Electrocardiography is unreliable in detecting potentially lethal hyperkalaemia in haemodialysis patients.

BACKGROUND: It is speculated, but unconfirmed, that the usual electrocardiographic manifestations of hyperkalaemia are less frequent and less pronounced in persons with end-stage renal disease (ESRD) than in those with normal renal function. We studied 74 consecutively selected stable haemodialysis patients to determine the prevalence of electrocardiographic changes of hyperkalaemia in stable persons with ESRD receiving haemodialysis. METHODS: Pre-dialysis serum potassium concentration and other electrolytes were measured and simultaneous 12-lead electrocardiogram obtained. RESULTS: The 74 study subjects (45 men, 29 women) comprised 63 blacks (85%), four Hispanics (6%), four whites (6%), and three Asians (4%) of mean+/-standard deviation age 55.5+/-14.7 years. Mean pre-dialysis potassium concentration was 4.9+/-0.71 mEq/l (range 3.3-6.7). No study subject evinced arrhythmia or any of the typical electrocardiographic changes associated with hyperkalaemia. There was no significant difference in T wave amplitude (F statistic=2.1; P=0.11) or T wave to R wave ratio (F statistic=2; P=0.12) between quartiles of serum potassium concentration. Also, T wave amplitude was equivalent in patients with serum potassium concentration >5.5 mEq/l (7.1+/-4.1 mm) or < or =5.5 mEq/l (5.2+/-3.5 mm) (P=0.13). Linear regression analysis showed that the total serum calcium concentration had an inverse relation with T wave amplitude (P=0.03) after adjustment for other factors (a high total serum calcium concentration was associated with a low T wave amplitude). CONCLUSION: Haemodialysis patients with hyperkalaemia may not exhibit the usual electrocardiographic sequella of hyperkalaemia, possibly due in part to fluctuations in serum calcium concentration. Thus, the absence of electrocardiographic changes in hyperkalaemic haemodialysis patients should be interpreted with caution.     

Angiotensin converting enzyme inhibitor induced hyperkalaemic paralysis

Secondary hyperkalaemic paralysis is a rare condition often mimicking the Guillain-Barré syndrome. There have been a few case reports of hyperkalaemia caused by renal failure, trauma, and drugs where the presentation has been with muscle weakness. A case of hyperkalaemic paralysis caused by an angiotensin converting enzyme inhibitor is reported.     

Acidosis,hypoxia and stress hormone release in response to one-minute inhalation of 80% CO2 in swine

The study pertains to a series of investigations on the effects of CO₂ inhalation as used for pre-slaughter anaesthesia in swine. Acid/base parameters, blood oxygen tension, plasma Na, K, Ca and stress hormone concentrations were monitored in Yorkshire swine before, during, and for 10 min after the animals were descended for 1 min into 80% CO₂ in air. Severe respiratory acidosis (P_aco2? 50 kPa, arterial pH ? 6.6) and hypoxia (P_ao2? 4 kPa) had developed after 45 s of the CO₂ inhalation. The corresponding changes in venous blood were less drastic (P_vCO2? 17 kPa, pH 7.1, P_vo2? 4 kPa). Readjustment to P_aCO2? 11 kPa, arterial pH 7.2, and P_ao2? 13 kPa had occurred at 1 min post CO₂. Four minutes later the respiratory acidosis had become converted into metabolic acidosis subjected to partial respiratory compensation (arterial pH 7.3 in the presence of moderate hypocapnia and hyperoxaemia). The cause of this metabolic acidosis (present also at 10 min post CO₂) was apparently hypoxia-induced anaerobic metabolism (= lactic acid production). Apparently due to hydrogen ion transport into the cells in exchange for other cations, hyperkalaemia (K? 6.6 mmol 1^-l), and a 7 mmol 1^-1 increase in plasma Na had developed at 1.5 min later. The CO₂ inhalation did not change the total plasma Ca significantly. The transport of the swine from the stable to the immediate pre-experimental situation induced a 3-fold increase in plasma Cortisol concentration (PC, to ? 130 mmol 1^-1). No further increase in PC occurred in response to the CO₂ inhalation. It indicates that no additional emotional strain was imposed upon the animals during the CO₂ exposure. Another possibility is that a maximal secretion of Cortisol was here reached already before the descent into the CO₂. The transport procedure caused only minor increases in plasma adrenalin (A) and noradrenaline (NA). However, during the CO₂ exposure plasma A and NA exhibited 15- and 50-fold rises, respectively (to 3.5 and 22 mmol l^-1, respectively). The main cause of the A/NA elevation seems to have been the severe respiratory acidosis.     

The effect of changes in core body temperature on the QT interval in beagle dogs: a previously ignored phenomenon, with a method for correction

BACKGROUND AND PURPOSE: Body core temperature (Tc) changes affect the QT interval, but correction for this has not been systematically investigated. It may be important to correct QT intervals for drug-induced changes in Tc. EXPERIMENTAL APPROACH: Anaesthetized beagle dogs were artificially cooled (34.2 degrees C) or warmed (42.1 degrees C). The relationship between corrected QT intervals (QTcV; QT interval corrected according to the Van de Water formula) and Tc was analysed. This relationship was also examined in conscious dogs where Tc was increased by exercise. KEY RESULTS: When QTcV intervals were plotted against changes in Tc, linear correlations were observed in all individual dogs. The slopes did not significantly differ between cooling (-14.85+/-2.08) or heating (-13.12+/-3.46) protocols. We propose a correction formula to compensate for the influence of Tc changes and standardize the QTcV duration to 37.5 degrees C: QTcVcT (QTcV corrected for changes in core temperature)=QTcV-14 (37.5 - Tc). Furthermore, cooled dogs were re-warmed (from 34.2 to 40.0 degrees C) and marked QTcV shortening (-29%) was induced. After Tc correction, using the above formula, this decrease was abolished. In these re-warmed dogs, we observed significant increases in T-wave amplitude and in serum [K(+)] levels. No arrhythmias or increase in pro-arrhythmic biomarkers were observed. In exercising dogs, the above formula completely compensated QTcV for the temperature increase. CONCLUSIONS AND IMPLICATIONS: This study shows the importance of correcting QTcV intervals for changes in Tc, to avoid misleading interpretations of apparent QTcV interval changes. We recommend that all ICH S7A, conscious animal safety studies should routinely measure core body temperature and correct QTcV appropriately, if body temperature and heart rate changes are observed.     

Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis

The incidence, causes and complications of severe rhabdomyolysis(creatine phosphokinase (CK) 5000 U/l) were studied during a7-year study period in a large university hospital population.This condition was present in 0.074% of all admitted patients.The mortality in the study group (n=93) was 32% and the incidenceof acute renal failure (ARF) 51%. Ischaemia was the most frequentcause, and drugs, alcohol and/or coma were the second most commoncause of severe rhabdomyolysis. Patients with rhabdomyolysisdue to ischaemia were older, had ARF more often, and also hadthe highest mortality. Hyperkalaemia (potassium 5.5 mmol/1)occurred in 13% of the patients, and all of them had or developedan impaired renal function. Hypocalcaemia (calcium 2.00 mmol/1)was found in 41%. The incidence of ARF and electrolyte disturbanceswas higher in patients with CK levels exceeding 15 000 U/l.Mortality was significantly higher in patients with ARF. Plasmaconcentrations of potassium and calcium correlated better withthe severity of renal failure than with the maximal height ofplasma CK.     

No impact of hyperkalaemia with renin-angiotensin system blockades in maintenance haemodialysis patients.

BACKGROUND: Renin-angiotensin system (RAS) blockades, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well accepted for the cardiorenal-protective benefits added to antihypertensive effects in chronic kidney diseases (CKD), but associated with an increased risk of hyperkalaemia. However, few studies have investigated the effect of RAS blockades on serum potassium in dialysis patients. METHODS: Hyperkalaemia associated with RAS blockades by ACEI and/or ARB was evaluated in 69 patients on maintenance haemodialysis, who underwent a three-period crossover study in four groups (no exposure to RAS blockades, ACEI or ARB alone and ACEI plus ARB treatments), lasting one month in each period. RESULTS: Sixty-two patients completed this prospective 3-month study, and no one stopped the study because of the development of hyperkalaemia and/or complications. Mean serum K was similar among the four periods (no exposure, 5.54+/-0.67 mmol/l; ACEI alone, 5.54+/-0.75 mmol/l; ARB alone, 5.50+/-0.66 mmol/l; ACEI+ARB combination, 5.42+/-0.66 mmol/l) and was also equal when compared between the two groups with and without exposure to RAS blockades (5.48+/-0.68 vs 5.54+/-0.67 mmol/l, P=NS). The incidence of severe hyperkalaemic episodes (>6.0 mmol/l) upon monthly predialysis serum K determination was 25.8% with no exposure to RAS blockades, 29.8% for ACEI alone, 19.6% for ARB alone and 17.7% for ACEI+ARB combination without statistically significant differences among the four periods (P=NS). Among covariables, the degree of Kt/V, intakes of other medications interfering with potassium homeostasis and diabetes mellitus did not result in any significant hyperkalaemic changes during the 3-month study period except anuric patients compared with non-anuric patients (5.58+/-0.69 vs 5.19+/-0.65 mmol/l, P<0.001). CONCLUSION: Neither monotherapy (ACEI or ARB) nor combination therapy (ACEI plus ARB) is associated with the additional risk of hyperkalaemia in patients on maintenance haemodialysis. However, those patients with anuria on RAS blockades warrant the cautious monitoring of serum K to prevent hyperkalaemia.     

Junctional bradycardia with verapamil in renal failure – care required even with mild hyperkalaemia

What is known and objective: Treatment for hypertension with verapamil has a favourable renoprotective effect and is generally considered safe in patients with mild to moderate renal failure. In this report, we highlight the vulnerability of patients with mild to moderate renal failure to verapamil side effects especially in the presence of hyperkalaemia. Case summary and what is new: We report two cases of junctional bradycardia with slow release (SR) verapamil therapy in the presence of mild hyperkalaemia in patients with mild to moderate chronic renal failure. Verapamil and hyperkalaemia may synergistically increase the vulnerability to atrioventricular conduction delay. Conclusion: Renal failure patients with baseline mild hyperkalaemia are particularly liable to bradyarrhythmias with SR verapamil. In such cases, we would recommend verapamil dose reduction and avoidance of SR formulation. In cases of verapamil toxicity, actively treating any level of hyperkalaemia is recommended.     

Hyponatraemia and hyperkalaemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities.

BACKGROUND: This study was designed to examine the hypothesis that the nephrotoxicities caused by cyclosporin and tacrolimus might differ in respect of sodium and potassium handling. METHODS: 125 patients were studied retrospectively for the first 90 days after renal transplantation. Eighty were treated initially with cyclosporin and 45 with tacrolimus. RESULTS: A serum sodium level of <135 mmol/l was present for 542/5171 (10.5%) days under tacrolimus treatment compared with 377/5486 (6.9%) days under cyclosporin treatment (P < 0.0001). Severe hyponatraemia, below 120 mmol/l, was also more prevalent under tacrolimus than cyclosporin treatment, P < 0.025. Nine patients, all receiving tacrolimus, were treated with fludrocortisone for fluid depletion and/or hyponatraemia. Serum potassium levels were higher in tacrolimus-treated patients (P < 0.0001), and subjects with hyponatraemia were more likely to experience hyperkalaemia (P < 0.0001). CONCLUSIONS: Hyponatraemia and hyperkalaemia were more frequent in tacrolimus-treated subjects. Taken together with previous work showing that hyperuricaemia is more frequent with cyclosporin treatment, and hypomagnesaemia with tacrolimus treatment, these findings are consistent with qualitative differences between the nephrotoxicities of cyclosporin and tacrolimus.     

Metabolic effects of amino acid solutions infused for renal protection during therapy with radiolabelled somatostatin analogues.

BACKGROUND: Infusion of amino acids (AAs) can reduce renal uptake of radiolabelled somatostatin analogues resulting in a lower kidney exposure during peptide radiotherapy of patients with neuroendocrine tumours. In this study, we investigated the metabolic effects related to the infusion of large amounts of amino acids in patients undergoing positron emission tomography (PET) studies with [(86)Y]DOTA(0)-D-Phe(1)-Tyr(3)-octreotide. METHODS: Twenty-four patients, in four consecutive groups of six, received a 4 h infusion of 120 g of mixed AAs and, in addition, either a 4 h infusion of 50 g of L-lysine (n = 6), a 10 h infusion of 240 g of mixed AAs (n = 6), a 4 h infusion of 50 g of L-lysine + L-arginine (Lys-Arg; n = 6) or no infusion (control; n = 6) in randomly ordered crossover studies. A number of clinical and biochemical parameters in blood and urine were measured over 24 h, including calculation of creatinine clearance, tubular reabsorption of inorganic phosphate (TRP) and fractional urate excretion. RESULTS: No clinical side effects occurred during the infusions except for nausea and vomiting under mixed AAs. Patients in the latter group showed an increase in serum urea, whereas patients receiving L-lysine showed an increase in serum potassium and chloride. Inorganic phosphate levels dropped at 2.5 h in all groups except controls, and a significant decrease in TRP was observed with mixed AAs but not with L-lysine or Lys-Arg. CONCLUSION: Although infusion of AA solutions can improve the effect of therapy by allowing the administration of higher doses of radiolabelled somatostatin analogues, each preparation has specific sides effects that should be taken into account with this type of therapy.