Recovery and long-term renal excretion of propofol, its glucuronide, and two di-isopropylquinol glucuronides after propofol infusion during surgery.

BACKGROUND: The metabolism of the short-acting anaesthetic agent propofol has been described over the first 24 h. However, the long-term disposition of propofol and its metabolites is unclear. We describe the pharmacokinetics (renal excretion rates and renal clearance) of propofol and its metabolites over 60 h. METHODS: Ten patients undergoing lung surgery were included in the study. They received anaesthesia with continuous i.v. propofol at an average rate of 10 mg min(-1). During surgery and 60 h thereafter, we sampled blood and urine. Propofol and its metabolites were measured using gradient high performance liquid chromatography (HPLC). RESULTS: In nine patients, propofol and its glucuronides were found in the plasma over the first 15 h. In the urine, however, even after 60 h, propofol and its quinol glucuronides were still detectable. One patient had a markedly different pharmacokinetic profile, showing a limited renal excretion or absorption of 12% of the dose. CONCLUSIONS: After an infusion of propofol, patients excrete propofol and its metabolites in the urine over a period in excess of 60 h. We hypothesize that (re)absorption of propofol and its metabolites by the kidney is a major process in elimination and that the reabsorbed compounds are gradually conjugated in the kidney and excreted in the urine. One patient showed a different pharmacokinetic profile for which we currently have no explanation.

Postpartum post-dural puncture headache: is your differential diagnosis complete?

We describe a patient with an intracerebral haemorrhage following an accidental dural puncture during an attempted epidural for pain relief in labour. Anaesthetists need to include intracerebral haemorrhage in the differential diagnosis of post-dural puncture headache in the puerperium.

Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of 173 ng/ml is described. For pain relief an epidural infusion at the level T1-2 with bupivacaine was started. Immediate pain relief was accompanied by short lasting respiratory depression and drowsiness.

Penetrating cardiac injuries--current evaluation and management of the stable patient.

Patients with penetrating cardiac injuries present in a stable or only mildly shocked condition--especially if the laceration has sealed off and the patient has been adequately resuscitated. A large proportion of patients presenting to our unit are in a reasonably stable condition after resuscitation, and rapid diagnosis may be difficult. We present our experience over a 5-year period (191 patients), with particular reference to the stable patient. All patients with penetrating precordial wounds should be assessed for a possible cardiac injury, especially if a period of hypotension has occurred. Clinical signs, central venous pressure, chest radiograph, pericardiocentesis and subxiphoid window are not always helpful in the diagnosis. Cardiac ultrasound is very useful (in the absence of haemothorax), and was performed in 103 of 191 patients, with 8 false-negatives and 3 false-positives. When an unstable patient presents with an obvious diagnosis use of cardiac ultrasound should be restricted. A subxiphoid window has diagnostic value where the cardiac ultrasound is inconclusive.

The Stanmore total hip replacement. A 22-year follow-up.

From a series of 135 patients (146 prostheses) who had had primary hip replacement in 1975 and 1976 we reported the outcome at ten years in 83 surviving patients in 1988 and that at 15 years in 44 surviving patients in 1994. Now, 22 years after the operation, we have reviewed the 21 patients who are still alive. Nineteen (20 hips) of these 21 patients (22 hips) with a mean age of 85.7 years still had their original prosthesis. Most patients were satisfied with the result, although the level of activity in many was reduced because of increasing age and other medical problems. The stem was stable in all 20 hips. Only one cup was definitely loose. Wear was observed in 40% of the cups but this was not a clinical problem. At the 22-year follow-up the cumulative survival rate of the prosthesis was 85%, of the stem 91% and of the cup 88%. Since 1975, 11 (7.5%) of the original 146 prostheses have been revised.

Naphthannelated azepinones: synthesis and antitumor activity.

5H-Benzo[b]naphth[2,3-e]azepine-6,13-diones 4a, 4b and 4H-naphtho[2,3-e]thieno[3,2-b]azepine-5,12-dione (6) were prepared by aldol condensation of phthalic dialdehyde (3) with the fused azepinediones 2a, 2b and 5, respectively. The Schmidt reaction of naphthacene-5,12-quinone (7) yielded 6H-benzo[e]naphth[2,3-b]azepine-7,12-dione (10). Several derivatives of the heterocyclic basic scaffolds 4, 6 and 10 were prepared by standard procedures, e.g. Grignard reaction, deoxygenation with triethylsilane, and sodium borohydride reduction. Evaluation of the synthesized compounds in the NCI in vitro cell line screening revealed a modest antitumor activity without marked cell line selectivity for the majority of the derivatives. The 2-bromo-5H-benzo[b]naphth[2,3-e]azepin-6(13H)-one (19) was the only representative in this series exhibiting a noteworthy growth inhibitory effect for human tumor cells.

Direct high-performance liquid chromatography determination of propofol and its metabolite quinol with their glucuronide conjugates and preliminary pharmacokinetics in plasma and urine of man.

Propofol (P) is metabolized in humans by oxidation to 1,4-di-isopropylquinol (Q). P and Q are in turn conjugated with glucuronic acid to the respective glucuronides, propofol glucuronide (Pgluc), quinol-1-glucuronide (Q1G) and quinol-4-glucuronide (Q4G). Propofol and quinol with their glucuronide conjugates can be measured directly by gradient high-performance liquid chromatographic analysis without enzymic hydrolysis. The glucuronide conjugates were isolated by preparative HPLC from human urine samples. The glucuronides of P and Q were present in plasma and urine, P and Q were present in plasma, but not in urine. Quinol in plasma was present in the oxidised form, the quinone. Calibration curves of the respective glucuronides were constructed by enzymic deconjugation of isolated samples containing different concentrations of the glucuronides. The limit of quantitation of P and quinone in plasma are respectively 0.119 and 0.138 microg/ml. The limit of quantitation of the glucuronides in plasma are respectively: Pgluc 0.370 microg/ml, Q1G 1.02 microg/ml and Q4G 0.278 microg/ml. The corresponding values in urine are: Pgluc 0.264 microg/ml, Q1G 0.731 microg/ml and Q4G 0.199 microg/ml. A pharmacokinetic profile of P with its metabolites is shown, and some preliminary pharmacokinetic parameters of P and Q glucuronides are given.

Ambulation with the reciprocating-gait orthosis. Experience in 15 children with myelomeningocele or paraplegia.

We reviewed 15 children with spina bifida or paraplegia who have used a reciprocating-gait orthosis between 1985 and 1995. All were nonfunctional ambulators. The level of the spinal lesions ranged from Th10 to L3. The mean age of fitting the orthosis was 5 years. 8 children have stopped using it at an average age of 10 years. The maximum ambulation level with the orthosis was a community ambulator in 4 children, household ambulator in 9 children and 2 remained nonfunctional ambulators. The average daily use was 6 hours by community ambulators to 0.5 hours nonfunctional ambulators. Bilateral dislocations of the hip, mild flexion deformities of the hips and knees and scoliosis were well tolerated with orthotic wear. Since functional ambulation could be achieved in 6 children with no quadriceps power, the use of this orthosis can be advocated for upper lumbar and low thoracic lesions. Strong motivation, realistic goals and expectations, the ability to participate in a training program and journeys for frequent orthosis repairs are of importance for successful use of this orthosis.