Managing peri-operative anaemiathe Papworth way. Dr Andrew A Klein Royal Papworth Hospital Cambridge UK

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1 Managing peri-operative anaemiathe Papworth way Dr Andrew A Klein Royal Papworth Hospital Cambridge UK

2 Conflicts of interest: Unrestricted educational grants/honoraria from CSL Behring, Brightwake Ltd, Vifor Pharma, Masimo, Fisher and Paykel and Pharmacosmos Editor-in-Chief of Anaesthesia

3 Learning Objectives Definition of anaemia Scale of the problem Causes and consequences of anaemia Challenges in pre-operative management Diagnosis Treatment The Papworth clinic

4 What is the Quality Statement? Patients with iron-deficiency anaemia who are having surgery should be offered iron supplementation before and after surgery. Pre-operative anaemia is associated with increased morbidity and mortality, and increased transfusion. Treating iron deficiency with iron supplements can reduce the need for blood transfusion. This avoids serious risks associated with blood transfusion e.g. infection, fluid overload and mismatch. May also reduce the length of hospital stays and cost to the NHS. Depending on the circumstances, the cause of the iron deficiency should be investigated before or after surgery.

5 What does this Quality statement mean? For Service providers (primary and secondary care services) ensure that systems are in place to offer iron supplementation before and after surgery For healthcare professionals (doctors, nurses and blood transfusion specialists) should offer iron supplementation before and after surgery For commissioners (clinical commissioning groups) commission services that offer iron supplementation before and after surgery For patients who are having an operation and have anaemia caused by a lack of iron should be offered iron before and after the operation.

6 Erythropoietin Do not offer erythropoietin to reduce the need for blood transfusion in patients having surgery, unless: the patient has anaemia and meets the criteria for blood transfusion, but declines it because of religious beliefs or other reasons or the appropriate blood type is not available because of the patient's red cell antibodies.

7 Iron Offer oral iron before and after surgery to patients with iron-deficiency anaemia. Consider intravenous iron before or after surgery for patients who: have iron-deficiency anaemia and cannot tolerate or absorb oral iron, or are unable to adhere to oral iron treatment (see the NICE guideline on medicines adherence) are diagnosed with functional iron deficiency Are diagnosed with iron-deficiency anaemia, and the interval between the diagnosis of anaemia and surgery is predicted to be too short for oral iron to be effective.

8 Which patients? The presence of anaemia should be investigated in all surgical procedures with expected moderate-to-high blood loss (> 500 ml) or transfusion risk >10% The diagnosis and treatment of anaemia and iron deficiency should commence as early as possible in the peri-operative period, and ideally as soon as the decision to undertake surgery is made.

9 Definition WHO: 13 g/dl men, 12 women (1968)

10 Gender bias Should we be aiming for an Hb > 130 g/l in men and women? Women are smaller than men Women have smaller body surface area and less blood Women bleed just as much as men!

11 Causes of anaemia Nutrient deficiency Iron Folate B12 Renal failure Chronic disease

12 Iron losses: Desquamation of skin and urinary cells Sloughing of intestinal cells Sweat Blood loss Iron absorbed from the diet into intestinal cells and exported into blood via ferroportin. Transferrin transports iron from stores (macrophages, hepatocytes) to utilisation sites (bone marrow, muscles)

13 Hepcidin Central regulator of iron homeostasis Small 25-amino acid peptide produced mainly in the liver. Acts by binding to Ferroportin. Blocks Ferroportin in intestinal cells leading to iron deficiency. Blocks Ferroportin in macrophages leading to inhibition of iron release and iron-restricted erythropoiesis.

14 All the same! Anaemia of chronic disease Functional iron deficiency Iron restriction anaemia

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16 All adult patients undergoing cardiac surgery at 12 ACTA-accredited UK centres,

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18 National variation in prevalence of anaemia % Patients 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% UK Centres Klein AA et al., The incidence and importance of anaemia in patients undergoing surgery in the UK the first Association of Cardiothoracic Anaesthetists national audit, Anaesthesia (2016); 71(6):

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24 US Veterans Database (NSQIP) (n=227,425) Anaemia (n=69,229; 30.4%) 30day mortality 30day composite morbidities (9 defined areas) Multivariate regression (9 defined subgroups) (56 cofactors)

25 Effect of Anaemia on Outcome

26 January 2012 to anaemic cardiac surgical patients Blood and bone marrow analysis Primary outcome was days alive and out of hospital.

27 Causes of anaemia in cardiac surgical patients Folate/B12 deficiency 6% Renal failure 10% Iron deficiency 84% Absolute iron deficiency 5% Iron restriction (chronic disease) 79%

28 Anaemia Pathways Get FBC as soon as possible (- should this be Primary Care?) Hb<130 g/l = move on to Anaemia Pathway Iron studies

29 Figure 2. Ferritin <30 mg l -1 Iron deficiency anaemia Altered Ferritin mg l -1 + Transferrin saturation <20% or C-reactive protein >5 mg l -1 Anaemia of chronic inflammation with iron deficiency Hb <130 g l -1 Iron tests Ferritin >100 mg l -1 + Transferrin saturation <20% or C-reactive protein >5 mg l -1 Anaemia of chronic inflammation Low Megalobastic anaemia Normal Vitamin B 12 Folate Normal Other anaemias Unknow cause Malignancy Drugs Endocrine Renal Adapted from M. Munoz et al., International consensus statement on the peri-operative management of anaemia and iron deficiency. Anaesthesia 2017 doi:10.111/anae.13773

30 Diagnose cause of anaemia Ferritin <30 Absolute iron deficiency Consider GI referral for endoscopy serum ferritin level <30 μg l -1 is the most sensitive (92%) and specific (98%) cut-off level for the identification of true iron deficiency; no further laboratory work-up is needed

31 Figure 2. Ferritin <30 mg l -1 Iron deficiency anaemia Altered Ferritin mg l -1 + Transferrin saturation <20% or C-reactive protein >5 mg l -1 Anaemia of chronic inflammation with iron deficiency Hb <130 g l -1 Iron tests Ferritin >100 mg l -1 + Transferrin saturation <20% or C-reactive protein >5 mg l -1 Anaemia of chronic inflammation Low Megalobastic anaemia Normal Vitamin B 12 Folate Normal Other anaemias Unknow cause Malignancy Drugs Endocrine Renal Adapted from M. Munoz et al., International consensus statement on the peri-operative management of anaemia and iron deficiency. Anaesthesia 2017 doi:10.111/anae.13773

32 Diagnose cause of anaemia Ferritin <100 CRP >5 mg.l- 1 and/or TSAT < 20% Strongly suggests iron deficiency. It also indicates inadequate iron stores for surgery during which moderate-to-high blood loss is expected

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34 Questions to Ask Who to treat? Where? Which drug? Timing of Surgery? Outcome data what to collect?

35 Oral Iron Needs time... Current recommendation is for 6-8 weeks pre surgery Dose 40-60mg day of elemental iron Side-effects Tolerance/compliance

36 Oral Iron Or alternate day dosing mg depending on the iron preparation used Response at 4 weeks 3 months to replace iron stores fully Consider treatment in non anaemics with severe iron deficiency and pregnant women with iron deficiency

37 Intravenous Iron Can t or won t take oral iron Fail to respond to oral iron in 4 weeks < 4 weeks to surgery Single dose as much as possible in one visit (20 mg/kg)* *Dose limitations per single administration vary between different IV iron preparations, please refer to the product SPC for full prescribing information

38 Experience with iv iron at Papworth Total Dose Iron therapy One visit/one intervention (up to 20 mg/kg) Minimal nursing time Good safety profile No major adverse events to date

39 Cardiac surgery Hb pre iron Hb pre surgery Hb difference Iron to surgery weeks weeks weeks weeks weeks weeks weeks weeks weeks weeks weeks weeks weeks Mean weeks

40 Conclusion Increasing incidence Significant healthcare burden Large impact on outcomes Iron deficiency most common cause (>80%) Diagnosis and treatment mandated by NHS, NICE, NHSBT, AAGBI Setting up an anaemia clinic in the NHS