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![ADAPTIVE MECHANISMS THAT ENSURE OXYGEN
DELIVERY TO TISSUES
Oxygen sensors
• kidneys,aortic and carotid body chemoreceptors and cells [hypoxia-inducible factor (HIF)].
• Adaptive physiological responses occur to compensate for anaemia-induced tissue hypoxia,
which supports cellular survival during anaemia.
The Respiratory adaptations during anaemia
• Increase in minute ventilation due to stimulation of respiration.
NO-mediated mechanisms
• The partial pressure of O2 in arterial blood (PaO2 ) and Hb O2 saturation (SaO2 ) are increased
• Help in ventilation-perfusion matching. This help for maintaining SaO2 in the presence of
reduced Hb](https://image.slidesharecdn.com/laast-231130161547-660e4918/85/anaemia-in-pregnancy-24-320.jpg)
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anaemia in pregnancy
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- 2. CONTENT • Introduction • Definition •Classification of anaemia in pregnancy • Haemoglobin structure • ODC • Pathophysiology of anaemia • Adaptive mechanisms that ensure oxygen delivery to tissues • Anaesthesia management
- 3. CONTENT… • Choice ofAnaesthesia Regional Anaesthesia General anaesthesia • Post operative management • Sickle cell anaemia • Thalassemia • Conclusion
- 4. INTRODUCTION • Anaemia isan independent modifiable perioperative risk factor • Pregnant women are particularly considered to be the most vulnerable group • Approximately 38% of all pregnant women worldwide are found to be anaemic, • Global prevalence of iron deficiency anaemia (IDA) in pregnancy ranges from 15% to 18%.
- 5. INTRODUCTION • WHO- 65-75%prevalence of anemia in pregnant women in india • Nearly half of the maternal death is due to anemia in southasian countries • 80% of these is contributed by india
- 6. DEFINITION • Anaemia isdefined as a qualitative or quantitative deficiency of haemoglobin or red blood cells in circulation, resulting in reduced oxygen (O2 )-carrying capacity of the blood to tissues and organs.
- 7. DEFINITION OF ANAEMIAIN PREGNANCY • Hb less than 11 mg/dl Or hct <0.33 inT1&3 • second trimester fall of 0.5mg/dl (dilutional)<10.5 • Qualitative/quantitative deficiency of the Hb or RBC • Leading to Decrease in O2 carrying capacity • Developing countries lower limit 10gm/dl
- 8. WHO CLASSIFICATION • Mild10-10.9g/dl • Moderate 7-9.9g/dl • Severe <7g/dl
- 9. CLASSIFICATION OF ANAEMIAIN PREGNANCY • Physiological • Acquired 1)Nutritional 2) Infection 3) Haemorrhagic 4) Bone marrow suppression-aplastic anaemia,drug 5) Renal disease • Genetic-Haemoglobinopathies-SCD,Thalassemia
- 10. HAEMOGLOBIN STRUCTURE • 4Polypeptide chains 2alpha chain,2beta chain • Iron containing prosthetic group(heme/ferriprotoporphyrin)
- 11. HAEMOGLOBIN STRUCTURE… Early embriogenesis •Theta and zeta chain instead of alpha chain • Ebsilon instead of beta chain After early embriogenesis • 2alpha+ 2beta -HgbA1 • 2apha +2 gama -HgbF • 2 alpha +2 delta HgbA2 By term • HbA1:HbF =1:1 • At 1 yr HbF < 1 %
- 12. HAEMOGLOBIN STRUCTURE… • Primarystructure: sequence of amino acid 141 AA , alpha,146 AA beta • Secondary structure 3 dimensinal shape of the amino acid side chain defined as secondary structure • Tertiary structure-four chain and heme prosthetic group relation defined as teritiary structure • Quarternary structure -binding of ligand 2,3DPG ,O2 with tertiary structure
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- 14. Double bohr effect •At materno fetal interface maternal blood taken up co2 and become more acidic- decrease o2 affinity to HB Leads to o2 delivery( 1st effect) • Fetal blood releases co2,more alkalotic - cause o2 affinity , fetal o2 uptake –second effect Double Haldane effect • HbF Oxygenated –release co2 • HbA deoxygenated –binds more co2 Help in adequate feto maternal gas exchange ODC…
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- 16. CARDIOVASCULAR CHANGE INPREGNANCY SVR Decreases Vascular compliance Plasma volume Increases 50% Peak by 36wk Blood cell volume Increases 20% Fall in haemetocrit Relative physiological anaemia Decreased vascular tone allow adequate blood flow
- 17. Natriuresis Placental progesteron HORMONAL CHANGES INPREGNANCY RAAS Stimulation Increase aldosterone Na,h2o reabsorption Increase blood volume 30-40% Plasma osmolarity decrease by 10% Na low normal level and potassium constant oestrogen Stimulate angiotensinoge n Fluid retention
- 18. HAEMATOLOGICAL CHANGES INPREGNANCY • RBC increase but not as much as blood volume Relative anemia 15% decrease in Hb pre pregnancy level(Average Hb 11.6,hct 35.5%) • Decreased blood viscosity – compensatory mechanism • Become pathological when Hb fall further(<10)
- 19. PATHOPHYSIOLOGY OF ANAEMIA Anaemiadue to acute blood loss- • sympathetic activation • Vaso constriction • Increase venous return • Increase stroke volume • Increase cardiac output • Increase velocity of blood flow • Constriction of capillary in skin and splanchnic circulatiom-redistribution of blood
- 20. PATHOPHYSIOLOGY OF ANAEMIA… Chronicanaemia • Increase in cardiac output-maintain adequate oxygen delivery • Maintain a constant arterial-venous O2 content difference and increase in O2 extraction ratio. • Increased 2,3-diphosphoglycerate (2,3-DPG)-rightward shift in ODC • The relative reduction in oxygen content is detected by tissue chemoreceptors, leading to further compensation and an increase in minute ventilation
- 21. PATHOPHYSIOLOGY OF ANAEMIA… Normal •Oxygen carried in blood =oxygen binded with Hb+dissolved O2 • Cao2=Hb x 1.37 x SaO2+0.0034xPao2 • Cao2 (on air) =15 x 1.37x 100+0.0034 x 100=21.1 ml/dl • Delivery of o2= CO X CaO2=5l/mnt x 21.1=1055 ml/mnt • Oxygen consumption=CO x(Cao2-Cv02)=250-270 ml/min • O2 extraction= 250/1000 = 25% • Anaemia • Hb drops,Cao2 decrease • Hence increases CO to increase o2 delivery • Oxygen consumption increases • excessive strain on myocardium-acute cardiac failure-increase in CO should be less than 10
- 23. • Mild anemia-asymptomatic • Moderate to severe anemia-Dyspnoea, palpitations, angina and signs of high CO, such as tachycardia, wide pulse pressure and systolic ejection murmur • Severe anemia-Long-standing hyperdynamic circulation increases the cardiac load, causing hypoxia, ventricular dysfunction,heart failure
- 24. ADAPTIVE MECHANISMS THATENSURE OXYGEN DELIVERY TO TISSUES Oxygen sensors • kidneys,aortic and carotid body chemoreceptors and cells [hypoxia-inducible factor (HIF)]. • Adaptive physiological responses occur to compensate for anaemia-induced tissue hypoxia, which supports cellular survival during anaemia. The Respiratory adaptations during anaemia • Increase in minute ventilation due to stimulation of respiration. NO-mediated mechanisms • The partial pressure of O2 in arterial blood (PaO2 ) and Hb O2 saturation (SaO2 ) are increased • Help in ventilation-perfusion matching. This help for maintaining SaO2 in the presence of reduced Hb
- 25. ADAPTIVE MECHANISMS THATENSURE OXYGEN DELIVERY TO TISSUES… Cardiovascular adaptations • Increase in CO • Reduction in systemic vascular resistance (SVR) hypoxia-sensing cells activate the sympathetic nervous system • Reduction in blood viscosity, • Systemic vasodilation • Increased venous return
- 26. ADAPTIVE MECHANISMS THATENSURE OXYGEN DELIVERY TO TISSUES… An increase in systemic O2 extraction • Three mechanisms helping for oxygen diffusion from microcirculation to tissues and thus sustain mitochondrial oxidative phosphorylation (aerobic respiration): a) Right shift of the oxygen dissociation curve b) Increased tissue blood flow -helping to increase oxygen diffusion from microcirculation to the tissues (c) increased capillary recruitment and density -Decrease the diffusion distance to the cells during anaemia. • These adaptation help in ATP generation under aerobic conditions and function as a primary oxygen sensor
- 27. ADAPTIVE MECHANISMS THATENSURE OXYGEN DELIVERY TO TISSUES… HIF(hypoxia inducible factor) mediated metabolic cellular adaptations • Help in balance between systemic oxygen delivery and consumption,survival during acute anaemia. • HIF has been described as a master regulator of hypoxia sensing and hypoxic cell signalling
- 28. FETOPLACENTAL UNIT ANDOXYGEN DELIVERY • Pregnancy Require Increase in oxygenation-towards the end of 1st trimester • Foetal haemoglobin (α2, γ2)- lower affinity for 2,3-diphosphoglycerate ->ODC shift to left • For any given arterial oxygen pressure (PaO2 ) greater arterial oxygen saturation (SaO2 ) in foetal blood • placenta acts as a pathway for oxygen transport to foetal circulation and provides oxygen to support its own metabolism • chronic hypoxia following anaemia in pregnancy can lead to intrauterine growth restriction • To compensate- there is a dramatic increase in placental vascularity along with increase in placental villous surface Increasing the maternal cardiac output-Uterine vessels receive an enhanced blood supply
- 29. DIAGNOSIS Symptoms • Fatigue • Weakness •Tiredness • Decreased functional capacity • Palpitation • Breathlessness • Fe deficiency anaemia-alter temp regulation-feel colder
- 30. DIAGNOSIS Signs • Pallor • Koilonychias •Angular stomatitis • Glossitis
- 31. DIAGNOSIS • All pregnantwomen should screened for anaemia -@ 1st antenatal visit,28 week • CBC-Hb,MCV,MCHC • Peripheral smear-microcytic ,hypochromic • Serum ferritin <30ng/mL
- 33. PREVENTION • WHO –dailydose of 30-60 mg iron supplementation(time of detection to throughout the pregnancy) • 400 mic/day folic acid prophylactic dose
- 34. TREATMENT • Mild tomoderate anemia-oral ferrus iron 80-100 mg/day • Intravenous iron –those with intolerance to oral iron,lack of response to oral iron,severe anaemia,advanced GA • Blood transfusion Based on clinical and investigations Rare if hb>8 predelivery/may need peripartum If critical anemia Hb<6g/dl,mind risk of cardiac failure-Leucodepleted RBC given carefully
- 35. ANESTHETIC CONSIDERATION • minimizefactors interfering with o2 delivery • Prevent any increase in o2 consumption, • optimize partial pressure of o2 in arterial blood • maintenance of stable hemodynamics • avoidance of hypothermia and hyperventilation. Anaemic patients with a Hb concentration<7.5 gm/dlhave a 50% decrease in O2 carrying capacity, -->further decrease due to surgical stress and pain-causes tachycardia and increases the oxygen demand. Hypotension, hypoxia, hypercarbia, respiratory depression and hypoglycaemia further increase the O2 demand.
- 36. ANAESTHESIA MANAGEMENT • Minimizingthe factors that further decrease O2 delivery or increase O2 consumption • Avoid hypoxia,hyperventilation,tachycardia,,hypotension,shivering • Balanced physiology to aid coagulation, prevent acidosis,hypocalcemia,hypothermia • Supplimental O2 while giving spinal • Minimize intra op bleeding-meticulous surgical technique,uterotonics,antyfibrinolytics • Major blood loss-blood transfusion,blood product guided by point of care coagulation tests
- 37. PRE-ANAESTHETIC EVALUATION History andexamination • History chronic poor tissue perfusion – tiredness,fatigue,breathlessness,palpitation,chest pain( planning the technique of anaesthesia) • H/O increased or acute blood loss from GIT, female genital tract • history of chronic diseases • History of prior transfusion, drug/alcohol intake • nutritional habits and history of anaemia • worm infestation • signs of high CO-tachycardia,wide pulse pressure,ESM
- 38. INVESTIGATIONS • CBC,reticulocyte countsmear,bloodgrouping • Stool,urine analysis,ESR,blood urea nitrogen level,s.creatine,bilirubin levels,s.proteins • Serum iron,TIBC,B12 &Folate level • Hb electrophoresis and ecg for any evidence of myocardial ischemia • ECHO
- 39. MINIMAL ACCEPTABLE LEVELOF HB AND NEED OF PRE- OPERATIVE TRANSFUSION • Does not exist-based on patients need,risk of developing complications of inadequate oxygenation • Rarely indicated if hb>10 • Almost always indicated when hb<6 • Hb -7-8 in labour or post partum-according to symptom and associated co existing medical condition,blood loss,threat of bleeding
- 40. OBSTETRIC MANAGEMENT • Normalvaginal delivery should be considered if there is no history of previous caesarean section/obstetric indication for caesarean delivery. • Labour epidural analgesia is beneficial in the first stage of labour along with supplemental oxygen. • Steroids, antibiotics and digitalization should be considered if signs of pulmonary oedema exist. • The second stage of labour should be curtailed by assisted vaginal delivery, and active management of third stage with uterotonics and tranexamic acid should be considered to prevent PPH. • Caesarean section performed for obstetric indications • Anaemia per se is also associated with increased risk of caesarean section
- 41. MONITORING • To assessthe adequacy of perfusion and oxygenation- ECG, NIBP, EtCO2, temperature monitoring, pulse oximetry and urineoutput. • If major blood losses are anticipated- as in placenta previa or acccreta 1-Serial Hb, haematocrit -monitor ongoing blood losses 2- Invasive monitoring (e.g. CVP) 3-Invasive arterial blood pressure monitoring 4-ABG analysis and measurement of mixed venous PvO2
- 42. CHOICE OF ANAESTHESIA •The main concern while choosing anaesthetic technique is to avoid hypoxia, maintain cardiac output and prevent a left shift of ODC. • Both regional and general anaesthesia can be administered for caesarean sections as both the techniques have their relative advantages and disadvantages; • selection depends upon the patient’s physical status and the circumstances at the time of surgery.
- 43. CHOICE OF ANAESTHESIA GA/REGIONAL Dependson • severity and types of anemia • Extent of physiological compensation • Concomitant medical condition • Type and nature of procedure • Anticipated blood loss
- 44. REGIONAL ANAESTHESIA • Regionalanaesthesia or central neuraxial block 1- low-dose spinal anaesthesia along with adjuvants 2-Epidural anaesthesia with intermittent/continuous catheter dosing 3- combined spinal-epidural anaesthesia (CSE)-Dense blockade and allows titratability of drug with stable hemodynamic along with post-operative analgesia. • Supplemental oxygen by face mask or nasal cannula to avoid hypoxia • left uterine displacement to prevent supine hypotension, • Restricted fluid infusions to maintain euvolemia and avoid fluid overload should be ensured. • Mild anxiolytics may be desirable but over-sedation should be avoided
- 45. REGIONAL ANAESTHESIA … Advantages of regional anaesthesia • provides good analgesia • Ability to provide supplemental O2 , • Decreased blood loss with stable hemodynamics, • Psychological benefit for the mother as she is aware of her childbirth. Disadvantage of central neuraxial blockade • Sudden hypotension due to sympathetic blockade extending above T4- impairment of tissue oxygenation • RA avoid in parturients with overt Vitamin B12 deficiencies with neurological symptoms- worsening of symptoms of subacute degeneration of spinal cord
- 46. REGIONAL ANAESTHESIA … •Extra precautions should be taken to avoid hypotension, hemodilution and subsequent heart failure or pulmonary oedema • which may occur on the return of vascular tone once the effect of spinal anaesthesia wears off
- 47. GENERAL ANAESTHESIA • Inseverely anaemic or moderately anaemic patients with cardiac decompensation. Advantages of general anaesthesia • rapid induction, • better cardiovascular stability • control of airway and ventilation, • and less hemodynamic changes, • allaying anxiety and preventing associated cardiovascular changes. Disadvantages of general anaesthesia • chances of aspiration, • hypoxemia during induction, • failed intubation • awareness to the mother and adverse neonatal effects.
- 48. GENERAL ANAESTHESIA…. • Intra-and post-operative optimization of cardiac output and oxygenation helps to improve the patient’s tolerance for anaemia • Can be achieved by reducing the oxygen demand, supplementing oxygen and early use of vasopressors to maintain adequate perfusion and tissue oxygen delivery. • Prevent pain and infection to reduce oxygen requirement.
- 49. GENERAL ANAESTHESIA…. • Measurestaken to prevent hypoxia • pre-oxygenation with 100% O2 and supplementing oxygen in the peri-operative period. • Measures and expertise to secure a definitive airway should be available • Adequate FiO2 , monitoring of ABG and ventilatory parameters, will prevent any undesirable decrease in O2 flux. • Intravenous anaesthetic agents should be slowly titrated to prevent any precipitous fall in CO, • Carefully positioned to minimize position associated volume shifts. • High concentration of volatile agents depresses both the myocardium as well as ventilation and may lead to hemodynamic instability. • Uterotonics and antifibrinolytics such as tranexamic acid should be administered to manage blood loss • Transfusion practices for blood and blood products should be guided by laboratory testing and point-of-care viscoelastic assays, •
- 50. GENERAL ANAESTHESIA…. • Anticipateand treat any adverse events, • fever, shivering and acute massive blood loss, • Mild tachycardia and wide pulse pressure may be physiological and should not be confused with light anaesthesia. • Temperature monitoring and measures to prevent hypothermia to maintain normal core body temperatures • Fluid warmers
- 51. AVOIDANCE OF HYPOXIA •preoxygenation • O2 supplement peri and post operative period • Maintanance of airway-to prevent fall in fio2 due to airway obstruction/difficult intubation • Measures and expertise to secure definitive airway shouldbe available immediately • Spontaneous ventilation-only for short procedure/high fio2 40-50%/high conc volatile agent depress myocardium,ventilation
- 52. AVOIDANCE OF HYPOXIA •Avoid ,treat condition causing increase o2 demand • Fever,shivering,acute massive blood loss hb<7 • N2o cautiously-folate,b12 deficiency
- 53. MINIMIZE DRUG INDUCEDDECREASE IN CO • IV agents slowly titrated –prevent precipitous fall in CO • Careful positioning-minimize position associated volume shift • Mild tachycardia,wide pulse pressure may be physiological –not be confused with light anaesthesia
- 54. FACTORS LEADING TOLEFT SHIFT OF ODC SHOULD BE AVOIDED • Avoid hyperventilation/respiratory alkalosis-Hypocapnia decreases CO-Maintain normocapnia. • Hypothermia should be avoided – i. Take all measures to ensure normal core body temperatures ii. IV fluids and blood products if any should be warmed
- 55. POST-OPERATIVE MANAGEMENT Anaemia maybe further aggravated • peri-operative blood loss • poor nutritional intake post-operatively • frequent blood sampling for laboratory investigations • Rise in hepcidin levels due to inflammatory response to surgeryinhibition of intestinal Fe absorption and reduce the Fe release from stores
- 56. POST-OPERATIVE MANAGEMENT… • Supplementationof oxygen to keep the available haemoglobin saturated. • Repeat assessment of Hb and correction should be done with blood transfusion if necessary. • Transfused RBC contains heme Fe (200–250 mg per unit) with a small amount of labile iron that is immediately available for erythropoiesis depending on the storage time of RBC. • Close monitoring of vital parameters -detect decompensation and early intervention. • Good postoperative analgesia for preventing tachycardia and further load on the CVS. • Ensure euvolemia, normothermia and normalizing the acid-base status.
- 57. POST-OPERATIVE MANAGEMENT… • Fedeficiency anemia- mild to moderate postpartum anaemia (PPA), asymptomatic or mildly symptomatic should be managed with oral Fe for 3 months. • parenteral Fe -if response with oral therapy is not adequate • Early ambulation and physical therapy to prevent venous thromboembolism should be ensured in the postpartum period
- 58. SICKLE CELL ANEMIA •sickle cell disease-trait/disease • Hbs -valine instead of glutamic acid in 6th position of beta chain • when deoxygenated hb aggregate -crisis • hypoxia pao2<50mmhg,acidosis,dehydration,stress,infection,hypothermia • chronic changes in cardiovascular system/dysfunction risk of preterm labour • transfusion only if severe anemia,hypoxemia,preeclampsia,septicemia,renal failure,acute chest pain syndrome,anticipated surgery,aplastic crisis • AIM for Hb >8g/dl,HbA>40%
- 59. SICKLE CELL ANEMIA •Anaesthetic management- avoidance of hypoxemia, hypovolemia, hypothermia and acidosis along with provision of good analgesia. • Both neuraxial and general anaesthesia are acceptable • effective pain management -opioid based neuraxial • avoid pain crisis • avoid dehydration • avoid hypoxemia and acidosis • avoid hypothermia • avoid NSAIDS • avoid transfusion due to antibodies • avoid risk of infection-antibiotics • cell salvage is contraindicated
- 60. THALASSAEMIA • microcytic, haemolyticanaemias-reduced synthesis of one or more of the polypeptide globin chains • Advances in the management of β-thalassaemia major by extensive blood transfusions and chelation therapy have prolonged life expectancy • Higher transfusion requirements in pregnancy worsen haemosiderosis and cardiac failure.
- 61. THALASSEMIA-ANESTHETIC CONSIDERATIONS • Dueto chronic anaemia with resultant tissue hypoxia • multiple transfusions leading to increased iron load especially in the myocardial cells • concomitant difficult airway. Cesarean delivery • General anaesthesia/central neuraxial anaesthesia • platelet count ,excluding history of spontaneous haemorrhage
- 62. COVID-19 INFECTION ANDIDA DURING PREGNANCY • Pregnancy exacerbates the acute inflammation typical to COVID-19, increasing the risk of developing a cytokine storm. • There exists a pathophysiological link between anaemia and severe COVID-19 during pregnancy, which can lead to a poor maternal and neonatal outcome.
- 63. COVID-19 INFECTION ANDIDA DURING PREGNANCY… • Serum levels of ferritin elevated in acute inflammatory conditions • critical role in the development of the cytokine storm. • Iron metabolism plays an important role in supporting the immune system to fight against invading microorganisms. • viral replication requires adequate iron levels within the host cells • The immune system reacts by decreasing the bioavailability of iron during the acute phase.
- 64. COVID-19 INFECTION ANDIDA DURING PREGNANCY… • fall in serum iron concentrations and an increase in serum ferritin. • This leads to decrease in availability of iron for erythropoiesis and thus aggravates iron deficiency anaemia. • The low Hb levels further disrupt the transport of O2 , causing hypoxia and eventually resulting in multiorgan dysfunction syndrome in pregnant COVID-19 patients • SARS-CoV-2 can interact with haemoglobin molecules on the erythrocyte cause the virus to attack the heme on the beta chain of haemoglobin and cause haemolysis • Patients with anaemia should hence be advised to take extra precautions to minimize the risk of exposure to the virus
- 65. CONCLUSIONS • The anaestheticimplications of anaemia in pregnancy are based on the understanding of the normal and compensatory mechanisms that optimize tissue oxygenation and iron homeostasis. • The main aim is to maintain a fine balance between the compensatory mechanisms and adequate tissue oxygenation in these parturients. • Both regional and general anaesthesia can be used judiciously. • Monitoring should aim at assessing the adequacy of perfusion and oxygenation and the magnitude of ongoing losses • Deleterious effects of chronic tissue hypoxemia along with threat of major blood losses in the perioperative period need to be anticipated and treated adequately.
- 66. REFERENCE • Roberta HHines et al.Stolting’s anaesthesia and co-existing disease 3rd edition.copyright 2018,Elsevier • David H Chestnut,MD et al.Chestnut’s obstetrics anesthesia principles and practice 6th edition.copyright 2020,Elsevier • Grewal A. Anemia and pregnancy: Anesthetic implications. Indian J Anaesth 2010;54:380-6 • Sunanda Gupta et al.Pathophysiologic and Anaesthetic Considerations in Iron Deficiency Anaemia and Pregnancy; An Update Journal of Obstetric Anaesthesia and Critical Care | Volume 11 | Issue 2 | July-December 2021;59-69