Children. Reduction on Introduction of Isotonic Maintenance Fluids? - PowerPoint PPT Presentation

Hyponatremia in Hospitalized Infants and Children. Reduction on Introduction of Isotonic Maintenance Fluids? Authors: Dipen Patel 1 , MD, Shikha Y Kothari 1 , MBBS, Somashekhar Nimbalkar , MD 1,2 , Rajendra Desai, MSc 2 and A. Phatak, MPH 2 . Affiliations: 1 Department of Pediatrics, Pramukhswami Medical College, Karamsad, 388325, India and 2 Central Research Services, Charutar Arogya Mandal, Karamsad, 388325, India.

No Conflicts of Interest to Disclose None of the authors have any conflict of interest to disclose. I wish there were some fancy ones though! (If there were, one slide will ever be enough) 11/4/2015 2

Background Dietary intake of water and electrolytes is closely matched by  renal and extrarenal excretion, and body composition remains essentially constant. Regulation of sodium balance through varying sodium excretion  is central to the control of effective circulatory volume. Hyponatremia is the most common electrolyte abnormality  found in hospitalized children, and is an independent predictor of increased medical costs, along with being an independent risk factor for patient mortality.

Hyponatremia BMJ 1992;304:1218-22 Over a period of six years (1984- 90) about 16 previously healthy children (aged under 16) who had developed symptomatic hyponatraemia and either died or suffered permanent brain damage. Hyponatraemic seizures and excessive intake of hypotonic fluids in young children BMJ 1999; 319 Case series of acute hyponatremia and convulsions caused by excessive intake of oral fluids with sodium levels as low as 116 mmol/L. 1/30/2014

Intravenous fluids for seriously ill children: Time to reconsider Duke, Trevor;Molyneux, Elizabeth M The Lancet; Oct 18, 2003; 362, 9392; 1/30/2014

Intravenous fluids for seriously ill children Time to reconsider • Hypotonic iv fluids given at maintenance rates might be unsafe, especially in developing countries as serum sodium concentration is not monitored • Sick patients have reduced free-water clearance, and hypotonic saline solutions at maintenance rates or greater put patients at risk of hyponatraemia and encephalopathy-the syndrome of water intoxication. • Safest empirical iv fluid for most children with serious infections, who cannot take enteral fluids, is 0.9% sodium chloride with dextrose 1/30/2014

Main Mechanisms of Hyponatremia 1. Dilution of extracellular fluid due impaired free-water excretion (AVP excess) 2. Increased urinary sodium losses 1/30/2014

1/30/2014 Companion 2014 Vadodara

How Common is it? • Hyponatraemia arises in between 20% and 45% of children with meningitis, pneumonia, encephalitis, septicaemia, cerebral malaria and somewhat less often in those with bronchiolitis. • 70% of infants with acute bronchiolitis had impaired free- water excretion; at recovery, free-water clearance was up to 15 times more than at the time of admission 1/30/2014

So have organizations taken note? 30 September 2007 Institute for Safe Medication Practices (ISMP) of both Canada (2008) and the USA (2009) 1/30/2014

Objectives Objective: To compare incidence of hyponatremia and  hypernatremia in children admitted to PICU, after the shift in maintenance I.V. fluid administration practices. Before 2010, department protocol entailed initial administration  of a hypotonic solution, 5% dextrose with 0.2% sodium chloride, to all patients upon hospital admission after correction of shock, etc After 2010, department practices changed. All patients were  administered an isotonic solution with the advised composition of 5% dextrose and 0.9% sodium chloride.

Methods • Study Site: Pediatric Intensive Care Unit (PICU), Shree Krishna Hospital, Karamsad-Gujarat-India • Inclusion Criteria: All children hospitalized to the PICU of SKH and administered intravenous fluids from January 2009 to December 2010, except those on an oral diet/nasogastric feed providing more than 20% of daily requirement. Karamsad, Anand District, Gujarat

Methods • Patients admitted from January 2009 to December 2009 were administered hypotonic maintenance fluid (5% Dextrose with 0.2%NaCl) • January 2010 onwards, patients were administered isotonic maintenance fluid (5%Dextrose with 0.9%NaCl) • Medical records of these patients were studied. • All demographic details and sodium level values were recorded, along with date and time of sending investigation. • Data was entered with Microsoft Excel, and Chi-square test with help of SPSS was used for analysis.

Results Particulars Isotonic Non Isotonic p-value Male gender 293(67.7%) 148(65.5%) 0.27 2009 113(26.1%) 187(82.7%) <0.001 2010 320(73.9%) 39(17.3%) Consciousness Conscious 122(28.17%) 64(28.3%) 0.96 Altered 311(71.8%) 162(72.3%) Inotropes required 224(51.7%) 99(43.8%) 0.18 Sodium imbalance Hyponatremia 145(33.5%) 116(51.3%) <0.001 Hypernatremia 91(21.0%) 40(17.7%) NS Mean(SD) Mean(SD) Sodium Level 139.45(11.14) 136.37(11.04) 0.001 Potassium Level 4.03(1.14) 4.29(1.04) 0.006 Outcome N= 425 N=221 Discharge 221(52.0%) 118(53.4%) NS DAMA 151(35.5%) 85(38.5%) Expired 53(12.5%) 18(8.1%) 11/4/2015 EAP 2015, OSLO 14

Results • Of 448 admitted children, 169 were female. • Of 198 admitted children in 2009, 99 (50%) had hyponatremia, as compared to 101 (40.4%) of 250 admitted children in 2010. • Incidence of hyponatremia after 24 hours’ intravenous hypotonic fluid administration was 23 ( 63.9% ) out of 36 • This incidence was significantly higher than the group administered isotonic fluids: 27 ( 30.7% ) out of 88 children ( p=0.0013 ).

Results • Incidence of hypernatremia was 8 ( 22.2% ) of 36 in children receiving hypotonic fluids, which did not significantly differ from incidence in children receiving isotonic fluids [17( 19.3% ) of 88, p=0.9 ]. • Effect on outcome did not significantly differ between two groups: • 20 ( 55.6% )of 36 children receiving hypotonic fluids either expired or took discharge against medical advice, as compared to 39 ( 44.3% )of the 88 receiving isotonic fluids ( p=0.347 ).

Box Plot (Comparing the incidence of hyponatremia in each group) ( p=0.0013 ).

Discussion • Most work on maintenance fluid requirements was done in the 1950`s, when children had a diet much lower in sodium. • The basis for using hypotonic fluids is an assumption that the sodium concentration in intravenous fluids should reflect that found in the diet of a healthy child. • But hospitalized children present numerous stimuli that augment production of ADH.

Is 0.9% Saline of Use? • Relation between arginine vasopressin levels and hyponatremia following percutaneous renal biopsy in children receiving hypotonic or isotonic intravenous fluids. RCT • Minimally invasive procedure is associated with high AVP levels resulting in hyponatremia & normal saline can effectively prevent hyponatremia even in presence of elevated AVP levels. • Even a minimal positive balance of hypotonic fluids can lead to water retention, vasoconstriction, antidiuresis and eventually fatal symptomatic hyponatremia that precipitates pulmonary edema, cerebral edema, transtentorial herniation, respiratory arrest, coma and death. • Kanda K, Nozu K, Kaito H, et al. in Pediatr Nephrol 2011; 26:99 – 104. 1/30/2014

Intravenous fluid regimen and hyponatraemia among children: a RCT. • First large prospective randomized fluid trial conducted in general pediatric patients who are nonsurgical and not admitted to the ICU. • 14.3% (8/56) of the children administered 0.18% saline in 5% dextrose at the standard maintenance rate (Group B) developed hyponatraemia compared with 1.72% of the children in Group A (0.9% saline in 5% dextrose at the standard maintenance rate) and 3.8% of those in Group C (0.18% saline in 5% dextrose at two-thirds of the standard maintenance rate). • Hypotonic fluids result in hyponatremia and that 0.9% sodium chloride prevents the development of hyponatremia. • This was at 72 h or till IV fluids while we had at 24 h a high 63% hyponatremic 1/30/2014 Kannan L, Lodha R, Vivekanandhan S, et al. in Pediatr Nephrol 2010; 25:2303 – 2309.

Many Systematic reviews in the previous three years Foster BA, Tom D, Hill V Hypotonic versus isotonic fluids in hospitalized children: a systematic review and meta-analysis. J Pediatr. 2014 Jul;165(1):163-169.e2. 11/4/2015 21