A. Davenport

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.

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.

Changes in Intracranial Pressure during Haemofiltration in Oliguric Patients with Grade IV Hepatic Encephalopathy

Seven consecutive patients with grade IV hepatic encephalopathy, due to fulminant hepatic failure complicated by oliguric renal failure were allocated at random to treatment with daily machine haemofiltration (MHF) or continuous arteriovenous haemofiltration (CAVHF). Intracranial pressure (ICP) was continuously monitored using a subdural catheter. Four patients received 17 treatments by MHF, and ICP increased from 8.4 +/- 1.5 mm Hg (mean + SEM) prior to treatment to 12.6 +/- 1.8 mm Hg on completion (p less than 0.05). Active intervention was required on twenty occasions to treat sustained increases in ICP (greater than 25 mm Hg maintained for 5 min or longer). A total of 12 haemofilters were used in the treatment of 3 patients by CAVHF. The ICP showed greater stability during CAVHF therapy, the mean pressure prior to treatment was 15.6 +/- 5.2 mm Hg and fell to 11.7 +/- 2.3 mm Hg at 4 h. Sustained increases in ICP occurred in only 1 patient as a preterminal event. These findings suggest that CAVHF is the preferred method of treatment in patients with fulminant hepatic failure complicated by oliguric renal failure who are at risk of developing cerebral oedema.

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.

Rebound Surges of Intracranial Pressure as a Consequence of Forced Ultrafiltration Used to Control Intracranial Pressure in Patients With Severe Hepatorenal Failure

Cerebral edema remains the most common immediate cause of death in patients with fulminant hepatic failure. We have used ultrafiltration as a method of controlling intracranial pressure (ICP) when other measures have failed. Two cases in which an initial decrease in ICP was followed by a marked rebound increase resulting in death are reported.

The Effect of Treatment With Recombinant Human Erythropoietin on Skeletal Muscle Function in Patients With End-Stage Renal Failure Treated With Regular Hospital Hemodialysis

The effect of treatment with recombinant human erythropoietin on skeletal muscle was investigated in 11 anemic transfusion-dependent patients on the hospital hemodialysis program. There were no significant changes in anthropomorphic measurements during the study, but the maximum voluntary contraction increased significantly for each muscle group studied (pre-erythropoietin and post-erythropoietin values, respectively, were as follows: biceps, median 170 N [range, 83 to 220 N] v 189 N [range, 89 to 245 N]; triceps, 88 N [range, 59 to 167 N] v 106 N [range, 95 to 185 N]; deltoid, 168 N [range, 78 to 247 N] v 193 N [range, 93 to 290 N]; and quadriceps, 202 N [range, 165 to 300 N] v 265 N [range, 185 to 335 N]; P < 0.05). There were no significant changes in muscle strength in a control group of regular hemodialysis patients. Programmed electrical stimulation of the quadriceps following erythropoietin treatment resulted in both a greater force generated and a longer duration of contraction. Following cessation of the electrical stimulus the relaxation rate for the type II fibers was quicker following erythropoietin therapy. This suggests that some of the benefit observed in physical well-being following correction of the anemia of chronic renal failure with erythropoietin is due to an improvement in voluntary skeletal muscle function.

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.

Cerebral function analyzing monitor and visual evoked potentials as a noninvasive method of detecting cerebral dysfunction in patients with acute hepatic and renal failure treated with intermittent machine hemofiltration.

We monitored the effect of 7 intermittent machine hemofiltration treatments in 4 patients with fulminant hepatic failure who had progressed to grade IV coma and developed acute oliguric renal failure. Prior to treatment the processed EEG showed excess slow wave activity, and the latency of the later visual evoked potentials (N2 and P2) was delayed. Following treatment there was a further increase in both EEG slow wave activity and latency of the N1, N2, and P2 potentials. Intracranial pressure increased from a median of 8 mm Hg (2-12, range) to 14 (8-28) following treatment, p < 0.05. There was a correlation between intracranial pressure and all of the later visual evoked potentials, for N3 r = 0.71, for P1 r = 0.39, and P2 r = 0.74, all p < 0.05. Although there appeared to be a good correlation between intracranial pressure and the noninvasive electrophysiological recordings, there were major changes in intracranial pressure, cerebral perfusion pressure, and cerebrospinal fluid pH during the first hour of treatment, during which time there were no discernable changes in EEG or evoked potentials. In this study, non-invasive neurophysiological methods were not found to be reliable as invasive methods in assessing acute, minute-by-minute changes in cerebral metabolism but these methods may have a role in the longer term in assessing patient prognosis.

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.