2. Critical Care in Pregnancy Lauren A. Plante, MD, MPH, FACOG Department of Obstetrics & Gynecology Department of Anesthesiology Division of Maternal-Fetal Medicine Thomas Jefferson University

3. Slide 3 Objectives 1. Explain hemodynamic, respiratory, and metabolic changes in the pregnant patient; 2. Identify determinants of fetal oxygen transport and how to assess and manage poor fetal oxygenation; 3. Identify two disease processes in the pregnant patient, describe how they differ compared to the non-pregnant patient, and understand how to manage the patient; and 4. Describe complications of preeclampsia/eclampsia and their management.

4. Slide 4 Critical Care in Obstetrics 0.2-0.5% of obstetrical admissions require transfer to an intensive care unit One-third are admitted to ICU antepartum –Half are delivered while still in the ICU (or in ICU care) Mortality among OB patients admitted to ICU is 5-6% (cf. overall maternal mortality <1 per 10,000)

5. Slide 5 Common Reasons for ICU Transfer

6. Slide 6 Basic Principles in OB Critical Care Two patients rather than one Interests may not coincide exactly, but maternal needs take precedence Fetal health, as a rule, is maximized when maternal medical condition is optimized Changes in maternal physiology; therefore, changes in normal values

7. Slide 7 Metabolism & Respiration Oxygen consumption increases by 40-60% during pregnancy Primarily due to metabolic needs of fetus, uterus, and placenta Secondarily because of increased cardiac and respiratory work

8. Slide 8 Lung Volumes and Capacities Tidal volume increases 45% No change in FEV1 No change FEV1/FVC ratio FRC reduced by 20% FRC further decreased (another 30% ) in the supine position

9. Slide 9 Oxygen Changes In Pregnancy Increase in oxygen consumption (~20%) Small increase in PaO2: usually >100 mm Hg on room air Reduced A-V O2 difference Widening of A-a gradient Slight decrease in affinity of hemoglobin for oxygen

10. Slide 10 Normal Arterial Blood Gas in Pregnancy Mild chronic compensated respiratory alkalosis pH ~7.44 PaCO2 28-32 mm Hg PaO2 >100 mm Hg HCO3- 18-22 mEq/L

11. Slide 11 Cardiovascular Changes Plasma volume increases 40-50% –Greater increase with multiple gestations Red cell mass increases 20-30% Physiologic hemodilution (not iron-deficiency anemia) and decrease in blood viscosity Blood pressure decreases 10-20%, with diastolic more affected; returns toward non-pregnant norms by the end of the third trimester

12. Slide 12 Cardiovascular Changes Plasma volume increases 40-50% –Greater increase with multiple gestations Red cell mass increases 20-30% Physiologic hemodilution (not iron-deficiency anemia) and decrease in blood viscosity

13. Slide 13 Central Hemodynamics Cardiac output 50% Stroke volume 25% Heart rate 25% LVEDV, EF CVP,PAoP, PAdP, LVSWI: SVR, PVR20%

14. Slide 14 Aortocaval Compression: Effect of Supine Position on Hemodynamics: Enlarging uterus can compress vena cava when patient is supine (less commonly, aortic compression) –Effects: decreased preload, decreased CO, decreased BP (“supine hypotension”) –After 20 weeks, maintain left uterine displacement while recumbent

15. Slide 15 Hemodynamic Changes in Labor Further increase in CO (40-70%) –Increased sympathetic tone augments stroke volume –Additional effect during contraction: autotransfusion of 300-500 ml blood

16. Slide 16 Hemodynamic Changes in Puerperium Relative hypervolemia and increased venous return Attributed to relief of caval compression, loss of intervillous circuit and, thus, autotransfusion CVP rises SV and CO increase by up to an additional 75% immediately postpartum

17. Slide 17 Changes in Renal Function Anatomic: dilation of the collecting system Renal plasma flow & GFR: increase 50% –Serum creatinine <0.6 mg/dl, BUN <10 Renal tubular function: increased sodium reabsorption, increased glucose excretion, decrease in uric acid reabsorption

18. Slide 18 GI and Hepatic Changes Decrease in LES tone, increase in resting intragastric pressure => favor reflux Decreased gastric motility => delayed gastric emptying Acid secretion higher in third trimester than nonpregnant Overall effect: more prone to acid aspiration

19. Slide 19 Changes in Liver Function Alkaline phosphatase: x 2-4 Total cholesterolx 2 Fibrinogen50% Albumin, total protein20% Transaminasesno change

20. Slide 20 Hematology and Coagulation Changes Hgb, Hct decrease as plasma volume increases Overall enhanced platelet turnover, clotting, and fibrinolysis Hypercoagulability Placenta contains thromboplastin, which can induce formation of fibrin and bypass intrinsic pathway

21. Slide 21 Fetoplacental Perfusion No autoregulation in uterine vascular bed => uterus behaves like a fully dilated system Uteroplacental perfusion is pressure-dependent (cannot compensate for abrupt drop in BP) Uterine vasculature unresponsive to changes in PO2 or PCO2

22. Slide 22 Fetoplacental Perfusion and Fetal Oxygenation Placenta is metabolically active; consumes a large fraction of the oxygen delivered to the gravid uterus Human placenta is probably a venous equilibrator: uterine venous PO2 is the upper limit fetal (umbilical) venous PO2

23. Slide 23 Determinants of Fetal Oxygenation Uterine venous PO2, not maternal arterial PO2, determines fetal oxygenation Factors affecting uterine venous PO2: –SvO2 in uterine venous blood SaO2, uteroplacental perfusion, placental and fetal O2 consumption, O2 capacity of maternal blood –Oxyhemoglobin dissociation curve (maternal) Hb structure, temperature, pH, 2,3-DPG

24. Slide 24 Fetal Oxygen Transport Fetal blood has a very low PO2, but oxygen transport from placenta to sites of fetal need is efficient Fetal Hgb has high O2 affinity Fetus has very high cardiac output relative to size and metabolic rate Uterine arterial PO2: 100 mm Hg Umbilical venous PO2: 28 mm Hg (70% saturation) Umbilical arterial PO2: 19 mm Hg (40% saturation) Uterine venous PO2: 35 mm Hg

25. Slide 25 Assessment of Fetal Oxygenation

26. Slide 26 Ionizing Radiation in Pregnancy First 2 weeks after conception (4 weeks from LMP): potential for loss of conceptus Weeks 2-10 after conception (4-12 weeks from LMP): period of organogenesis  teratogenesis possible After 10 weeks (12 weeks from LMP): minimal teratogenesis potential, but risk of impaired fetal growth, childhood leukemia Adverse effects unlikely at radiation doses less than 50-100 mGy (5-10 rad) Typical AP pelvis film ~0.16 mGy dose to fetus Typical CT of pelvis 20-50 mGy (depends on number of cuts, size of area studied) Radiation physicist or dosimetrist can help calculate dose, estimate risk Can substitute other modalities: US, MR; shield abdomen/pelvis unless direct need to image

27. Slide 27 National Radiologic Protection Board, 1998 X-ray examination Mean fetal dose Skull<0.01 mGy Chest<0.01 Abdomen1.4 Thoracic spine<0.01 Lumbar spine1.7 Pelvis1.1 IVP1.7 CT examination Mean fetal dose Head <0.005 mGy Chest 0.06 Abdomen8.0 Lumbar spine 2.4 Pelvis 25 Pelvimetry 0.2

28. Slide 28 Additional Radiation Worries Cognitive impairment –Dose-response with exposure 10-17 weeks –Loss of ~30 IQ points per 1,000 mGy fetal exposure Childhood cancers –Dose-response –One excess fatal childhood cancer per 33,000 population for each mGy intrauterine exposure –Not an indication to offer termination (ACOG 2004) ?Contrast media? –Gadolinium is OK

29. Slide 29 Pharmacology in Pregnancy Most drugs given to the mother do cross into the fetal compartment. This is not necessarily a problem. FDA classification A-B-C-D-X is not helpful, except: avoid category X. Teratogenesis is a theoretical concern with drug exposures in the first trimester. The extent and nature of the risk vary widely.

30. Slide 30 Resources for Drugs in Pregnancy Motherisk (a project of the Hospital for Sick Children, University of Toronto) –http://www.motherisk.org/prof/drugs.jsphttp://www.motherisk.org/prof/drugs.jsp –(416) 813-6780 (phone) Reprotox (database available free to residents in training, otherwise by subscription; hospital or university libraries may maintain a multiuser subscription) –http://www.reprotox.orghttp://www.reprotox.org Teris (computerized database available by subscription; your hospital or university library may keep a subscription) –http://depts.washington.edu/~terisweb/terishttp://depts.washington.edu/~terisweb/teris

31. Slide 31 Perinatal Pharmacology Increased total body water increases volume of distribution. Increased cardiac output and GFR speeds excretion of water-soluble drugs. Dilutional hypoalbuminemia decreases drug binding and increases free drug; may alter acceptable therapeutic range.

32. Conditions Not Specific to Pregnancy

33. Slide 33 Management of the Pregnant Trauma Patient Severity of maternal injuries determines both maternal and fetal outcome. However, even minor maternal injury can be associated with fetal loss. All pregnant patients with major traumatic injury require admission to a facility with both trauma and obstetrical services. Neonatal intensive care services may also be required. Assess and resuscitate the mother first. Then may assess fetus (if at or near viability). Then proceed with secondary survey of the mother.

34. Slide 34 Sepsis OB patients with clinical evidence of local infection: 8- 10% risk bacteremia OB patients with bacteremia rarely progress to sepsis: overall about 4% OB patients with septic shock: <20% mortality

35. Slide 35 Infections Associated with Septic Shock in Pregnancy Chorioamnionitis 0.5-10% PP endometritis: SVD<10% PP endometritis: CS12-50% Urinary 1-3% Septic abortion 1-2% Necrotizing fasciitis <1%

36. Slide 36 Management of Septic Shock in OB Patients Treat as if non-pregnant: fluids, antibiotics, etc; appropriate imaging; ventilatory support, hemodynamic monitoring as needed. Fetoplacental perfusion is dependent on adequate uterine blood flow—maintain BP. If still pregnant and uterus source of infection, delivery is indicated regardless of gestational age.

37. Slide 37 Management of Septic Shock in OB Patients What MAP to target? Can you distinguish central hemodynamics of normal pregnancy from those of sepsis? No human data on vasopressors Some animal data on dopamine All will increase resting uterine tone and decrease uteroplacental perfusion Use electronic fetal monitoring to help titrate Probably cannot use long-term

38. Slide 38 Management of Septic Shock in OB Patients Stress dose steroids can be used if patient would otherwise qualify Recombinant activated protein C…?

39. Slide 39 Acute Renal Failure in Pregnancy Incidence has been decreasing in US Probably 1/5,000 pregnancies currently Current mortality rate in US: 15% OB causes Non-OB causes PreeclampsiaPrerenal HELLPATN AFLPAcute interstitial nephritis Postpartum HUSGlomerulonephritis Bilateral renal cortical necrosis Acute obstruction

40. Slide 40 Management of Acute Renal Failure in Pregnancy Similar to that in non-pregnant patients Both hemodialysis and peritoneal dialysis acceptable –Recommend intensive dialysis (?effect of azotemia on fetus): usually daily –Maintain BUN <70 mg/dl, Cr <5 mg/dl If obstetric cause for renal failure, delivery may be indicated

41. Slide 41 Pregnancy and ARDS Incidence low (1/6,000-10,000 deliveries) Spectrum of causes widened: aside from usual causes ARDS, consider preeclampsia-eclampsia-HELLP, AFLP, anaphylactoid syndrome of pregnancy, tocolytic therapy Maternal mortality ~30%

42. Slide 42 ARDS in Pregnancy Antepartum: –Infectious causes 66% (8% PIH, 8% aspiration) –Mortality 25% Postpartum: –Infection 35%, PIH 29%, shock 18% –Mortality 50%

43. Slide 43 ARDS and Pregnancy Management similar to non-pregnant patient Lung-protective strategy has not been widely tested in pregnant patients with ARDS –Historical data: pregnancy increases barotrauma risk –Theoretical concerns with acidemia 2 hypercapnia Fetal oxygenation OK with maternal PaO2>60 but perfusion essential Delivery does not improve maternal condition or survival

44. Slide 44 Ventilator Management In Pregnancy Common reasons for mechanical ventilation: asthma, ARDS, altered level of consciousness When deciding whether intubation is needed, remember pregnancy norms for ventilation When setting ventilator, remember pregnancy norms for PaO2, PaCO2 PEEP is not contraindicated Use the fetal monitor

45. Slide 45 Airway Management Higher risk of failed intubation in pregnancy (even for the professionals) Be prepared for trouble

46. Slide 46 Ventilator Management in Pregnancy Decreased FRC means more likely to desaturate on disconnect Use sedation/paralysis as appropriate; fetus is not a consideration

47. Problems Unique to Obstetrics

48. Slide 48 Preeclampsia Affects 5-10% of pregnancies in US Syndrome of hypertension, proteinuria, and pathologic edema Unique to human pregnancy Exact etiology unknown –?immunologic contributions –?endothelial dysfunction –?uteroplacental ischemia

49. Slide 49 Treatment of Preeclampsia DELIVERY If mild, remote from term, some place for expectant management

50. Slide 50 Severe Preeclampsia BP >160 systolic or 110 diastolic Proteinuria >5 g/24 hours Oliguria (<500 ml/ 24 hours) Cerebral or visual disturbances Pulmonary edema or cyanosis HELLP syndrome Fetal growth restriction Eclampsia (seizures)

51. Slide 51 Complications of Preeclampsia Brain:edema, hemorrhage, infarction Eyes:retinal detachment, cortical blindness, papilledema CV:severe HTN, pulmonary edema Lung:pulmonary edema, aspiration Liver:hemorrhage, infarction, rupture Kidney:nephrotic syndrome, ARF Blood:thrombocytopenia, DIC, microangiopathic hemolytic anemia

52. Slide 52 Cardiovascular Findings in Preeclampsia Inadequate plasma volume expansion Increased vasoconstriction Hyperdynamic LV function Further decrease in colloid oncotic pressure Decreased COP-PCWP gradient Poor correlation between CVP and PCWP

53. Slide 53 Pulmonary Edema in Preeclampsia Reported as high as 2-3% –70% develop postpartum Contributing factors include decreased COP, alteration of capillary membrane permeability, elevated pulmonary vascular hydrostatic pressures Can be iatrogenic

54. Slide 54 Renal Dysfunction in Preeclampsia Renal plasma flow and GFR are diminished Oliguria in preeclampsia: –Most commonly prerenal –Up to one-third may manifest disproportionate vasospasm –<10%: decreased ECV because of LV dysfunction

55. Slide 55 HELLP Syndrome Hemolysis Elevated Liver enzymes Low Platelets A variant of severe preeclampsia…? Unlike most preeclampsia, not a disease of primigravidas May not meet BP criteria for preeclampsia

56. Slide 56 Complications of HELLP Syndrome Acute renal failure in 7% (usually ATN) Hepatic compromise is common Maternal mortality 1-3% Perinatal mortality 7-30% Resolves after delivery

57. Slide 57 DDx of HELLP Syndrome Easy to confuse with: –ITP –Chronic renal disease –Pyelonephritis –Cholecystitis –Gastroenteritis –Hepatitis –Pancreatitis –TTP –HUS –Acute fatty liver of pregnancy

58. Slide 58 Eclampsia Convulsions or coma, not attributed to any other cause, in a woman with signs or symptoms of preeclampsia Average rate in US 1/2,000 deliveries May occur antepartum, intrapartum, or up to 4 weeks postpartum Maternal mortality in US 0.5-2% Perinatal mortality in US 7-16% Treatment: magnesium; anti-hypertensives if needed; DELIVERY

59. Slide 59 Eclampsia – Complications Abruptio placentae6-17% HELLP syndrome14-20% DIC6-7% Pulmonary edema5-6% Neuro deficit2-9% ARF2-8% Cardiopulmonary arrest2-6% Death<1%

60. Slide 60 Acute Fatty Liver of Pregnancy Rare (1/7,000 to 1/13,000) but potentially fatal Maternal mortality until 1980 as high as 80%; more recently <20% Characterized by jaundice, coagulopathy, CNS disturbance, microvesicular fatty infiltration of liver

61. Slide 61 Acute Fatty Liver of Pregnancy Initial manifestations mild, nonspecific: nausea/vomiting (70%); RUQ or epigastric pain (50%) Jaundice follows in 1-2 weeks DDx includes viral hepatitis, cholestasis of pregnancy, atypical preeclampsia/HELLP Typical picture of hepatic failure: hypoglycemia, coagulopathy, encephalopathy, etc. Usually resolves after delivery (may take days or, rarely, weeks) Stabilize mother, then deliver Care like any other hepatic failure Limited role for transplantation

62. Slide 62 “Amniotic Fluid Embolus” A misnomer Better: anaphylactoid syndrome of pregnancy Characterized by sudden development of hypoxia, hypotension and cardiovascular collapse, coagulopathy

63. Slide 63 ASP/AFES Mortality 60-80% No improvement in survival when event occurs in tertiary care centers No predictability Clinical and hemodynamic similarities to other types of distributive shock (septic, distributive)

64. Slide 64 ASP/AFES General treatment strategies: Supportive care with initial insult; CPR if needed, ventilation with high FIO2, correct any dysrhythmias. Optimize preload; inotropic support if needed. Consider steroid administration.

65. Slide 65 CPR in Pregnancy Difficult to assure adequate cardiac output in supine position (vena cava and, possibly, aortic compression) => perform CPR with patient in left lateral tilt. Fetus is anoxic during maternal cardiac arrest; inadequate uterine perfusion even during effective CPR. Interval from maternal arrest to delivery is correlated with neonatal survival: if mother not resuscitated within 4 minutes, effect perimortem cesarean delivery. A-B-C-D (for delivery). Occasionally, relief of aortocaval compression by uterine evacuation may allow reestablishment of effective CO => improve maternal survival.

66. Slide 66 Perimortem Cesarean Section Consider if maternal resuscitation unsuccessful after 4-5 minutes of CPR If performed after 24 weeks gestation, perinatal survival is possible Even if perinate does not survive, may allow maternal resuscitation Speed counts: –<5 min from arrest to delivery: 70% perinatal survival 6-15 min: 12% perinatal survival

67. Slide 67 Managing the Pregnant Patient Multidisciplinary: If unit is closed, must still involve obstetrician in decision-making. After fetal viability, patient needs both critical care nurse and OB nurse. Maintain left uterine displacement. IM steroids (betamethasone or dexamethasone) after 24 weeks enhance fetal pulmonary maturation and improve neonatal survival. Continuous fetal monitoring from viability onward: excellent indicator of regional perfusion. No tocolytics to suppress contractions.

68. Slide 68 Managing a Pregnant Patient Plan ahead for delivery. Careful with diagnosis of “fetal distress”—ominous tracing more likely indicates a need for a change in maternal therapy. Can patient be safely transported to, or managed in, L&D? Vaginal delivery can be conducted in ICU. Anesthesiology support. Avoid cesarean delivery in ICU (unless perimortem)— move patient to L&D or OR.

69. Slide 69 Managing a Pregnant Patient At all costs, avoid sacrificing the mother for the sake of the fetus

70. Slide 70 Case Studies The following are case studies that can be used for review of this presentation. Review Cases End

71. Slide 71 Case #1 26-year-old woman, first pregnancy, admitted to community hospital at 28 weeks of pregnancy, c/o cough, abdominal pain, fever W/u suggested community-acquired pneumonia: begun on cephalosporin and azithromycin Status deteriorated over ~5 days: transferred to OB at referral center, O2 via facemask, continuous fetal monitoring Further deterioration over 48 hr: PaO2 60 mm Hg on 100%NRB, PaCO2 45. Intubated, transferred to MICU. Dx: ARDS

72. Slide 72 Case #1 PEEP 15 cm, FIO2 1.0 Continuous EFM with OB nurse at bedside Dropped BP: normalized with left uterine displacement and decreased PEEP. Lung- protective ventilatory strategy adopted. Sedation (propofol, benzodiazepines) Not improved after 2 weeks. No etiology apparent other than severe CAP. Trach, PEG. Team conference: offer delivery as course & prognosis of disease unclear and no signs improvement. Betamethasone for fetal lung maturity since newborn will be preterm. Deliver 2 days after steroids given. Transported back to OB floor for induction of labor & planned vaginal delivery. Critical care nurse at bedside. Induction of labor (<24 hr), forceps-assisted delivery; 1,500g newborn to NICU Mother transported back to MICU 2 hours postpartum Gradual improvement over next month Discharged home with no sequelae; baby home ~5 weeks

73. Slide 73 Case #2 37-year-old woman, 26 weeks pregnant, on methadone maintenance, seen for expanding discoloration on abdomen 3 days after minor domestic trauma Prior history includes rectovaginal fistula (following anal sphincter laceration at delivery 10 years earlier) that required diverting colostomy to heal, followed by end-to- end reanastomosis; later incisional hernia repaired w mesh PE: ecchymosis and necrosis in RUQ with purulent malodorous fluid seepage. Patient reported rapid expansion of lesion. BP 90/50, lactate 50

74. Slide 74 Case #2 Likeliest diagnosis: necrotizing soft-tissue infection Broad-spectrum antibiotics. Considered abdominal CT vs. direct exploration in OR Operative findings: necrotic abdominal wall; perforated ileum Resected abdominal wall and 3 feet of bowel; plan to leave abdomen open OB proceeded with cesarean delivery at time of exploratory laparotomy 900-gram newborn to NICU Mother home in 1 week with wound care plan, baby home in 6 weeks

75. Slide 75 Self Assessment Ready to test your knowledge? Take the Review Skip the Review

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87. Slide 87 Topics Webb JAW, Thomsen HS, Morcos SK, and Members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR.)The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol 2005; 15: 1234-40 Zeitlin J, Draper ES, Kollee L, Milligan D, Boerch K, Agostino R, Gortner L, Van Reempts P, Chabernaud J-L, Gadzinowski J, Breart G, Papiernik E, and the MOSAIC Research Group. Differences in rates and short-term outcome of live births before 32 weeks of gestation in Europe in 2003: results from the MOSAIC cohort. Pediatrics 2008; 21: e936-44