Fluid and electrolytes (Haemato-oncology patients, Schiehallion)

1. INTRODUCTION

The following guideline is intended as a basic introduction to fluid, nutrition and electrolyte management within the haematology/oncology department. Each section should be read in conjunction with any relevant RHC clinical guidelines.

2. RELATED DOCUMENTATION

3. AUTHORISED PERSONNEL/SPECIFIC STAFF COMPETENCIES

3.1 The management of patients will be directed by the Consultant/Associate Specialist or a senior member of the medical team.

3.2 The Medical/Nursing team will be responsible for admitting, assessing, investigating and administrating treatment, and monitoring response (see Appendix 1).

4. EQUIPMENT/MATERIALS

None.

5.1 Fluid Requirements

MINIMUM DAILY REQUIREMENTS

	FLUIDS	CALORIES
Up to 10kg	100ml/kg	100kcal/kg
Over 10kg	1000ml + 50ml/kg over 10kg	1000kcal + 50kcal/kg over 10kg
Over 20kg	1500ml + 20ml/kg over 20kg	1500kcal + 20kcal/kg over 20kg

Total volume of fluids per day should not exceed 4500ml in any patient
Use an accurate and up-to-date body weight to calculate fluid requirements
If the patient is very overweight, fluid is prescribed as per weight, no capping done, except the daily limit of 4500ml
If hyperhydration is required this should be calculated by body surface area (BSA) and not weight. In this case BSA should be capped for extremely overweight patients and adjusted to second centile for underweight patients. BSA charts are available on the ward.

Type of Intravenous Fluids:

There are 4 main types of intravenous fluid used within the haematology/oncology unit (see Appendix 2).

Sodium Chloride 0.45% and Glucose 2.5%
This is the standard hydration fluid within the unit – the sodium content is approximately 77mmol/L. Note that Sodium Chloride 0.45% and Glucose 5% is widely used throughout RHC and may be safely administered to many children, however as haematology/oncology patients often require hyperhydration, the large fluid volumes may result in an excessive carbohydrate load leading to issues with blood glucose control.

Plasma-Lyte 148
Plasma-Lyte is an iso-osmolar (pH 7.4) solution for intravenous infusion which contains sodium 140mmol/L, Potassium 5mmol/L & Magnesium 1.5mmol/L – its constituents are designed to match those of plasma. It also contains acetate & gluconate so is therefore a mild alkalinizing agent. Plasma-Lyte is used widely throughout RHC and may be appropriate in some haematology/oncology patients. However, there is currently no stability data available to run Plasma-Lyte concurrently with chemotherapy, therefore it should not be used as hydration in any child receiving chemotherapy. In addition, SPC advises caution in use in renal failure or in hyperkalaemia, therefore it should not be used as hyperhydration in a tumour lysis prevention protocol.

Glucose 5%
This is used as the base fluid in children receiving high dose Methotrexate and requiring alkalinisation because of the excess sodium added to the bag as Sodium Bicarbonate. The addition of Sodium Bicarbonate 8.4% 50mmol/L results in a solution approximately equivalent to Sodium Chloride 0.45% and Glucose 5%

Sodium Chloride 0.9% (Isotonic saline)
This is an isotonic fluid which contains 9 g/L Sodium Chloride and has an osmolarity of 308 mOsmol/L (approx). It contains 154 mmol/L sodium and 154 mmol/L chloride. This is the solution of choice for those with potential risk of or established hyponatraemia.

In some circumstances, children should be administered other isotonic fluids such as glucose 5%, or Hartmann’s solution/Ringer-Lactate solution. Therefore IV fluid choice should be tailored to each patient’s individual needs. These circumstances include:

peri and immediate post operative patients
if plasma sodium is at the lower normal reference range
intravascular volume depletion
hypotension
sepsis
excessive gastric, stoma or diarrhoea loss
salt-wasting syndromes and chronic conditions such as diabetes, cystic fibrosis, adrenal insufficiency, pituitary deficits and those requiring replacement of ongoing losses

Check blood electrolytes and glucose when starting IV fluids and at least every 24 hours thereafter

5.2 Nutrition

The nutrition team in the hospital will accept referrals for advice and management of difficult patients. Pharmacy will advise on initiating and incrementing PN, and each patient should be discussed daily with a ward pharmacist.

Basic Components:

These are general guidelines. individual patients may require more or less than the suggested target values given.

Most paediatric parenteral nutrition is presented as two separate solutions – an aqueous phase containing amino acids, carbohydrate and electrolytes, and a separate lipid phase. This is generally a result of stability issues in mixing aqueous & lipid phases within the volumes used in paediatric patients

Amino Acids

Increase slowly over 2 – 3 days to:

up to 10kg 5-3g/kg
10 - 20kg 2g/kg
20kg+ 5g/kg

An age appropriate protein source will be selected by preparative services, there is no need to specify.

Carbohydrate

Start at Glucose 10% and increase as appropriate

10% is the maximum carbohydrate concentration for peripheral administration
Max 18g/kg/day Glucose

Fat

Start at 0.5 – 1g/kg/day and increase as tolerated –

Max 3g/kg/day
Deranged LFTs and /or elevated bilirubin do not necessarily prohibit giving lipid, however caution is advised & be conservative when starting/incrementing.
Caution is also advised when giving lipid to a septic patient
Aim to keep triglycerides <2mmol/L
The standard lipid emulsion used in haematology/oncology patients is based on Soybean oil, Medium chain triglycerides, Olive oil and Fish oil – known as SMOF
It is thought that SMOF lipid emulsion may be associated with better liver tolerance
Some patients, especially those who have previously been administered Gemtuzumab Ozogamicin or Alemtuzumab are often intolerant of lipid. In these patients, perform baseline cholesterol and triglyceride levels, start at 0.25g/kg/day and increment slowly.
A kcal/amino acid ratio of at least 170kcal/gN₂ should be maintained. Calculate total calories as provided by carbohydrate and fat only (NOT protein). The ideal calorie ratio is 60% CHO : 40% Fat. Pharmacy will advise on this.

Electrolytes – Daily Requirements:

	Up to 10kg	10 – 20kg	20kg+
Na (mmol/kg)	2.5	2.5	2.5
K (mmol/kg)	2.5	2.5	2.5
Ca (mmol/kg)	0.5	0.25	0.2
Mg (mmol/kg)	0.25	0.2	0.2
PO4 (mmol/kg)	0.5	0.5	0.25

These are considered as baseline electrolyte requirements and can be used as a guide when initiating PN. Consider what electrolytes the patient has received from IV fluids in the 24 hours prior to starting parenteral nutrition as baseline figures given above may not be sufficient. Also consider factors that might promote loss and lead to increased requirements (e.g. AmBisome, diuretics etc.)

Trace elements:

<15kg Peditrace 1ml/kg or 1ml/100ml (whichever is less - max 10ml)
>15kg Additrace 0.25ml/kg/day (max 10ml)
Trace elements are added automatically
If, for any reason, you specifically do not want trace elements added, make this clear
Caution in renal/hepatic impairment – consider giving trace elements twice-weekly only
Trace element screen should be done after approx. 1 month on PN, then repeated at monthly intervals.
**NB: A high CRP affects assay results for trace elements – try to assay at a time when CRP is not elevated (if possible!)**

Vitamins:

Solivito (water-soluble Vitamins B1,2,6 & 12, Vitamin C, Folic Acid)
Added automatically at day 1 of PN. Solivito is added at 1ml/kg or 1ml/100ml (whichever is less – max 10ml)

Vitlipid (fat-soluble vitamins A,D,E & K)
Added automatically once lipid started. Vitlipid Infant 4ml/kg (max 10ml) is used until 11 years old then Vitlipid Adult 10ml added

In patients who are not able to tolerate lipid for an extended period discuss with pharmacy. Cernevit may be used which contains both water and fat soluble vitamins, but note this preparation does not contain Vitamin K.

Ordering:

Order PN Mon – Thurs on a daily basis
Order three days PN Fri for weekend/public holidays (festive holidays may differ – discuss with pharmacy)
Pharmacy will liaise with ward medical staff every day (Mon – Fri) for prescriptions
PN MUST BE CONFIRMED BY 1pm AT THE LATEST
All PN patients should have daily U/Es, LFTs, Mg, Bone Profile, Glucose & Triglycerides ordered
It is the responsibility of ward medical staff to ensure that biochemistry results are available in order to safely make decisions on an appropriate PN prescription
Aqueous PN and lipid should be prescribed daily on individual patient fluid prescription sheets.

5.3 Electrolyte Supplements

Sodium:

Hyponatraemia is common in paediatric haematology/oncology patients, often as a result of inappropriate administration of free water intravenously. A syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a common cause of hyponatraemia, particularly in brain tumour patients. It is also frequently associated with Vincristine therapy (exacerbated by concomitant administration of azole antifungal drugs). See Appendix 2 for table listing common drugs used in haemato-oncology patients that can cause SIADH (note that arginine vasopressin is also called antidiuretic hormone).

SIADH can also be seen in patients with respiratory conditions and/or other infections.
Beware of pseudohyponatremia which is a condition where serum sodium is <135mmol/L, but serum osmolality is maintained within normal limits (280-295 mOsm/kg H2O). Pseudohyponatraemia is caused by a displacement of serum water by elevated serum lipid (hyperlipidemia) or proteins (hyperproteinemia), or in cases of hyperglycaemia which causes increased movement of water out of cells. These patients should be considered as in isonatremic.
SIADH is diagnosed when the following criteria are met (taken from Bartter & Schwartz in 1967):

Criteria for Diagnosing SIADH

Decreased effective osmolality of the extracellular fluid (P_osm <275 mOsmol/kg H₂O).

Inappropriate urinary concentration (U_osm >100 mOsmol/kg H₂O with normal renal function) at some level of plasma hypo-osmolality.

Clinical euvolemia, as defined by the absence of signs of hypovolemia (ortostasis, tachycardia, decreased skin turgor, dry mucous membranes) or hypervolemia (subcutaneous odema, ascites).

Elevated urinary sodium excretion (>20-30 mmol/L) while on normal salt and water intake.

Absence of other potential causes of euvolemic hypo-osmolatlity: severe hypothyroidism, hypocortisolism (glucocorticoid insufficiency).

Normal renal function and absence of diuretic use, particularly thiazide diuretics.

H₂O = water; kg = kilogram; mmol = millimole; mOsmol = milliosmole; P_osm= plasma osmolality; SIADH = syndrome of inappropriate antidiuretic hormone secretion; U_osm= urine osmolality

Decreased effective osmality of the extracellular fluid
Ongoing sodium losses from vomitus, diarrhoea or stomas are frequently seen but renal leak is rare
Plasma and urinary electrolytes and osmolality MUST be obtained and a cause of hyponatraemia must be established before effective therapy can commence
A clinical evaluation of the patient’s hydration status is mandatory and this should include regular weights as well as examination of the fluid balance
Correcting the cause of hyponatraemia (frequently by fluid restriction rather than sodium supplementation) is the cornerstone of the management of hyponatraemia
Most hyponatraemic patients can be managed safely and appropriately with fluid restriction
Patients may become symptomatic when plasma sodium is <130mmol/L. Serious complications are more likely at plasma sodium levels <125mmol/L or following a rapid fall in plasma sodium.
If Sodium supplementation is necessary:

Dose

Acute supplementation:

Na required = (desired Na – observed Na) x 0.6 x weight(kg) (mmol)
Replace SLOWLY over 24 – 48 hours
Maintenance fluids (Sodium Chloride 0.9%) are sufficient for most deficits
Maintenance: 5 – 5mmol/kg/day

Preparations

Sodium Chloride 0.9% = Na 154mmol in 1000ml
Sodium Chloride 2.7% = Na 0.5mmol/ml (use only in acute hyponatraemia protocol)
Sodium Chloride 30% = Na 5mmol/ml

ORAL

Sodium Chloride SR 600mg = Na 10mmol + Cl 10mmol (Slow Sodium^â)
Sodium Chloride 30% oral = Na 5mmol/ml

Oral supplementation is unpleasant and rarely necessary. Patients should not be discharged on Sodium supplements without discussion with the consultant concerned and plans for routine Biochemistry monitoring.

A detailed management of symptomatic hyponatraemia and trust policy on management can be found here.

Potassium:

Supplement if K < 3mmol/L OR if symptomatic

Consider sources of ongoing losses, drug therapy etc before decision to treat.

Dose

Acute supplementation:

Maintenance:

0.2mmol/kg/hr
ECG monitoring is recommended above 0.2mmol/kg/hr (MAX 0.5mmol/kg/hr – PICU only)
Repeat U/Es 3 hours after acute supplementation

1 - 2mmol/kg/day

Administration

Standard volume:

Minimum volume:

usual max. conc. 40mmol/L

**CENTRAL ADMINISTRATION ONLY**
General agreement within RHC to use 80mmol/L as max concentration outwith PICU. More concentrated solutions have been used but max. conc. is 1mmol/ml
(NB ANECDOTAL EVIDENCE)

In exceptional circumstances a maximum concentration of 200mmol/L (ie 20mmol in 100ml) could be used following discussion with patients’ consultant and pharmacy. This equates to the maximum stable concentration which could be administered in a parental nutrition solution for central administration.

**Also consider use of K-sparing diuretics e.g. amiloride **

Preparations

IV	Potassium Chloride 15% = K 2mmol/ml (NB CONTROLLED DRUG) Glucose 2.5% and Sodium Chloride 0.45% with potassium chloride 20mmol/L Plasmalyte-148 (contains K 5mmol/L)
NB Potassium chloride 15% solution MUST ONLY be added to plain infusion bags. NEVER add additional potassium to a ready to use preparation containing potassium.
ORAL	Tablets Span K 600mg e/c8mmol K + 8mmol Cl (NB unlicensed preparation) Sando K dispersible 12mmol K + 8mmol Cl Liquid Potassium Chloride 1mmol/ml K + 1mmol/ml Cl
Patients should NEVER be discharged home on amiloride AND potassium supplements without consultant authorisation.

Calcium:

Supplement if corrected Ca < 2mmol/L OR if symptomatic.

Rarely necessary – consider sources of ongoing losses before decision to treat

Dose

Acute supplementation:

Maintenance:

0.07mmol/kg
(0.3ml/kg of Calcium Gluconate 10%)

0.25 – 1mmol/kg/day (in divided doses)

Administration

Standard volume:

Minimum volume:

Standard rate:

Maximum rate:

Dilute 1 in 5 (0.045mmol/ml)

Give undiluted (NB Central Line only)

0.0225mmol/minute

Urgent supplementation: slow bolus over 5–10 mins
Intermittent infusion: 0.35-0.9mmol/min
Continuous infusion: not greater than 20mmol/hr
(NB Central Line only)

Preparations

Calcium Gluconate 10% = Ca 0.225mmol/ml
(Use of Calcium Chloride is not recommended due to precipitation/incompatibility issues.)

ORAL

Tablets
Calcichew                 12.6mmol Ca
Calcichew Forte        25mmol Ca
(Calcichew preparation with D₃ also available)
Adcal 1500mg          15mmolCa
Adcal D₃ 750mg      7.5mmol Ca

Dispersible Tablets
Sandocal 1000 disp 25mmol Ca/tab
(dissolve 1 tab in 45ml water, gives 25mmol in 50ml volume approx)
Cacit 500 12.5mmol Ca/tab
(dissolve 1 tab in 20ml water, gives 12.5mmol in 25ml volume approx)

Liquid
Alliance Calcium Syrup 2.5mmol Ca/5ml
(NB unlicensed preparation)

Magnesium:

Supplement if Magnesium <0.6mmol/kg OR if symptomatic

Consider sources of ongoing losses, drug therapy etc before decision to treat

Dose

Acute supplementation:

Maintenance:

0.2mmol/kg
Repeat every 12 hours if necessary (BNF-C)
0.1-0.2mmol/kg
Repeat every 4-6 hours if necessary (Evelina)

0.2-0.25mmol/kg/day

Administration

Standard volume:
Minimum volume:

Standard rate:

Maximum rate:

Dilute 1 in 5 (0.4mmol/ml)
Dilute 1 in 2.5 (0.8mmol/ml)
OR CENTRALLY ONLY 1 – 2mmol/ml

Slow IV bolus over at least 10 mins
Rate should not exceed 0.4mmol/kg/min

Slow bolus for smaller doses (up to 8mmol)
Continuous infusion for bigger doses (up to 160mmol over 24 hours)

NB CENTRALLY ONLY

Preparations

IV:

Magnesium Sulphate 50% = 2mmol/ml Mg

ORAL:

Tablets
Magasorb: 6mmol Mg/tab
Magnesium Glycerrophosphate: 4mmol Mg/tab

Liquid
Maalox: 3.4mmol Mg/5ml
Magnesium Glycerrophosphate 1mmol/ml
Magnaspartate sachets – 10mmol/sachet
(dissolve 1 sachet in 50ml water. May be dissolved in 20ml water but note that this is off-label use)

Phosphate:

Supplement if phosphate < 0.7mmol/kg OR if symptomatic

This is rarely necessary, hypophosphataemia is usually dilutional. Tubular phosphate leak must be proven prior to consideration of supplementation. There is very poor compliance with oral phosphate supplements because of their unpleasant taste & side effects.

Dose

Acute supplementation:

Maintenance:

0.3-1mmol/kg/day

0.15 – 0.3mmol/kg/day

Administration

Standard volume:
Minimum volume:

Standard rate:

Maximum rate:

Dilute to 0.1mmol PO₄/ml
0.4mmol PO₄/ml

0.05mmol/kg/hour

IN EMERGENCY ONLY
0.5mmol/kg/hour

Preparation

IV:

Potassium Acid Phosphate 13.6% = 1mmol/ml
PO₄AND 1mmol/ml K
Phosphate Polyfusor – contains 50mmol PO₄, 8mmol Na, 9.5mmol K in 500ml

NB INTRAVENOUS PREPARATIONS CONTAIN POTASSIUM - SAFETY GUIDELINES AS FOR POTASSIUM CHLORIDE APPLY

ORAL:

Tablets
Phosphate Sandoz = PO₄ 16.1mmol / Na 20.4mmol / K 3.1mmol

Liquid
Potassium Acid Phosphate 13.6% = 1mmol/ml PO₄ + K
Molar Sodium Phosphate = PO₄ 1mmol / Na 1.6mmol / K 0.2mmol per ml
(NB Unlicensed product – use ONLY if K↑)

Appendix 1: Assessment of Hyponatraemia

Appendix 2: Drugs known to cause hyponatremia by affecting arginine vasopressin (AVP) production or action

Drugs known to cause hyponatremia by affecting arginine vasopressin (AVP) production or action
Mechanism	Drugs
Increased hypothalamic AVP production	Anti cancer agents: Vinc Alkaloids (vincristine, vinblastine) Platinum compounds (cisplatin, carboplatin)* Alkylating agents (cyclophosphamide, ifosfamide, melphalan) Others (methotrexate, interferon-x and interferon-y) Palliative medications: Opioid analgesics Antidepressants (tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors) Antipsychotics (phenothiazines, haloperidol) Anti epileptics (carbamazepine, oxcarbazepine, sodium valproate)
Potentiation of AVP actions	Anti cancer agents: Alkylating agents (cyclophosphamide) Palliative medications: Nonsteroidal anti-inflammatory drugs Anti epileptics (carbamazepine, lamotrigine) Antidiabetic agents (chlorpropamide, tolbutamide)
* Cisplatin may also cause hyponatremia by damaging renal tubules and interfering with sodium reabsorption. Adapted from Liamis G, Milionis H, Elisaf M. A review of drug-induced hyponatremia. Am J Kidney Dis 2008;52:144-153

References

BNF/ BNF-C (access via www.medicinescomplete.com)

www.clinicalguidelines.scot.nhs.uk/ggc-guideline-library

National Institute for Health and Care Excellence (NICE) guidelines (www.nice.org.uk)

Evelina London Paediatric Formulary

Handbook on Injectable Drugs (Trissel LA) American Society of Health-System Pharmacists (access via www.medicinescomplete.com)

Minimum Infusion Volumes for fluid restricted critically ill patients (4^th Edition Dec 2012). www.ukcpa.org

Editorial Information

Last reviewed: 01 March 2020

Next review: 31 March 2023

Author(s): Carol Mitchell & J Sastry

Version: 3

Approved By: Schiehallion Clinical Governance Group

Document Id: RHC-HAEM-ONC-008

NHSGGC Guidelines