Nonazotemic hyperkalemia with renal and extrarenal defects in potassium transport: association with high levels of digoxin-like immunoreactive factor

We report a hypertensive patient with nonazotemic hyperkalemia caused by a combined disturbance in both the internal and external balance of potassium. During a follow-up of 30 months, exacerbations of hyperkalemia were observed, interposed with a return to the previous baseline. Two brief normokalemic periods were recorded. Blood pressure tended to be higher during hyperkalemic peaks. The following findings were detected: (1) hyperchloremic hyperkalemic acidosis with normal glomerular filtration rate, adequately elevated plasma aldosterone levels, and normovolemia; (2) a tubular defect in potassium excretion, refractory to intravenous sodium sulfate (nonreabsorbable anion) and mineralocorticoids; (3) impaired tissue uptake of potassium under insulin administration; (4) exaggerated hyperkalemia following beta-adrenergic blockade and blunted hypokalemic response to a beta-agonist; and (5) a defect in Na/K transport in erythrocytes detected in vitro, coexistent with an elevated level of free digoxin-like immunoreactive factor in serum. These results suggest that our patient had a generalized abnormality in potassium transport.     

维持性血液透析患者透析前后血钾状态及其影响因素分析

目的观察维持性血液透析（MHD）患者透析前后血清钾离子浓度,并探讨影响其变化的临床因素。方法57例维持性血液透析患者,根据其是否服用血管紧张素转换酶抑制剂（ACEI）或血管紧张素Ⅱ受体拮抗剂（ARB）,将患者分为ACEI组、ARB组及非ACEI／ARB组;记录各组患者残余尿量及有无高钾血症临床表现,并取透析前后静脉血,测定血清钾、尿素氮（BUN）、血肌酐（SCr）、二氧化碳结合力（CO2CP）等指标,分析各组患者血钾浓度变化的差异及血钾浓度与其他临床因素之间的相关性。结果透析前高钾血症发生率36．8％（21／57）,其中76．2％（16／21）患者无高钾血症的临床表现;ACEI组、ARB组、非ACEI／ARB组透析前血钾水平分别为（6．0±0．95）mmol／L、（5．60±0．25）mmol／L、（4．72±0．95）mmol／L,其中ACEI组与其他2组之间差异有统计学意义（P〈0．01）,而ARB组与非ACEI／ARB组患者透析前血钾浓度差异无统计学意义（P〉0．05）;透析前血钾离子浓度与SCr、BUN浓度显著正相关（r=0．415、0．522,均P〈0．01）,但与患者残余尿量和透析前后CO2CP浓度变化无明显相关（r=0．559、0．411,均P〉0．05）。结论MHD患者透析前高钾血症发病率高,临床表现较隐匿,易被忽视;残余尿量并非判断患者是否易出现透析前高钾血症的可靠指标;增加透析次数,减量或停服ACEI,限制饮食中钾摄入是防治透析前高钾血症的有效方法。     

Correction of factitious hyperkalemia in hemolyzed specimens

BACKGROUND: Hemolysis in pediatric specimens is common due to difficult blood draws and small-bore intravenous catheters. Values of serum K+ become falsely elevated secondary to release of intracellular contents. If a reliable correction factor existed for this factitious elevation, repeat K+ measurements might be avoided. OBJECTIVE: The aim of the study was to establish a correction factor for factitiously elevated K+, using free plasma hemoglobin (p-Hgb) as a measure of in vitro hemolysis. METHODS: Twenty whole-blood specimens drawn from healthy adults via a 23-gauge needle were divided into 4 aliquots: (1) no manipulation, (2) mechanical hemolysis via a 27-gauge needle, (3) addition of potassium acetate (KAc), and (4) addition of KAc and mechanical hemolysis. KAc was added to mimic potentially significant hyperkalemia. All specimens had standard K+ and p-Hgb measurements performed. RESULTS: Nonhemolyzed and hemolyzed K+ ranged from 3.2 to 8.1 mEq/L and 3.5 to 10.0 mEq/L, respectively. A linear relationship existed between the change in K+ and p-Hgb from the nonhemolyzed to hemolyzed specimens. A correction factor for K+ of 0.00319 (95% confidence interval, 0.00290-0.00349) x p-Hgb was obtained. CONCLUSIONS: A reliable correction factor for factitious hyperkalemia in a clinically relevant range exists. By example, using the above correction factor, one can predict that the delta K+ in a specimen with 500 mg/dL of p-Hgb will be 1.6 mEq/L (range, 1.5-1.7). We suggest that when the lower bound of the predicted delta K+ results in a corrected value within the reference range, a second blood draw is unnecessary.     

Amelioration of metabolic acidosis by dietary potassium restriction in hyperkalemic patients with chronic renal insufficiency

Hyperkalemia has been implicated in the pathogenesis of metabolic acidosis in chronic renal insufficiency because acidosis is ameliorated after administration of medications that correct hyperkalemia: mineralocorticoids, diuretics, intestinal K+-binding agents. However, the acidosis-ameliorating effect of these medications may be a consequence not of their ability to correct hyperkalemia, but of their ability to directly stimulate renal or intestinal excretion of acid. To investigate the specific effect of correcting hyperkalemia, balance studies were performed wherein hyperkalemia was corrected solely by restriction of dietary K+ in three patients with moderate chronic renal insufficiency (Ccreat 36, 44, and 58 ml/min/1.73 m2, respectively). Reduction of K+ intake was effected by substitution of Na+ for K+ in the electrolyte supplement to a whole-food diet of low K+ content. This maneuver resulted in correction of hyperkalemia and sustained amelioration of metabolic acidosis in each patient. Net acid excretion increased only transiently, and not enough to fully account for the magnitude of the increment in plasma [HCO3-], suggesting that an extrarenal mechanism of HCO3- input to the systemic circulation was the major factor that ameliorated the systemic acidosis. Evidence of an extrarenal mechanism was obtained only during the phase of decreasing plasma [K+]. Subsequently, during sustained normokalemia, the increased plasma [HCO3-] was maintained as a consequence of a sustained increase in total renal H+ secretion, evidenced by complete reabsorption of the increased filtered load of HCO3- and no reduction in net acid excretion from control values. These results indicate that in some patients with moderate chronic renal insufficiency, metabolic acidosis is ameliorated when hyperkalemia is corrected by restriction of dietary K+ (Na+ substitution) without otherwise changing diet composition and without administration of medication. Amelioration of the acidosis is predominantly effected by extrarenal mechanisms, and is sustained by an increase in the set point at which plasma [HCO3-] is regulated by the kidney.     

Transfusion-associated hyperkalemia

The supernatant potassium concentration [K+] of red blood cell (RBC) units is frequently much higher than normal human plasma potassium levels, especially in units nearing the end of their storage life. Clinical hyperkalemia resulting from RBC transfusions has been recognized as a transfusion complication for decades, and there have been reported cardiac arrests attributed to transfusion-associated hyperkalemia. This review summarizes the evidence surrounding RBC [K+] levels, effects of irradiation and washing on [K+], the evidence for clinical hyperkalemia and cardiac arrests resulting from transfusion, predictors of post-transfusion hyperkalemia, and their preventative strategies. Key points include: (a) the [K+] (in mmol/L) increases linearly and is approximately equal to the number of days of RBC unit storage; (b) irradiation causes a rapid increase in [K+]; (c) there is potentially sufficient potassium in the supernatant of current RBC preparations to lead to hyperkalemia with large transfusion volumes; (d) any rise in patient potassium after transfusion is usually transient due to the redistribution of the potassium load; (e) transfusion-associated hyperkalemic cardiac arrests probably do occur, although it is difficult to prove this fact conclusively; and (f) promising strategies to combat transfusion-associated hyperkalemia include RBC washing, the use of in-line potassium filters, and the use of traditional treatments for hyperkalemia such as the use of insulin.     

University of Miami Division of Clinical Pharmacology therapeutic rounds: drug-induced hyperkalemia

Drug-induced hyperkalemia is an important but often overlooked problem encountered commonly in clinical practice. It may occur in the ambulatory as well as the impatient setting. Every evaluation of a hyperkalemic patient should include a careful review of medications to determine if a drug capable of causing or aggravating hyperkalemia is present. Medications generally produce hyperkalemia either by causing redistribution of potassium (beta2 -adrenergic blockers, succinylcholine, digitalis overdose, hypertonic mannitol) or by impairing renal potassium excretion. Drugs cause impaired renal potassium excretion by (1) interfering with the production and/or secretion of aldosterone (nonsterodial anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin-II receptor antagonists, heparin, cyclosporine, and FK 506) or (2) blocking the kaliuretic effects of aldosterone (potassium-sparing diuretics, trimethoprim, pentamidine, and nefamostat mesilate). Because severe renal insufficeiency is generally required to cause hyperkalemia, an elevated serum potassium concentration in a patient with mild-to-moderate renal failure should not be ascribed to renal failure alone. A careful search for "hidden" potassium loads and for causes of impaired tubular secretion of potassium (including drugs) is necessary. Finally, it is important to recognize that the causes of hyperkalemia may be additive. Patients may have more than one cause of hyperkalemia at the same time. Therefore, all potential causes of hyperkalemia, including drugs, should be systematically evaluated in every hyperkalemic patient.     

Extreme hyperkalemia

Hyperkalemia is a potentially fatal condition and is defined by a serum potassium level (K+) of greater than 5.5 mmol/L. The associated prevalence of cardiac arrhythmia increases directly with the degree of hyperkalemia. The danger in the majority of hyperkalemia cases is cardiac dysrhythmia, and often ventricular fibrillation or asystole is the terminating event. Although there are many previous reports addressing this threatening problem and associated therapeutic maneuvers, there have not been many previous reports citing the fatal concentration of hyperkalemia irrespective of the causes. However, it is uniformly accepted that a K+ concentration greater than 10.0 mmol/L is fatal unless urgent treatment is instituted. This report describes a case of nonfatal hyperkalemia of 14 mmol/L with intact survival and complete recovery. Potassium homeostasis is revisited, and some explanations are proffered regarding the protective mechanism against hyperkalemia, including transcellular flux, renal tubular function, and endocrine responses.     

Tall T waves during metabolic acidosis without hyperkalemia: a prospective study

The specific ECG characteristics of metabolic acidosis have not been satisfactorily defined in man. We addressed this question by prospectively studying 14 consecutive patients admitted with metabolic acidosis and without hyperkalemia. Arterial blood gas analysis and serum potassium determinations were performed during acidosis and after its correction. ECGs were recorded at the same times. Mean pHa increased from 7.11 +/- 0.05 to 7.40 +/- 0.01 (p less than .001) in response to an increase in total CO2 content from 6.8 +/- 1.4 to 21.2 +/- 0.7 mmol/L (p less than .001). Serum potassium concentration decreased only slightly after correction of the acidosis from 4.2 +/- 0.1 to 3.9 +/- 0.14 mmol/L (p less than .05). T waves were taller during acidosis than after correction (0.68 +/- 0.1 vs. 0.28 +/- 0.04 mV, p less than .001 and 0.64 +/- 0.08 vs. 0.38 +/- 0.04, p less than .005, in precordial leads V2 and V3, respectively). Moreover, the amplitude of T waves in V2 was correlated positively with the arterial concentration of H+ (r = .786, p less than .001) and negatively with the arterial total CO2 content (r = -.71, p less than .005). In addition to their augmented amplitude, T waves were peaked and symmetrical with a narrow base ("tent-shaped"). Thus, metabolic acidosis may be accompanied by an increase in the amplitude of T waves, even in the absence of hyperkalemia.     

Serum concentration of potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate, losartan potassium or candesartan cilexetil

OBJECTIVE: To retrospectively investigate elevation of serum potassium when spironolactone (25 or 50 mg/day) and furosemide were administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) to patients with chronic heart failure for 12 months and occurrence of hyperkalemia and hypokalemia because of concomitant administration of spironolactone plus an ACE-I or ARB and furosemide. METHODS: Patients with chronic heart failure, who visited departments of cardiovascular internal medicine and cardiovascular surgery at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine, uric acid, and serum sodium were determined in every patient at the time of start of treatment and at 3 and 12 months of treatment. Data from patients in Groups A (25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) and B (50 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) were analysed for differences with respect to the ACE-I and ARB used. RESULTS: When 50 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril) or 50 mg/day losartan potassium (losartan) or 8 mg/day candesartan cilexetil (candesartan) plus 40 mg/day furosemide were concomitantly used, the mean value of serum potassium was significantly elevated only in the group treated with 50 mg/day spironolactone regardless of the concomitant drug. The number of patients with hyperkalemia (>5.5 mEq/L) at 12 months of treatment was 12 (8.8%), while the number of patients with hypokalemia (相似文献   

Fluoride-induced hyperkalemia: the role of Ca2+-dependent K+ channels

Acute fluoride poisoning is associated with sudden cardiac death by an unknown mechanism. Because F- binds to Ca2+ to cause marked hypocalcemia, lowered serum Ca2+ concentrations have been thought to be a major underlying factor in the ventricular irritability of F(-)-toxic patients. However, correction of the hypocalcemia does not prevent sudden death. Paradoxically, while decreasing extracellular Ca2+ levels, in vitro studies have shown F- increases intracellular Ca2+, which is thought to trigger Ca2+-dependent K+ channels and produce a K+ efflux. The K+ efflux may be important clinically, as patients with F- overdose can exhibit hyperkalemia shortly before cardiovascular collapse. In erythrocyte suspensions, we found that propranolol, which increases the sensitivity of the Ca2+-dependent K+ channels, exacerbates the efflux, and quinidine, which blocks the channel, prevents the efflux. In six dogs, 35 mg/kg of sodium fluoride given intravenously produced intractable ventricular fibrillation within 140 minutes. Four dogs given 200 mg of quinidine sulfate with the sodium fluoride developed no ventricular arrhythmias. The data indicate that F--induced hyperkalemia is important in sudden cardiac death following acute fluoride toxicity and that this hyperkalemia is mediated by Ca2+-dependent K+ channels.     

Are sodium bicarbonate and potassium bicarbonate fully dissociated under physiological conditions?

In solutions containing 160 mmol/l Na+ and K+, respectively, measurements with an ion-selective electrode system (KNA1, Radiometer), showed apparent falls in the respective Na+ and K+ concentrations when C1- was replaced by HCO3-. After correction for the change in liquid junction potential, the fall was 9.2 mmol/l for Na+ and 7.3 mmol/l for K+. On the basis of these findings we conclude that sodium bicarbonate and potassium bicarbonate are not fully dissociated in solution, and that NaHCO3(0) and KHCO3(0) do exist as chemical components with association constants of 0.72 and 0.55, respectively. Using these association constants, normal plasma will contain 1.2 mmol/l NaHCO3(0) and 0.03 mmol/l KHCO3(0). Thus NaHCO3(0) accounts for virtually the same amount of CO2 as the physically dissolved fraction. A review of all the currently known CO2 species in plasma suggests that there may be a residue of about 2 mmol/l of unknown CO2 species in normal plasma.     

Pseudomyocardial infarction and hyperkalemia: A case report and subject review

A case of diabetic ketoacidosis with hyperkalemia and ECG evidence of pseudomyocardial infarction is presented. Electrocardiogram abnormalities resolved shortly after treatment of the elevated potassium. The electrophysiology of hyperkalemia and theories to explain observed ECG changes are discussed. Pseudoinfarction changes that may be peculiar to patients with diabetic ketoncidosis and hyperkalemia are examined.     

Electroneutral K+/HCO3- cotransport in cells of medullary thick ascending limb of rat kidney.

The renal medullary thick ascending limb (MTAL) of the rat absorbs bicarbonate through luminal H+ secretion and basolateral HCO3- transport into the peritubular space. To characterize HCO3- transport, intracellular pH (pHi) was monitored by use of the pH-sensitive fluorescent probe (2',7')-bis-(carboxyethyl)-(5,6)-carboxyfluorescein in fresh suspensions of rat MTAL tubules. When cells were preincubated in HCO3-/CO2-containing solutions and then abruptly diluted into HCO3-/CO2-free media, the pHi response was an initial alkalinization due to CO2 efflux, followed by an acidification (pHi recovery). The pHi recovery required intracellular HCO3-, was inhibited by 10(-4) M diisothiocyanostilbene-2-2'-disulphonic acid (DIDS), and was not dependent on Cl- or Na+. As assessed by use of the cell membrane potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine, cell depolarization by abrupt Cl- removal from or addition of 2 mM barium into the external medium did not affect HCO3(-)-dependent pHi recovery, and the latter was not associated per se with any change in potential difference, which indicated that HCO3- transport was electroneutral. The HCO3(-)-dependent pHi recovery was inhibited by raising extracellular potassium concentration and by intracellular potassium depletion. Finally, as measured by use of a K(+)-selective extracellular electrode, a component of K+ efflux out of the cells was HCO3- dependent and DIDS sensitive. The results provide evidence for an electroneutral K+/HCO3- cotransport in rat MTAL cells.     

猪冠状动脉内皮细胞舒张过程中高钾溶液的抑制作用

背景:目前高钾心脏停搏液已在心脏手术中广泛应用。但有关高钾溶液对冠状动脉内皮细胞舒张血管功能影响的研究尚少。 目的:探讨高钾溶液对猪冠状动脉内皮细胞功能的影响及其机制。 设计:随机对照的实验研究。 地点、材料和干预:2000-06/09从北京大红门肉联厂共取17只刚宰杀的生猪猪心(雌雄不限)。均置入4℃的KH中,30min内送回北京阜外医院体外循环研究室,10min内选其心外膜下冠状动脉前降支中下三分之一,切成3段3mm的血管环。按单纯随机抽样法将49条猪冠状动脉血管环分为7组,每组7条;分别为对照组、20mmol/L高钾组、50mmol/L高钾组、四乙胺组、格列苯脲(商品名:优降糖)组、50mmol/L高钾 四乙胺组、50mmol/L高钾 格列苯脲组。采用器官槽法,分别用Krebs-Henseleit重碳酸盐缓冲液(Krebs solution, KH)、20,50mmol/L的高钾溶液浸泡血管环1h。 主要观察指标:7μmol/L环加氧酶阻断剂吲哚美辛(商品名:消炎痛)和300μmol/L一氧化氮合成酶阻断剂N-硝基-L-精氨酸、1mmol/L钙激动性钾通道阻断剂四乙胺或3μmol/L ATP敏感性钾通道阻断剂优降糖的作用下,30nmol/L前列腺素F_(2α)。引发的预收缩强度和非受体介导钙离子载体(1×10~(-10)～1×10~(-6)mol/L)引发的内皮源性舒张反应。 结果:格列苯脲组、50mmol/L高钾 四乙     

Chronic hyperkalemia impairs ammonium transport and accumulation in the inner medulla of the rat.

Previously we demonstrated in rats that chronic hyperkalemia had no effect on ammonium secretion by the proximal tubule in vivo but that high K+ concentrations inhibited ammonium absorption by the medullary thick ascending limb in vitro. These observations suggested that chronic hyperkalemia may reduce urinary ammonium excretion through effects on medullary transport events. To examine directly the effects of chronic hyperkalemia on medullary ammonium accumulation and collecting duct ammonium secretion, micropuncture experiments were performed in the inner medulla of Munich-Wistar rats pair fed a control or high-K+ diet for 7-13 d. In situ pH and total ammonia concentrations were measured to calculate NH3 concentrations for base and tip collecting duct and vasa recta. Chronic K+ loading was associated with significant systemic metabolic acidosis and a 40% decrease in urinary ammonium excretion. In control rats, 15% of excreted ammonium was secreted between base and tip collecting duct sites. In contrast, no net transport of ammonium was detected along the collecting duct in high-K+ rats. The decrease in collecting duct ammonium secretion in hyperkalemia was associated with a decrease in the NH3 concentration difference between vasa recta and collecting duct. The fall in the NH3 concentration difference across the collecting duct in high-K+ rats was due entirely to a decrease in [NH3] in the medullary interstitial fluid, with no change in [NH3] in the collecting duct. These results indicate that impaired accumulation of ammonium in the medullary interstitium, secondary to inhibition of ammonium absorption in the medullary thick ascending limb, may play an important role in reducing collecting duct ammonium secretion and urinary ammonium excretion during chronic hyperkalemia.     

Regional characterization of agonist and depolarization-induced phosphoinositide hydrolysis in rat brain

The ability of various receptor agonists and elevated extracellular potassium to initiate inositol phospholipid hydrolysis in various regions of rat brain was examined by using a direct assay which involves prelabeling slices with [3H]inositol and assaying [3H]inositol phosphates ([3H]IPs) in the presence of lithium. Both carbachol and noradrenaline evoked an increase in [3H]IP accumulation in all cerebral regions, although there were marked topographical differences in maximal responsiveness. These marked differences do not seem to be due to regional differences in coupling as similar apparent affinities of full agonists and the relative intrinsic activities of partial agonists were obtained. Both carbachol and noradrenaline responses were antagonized equipotently in all the brain regions tested by the muscarinic and alpha-1 antagonists atropine and prazosin, respectively. However, the putatively selective muscarinic antagonist pirenzepine did show an (approximately 10-fold) apparent selectivity against the carbachol responses elicited in the forebrain regions from those in the pons-medulla. Evaluation of extracellular potassium to 18 mM resulted in an increased production of [3H]IPs in all brain regions except the cerebellum. Incubation of slices with the cholinesterase inhibitor physostigmine (50 microM) and the dihydropyridine Ca++ channel activator BAY-K-8644 (1 microM) greatly enhanced the responses produced by elevated K+ in the forebrain regions but had markedly weaker effects in the hindbrain regions. The elevated K+ response alone and the enhanced response in the presence of BAY-K-8644 were both antagonized significantly by the dihydropyridine antagonist (+)-PN-205-033 in all brain regions, by 70 to 80 and 70 to 95%, respectively.     

Influence of epinephrine and propranolol on transmembrane K transfer in anuric dogs with hyperkalemia.

In anuric dogs K loaded by infusion of 2 mEq of KCl per kg per hr the quantity of K transferred to intracellular fluid in ureter-ligated animals is considerably less than in nephrectomized ones; the combination of ureter ligation and hyperkalemia seems to suppress transmembrane K transfer. In the present investigation we found that treatment of K loaded ureter-ligated dogs with epinephrine markedly increased the animals' ability to transfer K to intracellular fluid, and that administration of propranolol (with and without epinephrine) reduced K transfer capacity below the control level. Further, we found that propranolol treatment of K-loaded nephrectomized dogs produced a striking diminution of K transfer ability. The data suggest that beta adrenergic receptors are importantly involved in the transmembrane K transfer of K-loaded anuric dogs, and that ureter ligation and hyperkalemia suppress K transfer capacity by blocking beta receptors.     

Levalbuterol is as effective as racemic albuterol in lowering serum potassium

Albuterol is an effective treatment for hyperkalemia through beta-adrenergic induction of potassium (K+) uptake. Levalbuterol, the R-enantiomer of racemic albuterol, is used for the treatment of asthma and 0.63 mg of levalbuterol has the same therapeutic efficacy as 2.5 mg of albuterol but with a decreased adverse effects profile. We hypothesized that levalbuterol can reduce serum K+ levels similarly to albuterol when used in equipotent doses. In a randomized, double blind, placebo-controlled prospective study, we compared the K+-lowering effects of nebulized saline and equipotent bronchodilatory doses of albuterol (10 mg) and levalbuterol (2.5 mg) in healthy adult volunteers. Nine subjects entered each of the three study groups. Serum K+ was measured at baseline, at 30 min (immediately after treatment), at 60 min, and at 90 min. All adverse effects were recorded. The three groups had similar baseline K+ values. Immediately after nebulization, only levalbuterol showed a significant decrease in potassium level (p = 0.024). At 30 and 60 min after treatment, both albuterol and levalbuterol groups had significantly lower K+ values compared to placebo. No significant difference occurred between the albuterol and levalbuterol groups. Levalbuterol caused fewer reported adverse effects compared to albuterol.     

Thyrotoxic hypokalemic periodic paralysis triggered by high carbohydrate diet

Thyrotoxic hypokalemic periodic paralysis is an uncommon disorder characterized by elevated thyroid hormone, muscle weakness or paralysis, and intracellular shifts of potassium leading to hypokalemia. This article presents a case of thyrotoxic hypokalemic periodic paralysis in a 22-year old Hispanic man with nonfamilial thyrotoxic hypokalemic periodic paralysis triggered by a high carbohydrate diet. Laboratory studies showed elevated thyroid hormone, decreased thyroid-stimulating hormone, and hypokalemia. Rapid reduction in thyroid hormone levels by giving antithyroid drugs such as propylthiouracil and prompt potassium therapy with frequent measurements of serum potassium levels during therapy to avoid catastrophic hyperkalemia when potassium starts to shift back from intracellular to extracellular compartments can lead to successful outcome.     

Amiodarone Attenuates Fluoride-induced Hyperkalemia in Vitro

Poisoning by hydrofluoric acid or fluoride salts results in hypocalcemia, hypomagnesemia, and hyperkalemia with subsequent cardiac dysrhythmias. In previous studies, quinidine attenuated fluoride-induced hyperkalemia in vitro, and enhanced survival in animals. Like quinidine, amiodarone is a potassium channel blocker, although amiodarone is more familiar to clinicians due to its recent inclusion in advanced cardiac life support (ACLS) protocols. OBJECTIVES: This in-vitro study of human erythrocytes was designed to determine whether amiodarone could attenuate fluoride-induced hyperkalemia. METHODS: Six healthy volunteers each donated 60 mL of blood on three occasions. Each specimen was divided into 12 tubes, incubated at 37 degrees C, and oxygenated with room air. An aqueous sodium fluoride (F(-)) solution was added to tubes 1-9. Incremental amounts of quinidine were added to tubes 1-4 (Q(1)-Q(4)) to attain calculated concentrations of 0.73 microg/mL, 1.45 microg/mL, 2.9 microg/mL, and 5.8 microg/mL, respectively. Incremental amounts of amiodarone were added to tubes 5-8 (A(1)-A(4)) to attain calculated concentrations of 0.38 microg/mL, 0.75 microg/mL, 1.5 microg/mL, and 3.0 microg/mL, respectively. Tubes 9-12 were controls for each of F(-), amiodarone, quinidine alone, and no additive, respectively. Extracellular potassium concentration ([K(+)]) was followed, and an objective endpoint was defined as the rise in potassium concentration at 6 hours. RESULTS: Fluoride produced a significant change in [K(+)] by 6 hours in all samples. Quinidine produced a J-shaped curve in its ability to attenuate the rise in [K(+)], with only one concentration, Q(3), demonstrating significance versus tube 9 (control). Amiodarone also demonstrated a J-shaped dose-response effect, with statistical significance at A(1), A(2), and A(3) versus tube 9 (control). There was no significant difference among the effective concentrations (Q(3), A(1), A(2), and A(3)) of both drugs. CONCLUSIONS: In this in-vitro model using human blood, amiodarone and quinidine both attenuated F(-)-induced hyperkalemia. Further study is indicated to determine whether amiodarone enhances survival in F(-)-poisoned animals.