Severe Lactic Acidosis Treated With Prolonged Hemodiafiltration in a Disseminated Histoplasmosis

Infections with Histoplasma are rarely seen in immunocompromized patients. We report the case of a renal transplant recipient who presented with disseminated histoplasmosis 3.5 years after transplant He presented severe lactic acidosis (LA), sepsis complicated by circulatory failure, renal failure, and liver dysfunction. We describe the successful use of continuous venovenous hemodiafiltration (CVVHDF) with regional citrate anticoagulation, treatment that stabilized our patient until infectious focus was identified and treated. The lactate was decreasing, concomitant with hemodynamic improvement, with reduction and suspension of the norepinephrine. The serum lactate level normalized 52 hours after CVVHDF initiated (from 28.9 to 2.2 mmol/L). Continuous renal replacement therapy was safely applied and can be recommended as an efficient method on adjuvant treatment of hyperlactatemia. ASAIO Journal 2009; 55:123-125.

Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta

We investigated the mechanism by which extracellular acidification promotes relaxation in rat thoracic aorta. The relaxation response to HCl-induced extracellular acidification (7.4 to 6.5) was measured in aortic rings pre-contracted with phenylephrine (Phe, 10(-6) M) or KCl (45 mM). The vascular reactivity experiments were performed in endothelium-intact and denuded rings, in the presence or absence of indomethacin (10(-5) M), L-NAME (10(-4) M), apamin (10(-6) M), and glibenclamide (10(-5) M). The effect of extracellular acidosis (pH 7.0 and 6.5) on nitric oxide (NO) production was evaluated in isolated endothelial cells loaded with diaminofluorescein-FM diacetate (DAF-FM DA, 5 mu M). The extracellular acidosis failed to induce any changes in the vascular tone of aortic rings pre-contracted with KCl, however, it caused endothelium-dependent and independent relaxation in rings pre-contracted with Phe. This acidosis induced-relaxation was inhibited by L-NAME, apamin, and glibenclamide, but not by indomethacin. The acidosis (pH 7.0 and 6.5) also promoted a time-dependent increase in the NO production by the isolated endothelial cells. These results suggest that extracellular acidosis promotes vasodilation mediated by NO, K(ATP) and SK(Ca), and maybe other K(+) channels in isolated rat thoracic aorta. (C) 2011 Elsevier B.V. All rights reserved.

The use of sodium-chloride difference and chloride-sodium ratio as strong ion difference surrogates in the evaluation of metabolic acidosis in critically ill patients

Purpose: Inorganic apparent strong ion difference (SIDai) improves chloride-associated acidosis recognition in dysnatremic patients. We investigated whether the difference between sodium and chloride (Na+-C1-) or the ratio between chloride and sodium (Cl-/Na+) could be used as SIDai surrogates in mixed and dysnatremic patients. Patients and Methods: Two arterial blood samples were collected from 128 patients. Physicochemical analytical approach was used. Correlation, agreement, accuracy, sensitivity, and specificity were measured to examine whether Na(+)-C1(-) and CI(-)/Na(+) could be used instead of SIDai in the diagnosis of acidosis. Results: Na(+)-C1(-) and CF/Na+ were well correlated with SIDai (R = 0.987, P < 0.001 and R = 0.959, P < 0.001, respectively). Bias between Na(+)-C1(-) and SIDai was high (6.384 with a limit of agreement of 4.4638.305 mEq/L). Accuracy values for the identification of SIDai acidosis (<38.9 mEq/L) were 0.989 (95% confidence interval [CI], 0.980-0.998) for Na+-C1- and 0.974 (95% CI, 0.959-0.989) for Cr/Na+. Receiver operator characteristic curve showed that values revealing SIDai acidosis were less than 32.5 mEq/L for Nata- and more than 0.764 for C17Na+ with sensitivities of 94.0% and 92.0% and specificities of 97.0% and 90.0%, respectively. Nata- was a reliable S IDai surrogate in dysnatremic patients. Conclusions: Nata- and CI-/Na+ are good tools to disclose S IDai acidosis. In patients with dysnatremia, Nata- is an accurate tool to diagnose SIDai acidosis. (C) 2010 Elsevier Inc. All rights reserved.

Congenital lactic acidosis: Evaluation of the properties of the A199T natural variant of human pyruvate dehydrogenase E1 alpha by in vitro mutation

One cause of congenital lactic acidosis is a mutation in the E1 alpha -subunit of the pyruvate dehydrogenase multienzyme complex. Little is known about the consequences of these mutations at the enzymatic level. Here we study the A199T mutation by expressing the protein in Escherichia coil. The specific activity is 25% of normal and the K-m for pyruvate is elevated by 10-fold. Inhibitors of lactate dehydrogenase might be a useful therapy for patients with such mutations. (C) 2001 Academic Press.

Protective effects of hypercapnic acidosis on ventilator-induced lung injury.

To investigate whether respiratory acidosis modulates ventilator-induced lung injury (VILI), we perfused (constant flow) 21 isolated sets of normal rabbit lungs, ventilated them for 20 min (pressure controlled ventilation [PCV] = 15 cm H(2)O) (Baseline) with an inspired CO(2) fraction adjusted for the partial pressure of CO(2) in the perfusate (PCO(2) approximately equal to 40 mm Hg), and then randomized them into three groups. Group A (control: n = 7) was ventilated with PCV = 15 cm H(2)O for three consecutive 20-min periods (T1, T2, T3). In Group B (high PCV/normocapnia; n = 7), PCV was given at 20 (T1), 25 (T2), and 30 (T3) cm H(2)O. The targeted PCO(2) was 40 mm Hg in Groups A and B. Group C (high PCV/hypercapnia; n = 7) was ventilated in the same way as Group B, but the targeted PCO(2) was approximately equal to 70 to 100 mm Hg. The changes (from Baseline to T3) in weight gain (Delta WG: g) and in the ultrafiltration coefficient (Delta K(f) = gr/min/ cm H(2)O/100g) and the protein and hemoglobin concentrations in bronchoalveolar lavage fluid (BALF) were used to assess injury. Group B experienced a significantly greater Delta WG (14.85 +/- 5.49 [mean +/- SEM] g) and Delta K(f) (1.40 +/- 0.49 g/min/cm H(2)O/100 g) than did either Group A (Delta WG = 0.70 +/- 0.43; Delta K(f) = 0.01 +/- 0.03) or Group C (Delta WG = 5.27 +/- 2.03 g; Delta K(f) = 0.25 +/- 0.12 g/min/cm H(2)O/ 100 g). BALF protein and hemoglobin concentrations (g/L) were higher in Group B (11.98 +/- 3.78 g/L and 1.82 +/- 0.40 g/L, respectively) than in Group A (2.92 +/- 0.75 g/L and 0.38 +/- 0.15 g/L) or Group C (5.71 +/- 1.88 g/L and 1.19 +/- 0.32 g/L). We conclude that respiratory acidosis decreases the severity of VILI in this model.

Acidosis D-Láctica secundaria a síndrome de intestino corto.

The short bowel syndrome appears for the reduction of intestinal absorptive surface due to functional or anatomical loss of part of the small bowel. We present the case of a 35-year-old woman with severe short bowel syndrome secondary to acute intestinal ischemia in adults, who presented at 5 years of evolution episodes of dizziness with gait instability and loss of strength in hands. The diagnosis was D-lactic acidosis. D-lactic acidosis is a rare complication, but important for their symptoms, of this syndrome. It is due to a change in intestinal flora secondary to an overgrowth of lactic acid bacteria that produce D-lactate. D-lactic acidosis should be looked for in cases of metabolic acidosis in which the identity of acidosis is not apparent, neurological manifestations without focality and the patient has short bowel syndrome or patients who have had jejunoileal bypass surgery. Appropriate treatment usually results in resolution of neurologic symptoms and prevents or reduces further recurrences.

Nephrocalcinosis in a patient with complete distal renal tubular acidosis.

A 35-year-old patient, diagnosed with distal renal tubular acidosis (dRTA), presented with metabolic acidosis (pH =7.1) together with hypokalaemia (2.8 meq/l), hyperlipidaemia and renal insuffi ciency (creatinine clearance = 60.8 ml/min). A 24 h urine examination showed an alkaline pH (7.5), hypercalciuria, hyperkaliuria hypocitraturia (1, 2 ,3). The patient was treated with potassium, citrate supplements and simvastatin . A typical renal colic occurred and an image study revealed considerable bilateral nephrocalcinosis, radio-opaque lithiasis in the left distal lumbar ureter and the right mid lumbar ureter with severe left ureter-hydronephrosis. Ureteroscopy and laser lithotripsy of left lumbar fragments were performed, continuing with the medical treatment (4).

Hyperlactatémie et acidose lactique chez le patient critique [Hyperlactatemia and lactic acidosis in the critically ill patient].

Hyperlactatemia is associated with an ominous prognosis in critical illness and must be rapidly detected. Lactate is produced by glycolysis through reduction of pyruvate, itself oxidized in the mitochondria. It is transported to the liver and converted to glucose through gluconeogenesis (Cori's cycle). Hyperlactatemia can result from excessive production or reduced clearance. Excess production can occur in aerobic conditions, following an increase in pyruvate generation, or in anaerobic conditions, due to impaired pyruvate oxidation. Reduced lactate clearance occurs as a result of liver hypoperfusion or hepatic failure. Lactate/pyruvate ratio, as well as the concomitant existence of metabolic acidosis (lactic acidosis), help distinguish the different mechanisms leading to hyperlactatemia, which are reviewed in detail in this article.

Präoperative Azidose und Entwicklung von Säuglingen nach Operation angeborener Herzfehler Preoperative acidosis and infant development following surgery for congenital heart disease.

OBJECTIVE: Prenatal diagnosis has been shown to decrease pre-operative acidosis and might prevent the occurrence of disturbed developmental outcome. The aim of this study is to evaluate parameters for acidosis and their predictive value on developmental outcome in newborns with congenital heart disease. METHODS: A total of 117 patients requiring surgery for structural heart disease in the first 31 days of life were included. Diagnosis was established either pre- or postnatally. Preoperative values of lactate, pH and base excess levels were compared to the occurrence of disturbed developmental outcome, i.e. an underperformance of more than 10% on the P90 of a standardized Dutch developmental scale. Patients were divided into groups according to blood levels of acidosis parameters, using receiver operating characteristics curves to determine cut-off values for pH, base excess and lactate. RESULTS: No significant difference in developmental outcome was found using values for pH or base excess as a cut-off level. Preoperative lactate values exceeding 6.1 mmol/l resulted in a significant increase in impaired development compared to infants with a pre-operative lactate lower than 6.1 mmol/l: 40.9% vs 15.1% in (p=0.03). CONCLUSIONS: Pre-operative lactate values might have a prognostic value on developmental outcome in newborns with congenital heart disease. The limited prognostic value of pH can be explained by the fact that pH can be easily corrected, while lactate better reflects the total oxygen debt experienced by these patients.

Severe transient neonatal lactic acidosis during prophylactic zidovudine treatment.

Zidovudine (ZDV) treatment during pregnancy, delivery and the postnatal period is effective in reducing the maternal-infant transmission of the human immunodeficiency virus. Reported adverse effects in the neonate during this longterm treatment are bone marrow suppression and elevation in aspartate aminotransferase activity. We report a case of severe ZDV-associated lactic acidosis in a neonate, which resolved rapidly following discontinuation of ZDV. The mechanisms leading to this side effect are poorly understood.

Acid-sensing ion channel 1a drives AMPA receptor plasticity following ischemia and acidosis in hippocampal CA1 neurons

The CA1 region of the hippocampus is particularly vulnerable to ischemic damage. While NMDA receptors play a major role in excitotoxicity, it is thought to be exacerbated in this region by two forms of post-ischemic AMPA receptor (AMPAR) plasticity - namely, anoxic long-term potentiation (a-LTP), and a delayed increase in the prevalence of Ca2+ -permeable GluA2-lacking AMPARs (CP-AMPARs). The acid-sensing ion channel 1a (ASIC1a) which is expressed in CA1 pyramidal neurons, is also known to contribute to post-ischemic neuronal death and to physiologically induced LTP. This raises the question - does ASIC1a activation drive the post-ischemic forms of AMPAR plasticity in CA1 pyramidal neurons? We have tested this by examining organotypic hippocampal slice cultures (OHSCs) exposed to oxygen glucose deprivation (OGD), and dissociated cultures of hippocampal pyramidal neurons (HPN) exposed to low pH (acidosis). We find that both a-LTP and the delayed increase in the prevalence of CP-AMPARs are dependent on ASIC1a activation during ischemia. Indeed, acidosis alone is sufficient to induce the increase in CP-AMPARs. We also find that inhibition of ASIC1a channels circumvents any potential neuroprotective benefit arising from block of CP-AMPARs. By demonstrating that ASIC1a activation contributes to post-ischemic AMPAR plasticity, our results identify a functional interaction between acidotoxicity and excitotoxicity in hippocampal CA1 cells, and provide insight into the role of ASIC1a and CP-AMPARs as potential drug targets for neuroprotection. We thus propose that ASIC1a activation can drive certain forms of CP-AMPAR plasticity, and that inhibiting ASIC1a affords neuroprotection.