Preoperative Anaemia in the Paediatric Patient: A South ...

Preoperative Anaemia in the Paediatric Patient:

A South African Perspective

Dr. Heidi MeyerRed Cross War Memorial Children’s Hospital

DISCLOSURESNone

Comprehensive Anaemia

Management

MinimisingBlood Loss

Rationale Management of Haemotherapy

Patient Blood Management

“Red-cell-containing components should not be used to

treat anaemias that can be corrected with specific

haematinic medications such as iron, vitamin B12, folic

acid, or erythropoietin.”1

Preoperative Anaemia in Paediatric Patients

Worse outcomes?How common is it?Screening?Effectively treat anaemia?

Does correcting anaemia improve outcomes?

WHO Definition of Anaemia2

Preoperative Anaemia and Outcomes:Paediatric Noncardiac Surgery

Increased postoperative mortality(OR 1.75, 95% CI, 1.15–2.65)3

Increased postoperative morbidity(OR 1.99, 95% CI 1.28-3.10)4

Increased perioperative transfusion(OR 3.60, 95% CI 1.83-7.05)4

Anaemia46.2%

No Anaemia53.8%

Anaemia No Anaemia

Mild Anaemia36.9%

Moderate Anaemia60.0%

Severe Anaemia 3.1%

Mild Anaemia Moderate Anaemia Severe Anaemia

Prevalence of Preoperative Anaemia in SAPSOS4

Variables Anaemic (n = 505) Nonanaemic (n = 589) P ValueHaemoglobin (median, IQR) 10.2 (9.4 - 10.8) 12.4 (11.9 - 13.5) <0.001 Age group (y), n/N (%)

³0.5-1 29/53 (54.7) 24/53 (45.3)³1-4 147/262 (56.1) 115/262 (43.9)³4-13 279/669 (41.7) 390/669 (58.3)³13-16 50/110 (45.5) 60/110 (54.5) 0.001

ASA physical status, n/N (%)1 310/720 (43.1) 410/720 (56.9)2 105/228 (46.1) 123/228 (53.9)³3 87/141 (61.7) 54/141 (38.3) <0.001

Co-morbidity, n/N (%)HIV/AIDS 23/34 (67.6) 11/34 (32.4) 0.013

Grade of surgery, n/N (%)Minor 244/529 (48.5) 285/529 (53.9)

Intermediate 227/491 (45.0) 264/491 (53.8)Major 31/71 (43.7) 40/71 (56.3) 0.199

Urgency of surgery, n/N (%)Elective 279/647 (43.1) 368/647 (56.9)Urgent 134/261 (51.3) 127/261 (48.7)

Emergency 92/186 (49.5) 94/186 (50.5) 0.918

Prevalence (%) of Anaemia in South African Hospitals

47.8

28

71

40.8

24

46.2

0 10 20 30 40 50 60 70 80

Marsicano D et. al. 2018, Noncardiac Surgery (8)

Conradie W et. al. 2020, Noncardiac Surgery (7)

Jadhunandan K et. al. 2020, Open intraabdominal Surgery (6)

ADULT STUDIES

Wege M 2015, 6m to 36m Acute Hospital Admissions (5)

(Faraoni D et. al. 2016, 1yr to <18yrs, Noncardiac Surgery) (3)

Meyer HM et. al. 2020, 6m to <16yrs, Noncardiac Surgery (4)

PAEDIATRIC STUDIES

SAVACG survey (1994)9

Anaemia 21.4%IDA 5%

n= 4 494

Primary Schools Feeding Scheme

(1994)

SAVACG survey (1994)Anaemia 21.4%

IDA 5%n= 4 494


(1994)

Food Fortification Programme

(2003)


IDA 5%n= 4 494

NFCS-FB-I (2005)10

Anaemia 28.9%IDA 7.6%

n= ?


(1994)


(2003)

SANHANES-1 (2013)11

Anaemia 18.8%IDA 8.1%

n= 511


IDA 5%n= 4 494

NFCS-FB-I (2005)Anaemia 28.9%

IDA 7.6%n= ?


(1994)


(2003)


IDA 5%n= 4 494

NFCS-FB-I (2005)Anaemia 28.9%

IDA 7.6%n= ?

SANHANES-1 (2013)Anaemia 18.8%

IDA 8.1%n= 511


(1994)


(2003)

DHS (2016)12

Anaemia 61.3%IDA ?

n= 1 094

National School Deworming Programme

(2016)

Screening ForIron Deficiency Anaemia in Children

Bone marrow

MCV

Serum Ferritin

Transferrin Saturation

Reticulocyte Haemoglobin Content

Serum Ferritin

WHO definitions14

< 12 μg/L in children < 5 years< 15 μg/L in children ≥ 5 years

If CRP > 5

< 30 μg/L in children < 5 years < 70 μg/L in children ≥ 5 years

Biomarkers Reflecting Inflammation and Nutritional Determinants of Anaemia15

Adjusted ferritin = unadjusted ferritin − β1(CRPobs − CRPref) − β2(AGPobs − AGPref)

Estimating the Burden of Iron Deficiency Anaemia Among African Children16

• 4853 children aged 0–8 years• Kenya, Uganda, Burkina Faso, South

Africa, and The Gambia

WHO definition vs BRINDA

Other iron biomarkers vs BRINDA

Reticulocyte Haemoglobin Content (CHr) to Detect Iron Deficiency in Hospitalised Children in SA17

• Functional iron available for erythropoiesis

• Not affected inflammation

69% anaemic58% IDACHr <29 pg vs TSAT ≤25% (Sensitivity 86%, Specificity 50%)

“ the simplest answer is most often correct.”

Helminths

HookwormSchistosomesAscariasisTrichuris

Mebendazole• Single dose 30.8% vs Multiple dose 96.1%18

Albendazole + Praziquantel

Craniosynostosis Studies

Author Type of Study

Study Size Intervention (n) Control (n) Results

Helfaer et al 199819Case-Control 60 EPO + Iron (30)

No Intervention (30)

Decreased Transfusion,

Increased Hct

Meneghini et al 200320

Case-Control 25 EPO + Iron + ANH (16)

No Intervention (9)


Meara et al 200521Case-Control 19 EPO + Iron + Vit K(10)

No Intervention (9)


Increased Hct

Krajewski et al 200822Case-Control 79 EPO + CS + Iron (41) Iron (38)


Increased Hct

Vega et al 201423Case-Control 60

CHoR Protocol: EPO + Iron + CS (32)



Increased Hb

Escher et al 201924Case-Control 36

Minnesota Protocol: EPO + Iron + TXA (14)



Increased Hb

Preoperative Haemoglobin and Perioperative Transfusion in Scoliosis Surgery After Iron Supplementation25

382 patientsIron Clinic4mg.kg-1.day-1

Duration of iron therapy

Hb>13.0 associated with decreased transfusion requirements

Transfusion vs No Transfusion46 days 55 days

[IQR 35-85] [IQR 32-70]

Primary Endpoint27:

Days alive and out of hospital from surgery to 30 days following operation

Primary Endpoints26:

Requirement for allogenic red cell transfusion

Mortality up to 30 days after surgery

Preoperative IV Iron to Treat Anaemia in Major Surgery25

No difference• Transfusion 68 (29%) vs. 67 (28%), p = 0.92• Death 2 (1%) vs. 2 (1%), p = 1.0• Anaemia was corrected in 42 (21%) of 244 patients in the IV iron group

Dose?Timing?Included anaemia due to other causes?

Craniosynostosis Studies

Author Type of Study

Study Size Intervention (n) Control (n) Results

Helfaer et al 199819Case-Control 60 EPO + Iron (30)



Increased Hct

Meneghini et al 200320

Case-Control 25 EPO + Iron + ANH (16)

No Intervention (9)


Meara et al 200521Case-Control 19 EPO + Iron + Vit K(10)

No Intervention (9)


Increased Hct

Krajewski et al 200822

Case-Control 79 EPO + CS + Iron (41) Iron (38)


Increased Hct

Vega et al 201423Case-Control 60

CHoR Protocol: EPO + CS (32)



Increased Hb

Escher et al 201924Case-Control 36

Minnesota Protocol: EPO + Iron + TXA (14)



Increased Hb

Erythropoetin?

600 U/kg weekly for 3-4 weeks19-24

e.g. 10kg child 18 000 units

EPOPrice (Rand) Adjust

1 April 2018

2 000 IU 48.62

4 000 IU 72.23

10 000 IU 221.93

30 000 IU 726.32

18 000 IU 870.78

Red Cell Concentrate = R1 426.73

The Future….

Prevalence of iron deficiency anaemia in paediatric surgical patients in SA?

The role of iron (PO/IV) in preoperative anaemia in children?

Preoperative clinic an opportunity for screening for anaemia?

Introduce screening for Hb for anaemia, oral iron, and deworming?

The role of EPO?

SAPSOS-2?

Thank You

References1. Rössler J, Kaserer A, Spahn GH, Spahn DR. Not all anemia is solely due to iron deficiency. J Thorac Dis.

2020;12(3):1130-1132. doi:10.21037/jtd.2019.12.129

2. WHO, Chan M. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva, Switz World Heal Organ. 2011:1-6. doi:2011

3. Faraoni D, Dinardo JA, Goobie SM. Relationship between preoperative anemia and in-hospital mortality in children undergoing noncardiac surgery. Anesth Analg. 2016;123(6):1582-1587. doi:10.1213/ANE.0000000000001499

4. Meyer HM, Torborg A, Cronje L, et al. The association between preoperative anaemia and postoperative morbidity in paediatric surgical patients: A secondary analysis of a prospective observational cohort study. Pediatr Anesth. 2020. doi:10.1111/pan.13872

5. Wege M. A retrospective review of the prevalence and management of anaemia in children in at Red Cross War Memorial Children’s Hospital. 2015.

6. Jadhunandan K, Moodley Y, Gopalan PD. Preoperative anaemia in patients undergoing open intra-abdominal surgery at a South African tertiary hospital. South African J Anaesth Analg. 2020;26(1):24-29. doi:10.36303/SAJAA.2020.26.1.2250

References7. Conradie WS, Biesman-Simons T, Roodt F, et al. A multicentre prospective observational study of the

prevalence of preoperative anaemia and iron deficiency in adult elective surgical patients in hospitals in Western Cape Province, South Africa. South African Med J. 2020;110(1):65-68. doi:10.7196/SAMJ.2020.v110i1.14051

8. Marsicano D, Hauser N, Roodt F, et al. Preoperative anaemia and clinical outcomes in the south africansurgical outcomes study. South African Med J. 2018;108(10):839-846. doi:10.7196/SAMJ.2018.v108i10.13148

9. Labadarios D, Van Middelkoop A. Children aged 6-71 months in South Africa, 1994: their anthropometric, vitamin A, iron and immunisation coverage status. The South African vitamin A consultative group (SAVACG), 1995.

10. Labadarios D, Louw R. Selected micronutrient status, iron status. In: Labadarios D, editor. National Food Consumption Survey-Fortification Baseline (NFCS-FB): South Africa, 2005. Tygerberg: University of Stellenbosch, 2007; p. 447-455.

11. Shisana O, Labadarios D, Rehle T, Simbayi L, Zuma K, Dhansay A, Reddy P, Parker W, Hoosain E, Naidoo P, Hongoro C, Mchiza Z, Steyn NP, Dwane N, Makoae M, Maluleke T, Ramlagan S, Zungu N, Evans MG, Jacobs L, Faber M, & SANHANES-1 Team (2013) South African National. National Health and Nutrition Examination Survey (SANHANES-1). Cape Town: HSRC Press

12. National Department of Health (NDoH), Statistics South Africa (Stats SA), South African Medical Research

References12. Council (SAMRC), and ICF. 2019. South Africa Demographic and Health Survey 2016. Pretoria, South Africa,

and Rockville, Maryland, USA: NDoH, Stats SA, SAMRC, and ICF.

13. Chaparro CM, Suchdev PS. Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann N Y Acad Sci. 2019;1450(1):15-31. doi:10.1111/nyas.14092

14. World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva, Switzerland: Author; 2011

15. Suchdev PS, Namaste SML, Aaron GJ, Raiten DJ, Brown KH, Flores-Ayala R. Overview of the biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project. Adv Nutr. 2016;7(2):349-356. doi:10.3945/an.115.010215

16. Muriuki JM, Mentzer AJ, Webb EL, et al. Estimating the burden of iron deficiency among African children. BMC Med. 2020;18(1):1-14. doi:10.1186/s12916-020-1502-7

17. Swart PDR, Rautenbach K, Raubenheimer JE. Reticulocyte haemoglobin content as a diagnostic tool for iron deficiency and iron-deficiency anaemia in ill infants and children. SAJCH South African J Child Heal. 2014;8(1):23-27. doi:10.7196/SAJCH.645

18. Palmeirim MS, Ame SM, Ali SM, Hattendorf J, Keiser J. Efficacy and Safety of a Single Dose versus a Multiple Dose Regimen of Mebendazole against Hookworm Infections in Children: A Randomised, Double-blind Trial. EClinicalMedicine. 2018;1:7-13. doi:10.1016/j.eclinm.2018.06.004

References19. Helfaer MA, Carson BS, James CS, Gates J, Della-Lana D, Kolk C Vander. Increased hematocrit and

decreased transfusion requirements in children given erythropoietin before undergoing craniofacial surgery. J Neurosurg. 1998;88(4):704-708. doi:10.3171/jns.1998.88.4.0704

20. Meara JG, Smith EM, Harshbarger RJ, Farlo JN, Matar MM, Levy ML. Blood-conservation techniques in craniofacial surgery. Ann Plast Surg. 2005;54(5):525-529. doi:10.1097/01.sap.0000157901.57961.3b

21. Meneghini L, Zadra N, Aneloni V, Metrangolo S, Faggin R, Giusti F. Erythropoietin therapy and acute preoperative normovolaemic haemodilution in infants undergoing craniosynostosis surgery. Paediatr Anaesth. 2003;13(5):392-396. doi:10.1046/j.1460-9592.2003.01091.x

22. Krajewski K, Ashley RK, Pung N, et al. Successful blood conservation during craniosynostotic correction with dual therapy using procrit and cell saver. J Craniofac Surg. 2008;19(1):101-105. doi:10.1097/scs.0b013e3180f6112f

23. Vega RA, Lyon C, Kierce JF, Tye GW, Ritter AM, Rhodes JL. Minimizing transfusion requirements for children undergoing craniosynostosis repair: The CHoR protocol. Clinical article. J Neurosurg Pediatr. 2014;14(2):190-195. doi:10.3171/2014.4.PEDS13449

24. Escher PJ, Tu A, Kearney S, et al. Minimizing transfusion in sagittal craniosynostosis surgery: the Children’s Hospital of Minnesota Protocol. Child’s Nerv Syst. 2019;35(8):1357-1362. doi:10.1007/s00381-019-04157-5

References25. Switzer T, Naraine N, Chamlati R, et al. Association between preoperative hemoglobin levels after iron

supplementation and perioperative blood transfusion requirements in children undergoing scoliosis surgery. Goobie S, ed. Pediatr Anesth. August 2020:pan.13987. doi:10.1111/pan.13987

26. Richards T, Baikady RR, Clevenger B, et al. Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial. Lancet. 2020;6736(20):1-9. doi:10.1016/S0140-6736(20)31539-7

27. ITACS trial (NCT02632760)

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