Morphine-6-glucuronide might mediate the prolonged opioid effect of morphine in acute renal failure.

1. A 43-year-old male developed acute kidney failure due to ethylene glycol poisoning. He was treated with bicarbonate to combat metabolic acidosis, ethanol as an antimetabolite and haemodialysis to remove the glycol and its toxic metabolites. He was kept on a respirator and sedated with morphine. Peritoneal dialysis was given for 36 d. Following sedation with morphine for 11 d, the patient was given naloxone and then extubated. The antidote had to be continued for 14 d to prevent respiratory depression, until kidney function improved. 2. Only morphine-6-glucuronide (M-6-G) was found in the plasma and CSF at concentrations which might explain the opioid effects observed in the patient during the days after the cessation of morphine treatment. The ratio of the area under the concentration-time curve (AUC) of morphine-3-glucuronide (M-3-G) to M-6-G was 2:1. The elimination half-lives of M-3-G and M-6-G were 55 and 82 h, respectively. The clearance data indicate that most of the glucuronides were eliminated by peritoneal dialysis during renal failure. 3. The data suggest that M-6-G exerts opioid effects and is retained in acute kidney failure. Morphine should therefore not be used preferentially as a sedative/analgesic in pronounced kidney failure.

Haemodialysis or haemoperfusion in severe salicylate poisoning?

Two cases of severe salicylate poisoning with maximal plasma levels of 6.9 and 8.9 mmol/l are described. In addition to supportive treatment and forced alkaline diuresis, one case was treated with haemoperfusion and the other with haemodialysis. The use of the same blood pump and blood flow allowed us to compare directly the effect of these methods in removing salicylate. There was a non-significant higher dialysance (mean 86 ml/min, s.d. +/- 8) than haemoperfusion clearance (mean 81 ml/min s.d. +/- 17) at a blood flow of 200 ml/min. As haemodialysis offers the theoretical advantage of correcting acid-base and electrolyte disturbances, does not trap platelets and has a lower heparin requirement, the present comparison indicates that haemodialysis is preferable when extracorporal elimination is indicated in salicylate poisoning.

[Elderly patients at a medical department. Their functional capacity upon admission as a predictor of a long stay in the hospital]. / Gamle i medisinsk avdeling. Funksjon ved innleggelsen som prediktor for langtidsopphold.

Data were recorded on mental function, urinary continence, ability to dress, falls, mobility, and vision in 340 patients aged 75 and over on admission to a medical department. Three months later, 213 patients had been discharged, 41 were still in hospital, 64 had died, and 22 had been transferred to another hospital or returned to a nursing home. Impairment of any of the functions tested, except vision, was associated with prolonged length of stay. Only two of 135 patients with no disability were still in hospital after three months, while for patients with three or more disabilities the number was 15 out of 56. Increasing age was associated with a tendency to prolonged length of stay. No such tendency was found among those who lived alone.

Mezlocillin pharmacokinetics in patients with normal and impaired renal functions.

The pharmacokinetics of intravenous bolus doses of 1.0 g of mezlocillin were studied in 13 persons with normal and reduced renal functions. In renal failure a moderate increase was observed for the terminal serum half-life(t1/2 beta). This changed from a mean of 1.1 h at a glomerular filtration rate of 100 ml/min to 1.6 h at 10 ml/min. The difference was not statistically significant. The excretion of unchanged drug in urine during 24 h was reduced from a mean of 59.4% (range, 52 to 77) in subjects with glomerular filtration rate above 50 ml/min to 10% (range, 7.9 to 12.1) in two patients with glomerular filtration rate of 10 to 20 ml/min. The volume of distribution during the beta-phase, Vd,b, was 14% of the body weight. Much of the antibiotic was metabolized, and this proportion increased upon reduction in renal function.

Meprobamate kinetics during and after terminated hemoperfusion in acute intoxications.

We report four cases of severe meprobamate intoxication. Maximal plasma levels reached 800 (176), 816 (180), 863 (190) and 923 mumol/l (203 mg/l). All patients survived without sequelae including one patient resuscitated from cardiac arrest. The clinical course was complicated by coma, hypotension, and hypothermia in all patients. Three cases were treated with charcoal hemoperfusion with mean hemoperfusion clearance ranging from 134-164 ml/min compared to 174 ml/min in one case treated with resin filter and the same blood flow of 200 ml/min. In two cases, a mean renal meprobamate clearance of 15 and 23 ml/min was calculated comprising only 9-15% of the hemoperfusion clearance. The amount of meprobamate removed by hemoperfusion ranged from 1.6-6.2 g. In one case, the half-life of plasma meprobamate during hemoperfusion was 2.6 hours compared to 8.3 hours after hemoperfusion. Thus the half-life was reduced more than 3-fold. These data show that hemoperfusion may be indicated in severe meprobamate intoxication.

Pharmacokinetic evaluation of haemoperfusion in phenobarbital poisoning.

Charcoal haemoperfusion was performed for 5-12 h in three patients with maximal plasma phenobarbital concentrations of 600, 946 and 1044 mumol/l (138, 217 and 240 micrograms/ml). During haemoperfusion with constant blood flow phenobarbital elimination followed first order kinetics with half-lives of 11.1, 10.0 and 7.2 h, respectively. After termination of the haemoperfusion there was no rebound effect in plasma phenobarbital concentration and the elimination was first order with half-lives of 51, 82 and 48 h, respectively. Thus, the plasma phenobarbital half-life was reduced by 78-88% during haemoperfusion. In the same period 76-86% of the total body clearance of phenobarbital was due to the haemoperfusion column at a calculated volume of distribution of phenobarbital of 1.1-1.21/kg. This is clear evidence for recommending haemoperfusion in cases of serious poisoning with phenobarbital.

Studies on methanol poisoning.

Eleven patients concomitantly poisoned with methanol are described. Their whole blood methanol concentration ranged from 137.2 mmol/l (4.39 g/l) to 7.4 mmol/l (0.24 g/l). The clinical course in most patients was mild, which was attributed to the concomitant and subsequent ethanol ingestion and rapid transport to dialysing units. One patient suffered permanent visual impairment of one eye while the others recovered completely. Symptoms of poisoning were most clearly correlated to the degree of metabolic acidosis. All patients were hemodialysed. In two patients the average dialysator clearance of methanol was 157 and 176 ml/min at blood flows of 200 and 215 ml/min, respectively. In the same patients the average dialysator clearance of ethanol was 149 and 164 ml/min. Assuming a volume of distribution of methanol of 0.7 l/kg, the dialysator represented about 89 and 95%, respectively, of the total body clearance of methanol during ethanol therapy. Ethanol in concentrations even lower than usually recommended may be useful as the only treatment of patients with blood methanol concentrations up to 15 mmol/l (0.5 g/l), provided there is no acidosis or visual impairment.

Benzodiazepine-receptor antagonist, a clinical double blind study.

In a double blind study including 18 patients in whom a benzodiazepine intoxication was suspected, the first specific benzodiazepine antagonist was compared to placebo. There was a highly significant effect on consciousness, all patients given antagonist awaked, usually within minutes. No adverse effects were observed. In 2 patients the clinical condition deteriorated 1 to 2 hrs after the antagonist was given. This might endanger intoxicated patients withdrawing from medical attention.