Case Report during pregnancy: Continuous fetal monitoring using umbilical artery Doppler flow velocity indices

Manisha Mishra, Ravindra Sawhney, Anil Kumar, Kumar Ramesh Bapna1, Vijay Kohli1, Harpreet Wasir1, Naresh Trehan1 Departments of Cardiaothoracic and Vascular Anesthesiology, 1Departments of Cardiaothoracic and Vascular Surgery, Medanta The Medicity, Gurgaon, Haryana, India

ABSTRACT The fetal death rate associated with cardiac surgery with (CPB) is as high as 9.5‑29%. We report continuous monitoring of fetal rate and umbilical artery flow‑velocity waveforms by transvaginal ultrasonography and their analyses in relation to events of the CPB in two cases in second trimester of pregnancy undergoing replacement. Our findings suggest that the transition of circulation from corporeal to extracorporeal is the most important event during surgery; the associated decrease in mean arterial pressure (MAP) at this stage potentially has deleterious effects on the fetus, which get aggravated with the use of vasopressors. We suggest careful management of CPB at this stage, which include partial controlled CPB at initiation and gradual transition to full CPB; this strategy maintains high MAP and avoids the use of vasopressors. Maternal and fetal monitoring can timely recognize the potential problems and provide window for the required treatment.

Received: 27‑04‑13 Accepted: 08‑10‑13 Key words: Cardiac surgery; Cardiopulmonary bypass; Fetal monitoring; Mitral valve disease; Pregnancy

INTRODUCTION review.[4] This report documents the procedure details and outcome of cardiac surgery in The incidence of heart disease in pregnant two pregnant women in second trimester of women ranges from 1% to 4%, accounting for pregnancy with rheumatic mitral valve disease 10‑15% of maternal deaths, which is similar to at our tertiary care referral hospital. the non‑pregnant women undergoing similar cardiac procedures on cardiopulmonary CASE REPORTS bypass (CPB).[1] The fetal mortality in such patients has remained unchanged at Case 1 9.5‑29%, with an average of 19% over the A 33‑year‑old gravida III, para II was admitted [1‑3] Access this article online past 25 years. Arguably, perioperative to our hospital at 16‑week gestation with Website: www.annals.in management of pregnant women undergoing palpitation and acute (NYHA PMID: cardiac surgery with CPB should take the Class IV). Her medical history revealed history *** well‑being of both mother and fetus into of balloon mitral (BMV) at the DOI: 10.4103/0971-9784.124141 consideration; fetal and maternal monitoring age of 21 years for rheumatic mitral valve Quick Response Code: during cardiac surgery with CPB can allow stenosis (MS). The MS was diagnosed during the greatest control of risk in the pregnant first pregnancy when she became symptomatic patient. Although, successful valve repair at 20 weeks gestation. On examination, and replacements during pregnancy have she was found to be in been reported.[4‑6] Most of these studies are with fast ventricular rate of 146 beats/min. case reports, at times organized as literature Transthoracic revealed

Address for correspondence: Dr. Manisha Mishra, D-2, Front Portion, SF, Kalindi Colony, New Delhi-110065, India. E-mail: [email protected]

46 Annals of Cardiac Anaesthesia  Vol. 17:1  Jan-Mar-2014 Mishra: Cardiac surgery during pregnancy and umbilical artery flow‑velocity indices monitoring a thickened, heavily calcified stenosed mitral valve vena cava cannulation, crystalloid prime, Capiox with an area of 0.6 cm2, moderately severe eccentric sx 18R hollow fiber membrane oxygenator (Terumo jet of mitral regurgitation and a clot in left atrial (LA) cardiovascular systems Inc., Elkton, MD 21921) and appendage, which ruled out BMV as a treatment 38 µ arterial filter (AFFINITY®, Medtronic, Inc. MN option. Hence, /replacement was the 55432). Initially, to avoid precipitous decrease in treatment of choice. Obstetrical examination revealed mean arterial pressure (MAP), partial CPB with a positive fetal viability and an ultrasound demonstrated single venous cannula was established then gradually, normal development consistent with the gestational after ensuring hemodynamic stability, full CPB was age of 16 weeks. established. Thereafter, was clamped, during clamping myocardium was protected by topical cooling Case 2 with ice slush and hyperkalemic, cold (4°C) blood A 26‑year‑old gravida II, para I was admitted with infused into the aortic root at 10 ml/kg complaints of breathlessness on exertion (NYHA body weight at 20 min interval. Systemic normothermia Class III) at 17 weeks of gestation. She had undergone at 35‑36°C was maintained. The MAP during CPB was BMV 3 years ago during her first pregnancy when aimed to be maintained at 70‑80 mmHg and the CPB she went into congestive cardiac failure at 24 weeks flow was kept between 2 and 2.5 L/m2/min. If MAP gestation. At present, she was in normal sinus rhythm was lower than 70 mmHg; initially, the CPB flow with a heart rate of 112 beats/min. Echocardiography was increased, vasoconstrictors were used sparingly. demonstrated severe MS with an area of 0.8 cm2, Hematocrit was maintained between 25-30% and moderate tricuspid valve regurgitation and moderate PaO 2 at 400 mmHg. Pulsatile flow was maintained hypertension. Surgery was the only throughout CPB, using Terumo Sarns™ Modular option at this stage of gestation. Perfusion System 8000 (Terumo CVS‑Ann Arbor MI 48103). Case 1 underwent mitral Both families were counseled about the risks of the with 27 mm (Epic™ St. Jude Medical Minnesota 55117 procedure. Progesterone 100 mg intramuscular was USA) bioprosthesis along with removal of LA clot and started a day prior to surgery. Services of a dedicated ligation of LA appendage. Case 2 underwent mitral obstetrician and a ultrasonologist were ensured inside valve replacement with similar 25 mm bioprosthesis the operating room to monitor fetal heart rate (FHR) along with tricuspid valve repair. Aortic cross clamp and interpret umbilical artery flow‑velocity waveform time was 30 min in Case 1 and 48 min in Case 2. After throughout the procedure. As both cases are similar in unclamping of the aorta, cardiac activity resumed their clinical profile and surgery was performed within after a single defibrillation with 10 joules in Case 1, an interval of 2 months following similar technique, whereas it returned spontaneously in Case 2. Both hence the anesthetic and CPB management are being the patients were weaned from CPB without any discussed together. Baseline FHR and rhythm were inotropic support; the CPB times were 38 min and recorded before induction of anesthesia. Anesthesia 55 min, respectively [Table 1]. After the patients were was induced with etomidate and fentanyl; vecuronium weaned off CPB, protamine was administered and 0.1 mg/kg was administered to facilitate endotracheal hemostasis completed. In both the cases after bypass, intubation. Anesthesia was maintained with O2: Air the FHR gradually increased (over 15 min) to 135‑150 mixture (50:50), isoflurane 1‑1.5%, fentanyl 5 µg/kg, beats/min. Patients were shifted to intensive care unit and incremental doses of vecuronium. During surgery, and continuous maternal and fetal monitoring was the patients were monitored with radial artery continued. Patients were extubated 6 h and 8 h after pressure, a pulmonary artery catheter placed through surgery. Post‑operative course was uneventful. the right internal jugular vein, and transesophageal echocardiography. Additionally, FHR and umbilical MAP, FHR and umbilical artery Doppler flow‑velocity indices artery flow‑velocity waveforms were continuously at the initiation of CPB and during CPB monitored by transvaginal ultrasonography (Siemens, Progressive deceleration of FHR was noted with the ACUSON X300™ ultrasound system and transvaginal onset of CPB in both the cases [Figure 1]. In Case 1, the ultrasound probe 9‑14 MHz) and analyzed in relation initiation of CPB was accompanied by fetal bradycardia, to events of the CPB. Heparin, 4 mg/kg was given the FHR decreased to 80 beats/min; the CPB flow was for anticoagulation and activated clotting time was increased to 3.5 L/m2/min, which led to an increase maintained at >550 s.[4] CPB management was in FHR to > 100/min. The FHR recovered completely standard and included aortic and two separate within 15 min of separation from CPB. In Case 2,

Annals of Cardiac Anaesthesia  Vol. 17:1  Jan-Mar-2014 47 Mishra: Cardiac surgery during pregnancy and umbilical artery flow‑velocity indices monitoring

Table 1: Summary of cardiac procedures done on both pregnant patients Variables Case 1 Case 2 Maternal Age (yrs) 33 26 BSA (m²) 1.7 1.4 Fetal gestation (wks) 16 15 Diagnosis RHD with RHD with Mitral stenosis mitral stenosis and LA Clot and Tricuspid Regurgitation Indication for surgery Cardiac failure Symptomatic severe MS Surgical procedure MVR MVR+Tricuspid repair Aortic clamp 30 48 time (min) CPB time (min) 38 55 Lowest Temperature 35.2° C 35.5° C Figure 1: Graphic depiction of fetal and maternal vital signs during surgery Hospital stay 6 days 10 days Fetal outcome Term, normal Fetal demise baby up, the resistive index (RI) increased to 1.96 and the Maternal outcome Good Good pulsatility index (PI) was 6.2 [Figure 3], which indicates RHD: Rheumatic heart disease, MVR: Mitral valve replacement, an increased utero‑placental resistance. Interestingly, MS: Mitral stenosis, LA: Left the arterial blood gases remained normal throughout the CPB and did not indicate any problem with the the FHR decreased to 40 beats/min after initiation of fetal circulation. CPB; this decrease in FHR was accompanied by a fall in MAP to 46 mmHg and responded transiently to an Outcome of pregnancy increase in pump flow rates. The MAP increased in a Case 1 recovered uneventfully and was discharged few minutes to 65 mmHg after the administration of from the hospital on the 6th post‑operative day. ephedrine 5 mg, yet the FHR did not increase above Serial fetal ultrasounds revealed a normal fetus. 60 beats/min on CPB. Hydrocortisone 100 mg was She underwent a full term normal vaginal delivery administered and infusion of nitroglycerin was started at 38 weeks gestation and delivered a healthy empirically in the hope of avoiding a further decrease normal baby. The Case 2 had normal FHR and fetal in FHR due to placental vasoconstriction leading to movements for the first four post‑operative days. On fetal hypoxia. The FHR recovered gradually until the 5th post‑operative day, FHR could not be located completion of operation. and fetal demise was detected, which was followed by spontaneous expulsion of fetus. The FHR and Doppler flow velocitymetry indices of umbilical artery flow were analyzed in order to diagnose DISCUSSION fetal hypoxia and/or acidosis, which are presumed to be associated with elevated placental vascular resistance. Cardiovascular changes during pregnancy are usually A thorough analysis of the Figures 2a‑d. substantiates well tolerated in healthy women. However, 1‑4% the above presumption. In Case 2, At the initiation of women of childbearing age have some degree of of CPB when the MAP decreased to 46 mmHg, the concomitant heart disease and they may present with Doppler flow velocity profile showed absence of compromised cardiac function.[1] The CPB induces diastolic flow and fetal bradycardia [Figure 2a], the a non‑physiologic hemodynamic state that can diastolic flow gradually appeared over 5 min as the adversely affect the mother and the fetus during cardiac MAP increased, though with vasopressors, but fetal surgery.[3,7] The CPB is accompanied by alterations in bradycardia persisted [Figure 2b]. The umbilical artery the cellular and protein components of the blood. Apart flow, both systolic and diastolic improved further after from hemodilution and coagulation protein changes, nitroglycerin infusion [Figure 2c]. At 30 min on CPB, activation of immune responses, particulate and air the FHR again decreased to 40 beats/min and once embolism and hypotension during CPB further add to again, the diastolic flow disappeared, despite a MAP of the deleterious effects of CPB.[3,4] These changes are 70 mmHg [Figure 2d]. The flow‑velocity indices went relatively well tolerated by the mother, to the extent

48 Annals of Cardiac Anaesthesia  Vol. 17:1  Jan-Mar-2014 Mishra: Cardiac surgery during pregnancy and umbilical artery flow‑velocity indices monitoring

Figure 2a: Umbilical artery Doppler flow velocity profile in Case 2. The Doppler Figure 2b: Umbilical artery Doppler flow velocity profile in Case 2. After 5 min flow velocity profile showed bradycardia with absence of diastolic flow immediately gradual appearance of diastolic flow, as the mean arterial pressure came up to at the initiation of cardiopulmonary bypass, mean arterial pressure was 46 mmHg 75 mm Hg with vasopressors, but fetal bradycardia persisted

Figure 2c: Umbilical artery Doppler flow velocity profile in Case 2. The umbilical Figure 2d: Umbilical artery Doppler flow velocity profile in Case 2. At 30 min artery flow, both systolic and diastolic improved further after nitroglycerine of cardiopulmonary bypass the fetal bradycardia, 40 beats/min and the absent infusion diastolic flow persisted despite a mean arterial pressure of 70 mm-Hg

women who undergo similar cardiac procedures on CPB.[7] Cardiovascular maternal morbidity and mortality during pregnancy correlate strongly with maternal functional status.[8,9] Four major risk factors predict adverse maternal outcomes: (1) History of transient ischemic attack, , or arrhythmia. (2) NYHA heart failure classification of three or four before onset of pregnancy (3) left‑heart obstruction‑mitral valve area <2 cm2, aortic valve area <1.5 cm2 (4) left ventricular ejection fraction <40%.[5] However, the fetal mortality rate during cardiac surgery with CPB still remains high, the maternal mortality rate range from Figure 3: Graphic demonstration of changes in resistive index and pulsatility 1.5% to 5% and the fetal mortality rate range from 9.5% index of umbilical artery flow during surgery to 29%.[1,2] Most adverse maternal and fetal outcomes from cardiac surgery during pregnancy are a result of that the maternal mortality rate associated with CPB CPB and the underlying cardiac status of the mother, in pregnant women is similar to that in non‑pregnant not the anesthetic agent used[10] in spite of the fact that

Annals of Cardiac Anaesthesia  Vol. 17:1  Jan-Mar-2014 49 Mishra: Cardiac surgery during pregnancy and umbilical artery flow‑velocity indices monitoring all the inhaled anesthetics and most of the intravenous renin‑angiotensin pathway, resulting in improved anesthetics are highly lipid soluble and freely cross the blood flow to the feto‑placental unit.[3,12] In both the placenta. Volatile anesthetics are also potent uterine cases pulsatile flow was used during CPB. In Case 2, relaxants and decrease uterine blood flow (UBF). the MAP decreased to 46 mmHg at the commencement All opioids may cause fetal respiratory depression, of CPB and responded transiently to increase in pump bradycardia and loss of beat‑to‑beat variability as they flow rates, and ephedrine had to be used to maintain readily cross the placental barrier. Etomidate is likely to MAP. This patient had prolonged bradycardia with have minimal impact on the fetus or UBF. Therefore, in increases in umbilical artery flow‑velocity indices RI addition to providing hemodynamic stability, etomidate and PI [Figures 2 and 3], which indicate increased is an excellent choice for anesthetic induction in the utero‑placental resistance. Many reports document parturient with cardiac disease.[5] abnormal FHR on CPB, which did not return to normal value for several hours post‑operatively.[1,5,7] An important event during CPB is the initial hypotension There is only one report of return of FHR after surgical that occurs when the circulation goes from corporeal to intervention despite its complete disappearance during extracorporeal. Maternal hypotension shortly after the CPB and not resulting in fetal mortality.[1] commencement of CPB is caused by a decrease in the systemic vascular resistance affected by reduced flow Sympathomimetic agents such as ephedrine and rate, hemodilution and release of vasoactive substances, phenylephrine can be used to maintain perfusion which can result in significant reduction in placental pressure and are considered to be safe during pregnancy, perfusion.[9,11] Although fetal bradycardia is known to this impression is largely due to the studies suggesting develop frequently during the initiation of CPB and to improved fetal acid‑base status with both these drugs normalize after CPB, it is likely to be caused by fetal in patients undergoing cesarean section under spinal hypoxia or acidosis, maternal hypothermia, maternal anesthesia.[13] Nitroglycerine is reported to be an effective hypoglycemia or administration of drugs that are tocolytic with the minimal complications and its use transferable through the placenta. Fetal hypoxia can during obstetric procedures has been described;[14] be caused by reduced oxygen content of the maternal however, in spite of its use in the second case, a stillbirth blood, reduced uterine perfusion pressure, or increased occurred after surgery on the 5th post‑operative day. uterine arterial resistance. Like fetal bradycardia, Based on published reports, fetal hypoxia or acidosis compensatory tachycardia that frequently follows is likely to show elevated placental vascular resistance fetal distress is also reported to indicate fetal hypoxia. or low cerebral vascular resistance, a phenomenon that Fetal bradycardia has been described as a response is most apparent in fetal growth retardation cases. With to the decrease in utero‑placental perfusion and the the use of Doppler velocitymetry, a relationship between resultant uterine contractions and can be corrected by findings, which reflect fetal hypoxia increased maternal blood flow by increasing CPB flow or acidosis and flow velocity waveform changes has rates, which is expected to increase placental perfusion. been established.[12,15] Various strategies to improve fetal During pregnancy, the placental blood vessels are survival have been advocated. Use of the intra‑aortic maximally dilated, the UBF is not autoregulated and is balloon pump in pregnancy has also been reported, directly proportional to the maternal MAP and inversely specifically in an attempt to improve uterine perfusion proportional to the uterine vascular resistance.[1,4] and to relieve profound fetal bradycardia.[16] Monitoring Sustained uterine contractions during cardiac surgery of FHR and the uterus has been reported to reduce fetal and CPB are accepted as the most important cause of fetal mortality rate to 9.5% by enabling early recognition of death.[3,4] The excitability of uterine muscle is probably potential problems during CPB and timely provision of enhanced by hormonal dilution, mainly by the dilution the required treatment.[3,8,11,17] of progesterone. The post‑operative administration of progesterone has successfully eliminated premature Chandrasekhar et al.,[5] suggested the following strategies labor.[3,11] In both our patients, progesterone therapy was during CPB for fetal protection: A high pump flow instituted in the peri‑operative period, which proved rate (2.5 L/min/m2) and perfusion pressure >70 mmHg beneficial in preventing uterine contractions during to maintain UBF; The maternal hematocrit be surgery and also in the post‑operative period. maintained >28% to optimize oxygen‑carrying capacity;[9] Pulsatile flow that prevents the drop in Pulsatile flow preserves endothelial nitric oxide placental perfusion and limits the rise in placental synthesis and decreases activation of the fetal vascular resistance that is observed with non‑pulsatile

50 Annals of Cardiac Anaesthesia  Vol. 17:1  Jan-Mar-2014 Mishra: Cardiac surgery during pregnancy and umbilical artery flow‑velocity indices monitoring flow;[12] In one series, the fetal mortality was 0% with 3. Abbas AE, Lester SJ, Connolly H. Pregnancy and the cardiovascular normothermic perfusion during CPB,[4] whereas it was system. Int J Cardiol 2005;98:179‑89. 4. John AS, Gurley F, Schaff HV, Warnes CA, Phillips SD, Arendt KW, 24% when hypothermic CPB was used. Finally, alpha stat et al. Cardiopulmonary bypass during pregnancy. Ann Thorac Surg pH management may be advantageous for maintenance 2011;91:1191‑6. of CO homeostasis and UBF.[5,12] The changes in CO 5. Chandrasekhar S, Cook CR, Collard CD. Cardiac surgery in the 2 2 parturient. Anesth Analg 2009;108:777‑85. tension can affect UBF; specifically, hypocapnia causes 6. de Souza JA, Martinez EE Jr, Ambrose JA, Alves CM, Born D, Buffolo E, utero‑placental vasoconstriction, whereas hypercapnia et al. Percutaneous balloon mitral valvuloplasty in comparison with open increases UBF. All the above‑mentioned strategies mitral valve commissurotomy for mitral stenosis during pregnancy. J Am Coll Cardiol 2001;37:900‑3. were followed while managing these two cases, yet 7. Patel A, Asopa S, Tang AT, Ohri SK. Cardiac surgery during pregnancy. there was fetal demise in second case. This could be Tex Heart Inst J 2008;35:307‑12. attributed to maternal hypotension, which occurred 8. Drenthen W, Pieper PG, Roos‑Hesselink JW, van Lottum WA, Voors AA, at the commencement of CPB, possibly leading to Mulder BJ, et al. Outcome of pregnancy in women with congenital heart disease: A literature review. J Am Coll Cardiol 2007;49:2303‑11. sustained fetal hypoxia. The deceleration of fetal heart 9. Arnoni RT, Arnoni AS, Bonini RC, de Almeida AF, Neto CA, Dinkhuysen JJ, and the changes in the Doppler flow‑velocity indices et al. Risk factors associated with cardiac surgery during pregnancy. of umbilical artery also give an indication of fetal Ann Thorac Surg 2003;76:1605‑8. 10. Arendt K, Abel M. The pregnant patient and cardiopulmonary bypass. hypoxia, which probably got aggravated with the use In: Cohen NH, editor. Medically Challenging Patients Undergoing of vasopressors. : A Society of Cardiovascular Anesthesiologists Monograph. Philadelphia, PA: Lippincott Wiliams and Wilkins; 2009. p. 215‑44. In summary, the chief concerns in the optimal 11. Iscan ZH, Mavioglu L, Vural KM, Kucuker S, Birincioglu L. Cardiac surgery management of pregnant patients undergoing CPB during pregnancy. J Dis 2006;15:686‑90. are maintaining high pump flow rates, normothermic 12. Vedrinne C, Tronc F, Martinot S, Robin J, Allevard AM, Vincent M, et al. CPB, pulsatile perfusion and keeping the CPB time as Better preservation of endothelial function and decreased activation of the fetal renin‑angiotensin pathway with the use of pulsatile flow during short as possible. The most important event during experimental fetal bypass. J Thorac Cardiovasc Surg 2000;120:770‑7. surgery is the transition of corporeal circulation to 13. Habib AS. A review of the impact of phenylephrine administration extracorporeal; the decrease in MAP at this stage may on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth have potential deleterious effects on the fetus and Analg 2012;114:377‑90. should be avoided. It is advisable to establish gradually 14. O’Grady JP, Parker RK, Patel SS. Nitroglycerin for rapid tocolysis: full CPB, maintaining high MAP and avoiding the use Development of a protocol and a literature review. J Perinatol 2000;20:27‑33. of vasoconstrictors, which may have a profound effect 15. Jahangiri M, Clarke J, Prefumo F, Pumphrey C, Ward D. Cardiac surgery on the placental unit. Maternal and fetal monitoring can during pregnancy: Pulsatile or nonpulsatile perfusion? J Thorac enable early recognition of potential problems during Cardiovasc Surg 2003;126:894‑5. 16. Willcox TW, Stone P, Milsom FP, Connell H. Cardiopulmonary bypass in CPB and timely initiation of the required treatment pregnancy: Possible new role for the intra‑aortic balloon pump. J Extra thereby ameliorating fetal hypoperfusion and hypoxia Corpor Technol 2005;37:189‑91. and minimizing the risks to the mother and the fetus. 17. Karahan N, Oztürk T, Yetkin U, Yilik L, Baloglu A, Gürbüz A. Managing severe heart failure in a pregnant patient undergoing cardiopulmonary bypass: Case report and review of the literature. J Cardiothorac Vasc REFERENCES Anesth 2004;18:339‑43.

1. Mahli A, Izdes S, Coskun D. Cardiac operations during pregnancy: Cite this article as: Mishra M, Sawhney R, Kumar A, Bapna KR, Kohli V, Review of factors influencing fetal outcome. Ann Thorac Surg Wasir H, et al. Cardiac surgery during pregnancy: Continuous fetal monitoring using umbilical artery Doppler flow velocity indices. Ann Card Anaesth 2000;69:1622‑6. 2014;17:46-51. 2. Davies GA, Herbert WN. Congenital heart disease in pregnancy. J Obstet Gynaecol Can 2007;29:409‑14. Source of Support: Nil, Conflict of Interest: None declared.

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