Influence of glucagon on plasma levels of potassium in man

Summary To investigate the role played by glucagon in the regulation of plasma potassium, we have examined the behaviour of this ion during four 2 h infusions of saline, glucagon (200 ng/min), cyclic somatostatin (priming dose of 50 g followed by 5.8 g/min) and somatostatin plus glucagon in 6 normal volunteers. Glucagon alone produced no change in potassium, despite an increase in insulin. Somatostatin, in addition to depressing insulin, produced a slight but significant (p < 0.01) increase in potassium ( max: 0.2–0.8 mmol/l: mean ± SEM, 0.4±0.1). Infusion of somatostatin together with glucagon suppressed the glucagon-induced increase in insulin and greatly augmented the increase in blood glucose. Potassium rose significantly more (p < 0.02) than after somatostatin alone ( max: 0.5–1.3 mmol/l; mean 0.9±0.1), indicating that hyperkalaemia results from hyperglucagonaemia in the absence of insulin. Evidence is presented that this last phenomenon is not mediated by hyperglycaemia or by a reduction in aldosterone secretion. It is suggested that low blood insulin and increased glucagon could be one of the mechanisms that underlie or magnify the hyperkalaemia observed in cases of serious stress or decompensated diabetes.     

Apparent hyperkalaemia from blood sampled from an arterial cannula

Blood samples were obtained from a radial artery cannula ina 60-yr-old man during coronary artery surgery. Serum potassiumconcentrations of 9.3, 8.4, and 7.4 mmol litre^–1 wereobtained. A simultaneous venous blood sample gave a serum potassiumconcentration of 4.4 mmol litre^–1. The ECG was unchanged.After the arterial cannula was repositioned, subsequent bloodsamples gave expected ranges of serum potassium concentration.We suggest that the initial arterial cannula position causeda high shear rate in the blood when samples were withdrawn,causing haemolysis and hyperkalaemia.     

An unusual case of hyperkalaemia-induced cardiac arrest in a paediatric patient during transfusion of a 'fresh' 6-day-old blood unit

A well-recognized complication of the transfusion of red blood cells (RBCs) is hyperkalaemia. This occurs in paediatric or adult patients receiving massive transfusion and can lead to cardiac arrest. Hyperkalaemia may follow the transfusion of 'stored' RBCs and/or haemolysed units, and depends on the quantity and rate of transfusion. We report on an unusual case of hyperkalaemia-induced cardiac arrest during transfusion of a 'fresh' blood unit. A 62-day-old baby girl was scheduled for a construction of a Blalock-Taussig shunt, after the completion of anastomosis, and upon release of vascular control, there was bleeding at the anastomotic site that was controlled with a suture placement. To compensate for the blood loss, a stat order was given for a push of 120 mL of RBCs over 10 min through the inferior vena cava central line. The blood unit was 6 days old and had been gamma-irradiated 48 h earlier. Shortly after the transfusion, the patient's electrocardiogram showed changes typical of hyperkalaemia; she then went into cardiac asystole. The blood unit potassium concentration was 55.3 mmol L-1, which flushed the atrioventricular node during transfusion. This is the first report of a high potassium level found in a 'fresh', less than 7 days old, nonhaemolysed RBC blood unit. The high concentration of potassium in this unit seems to be due to accelerated alterations of the RBC sodium/potassium adenosine triphosphatase pump (Na+/K+ pump), resulting in the release of intracellular potassium. This early and severe alteration of the pump and the unusually high potassium level may be due to as yet unexplained causes, warranting awareness, future investigation and routine saline washing of 'fresh' RBCs for paediatric patients who are candidates for central line transfusion.     

Immediate control of life-threatening digoxin intoxication in a child by use of digoxin-specific antibody fragments (Fab)

Digoxin-immune antibody fragments (Fab) for treatment of digitalis intoxication was introduced in 1976. Many reports have been published concerning this therapy for children, but few have focused on its immediate reversal of cardiac as well as extracardiac life-threatening manifestations of digoxin toxicity. We present a case of life-threatening digitalis intoxication in a child with postoperative renal insufficiency, after a Sennings procedure for transposition of the great arteries. Digoxin administration according to the nationally recommended dosage and intervals unexpectedly resulted in serum levels in the toxic range. Severe cardiac arrhythmias, haemodynamic instability and a rapid-increasing serum potassium level resulted. This report demonstrates how administration of Fab according to the manufacturer's dosage recommendation reversed the tachyarrhythmia immediately and re-established a normal level of serum potassium within minutes.     

Development,implementation and cost-effectiveness of a protocol for review of combination diuretic prescribing

AIMS: To determine the extent of inappropriate prescribing of combination diuretics and the cost implications of protocol implementation. METHODS: Pharmacist-run medication review clinics in two general practices in Bradford, UK. RESULTS: Sixty-one patients, mean +/- s.d. age 75.8 +/- 12.0 years, were reviewed. Thirty-six met protocol criteria; 30 (49.2%) patients had their potassium-sparing diuretics (PSDs) discontinued. Mean (95% confidence interval) reduction in serum potassium concentrations after intervention in these 30 patients was 0.26 (0.09, 0.43) mmol l(-1) (P < 0.01). Twenty-eight (93.3%) patients were within the reference range at follow-up; none was below. CONCLUSIONS: Of prescribed PSDs, 59% were found to be unnecessary. Using the developed protocol potentially improves drug safety and enables cost savings.     

Serious adverse events experienced by patients with chronic heart failure taking spironolactone

In patients with chronic heart failure, spironolactone added to conventional treatment may lead to serious and, occasionally, fatal hyperkalaemia. In some cases this seems to happen because spironolactone causes diarrhoea. Four cases involving men with New York Heart Association functional class III heart failure are presented. As these cases revealed, close monitoring of blood chemistry is mandatory after starting spironolactone, and patients should be advised to stop spironolactone immediately if diarrhoea develops.     

Renal and adrenal mechanisms in cyclosporine-induced hyperkalaemia after renal transplantation

Abstract. CsA associated hyperkalaemia was investigated in 24 renal transplant recipients 6 months after transplantation. ⁵¹Cr-EDTA-, PAH-, lithium and sodium clearances, 24 h urinary creatinine and potassium excretions, plasma renin activity and aldosterone concentrations were measured. Transtubular potassium concentration gradient (TTKG) was calculated. An ACTH test was performed to document adrenal function. Eleven patients had hyperkalaemia. The TTKGs were low normal or reduced in both normo-and hyperkalaemic patients implying inhibition of K⁺ secretion. The hyperkalaemic patients received more CsA (mean dose 21.3 vs. 9–7 mgkg^-1d^-1, P = 0.01), and had lower lithium clearances (mean 9.9 vs. 170 mLmin^-1 1.73m^-2, P <005). Adrenal function had no clear effect. Serum potassium concentration correlated with CsA dose (r=0.773, P<0.001) and inversely with lithium clearance (r = -0.568, P<0.01) suggesting that CsA induced decrease in distal tubular flow rate reduced K⁺ excretion. Hyperkalaemia was not fully explained by renal mechanisms.     

WNK4 regulates airway Na+ transport: study of familial hyperkalaemia and hypertension

Background WNK [With No K (lysine)] kinases are essential for regulation of blood pressure and potassium homeostasis. WNK4 expression was recently found not only in the distal nephron but also in chloride‐transporting epithelia. To establish a physiological role for this distribution we studied patients with familial hyperkalaemia and hypertension (FHH), [pseudohypoaldosteronism type II (PHAII)], which is caused by mutations in WNK4. Design Measurement of nasal potential difference (NPD) and sweat electrolytes were performed in controls, in six subjects with FHH and ten subjects with cystic fibrosis (CF). Results Basal NPD was higher in FHH compared with controls (n = 20): 22·8 ± 5·7 vs. 16·2 ± 5·3 mV, respectively (P = 0·014). Maximal response to amiloride was also higher in FHH compared with controls: 14·8 ± 3·5 vs. 10·0 ± 4·8 mV, respectively (P = 0·03). In CF these values were 42·9 ± 9·3 and 29·9 ± 7·4 mV, respectively. The kinetics of the amiloride effect were faster in FHH, and as first reported here also in CF, compared with controls. At 30 s, amiloride‐inhibitable residual PD in FHH was 50 ± 30 vs. 81 ± 9% in controls (P = 0·0003) and 56 ± 7% in CF. The response to chloride‐free and isoproterenol solutions, which determines chloride transport activity, was similar in FHH compared with controls [16·0 ± 8·6 vs. 10·4 ± 5·9 mV (P = 0·08)]. Sweat conductivity in FHH was 49·7 ± 7·3 vs. 38·2 ± 8·1 mmol (NaCl eq) L^?1 in 16 controls (P = 0·007) and 94·0 ± 19·3 in CF. Conclusions Mutant WNK4 increases Na⁺ transport in airways, and therefore it is regulated by wild‐type WNK4. This may be caused by a regulation of ENaC or a K⁺ channel.