Acute Management of Hypercalcaemia

Document Control

Title Acute Management of Hypercalcaemia

Author Author’s job title Medical consultant Directorate Department Medicine Medical Assessment Unit/Medicine Date Version Status Comment / Changes / Approval Issued 0.1 Jan Draft Initial version for consultation 2019 1.0 May Final Approved by Drugs and Therapeutics Committee 16th May 2019 2019. Main Contact Gastroenterologist or Clinical Tel: Direct Dial – effectiveness lead Tel: Internal – Medical Assessment Unit North Devon District Hospital Raleigh Park Barnstaple, EX31 4JB Lead Director Medical clinical lead Superseded Documents

Issue Date Review Date Review Cycle May 2019 May 2022 Three years Consulted with the following stakeholders:  Medical Trust grade  Clinical Effectiveness Lead  Gastroenterologist and Clinical lead for medicine  Biochemical Sciences lead  Pharmacist Approval and Review Process  Drugs and Therapeutics Local Archive Reference G:\\ Acute Management of Hypercalcaemia Local Path General Medicine - Acute Management of Hypercalcaemia Filename Acute Management of Hypercalcaemia Policy categories for Trust’s internal Tags for Trust’s internal website (Bob) website (Bob) Hypercalcaemia, bisphosphonates, Pharmacy Calcium, Workforce Zoledronic acid, Pamidronate

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Contents

Document Control ...... 1 1. Purpose ...... 3 2. Definition of hypercalcaemia ...... 3 3. Definition of ionised versus adjusted calcium ...... 3 4. Responsibilities ...... 3 5. Hypercalcaemia ...... 4 6. Causes ...... 5 7. Assessment ...... 5 8. Management ...... 6 9. Further management considerations ...... 7 10. Monitoring Compliance with and the Effectiveness of the Policy ...... 8 11. Equality Impact Assessment ...... 8 12. References ...... 9 13. Associated Documentation ...... 9 14. Appendix 1 – Quick management reference guide ...... 10

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1. Purpose

The purpose of this document is to detail the process for management of hypercalcaemia in adults

The policy applies to all staff involved in managing patients with hypercalcaemia

Implementation of this policy will ensure that:

 Hypercalcaemia is identified and managed appropriately and in a timely fashion  There is a standard pathway to follow across the trust  The information is readily available

2. Definition of hypercalcaemia

 Normal adult (adjusted) calcium level: 2.20-2.60mmol/l  Mild: 2.60-3.00 (not usually medical emergency, usually asymptomatic )  Moderate: 3.00-3.50 (can be medical emergency, can be symptomatic)  Severe: >3.50 (usually a medical emergency)

3. Definition of ionised versus adjusted calcium

 Calcium levels are often recorded as both ionised and adjusted  Ionised – this is the physiologically active calcium  Adjusted calcium – this calcium is bound to protein (mainly albumin) and so will be affected by changes in albumin level

4. Responsibilities

4.1. Role of Medical Director

Ensuring adherence to the policy

4.2. Role of Clinicians

Identifying and recognising hypercalcaemia and managing it according to policy guidelines, unless good reasons exist to deviate from the guidance.

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4.3. Role of Nursing Staff

To adhere to policy guidelines and treat patients appropriately and in a timely manner, and recognising unsafe prescriptions.

4.4. Role of Pharmacy Staff

To provide advice and guidance in line with policy, recognising unsafe prescriptions where possible.

4.5. Role of Biomedical Scientists

Carrying out investigations and informing clinical staff in a timely fashion of abnormal results requiring urgent action

Laboratory staff will call clinical teams if adjusted calcium levels are above 2.8 mmol/L

4.6. Role of Drugs and Therapeutics Group

The Drugs and Therapeutics Group is responsible for:

 Acting as an oversight for the policy  Confirming and publishing the policy

5. Hypercalcaemia

5.1. Background

99% of calcium in adults is held within bone.

Serum concentration tightly regulated. Intracellular compartments very sensitive to change.

It is highly bound to albumin, and therefore should be adjusted for serum albumin levels

Critical in many essential roles within the body, including clotting, muscle contraction, nerve conduction, insulin release and bone structure.

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5.2. Signs and symptoms

Symptoms usually arise with a corrected level above 3.0mmol/l

“Moans, bones, stones, groans, psychological overtones”  Loss of appetite, nausea and vomiting, abdominal pain, constipation  Polyuria and polydipsia  Fatigue, weakness, muscle aches.  Confusion, depression, headache, coma  Renal calculi/colic, renal impairment, calcified vessels/organs, band keratopathy (calcified cornea)  Pancreatitis  Reduced QTc, dysrhythmias, cardiomyopathy

6. Causes

90% of hypercalcaemia cases due to hyperparathyroidism or malignancy

6.1. Less common causes

Endocrine: primary hyperparathyroidism, tertiary hyperparathyroidism, adrenal insufficiency, thyrotoxicosis

Metabolic: dehydration, rhabdomyolysis, familial hypocalciuric hypercalcaemia,, milk alkali syndrome, Paget’s disease, phaechromocytoma

Medication: calcium supplements, thiazide diuretics, lithium, theophylline toxicity, hypervitaminosis D and A (rare)

Granulomatous disease: e.g. sarcoid

7. Assessment 7.1. History Key points see signs and symptoms. Include  Night sweats, weight loss  Cough, GI symptoms  Medications, including over the counter  Family history

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7.2. Examination  Assess cognitive impairment,  Fluid status,  Check for underlying cause neck/lymph nodes/ respiratory/abdomen/ breast 7.3. Initial investigations  ECG – look for short QTc or other conduction abnormalities  Calcium, phosphate, U+E and PTH

8. Management

8.1. Acute management (see appendix 1) Review of medications, e.g. calcium and vitamin D supplements, diuretics

Rehydrate – 0.9% Sodium Chloride 4-6 litres over 24 hours, depending on severity

- Caution regarding fluid overload, heart failure, renal failure and elderly

- Consider dialysis in severe renal failure (discuss with senior or renal team)

Once rehydrated if further treatment needed

Bisphosphonates - Caution with renal impairment –especially if eGFR <30

 Zoledronic acid 3 - 4mg in 100mls Sodium Chloride 0.9% over 15 minutes (lower dose in renal impairment or less severe hypercalcaemia) (see appendix 1)  Pamidronate (see Appendix 1)  Ibandronic acid 2-4mg – consider in renal impairment – seek senior advice and discuss with pharmacist, can be considered if eGFR <30 Consider steroids in lymphoma

Monitor calcium levels daily

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9. Further management considerations

Determine underlying cause – 90% are due to malignancy or hyperparathyroidism

9.1. Further Investigations  Check albumin PTH, U+E, LFTs, phosphate, magnesium, TFTs  ECG  USS renal tract to explore for calcification or calculi  24 hour urinary calcium levels  Imaging of parathyroid glands, e.g. USS or Nuclear Medicine 9.2. Second line treatments

Calcium PTH Diagnosis

High High Primary or tertiary hyperparathyoidism

High Low Malignancy or other less common causes

 Calcitonin – consider if poor response to bisphosphonates – discuss with senior or endocrinologist  Glucocorticoids (e.g. prednisolone 40mg) – helpful in lymphoma or granulomatous disease  Calcimimetics (e.g. cinacalet) – for primary hyperparathyroidism  Parathyroidectomy – consider in primary hyperparathyroidism if severe hypercalcaemia and poor response to other measures  Nb. Loop diuretics can be helpful in fluid overload but do not lower calcium levels

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10. Monitoring Compliance with and the Effectiveness of the Policy

10.1. Standards/ Key Performance Indicators Key performance indicators comprise:

 Successful management of hypercalcaemia  Number of patients with hypercalacaemia that are not resolved within 5 days  Number of patients who have a cause of their hypercalcaemia diagnosed (or suspected diagnosis) within 5 days

10.2. Process for Implementation and Monitoring Compliance and Effectiveness  When the policy document has been approved by all relevant parties, a copy will be sent to all ward managers and uploaded onto BOB  Policy will be presented at audit meetings and grand round  Management of hypercalcaemia falling outside of policy will be reported by all staff and escalated to the appropriate team and investigated  The guidance will be hosted on the IV fluids and electrolytes page on BOB  An audit will be undertaken comparing before and after implementation practice

11. Equality Impact Assessment

The author must include the Equality Impact Assessment Table and identify whether the policy has a positive or negative impact on any of the groups listed. The Author must make comment on how the policy makes this impact.

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Table 1: Equality impact Assessment

Positive Negative No Group Comment Impact Impact Impact Age  Policy will improve management of Disability  hypercalcaemia, which is more common in elderly and those with underlying health conditions Gender  Gender Reassignment  Human Rights (rights  to privacy, dignity, liberty and non- degrading treatment), marriage and civil partnership Pregnancy  Maternity and  Breastfeeding Race (ethnic origin)  Religion (or belief)  Sexual Orientation 

12. References

 Society for endocrinology: Endocrine Emergency Guidance: Emergency Management of Acute Hypercalcaemia in adult patients 2016 (www.endocrinology.org/policy)  LeGrand, S.B., Leskuski, D. & Zama, I. (2008) Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Annals of Internal Medicine, 149(4), 259-263.  Medusa IV guide: http://www.injguide.nhs.uk/IVGuideDisplay.asp (Accessed 16/01/19)

13. Associated Documentation

 Symptom Management in Palliative Care Guidelines

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14. Appendix 1 – Quick management reference guide 14.1. Adjusted calcium – severity of hypercalcaemia: 2.2-2.6 mmo/l <3.0 mmol/l Mild 3.0-3.5 mmol/l Moderate >3.5 mmol/l Severe Normal

Normal range Can be Usually symptomatic Requires urgent asymptomatic correction due to risk of May be well tolerated if dysrhythmia, seizure subacute rise and decreased GCS

Step 1 – IV fluids

 0.9% Sodium Chloride IV 4-6 litres over 24 hours  Caution re: heart failure / renal failure and elderly patients, or evidence of fluid overload  Review medications

Step 2 – Bisphosphonates – Once patient rehydrated if further treatment needed Option 1:  Zoledronic acid 3- 4mg over 15 minutes. Diluted in 100mls Sodium Chloride 0.9% or 5% Glucose

Baseline Creatinine Clearance (ml/min) Zoledronic acid Recommended Dose* > 60 4.0 mg zoledronic acid 50–60 3.5 mg* zoledronic acid 40–49 3.3 mg* zoledronic acid 30–39 3.0 mg* zoledronic acid

https://www.medicines.org.uk/emc/product/3117/smpc Option 2: Calcium level: Pamidronate dose:  Pamidronate 30-90mg 2.6-3.0 mmol/l 30mg  20-60mg/hr 3.0-3.5 mmol/l 60mg  Diluted in 250-500mls 0.9% Sodium Chloride >3.5 mmol/l 90mg Option 3:  Ibandronic acid  2-4mg  Better option in renal impairment – still needs discussion with pharmacist/senior

Step 3 – Recheck calcium

 Recheck calcium daily, but bisphosphonates take 48+ hours to have a significant effect

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