A. M. Davison

Comparison of the use of standard heparin and prostacyclin anticoagulation in spontaneous and pump-driven extracorporeal circuits in patients with combined acute renal and hepatic failure

Although prostacyclin has been reported to be an effective extracorporeal anticoagulant for intermittent haemofiltration and dialysis treatments, it has been suggested that it is inferior to heparin in preventing clotting in spontaneously driven continuous haemofiltration and/or dialysis circuits. We studied the effectiveness of both heparin and prostacyclin as anticoagulants in a variety of extracorporeal circuits in 17 patients with combined acute hepatic and renal failure who were at risk of haemorrhage. Although there were no differences in the pump-assisted extracorporeal circuits, prostacyclin was found superior to heparin during spontaneously driven continuous arteriovenous haemofiltration and/or dialysis. During some 2,600 h of prostacyclin therapy, there were only 3 episodes of haemorrhage that required blood transfusion compared to 8 major haemorrhages and 2 deaths from intracerebral haemorrhage during 600 h of anticoagulation with heparin. The median filter life was greater with prostacyclin, 60 h (42-72), compared to heparin, 8 h (4-16), p < 0.01. This study suggests that prostacyclin is superior to heparin in maintaining the integrity of a spontaneous arteriovenous extracorporeal circuit in patients at risk of major haemorrhage.

Effect of posture on intracranial pressure and cerebral perfusion pressure in patients with fulminant hepatic and renal failure after acetaminophen self-poisoning

We measured the effect of posture on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in eight patients admitted with grade 4 hepatic coma due to fulminant hepatic failure complicated by renal failure. Upward head elevation greater than 20 degrees did not consistently reduce ICP; instead, ICP increased in three patients who later died of cerebral edema. CPP was reduced significantly by elevation greater than 20 degrees, falling to less than 50 mm Hg in those patients who subsequently died of cerebral edema. Our study does not support the current practice of nursing patients with hepatic coma, who are at risk of dying from cerebral edema, in head-upright postures greater than 20 degrees.

Hyperlactataemia and Metabolic Acidosis during Haemofiltration Using Lactate-Buffered Fluids

We have investigated the effect of an exogenous lactate load given during machine haemofiltration treatment in 22 patients with acute renal failure and 12 patients with chronic renal failure, without any overt evidence of liver disease. Hyperlactataemia occurred in all patients, but the expected changes in acid base status, an increase in bicarbonate and a reduction in arterial hydrogen ions were observed in less than 40% of the treatments in the acute renal failure group. Ultrafiltrate losses of lactate and bicarbonate could not alone explain the changes in acid-base status. There was a positive correlation between the increase in arterial lactate and hydrogen ion concentrations, r = 0.52, p less than 0.01. Lactate accumulation in patients at, or close to, their threshold for lactate utilisation may result in further depression of cardiac function and peripheral lactate utilisation. Hyperlactataemia due to use of lactate-based dialysis/haemofiltration solutions in critically ill patients may result in a worsening of the acid-base status, and arterial pH should be monitored so that bicarbonate solutions can be substituted if the changes are progressive.

Prevalence of Helicobacter pylori in Patients with End-Stage Renal Failure and Renal Transplant Recipients

The prevalence of Helicobacter pylori was determined using an ELISA technique for IgG antibodies to H. pylori in 76 patients with end-stage renal failure who were receiving regular haemodialysis and 202 patients with functioning renal transplants. Twenty-seven (34%) of the haemodialysis group and 58 (29%) of the transplant group were positive for H. pylori IgG antibodies, and the prevalence did not differ significantly from that in 247 age-matched healthy controls. In the haemodialysis group, patients positive for H. pylori were older, median age 60 years (range 22-73), compared to those patients without H. pylori antibodies, median age 52 years (range 22-75), p less than 0.05, more suffered from dyspeptic symptoms, 35 vs. 10% (p less than 0.01), yet fewer had been prescribed aluminium-containing antacids, 38 vs. 78% (p less than 0.01). In the transplanted group, those positive for H. pylori were more symptomatic for dyspepsia, 30 vs. 11% (p less than 0.01), and had lower serum creatinine values, 136 +/- 10 mumol/l (mean +/- SEM) vs. 172 +/- 12 mumol/l (p less than 0.05), compared to those without H. pylori antibodies. Almost all the transplant patients with H. pylori antibodies were taking steroids (98%) compared to 84% of those without antibodies (p less than 0.05). The prevalence of antibodies to H. pylori in this study was increased in symptomatic dyspeptic subjects and reduced in those patients prescribed aluminium-containing phosphate binders.

The effect of treatment with recombinant human erythropoietin on the histological appearance and glycogen content of skeletal muscle in patients with chronic renal failure treated by regular hospital haemodialysis

The effect of treatment with recombinant human erythropoietin on the histological appearance and glycogen content of the anterior tibialis muscle was studied in 10 patients with chronic renal failure treated by regular haemodialysis. Repeat muscle biopsies taken when the target haemoglobin concentration of 11 g/dl was achieved showed an increase in median glycogen content from 35 mg/g fat-free dry muscle to 51 mg/g (p < 0.05). The histological appearance showed a marked improvement in muscle fibre diameters, in particular for the type I fibres and a reduction in cytoarchitectural abnormalities. These changes would be expected to produce an increase in both muscle strength and performance and are most probably a consequence of an increase in muscle oxygen delivery.

Effect of the direction of dialysate flow on the efficiency of continuous arteriovenous haemodialysis.

We have investigated the effect of the direction of the dialysate flow during continuous arteriovenous haemodialysis. Under similar conditions countercurrent flow was more efficient than concurrent flow in terms of both urea clearance (mean +/- SEM), 23.5 +/- 0.5 compared to 18.4 +/- 0.4 ml/min (p less than 0.001) and creatinine clearance, 21.1 +/- 0.5 compared to 15.6 +/- 0.4 ml/min (p less than 0.001). There was a greater drop in pressure along the blood compartment of the haemodiafilter during countercurrent flow, 16 +/- 0.8 compared to 13 +/- 0.3 mm Hg (p less than 0.05) during concurrent flow, and this was associated with a greater ultrafiltration rate, 7.2 +/- 0.6 compared to 6.0 +/- 0.5 ml/min. The differences in diffusion, back diffusion and convection between the two systems resulted in a net gain of lactate/bicarbonate and a net loss of chloride during countercurrent dialysate flow, and a net loss of lactate/bicarbonate with a gain of chloride during concurrent flow. These losses would have to be corrected in the clinical setting of patients who had been continuously treated by these systems for several days.

Adverse Effects on Cerebral Perfusion of Prostacyclin Administered Directly into Patients with Fulminant Hepatic Failure and Acute Renal Failure

Prior to commencing renal replacement therapy, 8 patients with fulminant hepatic failure and acute renal failure were treated with an infusion of prostacyclin, 5 ng/kg/min, for 30 min, administered directly into the femoral vein. During this period, several adverse effects were noted. There was a reduction in mean arterial blood pressure from a median of 82 (range 65-93) to 67 mm Hg (55-80), p less than 0.01; and an increase in intracranial pressure from a median of 14 (6-33) to 17 mm Hg (6-42), p less than 0.05; with a consequent reduction in cerebral perfusion pressure from a median of 63 (43-77) to 43 mm Hg (15-74), p less than 0.05. There was a reduction in arterial oxygen tension from a median of 19 (13-28) to 16 kPa (12-27), p less than 0.05; and no change in cardiac output, from a median of 6.7 (4.9-11.2) to 6.5 l/min/m2 (3.8-11.0), p greater than 0.05). The administration of prostacyclin into this group of critically ill patients, at risk of death due to cerebral oedema/hypoxia, produced both a reduction in cerebral perfusion pressure and a reduction in total cerebral oxygen delivery.

Factors influencing the intestinal absorption of calcium and phosphorus following renal transplantation

After successful renal transplantation there is continuing malabsorption of calcium and phosphorus. This is due in part to impaired glomerular filtration rate, and in part to the action of steroid on calcium and phosphorus absorption. The effect of steroids is most marked over the first 18 months after transplantation and causes significant malabsorption of calcium and phosphorus even though good graft function is established. Calcium and phosphorus malabsorption can be improved by exogenous 1,25-dihydroxy vitamin D (oral 1 alpha-OH D3 or 1,25-[OH]2D3).

Blood Lactate Is Reduced following Successful Treatment of Anaemia in Haemodialysis Patients with Recombinant Human Erythropoietin both at Rest and after Maximal Exertion

The effect of increasing haemoglobin by erythropoietin therapy on exercise capacity was investigated in 11 regular haemodialysis patients, previously transfusion dependent. Exercise work load increased from a median of 100 W (95% confidence limit, 25-135) to 120 (45-180; p < 0.05) following erythropoietin, and the duration of the exercise test from 13 (3.5-20) to 15.5 min (4-22; p < 0.05). Resting blood lactate concentration decreased from 0.8 (0.6-1.6) to 0.3 mmol/l (0.3-0.4), p < 0.05, following treatment with erythropoietin, as did blood lactate concentration at maximal exertion from 2.0 (1.0-4.1) to 1.8 mmol/l (0.5-2.8; p < 0.05). In association with the increase in haemoglobin from a median of 6 (5.1-6.8) to 11.1 g/dl (11-11.9) following erythropoietin therapy, patients were able to achieve greater exercise capacity both in terms of maximum work load and duration of exercise in association with a reduced resting arterial lactate and a similar exercise-induced lactate production. This suggests that treatment had improved muscle function in terms of lactate production and/or utilisation. This was probably due to the increase in tissue oxygen delivery, as there was an increase in the median arterial oxygen content from 79 (65-85) to 150 ml O2 (144-157) following erythropoietin treatment.

Are changes in intracranial pressure during intermittent machine haemofiltration dependent upon membrane biocompatibility

We measured the intracranial pressure, using a subdural catheter in three patients admitted with grade 4 hepatic encephalopathy following paracetamol (aminocetaphen) self poisoning. Acute oliguric renal failure was present in all cases and was treated with daily intermittent machine haemofiltration. Hypovolaemia prior to treatment was corrected and a total of 14 isovolaemic 17 litre exchanges carried out using either a Gambro FH77 (8) or Hospal 3600 (6) haemofilter. Intracranial pressure (ICP) increased during treatment with both types of filter, but the increase was greater in the Gambro FH77 treated group, mean ICP increased from 7.6 ± 2 mmHg to 12 ± 3 mmHg at 3 hours (p< 0.05), this was associated with a greater fall in the percentage change from the pretreatment value of both arterial oxygen tension and total peripheral white blood cell count during the first hour of treatment compared to the Hospal 3600 treated group, 8 ± 2% vs 1 ± 2% (p< 0.05) and 5 ± 2% vs 3 ± 2% (p< 0.05). This suggests that membrane biocompatibility may also play a role in the development of increased intracranial pressure during intermittent machine haemofiltration.