03 Dr Anju Grewal ANEMIA IN PREGNANCY (1).pptx

Anemia in pregnancy

1. ANEMIA IN PREGNANCY ANJU GREWAL PROFESSOR & HEAD DEPT OF ANESTHESIOLOGY AIIMS BATHINDA, PUNJAB, INDIA ARC 2023 Mumbai 1

2. CASE A 40 yr old at 35 week is scheduled for elective Category-III cesarean section 15 days later History of previous two LSCS, breathlessness, & palpitations on exertion O/E: Pale, Tachycardic (120/min), Normotensive Preop Investigations: Hb 7.5 gm%, Platelet Count – Normal ARC 2023 Mumbai 2

3. DEFINITION Anaemia is a qualitative or quantitative deficiency of hemoglobin (Hb) or red blood cells (RBC) in circulation Hb conc. < 11gm % or haematocrit < 0.33 in 1 st and 3 rd trimesters and < 10.5 gm% in 2 nd trimester For developing countries : cut off level is 10 gm % WHO technical report Series no. 405, Geneva 1968 Centre for disease control, MMWR 1989;38:400-4 ARC 2023 Mumbai 3

4. Degree Hb gm/dL Haematocrit Mild 10 -10.9 30-32.7% Moderate 7-9.9 21-29.7% Severe <7 <21% WHO Classification of Anemia ARC 2023 Mumbai 4

5. VARIOUS DEFINITIONS OF ANEMIA ARC 2023 Mumbai 5

6. Definitions of Anaemia: Need for Review A 2017 international consensus statement on peri-operative anaemia recommends that patients undergoing major surgery, including obstetric population , undergo investigation & treatment for anaemia with aim of achieving Hb level > 13g./dl Women have lower total red cell mass, & lower total body iron stores compared with men; thus, same total blood loss will have a proportionally greater effect in women Hence need for redefining pre-operative haemoglobin targets in women planned to have caesarean section ARC 2023 Mumbai 6 Anaesthesia 2019, 74, 237–245 Ferguson and Dennis | Peri-operative anaemia in pregnancy

7. Current Definition Till new guidelines are finalized, existing threshold for anaemia during pregnancy is Hb <110 g/L in the first trimester, <105 g/L in second and third trimesters <100 g/L in the postpartum period ARC 2023 Mumbai 7 Hb may fall physiologically by approx. 5 g.l -1 during 2 nd Trimester

8. Causes of Anemia in Pregnancy A. Physiological anaemia of pregnancy B. Acquired: a. Nutritional- Iron deficiency, folate deficiency, B-12 deficiency b. Infections- Malaria, hookworm infestation, etc c. Haemorrhagic - Acute or chronic blood loss d. Bone marrow suppression- Aplastic anaemia , drugs, etc. e. Renal disease C. Genetic haemoglobinopathies: Sickle cell disease, T halassaemia ARC 2023 Mumbai 8

9. Normal Iron Requirements Total volume of RBC increase is: 450 ml 1 ml of RBC contains 1.1 mg Fe 450 ml X 1.1 mg/ml = 500 mg Daily average is 6.3 mg/day plus 1mg/day for lactation Iron requirement for normal pregnancy is: 1gm 225 mg: fetus growth 80 mg : placental development 250mg: blood loss vaginal delivery of mother Total body iron is approximately 3–4 g, of which 1–2 mg is lost daily, & an additional 1 mg is lost during menstruation each month ARC 2023 Mumbai 9

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12. Diagnosis of Iron deficiency Anemia ARC 2023 Mumbai 12 Anaemia is the end result of Iron deficiency Erythropoiesis may be preserved, restricted or blunted Hence burden of Iron deficiency goes unrecognised - NAID Investigation of choice Hb S. Ferritin concentration [ ferritin cut-off of < 15 μg.l -1 ] Ferritin serves as an indirect measure of body's total iron storage

13. Diagnosis of Iron deficiency Anemia ARC 2023 Mumbai 13 Ferritin is an acute phase protein & may be elevated as a result of inflammatory pathologies, surgery and even pregnancy itself Therefore, a normal level does not exclude iron deficiency. Recent WHO guidance recommends a threshold of < 70 μg.l -1 to diagnose iron deficiency in adults with infection or inflammation & 30 μg.l -1 indicating high risk of IDA

14. Transferrin & Other novel markers of Iron status Transferrin saturation: WHO recommends a threshold of < 16% for iron deficiency, or < 20% in patients with co-existing inflammation The use of more novel markers of iron status, such as hepcidin, soluble transferrin receptor and erythroferrone, is currently an active area of research ARC 2023 Mumbai 14

15. Hb 13.5 – 14 gm % R.B.C. 4.5 – 4.7 million/cu mm Serum Iron 50 – 150 μg / dL ↓ TIBC 300 – 360 μg / dL ↑ Transferrin saturation 25 – 50 % ↓ S. Ferritin level 30-200 μg / L ↓ Red Cell protoporphyrin 30 μg / dL Erythropoietin 15.20 U / L MCV 76 – 100 fL MCH 27 – 33 pg MCHC 33.37 gm / dL PCV 32 – 40 % Investigations with Normal Levels ARC 2023 Mumbai 15

16. Hepcidin- ferroportin interaction and major systemic iron pathways ARC 2023 Mumbai 16 Approximately 1mg of iron is absorbed daily in gut. Ferroportin is the sole mammalian exporter of iron and delivers stored, dietary or recycled iron to blood plasma In plasma, iron is taken up by transferrin. A small proportion is used for muscle function and development of neural tissue, while rest is used by bone marrow for erythropoiesis At the end of their life cycle, red blood cells are taken up by macrophages and approximately 25mg of iron is recycled daily through this pathway which is the major source of body iron.

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18. Hepcidin- ferroportin interaction and major systemic iron pathways ARC 2023 Mumbai 18 Hepcidin expression results in degradation of ferroportin which impairs release of iron from macrophages and duodenal enterocytes Hepcidin levels increased in- Inflammation High levels of free Iron Hepcidin levels Decreased Iron Deficiency Hypoxia Blood loss

19. Does presence of Inflammation effect management modalities of Anemia ? ARC 2023 Mumbai 19

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21. Oral Iron + B12, Folic acid supplementation Blood transfusion Parenteral Injectable Iron Human Recombinant Erythropoietin Modalities of Management Benson et al. | Iron de fi ciency and anaemia in women ’ s health Anaesthesia 2021, 76 (Suppl. 4), 84 – 95 ARC 2023 Mumbai 21

22. Oral Iron Therapy Ideal dose – 100- 200 mg per day (prophylactic) Ferrous gluconate, ferrous fumarate, ferrous succinate, ferrous sulphate, ferrous ascorbate citrate Rise in Hb – 0.8 gm / dl / week Side effects -G I upset most common Alternate‐day dosing may result in better absorption and fewer side effects, likely due to increased levels of hepcidin Pre-operative oral iron should be commenced when the interval before surgery is 6–8 weeks ARC 2023 Mumbai 22

23. Parenteral Therapy : Indications Pregnant women with severe IDA, presenting late in pregnancy Non -responder to oral Iron from second trimester onwards with con fi rmed iron-de fi ciency anaemia After 34 weeks ’ gestation with Hb 8.0 – 10.0 g/dl needing Rapid correction (e.g. Jehovah ’ s Witness, Placenta accreta) Inability to maintain iron balance ( haemodialysis ) ARC 2023 Mumbai 23

24. Advantage of Parenteral Iron Bypasses ‘hepcidin block’ that limits absorption of oral iron in presence of inflammation Newer iron preparations such as ferric carboxymaltose and iron isomaltoside permit delivery to reticuloendothelial system in a slow and controlled manner in order to limit amount of toxic unbound circulating free iron ARC 2023 Mumbai 24

25. IV Iron Therapy Total dose infusion (TDI) Dose = 0.3 X Wt (100 – Hb %)  gives mg of elemental iron or (deficiency in Hb X 250) + 50% (for stores) = mg of iron Given @10 drops/min X 30 min. (diluted in normal saline or 5% dextrose) → no reaction → ↑ to 45 drops/min Either iron dextran or iron sucrose ( safe, less side effects) Anaphylactoid reaction - Chest pain, rigors, chills, fall in BP, dyspnea - hemolysis Hb rise : 0.7 – 1gm/100 ml/ wk ARC 2023 Mumbai 25

26. WHAT IS UNIQUE TO ANEMIA IN A PARTURIENT ? ARC 2023 Mumbai 26

27. PHYSIOLOGICAL CHANGES O 2 DEMAND maternal metabolic rate & fetal metabolic processes O 2 CONSUMPTION VO 2 increases by term & by 40-60% during labor O 2 DELIVERY CaO 2 x C.O. x 10 dl/L Oxygen (O 2 ) delivery to tissues is a function of cardiac output (C.O.) & total arterial oxygen content (CaO 2 ) Along with Degree of affinity of Hb for O 2 →Tissue O 2 extraction ARC 2023 Mumbai 27

28. UNIQUE PHYSIOLOGICAL CHANGES Adaptive hypervolemia and consequent ‘Physiologic anemia’ of pregnancy Hb and hematocrit of 11.6g/dl and 35.5% respectively ARC 2023 Mumbai 28

29. OXYGEN DISSOCIATION CURVE (ODC) IN PREGNANCY ARC 2023 Mumbai 29

30. ANEMIA: REDUCES ARTERIAL O 2 CONTENT As there is a deficiency of Hb or red blood cells (RBC) in circulation the O 2 carrying capacity of blood gets reduced.. .. Results in a further decrease in arterial O 2 content ARC 2023 Mumbai 30

31. ANEMIA: REDUCES ARTERIAL O 2 CONTENT OXYGEN CONTENT OF ARTERIAL BLOOD {CaO 2 } CaO 2 = 1.38 X Hb X SaO 2 + (0.0031 X PO 2 ) NORMAL PATIENT CaO 2 = (15 X 1.38 X 98) + (0.0031 X 100) CaO 2 = 20 ml ANEMIC PATIENT CaO 2 = (7.5 X 1.38 X 98) + (0.0031 X 100) CaO 2 = 15 ml ARC 2023 Mumbai 31

32. ANEMIA: REDUCES ARTERIAL O 2 CONTENT OXYGEN CONTENT OF ARTERIAL BLOOD {CaO 2 } CaO 2 = 1.38 X Hb X SaO 2 + (0.0031 X PO 2 ) NORMAL PATIENT CaO 2 = (15 X 1.38 X 98) + (0.0031 X 100) CaO 2 = 20 ml ANEMIC PATIENT CaO 2 = (7.5 X 1.38 X 98) + (0.0031 X 100) CaO 2 = 15 ml ARC 2023 Mumbai 32

33. Full term-Pregnancy Anemia ARC 2023 Mumbai 33

34. O 2 extraction depends on affinity of Hb molecule to O 2 (ODC)& VO 2 Oxygen delivery = CaO 2 × Cardiac output × 10 dl/L CaO 2 1.38 X Hb X SaO 2 + (0.0031 X PO 2 ) Oxygen consumption (VO 2 ) = C.O. X CaO 2 – CvO 2 = C.O. X Hb X 1.38 X (SaO 2 – SvO 2 ) NORMAL PHYSIOLOGY OF OXYGEN DELIVERY TO TISSUES Venous O 2 Content CvO 2 ≈ SvO 2 ARC 2023 Mumbai 34

35. Compensatory mechanisms Shift of ODC to right  in CO  in 2,3 DPG level in RBC  in P 50 Decreased viscosity of blood, increasing tissue blood flow. Release of renal erythropoetin stimulates bone marrow- produces additional RBC ARC 2023 Mumbai 35

36. Increase in cardiac output ↑↑ ‘ODC CURVE’ SHIFTS TO RIGHT Utero -placental bed PHYSIOLOGICAL + PATHOLOGICAL ANEMIA Decrease in Normal COMPENSATORY MECHANISMS Increase in O 2 extraction Severe anemia Normal or ↓ CvO 2 & SvO 2 ↑ PaO 2 ↓ blood viscosity VO 2 = CO ↓ x Hb ↓ x 13.8 x (SaO 2 – SvO 2 ↓ ) ARC 2023 Mumbai 36

37. Maternal complications-angina, right heart failure and fetal hypoxemia & acidemia can occur ACUTE BLOOD LOSS, PREEXISTING HEART DISEASE, DM /PIH which can critically decrease the cardiac output, & cause hypoxemia Compensated CHRONIC ANEMIA MAXIMAL Anemic parturient is more dependent on Cardiac Output for O 2 delivery ARC 2023 Mumbai 37

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39. Compensatory mechanisms to Acute blood loss In case of anaemia , due to acute blood loss [obstetric haemorrhage ], sympathetic activation leads to vasoconstriction increase in stroke volume & venous return causing increased velocity of blood flow and cardiac output Second, constriction of capillary bed in skin and splanchnic circulation redistributes blood to vital organs. ARC 2023 Mumbai 39

40. Adaptations in Acute Anemia i ) Resp:  MV Increased V-P matching Increased PaO2 & SaO2 ii) CVS:  SNS activity Increase CO,  Venous return Decrease SVR  Blood viscosity iii) Increased tissue extraction of O2: Rt shift ODC Increase tissue blood flow Increased cap recruitment & density ARC 2023 Mumbai 40

41. “Oxygen sensors ” To support cellular survival during acute anemia induced tissue hypoxia Kidneys : Decrease in renal PO2 …increases Renal Erythropoietin Aortic/ Carotid chemoreceptors : Increased sympathetic activity, increases cardiac output…& cellular responses that optimize tissue O2 delivery Hypoxia-inducible factor from cells ARC 2023 Mumbai 41

42. CASE A 40 yr old at 35 week is scheduled for elective Category-III cesarean section 15 days later History of previous two LSCS, breathlessness, & palpitations on exertion O/E: Pale, Tachycardic (120/min), Normotensive Preop Investigations: Hb 7.5 gm%, Platelet Count – Normal ARC 2023 Mumbai 42

43. ANAESTHETIC CONSIDERATIONS Preoperative assessment including History, Examination, Investigations should elicit: Establishing presence of anemia Cause Type & Severity of Anemia Adequacy of compensatory mechanisms Co-morbid problems ARC 2023 Mumbai 43

44. ANAESTHETIC CONSIDERATIONS IDENTIFY HIGH RISK PARTURIENTS & EXTENT OF COMPENSATION CORRECT CAUSE & REDUCE SEVERITY, IF TIME PERMITS OPTIMISE THERAPIES THAT IMPROVE MATERNAL & FETAL OXYGEN DELIVERY FORMULATE PERIOPERATIVE ANESTHESIA PLAN ARC 2023 Mumbai 44

45. Formulate Anaesthesia Plan Type of Anesthetic regime will depend upon: Severity & type of anemia Extent of physiological compensation Co-morbid medical conditions Type & nature of procedure Anticipated blood loss ARC 2023 Mumbai 45

46. ANESTHETIC CONCERNS Optimize maternal & fetal oxygen delivery Minimize factors interfering with O 2 delivery Optimize the partial pressure of O 2 in the arterial blood Prevent any increase in oxygen consumption Prevent any fall in cardiac output Prevent & treat factors which shift ODC to left ARC 2023 Mumbai 46

47. Optimize cardiac output ↑↑ KEEP ‘ODC CURVE’ TO RIGHT A decrease in SvO 2 indicates therapeutic intervention to maximize O 2 delivery Utero -placental bed Decreased OPTIMIZE ANESTHETIC GOALS Increase O 2 extraction Measure ↓ in SvO 2 OPTIMIZE CaO 2 ↑ PaO 2 Anticipate & treat blood losses ↓ blood viscosity ARC 2023 Mumbai 47

48. Parturient 2 nd trimester Chronic Anemia Hb < 6gm /dl CLINICAL SCENARIOS: ELECTIVE vs EMERGENCY SURGERY CHOICE OF ANESTHESIA TECHNIQUE ARC 2023 Mumbai 48

49. Full term-Pregnancy Chronic Anemia Acute anemia CLINICAL SCENARIOS: EMERGENCY SURGERY & ON- GOING LOSS CHOICE OF ANESTHESIA TECHNIQUE ARC 2023 Mumbai 49

50. CHOICE OF ANETHESIA TECHNIQUE REGIONAL ANESTHESIA Lesser interference with hemodynamics Decreased blood loss Intermittent epidural, Low dose spinal with adjuvants and Peripheral nerve blocks should be advocated whenever feasible GENERAL ANESTHESIA Preferred - Major blood losses with comorbid medical illnesses Unstable, Symptomatic severely anemic parturients (Hb < 6-7gm/dl) Requires careful titration ARC 2023 Mumbai 50

51. MONITORING Non-invasive monitoring ECG NIBP EtCo2 Temperature monitoring Pulse oximetry, Urine Output Invasive monitoring CVP IABP ABG SvO 2 Scv O 2 -surrogate marker for transfusion requirement Serial Hb and Haematocrit values to monitor on-going blood losses Aimed at assessing the adequacy of perfusion and oxygenation ARC 2023 Mumbai 51

52. Avoidance of hypoxia Preoxygenation with 100% O2. b. Oxygen supplementation should be given in the peri - and postoperative period. c. Maintenance of airway is important to prevent fall in FiO2 due to airway obstruction, difficult intubation, etc. Hence measures and expertise to secure a definitive airway should be available immediately . Considerations during Induction of Anesthesia ARC 2023 Mumbai 52

53. Regional anaesthesia : Be Careful On return of Vascular tone : Hypotension, Hemodilution, Heart failure Pulmonary oedema Worsening of symptoms of Subacute degeneration: avoid in Vitamin B12 deficiencies with neurological symptoms ARC 2023 Mumbai 53

54. If she did not have a previous H/O CS? MANAGEMENT OF LABOR • Ist stage : - Make patient comfortable - Provide pain relief, Oxygen - Prevent pulmonary edema • IInd stage: - Shorten by forceps • IIIrd stage: - Active management, prevent PPH • Puerperium: - Rest, Iron, Folic acid for 3 months ARC 2023 Mumbai 54

55. Spontaneous ventilation technique only for short procedures High FiO2 (40-50%) is administered to overcome effects of hypoventilation. High concentration of volatile agents depresses both myocardium as well as ventilation resulting in an undesirable decrease in O2 flux. What if she needs Anesthesia for a vaginal laceration secondary to Instrumental Vaginal Delivery? ARC 2023 Mumbai 55

56. Minimize drug-induced decreases in CO Intravenous induction of anaesthesia should be slowly titrated to prevent precipitous fall in CO Careful positioning of the patient to minimize position associated volume shifts Mild tachycardia and wide pulse pressure may be physiological and should not be confused with light anaesthesia. Points to consider during GA! ARC 2023 Mumbai 56

57. Factors leading to left shift of ODC should be avoided Avoid hyperventilation to minimize respiratory alkalosis. Hypocapnia also decreases CO. Maintain normocapnia . Hypothermia should be avoided Treat and avoid conditions that increase O2 demands like postop Pain, fever, shivering, etc Nitrous oxide should be used cautiously in patients with folate and Vitamin B-12 deficiency Points to consider during GA! ARC 2023 Mumbai 57

58. What if Hb is <2.5g/dl, no blood is available/ Jehovah’s witness / Alloantibodies and Hemolytic anemia? Sedate patient, paralyse on NMB to reduce oxygen demand. Hematinic agents Delivery of high oxygen concentration Hyperbaric oxygen therapy to increase level of O2 dissolved in plasma. Artificial oxygen carriers ARC 2023 Mumbai 58

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60. Benefits Vs Risks of transfusion Replenishment of O 2 -carrying capacity Maximizes O 2 delivery to tissues Transfuse when indicated using leukoreduced red cells under strict monitoring Transfusion-associated risks - pulmonary edema, immune suppression Increases blood viscosity hence may reduce blood flow & O 2 delivery Stored blood has greater affinity for O 2 , due to decreased concentrations of 2,3-DPG in erythrocytes to 1 μmol /g of Hb at 21 days of storage ARC 2023 Mumbai 60

61. Optimization : Need for transfusion Need based on both clinical and hematological grounds Healthy myocardium compensates for the low Hb or Hct levels (≥7-8 gm/dL of Hb or 21-24% Hct) in order to optimize O 2 delivery Asymptomatic patients should not receive any transfusions ARC 2023 Mumbai 61

62. Optimization : Need for transfusion Symptomatic parturients with Hb <7-8gm/dl may need transfusion on an informed individual basis Symptoms /signs of decompensation (unstable patients with end organ dysfunction) with co-existing medical conditions or continuing major blood loss ARC 2023 Mumbai 62

63. Optimization : Need for transfusion Transfusion is needed in severely anemic symptomatic parturients with maternal Hb <6 g/dL has association with fetal morbidity and mortality Maternal decompensation may occur However a single trigger or minimum acceptable Hb does not exist ARC 2023 Mumbai 63

64. Paradoxically, both anaemia and transfusion are independently associated with organ injury and increased morbidity. Treatment strategies to optimize haematopoiesis , manipulate physiological responses, and minimize blood loss are necessary to improve outcomes in anaemic patients. ARC 2023 Mumbai 64

65. Goodnough, Shander , & coworkers have organized these strategies into 3 main pillars: ARC 2023 Mumbai 65 Three Pillars of PBM: Pre-emptive counter measures Pre / Inta / Postop Compre-hensive anemia management Minimization of allogenic (unnecessary) blood loss Harness & optimize patient-specific physiological tolerance of anemia

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67. Patient blood management (PBM) is timely application of evidence-informed medical and surgical concepts designed to maintain Hb concentration, optimise haemostasis , and minimise blood loss in an effort to improve patient outcomes Aims to provide recommendations on prevention & treatment of postpartum haemorrhage (PPH) as part of PBM in obstetrics ARC 2023 Mumbai 67 Transfusion Medicine , 2018, 28 , 22–39 Blood Transfus 2019; 17 : 112-36 DOI 10.2450/2019.0245-18 Best Practice & Research Clinical Anaesthesiology 36 (2022) 359 e 369

68. Detection, classification, Prevention ARC 2023 Mumbai 68 Pre -Anesthetic consultation before delivery to Identify at risk mothers for PPH Full Blood count at 28 weeks & anytime if anaemia is present Ferritin Levels need to be checked Oral Iron trial for IDA evaluation Initiate daily oral Ferrous iron (30–60mg)&folic acid (400 𝜇 g) supplementation as part of routine antenatal care & continue it up to 3month postpartum

69. IV Iron, ESA & Blood transfusion IV iron for severe IDA (Hb <8gm/dl) or newly diagnosed IDA > 34 weeks Failure to respond or intolerant to oral Iron Erythropoietin Stimulating Agents (ESA): M oderate to severe anaemia not responding to IV iron due to inappropriate synthesis of endogenous erythropoietin levels, (blunted erythropoiesis due to infection and/or inflammation), in consultation with a haematologist S ingle-unit transfusion followed by clinical reassessment is permitted Obstetric units should have guidelines for red blood cell (RBC) transfusion ARC 2023 Mumbai 69

70. Acute normovolemic hemodilution & Cell Salvage in Obstetrics Reported on few occasions For patients with invasive placentation who refuse use of allogeneic blood products, ANH has been used in conjunction with cell salvage and pre-operative iron supplementation as part of a multimodal PBM strategy Because a hematocrit of 30% is considered best compromise between oxygen transport and blood fluidity, this value is frequently used as desired hematocrit when calculating ANH ARC 2023 Mumbai 70

71. CONCLUSION Evaluate extent of activated compensatory mechanisms Identify High risk Parturients : concomitant medical diseases acute ongoing blood losses Anticipate & prevent decompensation Monitor adequacy of tissue perfusion & oxygenation No single Hb value can trigger need for PRBC transfusion ARC 2023 Mumbai 71

72. CONCLUSION Anesthetic management aims at Optimizing tissue O 2 delivery both to mother & fetus Avoidance of hypoxemia, hypovolemia, hypotension, hypo /hyper-thermia along with provision of good analgesia Both neuraxial and general anesthesia are acceptable Main aim is to maintain a fine balance between compensatory mechanisms & adequate tissue oxygenation ARC 2023 Mumbai 72

73. “ Anaemia should never be regarded as an innocent bystander” Nissenson AR et al, Arch Int Medicine 2003 ARC 2023 Mumbai 73

74. THANK YOU ALL !! ARC 2023 Mumbai 74

75. ARC 2023 Mumbai 75 A.J. Butwick, N. McDonnell. Antepartum and postpartum anemia: a narrative review. International Journal of Obstetric Anesthesia xxx (2021) https://doi.org/10.1016/j.ijoa.2021.102985