creatine clearance. Dopexamine is at least as effective as dopamine for renal protection in patients who undergo liver transplantation.

Acute Kidney Injury

Reversible renal failure following opioid administration.

A patient who received intravenous papaveretum during and after operation developed anuria and biochemical evidence of impaired renal function in the first 6 hours after surgery. Administration of naloxone 0.4 mg was associated with a sustained improvement in urine output. Mean arterial pressure did not change significantly. The impairment of renal function may have been related to high plasma concentrations of codeine, one of the constituents of papaveretum.

Acute Kidney Injury

Midazolam infusions in critically ill patients.

Fifty consecutive patients were studied prospectively to assess the effects of a continuous intravenous infusion of midazolam hydrochloride for sedation in patients requiring intensive care. Patient comfort was acceptable in all patients. However, to maintain the same degree of sedation it was necessary to increase the daily dose of midazolam indicating that benzodiazepine tolerance may have been developing. The time taken to awaken following cessation of a midazolam infusion was prolonged in some patients. In those patients with renal failure the mean (+/- SD) value was 44.6 +/- 42.5 h compared to patients without renal failure in whom it was 13.6 +/- 16.4 h (P less than 0.01). Two patients with combined hepatic and renal failure took 124 and 140 h to awaken. Continuous intravenous infusion of midazolam offers good patient comfort but increasing dose requirements in critically ill patients may lead to drug accumulation and delayed awakening. The risks of cumulation may be increased if the drug is given by continuous infusion for prolonged periods without intermittent assessment of the patient's conscious state.

Adolescent

Changes in alveolar-arterial oxygen partial pressure difference during orthotopic liver transplantation.

Changes in the alveolar-arterial oxygen partial pressure difference (PAO2-PaO2) were measured in 39 patients undergoing orthotopic liver transplantation without veno-arterial or veno-venous bypass. The operation can be divided into an initial dissection phase, an anhepatic phase when the hepatic artery, portal vein and vena cava are clamped, and a post-anhepatic phase after the vascular clamps are released. There was an initial increase in (PAO2-PaO2) during the dissection phase, followed by an immediate decrease when the liver was removed. This decrease continued throughout the anhepatic period, but a further increase in (PAO2-PaO2) occurred after release of all the vascular clamps and during abdominal closure.

Adolescent

Plasma concentrations of bupivacaine after intercostal nerve block in patients after orthotopic liver transplantation.

Bilateral intercostal nerve blocks were performed on 12 occasions in 11 patients after liver transplantation. Group 1 (six patients) received bupivacaine 2 mg kg-1 on one occasion; in group 2 (five patients) bupivacaine 2 mg kg-1 with adrenaline 1:200,000 was injected on two occasions separated by 6 h. Arterial blood was sampled repeatedly and analysed for total bupivacaine concentrations by high performance liquid chromatography (HPLC). Six patients had bupivacaine concentrations within the putative toxic threshold of 2-4 micrograms ml-1. The use of adrenaline-containing solutions neither slowed absorption reliably nor decreased peak concentrations of bupivacaine. Cumulation of bupivacaine occurred in group 2. No patient had adverse effects attributable to the bupivacaine.

Adolescent