1. Slide 1 Intravenous Fluids in Children NPSA Guidelines Dr Pam Cupples SPAN Meeting Friday the 20 th of April 2007 Dunkeld

2. Slide 2 Aims  Historical approach to fluid management based on Holliday & Segar’s ‘4/2/1’ formula  Problems with hypotonic fluids in the Paediatric Population  NPSA guidelines

3. Slide 3 Maintenance Fluid Requirements Maintenance fluid requirements parallel energy metabolism  Energy Expenditure - using tables and nomogram Darrow et Pratt, JAMA 1950  Body surface Area – Crawford et al, Pediatrics 1950  Age - Wallace, Am. J. Clin. Path. 1953  Weight – Holliday & Segar, Pediatrics 1957

4. Slide 4 Holliday & Segar’s Formula  ‘healthy’ infants and children  Energy expenditure at rest and during activity  Energy expenditure equated to water requirements  1ml of water required to burn 1 calorie 1.2mls water are consumed1.2mls water are consumed 0.2mls water are produced0.2mls water are produced  3mmols/kg of Na  2mmol/kg of K  Infants require ~ 100cal/kg/day  Older Children ~ 75cal/kg/day  Adults ~ 35cal/kg/day Calorie Requirements 100cal/kg/day<10kg 50cal/kg/day10-20kg 20cal/kg/day>20kg Hypotonic fluid 0.18% NaCl with 4% Dextrose

5. Slide 5 How we got the ‘4-2-1’ rule Calorie Requirements Based on Weight 0-10kg: 100cal/kg/day 10-20kg: 1000cal + 50cal/kg/day for each kg over 10kg > 20kg: 1500cal + 20cal/kg/day for each kg over 20kg Water Requirements – ‘ 4-2-1 rule’ 0-10kg: 100 water/kg/day ( 4ml / kg/ hour) 10-20kg: 1000 water + 50 water/kg/day for each kg over 10kg ( 2ml/kg/hour) > 20kg: 1500 water + 20 water/kg/day for each kg over 20kg (1ml/kg/hour)

6. Slide 6 Holliday & Segar - the flaws The Maintenance Need for Water in Parenteral Fluid Therapy– Pediatrics 1957 WEIGHT  Illner et al 2000 - resting energy expenditure is based on fat free mass  Accounts for 80% of the BMR but only 7% of the total body mass  Calculating energy expenditure based on weight significantly over estimates the calorie requirements and hence the water requirements

7. Slide 7 Energy Expenditure  No allowance for the different energy expenditure in acute disease / post surgery  Actual energy expenditure is 50% lower than values used by Holliday & Segar –Briassoulis et al, 2000 –Lindahl et al, 1988  Lower energy requirements due to : –50% of calorie expenditure allowed for growth –Catabolic state –Inactivity –PICU setting – IPPV / sedated and paralysed  Exceptions – fever,sepsis & burns

8. Slide 8 Water Losses  Insensible water losses 27ml/kg/day –Heeley & Talbot, 1955  50% of this value – Lamke, 1977 –Skin 7ml/kg/day –Lungs 5ml/kg/day  Urinary losses –50-60ml/kg/day Holliday & Segar, 1957  No allowance for non-osmotic stimuli for ADH –Stress, pain, surgery, fever –Drugs – opioids, NSAIDs –Urinary volume reduced to 25ml/kg/day  Endogenous water production from tissue catabolism –  in acute illness

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10. Slide 10 Hazards of Hypotonic Fluids Acute Hospital Acquired Hyponatraemia  Prescription of hypotonic fluids  Provision of excess free water in conditions where patient unable to excrete the excess water load  Non – osmotic stimuli for ADH

11. Slide 11 Non Osmotic Stimuli for ADH Secretion –Stress –Pain –Post-operative period –Sepsis –Pyrexia –Nausea & vomiting –Co-existing medical conditions CNS infectionsCNS infections Respiratory disordersRespiratory disorders Metabolic & endocrine disordersMetabolic & endocrine disordersDrugs  Morphine  NSAID’s  SSRI’s  Barbiturates  Carbamazepine  Clofibrate  Isoprenaline  Chlorpropamide  Vincrisitine

12. Slide 12 Hazards of Hypotonic Fluids Acute Hospital Acquired Hyponatraemia  Acute Hyponatraemia – Na < 136mmols/L occurring within 48 hours –Severe hyponatraemia if Na < 130mmols/L –Or any level of hyponatraemia associated with clinical signs –Risk group ChildrenChildren Premenopausal womenPremenopausal women HypoxiaHypoxia –Hyponatraemic encephalopathy 50% of children with Na<125mmol/L50% of children with Na<125mmol/L 8% mortality rate8% mortality rate –Risk of developing hyponatraemia with hypotonic fluids is 17.2 times than with isotonic fluids Choong et al, 2006Choong et al, 2006 –Children have a poorer outcome than adults for a given level of hyponatraemia

13. Slide 13 Acute Hospital Acquired Hyponatraemia – children at risk Common symptoms  Headache  Nausea & vomiting  Weakness Advanced signs  Seizures  Respiratory arrest  Dilated pupils  Decorticate posturing  Coma  Pulmonary oedema

14. Slide 14 Risks of Hypotonic Fluids 50 cited cases of child death or neurological injury in the international literature 4 deaths and 1 ‘near miss’ in the UK since 2000  Post-op setting in previously healthy children  Minor surgical procedures

15. Slide 15 Conclusions  Hypotonic fluids are not benign but potentially dangerous –17.2 times more likely to develop hyponatraemia with hypotonic fluids than with isotonic  Isotonic fluids offer a safe alternative to hypotonic fluids with no risk of hypernatraemia  Fluid regimes should be tailored to the individual  Appropriate monitoring –Weight, baseline U&E’s

16. Slide 16 Background to the NPSA  March 2003 – RCA asked by the RCPCh to issue warning re. The use of 0.18% Saline in 4% Dextrose  November 2004 – Inquiry set to investigate the deaths of 3 children from hyponatraemia following a documentary  Audit in 2004/2005 – few anaesthetists had seen the warning  NPSA – advice to healthcare professionals on how to reduce risk develop solutions and introduce them into clinical practice

17. Slide 17 NPSA Plan of Action  July 2005 – form an internal working group to assess problem  August 2005 – External working group appointed after  October to November 2005 – meetings of the external group to discuss evidence collected  Dec 2005 – draft of the safe practice recommendations  Jan-Feb 2006 – Wide stakeholder consultation on draft  April 2006 – publish NPSA guidance

18. Slide 18 NPSA – Patient safety alert 22: Reducing the risk of hyponatraemia when administering intravenous infusions to children (Alert 5 of 5) Applies to all paediatric patients from 1 month to 16 years 28 th March 2007  Remove 0.18% NaCl / 4%Dextrose from general stock  Produce and disseminate clinical guidelines for the fluid management of paediatric patients  Adequate training and supervision of staff  Reinforce safe practice  Promote the recording and reporting of hospital acquired hyponatraemia  Audit programme to ensure that the NPSA recommendations are being adhered to

19. Slide 19 NPSA guidelines  Template for developing local guidelines for the prescription & monitoring infusions in children  Importance of rigorous clinical and laboratory monitoring  Prescription of fluids same importance and consideration as other medicines  Fluids must be individualised  Calculate fluid balance and monitor plasma Na

20. Slide 20  Oral fluids preferable to iv  Resuscitation Fluids – bolus of 0.9% saline  Deficit – calculated and replaced as 0.9% saline or 0.9% saline with 5% dextrose  Replace over 24 hours  Maintenance – do not use 0.18% saline with 4% dextrose  0.45%saline with 5% dextrose Children at high risk – only isotonic fluids   Peri and post operative   Na levels lower end of normal or <135mmol/L   Volume depleted   Hypotension   CNS infection   Head injury   Bronchiolitis   Sepsis   Excessive gastric / GI losses   Chronic conditions – CF,IDDM   Salt wasting syndromes

21. Slide 21 NPSA Guidelines Ongoing losses  Assessed 4 hourly  Replacement fluid should reflect the type of electrolyte composition of the fluid being lost  Isotonic safest choice Monitoring  Robust regime  Weight of child  Baseline and daily measurements of Na, K, urea & Cr  More frequent if Na already low or clinical picture changes Training  E-modules to assess current level of competencies & knowledge  Doctors in training (80-90%)  Review their fluid prescriptions IV Prescription Charts  Review & redesign – include guidelines on fluid presciptions  Monitoring data required  How to calculate fluid requirements

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23. Slide 23 www.npsa.nhs.uk/health/alerts

24. Slide 24 Arieff et al, BMJ 1992  Prospective clinical case study  16 children who died or developed permanent neurological damage  0.34% incidence of post-op hyponatraemia (83 affected out of 24,412 patients)  8.4% mortality rate ( 7 deaths) Halberthal et al, BMJ 2001  23 patients –13 hyponatraemic in post-op period –15 referred to critical care 11 from wards and 4 from other institutes11 from wards and 4 from other institutes –Seizures (18) and vomiting (17) –5 had Rx withdrawn due to brainstem herniation –1 patient sustained permanent, severe neurological damage –16 / 23 receiving maintenance fluids at 50% more than recommended values

25. Slide 25 Paut et al, Ann Fr Anesth Reanim 2000  7 Children 3-6 years  ASA 1-2  Scheduled surgical procedures  Vomiting, seizures, status or  GCS (5/7)  1 respiratory arrest with Na 120mmol/L  All had hypotonic fluids  3/7 IPPV  Rx – fluid restriction, NaCl  1 death McRae et al, Int J Pediatr Otorhinolaryngol 1994  3 post-op tonsillectomy patients  2 deaths

26. Slide 26 Choong et al, 2006  Systematic review  6 studies satisified inclusion criteria – 2 unmasked RCT –1 non randomised CT –3 observational studies  Mean Na in hypotonic group –3.39mmol/L  Small number of studies with small group size –Total of 404 patients

27. Slide 27 Holliday & Segar 0-10kg: 100cal/kg/day 10-20kg: 1000cal + 50cal/kg/day for each kg over 10kg > 20kg: 1500cal + 20cal/kg/day for each kg over 20kg