HYPERKALAEMIA GUIDELINE 2019

Clinical Practice Guidelines

Treatment of Acute Hyperkalaemia in Adults

Authors:

Dr Annette Alfonzo

Consultant Nephrologist & Clinical Director, Faculty member of European Resuscitation Council,

Victoria Hospital Kirkcaldy, Fife

Dr Alexander Harrison

Consultant in Nephrology and Intensive Care,

Brighton and Sussex University Hospitals NHS Trust

Dr Richard Baines

Consultant Nephrologist and Head of Renal and Transplant Service,

University Hospitals of Leicester NHS Trust

Dr Ann Chu

Academic Clinical Fellow Renal Medicine and Medical Education, Imperial College London

Mr Simon Mann

Renal Pharmacist, Lancashire Teaching Hospitals NHS Foundation Trust

Mr Murdoch MacRury

Patient representative

Final version: June 2020

Review date: June 2025

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 2

Endorsements

The National Institute for Health and Care Excellence (NICE) has accredited the process used by the Renal

Association to produce its Clinical Practice Guidelines. Accreditation is valid for 5 years from January 2017.

More information on accreditation can be viewed at www.nice.org.uk/accreditation

Method used to arrive at a recommendation

The recommendations for the first draft of this guideline resulted from a collective decision reached by

informal discussion by the authors and, whenever necessary, with input from the Chair of the Clinical

Practice Guidelines Committee. If no agreement had been reached on the appropriate grading of a

recommendation, a vote would have been held and the majority opinion carried. However this was not

necessary for this guideline.

Conflicts of Interest Statement

All authors made declarations of interest in line with the policy in the Renal Association Clinical Practice

Guidelines Development Manual. Further details can be obtained on request from the Renal Association.

Acknowledgements

The authors wish to thank Dr Charlie Tomson, retired Consultant Nephrologist and former Chair of the UK

Renal Association (2010-2012), Professor Ketan Dhatariya, Chair of the Joint British Diabetes Society for In-

Patient Care (JBDS-IP), Dr Clare Crowley, Consultant Pharmacist (Medicines Saftety) at Oxford University

Hospitals and Mr Murdoch MacRury for his insight into the treatment of hyperkalaemia from a patient’s

perspective. We also wish to acknowledge the contributions of the original writing group whose

collaborative efforts produced the 2014 Hyperkalaemia guideline.

 
Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020                     3 
 
Contents 
Executive Summary of changes since 2014 Hyperkalaemia Guideline ................................................................5 
Guideline development ........................................................................................................................................7 
Introduction ..........................................................................................................................................................8 
Summary of Clinical Practice Guidelines for Hyperkalaemia ............................................................................ 10 
Tables ................................................................................................................................................................. 17 
Figures ............................................................................................................................................................... 18 
Summary of Audit Measures ............................................................................................................................. 19 
Hyperkalaemia in the Community (Guidelines 1.1 – 12.1) ................................................................................ 22 
Introduction ................................................................................................................................................... 22 
Patient monitoring  (Guidelines 1.1-1.2) ....................................................................................................... 26 
Management of patients receiving RAASi drugs  (Guidelines 2.1-2.7).......................................................... 30 
Threshold for treatment of hyperkalaemia  (Guideline 3.1) ......................................................................... 33 
Indications for hospital assessment  (Guidelines 4.1 - 4.2) ........................................................................... 35 
Treatment:  Dietary interventions  (Guideline 5.1) ....................................................................................... 37 
Treatment:  Sodium bicarbonate  (Guideline 6.1) ......................................................................................... 39 
Treatment:  Diuretics  (Guideline 7.1) ........................................................................................................... 41 
Treatment:  Calcium resonium  (Guideline 8.1) ............................................................................................ 42 
Treatment:  Patiromer  (Guidelines 9.1-9.3) ................................................................................................. 44 
Treatment:  Sodium zirconium cyclosilicate  (Guidelines 10.1-10.3) ............................................................ 49 
Prevention  (Guidelines 11.1-11.3) ................................................................................................................ 53 
Treatment Algorithm: Community  (Guideline 12.1) .................................................................................... 57 
Hyperkalaemia in Hospital ................................................................................................................................. 59 
Introduction ................................................................................................................................................... 59 
Clinical assessment (Guidelines 13.1-13.2) ................................................................................................... 61 
ECG and cardiac monitoring (Guidelines 14.1-14.2) ..................................................................................... 63 
Laboratory analysis (Guidelines 15.1-15.3) ................................................................................................... 68 
Treatment (Guidelines 16.1-16.6) ................................................................................................................. 73 
Blood monitoring (Guidelines 17.1-17.2) .................................................................................................... 101 
Treatment of hyperkalaemia in haemodialysis patients (Guidelines 18.1-18.4) ........................................ 105 
Referral to specialist services and escalation of care (Guidelines 19.1-19.6) ............................................. 110 
Minimum standards for patient transfer (Guidelines 20.1-20.2) ................................................................ 112 
Prevention (Guidelines 21.1-21.4) ............................................................................................................... 114 

 
Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020                     4 
 
Treatment Algorithm:  Hospital (Guidelines 22.1) ...................................................................................... 118 
Hyperkalaemia in Resuscitation ...................................................................................................................... 120 
Introduction ................................................................................................................................................. 120 
References ................................................................................................................................................... 121 
Hyperkalaemic cardiac arrest – Special circumstance (Guidelines 23.1-23.2) ............................................ 121 
Audit Measure ............................................................................................................................................. 121 
Rationale (Guidelines 23.1) ......................................................................................................................... 121 
References ................................................................................................................................................... 122 
Resuscitation strategy in dialysis patients  (Guidelines 24.1-24.2) ............................................................. 123 
Treatment:  Calcium chloride (Guidelines 25.1) .......................................................................................... 128 
Treatment:  Insulin-glucose (Guidelines 25.2)............................................................................................. 129 
Treatment:  Sodium bicarbonate (Guidelines 25.3) .................................................................................... 132 
Treatment:  Initiation of dialysis during cardiac arrest (Guidelines 25.4) ................................................... 133 
Prevention (Guidelines 26.1-26.2) ............................................................................................................... 140 
Lay summary .................................................................................................................................................... 143 
Appendices ...................................................................................................................................................... 144 
Appendix 1: Oral potassium lowering drugs. .............................................................................................. 145 
Appendix 2:  Summary of clinical trials of oral potassium lowering drugs ................................................. 146 
Appendix 3A: Drug administration and safety -  IV calcium preparations .................................................. 147 
Appendix 3B: Drug administration and safety –Insulin-glucose infusion .................................................... 149 
Appendix 3C: Drug administration and safety - Salbutamol ....................................................................... 151 
Appendix 3D: Drug administration and safety – Patiromer ........................................................................ 152 
Appendix 3E: Drug administration and safety – Sodium zirconium cyclosilicate........................................ 153 
Appendix 3F: Drug administration and safety – Calcium resonium ............................................................ 154 
Appendix 4 – Sine wave ECG ....................................................................................................................... 155 
Appendix 5 – Hyperkalaemia Algorithm - Community ................................................................................ 156 
Appendix 6 – Hyperkalaemia Algorithm – Hospital ..................................................................................... 157 
Appendix 7 – Hyperkalaemia Algorithm – Resuscitation ............................................................................ 158 
Abbreviations................................................................................................................................................... 159 
 
 
 
 

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 5

Executive Summary of changes since 2014 Hyperkalaemia Guideline

Format of the Guideline

The 2020 Hyperkalaemia guideline has been divided into 3 sections to allow easy navigation:

• Section I: Management of Hyperkalaemia in the Community

• Section II: Management of Hyperkalaemia in Hospital

• Section III: Management of Hyperkalaemia in Resuscitation

New therapies for treating hyperkalaemia

Sodium zirconium cyclosilicate (SZC)

SZC is an oral potassium binder approved by NICE in September 2019 for the following indications:

• life-threatening hyperkalaemia (K

≥ 6.5 mmol/l) alongside standard treatment with insulin-glucose

and salbutamol.

• confirmed serum K

≥ 6.0 mmol/l in out-patients with CKD Stage 3b-5 (not on dialysis) or heart

failure receiving a sub-optimal dose of RAASi therapy.

Patiromer

Patiromer is an oral potassium binder approved by NICE in February 2020 for the following indications:

• life-threatening hyperkalaemia (K

≥ 6.5 mmol/l) alongside standard treatment with insulin-glucose

and salbutamol.

• confirmed serum K

≥ 6.0 mmol/l in out-patients with CKD Stage 3b-5 (not on dialysis) or heart

failure receiving a sub-optimal dose of RAASi therapy or who are not taking RAASi because of

hyperkalaemia.

NICE has recommended that therapy with either SZC or Patiromer is started in secondary care and

discontinued if RAASi therapy is stopped.

New recommendations for therapies in treating hyperkalaemia

Insulin-glucose infusion

The 2014 Hyperkalaemia Guideline recommended the use of 10 units of soluble insulin with 25g glucose. In

recent years, there have been multiple published reports of a high incidence of iatrogenic hypoglycaemia.

This has prompted review of this treatment regimen.

The most consistent risk factor for iatrogenic hypoglycaemia is a low pre-treatment blood glucose. Reducing

the dose of insulin alone did not consistently reduce hypoglycaemic episodes. There is more evidence to

support increasing the total glucose load to 50g. The lowest risk of severe hypoglycaemia was associated

with continuous delivery of glucose.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 6

Preserving efficacy is essential in treating hyperkalaemia. There is some evidence to suggest that

conventional dose insulin (10 units) has a greater K

-lowering effect than low dose insulin. Analysis of

studies using 10 units insulin also show a trend towards greater efficacy with worsening hyperkalaemia.

These observations require confirmation before a reduction in insulin dose can be recommended.

The 2020 Hyperkalaemia Guideline for moderate or severe hyperkalaemia recommends:

• Give 10 units soluble insulin with 25g glucose

• Give 10% glucose by infusion @ 50ml/hr for 5 hours (25g) to patients with a pre-treatment blood

glucose < 7.0 mmol/l to prevent hypoglycaemia.

• Blood glucose monitoring is required for up to 12 hours after glucose-insulin infusion.

Hyperkalaemic Cardiac Arrest

This is the most serious consequence of hyperkalaemia and yet the most effective treatment, dialysis, is

rarely used. The largest study of hyperkalaemic cardiac arrest demonstrated that survival in patients with

extreme hyperkalaemia (K > 9.0 mmol/l) treated without dialysis was very poor. Over the past three

decades, successful outcomes with all dialysis modalities have been reported during CPR. ECMO enhances

neurological outcome. This approach will be guided by the suitability of the patient and availability of clinical

expertise and equipment.

The 2020 Hyperkalaemia Guideline suggests that dialysis is considered for refractory hyperkalaemic cardiac

arrest and provides a protocol for the initiation of dialysis during resuscitation.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 7

Guideline development

Purpose

This guideline provides an updated version of the original Hyperkalaemia guideline (2014). The main aims

are to provide evidence-based recommendations for the treatment of chronic hyperkalaemia in the

community, acute hyperkalaemia in the hospital setting and to reduce the risk of complications associated

with hyperkalaemia itself and its treatment.

Scope

The original RA Hyperkalaemia Guideline (2014) focussed predominantly the management of hyperkalaemia

in secondary care. The current RA Hyperkalaemia Guideline (2020) provides a comprehensive overview of

the detection and treatment of hyperkalaemia in the community and hospital settings.

Review of Evidence

The literature was reviewed using a multiple database search - PubMed (1960-2020), Ovid MEDLINE (1946-

2020), EMBASE (1974-2020), Science Direct (1995-2020), The Cochrane Library (1995-2020), Web of

Knowledge (2001-2020) for all human studies published in English pertaining to the treatment of

hyperkalaemia in adults. Websites searches included National Institute for Health and Care Excellence

(NICE), Scottish Medicines Consortium (SMC), Healthcare Improvement Scotland, Medicines and Healthcare

products Regulatory Agency (MHRA) and European Medicines Agency (EMA).

The keywords used for literature search were – hyperkalaemia, potassium, treatment,

pseudohyperkalaemia, spurious hyperkalaemia, ECG, point or care, near patient testing, insulin,

hypoglycaemia, salbutamol, calcium, bicarbonate, diet, resonium, patiromer, sodium zirconium cyclosilicate,

dialysis, arrhythmias, resuscitation, and cardiac arrest.

The writing process followed the Renal Association Guideline development manual. The guideline comprises

of a series of guideline statements accompanied by supporting evidence and audit measures. The

recommendations in each guideline statement have been graded using the GRADE system

(www.gradeworkinggroup.org) in evaluating the strength of each recommendation (1 = strong, 2 = weak)

and quality of evidence (A= high, B = moderate, C= low, D = very low). Each guideline statement begins with

a recommendation (Grade 1 evidence) or a suggestion (Grade 2 evidence).

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 8

Introduction

There is no universally accepted definition of hyperkalaemia. This guideline has adopted the European

Resuscitation Council (ERC) Guideline definition with a threshold serum potassium (K+) level of ≥ 5.5

mmol/l, established in 2005

and maintained to current date.

2, 3

It is further classified by severity into mild

(5.5-5.9 mmol/l), moderate (6.0-6.4 mmol/l) or severe (≥ 6.5 mmol/l). Hyperkalaemia is a common medical

emergency when it presents acutely. The presence of persistent hyperkalaemia in the community is often

regarded as chronic, usually in the context of drugs that exacerbate the condition.

The incidence of hyperkalaemia in hospital patients ranges from 1.1% and 10%.

4-8

The incidence in the

community varies dependent on the case mix of the population studied. Studies in the general population

report an incidence of hyperkalaemia (K+ >5.5 mmol/l) ranging from 2.3 - 7.2% in patients with an eGFR > 60

ml/min

9, 10

and 2.9 - 40% in patients with an eGFR < 30 ml/min.

11-13

In-hospital mortality is significantly higher in patients with hyperkalaemia (18.1%) compared to those with

hypokalaemia (5.0%) or normokalaemia (3.9%).

A U-shaped association between serum potassium and

mortality has been shown in patients with ischaemic heart disease,

CKD

11, 15, 16

and in patients receiving

longterm haemodialysis (HD).

Patients with severe hyperkalaemia (K+ > 6.5 mmol/l) are most at risk and in

one report, the hospital mortality was 30.7%.

The treatment of hyperkalaemia is likely to evolve in the coming years with the availability of novel drugs

and the development of new strategies to improve safety. Clinical decisions on when to treat and how

aggressively to treat require a patient centred approach guided by the clinical setting and rate of change in

serum K+ level. Patients with moderate levels of hyperkalaemia pose the greatest dilemma, especially when

acuity is low, but warrant intervention to avoid deterioration. Severe hyperkalaemia risks arrhythmias and

cardiac arrest, therefore prompt recognition and intervention is required.

References

1. Soar, J., et al., European Resuscitation Council Guidelines for Resuscitation 2005 - Section 7. Cardiac

arrest in special circumstances. Resuscitation, 2005. 67: p. S135-S170.

2. Soar, J., et al., European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac

arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidental

hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution.

Resuscitation, 2010. 81(10): p. 1400-33.

3. Truhlar, A., et al., European Resuscitation Council Guidelines for Resuscitation 2015: Section 4.

Cardiac arrest in special circumstances. Resuscitation, 2015. 95: p. 148-201.

4. Acker, C.G., et al., Hyperkalemia in hospitalized patients: causes, adequacy of treatment, and results

of an attempt to improve physician compliance with published therapy guidelines. Arch Intern Med,

1998. 158(8): p. 917-24.

5. Paice, B., et al., Hyperkalaemia in patients in hospital. Br Med J (Clin Res Ed), 1983. 286(6372): p.

1189-92.

6. Moore, M.L. and R.R. Bailey, Hyperkalaemia in patients in hospital. N Z Med J, 1989. 102(878): p.

557-8.

7. Einhorn, L.M., et al., The frequency of hyperkalemia and its significance in chronic kidney disease.

Arch Intern Med, 2009. 169(12): p. 1156-62.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 9

8. Conway, R., et al., Serum potassium levels as an outcome determinant in acute medical admissions.

Clin Med (Lond), 2015. 15(3): p. 239-43.

9. Chang, A.R., et al., Antihypertensive Medications and the Prevalence of Hyperkalemia in a Large

Health System. Hypertension, 2016. 67(6): p. 1181-8.

10. Horne, L., et al., Epidemiology and health outcomes associated with hyperkalemia in a primary care

setting in England. BMC Nephrol, 2019. 20(1): p. 85.

11. Korgaonkar, S., et al., Serum potassium and outcomes in CKD: insights from the RRI-CKD cohort study.

Clin J Am Soc Nephrol, 2010. 5(5): p. 762-9.

12. Sarafidis, P.A., et al., Prevalence and factors associated with hyperkalemia in predialysis patients

followed in a low-clearance clinic. Clin J Am Soc Nephrol, 2012. 7(8): p. 1234-41.

13. Turgutalp, K., et al., Community-acquired hyperkalemia in elderly patients: risk factors and clinical

outcomes. Ren Fail, 2016. 38(9): p. 1405-1412.

14. Goyal, A., et al., Serum potassium levels and mortality in acute myocardial infarction. JAMA, 2012.

307(2): p. 157-64.

15. Hayes, J., et al., Association of hypo- and hyperkalemia with disease progression and mortality in

males with chronic kidney disease: the role of race. Nephron Clin Pract, 2012. 120(1): p. c8-16.

16. Collins, A.J., et al., Association of Serum Potassium with All-Cause Mortality in Patients with and

without Heart Failure, Chronic Kidney Disease, and/or Diabetes. Am J Nephrol, 2017. 46(3): p. 213-

221.

17. Kovesdy, C.P., et al., Serum and dialysate potassium concentrations and survival in hemodialysis

patients. Clin J Am Soc Nephrol, 2007. 2(5): p. 999-1007.

18. An, J.N., et al., Severe hyperkalemia requiring hospitalization: predictors of mortality. Crit Care, 2012.

16(6): p. R225.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 10

Summary of Clinical Practice Guidelines for Hyperkalaemia

Section I: Community

Guideline 1.1 – Monitoring of patients at risk of Hyperkalaemia in the community.

We recommend that patients known to have CKD, heart failure and/or diabetes, who are at risk of

hyperkalaemia, undergo regular blood monitoring at a frequency (2-4 times per year) dependent on level of

renal function and degree of proteinuria. (1B)

Guideline 1.2.1 – Monitoring of patients after an episode of mild hyperkalaemia detected in the

community.

We recommend that the serum K+ is repeated within 3 days, or as soon as feasible, if an episode of mild

hyperkalaemia (K+ 5.5 – 5.9 mmol/l) is detected unexpectedly in the community. (1C)

Guideline 1.2.2 – Monitoring of patients after an episode of moderate hyperkalaemia detected in the

community.

We recommend that the serum K+ is repeated within 1 day of an episode of moderate hyperkalaemia (K+ 6.0

– 6.4 mmol/l) when detected in the community. (1C)

Guideline 1.2.3 – Monitoring of patients after an episode of severe hyperkalaemia detected in the

community.

We recommend that patients with severe hyperkalaemia (K+ ≥ 6.5 mmol/l) detected in the community are

admitted for immediate assessment and treatment. (1B)

Guideline 2.1 – Assessment of patients prior to initiation of ACE-I or ARB.

We recommend that urea and electrolytes should be assessed prior to initiation of ACE-I or ARB and these

drugs should be used with caution if the serum K+ is > 5.0 mmol. (1A)

Guideline 2.2 – Assessment of patients prior to initiation of Mineralocorticoid Receptor Antagonists

(MRA).

We suggest that initiation of MRAs should be avoided in patients with a baseline serum K+ > 5.0mmol/l or

eGFR < 30 ml/min. (1B)

Guideline 2.3 – Monitoring of patients after initiation of ACE-I and ARB.

We recommend that urea and electrolytes should be assessed at 1 – 2 weeks after initiation of ACE-I or ARB

and after every dose titration. (1A)

Guideline 2.4 – Monitoring of patients after initiation of MRAs.

We recommend that urea and electrolytes should be assessed at 1 week after initiation of MRA or after dose

up-titration, then monthly for the first 3 months, 3-monthly for the first year and 4-monthly thereafter. (1A)

Guideline 2.5 – Management of hyperkalaemia in patients treated with RAASi drugs.

We suggest increased frequency of monitoring in patients with a serum K+ between 5.5-5.9 mmol/l and

consideration of dose reduction of RAASi drugs (ACE-I, ARB, MRA). (1B)

Guideline 2.6 – Management of hyperkalaemia in patients treated with RAASi drugs during acute illness.

We recommend that RAASi drugs be withheld during acute intercurrent illness (e.g. sepsis, hypovolaemia

and/or AKI) at all severities of hyperkalaemia. (1D)

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 11

Guideline 2.7 – Cessation of RAASi drugs in patients with moderate or severe hyperkalaemia.

We recommend cessation of RAASi drugs in patients with serum K ≥ 6 mmol/l who do not meet the criteria

for treatment with patiromer or sodium zirconium cyclosilicate. (1B)

Guideline 3.1 – Threshold for treating Hyperkalaemia in the community.

We recommend that interventions to lower serum potassium be instituted in patients with a serum K+ ≥ 5.5

mmol/l. (1B)

Guideline 4.1 – Indication for assessment in hospital for patients with severe hyperkalaemia detected in

the community.

We recommend urgent hospital assessment for all patients with severe hyperkalaemia (serum K+ ≥ 6.5

mmol/l) detected in the community. (1A)

Guideline 4.2 – Indication for assessment in hospital for patients with mild-moderate hyperkalaemia

detected in the community.

We suggest hospital assessment for acutely unwell patients with mild (serum K+ 5.5 – 5.9 mmol/l) or

moderate hyperkalaemia (serum K+ 6.0 - 6.4 mmol/l), particularly in the presence of an acute kidney injury.

(1B)

Guideline 5.1 – Dietary Intervention for managing Hyperkalaemia in the community.

We recommend that a low potassium diet is instituted for patients with persistent hyperkalaemia with a

serum K+ > 5.5 mmol/l. (1B)

Guideline 6.1 – Sodium bicarbonate for management of Hyperkalaemia in the community

We recommend that sodium bicarbonate is used in CKD patients with a serum bicarbonate level < 22 mmol/l

with or without hyperkalaemia. (1B)

Guideline 7.1 – Use of diuretics for managing Hyperkalaemia in the community

We suggest that loop diuretics may be a useful adjunct for the treatment of chronic hyperkalaemia in

patients who are non-oliguric and volume replete. (2C)

Guideline 8.1 – Calcium resonium for the management of Hyperkalaemia in the community.

We suggest that calcium resonium may be used as a short-term measure to lower serum potassium to a

level of ≤ 5 mmol/l in patients with mild to moderate hyperkalaemia. (2C)

Guideline 9.1 – Patiromer for the management of Hyperkalaemia in the community

We recommend that Patiromer is an option in the management of persistent hyperkalaemia with a

confirmed serum K+ ≥ 6.0 mmol/l in out-patients with CKD Stage 3b-5 (not on dialysis) or heart failure

receiving a sub-optimal dose or not receiving RAASi therapy due to hyperkalaemia. (1A)

Guideline 9.2 – Patiromer for the management of Hyperkalaemia

We recommend that treatment with Patiromer is discontinued if RAASi therapy is stopped. (1A)

Guideline 9.3 – Patiromer for the management of Hyperkalaemia

We recommend that Patiromer is initiated in secondary care only. (1A)

Guideline 10.1 – Sodium Zirconium Cyclosilicate for the management of Hyperkalaemia

We recommend that Sodium Zirconium Cyclosilicate (SZC) is an option in out-patients for the management

of persistent hyperkalaemia with a confirmed serum K+ ≥ 6.0 mmol/l in patients with CKD Stage 3b-5 (not on

dialysis) or heart failure receiving a sub-optimal dose of RAASi therapy. (1A)

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 12

Guideline 10.2 – Sodium Zirconium Cyclosilicate for the management of Hyperkalaemia

We recommend that treatment with Sodium Zirconium Cyclosilicate (SZC) in out-patients is discontinued if

RAASi therapy is stopped. (1A)

Guideline 10.3 – Sodium Zirconium Cyclosilicate for the management of Hyperkalaemia

We recommend that Sodium Zirconium Cyclosilicate (SZC) is initiated in secondary care only. (1A)

Guideline 11.1 – Prevention of Hyperkalaemia in the community: monitoring

We recommend monitoring of renal function in patients at risk of hyperkalaemia with known CKD, heart

failure, diabetes and in any patient taking RAASi medication. (1A)

Guideline 11.2 – Prevention of Hyperkalaemia in the community: prescribing

We recommend caution in prescribing trimethoprim to patients with renal impairment or those taking RAASi

drugs. (1A)

Guideline 11.3 – Prevention of Hyperkalaemia in the community: sick day rules

We recommend that healthcare professionals provide advice to patients regarding the risks of AKI and

hyperkalaemia during acute illness and measures to avoid these complications. (1B)

Guideline 12.1 – Treatment Algorithm for Hyperkalaemia in the community

We recommend that the treatment of hyperkalaemia in patients in the community and out-patient setting is

guided by its severity and clinical condition of the patient as summarised in the treatment algorithm. (1B)

Section II: Hospital

Guideline 13.1 – Hyperkalaemia: Clinical Assessment; History and examination

We recommend that all patients presenting with hyperkalaemia undergo a comprehensive medical and drug

history and clinical examination to determine the cause of hyperkalaemia. (1B)

Guideline 13.2 – Hyperkalaemia: Clinical Assessment; NEWS

We recommend that all patients with known or suspected hyperkalaemia undergo urgent clinical assessment

using an early warning scoring system to assess level of acuity. (1C)

Guideline 14.1 – Hyperkalaemia: ECG

We recommend that all hospitalised patients with a serum K + level ≥ 6.0 mmol/L have an urgent 12-lead

ECG (electrocardiogram) performed and assessed for changes of hyperkalaemia. (1B)

Guideline 14.2 – Hyperkalaemia: Cardiac monitoring

We recommend a minimum of continuous 3-lead ECG monitoring for all patients with a serum K+ ≥ 6.5

mmol/L, patients with features of hyperkalaemia on 12-lead ECG, and in patients with a serum K+ 6.0-6.4

mmol/L who are clinically unwell or in whom a rapid rise in serum K+ is anticipated, ideally in a higher-

dependency setting. (1C)

Guideline 15.1 – Hyperkalaemia: Laboratory tests

We recommend that a lithium heparin anti-coagulated specimen is the sample type of choice when rapid

turnaround of urea and electrolytes results is required. (1B)

Guideline 15.2 – Hyperkalaemia: Blood gas analysis

We recommend that in emergencies, K+ level is measured from an arterial or venous blood sample using a

point-of-care blood gas analyser whilst awaiting the results from a formal laboratory measurement. (1B)

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 13

Guideline 15.3 – Hyperkalaemia: Pseudo-hyperkalaemia

We recommend that urea and electrolytes are measured using paired lithium heparin and clotted serum

samples from a large vein using gentle traction with prompt laboratory analysis if pseudo-hyperkalaemia is

suspected. (1A)

Guideline 16.1 – Hyperkalaemia: Summary of treatment strategy

We recommend that the treatment of hyperkalaemia in hospital follow a logical 5-step approach. (1B)

Guideline 16.2 – Hyperkalaemia: STEP 1 - Protect the heart; intravenous calcium salts

We recommend that intravenous calcium chloride or calcium gluconate, at an equivalent dose (6.8mmol), is

given to patients with hyperkalaemia in the presence of ECG evidence of hyperkalaemia. (1C)

Guideline 16.3.1 – Hyperkalaemia: STEP 2 - Shift K+ into cells; insulin-glucose infusion

We recommend that insulin-glucose (10 units soluble insulin in 25g glucose) by intravenous infusion is used

to treat severe hyperkalaemia (K+ ≥ 6.5 mmol/l). (1B)

Guideline 16.3.2 – Hyperkalaemia: STEP 2 - Shift K+ into cells; insulin-glucose infusion

We suggest that insulin-glucose (10 units soluble insulin in 25g glucose) by intravenous infusion is used to

treat moderate hyperkalaemia (K+ 6.0 – 6.4 mmol/l). (2C)

Guideline 16.3.3 – Hyperkalaemia: STEP 2 - Shift K+ into cells; avoiding hypoglycaemia

We suggest pre-emptive initiation of an infusion of 10% glucose at 50ml/ hour for 5 hours (25g) following

insulin-glucose treatment in patients with a pre-treatment blood glucose < 7.0 mmol/l to avoid

hypoglycaemia (target blood glucose 4-7 mmol/l). (2D)

Guideline 16.4.1 – Hyperkalaemia: STEP 2 – Shift K+ into cells; Salbutamol

We recommend nebulised salbutamol 10-20 mg is used as adjuvant therapy for severe (K+ ≥ 6.5 mmol/L)

hyperkalaemia. (1B)

Guideline 16.4.2 – Hyperkalaemia: STEP 2 – Shift K+ into cells; Salbutamol

We suggest that nebulised salbutamol 10-20 mg may be used as adjuvant therapy for moderate (K+ 6.0-6.4

mmol/L) hyperkalaemia. (2C)

Guideline 16.4.3 – Hyperkalaemia: STEP 2 – Shift K+ into cells; Salbutamol

We recommend that salbutamol is not used as monotherapy in the treatment of severe hyperkalaemia. (1A)

Guideline 16.5 Hyperkalaemia: STEP2 –Shift K into cells; Sodium bicarbonate

We suggest that intravenous sodium bicarbonate infusion is not used routinely for the acute treatment of

hyperkalaemia. (2C)

Guideline 16.6.1 – Hyperkalaemia: STEP 3 – Remove K+ from body; Potassium binders

We recommend that Sodium Zirconium Cyclosilicate is used as an option in the emergency management of

acute life-threatening hyperkalaemia (serum K+ ≥ 6.5 mmol/l). (1B)

Guideline 16.6.2 – Hyperkalaemia: STEP 3 – Remove K+ from body; Potassium binders

We suggest that Patiromer is an option for the emergency management of acute life-threatening

hyperkalaemia (serum K+ ≥ 6.5 mmol/l). (1C)

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 14

Guideline 16.6.3 – Hyperkalaemia: STEP 3 – Remove K+ from body; Cation-exchange resin

We suggest that calcium resonium is not used in the emergency management of severe hyperkalaemia, but

may be considered in patients with moderate hyperkalaemia. (2B)

Guideline 17.1.1 – Hyperkalaemia: STEP 4 - Blood monitoring; serum potassium

We recommend that the serum K+ is monitored closely in all patients with hyperkalaemia to assess efficacy

of treatment and to monitor for rebound hyperkalaemia after the initial response to treatment wanes. (1B)

Guideline 17.1.2 – Hyperkalaemia: STEP 4 - Blood monitoring; serum potassium

We suggest that serum K+ is assessed at least 1, 2, 4, 6 and 24 hours after identification and treatment of

moderate or severe hyperkalaemia. (2C)

Guideline 17.2 – Hyperkalaemia: STEP 4 - Blood monitoring; blood glucose

We recommend that the blood glucose concentration is monitored at regular intervals (0, 15, 30, 60, 90, 120,

180, 240, 360, 480 and 720 minutes) up to 12 hours after administration of insulin-glucose infusion in all

patients with hyperkalaemia. (1C)

Guideline 18.1 - Hyperkalaemia: Treatment in haemodialysis patients

We recommend that haemodialysis patients with severe hyperkalaemia (serum K+ 6.5 mmol/L) receive

dialysis treatment urgently. (1A)

Guideline 18.2 - Hyperkalaemia: Treatment in haemodialysis patients

We recommend that haemodialysis patients with severe hyperkalaemia (serum K+ 6.5 mmol/L) and toxic

ECG changes be treated with intravenous calcium salt to reduce risk of arrhythmias even when dialysis is

immediately available. (1C)

Guideline 18.3 - Hyperkalaemia: Treatment in haemodialysis patients

We recommend that haemodialysis patients with severe hyperkalaemia (serum K+ 6.5 mmol/L) be treated

with standard medical therapies to lower serum potassium if dialysis is not immediately available. (1B)

Guideline 18.4 - Hyperkalaemia: Treatment in haemodialysis patients

We suggest that potassium binders may be considered to reduce the risk of hyperkalaemia during the inter-

dialytic period. (1B)

Guideline 19.1 - Hyperkalaemia: Specialist Referral

We suggest that patients with severe hyperkalaemia (serum K+ 6.5 mmol/L) be referred to their local renal

or critical care team for an urgent opinion, guided by the clinical scenario and its persistence after initial

medical treatment. (2C)

Guideline 19.2 - Hyperkalaemia: Referral to critical care services

We recommend that for patients with severe hyperkalaemia, and where there is no provision of renal

services on site, referral is made to the local critical care team in the first instance, guided by the clinical

scenario and established local policies. (1C)

Guideline 19.3 - Hyperkalaemia: Escalation of care

We recommend that patients are referred to the critical care team by a senior member of the referring team

if escalation of care is required from the outset or if the patient fails to respond to initial treatment. (1B)

Guideline 19.4 - Hyperkalaemia: Treatment facilities - Critical care

We recommend that patients with severe hyperkalaemia and problems with airway, breathing, circulation

and/or conscious level, be referred to the local critical care team in the first instance. (1C)

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 15

Guideline 19.5 – Hyperkalaemia: Treatment facilities – Ward, Enhanced Care or Critical Care area

We recommend that stable patients with severe hyperkalaemia be admitted to an area with facilities for

continuous cardiac monitoring which are sufficiently staffed to support clinical monitoring and treatment,

including an acute medical unit, renal unit, coronary care unit, enhanced care area, or critical care unit (HDU

or ICU) depending on local facilities or practice. (1C)

Guideline 19.6 – Hyperkalaemia: RRT in treatment of hyperkalaemia in acutely unwell patients.

We recommend that the decision on timing, suitability and modality for initiation of RRT in patients with life-

threatening hyperkalaemia, either from the outset or resistant to initial medical therapy, is taken urgently by

a nephrologist or critical care specialist. (1C)

Guideline 20.1 - Hyperkalaemia: Transfer to renal services

We suggest that transfer to renal services be considered in clinically stable patients in whom hyperkalaemia

cannot be controlled (i.e. serum K+ < 6.5 mmol/L) using medical measures, particularly in the presence of

advanced or oliguric renal failure (either AKI or CKD). (2C)

Guideline 20.2 - Hyperkalaemia: Minimum standards for safe patient transfer

We suggest that any inter- or intra-hospital patient transfer is coordinated by senior clinicians and follows

national guidelines. (2B)

Guideline 21.1 – Hyperkalaemia: Prevention of hyperkalaemia in hospitalised patients

We recommend that the need for prescribed medication which can cause hyperkalaemia are reviewed in the

context of the current illness and level of renal function both on and during hospital admission. (1B)

Guideline 21.2 – Hyperkalaemia: Prevention of hyperkalaemia in hospitalised patients

We recommend a low potassium diet for hospitalised patients with moderate or severe hyperkalaemia. (1C)

Guideline 21.3 – Hyperkalaemia: Prevention of hyperkalaemia in hospitalised patients

We recommend that community blood monitoring is arranged on discharge for all patients who have

required treatment for hyperkalaemia during hospital admission. (1B)

Guideline 21.4 – Hyperkalaemia: Prevention of hyperkalaemia in hospitalised patients

We recommend that the risk of recurrence of hyperkalaemia is considered before reinstating previous

medication that may have contributed to the episode. (1B)

Guideline 22.1 – Hyperkalaemia; Algorithm in Hospital

We recommend that hyperkalaemia in hospitalised patients is managed using the treatment algorithm which

provides guidance on the medical therapies and the need for initiation of renal replacement therapy. (1B)

Section III: Resuscitation

Guideline 23.1 – Hyperkalaemia; Cardiac Arrest - special circumstance

We recommend that hyperkalaemia is considered in all patients who have a cardiac arrest, as part of

identifying and treating a reversible cause using the 4 Hs and 4 Ts approach. (1A)

Guideline 24.1 – Hyperkalaemia; Cardiac Arrest – Resuscitation strategy in haemodialysis patients

We recommend that standard ALS practice in cardiac arrest be applied to patients requiring dialysis. (1A)

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 16

Guideline 24.2 – Hyperkalaemia; Cardiac Arrest – Defibrillation practice in haemodialysis patients

We recommend disconnection from dialysis equipment prior to defibrillation unless the dialysis machine is

defibrillator-proof. (1C)

Guideline 25.1 – Cardiac Arrest: Treatment - Intravenous calcium

We recommend that intravenous calcium chloride is administered if hyperkalaemia is known or suspected to

be the cause of cardiac arrest. (1C)

Guideline 25.2.1 – Cardiac Arrest: Treatment – Insulin-glucose

We recommend that 10 units soluble insulin and 25g glucose is administered if hyperkalaemia is known or

suspected to be the cause of cardiac arrest. (1B)

Guideline 25.2.2 – Cardiac Arrest: Treatment – Insulin-glucose

We suggest 10% glucose infusion be initiated if the blood glucose is < 7.0 mmol/l at the time of cardiac

arrest. (2C)

Guideline 25.3 – Hyperkalaemia; Cardiac Arrest – Sodium bicarbonate

We suggest that sodium bicarbonate is administered if hyperkalaemia is known or suspected to be the cause

of cardiac arrest. (2C)

Guideline 25.4 – Hyperkalaemia; Cardiac Arrest – Initiation of dialysis during CPR

We suggest that renal replacement therapy with ongoing CPR may be considered for hyperkalaemic cardiac

arrest, if hyperkalaemia is resistant to medical therapy and appropriate staff and facilities are available. (2C)

Guideline 26.1 – Hyperkalaemia; Prevention of Cardiac Arrest in Hyperkalaemia

We recommend that hyperkalaemia is treated urgently in patients with severe hyperkalaemia (K+ ≥ 6.5

mmol/l) and in those with ECG changes suggestive of severe hyperkalaemia. (1C)

Guideline 26.2 – Hyperkalaemia; Prevention of Cardiac Arrest in Hyperkalaemia

We recommend continuous cardiac monitoring for patients with severe hyperkalaemia (K+ ≥ 6.5 mmol/l) in a

setting appropriate for the level of care required. (1C)

Guideline 26.1 – Hyperkalaemia; Algorithm in Cardiac Arrest

We recommend that cardiac arrest attributable to hyperkalaemia is managed using the treatment algorithm

which provides guidance on the medical therapies and the need for initiation of renal replacement therapy

during CPR. (1C)

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 17

Tables

Table 1: Risk factors with odds ratio of developing hyperkalaemia in community studies.

Table 2: Prevalence and outcome of hyperkalaemia in patients with eGFR> 60 ml/min in community studies.

Table 3: Prevalence of hyperkalaemia and mortality rate in patients with CKD.

Table 4: Interval for repeat blood monitoring following an episode of hyperkalaemia.

Table 5: Drugs that pose an additive effect on risk of hyperkalaemia in patients receiving RAASi and MRAs.

Table 6: Studies of efficacy of Patiromer in the treatment of hyperkalaemia.

Table 7: Studies of the efficacy of SZC in treatment of hyperkalaemia

Table 8: Drugs implicated in development of hyperkalaemia and exacerbating factors.

Table 9: Factors associated with an increased risk of hyperkalaemia.

Table 10: Mechanism of action of drugs used in treatment of hyperkalaemia.

Table 11: Calcium content of IV calcium salts used in treatment of hyperkalaemia.

Table 12: Incidence and risk factors associated with iatrogenic hypoglycaemia after insulin-glucose infusion

for treatment of hyperkalaemia.

Table 13: Prospective and Retrospective studies of Insulin-glucose therapy.

Table 14: Efficacy and risk of hypoglycaemia with conventional regimen - 10 units Insulin with 25g glucose

(studies without efficacy data excluded)

Table 15: Comparison of studies performed using 5 versus 10 units insulin (studies without efficacy data

excluded).

Table 16: Comparison of studies performed using weight-base Insulin regimen.

Table 17: Studies using 50% glucose in treatment of hyperkalaemia.

Table 18: Risk Factors for Hypoglycaemia following treatment with Insulin-Glucose

Table 19: Efficacy of Nebulised Salbutamol.

Table 20: Studies investigating efficacy of nebulised salbutamol in hyperkalaemia.

Table 21: Proportion of patients taking SZC 10g three times daily achieving restoration of normokalaemia (K

3.5-5.0 mmol/l) during acute phase.

Table 22: Factors associated with an increased risk of hyperkalaemia in HD patients.

Table 23: Dialysate K+ prescription in chronic HD patients.

Table 24: Minimum standards for safe patient transfer.

Table 25: Drugs commonly associate with hyperkalaemia.

Table 26: Incidence and outcome of cardiac arrest in out-patient dialysis units.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 18

Table 27: Timing of cardiac arrest during dialysis in out-patient centres.

Table 28: Outcome of cardiac arrest in patients receiving haemodialysis (HD) in an outpatient dialysis facility

versus all in-hospital cardiac arrests.

Table 29: Special considerations during resuscitation in haemodialysis patients.

Table 30: Outcome of hyperkalaemic cardiac arrest with RRT during CPR.

Table 31: Summary of procedure for initiation of dialysis during CPR.

Figures

Figure 1: Progressive changes in ECG with increasing severity of hyperkalaemia.

Figure 2: ECG in a patient with severe hyperkalaemia (serum K+ 9.1 mmol/l) illustrating peaked T waves (a),

diminished P waves (b) and wide QRS complexes (c).

Figure 3: Arrhythmias in patients with severe hyperkalaemia illustrating bradycardia with wide QRS [K+ 9.6

mmol/L] (a), sine wave with pause [K+ 9.3 mmol/L] (b) and sine wave without pause [K+ 8.4 mmol/L] (c) and

ventricular tachycardia [K+ 9.1 mmol/L] (d).

Figure 4: There are five key steps in the treatment of hyperkalaemia (never walk away without completing all

of these steps).

Figure 5: ECG on admission (a) and following 20ml 10% calcium gluconate IV (b) in a patient with serum K+

9.3 mmol/L who presented with generalised weakness.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 19

Summary of Audit Measures

The Renal Association encourages non-renal specialties to record audit measures for all patients diagnosed

with hyperkalaemia irrespective of whether or not they are referred to renal services. Hospital laboratories

should be capable of providing data to help audit compliance with these guidelines. It is recommended that

the following audit measures be recorded for patients with hyperkalaemia.

1. Frequency of hospital admission for severe hyperkalaemia (serum K+ > 6.5 mmol/l) detected on

routine blood test in the community.

2. Frequency of blood monitoring of patients receiving RAASi drugs in the community.

3. Proportion of patients admitted to hospital with severe hyperkalaemia detected in the community

who subsequently did not warrant emergency treatment on repeat testing.

4. Proportion of patients with moderate hyperkalaemia who have received dietary potassium advice in

the renal out-patient setting.

5. The proportion of out-patients with moderate hyperkalaemia (serum K+ 6.0 - 6.4 mmol/l) treated

with patiromer who achieved a serum K+ ≤ 5.0 mmol/l within 1 week.

6. The proportion of out-patients who achieve maximal dose RAASi therapy whilst taking patiromer.

7. The proportion of out-patients with moderate hyperkalaemia (serum K+ 6.0 - 6.4 mmol/l) treated

with SZC who achieved a serum K+ ≤ 5.0 mmol/l within 48 hours.

8. The proportion of out-patients who achieve maximal dose RAASi therapy whilst taking SZC.

9. Proportion of patients with severe hyperkalaemia (Serum K+ ≥ 6.5 mmol/l) on admission to hospital

who had been provided with ‘Sick Day Rules’ advice.

10. Length of hospital stay and in-hospital mortality of patients admitted with hyperkalaemia.

11. Proportion of patients with a serum K + level ≥ 6.0 mmol/L who had a 12-lead ECG recorded before

and after treatment for hyperkalaemia.

12. The frequency of ECG changes in patients treated with intravenous calcium salts.

13. The proportion of patients with severe hyperkalaemia (K+ ≥ 6.5 mmol/L) treated with insulin-glucose

infusion.

14. The proportion of patients with acute severe hyperkalaemia (serum K+ ≥ 6.5 mmol/l) treated with

Sodium Zirconium Cyclosilicate.

15. The proportion of patients with acute severe hyperkalaemia (serum K+ ≥ 6.5 mmol/l) treated with

Patiromer.

16. The proportion of patients in whom serum K+ was measured at least once within 2 hours of

treatment for severe hyperkalaemia [Audit Standard: 100%].

17. The proportion of patients who have at least one blood glucose test performed within 1 hour of

completion of insulin-glucose infusion [Audit Standard: 100%].

18. The frequency of hypoglycaemia occurring in patients receiving treatment with insulin-glucose for

hyperkalaemia.

19. The incidence of patients requiring emergency dialysis for severe hyperkalaemia.

20. The frequency of hyperkalaemia developing beyond 24 hours of hospital admission.

21. The frequency of prescribed drugs potentially contributing to hyperkalaemia.

22. All cardiac arrests should be audited – hospital participation in the National Cardiac Arrest Audit is

encouraged as part of quality improvement and benchmarking.

23. The proportion of patients treated with intravenous calcium for hyperkalaemic cardiac arrest.

24. The proportion of patients treated with sodium bicarbonate for hyperkalaemic cardiac arrest.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 20

25. The number and outcome of patients with refractory hyperkalaemic cardiac arrest treated with

dialysis initiation during CPR.

Future Research

There are numerous unanswered questions about the treatment of patients with hyperkalaemia. Areas for

future research include:

1. The optimal dose of insulin and glucose to treat acute hyperkalaemia required to minimise

iatrogenic hypoglycaemia without compromising efficacy.

2. The efficacy of potassium binders (patiromer and sodium zirconium cyclosilicate) in combination

with insulin-glucose infusion in the treatment of severe hyperkalaemia in hospitalised patients.

3. The efficacy of potassium binders (patiromer and sodium zirconium cyclosilicate) in the treatment of

moderate hyperkalaemia without the administration of insulin-glucose in hospitalised patients.

4. The efficacy of sodium bicarbonate in the treatment of severe hyperkalaemia in patients with AKI.

Future Developments

The delivery of a specified dose of glucose is dependent on the available preparations. Hyperkalaemia is a

medical emergency, therefore ease of administration is key. The only preparation available that provides

the required amount of glucose (25g) is the 50% solution.

1. Preparations of 10% (250ml) and 20% (125ml) glucose solutions in volumes appropriate for the

treatment of hyperkalaemia.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 21

Section I

Management of Hyperkalaemia

in the Community and Out-patient Clinic

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 22

Hyperkalaemia in the Community (Guidelines 1.1 – 12.1)

Introduction

Hyperkalaemia is commonly detected in the community and the patient groups most at risk are those with

CKD, diabetes mellitus and heart failure. Hyperkalaemia may also occur in the context of an AKI triggered by

acute illness, initiation or titration of RAASi medications, or worsening of heart failure.

Hyperkalaemia

develops in approximately 10% of out-patients within one year after initiation of RAASi drugs, thereby

limiting treatment in the patients who receive the greatest benefit from this therapy.

The management of patients with heart failure is challenging given the high prevalence of renal impairment

and increased risk of hyperkalaemia. In clinical trials of RAASi monotherapy, the incidence of hyperkalaemia

ranges from 3 – 7%.

The overall incidence of hyperkalaemia was generally higher in clinical trials involving

aldosterone antagonists.

Combination therapy of RAASi and aldosterone antagonist increases the risk of

hyperkalaemia and hospitalisation.

Mortality in patients with heart failure is significantly increased with

worsening severity of hyperkalaemia: serum K+ levels between 4.8 – 5.0 mmol/l (HR 1.34), 5.1 – 5.5 mmol/l

(HR 1.60) and 5.6 – 7.4 mmol/l (HR 3.31).

Table 1: Risk factors with odds ratio of developing hyperkalaemia in community studies.

Several risk factors contribute to community-acquired hyperkalaemia as shown in Table 1. The presence of

multiple co-morbidities or other risk factors further increase the risk of hyperkalaemia.

6-9

RAASi drugs are

frequently implicated in AKI and hyperkalaemia, but there are conflicting reports in the literature.

10, 11

Given

the potential risk of AKI, ‘sick day rules’ guidance recommending the cessation of RAASi drugs during acute

illness has been proposed by some groups including NICE, but this remains controversial.

1, 10, 12, 13, 14

Risk Factor for

Hyperkalaemia

Odds Ratio

[Turgutalp] [6]

Odds Ratio

[Sarafidis] [7]

Odds Ratio

[Nakhoul] [8]

Odds Ratio

[Horne] [9]

Renal Failure

5.55

2.06

( eGFR < 15)

1.25

(per 5ml/min

decrease)

1.04

Diabetes

1.53

0.95

Heart Failure

0.95

≥2 Co-morbidities

2.22

Serum bicarbonate <

1.30

ARB

2.68

1.85

1.4

15.89

ACE-I

2.24

1.85

1.4

13.63

Spironolactone

2.53

2.10

7.77

NSAIDS

2.68

Beta blocker

2.14

1.06

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 23

Study

Country

Setting

eGFR

ml/min

Definition

of HyperK

mmol/l

Prevalence

HyperK

Mortality risk

with HK

Liamis

2013

Netherlands

General

population

(age > 55)

5179

>60

≥6.0

0.3

OR 2.08

Chang

2016

USA

Health

care

system –

HBP

(age ≥ 18)

155,695

>60

10.8

>5.5

2.3

Hughes-

Austin

2017

USA

Multi-

ethnic

general

population

(age ≥65)

9651

>60

≥5.0

2.8

HR 1.41

Horne

2019

General

population

(age ≥ 18)

195,178

>60

5.0 – 5.4

91.2

∞

2.51

5.5 – 6.0

7.2

∞

3.83

1.6

∞

12.57

Table 2: Prevalence and outcome of Hyperkalaemia in patients with eGFR> 60 ml/min in community

studies.

OR- Odds Ratio;

HR- Hazard Ratio;

∞

All-cause mortality; HBP – hypertensive; NA – not available

The reported incidence of hyperkalaemia in the general population is variable depending on the specific

patient group, study design, level of renal function and definition of hyperkalaemia.

6, 9, 15-19

The prevalence of

hyperkalaemia in patients with an eGFR > 60 ml/min is shown in Table 2. In a large UK primary care study,

the overall incidence rate of a hyperkalaemic event was 2.9 per 100 person years.

In this study, the use of

RAASi was strongly associated with hyperkalaemia with an odds ratio of 13.6 - 15.9.

Hyperkalaemia is more common in patients with CKD and the incidence increases with declining renal

function. Sarafadis et al found that over 30% of patients experienced hyperkalaemia (K+ > 5.5 mmol/l) in the

pre-dialysis setting (eGFR < 15 ml/min).

A summary of the prevalence of hyperkalaemia in patients with

CKD is shown in Table 3.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 24

Study

Country

Setting

eGFR

ml/min

Definition

of HyperK

mmol/l

Prevalence

HyperK

Mortality by

level

Korgaonkar

2010

USA

Renal Clinic

820

25.4

≥5.5

7.9

HR 1.57

Sarafidis

2012

Low

Clearance

clinic

238

14.5

5.0 – 5.4

22.7

5.5 – 5.9

23.1

≥6.0

8.4

Nakhoul

2015

USA

CKD

Registry

(USA)

36,359

5.0 – 5.4

OR 1.12

>5.5

3.3

OR 1.65

Turgutalp

2016

Turkey

Elderly

population

(age > 65)

40,092

23-35

≥5.5

2.9

AUC values by

age

p< 0.001

Luo

2016

USA

Health care

system

(age ≥ 18)

55,266

< 60

5.0 – 5.4

14.9

*IRR 1.01

5.5 – 5.9

3.9

*IRR 1.11

≥6.0

1.1

*IRR 3.08

Furuland

2018

Health care

database

191,964

50.9

5.0 – 5.4

45.1

*IRR 1.1

5.5 – 5.9

15.9

*IRR 1.60

≥6.0

4.9

*IRR 2.88

Table 3: Prevalence of hyperkalaemia and mortality rate in patients with CKD.

NA – not available;

HR – Hazard Ratio;

OR - Odds Ratio; AUC- Area Under Curve; *IRR- Incident rate ratio

Hyperkalaemia is associated with increased hospitalisation, prolongation of hospital stay and increased

mortality. Horne et al showed the incidence rates for all-cause hospitalisation in adults was 14.1 per 100

person years.

Turgutalp et al demonstrated a higher incidence of hospitalisation for hyperkalaemia in the

elderly population: age 65-74 years (46%), age 75-84 years (44%) and ≥ 85 years (74%).

Mortality increases

with worsening severity of hyperkalaemia in the general population and in patients with CKD.

8, 9, 18, 19

This chapter focuses on the detection, treatment and prevention of hyperkalaemia in the community. It will

address the management of patients receiving RAASi drugs, indications for hospital admission and the use of

novel oral potassium lowering drugs.

References

1. Clark, A.L., et al., Change in renal function associated with drug treatment in heart failure: national

guidance. Heart, 2019. 105(12): p. 904-910.

2. Palmer, B.F. and D.J. Clegg, Diagnosis and treatment of hyperkalemia. Cleve Clin J Med, 2017. 84(12):

p. 934-942.

3. Tromp, J. and P. van der Meer, Hyperkalaemia: aetiology, epidemiology, and clinical significance. Eur

Heart J Suppl, 2019. 21(Suppl A): p. A6-A11.

4. Juurlink, D.N., et al., Rates of hyperkalemia after publication of the randomized aldactone evaluation

study. New England Journal of Medicine, 2004. 351(6): p. 543-551.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 25

5. Aldahl, M., et al., Associations of serum potassium levels with mortality in chronic heart failure

patients. Eur Heart J, 2017. 38(38): p. 2890-2896.

6. Turgutalp, K., et al., Community-acquired hyperkalemia in elderly patients: risk factors and clinical

outcomes. Ren Fail, 2016. 38(9): p. 1405-1412.

7. Sarafidis, P.A., et al., Prevalence and factors associated with hyperkalemia in predialysis patients

followed in a low-clearance clinic. Clin J Am Soc Nephrol, 2012. 7(8): p. 1234-41.

8. Nakhoul, G.N., et al., Serum Potassium, End-Stage Renal Disease and Mortality in Chronic Kidney

Disease. Am J Nephrol, 2015. 41(6): p. 456-63.

9. Horne, L., et al., Epidemiology and health outcomes associated with hyperkalemia in a primary care

setting in England. BMC Nephrol, 2019. 20(1): p. 85.

10. Whiting, P., et al., What are the risks and benefits of temporarily discontinuing medications to

prevent acute kidney injury? A systematic review and meta-analysis. BMJ Open, 2017. 7(4): p.

e012674.

11. Mansfield, K.E., et al., Prescription of renin-angiotensin system blockers and risk of acute kidney

injury: a population-based cohort study. BMJ Open, 2016. 6(12): p. e012690.

12. Doerfler, R.M., et al., Usability Testing of a Sick-Day Protocol in CKD. Clin J Am Soc Nephrol, 2019.

14(4): p. 583-585.

13. Martindale, A.M., et al., Understanding the implementation of 'sick day guidance' to prevent acute

kidney injury across a primary care setting in England: a qualitative evaluation. Bmj Open, 2017.

7(11).

14. National Institute for Health and Care Excellence. Acute kidney Injury: prevention, detection and

management. Clinical guideline [CG169]. London, 2013.

15. Liamis, G., et al., Electrolyte disorders in community subjects: prevalence and risk factors. Am J Med,

2013. 126(3): p. 256-63.

16. Chang, A.R., et al., Antihypertensive Medications and the Prevalence of Hyperkalemia in a Large

Health System. Hypertension, 2016. 67(6): p. 1181-8.

17. Hughes-Austin, J.M., et al., The Relation of Serum Potassium Concentration with Cardiovascular

Events and Mortality in Community-Living Individuals. Clinical Journal of the American Society of

Nephrology, 2017. 12(2): p. 245-252.

18. Furuland, H., et al., Serum potassium as a predictor of adverse clinical outcomes in patients with

chronic kidney disease: new risk equations using the UK clinical practice research datalink. BMC

Nephrol, 2018. 19(1): p. 211.

19. Luo, J., et al., Association between Serum Potassium and Outcomes in Patients with Reduced Kidney

Function. Clin J Am Soc Nephrol, 2016. 11(1): p. 90-100.

20. Korgaonkar, S., et al., Serum potassium and outcomes in CKD: insights from the RRI-CKD cohort study.

Clin J Am Soc Nephrol, 2010. 5(5): p. 762-9.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 26

Patient monitoring (Guidelines 1.1-1.2)

Guideline 1.1 – Monitoring of patients at risk of Hyperkalaemia in the community.

We recommend that patients known to have CKD, heart failure and/or diabetes, who are at risk of

hyperkalaemia, undergo regular blood monitoring at a frequency (2-4 times per year) dependent on level of

renal function and degree of proteinuria. (1B)

Guideline 1.2.1 – Monitoring of patients after an episode of mild hyperkalaemia detected in the

community.

We recommend that the serum K+ is repeated within 3 days, or as soon as feasible, if an episode of mild

hyperkalaemia (K+ 5.5 – 5.9 mmol/l) is detected unexpectedly in the community. (1C)

Guideline 1.2.2 – Monitoring of patients after an episode of moderate hyperkalaemia detected in the

community.

We recommend that the serum K+ is repeated within 1 day of an episode of moderate hyperkalaemia (K+ 6.0

– 6.4 mmol/l) when detected in the community. (1C)

Guideline 1.2.3 – Monitoring of patients after an episode of severe hyperkalaemia detected in the

community.

We recommend that patients with severe hyperkalaemia (K+ ≥ 6.5 mmol/l) detected in the community are

admitted for immediate assessment and treatment. (1B)

Audit measure

1. Frequency of hospital admission for severe hyperkalaemia (serum K+ > 6.5 mmol/l) detected on

routine blood test in the community.

Rationale (Guideline 1.1 – 1.2)

Patients with CKD are at risk of hyperkalaemia and progression of their underlying kidney disease, therefore

require regular blood monitoring in the community. The NICE CKD Guideline suggests that the frequency of

monitoring should be tailored to the level of renal function, rate of decline in renal function and degree of

proteinuria.

Patients with CKD 1-3 require monitoring at least 1-2 times per year and patients with CKD 4-5

require monitoring at least 2-4 times per year. More frequent monitoring is indicated during acute illness

and following an episode of AKI or hyperkalaemia.

Several observational studies have reported the frequency of blood monitoring in patients with CKD in

relation to detection of hyperkalaemic events. Chang et al showed that the proportion of patients who had

a serum K+ level performed over a 3 year period was 0 tests/ year (20%), <2 tests/ year (58%), 2-3 tests/ year

(16%) and ≥4 tests/ year (6%).

In patients with an eGFR < 30ml/min who had ≥4 tests per year,

hyperkalaemia was found in 30%.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 27

Luo et al reported the frequency of blood monitoring stratified by level of renal function and level of serum

K+.

In patients with an eGFR < 30 ml/min, the mean frequency of tests per year was 1.69 ± 1.35 (serum K+

5.5 – 5.9 mmol/l) and 1.37 ± 0.98 (serum K+ ≥ 6 mmol/l) respectively. In patients with an eGFR 50-59 ml/min,

the mean frequency of tests per year was 1.34 ± 0.92 (serum K+ 5.5 – 5.9 mmol/l) and 1.21 ± 0.73 (serum K+

≥ 6 mmol/l) respectively. Similar to Chang et al, detection of hyperkalaemia increases with frequency of

testing. Overall, the frequency of monitoring in these studies was generally 1-2 times per year, with more

frequent testing in patients with an eGFR < 30 ml/min.

The interval between hyperkalaemic episodes was reported in a large retrospective cohort of patients with

CKD.

This study utilised data from primary care records for approximately 7% of the UK population over a

mean follow-up of 4.9 years. Patients experiencing at least one episode of hyperkalaemia was stratified in

three groups: serum K+ 5.0 – 5.4 mmol/l (45.2%), 5.5 – 5.9 mmol/l (15.9%) and ≥ 6.0 mmol/l (4.9%). The

time interval to a recurrent episode of hyperkalaemia progressively shortened in each severity group. The

interval between the first to second episodes in patients with serum K+ 5.5 – 5.9 mmol/l was 0.84 years and

reduced to 0.59 years between the second and third episode and 0.48 years between the third and fourth

episode. The interval between recurrent episodes was shorter in patients with serum K+ ≥ 6 mmol/l (0.65,

0.41 and 0.30 years respectively).

This collective data would suggest that monitoring serum K+ at least twice per year in patients at risk of

hyperkalaemia is a reasonable approach. The frequency of monitoring should be increased to at least four

times per year in patients with an eGFR < 30 ml/min and in patients with a serum K+ ≥ 6 mmol/l given the

high risk of recurrence.

The interval for blood monitoring after a hyperkalaemic event is less well documented. Horne et al

demonstrated that only 5.8% of patients had a repeat serum K+ performed within 14 days of the

hyperkalaemic event, but a large number of patients had a serum K+ < 5.5 mmol/l which may have been

perceived to be non-urgent.

A repeat level occurred more commonly in patients with K+ > 6.0 mmol/l

(55.3%) compared with those with a serum K+ 5.6 – 6.0 mmol/l (23.4%) or serum K+ 5.0 – 5.5 mmol/l (3.9%).

In patients with a serum K+ > 6.0 mmol/l at the index event, 36.8% had an elevated K+ level on re-testing.

‘Think Kidneys’ have provided practical guidance on repeat testing after a hyperkalaemic episode.

The

timing is guided by the level of hyperkalaemia and clinical context. In patients with mild hyperkalaemia (K+

5.5 – 5.9 mmol/l), a repeat test is recommended within 3 days if the result was unexpected or as soon as

feasible if the patient is clinically stable. In patients with moderate hyperkalaemia (K+ 6.0 – 6.4 mmol/l), a

repeat test is recommended within 1 working day if detected on a routine check in a stable patient, but

referral to hospital should be considered if clinically unwell or if an AKI is present. Patients with severe

hyperkalaemia (K+ ≥ 6.5 mmol/l) warrant urgent referral to hospital for immediate assessment and

The more often you test, the more often you will detect hyperkalaemia,

especially in patients at risk.

Patients with CKD 4-5 have a high risk of hyperkalaemia and warrant

regular testing.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 28

treatment if required. The recommended interval for repeat testing after a hyperkalaemic episode is

summarised in Table 4.

Severity of

Hyperkalaemia

Clinically well

(no AKI)

Unexpected result

Clinically unwell or AKI

MILD

5.5 – 5.9 mmol/l

Repeat within 14

days

Repeat within 3 days

Consider if hospital referral is

indicated

Assess for cause (drugs, diet) and address in community

MODERATE

6.0 – 6.4 mmol/l

Repeat within 1

working day*

Repeat within 24

hours

Refer to hospital

Assess for cause (drugs, diet) and address community or hospital

SEVERE

≥ 6.5 mmol/l

Refer to hospital for immediate assessment and treatment

Assess for cause and address during hospital admission

Table 4: Interval for repeat blood monitoring following an episode of hyperkalaemia.

Need for hospital referral will be guided by clinical circumstance and risk of further deterioration.

*Routine bloods tests unavailable at weekends and out of hours from community.

(Modified from Think Kidneys Guideline)

There is increasing use of point of care testing (POCT) in the hospital setting for rapid potassium

measurement, but achieving rapid blood analysis in the community can be challenging. POCT has been

validated in several studies in the hospital setting within the Emergency Department and Critical Care.

7-12

POCT has also been shown to improve early recognition of hyperkalaemia in patients with CKD presenting to

the Emergency Department.

Use of POCT in the pre-hospital setting is less well reported.

14,15

A study of

the utilisation and validation of POCT devices by community paramedics demonstrated good correlation with

laboratory measurement.

Technology is rapidly developing with the use of medical biosensors and Smart

phone technology potentially making POCT easily accessible for patients.

References

1. National Institute for Health and Care Excellence: Chronic kidney disease. Scenario: Management of

chronic kidney disease. Last revised in May 2020. www.cks.nice.org.uk/chronic-kidney-

disease#!scenarioRecommendation:1.

2. Chang, A.R., et al., Antihypertensive Medications and the Prevalence of Hyperkalemia in a Large

Health System. Hypertension, 2016. 67(6): p. 1181-8.

3. Luo, J., et al., Association between Serum Potassium and Outcomes in Patients with Reduced Kidney

Function. Clin J Am Soc Nephrol, 2016. 11(1): p. 90-100.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 29

4. Furuland, H., et al., Serum potassium as a predictor of adverse clinical outcomes in patients with

chronic kidney disease: new risk equations using the UK clinical practice research datalink. BMC

Nephrol, 2018. 19(1): p. 211.

5. Horne, L., et al., Epidemiology and health outcomes associated with hyperkalemia in a primary care

setting in England. BMC Nephrol, 2019. 20(1): p. 85.

6. 'Think Kidneys' - Changes in kidney function and serum potassium during ACE/ARB/diuretic

treatment in primary care. A position statement from Think Kidneys, the Renal Association and the

British Society for Heart Failure; 2017. www.thinkkidneys.nhs.uk

7. Mirzazadeh, M., et al., Point-of-care testing of electrolytes and calcium using blood gas analysers: it

is time we trusted the results. Emerg Med J, 2016. 33(3): p. 181-6.

8. Dashevsky, M., et al., Agreement Between Serum Assays Performed in ED Point-of-Care and Hospital

Central Laboratories. West J Emerg Med, 2017. 18(3): p. 403-409.

9. Florkowski, C., et al., Point-of-care testing (POCT) and evidence-based laboratory medicine (EBLM) -

does it leverage any advantage in clinical decision making? Crit Rev Clin Lab Sci, 2017. 54(7-8): p.

471-494.

10. Allardet-Servent, J., et al., Point-of-Care Versus Central Laboratory Measurements of Hemoglobin,

Hematocrit, Glucose, Bicarbonate and Electrolytes: A Prospective Observational Study in Critically Ill

Patients. PLoS One, 2017. 12(1): p. e0169593.

11. Chacko, B., et al., Electrolytes assessed by point-of-care testing - Are the values comparable with

results obtained from the central laboratory? Indian J Crit Care Med, 2011. 15(1): p. 24-9.

12. Gibbons, M., et al., How closely do blood gas electrolytes and haemoglobin agree with serum values

in adult emergency department patients: An observational study. Emerg Med Australas, 2019. 31(2):

p. 241-246.

13. You, J.S., et al., Evaluating the utility of rapid point-of-care potassium testing for the early

identification of hyperkalemia in patients with chronic kidney disease in the emergency department.

Yonsei Med J, 2014. 55(5): p. 1348-53.

14. Blanchard, I.E., et al., Community paramedic point of care testing: validity and usability of two

commercially available devices. BMC Emerg Med, 2019. 19(1): p. 30.

15. Tortella, B.J., et al. Precision, Accuracy, and Managed Care Implications of a Hand-Held Whole Blood

Analyzer in the Prehospital Setting. Am J Clin Pathol, 1996. 106:p.124-127.

16. Liu, J., et al., Point-of-care testing based on smartphone: The current state-of-the-art (2017-2018).

Biosens Bioelectron, 2019. 132: p. 17-37.

Renal Association Clinical Practice Guidelines – Treatment of Acute Hyperkalaemia in Adults – July 2020 30

Management of patients receiving RAASi drugs (Guidelines 2.1-2.7)