[Hyperammonemic encephalopathy in multiple myeloma]. / Hyperammonämische Enzephalopathie bei multiplem Myelom.

HISTORY AND CLINICAL FINDINGS: A 54-year old man had suffered from advanced multiple myeloma for two years. After initially good response the myeloma was refractrory to treatment with dexamethasone, cyclophosphamide, bortezomibe, zoledronate and additionally doxorubicine. The patient then complained of dyspnea without clinical signs of cardiopulmonary disease. INVESTIGATIONS: Arterial blood gas analysis showed hyperventilation with respiratory alkalosis and normal alveolo-arterial gradient as the reason for the dyspnea. With a normal MRI of the brain and lumbal puncture, a neurological disease could be excluded. Serum calcium, creatinine and serum viscosity were normal. Eventually, serum ammonia levels were found to be substantially elevated (144 µmol/l) and hyperammonemic encephalopathy was diagnosed. TREATMENT AND COURSE: Therapy with bortezomib and high dose dexamethason was repeated, and the patient also received bendamustin. Despite this treatment, he lost consciousness and died after two weeks because of aspiration pneumonia. CONCLUSION: The existence of respiratory alkalosis and multiple myeloma should prompt a search for hyperammonemia.

[A newborn infant with hyperventilation]. / Et nyfødt barn med hyperventilasjon.

Respiratory alkalosis is an early sign of urea cycle disorder. A high level of plasma ammonia will strengthen this suspicion. It is of great importance to transfer the infant as soon as possible to a unit capable of giving specific treatment with Na-benzoate, Na-phenylbutyrate, argininchloride and carglumic acid. The early treatment may also include haemodialysis, which is preferred over peritoneal dialysis or exchange transfusion. We here describe an infant with respiratory alkalosis within the first two days of life and a high plasma level of ammonia (> 700 micromol/L). He did not respond to conventional therapy and died 48 hours after birth in spite of specific treatment. DNA-analysis showed a gene defect in the OTC gene, c.67C >T (p.R23X), a known mutation leading to urea cycle disorder (OTC). It is important to detect carriers among older siblings and to inform the parents of the possibility of prenatal diagnostics.

Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate.

Experimental studies suggest that both alkalinisation and sodium loading are effective in reducing cardiotoxicity independently. Species and experimental differences may explain why sodium bicarbonate appears to work by sodium loading in some studies and by a pH change in others. In the only case series, the administration of intravenous sodium bicarbonate to achieve a systemic pH of 7.5-7.55 reduced QRS prolongation, reversed hypotension (although colloid was also given) and improved mental status in patients with moderate to severe tricyclic antidepressant poisoning. This clinical study supports the use of sodium bicarbonate in the management of the cardiovascular complications of tricyclic antidepressant poisoning. However, the clinical indications and dosing recommendations remain to be clarified. Hypotension should be managed initially by administration of colloid or crystalloid solutions, guided by central venous pressure monitoring. Based on experimental and clinical studies, sodium bicarbonate should then be administered. If hypotension persists despite adequate filling pressure and sodium bicarbonate administration, inotropic support should be initiated. In a non-randomised controlled trial in rats, epinephrine resulted in a higher survival rate and was superior to norepinephrine both when the drugs were used alone or when epinephrine was used in combination with sodium bicarbonate. Sodium bicarbonate alone resulted in a modest increase in survival rate but this increased markedly when sodium bicarbonate was used with epinephrine or norepinephrine. Clinical studies suggest benefit from norepinephrine and dopamine; in an uncontrolled study the former appeared more effective. Glucagon has also been of benefit. Experimental studies suggest extracorporeal circulation membrane oxygenation is also of potential value. The immediate treatment of arrhythmias involves correcting hypoxia, electrolyte abnormalities, hypotension and acidosis. Administration of sodium bicarbonate may resolve arrhythmias even in the absence of acidosis and, only if this therapy fails, should conventional antiarrhythmic drugs be used. The class 1b agent phenytoin may reverse conduction defects and may be used for resistant ventricular tachycardia. There is also limited evidence for benefit from magnesium infusion. However, class 1a and 1c antiarrhythmic drugs should be avoided since they worsen sodium channel blockade, further slow conduction velocity and depress contractility. Class II agents (beta-blockers) may also precipitate hypotension and cardiac arrest.

Propranolol blocks the hypophosphaturia of acute respiratory alkalosis in human subjects.

Respiratory alkalosis (RA) is seen in diverse clinical conditions including tissue hypoxia, malignancy, neurologic disorders, febrile states, pregnancy, and hepatic failure. Acute RA causes hypophosphaturia in rats, and this effect on renal phosphate handling is reversed by beta-adrenoreceptor antagonism. The objective of the present study was to determine the effect of acute RA on phosphate excretion in human patients in the absence and presence of beta-adrenoreceptor antagonism with propranolol. Twelve normal volunteers, 6 women and 6 men, were studied in two phases, once with placebo and once with intravenous infusion of propranolol. In both groups, 30-minute renal clearances were taken during normoventilation (NV) and during acute RA induced by voluntary hyperventilation. Acute RA produced a significant decrease in plasma phosphate (PPi) in the absence (deltaPPi = -0.16 +/- 0.03 mmol/L) and the presence (deltaPPi = -0.16 +/- 0.05 mmol/L) of propranolol. In the placebo group, fractional excretion of phosphate (FEPi) decreased from 24.1% +/- 3.4% in NV to 19.2% +/- 2.6% in RA. This was associated with a significant decrease in parathyroid hormone (PPTH), from 3.38 +/- 0.28 pmol/L in NV to 2.54 +/- 0.30 pmol/L in RA. In the propranolol group, FEPi did not change significantly, from 19.1% +/- 2.7% in NV to 18.7% +/- 3.0% in RA. This also occurred in the face of a decrease in PPTH, from 4.39 +/- 0.53 pmol/L in NV to 2.78 +/- 0.33 pmol/L in RA. Thus propranolol selectively changes the response of FEPi to acute RA while leaving the PPi and PPTH responses unaltered. This suggests that beta-adrenoreceptors play a role in the regulation of the response of renal phosphate handling during acute RA and that this role involves a direct tubular effect on phosphate reabsorption, independent of filtered load and hormonal status. We conclude that beta-adrenoreceptor antagonism blunts the hypophosphaturic effect of acute respiratory alkalosis in human subjects.

Alcalosis metabólica hipokalémica

Se expone un caso de síndrome de Bartter en un lactante menor de dos meses de edad con antecedente prenatal de polihidramnios y parto pretérmino. Con historia de vómito, diarrea y estreñimiento ocasional, asociado con retardo pondoestatural. Este paciente presentó cuadro de bronconeumonía viral la cual evolucionó en forma tórpida con aumento del síndrome de dificultad respiratoria (SDR) y deterioro del estado general por lo cual hubo necesidad de trasladarlo a la unidad de cuidado intensivo de pediatría. Allí se corroboró la presencia de alcalosis metabólica hipokalémica e hipoclorémica con aumento de la excreción urinaria de K, Na y Cl y defecto en la habilidad de concentrar la orina. Aunado a esto se detectó hiperreninemia, poliuria y aldosterona elevada. La tensión arterial fue normal con un percentil menor de cinco para el peso y de 10 para la talla. Con base en todo lo anterior se pudo confirmar el diagnóstico de síndrome de Bartter

Efecto de la acetazolamida en pacientes portadores de bronquitis crónica obstructiva y alcalosis metabólica / Acetazolamide effect in patients with obstructive chronic bronchitis and metabolic alkalosis

Nueve pacientes portadores de bronquitis crónica obstructiva hipercápnica y alcalosis metabólica recibieron oralmente una dosis inicial de 500 mg de acetazolamida seguida durante 6 días de una dosis diaria de 250 mg; la serie control estuvo constituída por 7 pacientes de características similares. El grupo tratado mostró una disminución de la PaCO2 desde 59 a 45 mmHg (p<0.001) y del bicarbonato real (de 36 a 26 mEq/L;p<0.0025), con ascenso no significativo de la PaCO2 pero sí de la relación PaCO2/FiO2, que aumentó en promedio desde 212 a 266 mmHg (p<0.01). El grupo control también disminuyó significativamente la PaCO2 y el bicarbonato aunque en un nivel menor; no se modificó la PaO2 pero si aumentó la PaO2/FiO2, aunque también en nivel menor, siendo significativa sólo la diferencia de PaCO2 y relación PaO2/FiO2 entre ambos grupos desde el primer día de tratamento. Ni la ventilación minuto ni el PH se modificaron significativamente en ninguno de los grupos. Se concluye que: 1o. La acetazolamida mejora la PaO2 y PaCO2 mas rapidamente que lo que ocurre en los pacientes no tratados, 2o. No hay peligro de acidosis metabólica severa con el esquema utilizado y 3o. La dosis inicial tiene un efecto rápido apreciable en forma significativa dentro de las primeras 24 horas

[The use of oral potassium chloride (BS 560) in the treatment of mixed acid-base imbalance in patients with chronic broncho-pulmonary diseases]. / L'impiego del cloruro di potassio per via orale (BS 560) nella correzione delle turbe dell'equilibrio acido-base a carattere misto in pazienti broncopneumopatici cronici.

The Authors, after giving an outline of metabolic alterations on acid-base balance in chronic obstructive lung disease, describe the need of correction of electrolytic umbalance, signally in relationship to metabolic alkalosis dued to hypochloremia. The Authors emphasize the importance of correction of jonic balance during long term therapy in such patients, especially diuretic and steroid long term treatment. The Authors studied the comparative effects on jonic assessment by correction with potassium chloride e.v. and potassium chloride by oral administration with a new capsulate preparation, (BS 560). Last they underline the good tolerance of this preparation and report the favourable effects on electrolytic patterns.

Complex acid-base disorders in subacute necrotizing encephalomyelopathy (Leigh's syndrome).

This report describes a case of subacute necrotizing encephalomyelopathy (Leigh's syndrome) in a 7-month-old boy. The clinical data suggest an association with a disorder of renal tubular acidification, characterized by both (proximal) type II and (distal) type I renal tubular acidosis (hybrid type). Concomitantly, the initial uncompensated metabolic acidosis evolved into a mixed metabolic acidosis and respiratory alkalosis-features of this syndrome not previously reported.

Intravenous sodium lactate administration in respiratory alkalosis secondary to severe brain injuries.

In acute cerebrovascular accidents the uptake of lactate by the brain tissue is enhanced, possibly in an attempt to buffer the increased local lactic acidosis. In this paper the results obtained by the administration of the lactate in 78 cases of hyperventilatory syndromes secondary to acute brain injuries, and the biochemistry of the cerebrospinal fluid and blood, are reported.

A diagram to facilitate the understanding and therapy of mixed acid base disorders.

A diagram based on in-vivo relationships between arterial hydrogen ion activity (H+) and carbon dioxide tension (PCO2) in primary abnormalities of acid base homeostasis is presented. It is designed to facilitate the interpretation of pH data by including the 95% confidence limits described in patients with simple metabolic and respiratory acid base disorders. These bands have been formulated from observation of simple acid base abnormalities and indicate the appropriate respiratory or renal compensatory response to the primary pH defect. A plot which falls outside these limits therefore indicates the presence of a mixed acid base disorder. The diagram presents a physiological approach to clinical disorders of pH regulation demonstrating maintenance of intra-cellular fluid homeostasis during primary extracellular fluid disturbances. Diagnostic and therapeutic advantages are further illustrated and discussed in six case reports.

Arterial blood gases in acute pulmonary edema.

Arterial blood gas and pH measurements in 82 patients with acute pulmonary edema of cardiogenic origin entering the emergency department varied widely and were unpredictable using clinical examination. The mean arterial oxygen tension (PaO2) measured in 71 patients breathing room air was 59 mm Hg. Fourteen of the 82 patients were acidemic; 35, alkalemic and 33 had a pH in the normal range. The acidemic group had markedly lower PaO2, all under 60 mm Hg. Oxygen and furosemide were used in all cases and effectively corrected the hypoxia and reduced pulmonary congestion. Other drugs used included aminophylline (14 patients), morphine sulfate (9 patients) and digoxin (3 patients). Five of the nine patients who received morphine were hypercarbic initially but the CO2 retention did not worsen. No patient died during the initial 48 hours. This study reiterates the importance of directing therapy at ventilatory and cardiac abnormalities and points out the value of arterial blood gas monitoring to assess the initial status, monitor the patient's course, and to select drug therapy.