Transient Hyperkalemia Research Articles

Concentrated potassium chloride infusions in critically ill patients with hypokalemia.

Although concentrated infusions of potassium chloride commonly are used to treat hypokalemia in intensive care unit patients, few studies have examined their effects on plasma potassium levels. Forty patients with hypokalemia were given infusions of 20 mmol of potassium chloride in 100 mL of normal saline over 1 hour; 26 patients received the infusions through the central vein and 14 patients through the peripheral vein. Plasma potassium ([K]p) was measured at 15-minute intervals during and after the infusion in 31 patients. delta K was defined as the difference between each potassium determination and baseline plasma potassium concentration. Continuous electrocardiographic recording was carried out during the infusion and during the 1-hour period immediately preceding the infusion. Mean baseline [K]p was 2.9 mmol/L and all subsequent plasma concentrations significantly increased from baseline. Mean peak [K]p was 3.5 mmol/L, [K]p (1 hour postinfusion) was 3.2 mmol/L, and mean postinfusion delta K was 0.48 mmol/L (range -0.1-1.7 mmol/L). Arrhythmias, changes in cardiac conduction intervals, and other complications did not occur. The frequency of premature ventricular beats decreased significantly during the infusion compared with that of the control period. The high concentration (200 mmol/L) and rate of delivery (20 mmol/hr) of the potassium chloride infusions were well tolerated, decreased the frequency of ventricular arrhythmias, and did not cause transient hyperkalemia.

Effects of catecholamines on plasma potassium: the role of alpha- and beta-adrenoceptors.

The sympathetic nervous system plays an important role in the control of plasma potassium levels. Administration of adrenaline or noradrenaline evokes, in the majority of mammal species a dual response: first a short transient hyperkalaemia, followed by a maintained hypokalaemia. Alpha 1- and alpha 2-adrenoceptors mediate the initial hyperkalaemia through the activation of hepatic Ca(2+)-dependent-K(+)-channels. Stimulation of beta 1- and beta 2-adrenoceptors induces the late hypokalaemia by stimulation of skeletal muscle Na(+)-K(+)-ATPase. Beta 3-adrenoceptor stimulation may also have an effect on plasma potassium control since administration of selective beta 3-adrenoceptor agonists induces a decrease in plasma potassium. The simultaneous infusion of phenyleprine (alpha-adrenoceptor agonist) and isoprenaline (beta-adrenoceptor agonist) increases plasma potassium levels: this effect is several times larger than the algebric summation of the changes in plasma potassium when each agent is infused separately, thus suggesting potentiation. The physiological (changes in cell volume and function secondary to changes in ion fluxes) and clinical implications (pathophysiological conditions with hypo or hyperkalaemia, hyperkalaemic periodic paralysis, ventricular arrythmias) of these findings are discussed.

Rapid Correction of Hypokalemia: A Note of Caution-Reply

In Reply— Dr Spital makes a plea for more data demonstrating the serum potassium response during potassium chloride infusions. It is conceivable that transient hyperkalmia could occur at the end of an infusion period and resolve prior to obtaining a postinfusion serum potassium measurement. However, since the chief danger of transient hyperkalemia is ventricular tachyarrhythmia, it is reassuring that there were no instances of such rhythm disturbances occurring during the infusion periods in our study1population. Nevertheless, we agree that it would be enlightening to know the serum potassium response during these infusions, as well as to have a more sensitive indicator of possible electrophysiologic effects short of ventricular tachycardia. To this end, we are currently completing a prospective clinical study investigating the pharmacokinetic effects of potassium infusions identical to those selected in our retrospective study. By performing potassium measurements every few minutes during and after the infusion and

Hyperkalemia in acute glomerulonephritis due to transient hyporeninemic hypoaldosteronism

Transient hyperkalemia has been reported to occur in patients with acute glomerulonephritis, but the pathogenetic mechanism has not been investigated systematically. We studied the mechanism of hyperkalemia (5.7 to 6.7 mmol/liter) in four men with post-infectious glomerulonephritis. All four patients had clinical findings consistent with acute glomerulonephritis (edema, hypertension, proteinuria, hematuria, and an elevated ASO titer) and a renal biopsy performed in three of the patients confirmed the diagnosis. In comparison to normal subjects (N = 18), plasma aldosterone (5.4 +/- 1.6 vs. 22.8 +/- 2.6 ng/dl, P less than 0.005) and plasma renin activity (0.3 +/- 0.2 vs. 4.3 +/- 0.6 ng/ml/hr, P less than 0.005) were reduced. Hyperkalemia resolved within one to two weeks in two patients as the nephritis resolved and diuresis ensued, and aldosterone and renin levels obtained at follow-up visits were normal. Hyperkalemia persisted despite furosemide-induced diuresis in the other two patients, but resolved with fludrocortisone treatment. Thus, hyperkalemia in patients with acute glomerulonephritis is a manifestation, in part, of hyporeninemic hypoaldosteronism. It is ameliorated by mineralocorticoid therapy and improves spontaneously with resolution of the glomerulonephritis.

A comparison of the effects of central ν peripheral bolus injections of potassium chloride on aortic root potassium concentrations in swine

Clinically relevant doses of potassium chloride (equivalent to 2 mEq/60 kg of body weight) were administered as rapid intravenous (IV) boluses to healthy halothane-anesthetized pigs. Potassium was given either peripherally through a standard IV ear catheter or centrally through the central venous port of a pulmonary artery catheter. Multiple injections were made in each pig, and cardiac output was varied by changing end-tidal halothane concentration. The aortic root potassium concentration was measured every three to six seconds for 90 seconds following potassium administration in each pig. Monitored variables included end-tidal halothane, end-tidal carbon dioxide, pulmonary artery pressure, mean arterial blood pressure, cardiac output, electrocardiogram, and temperature. Following both peripheral and central administration of potassium chloride, aortic root potassium increased significantly. However, the time required to achieve the peak aortic root potassium concentration was significantly less after central administration. In addition, the change in aortic root potassium concentration was greater following central administration compared with peripheral. The change in aortic root potassium concentration correlated inversely with cardiac output only after central, but not peripheral injection. Despite marked transient hyperkalemia in all animals, no electrocardiographic evidence of hyperkalemia could be demonstrated. It is concluded that small bolus doses of potassium chloride (2 mEq/60 kg) can be given safely either peripherally or centrally in normal, hemodynamically stable swine.

Transient hyperkalaemia immediately after acute haemorrhage in rats

Transient hyperkalaemia immediately after acute haemorrhage in rats

Hyperkalemia, hyperglycemia, and plasma levels of cyclic AMP and cyclic GMP induced by portal vein injection of cyclic nucleotides and their butyryl derivatives into dogs.

The levels of serum potassium, blood glucose, and plasma adenosine cyclic 3':5'-monophosphate (cAMP) and guanosine cyclic 3':5'-monophosphate (cGMP) were studied after the portal vein injection of cyclic nucleotides and their derivatives, (cAMP, cGMP, N6, O2'-dibutyryl adenosine 3':5'-monophosphate (DBcAMP), N6-monobutyryl adenosine cyclic 3':5'-monophosphate (NMBcAMP), and O2'-monobutyryl adenosine cyclic 3':5'-monophosphate (OMBcAMP), into dogs. Dose-related hyperglycemic responses were observed after the injection of DBcAMP (1-8 mg/kg). Transient and prominent hyperkalemia and hyperglycemia were caused by the injection of DBcAMP, NMBcAMP, and OMBcAMP (4 mg/kg). The hyperkalemic response was highest with NMBcAMP (1.22 mequiv./L), followed by OMBcAMP (0.64), DBcAMP (0.54), cGMP (0.47), and cAMP (0.41), whereas the hyperglycemic response was highest with NMBcAMP (146 mg/100 mL), followed by DBcAMP (93.6), OMBcAMP (77.1), and cAMP (56.0), and there was only a slight change with cGMP (28.4) compared with the control. The plasma level of cAMP was maximal with DBcAMP (1.92 nmol/mL), followed by NMBcAMP (1.28) and OMBcAMP (0.76), whereas the plasma levels of cGMP showed no evident change, except that caused by DBcAMP (0.27). Of the cyclic nucleotides tested, NMBcAMP was found to be most potent in causing both hyperkalemia and hyperglycemia. Based on these results, possible correlations between hyperkalemia, hyperglycemia, and plasma levels of cAMP and cGMP are discussed.

A Study on Change in Serum K+, Na+ and Cl- Concentsations after Injection of Flaxedil-Pentothal Sodium-Succinyleholine

Transient hyperkalemia is well known to occur in man following intravenous administration of succinylcholine chloride. To study on change of the serum level of K+, Na+ & Cl- after injetion of succinylcholine in healthy adults, physical status 1 or 2 adopted by the American society of Anesthesiologists, we studied in two grcups: pentothal sodium-succinylcholine injetion group (group 1) as control, flaxedil-pentothal sodium-succinylcholine injetion group(group 2) as experimental. The following results were obtained: 1. Serum K+ was slightly increased in both groups, 2mEq/L at 3rd minute in control group, 2mEq/L at 1st minute in experimental group after succinylcholine injection, but no statistical significance was noticed in either group. 2. Serum Na+ was decreased 3mEq/L immediately after pentothal sodium injetion and then sliyhtly increased untill 10th minute in control group. In experimental group lower level than control was observed untill 15th minute, with the maximum decrease of 7mEq/L at 5th minute. But no statistical significance was noticed in either group. 3. Serum Cl was slightly decreased untill 10th minute with the maximum decrease of 4mEq/L at 5th minute in control group. In experimental group, it was slightly increased untill 5th minute. But no significance was noticed in either group.

Effect of direct current countershock on atrial and ventricular electrophysiological properties and myocardial potassium efflux in the thoracotomised dog.

We reinvestigated the effect of direct current countershock (DCS) on atrial and ventricular electrophysiological properties and myocardial K+ release in the open-chested dog. This model allowed direct application of the electroshock paddles to the heart permitting reproducible energy input, simultaneous and comparative epicardial recordings for the measurement of conduction times (CT) and current threshold in different tissues, the determination of monophasic action potential duration (MAPD) with suction electrodes, and the measurement of coronary sinus K+ concentration [K+]cs. DCS produced changes in atrial and ventricular CT, in excitability, and in atrioventricular conduction (AVCT) even in the presence of cholinergic and (β-adrenergic receptor blockade. The type of electrophysiological response and its temporal relationship to [K+]cs after DCS suggest the DCS-induced release of myocardial K+ to play a role both in the antidysrhythmic effect of DCS and in the dysrhythmias following DCS. These effects were quite distinguishable both electrophysiologically and temporally from those of acetylcholine and catecholamines. More specifically, acetylcholine's effect on sinus rate, atrial APD, AVCT, and perhaps atrial excitability persisted for less than 10 s. The effect of catecholamines on automaticity and ectopic activity had a similar time course. The alterations in CT and excitability (often biphasic) attributable to the transient K+ elevation induced by DCS persisted for a half minute or longer. It seems DCS may have 2 antidysrhythmic phases: the first being immediate involving synchronisation of the non-refractory myocardium and the suppression of automaticity; the latter being delayed and dependent on transient local hyperkalemia.

Metabolic consequences of glucose-insulin-potassium infusion in treatment of acute myocardial infarction

Eighteen patients treated with glucose-insulin-potassium infusion for anaerobic support of acutely ischemic myocardial tissue were studied to ascertain the metabolic consequences of this therapy for acute myocardial infarction. Twelve patients with acute myocardial infarction were treated in a conventional manner and served as control subjects. The glucose-insulin-potassium solution was composed of 300 g of glucose, 50 units of regular insulin and 80 mEq of potassium ion per liter, and was infused at a rate of 1.5 ml/kg per hour through the right atrial port of an indwelling Swan-Ganz thermodilution catheter. Serial measurements of serum electrolytes, cardiac and hepatic enzymes, glucose and osmolality were obtained every 4 to 6 hours for 4 days. Twenty-four hour urinary volume and potassium levels were measured daily. Pulmonary arterial end-diastolic pressure was measured hourly and the cardiac index daily for the duration of the study. Serum potassium increased to 5 mEq/liter during the infusion and to more than 6 mEq/IHer after infusion in 28 percent of patients. No recognizable complications or arrhythmias accompanied this transient hyperkalemia. Potassium balance studies revealed a net total body potassium ion gain of 120 mEq during the study. The second most frequent finding was an elevation of serum glucose (mean 175 mg/100 ml); in all instances this was controlled with supplemental administration of insulin. The serum osmolality and fluid balance remained normal in all patients during the study. Serum glutamic oxaloacetic transaminase (SGOT) and fraction 5 of lactic dehydrogenase (LDH) were Increased in 34 percent of the patients during the last 12 to 18 hours of the glucose-insulin-potassium infusion. Characterization of these enzymes suggested a hepatic origin for these changes. This study suggests that glucose-insulin-potassium infusion is a relatively safe procedure in which postinfusion hyperkalemia is the most serious potential complication.

Acute, subacute and 23-day chronic marihuana inhalation toxicities in the rat

The acute, 5-day and 23-day toxicities of Δ 9-THC-impregnated (9% Δ 9-THC) and nonimpregnated marihuana (2.2% Δ 9-THC) cigarettes were determined in Fischer rats. Human smoking conditions were simulated by providing a 50-ml puff of 2-sec duration with a 30-sec exposure interval followed by a 30-sec purge period, each min, through use of an automatic smoking machine. The calculated inhalation doses ranged from 7 to 60 mg/kg acutely from 3.4 to 18.1 mg/kg subacutely, and from 0.7 to 4.2 mg/kg after chronic administration. Acute toxicity was manifested by dose-related hypothermia, hypopnea, loss of coordination, ataxia and prostration. Upon removal from the inhalator, high-dosed animals were depressed and low-dosed animals displayed increased activity rapidly followed by depression. Recovery was nearly complete by 24 hr in the acute trial and by day 6 in the subacute study. Body weights were normal; histopathologic examinations did not reveal any abnormalities. In the 5-day subacute toxicity study rats displayed transitory incoordination, hypothermia, hypopnea and initial increased activity at the lower doses followed by a persistent depression. Rate of body growth was normal, but there was an increase in the weight of reproductive organs. A transient hyperkalemia and hyperproteinemia were seen, but histopathologic examinations gave essentially normal results. Food intake and liver glycogen were increased. When lethality occurred, it was due to respiratory arrest. In the chronic study, there was a dose-related CNS depression and vocalization in the first week of exposure. Low- and middle-dosed animals were hyperactive in the first 10 min post-exposure, but all rats were depressed within 1–2 hr and generally recovered by 6 hr. In the second week of exposure, dose-related ataxia, prostration, “popcorn” response and vocalization were observed; cumulative toxicity occurred in 2 of the high-dosed males. Tolerance to prostration, ataxia, vocalization and exploratory activity developed after 8–12 exposures. After 3 weeks of exposure, hyperactivity and hypersensitivity were seen in low- and middle-dosed groups while high-dosed females exhibited fighting aggression and high-dosed males were depressed or tranquil. During the fourth and last week of exposure, tolerance developed to CNS stimulation in all groups, and animals were either normal or tranquil. Clinical signs were primarily affected in the first week of exposure: a 30–75% dose-related decrease in exploratory activity, hyperthermia at lower doses and hypothermia at the high dose, and a 15–30% decrease in respiration rate at mid and high doses. On day 14, hemochemistry, urinalysis and histopathology were normal but a 10% increase in testes (0.7 mg/kg), and a 15–40% increase in adrenal weights for both sexes was observed, although growth rate was normal. During prolonged exposure, there was a 10% decline in growth rate for males receiving the high dose, but food intake increased 14–29%; in females, body weight was maintained while food consumption fell 5–12%. Generally, continued exposure did not alter rectal temperature, respiration rate, urinalysis or hemochemistry, but a slight decline in hematocrit value was observed at the high-dose level. Histopathologic findings were essentially negative. The inhalation studies reveal that doses of Δ 9-THC, similar to those used by man, rapidly initiate behavioral and physiological changes. Tolerance developed to most of these changes during chronic treatment. Some cumulative toxicity and fighting episodes can occur in the rat after inhalation of marihuana smoke, despite the lack of morphologic changes.

Effects of systemic hypoxemia and catecholamines on arterial potassium ion concentrations before and after β-adrenergic blockade

Arterial blood potassium concentrations were measured in dogs before, during and following adrenaline and noradrenaline infusion and systemic hypoxemia. Adrenaline infusion produced marked but transient hyperkalemia that was followed by significant hypokalemia. Systematic hypoxemia resulted in a large increase in the arterial blood concentration of potassium that was not followed by hypokalemia. Noradrenaline infusion resulted in a small increase in arterial potassium but no significant hypokalemia. Beta-adrenergic blockade diminished and delayed the maximum increases in arterial potassium concentration associated with hypoxemia and adrenaline and blocked completely the marked hypokalemia that followed adrenaline infusion. The absence of hypokalemia following hypoxemia and the presence of it with adrenaline infusion offers suggestive evidence that the potassium changes associated with systemic hypoxemia may not be mediated solely through adrenaline release.

Adrenergic beta blockade and changes in plasma potassium following epinephrine administration

Injection of epinephrine, 5 μg/kg in the dog produced, among other effects, two well known effects on metabolism: hyperglycemia and a transient hyperkalemia followed by hypokalemia. The effects were compared with those found in dogs pretreated with a beta adrenoceptor blocking agent. Our results show that after either 0.05 mg/kg or 0.5 mg/kg of d, 1-propranolol, hyperglycemia and hypokalemia to epinephrine were significantly changed. The early increase of serum potassium by epinephrine was reduced and delayed by the beta blocking agent; the hypokalemic effect was clearly prevented by the three doses of propranolol used (0.05, 0.5 and 2 mg/kg) suggesting a possible relation between the mechanism producing hypokalemia and the beta adrenoceptors blocked by propranolol.

Aldosteronism and Precocious Puberty Due to an Ovarian Androblastoma (Sertoli Cell Tumor)¹

This report describes a 9-year-old girl with precocious puberty and aldosteronism associated with an ovarian Sertoli cell tumor. After excision of the neoplasm there was amelioration of the manifestations of early feminization and aldosteronism. It is our impression that both endocrinopathies were induced by secretions from the ovarian tumor. Grossly both adrenals, and microscopically the simultaneously excised right adrenal, were normal. Transient hyperkalemia and absence of urinary aldosterone shortly after surgery suggested previous suppression of the remaining adrenal by an abnormal source of aldosterone. Functional ovarian neoplasms are a rare cause of early feminization. Sertoli cell tumors are uncommon; they are functional and secrete estrogens, but have not been shown to possess adrenocortical activity. Homogenates of this tumor exhibited low levels of aldosterone-forming and other adrenal steroidogenic enzymatic activities.