anemia in pregnancy -to physiological changes

Anemia in pregnancy to chenge there anatomy

1. ANEMIA IN PREGNANCY MODERATED BY : DR SHAHIDA KHATOON PRESENTED BY : DR HIMANSHU DUBEY

2. 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 series no 405

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

4. VARIOUS DEFINITIONS OF ANEMIA ARC 2023 Mumbai

5. 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

6. 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 Hb may fall physiologically by approx 0.5 g.l -1 during 2 nd Trimester

7. 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

8. 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

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

10. Diagnosis of Iron deficiency Anemia 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 to diagnose iron deficiency in adults with infection or inflammation & 30 μg./l indicating high risk of IDA

11. 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

12. 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

13. Hepcidin- ferroportin interaction and major systemic iron pathways 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.

14. Hepcidin- ferroportin interaction and major systemic iron pathways 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

15. Does presence of Inflammation effects management modalities of Anemia ?

16. Oral Iron + B12, Folic acid supplementation Blood transfusion Parenteral Injectable Iron Human Recombinant Erythropoietin Modalities of Management

17. 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 -GI 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

18. Parenteral Therapy : Indications Pregnant women with severe IDA, presenting late in pregnancy Non -responder to oral Iron from second trimester onwards with con firmed iron-deficiency anaemia After 34 weeks’ gestation with Hb 8.0 –10.0 g/dl needing Rapid correction (e.g. Placenta accreta) Inability to maintain iron balance ( haemodialysis )

19. 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

20. IV Iron Therapy Total dose infusion (TDI) Dose = [ desired hb-patients hb]x 2.4 x patient’s weight+500 [ 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

21. PHYSIOLOGICAL CHANGES ARC 2023 Mumbai 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

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

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

24. 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

25. 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

26. 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

27. ARC 2023 Mumbai 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

28. 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

29. 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

30. 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

31. 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.

32. 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

33. “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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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 ARC 2023 Mumbai Serial Hb and Haematocrit values to monitor on-going blood losses Aimed at assessing the adequacy of perfusion and oxygenation

41. 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

42. 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

43. If she did not have a previous H/O CS MAN AGEMENT 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

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

51. 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

52. anemia and transfusion 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.

53. Goodnough, Shander , & coworkers have organized these strategies into 3 main pillars: 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

54. Detection, classification, Prevention 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

55. 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

56. 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

57. 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

58. 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

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