Unexplained acidosis of malnutrition: a study by ion-exchange chromatography/mass spectrometry.

Keto-acidosis is usually associated with uncontrolled diabetes and typically poses few diagnostic problems when presenting as hyperglycaemia, metabolic acidosis and a high anion gap. An emaciated patient suffering from Duchenne Muscular Dystrophy and volume depletion presented with acidosis of unknown origin. Preliminary investigations appeared to rule out lactic acidosis, diabetic keto-acidosis and acidosis due to base loss. We have previously reported a technique utilizing liquid chromatography coupled to mass spectrometry (LC-MS) which can be used to characterize the underlying aetiology of acidosis and applied it to ultrafiltrate derived from a blood sample taken from this patient. The anion profile obtained on the chromatogram showed elevated levels of acetoacetate and hydroxybutyrate but no evidence of lactic acidosis, nor was the profile typical of that seen in 'unexplained' acidosis. We concluded that the patient was suffering from keto-acidosis associated with starvation and dehydration, the biochemical features being obscured by both the patient's chronic malnutrition and minimal muscle mass. A combination of enteral feeding and rehydration led to prompt resolution of the patient's metabolic acidosis.

Continuous venovenous haemofiltration for the treatment of theophylline toxicity.

In patients with severe theophylline toxicity charcoal haemoperfusion is the recommended method for rapid reduction of serum theophylline levels. However, access to this technique is limited in most hospitals. This case report shows that continuous venovenous haemofiltration, a technique available in most hospitals, is an effective alternative to charcoal haemoperfusion.

Bicarbonate-based haemofiltration in the management of acute renal failure with lactic acidosis.

Continuous haemofiltration with lactate-based replacement fluid is widely used for the treatment of acute renal failure (ARF). In the presence of lactic acidosis, such treatment exacerbates rather than improves the clinical state. Continuous haemofiltration using a locally-prepared bicarbonate-based replacement fluid was performed in 200 patients over 7 years. All the patients had ARF with concomitant lactic acidosis, or demonstrated lactate intolerance after starting haemofiltration with lactate-based replacement fluids. In every case it was possible to correct the acidosis without inducing either extracellular volume expansion or hypernatraemia. In 89 patients (45%), the lactic acidosis resolved while being treated with bicarbonate-based haemofiltration. Fifty-seven patients (28.5%) survived. Significant differences at presentation in the group who survived, compared with those who died, were seen in age (50.8 vs. 57.1), mean arterial pressure (68.5 vs. 60.0 mmHg) and APACHE II score (32.1 vs. 38.9). Neither the severity of the presenting acidosis nor the arterial blood lactate appeared to predict outcome. Patients who developed ARF and lactic acidosis after cardiac surgery had a low survival rate. The combination of ARF and lactic acidosis that cannot safely be treated by haemofiltration using lactate-based replacement fluids can be managed with bicarbonate-based haemofiltration.

Magnetic resonance renography: optimisation of pulse sequence parameters and Gd-DTPA dose, and comparison with radionuclide renography.

The aim of this study was to assess the feasibility of magnetic resonance renography (MRR) using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in comparison with conventional radionuclide renography (RR) using technetium-99m-DTPA (99mTc-DTPA). MRR has many advantages over RR, including lack of ionising radiation, increased spatial resolution, and visible background anatomy. By optimising the pulse sequence, we developed an MRR protocol in which signal intensity is linear with Gd-DTPA concentration over a clinically relevant range. Twenty-nine patients and a volunteer were studied using this protocol. Magnetic resonance renography was performed using three different doses of Gd-DTPA: 0.1 mmol kg-1 (n = 13), 0.05 mmol kg-1 (n = 7), and 0.025 mmol kg-1 (n = 9). Each patient was also assessed using radionuclide renography. The resulting renograms were assessed in terms of time to peak signal intensity, signal decrease after peak, and kidney function ratios calculated from both the areas underneath and the slopes of the uptake curves. We have shown that the MR renograms obtained using low dose Gd-DTPA correlate best with the radionuclide renograms. Remaining discrepancies may be explained by variations in the injection procedures (hence in arterial input functions) and the limited coverage of the three MRR slices compared to the whole body projection of RR. Furthermore, at high local concentrations, signal becomes independent of T1 and is dominated by T2.

Bicarbonate therapy and intracellular acidosis.

1. The correction of metabolic acidosis with sodium bicarbonate remains controversial. Experiments in vitro have suggested possible deleterious effects after alkalinization of the extracellular fluid. Disequilibrium of carbon dioxide and bicarbonate across cell membranes after alkali administration, leading to the phenomenon of 'paradoxical' intracellular acidosis, has been held responsible for some of these adverse effects. 2. Changes in intracellular pH in suspensions of leucocytes from healthy volunteers were monitored using a fluorescent intracellular dye. The effect in vitro of increasing extracellular pH with sodium bicarbonate was studied at different sodium bicarbonate concentrations. Lactic acid and propionic acid were added to the extracellular buffer to mimic conditions of metabolic acidosis. 3. The addition of a large bolus of sodium bicarbonate caused intracellular acidification as has been observed previously. The extent of the intracellular acidosis was dependent on several factors, being most evident at higher starting intracellular pH. When sodium bicarbonate was added as a series of small boluses the reduction in intracellular pH was small. Under conditions of initial acidosis this was rapidly followed by intracellular alkalinization. 4. Although intracellular acidification occurs after addition of sodium bicarbonate to a suspension of human leucocytes in vitro, the effect is minimal when the conditions approximate those seen in clinical practice. We suggest that the observed small and transient lowering of intracellular pH is insufficient grounds in itself to abandon the use of sodium bicarbonate in human acidosis.

An inhibitor of the sodium pump obtained from human placenta.

BACKGROUND: Much effort has been expended in the search for an endogenous inhibitor of the cellular sodium/potassium pump, a compound of major physiological importance, which has been implicated in the mechanism of essential hypertension. Others have suggested that ouabain or an isomer of ouabain may be the endogenous pump inhibitor. Neonatal cord serum contains an inhibitor of the sodium pump; we attempted to isolate and characterise this substance from human placentas. METHODS: Homogenised placentas were dialysed and the resulting solutes were trapped on octadecylsilyl silica and then separated by high-performance liquid chromatography. Measurement of the activity of the sodium pump of human leucocytes was used to test each fraction for the presence of the inhibitor. FINDINGS: An inhibitor of the sodium pump was obtained by this technique in a mass spectrometrically pure form with a mass of 370 Da, an empirical formula of C24H34O3 and only one hydroxyl group. The characteristic fragmentation pattern observed in negative-ion mass spectrometry was compared with those of various model compounds; this comparison suggested that the active material was a dihydropyrone-substituted steroid. INTERPRETATION: These results suggest that a dihydropyrone-substituted steroid is an endogenous regulator of the sodium pump in humans and, presumably, other mammals. Proof of the endogenous origin will require the demonstration of a previously unrecognised biosynthetic pathway.

Use of continuous haemofiltration to assess the rate of lactate metabolism in acute renal failure.

1. Whole-blood lactate levels were measured at different rates of haemofiltration in 10 patients with acute renal failure undergoing conventional continuous haemofiltration using lactate-buffered replacement fluid. 2. The results enable both basal production rates and the metabolic clearance of lactate to be estimated in man.

Free radical reactions involving the angiotensin converting enzyme inhibitor captopril.

Using the pulse radiolysis technique, absolute rate constants have been obtained for the reaction of captopril with several free radicals. The results demonstrate that although captopril reacts rapidly with a number of free radicals, such as the hydroxyl radical (k = 5.1 × 10(9) dm(-3)mol(-1)s(-1)) and the thiocyanate radical anion (k = 1.3 × 10(7) dm(-3)mol(-1)s(-1)), it is not exceptional in this ability. Similarly, the reactions with carbon centred radicals although rapid are an order of magnitude slower than those observed with glutathione. Additional lipid peroxidation studies further demonstrate that captopril is a much less effective antioxidant than glutathione. The data go some way to supporting the view that any attenuation of reperfusion injury by captopril is not through a direct free radical scavenging mechanism but may be afforded by other, non-radical-mediated mechanisms.

Basic simulations for anaesthetists. A pilot study of the ACCESS system.

This paper describes the design and initial testing of the ACCESS (Anaesthetic Computer Controlled Emergency Situation Simulator) system, which has been designed to simulate anaesthetic emergencies with the aim of providing training for junior doctors. The simulations require little or no capital expenditure with minimal use of time by staff or trainees. They are based on standard anaesthetic equipment, with a microcomputer providing an image of commonly used instruments. Problems are presented as scenarios administered by the teacher, and test the skills of the pupil. During 64 scenarios, five trainees caused two 'deaths' and solved the problems in a median time of 2.5 min, while an experienced group of anaesthetists caused one 'death' and took 1.8 min. The simulation was rated by the pupils as easy to use, realistic and a valuable educational tool.

Acute renal failure treated by haemofiltration: factors affecting outcome.

Two hundred and fifty consecutive patients with acute renal failure treated by continuous haemofiltration on one intensive care unit (ICU) were studied prospectively to investigate the possibility of predicting outcome at the time of referral. Logistic regression analysis was used to identify important prognostic factors and the regression coefficients were used to weight a scoring system for the severity of illness of patients with acute renal failure. Overall survival was 53% with improvement over the course of the study. Multivariate analysis showed that outcome was related to age, need for artificial ventilation, use of inotropes, urine volume, serum bilirubin, arterial base deficit and serum creatinine. The scoring system based on the first five of these variables had a specificity of predicting death of 67% and a sensitivity of 76%.