Saline Loading in Patients with Acute Diarrhoea Associated Haemolytic Uraemic Syndrome

1. Saline Loading in Patients with Acute Diarrhoea Associated Haemolytic Uraemic Syndrome Dr Sheetal Bhojani Royal Hospital for Sick Children, Glasgow

2. Background Haemolytic uremic syndrome (HUS) consists of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure It is one of the commonest causes of acute renal failure in children It typically follows enteral infection caused by Verocytotoxin producing Escherichia Coli (VTEC) 5 – 15% of children infected with VTEC develop HUS

3. Incidence of VTEC Infection

4. Age-related risk of HUS with VTEC infection

5. HUS outbreak in Europe in May 11 Outbreak in Germany. Smaller numbers identified in Sweden, Denmark, the Netherlands, Spain, Canada, USA and the UK Approximately, 3785 cases and 45 deathsdue to HUS E.Coli O104:H4 was the causative strain for the outbreak This VTEC strain has been only detected once in Scotland in 2005

6. Case 1 4 year old male Presented to DGH with 3 day history of bloody diarrhoea and vomiting Continued to pass urine Given IV fluids for 4 days Bloods : active haemolysis (blood film – fragmented red cells) and deteriorating renal function without oliguria Transferred to RHSC for further management

7. Investigations on admission to RHSC Glasgow: Hb 70 gm/lit Platelets 69 x 109/lit Blood film – fragmentation, anisocytosis Urea 16.3 mmol/lit Creatinine 91 umol/li LDH 2048 I.U/lit Stool cultures – E.Coli O157:H7 was isolated

8. Treatment Intravenous fluids (0.9% NaCl + 5% D) for 24 hours Blood transfusions x 2 Satisfactory urine output No renal replacement therapy required Renal function improved in 6 days Bloods on discharge Hb 100, Platelets 163 Urea 6.6, creatinine 43 LDH 1061

9. Case 2 10 year old girl Referred by GP History of vomiting, diarrhoea (no blood) and abdominal pain for 8 days History of reduced urine output (as per parents)

10. Investigations Bloods on admission to RHSC Glasgow Hb 106, Platelets 30 Blood film – anisocytosis, polychromasia, fragments Urea 22.8, Creatinine 175 LDH 1044 Antibody to E.coli O157 - positive

11. Treatment Intravenous fluids – bolus (10ml/kg 0.9% NaCl) + maintenance (0.9%NaCl+ 5% D) for 4 days Blood transfusion x 2 No renal replacement therapy required Renal function improved in 5 days Bloods on discharge Hb 99, Platelets 82 Urea 14.5, Creatinine 107

12. Relative Nephroprotection During Escherichia coli O157:H7 Infections: association with intravenous volume expansion Julie A. Ake, Srdjan Jelacic, Marcia A. Ciol, Sandra L. Watkins, Karen F. Murray, Dennis L. Christie, Eileen J. Klein and Phillip I. Tarr Pediatrics 2005;115;e673

13. Prospective single centre cohort study • Included 29 patients with HUS, aged <10 years • Infected children were enrolled when - they presented with acute bloody diarrhoea or - as contacts of patients who were known to be infected with E coli O157:H7 or - if they had E coli O157:H7 confirmed on culture or - if they presented with HUS

14. HUS was defined by • The presence of hemolytic anemia (hematocrit of 30%, with fragmented erythrocytes on peripheral-blood smear) • Thrombocytopenia (platelet count of 150 000/mm3) • Renal insufficiency (serum creatinine concentration that exceeded the upper limit of normal for age) • Oligo-anuria was defined as a urine output 0.5 mL/kg per hour for 24 consecutive hours

15. Results • 13 patients developed non oligo-anuric renal failure and 16 patients, oligo-anuric renal failure • Patients with non oligo-anuric renal failure received earlier (in the illness) and more intravenous fluids and sodium before HUS developed • All patients with oligo-anuric renal failure required dialysis • Median length of hospital stay after diagnosis of HUS was 12 days in oligo-anuric patients and 6 days in non oligo-anuric patients • The serum sodium concentrations at HUS onset were significantly higher in the non oligo-anuric group than in the oligo-anuric group (p 0.001)

16. Conclusion • Early recognition of HUS and parenteral volume expansion during E coli O157:H7 infections, well before HUS develops, is associated with attenuated renal failure • Isotonic intravenous fluids are superior to hypotonic fluids for use as maintenance

17. Early Volume Expansion During Diarrhoea and Relative Nephroprotection During Subsequent Hemolytic Uremic Syndrome • Christina A. Hickey, T. James Beattie, Jennifer Cowieson, Yosuke Miyashita, C. Frederic Strife, Juliana C. Frem, Johann M. Peterson, Lavjay Butani, Deborah P. Jones, Peter L. Havens, Hiren P. Patel, Craig S. Wong, Sharon P. Andreoli, Robert J. Rothbaum, Anne M. Beck, Phillip I. Tarr • Arch Pediatr Adolesc Med. 2011;165(10):884-889

18. Objectives • To determine if interventions during the pre-HUS diarrhoea phase are associated with maintenance of urine output during HUS

19. Settings • Ten paediatric hospitals in the United States and one in Scotland • Prospective observational cohort study

20. Methodology 50 children <18 years of age with HUS were included in the study Interventions Intravenous fluids were given within the first 4 days of the onset of diarrhoea

21. Results 34 (68%) of the 50 participants developed oligoanuria 21 of them had received no intravenous fluids in the first 4 days of illness The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% CI 1.1 - 2.4, p=0.02) Children with oligoanuric HUS received less total intravenous fluid (p=0.02) and sodium (p=0.05) in the first 4 days of illness than those with normal urine output

22. Results • Multivariable analysis confirmed that fluid volume given in the first 4 days of illness was significantly associated with nephroprotection after controlling for other variables (age, antibiotics, total intravenous sodium) that might have affected the development of oligoanuria

23. Conclusion Intravenous volume expansion early in illness is associated with better renal outcome

24. Limitations • Volume of fluids to be given and the optimal sodium content (authors recommend isotonic fluids) • Risk benefits of giving fluids to patients with deteriorating renal function (although no patient developed pulmonary oedema)

25. Issues • Delayed microbiological diagnosis – sometimes difficult to identify patients at risk • Positive stool cultures – depends on the stage of illness at the time of presentation • Defining cases who need intravenous fluids • Only 5 -15% of VTEC infected cases develop HUS • Only about 50% of cases have positive stool culture (2nd paper)

26. Issues • Hesitancy in giving fluids to children at the risk of renal failure (risk of cardiopulmonary overload and hypertension) • How much fluid? – randomised controlled trials required • When to give fluids? – 10/11 patients from Glasgow developed oligo- anuria. Should fluids start earlier?

27. Intravenous Fluids • In the study – patients with normal urine output received median total fluids of 1.7 lit/m2 (0 – 7.5 lit/m2) Case 1 : • 4 year old received total fluids of 5.2lit/m2 Case 2 • 10 year old received total fluids of 4.3lit/m2

28. Clinical Question • 5 year old male presents with bloody diarrhoea and vomiting • Stool cultures – E coli O157:H7 • Normal bloods (FBC and renal function) Action • Do we give IVF? If yes, how much, how long? • How often do we monitor bloods? • Clinical information for parents

29. Thank you