Dependency of renal potassium excretion on Na,K-ATPase transport rate

Potassium secretion may depend on the transport rate of Na, K-ATPase in basolateral cell membranes of distal tubular cells. To examine this hypothesis experiments were performed in anaesthetized dogs during inhibition of proximal potassium reabsorption by acetazolamide or mannitol (fractional potassium excretion 1.2-1.4) or additional stimulation of potassium secretion by ethacrynic acid (fractional potassium excretion 2.1). Ouabain in a dose which inhibits 70–80% of the Na, K-ATPase activity reduced fractional potassium excretion to 0.8-0.9 by an effect on distal tubular secretion since potassium transport in the proximal tubules was not affected. Ouabain-sensitive potassium excretion varied in proportion to ouabain-sensitive sodium reabsorption during variation in glomerular nitration rate, even at urinary sodium concentrations exceeding 80 mmol 1^-1. In experiments without ouabain, saline infusion raised potassium excretion and sodium reabsorption until maximal Na, K-ATPase transport rate was reached, as judged from heat production measurements, but not during further increments in urine flow. After inhibition of Na, K-ATPase activity by hypokalaemia, potassium excretion and cortical heat production remained constant over a wide range of urine flow and sodium excretion. We conclude that potassium secretion is dependent on intact Na, K-ATPase activity and is stimulated by sodium delivery to the distal nephron until maximal transport rate of the enzyme is reached.     

Anaesthetic management of a child with Bartter’s syndrome

We report the anaesthetic management of an eight-year-old asthmatic boy with Bartter’s syndrome who had bilateral orchidopexy with caudal epidural analgesia. Bartter’s syndrome is a rare congenital disorder characterized by hypokalaemic hypochloraemic metabolic alkalosis, hyperaldosteronism, hyperreninaemia and hyperplasia of the juxtaglomerular apparatus of the kidneys. Characteristically, although these patients are normotensive they may be hypovolaemic. They may have unstable baroreceptor responses and show marked resistance to vasopressors. Hence, fluid, acid-base and electrolyte imbalances along with haemodynamic instability pose particular problems in their anaesthetic management. Previous case reports have described the management of these patients with general anaesthesia, our patient had his orchidopexy with caudal epidural analgesia using plain bupivacaine 0.5%. The patient was haemodynamically stable throughout surgery and was comfortable with caudal analgesia as the sole anaesthetic. Hypovalaemia, acid-base status and electrolyte imbalance were treated before instituting caudal epidural analgesia. We present this case report which describes the anaesthetic considerations in the light of the pathophysiology of Bartter’s syndrome.     

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

AIMS

Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.

METHODS

Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken.

RESULTS

One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m⁻². Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide.

CONCLUSIONS

Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.     

Severe metabolic complications from theophylline intoxication

Theophylline is commonly used in the treatment of bronchospastic lung disease. In addition to gastrointestinal and cardiac dysfunction, hypokalaemia, lactic and ketoacidosis can complicate theophylline overdose. Clinicians frequently fail to identify theophylline's role when complications develop. A case of an 80-year-old man who developed profound metabolic disturbances while hospitalized is presented. The typical causes of these abnormalities were absent, theophylline levels were elevated, and the patient recovered after theophylline was held. Based on our case and review of the literature, we discuss the reasons why theophylline toxicity is under-recognized, and propose mechanisms for the rare metabolic abnormalities identified in this case. A high index of suspicion for theophylline toxicity should be maintained and it should be considered when unexplained acidosis or hypokalaemia occur.     

Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia

We report on a patient with hypokalaemia and severe ventricular tachycardia of torsades de pointes type which turned out to be caused by an apparent mineralocorticoid excess syndrome associated with liquorice consumption. The patient, a 44-year-old woman, attended the hospital because of irregular heart rhythm and she displayed repeated episodes of life-threatening torsades de pointes ventricular tachycardia. The initial serum potassium was low: 2.3 mmol L-1. The patient was treated with potassium and magnesium infusions, and the dysrhythmias eventually ceased. Endocrinological investigations showed no indication of Cushing's syndrome or hyperaldosteronism. After some time it became clear that the patient had ingested moderately large amounts of liquorice every day for 4 months. After the patient stopped this habit the hypokalaemia and dysrhythmias did not recur and after more than 1 year there are no signs of cardiac illness.     

Bartter's syndrome and diabetes mellitus

Abstract. We here report a case of Bartter's syndrome occurring in association with diabetes mellitus. The patient, an insulin-dependent diabetic, presented with hypokalaemia, inappropriate kaliuresis and metabolic alkalosis. He had high plasma renin activity, relatively low plasma aldosterone, and resistance to infused angiotensin II. A high potassium diet raised total body potassium and serum potassium, did not affect plasma renin activity, but raised plasma aldosterone significantly and did not alter the resistance to angiotensin II. Indomethacin administered acutely reduced urinary potassium and kallikrein excretion and, on chronic administration, lowered plasma renin activity, urinary chloride excretion, and raised serum potassium. Salt restriction resulted in a prompt and significant reduction in urinary sodium and chloride excretion. Urinary kallikrein excretion was very high throughout, increased with sodium restriction, and decreased with sodium loading. Oral potassium supplementation partially corrected the hypokalaemia, but did not affect blood sugar control. In this patient the primary defect appears to have been primary urinary potassium wasting, rather than sodium or chloride wasting. The striking effects of indomethacin suggest that prostaglandins may play a fundamental role in the genesis of the syndrome.     

Anaesthesia for Conn''s syndrome

We describe the peri-operative management of two patients undergoing bilateral adrenalectomy for Conn's syndrome; one using an open surgical approach and the other a laparoscopic technique. The first patient, aged 64 years, died of a myocardial infarction 5 days postoperatively; the second, aged 29 years, had an uneventful recovery. The pre-operative preparation, peroperative management and postoperative care of these patients are detailed, and the pathophysiology and clinical management of Conn's syndrome are reviewed.     

Hypokalaemia and hyperkalaemia

Disturbances in potassium homoeostasis presenting as low or high serum potassium are common, especially among hospitalised patients. Given the fact that untreated hypokalaemia or hyperkalaemia is associated with high morbidity and mortality, it is critical to recognise and treat these disorders promptly. In this article, normal potassium homoeostasis is reviewed initially and then a pathophysiological approach to work-up and management of hypokalaemia and hyperkalaemia is presented. Recent advances with respect to the role of kidney in handling of the potassium, the regulation of renal ion transporters in hypokalaemia, and treatment of hypokalaemia and hyperkalaemia will be discussed.


     

Effects of BRL38227, salbutamol,and aminophylline,alone and in combination,on plasma potassium and on the heart

The present study was undertaken in order to examine the effects of the potassium channel activator BRL38227 and of aminophylline on hypokalaemia, cardiac stimulation (increased heart rate and contractility, dQ/dt), and electrocardiogram (ECG) changes induced by the β₂-adrenoceptor agonist, salbutamol in the anaesthetised cat. Salbutamol (1.25 μg.kg^?1min^?1), but not BRL38227 (0.1–1.0 μg.kg^?1 min^?1), infusion elicited a marked hypokalaemia (plasma K⁺ >2.5 mmolliter ^?1). This dose of salbutamol also elicited an immediate cardiac stimulation which appeared to be maximal and changes in ECG were evident as a reduction in QTc interval (20%) and T-wave height (80%). Cardiac stimulation following either BRL38227 or aminophylline was more gradual in onset, the maximum response being about 50–80% of the salbutamol effect. No ECG changes were observed in cats receiving BRL38227 whilst T-wave amplitude was reduced (50–60%) following aminophylline. Combination of salbutamol with aminophylline resulted in a greater degree of hypokalaemia, cardiac stimulation, and T-wave depression. The salbutamol-induced reduction in QTc was converted to a slight prolongation after infusion for 75 min. The ECG changes observed were not indicative of arrhythmia. Conversely, BRL38227 had no effect on salbutamol-induced hypokalaemia, cardiac stimulation, or T-wave depression, though the degree of QTc interval shortening was reduced. When BRL38227 was administered in conjunction with aminophylline, plasma potassium and QTc were unchanged. Depression of T-wave amplitude by aminophylline was slightly reduced in the combination group. Effects on heart rate and dQ/dt were similar to those seen for BRL38227 alone. Salbutamol-induced hypokalaemia was reversed by the nonselective β-adrenoceptor antagonist, propranolol, but not by the β¹-adrenoceptor selective antagonist, atenolol, confirming a β²-adrenoceptor selective effect. Cardiac stimulation was reversed by both propranolol and atenolol. In conclusion, salbutamol-induced hypokalaemia, cardiac stimulation, and ECG changes, as well as the additive effect of aminophylline, were demonstrated in the anaesthetised cat, but were unchanged by BRL38227. Furthermore, combination of BRL38227 with aminophylline did not result in any adverse effects on the parameters measured. Thus, on the basis of these results in the cat, combination of BRL38227 with the bronchodilator drugs, salbutamol or aminophylline, would not be expected to exacerbate the cardiovascular effects of these drugs. © 1992 Wiley-Liss, Inc.     

How many cisplatin administration protocols does your department use?

GREYSTOKE A.P., JODRELL D.I., CHEUNG M., RIVANS I. & MACKEAN M.J. (2009) European Journal of Cancer Care 19 , 80–90
How many cisplatin administration protocols does your department use? The introduction, 30 years ago, of the co‐administration of appropriate hydration and ensuring a diuresis occurs during the administration of cisplatin was important in its development, allowing clinically significant doses to be given with acceptable rates of toxicity. The clinical usage of cisplatin has increased and hydration protocols have been amended to increase patient comfort and reduce resource utilization. We suspected that this had led to unnecessary variations in practice both in clinical trials and subsequently in the clinic. Therefore, we reviewed practice in the Edinburgh Cancer Centre and discovered that 25 different hydration protocols were in use, with wide variation in dilution of cisplatin, total fluid administered, use of electrolyte (potassium and magnesium) supplementation and diuretics. These differences are a reflection of adoption of variations in hydration regimes published in pivotal clinical trials. A review of the available evidence relating to cisplatin associated hydration regimens was performed and recommendations will be made for the future design of evidence‐based protocols.