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Review
. 2015 Oct 29;10(10):CD010344.
doi: 10.1002/14651858.CD010344.pub2.

Pharmacological interventions for the acute management of hyperkalaemia in adults

Josh Batterink  1 , Tara A Cessford  2 , Robert Ai Taylor  1
Affiliations
Review

Pharmacological interventions for the acute management of hyperkalaemia in adults

Josh Batterink et al. Cochrane Database Syst Rev. .

Abstract
in English, Spanish

Background: Hyperkalaemia is a potentially life-threatening electrolyte disturbance which may lead to cardiac arrhythmias and death. Renal replacement therapy is known to be effective in treating hyperkalaemia, but safe and effective pharmacological interventions are needed to prevent dialysis or avoid the complications of hyperkalaemia until dialysis is performed.

Objectives: This review looked at the benefits and harms of pharmacological treatments used in the acute management of hyperkalaemia in adults. This review evaluated the therapies that reduce serum potassium as well as those that prevent complications of hyperkalaemia.

Search methods: We searched Cochrane Kidney and Transplant's Specialised Register to 18 August 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria: All randomised controlled trials (RCTs) and quasi-RCTs looking at any pharmacological intervention for the acute management of hyperkalaemia in adults were included in this review. Non-standard study designs such as cross-over studies were also included. Eligible studies enrolled adults (aged 18 years and over) with hyperkalaemia, defined as serum potassium concentration ≥ 4.9 mmol/L, to receive pharmacological therapy to reduce serum potassium or to prevent arrhythmias. Patients with artificially induced hyperkalaemia were excluded from this review.

Data collection and analysis: All three authors screened titles and abstracts, and data extraction and risk of bias assessment was performed independently by at least two authors. Studies reported in non-English language journals were translated before assessment. Authors were contacted when information about results or study methodology was missing from the original publication. Although we planned to group all studies of a particular pharmacological therapy regardless of administration route or dose for analysis, we were unable to conduct meta-analyses because of the small numbers of studies evaluating any given treatment. For continuous data we reported mean difference (MD) and 95% confidence intervals (CI).

Main results: We included seven studies (241 participants) in this review. Meta-analysis of these seven included studies was not possible due to heterogeneity of the treatments and because many of the studies did not provide sufficient statistical information with their results. Allocation and blinding methodology was poorly described in most studies. No study evaluated the efficacy of pharmacological interventions for preventing clinically relevant outcomes such as mortality and cardiac arrhythmias; however there is evidence that several commonly used therapies effectively reduce serum potassium levels. Salbutamol administered via either nebulizer or metered-dose inhaler (MDI) significantly reduced serum potassium compared with placebo. The peak effect of 10 mg nebulised salbutamol was seen at 120 minutes (MD -1.29 mmol/L, 95% CI -1.64 to -0.94) and at 90 minutes for 20 mg nebulised salbutamol (1 study: MD -1.18 mmol/L, 95% CI -1.54 to -0.82). One study reported 1.2 mg salbutamol via MDI 1.2 mg produced a significant decrease in serum potassium beginning at 10 minutes (MD -0.20 mmol/L, P < 0.05) and a maximal decrease at 60 minutes (MD -0.34 mmol/L, P < 0.0001). Intravenous (IV) and nebulised salbutamol produced comparable effects (2 studies). When compared to other interventions, salbutamol had similar effect to insulin-dextrose (2 studies) but was more effective than bicarbonate at 60 minutes (MD -0.46 mmol/L, 95% CI -0.82 to -0.10; 1 study). Insulin-dextrose was more effective than IV bicarbonate (1 study) and aminophylline (1 study). Insulin-dextrose, bicarbonate and aminophylline were not studied in any placebo-controlled studies. None of the included studies evaluated the effect of IV calcium or potassium binding resins in the treatment of hyperkalaemia.

Authors' conclusions: Evidence for the acute pharmacological management of hyperkalaemia is limited, with no clinical studies demonstrating a reduction in adverse patient outcomes. Of the studied agents, salbutamol via any route and IV insulin-dextrose appear to be most effective at reducing serum potassium. There is limited evidence to support the use of other interventions, such as IV sodium bicarbonate or aminophylline. The effectiveness of potassium binding resins and IV calcium salts has not been tested in RCTs and requires further study before firm recommendations for clinical practice can be made.

Antecedentes: La hiperpotasemia es un trastorno de los electrólitos potencialmente mortal que puede provocar arritmias cardíacas y muerte. Se sabe que el tratamiento de reemplazo renal es efectivo para tratar la hiperpotasemia, pero se necesitan intervenciones farmacológicas seguras y eficaces para prevenir la diálisis o evitar las complicaciones de la hiperpotasemia hasta que se realice la diálisis.

Objetivos: Esta revisión analizó los efectos beneficiosos y perjudiciales de los tratamientos farmacológicos utilizados en el tratamiento agudo de la hiperpotasemia en adultos. Esta revisión evaluó los tratamientos que reducen el potasio sérico, así como los que previenen las complicaciones de la hiperpotasemia. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en el registro especializado del Grupo Cochrane de Riñón y Trasplantes (Cochrane Kidney and Transplant Group) hasta el 18 de agosto de 2015 mediante contacto con el coordinador de búsqueda de ensayos y se utilizaron términos de búsqueda relevantes para esta revisión. CRITERIOS DE SELECCIÓN: En esta revisión se incluyeron todos los ensayos controlados aleatorios (ECA) y cuasialeatorios que analizaron cualquier intervención farmacológica para el tratamiento agudo de la hiperpotasemia en adultos. También se incluyeron los diseños no estándar de estudios como los estudios cruzados (crossover). Los estudios elegibles reclutaron adultos (18 años de edad o más) con hiperpotasemia, definida como una concentración de potasio sérico ≥ 4,9 mmol/l, para recibir tratamiento farmacológico con el objetivo de reducir el potasio sérico o prevenir las arritmias. Los pacientes con hiperpotasemia artificialmente inducida se excluyeron de esta revisión. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Los tres revisores examinaron los títulos y los resúmenes, y la extracción de los datos y al menos dos revisores realizaron la evaluación del riesgo de sesgo de forma independiente. Los estudios informados en revistas de idiomas diferentes al inglés se tradujeron antes de la evaluación. Se estableció contacto con los autores cuando faltó información acerca de los resultados o la metodología del estudio en la publicación original. Aunque se planificó agrupar todos los estudios de un tratamiento farmacológico particular independientemente de la vía de administración o la dosis para el análisis, no fue posible realizar los metanálisis debido al escaso número de estudios que evaluaron cualquier tratamiento administrado. Para los datos continuos se informó la diferencia de medias (DM) y los intervalos de confianza (IC) del 95%.

Resultados principales: Se incluyeron siete estudios (241 participantes) en esta revisión. El metanálisis de estos siete estudios incluidos no fue posible debido a la heterogeneidad de los tratamientos y a que muchos de los estudios no proporcionaron información estadística suficiente con sus resultados. La metodología de asignación y del cegamiento se describió de forma deficiente en la mayoría de los estudios. Ningún estudio evaluó la eficacia de las intervenciones farmacológicas para la prevención de resultados clínicamente relevantes como la mortalidad y las arritmias cardíacas; sin embargo, hay pruebas de que varios tratamientos de uso habitual reducen eficazmente los niveles de potasio sérico. El salbutamol administrado vía nebulizador o inhalador de dosis fija (IDF) redujo significativamente el potasio sérico en comparación con placebo. El efecto máximo de 10 mg de salbutamol nebulizado se observó a los 120 minutos (DM ‐1,29 mmol/l; IC del 95%: ‐1,64 a ‐0,94) y a los 90 minutos para 20 mg de salbutamol nebulizado (un estudio: DM ‐1,18 mmol/l; IC del 95%: ‐1,54 a ‐0,82). Un estudio informó que 1,2 mg de salbutamol vía IDF produjo una disminución significativa en el potasio sérico que comenzó a los diez minutos (DM ‐0,20 mmol/l; p < 0,05) y una disminución máxima a los 60 minutos (DM ‐0,34 mmol/l; p < 0,0001). El salbutamol intravenoso (IV) y nebulizado produjo efectos equivalentes (dos estudios). En comparación con otras intervenciones el salbutamol tuvo un efecto similar a la insulina‐dextrosa (dos estudios), pero fue más eficaz que el bicarbonato a los 60 minutos (DM ‐0,46 mmol/l; IC del 95%: ‐0,82 a ‐0,10; un estudio). La insulina‐dextrosa fue más eficaz que el bicarbonato IV (un estudio) y la aminofilina (un estudio). La insulina‐dextrosa, el bicarbonato y la aminofilina no se analizaron en estudios controlados con placebo. Ninguno de los estudios incluidos evaluó el efecto del calcio IV o las resinas quelantes de potasio en el tratamiento de la hiperpotasemia.

Conclusiones de los autores: Las pruebas para el tratamiento farmacológico agudo de la hiperpotasemia son limitadas, y no hay estudios clínicos que demuestren una reducción en los resultados adversos de los pacientes. De los agentes estudiados, el salbutamol por cualquier vía y la insulina‐dextrosa IV parecen ser más eficaces en la reducción del potasio sérico. Hay pruebas limitadas para apoyar la administración de otras intervenciones como bicarbonato de sodio IV o aminofilina. La efectividad de las resinas quelantes de potasio y las sales de calcio IV no se ha probado en ECA y requiere estudios adicionales antes de poder hacer recomendaciones sólidas para la práctica clínica.

PubMed Disclaimer

Conflict of interest statement

  1. Josh Batterink: none known

  2. Tara A Cessford: none known

  3. Robert AI Taylor: none known.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1 10 mg nebulised salbutamol versus placebo, Outcome 1 Serum potassium.
2.1
2.1. Analysis
Comparison 2 20 mg nebulised salbutamol versus placebo, Outcome 1 Serum potassium.
3.1
3.1. Analysis
Comparison 3 10 mg versus 20 mg nebulised salbutamol, Outcome 1 Serum potassium.
4.1
4.1. Analysis
Comparison 4 0.5 mg IV versus 10 mg nebulised salbutamol, Outcome 1 Serum potassium.
5.1
5.1. Analysis
Comparison 5 IV salbutamol versus IV insulin‐dextrose, Outcome 1 Serum potassium.
6.1
6.1. Analysis
Comparison 6 20 mg nebulised salbutamol versus IV insulin‐dextrose, Outcome 1 Serum potassium.
7.1
7.1. Analysis
Comparison 7 20 mg nebulised salbutamol versus 20 mg nebulised salbutamol plus IV insulin‐dextrose, Outcome 1 Serum potassium.
8.1
8.1. Analysis
Comparison 8 IV salbutamol versus IV salbutamol plus IV insulin‐dextrose, Outcome 1 Serum potassium.
9.1
9.1. Analysis
Comparison 9 IV salbutamol versus IV insulin‐dextrose plus sodium bicarbonate, Outcome 1 Serum potassium.
10.1
10.1. Analysis
Comparison 10 IV salbutamol versus IV salbutamol plus IV insulin‐dextrose plus IV sodium bicarbonate, Outcome 1 Serum potassium.
11.1
11.1. Analysis
Comparison 11 IV Insulin‐dextrose versus IV sodium bicarbonate, Outcome 1 Serum potassium.
12.1
12.1. Analysis
Comparison 12 IV insulin‐dextrose versus IV aminophylline, Outcome 1 Serum potassium.
13.1
13.1. Analysis
Comparison 13 IV insulin‐dextrose versus IV insulin‐dextrose plus 20 mg nebulised salbutamol, Outcome 1 Serum potassium.
14.1
14.1. Analysis
Comparison 14 IV insulin‐dextrose versus IV insulin‐dextrose plus IV salbutamol, Outcome 1 Serum potassium.
15.1
15.1. Analysis
Comparison 15 IV insulin‐dextrose versus IV insulin‐dextrose plus IV sodium bicarbonate, Outcome 1 Serum potassium.
16.1
16.1. Analysis
Comparison 16 IV insulin‐dextrose versus IV salbutamol IV plus IV sodium bicarbonate, Outcome 1 Serum potassium.
17.1
17.1. Analysis
Comparison 17 IV insulin‐dextrose versus IV insulin‐dextrose plus IV sodium bicarbonate plus IV salbutamol, Outcome 1 Serum potassium.
18.1
18.1. Analysis
Comparison 18 IV sodium bicarbonate versus IV salbutamol plus IV sodium bicarbonate, Outcome 1 Serum potassium.
19.1
19.1. Analysis
Comparison 19 IV sodium bicarbonate versus IV insulin‐dextrose plus IV salbutamol, Outcome 1 Serum potassium.
20.1
20.1. Analysis
Comparison 20 IV insulin‐dextrose plus sodium bicarbonate versus IV insulin‐dextrose plus IV salbutamol, Outcome 1 Serum potassium.
21.1
21.1. Analysis
Comparison 21 IV insulin‐dextrose plus IV sodium bicarbonate versus IV insulin‐dextrose plus IV sodium bicarbonate plus IV salbutamol, Outcome 1 Serum potassium.
22.1
22.1. Analysis
Comparison 22 IV salbutamol plus IV sodium bicarbonate versus IV insulin‐dextrose plus IV salbutamol, Outcome 1 Serum potassium.
23.1
23.1. Analysis
Comparison 23 IV insulin‐dextrose plus IV salbutamol versus IV insulin‐dextrose plus IV sodium bicarbonate plus IV salbutamol, Outcome 1 Serum potassium.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD010344

References

References to studies included in this review

Allon 1989 {published and unpublished data}
    1. Allon M, Copkney C, Dunlay RW. Acute treatment of hyperkalemia in hemodialysis (HD) patients with nebulized albuterol [abstract]. Kidney International 1989;35(1):238. [CENTRAL: CN‐00583886]
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Allon 1990 {published data only}
    1. Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney International 1990;38(5):869‐72. [MEDLINE: ] - PubMed
Balanzario 2003 {published data only}
    1. Balanzario JM, Nuevo JJ, Gaeta DE, Rivera LL, Ayala GV, Lopez LR. Effect of intravenous salbutamol vs salbutamol in micronebulizator in the hyperkalemia due to chronic renal failure [Efecto del salbutamol intravenoso vs salbutamol en micronebulizador en la hipercaliemia por insuficiencia renal cronica]. Medicina Interna de Mexico 2003;19(4):202‐5. [EMBASE: 2007509847]
Liou 1994 {published data only (unpublished sought but not used)}
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Mahajan 2001 {published data only}
    1. Mahajan SK, Mangla M, Kishore K. Comparison of aminophylline and insulin‐dextrose infusions in acute therapy of hyperkalemia in end‐stage renal disease patients. Journal of the Association of Physicians of India 2001;49:1082‐5. [MEDLINE: ] - PubMed
Mandelberg 1999 {published data only}
    1. Mandelberg A, Krupnik Z, Houri S, Smetana S, Gilad E, Matas Z, et al. Salbutamol metered‐dose inhaler with spacer for hyperkalemia: how fast? How safe?. Chest 1999;115(3):617‐22. [MEDLINE: ] - PubMed
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Allon 1993 {published data only}
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Allon 1995 {published data only}
    1. Allon M, Shanklin N. Effect of albuterol treatment on subsequent dialytic potassium removal. American Journal of Kidney Diseases 1995;26(4):607‐13. [MEDLINE: ] - PubMed
Allon 1996 {published data only}
    1. Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol. American Journal of Kidney Diseases 1996;28(4):508‐14. [MEDLINE: ] - PubMed
Blumberg 1998 {published data only}
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Buysse 2012 {published data only}
    1. Buysse JM, Huang IZ, Pitt B. PEARL‐HF: prevention of hyperkalemia in patients with heart failure using a novel polymeric potassium binder, RLY5016. Future Cardiology 2012;8(1):17‐28. [MEDLINE: ] - PubMed
De Wolf 1993 {published data only}
    1. Wolf A, Frenette L, Kang Y, Tang C. Insulin decreases the serum potassium concentration during the anhepatic stage of liver transplantation. Anesthesiology 1993;78(4):677‐82. [MEDLINE: ] - PubMed
Gruy‐Kapral 1998 {published data only}
    1. Gruy‐Kapral C, Emmett M, Santa Ana CA, Porter JL, Fordtran JS, Fine KD. Effect of single dose resin‐cathartic therapy on serum potassium concentration in patients with end‐stage renal disease. Journal of the American Society of Nephrology 1998;9(10):1924‐30. [MEDLINE: ] - PubMed
Kim 1996 {published data only}
    1. Kim HJ, Cho GS, Yang SC. The combined regimen of bicarbonate and beta2‐agonist (salbutamol) in acute therapy of hyperkalemia in hemodialysis patients [abstract]. Nephrology Dialysis Transplantation 1996;11(6):A161. [CENTRAL: CN‐00261267]
Kim 2007a {published data only}
    1. Kim DM, Chung JH, Yoon SH, Kim HL. Effect of fludrocortisone acetate on reducing serum potassium levels in patients with end‐stage renal disease undergoing haemodialysis. Nephrology Dialysis Transplantation 2007;22(11):3273‐6. [MEDLINE: ] - PubMed
Lens 1987 {published data only}
    1. Lens XM, Montoliu J, Cases A, Campistol JM. Absence of synergistic effect between salbutamol (S) and aminophylline (A) for the treatment of hyperkalemia in renal failure [abstract]. 24th Annual Congress. EDTA‐ERA; 1987 Oct 25‐29; West Berlin, Germany. 1987:75. [CENTRAL: CN‐00601990]
Lens 1989 {published data only}
    1. Lens XM, Montoliu J, Cases A, Campistol JM, Revert L. Treatment of hyperkalaemia in renal failure: salbutamol v. insulin. Nephrology Dialysis Transplantation 1989;4(3):228‐32. [MEDLINE: ] - PubMed
    1. Lens XM, Montoliu J, Cases A, Revert L. Treatment of hyperkalemia in renal failure: Salbutamol versus glucose and insulin [abstract]. Kidney International 1987;32(4):623. [CENTRAL: CN‐00583537]
McClure 1994 {published data only}
    1. McClure RJ, Prasad VK, Brocklebank JT. Treatment of hyperkalaemia using intravenous and nebulised salbutamol. Archives of Disease in Childhood 1994;70(2):126‐8. [MEDLINE: ] - PMC - PubMed
Mocan 1993 {published data only}
    1. Mocan MZ, Mocan G, Mocan H, Gorin B. Inhaler salbutamol for acute hyperkalemia in renal failure. Israel Journal of Medical Science 1993;29(1):39‐41. [MEDLINE: ] - PubMed
Mustaq 2006 {published data only}
    1. Mushtaq MA, Masood M. Treatment of hyperkalemia with salbutamol and insulin. Pakistan Journal of Medical Sciences 2006;22(2):176‐9. [EMBASE: 2006258815]
Pancu 2003 {published data only}
    1. Pancu D, LaFlamme M, Evans E, Reed J. Levalbuterol is as effective as racemic albuterol in lowering serum potassium. Journal of Emergency Medicine 2003;25(1):13‐6. [MEDLINE: ] - PubMed
Wang 1976 {published data only}
    1. Wang P, Clausen T. Treatment of attacks in hyperkalaemic familial periodic paralysis by inhalation of salbutamol. Lancet 1976;307(7953):221‐3. [MEDLINE: ] - PubMed

References to studies awaiting assessment

AMETHYST‐DN Study 2015 {published data only}
    1. Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: The AMETHYST‐DN Randomized Clinical Trial. JAMA 2015;314(2):151‐61. [MEDLINE: ] - PubMed
    1. Pitt B, Bushinsky D, Garza D, Stasiv Y, Du Mond C, Berman L, et al. 1‐year safety and efficacy of patiromer for hyperkalemia in heart failure patients with chronic kidney disease on renin‐angiotensin‐aldosterone system inhibitors [abstract]. Journal of the American College of Cardiology 2015;65(10 Suppl 1):A855. [EMBASE: 71833912]
Ash 2015 {published data only}
    1. Ash SR, Singh B, Lavin PT, Stavros F, Rasmussen HS. A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS‐9, is safe and efficient. Kidney International 2015;88(2):404‐11. [MEDLINE: ] - PMC - PubMed
    1. Singh B, Ash SA, Lavin PT, Yang A, Rasmussen HS. ZS‐9, a novel selective cation trap, leads to a rapid and predictable rate of decline in serum potassium in patients with chronic kidney disease and hyperkalemia [abstract]. Journal of the American College of Cardiology 2014;63(12 Suppl 1):A369. [EMBASE: 71406393]
    1. Singh B, Ash SR, Lavin PT, Yang A, Rasmussen HS. Acid‐base balance in a phase 2 trial of ZS‐9 for hyperkalaemia in patients with chronic kidney disease [abstract]. Nephrology Dialysis Transplantation 2014;29(Suppl 3):iii155. [EMBASE: 71491879]
Chothia 2014 {published data only}
    1. Chothia MY, Halperin ML, Rensburg MA, Hassan MS, Davids MR. Bolus administration of intravenous glucose in the treatment of hyperkalemia: a randomized controlled trial. Nephron. Physiology 2014;126(1):1‐8. [MEDLINE: ] - PubMed
HARMONIZE Study 2014 {published data only}
    1. El‐Shahawy MA, Rasmussen HS, Lavin PT, Yang A, Qunibi W. Treatment of hyperkalemia with ZS‐9, a selective nonabsorbed cation exchange resin, does not lead to hypomagnesemia: results from two multicenter, randomized, double blind, placebo‐controlled phase 3 trials [abstract]. Journal of the American College of Cardiology 2015;65(10 Suppl 1):A842. [EMBASE: 71833899]
    1. Kosiborod M, Rasmussen HS, Lavin P, Qunibi WY, Spinowitz B, Packham D, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA 2014;312(21):2223‐33. [MEDLINE: ] - PubMed
    1. Lerma E, Kosiborod M, Rasmussen HS, Lavin PT, Yang A, Qunibi W. Sodium zirconium cyclosilicate (ZS‐9) for hyperkalemia in stage 4/5 CKD subgroup of the phase 3 HARMONIZE study [abstract]. American Journal of Kidney Diseases 2015;65(4):A54. [EMBASE: 71875137]
    1. Peacock W, Rafique Z, Rasmussen H, Lavin P, Yang A, Levy P, et al. Sodium zirconium cyclosilicate (ZS‐9) for severe hyperkalemia: A post‐HOC analysis of the phase 3 HARMONIZE trial [abstract]. Academic Emergency Medicine 2015;22(5 Suppl 1):S69. [EMBASE: 71878784]
    1. Qunibi W, Kosiborod M, Rasmussen HS, Lavin PT, Yang A, Lerma E. Safety of sodium zirconium cyclosilicate (ZS‐9) in hyperkalemia: Analysis of GI effects in the phase 3 HARMONIZE study [abstract]. American Journal of Kidney Diseases 2015;65(4):A69. [EMBASE: 71875193]
Nasir 2014 {published data only}
    1. Nasir K, Ahmad A. Treatment of hyperkalemia in patients with chronic kidney disease: a comparison of calcium polystyrene sulphonate and sodium polystyrene sulphonate. Journal of Ayub Medical College, Abbottabad: JAMC 2014;26(4):455‐8. [MEDLINE: ] - PubMed
OPAL‐HK Study 2015 {published data only}
    1. Pitt B, Weir MR, Mayo MR, Garza D, Christ‐Schmidt H, Wittes J, et al. Patiromer lowers serum potassium and prevents recurrent hyperkalemia in patients with heart failure and CKD when treated with RAAS inhibitors: Results from OPAL‐HK [abstract]. European Journal of Heart Failure 2015;17:90. [EMBASE: 71902792] - PMC - PubMed
    1. Weir M, Bushinsky D, Mayo M, Garza D, Stasiv Y, Arthur S, et al. Patiromer reduced recurrent hyperkalemia in advanced CKD patients on RAASI [abstract]. American Journal of Kidney Diseases 2015;65(4):A90. [EMBASE: 71875267]
    1. Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. New England Journal of Medicine 2015;372(3):211‐21. [MEDLINE: ] - PubMed
Packham 2015 {published data only}
    1. El‐Shahawy M, Rasmussen HS, Lavin PT, Yang A, Packham DK. Acute‐phase efficacy of ZS‐9 in patients with baseline serum potassium levels above 5.5 MEQ/l: Analysis from a phase 3, multicenter, randomized, double blind, placebo‐controlled trial [abstract]. Journal of the American College of Cardiology 2015;65(10 Suppl 1):A878. [EMBASE: 71833935]
    1. El‐Shahawy MA, Rasmussen HS, Lavin PT, Yang A, Packham DK. Acute‐phase efficacy in a phase 3 multicenter, randomised, double‐blind, placebo‐controlled trial of ZS‐9 for hyperkalaemia [abstract]. Nephrology Dialysis Transplantation 2014;29(Suppl 3):iii178. [EMBASE: 71491947]
    1. El‐Shahawy MA, Singh B, Rasmussen HS, Lavin PT, Yang A, Qunibi W. Maintenance of normal serum K+ with ZS‐9 once daily in patients with CHF: Subgroup analysis of a phase 3 multicenter, randomised, double‐blind placebo‐controlled trial of patients with hyperkalaemia [abstract]. European Heart Journal 2014;35(Suppl 1):722. [EMBASE: 71649437]
    1. Packham DK, Rasmussen HS, Lavin PT, El‐Shahawy MA, Roger SD, Block G, et al. Sodium zirconium cyclosilicate in hyperkalemia. New England Journal of Medicine 2015;372(3):222‐31. [MEDLINE: ] - PubMed
    1. Qunibi W, Rasmussen HS, Lavin PT, Yang A, Singh B. ZS‐9 maintains normokalemia in hyperkalemic patients despite continuing RAAS inhibitors: a subgroup analysis from a phase 3 multicenter, randomized, double blind, placebo‐controlled trial [abstract]. Journal of the American College of Cardiology 2015;65(10 Suppl 1):A792. [EMBASE: 71833849]
Ramos‐Penafiel 2015 {published data only}
    1. Ramos‐Penafiel CO, Tovilla‐Ruiz CK, Galvan‐Flores F, Castaneda‐Rodriguez R, Espinoza MA, Duran‐Guzman R, et al. Efficacy of hyperK‐cocktail versus regular insulin in the management of hyperkalemia [Eficacia de hiperK‐cocktail vs insulina regular en el tratamiento de la hipercalemia]. Medicina Interna de Mexico 2015;31(1):50‐6. [EMBASE: 2015244383]

References to ongoing studies

NCT02163499 {published data only}
    1. Rasmussen H. Multicenter, multi‐dose, open‐label maintenance of long‐term safety and efficacy of sodium zirconium cyclosilicate (ZS) in hyperkalemia, including a randomized, double‐blind, placebo‐controlled withdrawal. clinicaltrials gov/ct2/show/NCT02163499 (accessed 18 August 2015).

Additional references

Alfonzo 2014
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Berlyne 1966
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