Clinical Review Hyperkalaemia

For the full versions of these articles see bmj.com Clinical Review

Hyperkalaemia

Moffat J Nyirenda,1 Justin I Tang,1 Paul L Padfield,2 Jonathan R Seckl1

1Endocrinology Unit, Centre for Hyperkalaemia is defined as serum potassium concen- Summary points Cardiovascular Science, Queen’s tration greater than 5.5 mmol/l. Its prevalence in the Medical Research Institute, Hyperkalaemia is usually caused by a combination of University of Edinburgh, Edinburgh general population is unknown, but it is thought to occur factors, but renal failure and drugs are often implicated 1 EH16 4TJ in 1-10% of patients admitted to hospital. The rate of Increased use of drugs that interact with the renin- 2Metabolic Unit, Western General morbidity and mortality associated with hyperkalaemia angiotensin-aldosterone system has caused the Hospital, Lothian University has risen greatly with the use of drugs that target the prevalence of hyperkalaemia to rise Hospitals NHS Trust, Edinburgh renin-angiotensin system, and since publication 10 years Correspondence to: M Nyirenda Hyperkalaemia can cause life threatening cardiac [email protected] ago of a randomised trial that showed that adding an arrhythmias and should be urgently managed aldosterone receptor antagonist to usual treatment for ECG changes correlate poorly with the degree of potassium Cite this as: BMJ 2009;339:b4114 congestive failure improved outcomes.2‑5 disturbance doi: 10.1136/bmj.b4114 Potassium is the most abundant cation in the human body and has key roles in the excitatory properties range from 40 mmol to 200 mmol per day, potassium needed for conduction of nerve impulses and muscle levels in serum remain within the relatively narrow contraction. Ninety eight per cent of the body’s potas- normal range. Derangements in potassium regulation, sium is in the intracellular fluid (concentration about and resultant changes in serum potassium concentra- 140 mmol/l), with only 2% in extracellular fluid (3.8-5.0 tion, may alter membrane excitability. Disorders of mmol/l). A complex interplay of regulatory mechanisms plasma potassium can therefore have profound effects is needed to maintain normal potassium balance, which on nerve, muscle, and cardiac function. involves the transfer of potassium between the extracellular and intracellular compartments (fig 1). In the What are the common causes of hyperkalaemia? long term potassium homoeostasis is mainly governed Multiple factors are often involved in the pathogen- by regulation of renal potassium excretion, notably by esis of hyperkalaemia, which commonly results from the actions of aldosterone (fig 2). These mechanisms decreased potassium excretion or increased release of ensure that although total daily potassium intake could potassium from cells.6 Hyperkalaemia can be spurious, and this possibility should be excluded first, except in severe cases when immediate treatment is needed.

ICF ECF Spurious hyperkalaemia [K+] = 140 [K+] = 4 Spurious hyperkalaemia (also called pseudohyperkalaemia) occurs when the reported laboratory potassium Insulin and β agonists shift potassium into cells values do not reflect actual in vivo concentrations— Nucleus K+ usually because platelets, leucocytes, or erythrocytes 2K+ have released intracellular potassium in vitro. It can ATPase Acidosis, hyperosmolarity, cell lysis shift potassium be excluded by sending a new sample for analysis or out of cells by simultaneously measuring potassium in plasma and 3Na+ serum; serum potassium concentration is usually 0.2– 0.4 mmol/l higher than that in plasma, owing to release during normal clotting. Box 1 lists common causes of spurious hyperkalaemia. Fig 1 | Schematic representation of regulation of transcellular potassium movement. Cellular potassium concentration is controlled by an active uptake mechanism regulated by Na-K-ATPase Hyperkalaemia due to increased potassium intake and a passive leak mechanism driven by the electrochemical gradient favouring potassium exit Excessive dietary intake of potassium is an uncommon from the cell. The rate of leak is dependent on the permeability of the potassium channels in the cause of hyperkalaemia, unless concurrent decreased cell membrane. Insulin and β2 adrenergic agonists (acting via cyclic AMP) promote potassium uptake into cells by stimulating the Na-K-ATPase pump. Insulin deficiency and β blockers excretion is a factor. High potassium intake should be increase potassium movement out of cells leading to hyperkalaemia. Acidosis, hyperosmolarity, avoided in patients with compromised renal function. or cell lysis also cause potassium to leave cells and can cause hyperkalaemia. ECF=extracelluar Box 2 lists foods rich in potassium. Hyperkalaemia fluid; ICF=intracellular fluid can also occur with blood transfusion (due to release

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Hyperkalaemia caused by shift of potassium out of cells Blood Aldosterone Lumen Several endogenous and exogenous factors can affect transfer of potassium between the extracellular and intracellular fluid to raise the concentration in serum. However, this mechanism is rarely the sole cause of Gene transcriptionan severe hyperkalaemia, except when excessive release in nucleusuc of intracellular potassium occurs with tissue injury or necrosis—for example, in rhabdomyolysis, tumour lysis, and severe burns. Box 3 shows causes of hyperkalaemia 3Na+ due to potassium redistribution. ATPase ENaC Na+ 2K+ Hyperkalaemia caused by reduced excretion of potassium The kidneys are the main route of potassium elimination, and renal failure is the major cause of hyperkalaemia, K+ K+ K+ accounting for up to 75% of cases of severe hyperkalae- 1 H+ mia. In patients with chronic kidney disease, the capac- ity to excrete potassium is reasonably well maintained until renal failure is advanced (glomerular filtration rate <15-20 ml/min); until then hyperkalaemia is not usually seen unless intake of potassium is high or the patient is Fig 2 | Schematic representation of mineralocorticoid action in target cell in renal cortical collecting duct. On entering the cell, aldosterone binds to the mineralocorticoid receptors taking a drug that promotes hyperkalaemia. (MR). The ligand-receptor complex translocates to the nucleus and binds to hormone response Damage to the juxtaglomerular apparatus with result- elements, increasing transcription of specific genes, which in turn signal to increase activities ing deficit in renin production can cause hyporeninaemic of apical sodium channels (ENaC) and the basolateral Na-K-ATPase. This leads to increased hypoaldosteronism, which can also cause hyperkalaemia intracellular potassium concentration and a greater diffusion gradient for potassium to diffuse in the absence of severe renal failure. Hyporeninaemic into the lumen. Increased uptake of sodium leads to more negative lumen charge, facilitating hypoaldosteronism is also known as type 4 renal tubular the diffusion of potassium into the lumen. Disorders of aldosterone action are common causes acidosis because it is often, but not always, associated of hyperkalaemia. Renal potassium excretion is also affected by urine flow rate and delivery of with mild to moderate metabolic acidosis with a nor- sodium to the distal nephron mal anion gap. Diabetic nephropathy is the most com- of potassium from haemolysis), when intravenous mon underlying cause. Hypoaldosteronism can also be potassium is administered too rapidly in treatment of caused by primary disorders of the adrenal gland (such hypokalaemia, or when total parenteral nutrition con- as Addison’s disease or congenital steroidogenic enzyme tains high concentrations of potassium. defects, most commonly 21 hydroxylase deficiency) or by reduced mineralocorticoid activity due to resistance to the action of aldosterone action in the kidney. The lat- Box 1 | Causes of spurious hyperkalaemia ter problem is often seen in sickle cell anaemia, systemic Laboratory error lupus erythematosus, amyloidosis, and obstructive neph- Delayed analysis ropathy or with use of potassium sparing diuretics. In Blood collected from vein into which potassium is infused rare cases, it is caused by mutations of the gene encoding Excessive tourniquet or repeated fist clenching the mineralocorticoid receptor or its major downstream Haemolysis via small needle or traumatic venepuncture targets, including the epithelial sodium channel ENaC. Prolonged storage of blood In general, an abnormality in mineralocorticoid Severe leucocytosis or thrombocytosis level by itself does not produce hyperkaelemia if Uncommon genetic disorders (familial sufficient amount of sodium is delivered to the dis- pseudohyperkalaemia) tal nephron. Thus, patients with Addison’s disease do not usually exhibit hyperkalaemia if they have adequate salt intake; it is only when sodium intake is Box 2 | Foods with high potassium content restricted or they otherwise become volume depleted Salt substitutes that hyperkalaemia develops. Disturbances of urinary Figs flow rate or delivery of sodium to the distal neph- Molasses ron are therefore also important in the pathogenesis Seaweed of hyperkalaemia. These defects can be intrinsic or Chocolates (more commonly) caused by drugs (box 3, box 4). Bran cereal, wheat germ Vegetables (such as spinach, tomatoes, mushrooms, Which drugs cause hyperkalaemia? carrots, potatoes, broccoli, lima beans, cauliflower) Drugs can interfere with potassium homoeostasis by Dried fruit, nuts, and seeds promoting transcelluar potassium shift or by impair- Fruits (such as banana, kiwi fruit, orange, mango, ing renal potassium excretion (for example, through cantaloupe) effects on aldosterone action, sodium delivery to the Adapted from the National Kidney Foundation website (www.kidney. 1 3 6 org/news/newsroom/fs_new/potassiumCKD.cfm) distal nephron, or function of collecting tubules). In a prospective study of 242 consecutive patients admitted

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with hyperkalaemia, 63% were taking drugs that interfere Box 3 | Causes of hyperkalaemia with potassium balance.1 The risk of hyperkalaemia is Potassium redistribution (intracellular to extracellular fluid) particularly great when such drugs are given to patients Exercise with underlying renal insufficiency. The elderly and Tissue necrosis or lysis (rhabdomyolysis, tumour lysis patients with diabetes are especially susceptible. Doc- syndrome, severe burns) tors should therefore prescribe such drugs with caution Insulin deficiency in these populations; it is best to start with low doses and Metabolic acidosis (especially with mineral acids) to recheck serum potassium within a week of starting Hyperosmolarity (hyperglycaemia, mannitol infusion) the drug, and with each increase in dose. There are no Drugs (for example, succinylcholine, β blockers, digoxin consensus guidelines as to what constitutes timely follow- toxicity) up, but the frequency with which serum potassium is Hyperkalaemic periodic paralysis monitored will depend on the level of renal impairment, Decreased excretion of potassium the presence of diabetes, and concurrent use of other Renal failure (glomerular filtration rate <20 ml/min) hyperkalaemia inducing medications. Particular caution Decreased mineralocorticoid activity should be exercised in patients with underlying cardiac Hyporeninaemic hypoaldosteronism (chronic renal failure, conduction defects, in whom even minor increases in diabetic nephropathy, NSAIDs) serum potassium can precipitate severe arrhythmias. A Adrenal insufficiency (Addison’s disease, congenital comprehensive list of drugs associated with hyperkalae- enzyme defects) mia is given in box 4. We will briefly discuss some of the Aldosterone blocking drugs (see box 4) most commonly prescribed ones. End organ unresponsiveness to aldosterone (sickle cell Angiotensin converting enzyme (ACE) inhibitors and anaemia, systemic lupus erythematosus, amyloidosis, and angiotensin II receptor blockers (ARBs) are increasingly obstructive nephropathy) used for renoprotection and to reduce cardiovascular Decreased urine flow rate or sodium delivery to distal nephron mortality in patients at high risk, particularly those with Severe volume contraction diabetes. They also are standard treatment in the man- Rare genetic disorders, such as Gordon’s syndrome agement of patients with chronic heart failure. ACE inhibitors and ARBs predispose to hyperkalaemia because they impair aldosterone secretion and reduce renal perfusion (and thus glomerular filtration rate), both Box 4 | Drug induced hyperkalaemia of which decrease excretion of potassium by the kidneys. Drugs that alter transmembrane potassium movement However, in general, they do not cause hyperkalaemia in β blockers patients with normal renal function; indeed, the degree Digoxin of aldosterone suppression is usually not sufficient to Hyperosmolar solutions (mannitol, glucose) substantially impair potassium excretion unless pre- Suxamethonium existing hypoaldosteronism from other causes (disease Intravenous cationic amino acids state or from other drugs) is present. Unfortunately, most Potassium containing agents patients targeted for renovascular benefits of these drugs Potassium supplements (such as those with diabetes, renal failure, or heart fail- Salt substitutes ure) are at high risk of developing hyperkalaemia. About Herbal medicines (such as alfalfa, dandelion, horsetail, 10% of outpatients develop hyperkalaemia within a year 1 3 7 8 milkweed, and nettle) of starting treatment with ACE inhibitors or ARBs. Stored red blood cells (haemolysis releases potassium) Moreover, these drugs contribute to hyperkalaemia in 10-38% of patients admitted to hospital with the condi- Drugs that reduce aldosterone secretion tion, with the risk increasing substantially when higher ACE inhibitors doses are used or when they are used in combination or Angiotensin II receptor blockers with other hyperkalaemia inducing drugs.5 NSAIDs Aldosterone (mineralocorticoid) receptor antago- Heparins nists are also commonly prescribed to treat patients Antifungals (ketoconazole, fluconazole, itraconazole) with congestive cardiac failure since the Randomized Ciclosporin Aldactone Evaluation Study showed that the addition of Tacrolimus spironolactone to standard treatment is associated with Drugs that block aldosterone binding to mineralocorticoid significant reduction in morbidity and mortality.2 Seri- receptor ous hyperkalaemia occurred in only 2% of patients in Spironolactone the study, where the average serum creatinine concen- Eplerenone tration was 106 µmol/l and the dose of spironolactone Drospirenone did not exceed 25 mg daily. By contrast, population Drugs that inhibit activity of epithelial sodium channel based time-series analyses have demonstrated signifi- Potassium sparing diuretics (amiloride, triamterene) cant increases in rates of hospitalisation and mortal- Trimethoprim ity from hyperkalaemia.4 9 10 This is probably because Pentamidine these studies included patients with more severe renal dysfunction who were given higher doses of

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spironolactone. These patients were also more likely Sources and selection criteria than those in the clinical trial to be taking potassium We searched PubMed for articles whose titles included the supplements or other drugs that impair potassium excre- terms “hyperkalaemia” or “potassium homoeostasis” and tion. The risk was highest in patients who took spironol- restricted the search to articles published in English in the actone in combination with ACE inhibitors or ARBs, past 15 years. We also searched contemporary textbooks. particularly in elderly patients with renal failure.11 12 Non-steroidal anti-inflammatory drugs (NSAIDs) show gradual progression in changes, others progress inhibit renin secretion (leading to hypoaldosteronism from benign to potentially fatal ventricular arrhythmias and reduced potassium excretion) and can impair renal without warning. function. These agents should be prescribed judiciously Assessment of a patient with hyperkalaemia should in patients with diabetes or renal insufficiency, particu- include a thorough review of the medical history to larly if they are concurrently receiving ACE inhibitors identify potential contributing factors such as renal fail- or ARBs.13 ure, diabetes, adrenal insufficiency, and use of drugs that cause hyperkalaemia. Laboratory blood tests How is hyperkalaemia diagnosed? should be directed towards causes suggested by the Hyperkalaemia is often asymptomatic and discov- history and physical examination, and should include ered on routine laboratory tests. When symptoms urea, creatinine, electrolytes, and serum osmolarity are present, they are non-specific and predominantly (acute increase in osmolarity can cause potassium to related to muscular function (paresthesiae, muscle exit from cells). Analysis of urine potassium concen- weakness, fatigue) or cardiac function (palpitations). trations could help to ascertain whether renal potas- Hyperkalaemia may produce progressive abnormali- sium elimination is appropriate. In selected patients, ties on the electrocardiogram (ECG), including peaked additional specialised tests such as measurement of the T waves, flattening or absence of P waves, widening fractional excretion of potassium or transtubular potas- of QRS complexes, and sine waves (fig 3).14 How- sium gradient may be useful in distinguishing between ever, electrocardiography is not a sensitive method renal and non-renal causes of hyperkalaemia.15 for detecting hyperkalaemia. In a study by Acer and colleagues nearly half the patients with serum potas- How is severe hyperkalaemia managed? sium concentration greater than 6.5 mmol/l did not Guidelines for treatment of hyperkalaemia are based have ECG changes.1 Moreover, whereas some patients on consensus or expert opinion because of a lack of controlled clinical trials.16 Treatment should be aimed at restoring normal potassium balance, preventing serious Tall peaked T wave complications, and treating the underlying causes. Figure 4 shows a general approach in management of patients with hyperkalaemia. Mild to moderate hyperkalaemia can be treated with a loop diuretic to increase urinary potassium excretion. Dietary potassium is restricted and hyperkalaemic drugs should be minimised or withdrawn. If a patient has renal failure a diuretic may not be effective and other measures, including dialysis, may be needed. Tall peaked Severe hyperkalaemia is a life threatening state because T wave it can cause catastrophic cardiac and neuromuscular effects, such as cardiac arrest and paralysis of the respiratory muscles. Therefore prompt and aggressive treat- Loss of P wave ment is necessary. Most authorities consider that serum potassium concentration of greater than 6.0 mmol/l with ECG changes, or greater than 6.5 mmol/l regardless of the ECG, represents severe hyperkalaemia that warrants urgent treatment.17 18 If the patient’s ECG suggests hyperkalaemia, or in a clinical scenario such as cardiac arrest Widened QRS with tall T wave in a patient having chronic dialysis, for example, therapy is frequently started without waiting for laboratory confir- mation. Other factors that might necessitate pre-emptive treatment of hyperkalaemia include a rapid rise of serum potassium, the presence of significant acidosis, and rapid deterioration in renal function. Most guidelines and experts advise that severe hyperkalaemia should be treated in an inpatient setting to allow continuous cardiac monitoring, because even patients without symptoms or ECG changes can swiftly 14 Fig 3 | ECG changes in patients with hyperkalaemia develop life threatening arrhythmias. Although urgent

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augment the effect of insulin. Patients with acidosis may Raised potassium level also be treated with intravenous sodium bicarbonate (500 ml of a 1.26% solution [75 mmol] over 60 minutes) Is the increase genuine? (see box 1 for causes of spurious hyperkalaemia) although the benefit is uncertain and routine bicarbonate YesNo treatment for hyperkalaemia remains controversial. 18 21 Is potassium >6.5 mmol/l or No treatment needed Thirdly, further interventions are undertaken to are ECG changes present? remove potassium from the body. Potent loop diuret- YesNo ics (for example, 40-80 mg of intravenous furosemide) enhance renal potassium excretion by increasing urine Emergency treatment* Non-emergency treatment† flow and sodium delivery to the distal nephron. However, diuretics only work if the patient has adequate renal func- Give IV calcium gluconate Dietary restriction Stop any potassium sparing diuretic tion, and many patients with hyperkalaemia have acute Potassium binding resin or chronic renal failure. Cation exchange resins, which Give IV insulin with glucose Use of diuretic depending on underlying cause and/or nebulised salbutamol remove potassium from extracellular fluid via the gut in exchange for sodium, are also commonly used, although 22 Give furosemide and/or calcium resonium their effectiveness is debatable. They act more quickly Consider dialysis when given as enemas (for example, calcium resonium 30 mg) than when given orally (15 mg four time a day); Long term measures to prevent recurrence it may take 6 hours to achieve a full effect. Dialysis is the definitive treatment for patients with severe hyperkalae- *Management of severe hyperkalaemia should be undertaken in an inpatient setting with continuous cardiac monitoring mia and advanced chronic kidney disease. †Patients with moderate hyperkalaemia (serum potassium 6.0-6.5 mmol/l) should probably be admitted to hospital for supervised lowering of serum potassium Long term management of hyperkalaemia After acute treatment, measures should be estab- Fig 4 | Algorithm for diagnosis of hyperkaelemia. IV=intravenous lished to prevent recurrence of hyperkalaemia. The first step is to carefully review the patient’s dialysis to remove potassium from the body would be medication and to avoid or minimise drugs that the definitive treatment, delays in starting this treatment increase potassium retention. Because ACE inhibi- are inevitable. A 2005 Cochrane systematic review of tors and ARBs slow the progression of chronic emergency interventions for hyperkalaemia recom- mended that immediate temporising treatment incor- Tips for non-specialistS porates three key measures.19 • In patients without predisposition to hyperkalaemia, The first step is to stabilise the myocardium to reduce recheck serum potassium to rule out spurious its susceptibility to ventricular arrhythmias. Intravenous hyperkalaemia, unless ECG changes suggest that calcium is used to directly antagonise the membrane emergency treatment is warranted effects of hyperkalaemia, stabilising cardiac conduc- • Do not overlook hidden causes of hyperkalaemia, such tion. Calcium gluconate in a volume of 10 ml of 10% as herbs, salt substitutes, and over the counter drugs solution is infused over 3–5 minutes with cardiac moni- (such as NSAIDs) toring. Calcium infusion does not affect serum potas- • ACE inhibitors and ARBs should be started at low doses sium level, but beneficial ECG changes can be seen and potassium checked a week after starting treatment after 1-3 minutes of administration and the effect can or after increasing dose last for 30-60 minutes. The infusion can be repeated if • All patients with hyperkalaemia should undergo 12 lead no effect is seen within 5-10 minutes. Caution should electrocardiography be exercised when replacing calcium in patients tak- • ECG changes and cardiac arrhythmias associated with ing digoxin because calcium potentiates myocardial hyperkalaemia are true medical emergencies toxicity to digoxin.20 The second step is to shift potassium from the extracellular to the intracellular fluid compartment so as to Questions for ongoing and future research rapidly decrease serum potassium. This shift is achieved • How important are the different risk factors for hyperkalaemia, and how does the clinician define them by administration of insulin or β2 agonist, both of which stimulate the Na+/K+ pump. Insulin is given as an intra- quantitatively in an individual? venous bolus along with sufficient glucose to prevent • With increasing use of cardioprotective or renoprotective development of hypoglycaemia (usually 10 units of insu- treatments that promote potassium retention, what is the best way to monitor potassium levels? lin with 50 ml of 50% dextrose given over 5 minutes). The hypokalaemic effect of this treatment can be seen • Do patients with chronic hyperkalaemia actually achieve within 20 minutes, peaking between 30 and 60 min- balance for potassium—if so, how is this balance achieved? utes, and it may last for 6 hours. Salbutamol is the most commonly used selective β agonist. It is usually given • Further understanding of the molecular pathways 2 responsible for maintaining potassium concentration through a nebuliser (10-20 mg in 4 ml of saline). An in extracellular fluid, to develop novel therapeutic effect may be seen in 30 minutes, with maximum effect strategies to treat life threatening hyperkalaemia. at 90–120 minutes. Salbutamol can be used alone or to

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Additional educational resources 2 Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart Resources for clinicians failure. N Engl J Med 1999;341:709-17. 3 Perazella MA. Drug-induced hyperkalemia: old culprits and new • Rose BD. Clinical manifestations and treatment of hyperkalemia. UpToDate (online). offenders. Am J Med 2000;109:307-14. Version 15.1. 2007 (www.uptodateonline.com) 4 Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, et al. Rates of hyperkalemia after publication of the randomized aldactone • Mahoney BA, Smith WAD, Lo D, Tsoi K, Tonelli M, Clase C. Emergency interventions for evaluation study. N Engl J Med 2004;351:543-51. hyperkalaemia. Cochrane Database Syst Rev 2005;(2):CD003235 (www.cochrane.org/ 5 Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N reviews/en/ab003235.html) Engl J Med 2008;358:1547-59. • Guidelines and Audit Implementation Network (www.gain-ni.org/Guidelines/ 6 Hollander-Rodgriguez JC, Calvert JF Jr. Hyperkalemia. Am Fam Physician hyperkalaemia_guidelines.pdf)—guidelines for the treatment of hyperkalaemia in adults 2006;73:283-90. 7 Ahuja T, Freeman D Jr, Mahnken JD, Agraharkar M, Siddiqui M, Memon • American Heart Association (http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA. A. Predictors of the development of hyperkalemia in patients using 105.166563v1.pdf)—Current (2005) guidelines for treatment of hyperkalaemia angiotensin-converting enzyme inhibitors. Am J Nephrol 2000;20:268-72. 8 Reardon LC, Macpherson DS. Hyperkalemia in outpatients using • US Department of Agriculture (www.health.gov/dietaryguidelines/dga2005/document/ angiotensin-converting enzyme inhibitors. Arch Intern Med 1998;158:26- html/appendixB.htm#appB1)— list of potassium and calorific content of different foods 32. 9 Cruz CS, Cruz AA, Marcilio de Souza CA. Hyperkalemia in congestive heart Resources for patients failure patients using ACE inhibitors and spironolactone. Nephrol Dial Transplant 2003;18:1814-9. • National Kidney Foundation (www.kidney.org/atoz/content/potassium.cfm)—information 10 Bozkurt B, Agoston I, Knowlton AA. Complications of inappropriate use of on potassium content of foods spironolactone in heart failure: when an old medicine spirals out of new guidelines. J Am Coll Cardiol 2003;41:211-4. 11 Svensson M, Gustafsson F, Galatius S, Hildebrandt PR, Atar D. How prevalent is hyperkalemia and renal dysfunction during treatment with renal disease, use of other measures to control the spironolactone in patients with congestive heart failure? J Card Fail hyperkalaemia or dose reduction are preferable to 2004;10:297-303. discontinuing these drugs. Dietary advice to restrict 12 Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. potassium intake to 40-60 mmol a day is prudent. Cochrane Database Syst Rev 2009;(3):CD007004. Diuretics may be effective in promoting renal potas- 13 Perazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. sium loss to prevent recurrence of hyperkalaemia. Am J Med 2001;111:64-7. Thiazide diuretics may be used in patients with pre- 14 Slovis C, Jenkins R. ABC of clinical electrocardiography: conditions not primarily affecting the heart. BMJ 2002;324:1320-3. served renal function, but are usually ineffective when 15 Ethier JH, Kamel KS, Magner PO, Lemann J, Halperin ML. The transtubular the glomerular filtration rate is less than 40 ml/min, potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kid Dis 1990;4:309-15. when a loop diuretic such as furosemide is preferable. 16 Kim H-J, Han S-W. Therapeutic approach to hyperkalaemia Nephron Fludrocortisone may be used in patients with hyporen- 2002;92(suppl 1):33-40. 17 Charytan D, Goldfarb DS. Indications for hospitalization of patients with inaemic hypoaldosteronism. However, this drug can hyperkalemia. Arch Intern Med 2000;160:1605-11. cause fluid retention and hypertension, and should be 18 Greenberg A. Hyperkalaemia: treatment options. Semin Nephrol used with caution—particularly in patients with type 2 1998;18:46-57. 19 Mahoney BA, Smith WA, Lo DS, Tsoi K, Tonelli M, Clase CM. Emergency diabetes, who often have co-existing hypertension. interventions for hyperkalaemia. Cochrane Database Syst Rev Contributors: MJN wrote the first draft. All authors took part in researching 2005;(2):CD003235. and writing the paper. MJN edited the final manuscript and is guarantor. 20 Davey M. Calcium for hyperkalemia in digoxin toxicity. Emerg Med J 2002;19:183. Competing interests: None declared. 21 Allon M, Shanklin N. Effect of bicarbonate administration on plasma Provenance and peer review: Commissioned, externally peer reviewed. potassium in dialysis patients: interactions with insulin and albuterol. Am J Kidney Dis 1996;28:508-14. 1 Acker CG, Johnson JP, Palevsky PM, Greenberg A. Hyperkalemia in 22 Kamel KS, Wei C. Controversial issues in the treatment of hyperkalaemia. hospitalized patients: causes, adequacy of treatment, and results of Nephrol Dial Transplant 2003;18:2215-8. an attempt to improve physician compliance with published therapy guidelines. Arch Intern Med 1998;158:917-24. Accepted: 5 September 2009

Corrections and clarifications Potential causes and health effects of rising global food prices Picture of the week In this Analysis article by Karen Lock and colleagues (BMJ The Picture of the week in the print publication of 19 September 2009;339:b2403, print publication 1 Aug, pp 269-72), the graphs 2009 showed an example of the “lying down game,” and the for figure 1 and figure 2 were wrongly switched at page proof stage. caption gave a link to a doc2doc discussion about certain hospital The captions to the graphs were correctly placed and numbered, staff who got into trouble for playing the game. The correct link is but the graph that was with the figure 1 caption should have been http://ow.ly/oI2I. with the figure 2 caption, and vice versa. Minerva Rosiglitazone and pioglitazone: Beware macular oedema In a picture item in Minerva (BMJ 2009;339:b3319, print The second author of this letter by Rosemary G Lambley and publication 22 Aug, p 466) we spelt the author’s name wrongly. He colleagues (BMJ 2009; 339: b3856, print publication 26 Sep, p is John-Paul [not Jean-Paul] Smith. 709) is Kaveh Vahdani [not Kave Vahdani, as published]. A/H1N1 flu pandemic: By any maths would be as weak Sarcoidosis: Technique to enable diagnosis During the editing of this Letter by Ron Law (BMJ 2009;339:b3959, During the editing of this Letter by Andrew R L Medford and print publication 3 Oct, p 768) we managed to delete a reference colleagues (BMJ 2009;339:b3962, print publication 3 Oct, pp relating to New Zealand infection rates. This is: Baker MG, Wilson 766-7) we managed to transpose the authors’ addresses. Thus, N, Huang QS,Paine S, Lopez L, Bandaranayake D, et al. Pandemic Dr Medford is at North Bristol Lung Centre, Southmead Hospital, influenza A(H1N1)v in New Zealand: the experience from April Bristol, whereas Sanjay Agrawal and Jonathan Bennett are at the to August 2009. Euro Surveill 2009;14(34):pii=19319. www. Department of Respiratory Medicine, Glenfield Hospital, Leicester. eurosurveillance.org/ViewArticle.aspx?ArticleId=19319.

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