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Anaesthetic considerations in a parturient with critical coronary artery disease and a drug-eluting stent presenting for caesarean section
International Journal of Obstetric Anesthesia (2005) 14, 167–171 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2004.10.010
CASE REPORT
Anaesthetic considerations in a parturient with critical coronary artery disease and a drug-eluting stent presenting for caesarean section J. A. Cuthill, S. Young, I. A. Greer, K. Oldroyd Department of Anaesthesia, Princess Royal Maternity Hospital, Department of Obstetrics & Gynaecology, University of Glasgow, and Department of Cardiology, Western Infirmary, Glasgow, UK SUMMARY. A parturient presented with her first symptoms of coronary artery disease at 18 weeks’ gestation. Following an angiogram, a drug-eluting stent was inserted, resulting in resolution of her symptoms. The patient was prescribed anti-platelet medication including clopidogrel. She was delivered by elective caesarean section at 35 weeks under general anaesthesia. The anaesthetic management is discussed and a review of the literature presented. 2004 Elsevier Ltd. All rights reserved. Keywords: Coronary stent; Drug-eluting; Coronary heart disease in pregnancy; Clopidogrel
pregnancies. There was no family history of coronary heart disease. She was taking no medication. Examination was unremarkable apart from a benign-sounding flow murmur at the left sternal edge. Her electrocardiogram (ECG) showed isolated T-wave inversion in lead aVL. She had good left ventricular systolic function on echocardiography with no ventricular hypertrophy and normal valves. A Bruce protocol exercise test was terminated after 4 min 8 s due to chest pain and widespread ischaemic ST-T wave changes. She was prescribed aspirin 75 mg daily, atenolol 25 mg daily and glyceryl trinitrate spray as required and referred both to the obstetric medicine clinic at the Princess Royal Maternity Hospital and to a cardiologist. Following discussion between the cardiologist and obstetricians, she underwent coronary angiography at 26 weeks. This showed severe ostial left main stem stenosis with moderate disease in the left anterior descending artery, its diagonal branches and the proximal segment of the left circumflex artery. The right coronary artery was also noted to have mild luminal irregularity. Four days later she was reviewed at the obstetric medicine clinic. She reported that her symptoms had worsened following angiography. At this point clopidogrel 75 mg daily and enoxaparin 40 mg daily were prescribed. The cardiothoracic surgeons did not consider her a candidate for coronary bypass surgery at this stage in her pregnancy and a decision was made to proceed to percutaneous coronary intervention. She remained on
INTRODUCTION Although uncommon in pregnancy, ischaemic heart disease can present the obstetric anaesthetist with major challenges. Recent advances in cardiological management further influence the decision-making process. The following case report illustrates some of these difficulties and reviews the current relevant literature.
CASE REPORT A 38-year-old woman, para 4 + 0, was referred to the chest pain clinic by her general practitioner at 18 weeks’ gestation complaining of a five-month history of chest discomfort, mainly on exertion. She smoked 20 cigarettes a day and had a past history of hypertension, which had worsened following each of her four previous Accepted October 2004 J.A. Cuthill, Senior House Officer in Anaesthesia; S. Young, Consultant Anaesthetist, Princess Royal Maternity Hospital, 16 Alexandra Parade, Glasgow, G31 2ER; I.A. Greer, Regius Professor of Obstetrics and Gynaecology, Wolfson Medical School Building, University of Glasgow, Glasgow G12 8QQ; K. Oldroyd, Consultant Cardiologist, Western Infirmary, Dumbarton Road, Glasgow, G12, UK. Correspondence to: S. Young, Consultant Anaesthetist, Department of Anaesthetics, Princess Royal Maternity Hospital, 16 Alexandra Parade, Glasgow G31 2ER. Tel.: +0141 211 4620. E-mail: [email protected]. 167
168 International Journal of Obstetric Anesthesia aspirin 75 mg, but labetalol 100 mg twice daily was substituted for atenolol on the advice of the obstetricians. At 28 weeks a 3 · 8 mm sirolimus eluting stent (Cyphere; Cordis, Johnson and Johnson) was inserted into the left main coronary artery. Further angiographic views confirmed the presence of moderately severe disease distal to the stent, in the mid-segment of the left anterior descending artery, a diagonal branch and the proximal segment of the left circumflex artery. It was considered, however, that no further revascularisation was required at this point. She was discharged on clopidogrel 75 mg and aspirin 75 mg daily as is standard cardiological practice, and additionally on labetalol 100 mg twice daily and enoxaparin 40 mg daily, to compensate for the relative hypercoagulable state of pregnancy as perceived by the obstetricians. At 35 weeks the patient was delivered by elective caesarean section. It was considered that in a patient who had residual widespread coronary atherosclerosis despite stent placement, caesarean section would be safer than spontaneous vaginal delivery from the standpoint of haemodynamics and myocardial oxygen delivery. It was also considered preferable to deliver her at 35 weeks in order to reduce any additional stress on the cardiovascular system in the last few weeks of pregnancy when there was relatively little potential gain for the fetus from continuing the pregnancy. In addition, although there is evidence to permit the use of neuraxial anaesthesia with both aspirin and low-molecular-weight heparin, there are few data regarding the risk of adding clopidogrel to this combination. The cardiologist considered it important that her anti-platelet medication was continued peri-operatively. Thus, her drug regime precluded regional anaesthesia due to the potential risk of spinal or epidural haematoma, and general anaesthesia was selected. She received enoxaparin 40 mg as a prophylactic dose on the evening before surgery and her aspirin and clopidogrel were withheld on the morning of surgery as she was fasting – the anti-platelet effect was not expected to be influenced by this short omission. Before induction of anaesthesia, large bore i.v. access and intra-arterial blood pressure monitoring were instituted and a glyceryl trinitrate patch applied. She required esmolol 10 mg to control transient hypertension of 180/95 mm Hg just before induction. Following preoxygenation for 3 min, we carried out a rapid sequence induction with left lateral tilt and cricoid pressure using etomidate 20 mg, suxamethonium 100 mg and a remifentanil infusion (initially 0.6 lgÆkg 1min 1). The pressor response to intubation was obtunded by lidocaine 1 mg/kg and alfentanil 1.5 mg. Induction was uncomplicated apart from a transient self-limiting bradycardia occurring during intubation. The lowest oxygen saturation was 95%. A right internal jugular central venous
line was inserted after induction to guide fluid replacement, as there was the potential for a larger blood loss than usual. Anaesthesia was maintained with isoflurane in oxygen and air. Remifentanil was infused at a rate of 0.2–0.3 lgÆkg 1min 1 to maintain the pulse rate around 75 to 80 beats/min. The caesarean section was uncomplicated surgically, a baby boy weighing 2.03 kg with Apgar scores of 5 at 1 min and 8 at 5 min was delivered 13 min after induction of anaesthesia. Remifentanil was continued after delivery, although she also received i.v. morphine boluses to a total of 17 mg during the remainder of the procedure. She remained haemodynamically stable intraoperatively, with a pulse rate of 70–85 beats/min, systolic pressure 110–150 mmHg and diastolic pressure 70–80 mm Hg. There were no ischaemic changes on ECG. To avoid any precipitous drop in blood pressure, an i.v. bolus dose of oxytocin was withheld and she received 20 units as an infusion in Hartmann’s solution 500 mL over one hour. The uterus was well contracted at the conclusion of surgery. Blood loss was estimated at 500 mL and 2500 mL crystalloid was infused perioperatively. Haemodynamic responses to extubation were obtunded by fentanyl and esmolol boluses. She was returned to the high dependency unit with a morphine patientcontrolled analgesia pump and was prescribed regular paracetamol. Non-steroidal anti-inflammatory drugs were withheld due to the increased risk of bleeding. Full invasive monitoring was continued postoperatively. In the first 2 h she required several i.v. boluses of labetalol 5–10 mg for hypertension. Four hours postoperatively she became oliguric and her blood pressure fell to 100/60 mm Hg. There was no obvious source of blood loss. Repeat full blood count showed a fall in haemoglobin from 11.3 g/dL pre-operatively to 6.3 g/dL. Coagulation remained normal. An ultrasound showed evidence of intra-abdominal clot with fluid in the paracolic gutter. She was transfused a total of four units of packed red cells which increased her haemoglobin to 9.0 g/dL and resolved her oliguria. She remained well for the next three days with no further bleeding or drop in haemoglobin and no anginal symptoms. Postoperative troponin levels were <0.2 lg/L and she had no new ECG changes. Six months post partum she has had no recurrence of her angina and a repeat Bruce protocol exercise test was negative at high workload. Accordingly no further coronary angiography or revascularisation is planned.
DISCUSSION Coronary artery disease in pregnancy has been uncommon in UK practice and there are few published case
Anaesthesia in coronary artery disease with a drug-eluting stent 169 reports.1–4 The prevalence of all cardiac lesions in women of reproductive age is estimated at 0.4% to 4.5%, while the incidence of myocardial infarction in pregnancy is estimated as 0.01%.5 The increased cardiovascular demands of pregnancy are well known and can worsen myocardial ischaemia in at-risk patients by altering the balance between myocardial oxygen supply and demand. A rise in blood volume, cardiac output and heart rate increases myocardial workload and oxygen consumption. In addition, myocardial oxygen supply may be reduced by the physiological anaemia of pregnancy and the lower diastolic pressure resulting from decreased systemic vascular resistance.6 The West of Scotland has one of the highest rates of coronary heart disease in the World, particularly in women7 and it is not unusual for patients to present with severe disease in their thirties. Pregnancy may be the final contributing factor that leads to symptoms in young women with prior asymptomatic disease. The development of coronary stenting coupled with improvements in adjunctive anti-platelet therapy has led to an increasing use of percutaneous intervention in the treatment of coronary artery disease.8 As far as we are aware, there is no published material on the use of coronary stents during pregnancy, although there is some experience of angioplasty.3 The sirolimus eluting stent used in this patient is the first drug-eluting coronary stent to be approved for clinical use, having received its CE (European Conformity) mark in April 2002 with FDA approval following in April 2003.9 It is coated with a formulation of sirolimus, a macrocytic lactone produced by Streptomyces hygroscopicus. Sirolimus is an immunosuppressant which inhibits both the activation of T lymphocytes and the proliferation of vascular smooth muscle and endothelial cells. It has been shown to decrease the rate of restenosis when compared to conventional bare metal stents,10 but there are no data on its use in pregnancy. Various trials have shown that the use of dual antiplatelet therapy, most commonly aspirin and clopidogrel, reduces the risk of subacute thrombosis following coronary stent implantation.11,12 In addition, continuing this therapy for up to one year after stenting has been shown to give a 26.9% relative reduction in the combined risk of death, myocardial infarction or stroke when compared to short-term therapy.13 All previous studies looking specifically at the Cyphere stent have used aspirin and clopidogrel in various dose regimes before and after stent placement.10,14 Discontinuation of clopidogrel is associated with a significant rate of stent thrombosis. 12 The fact that our patient was taking aspirin, clopidogrel and prophylactic enoxaparin decreased our options for anaesthetic management of this case. A rare complication of regional anaesthesia is epidural haematoma,
the consequences of which can be disastrous. Aspirin therapy does not increase this risk15 and most anaesthetists would probably still be willing to perform regional block in those patients taking aspirin. There are clear guidelines regarding the use of low-molecular-weight heparin in conjunction with central neuraxial block. These state that epidural anaesthesia is safest when performed 12 h after a prophylactic dose of low-molecularweight heparin.16,17 The estimated risk of haematoma following epidural block is 1:70 000 when heparin prophylaxis is prescribed. This increases to 1:8500 with the addition of aspirin.17 The addition of clopidogrel to aspirin, however, significantly increases the bleeding time.18 It has been shown that, in patients undergoing coronary bypass surgery while taking clopidogrel, there is an increase in the number of haemorrhagic complications with a greater need for surgical re-exploration, transfusion of packed red cells and the use of cryoprecipitate.19,20 No series has been performed to evaluate the risk of clopidogrel and neuraxial block and the safety of concurrent clopidogrel and aspirin has not been established. There have certainly been three reports of epidural haematoma attributed to clopidogrel and two cases of severe bleeding following lumbar sympathetic block.17 We felt that the risk of combining aspirin and clopidogrel with low-molecular-weight heparin was significant and in our view, regional anaesthesia was contraindicated. In addition, the cardiovascular responses to regional anaesthesia include hypotension secondary to sympathetic blockade, which is often more profound in hypertensive patients such as ours.21 It has been shown that a decline in blood pressure of greater than 30% is usually associated with a fall in cardiac output22 and this, combined with either bradycardia or reflex tachycardia – frequent occurrences, especially during spinal anaesthesia – results in major circulatory changes that could be life threatening in a patient with critical coronary artery disease. Our options were therefore spontaneous delivery with opioid analgesia if required or caesarean section under general anaesthesia. There is no general consensus as to the mode of delivery appropriate for patients with ischaemic heart disease. A previous case report of two pregnancies following myocardial infarction stated that the mode of delivery should be based solely on obstetric indications, allowing the mother to progress to spontaneous labour and deliver with no need for invasive haemodynamic monitoring, provided ventricular function was intact.5 Labour results in further increases in heart rate, cardiac output and systemic vascular resistance over and above those of pregnancy23 with an increase in central venous pressure and pre-load during contractions.24 These changes increase the myocardial oxygen demand
170 International Journal of Obstetric Anesthesia and may precipitate cardiac failure in some patients with poor ventricular function. Anxiety and pain, which may be difficult to control fully without epidural analgesia, act to increase cardiac work further due to catecholamine release. Our patient was known to have relatively widespread coronary artery disease distal to the stent placement. Had this not been the case, it could have been safer to allow her to progress to spontaneous labour with i.v. opioid analgesia if required. This would have almost completely removed the significant risk of general anaesthesia in pregnancy and of spinal or epidural haematoma resulting from neuraxial blockade. The patient had had four previous uncomplicated pregnancies and the risk of complications requiring operative or instrumental intervention was thought to be low. Despite this, it was felt that the benefits of a well prepared elective general anaesthetic carried out within normal office hours outweighed the physiological strain that would be placed on our patient if allowed to deliver spontaneously, particularly in the second stage of labour, and the small but significant risk of needing emergency intervention, possibly overnight and initiated by the most junior of the anaesthetic team. The aim of our general anaesthetic plan was to provide a stable blood pressure at all times and to avoid tachycardia, which would decrease myocardial oxygen supply. As far as possible, we attempted to provide this by using boluses of esmolol, alfentanil or lidocaine to obtund any pressor response. This proved successful. In caesarean sections under general anaesthesia, normal practice is to withhold opioid analgesia and use low minimal alveolar concentrations of volatile anaesthetic until after delivery of the baby to avoid the problems of neonatal sedation and respiratory depression. In our patient, this would probably have caused tachycardia and hypertension, both of which would have been detrimental to coronary oxygenation. Remifentanil was used as an infusion as it is quickly and easily titratable to both pain and cardiovascular parameters and has been shown to cause minimal neonatal depression.25 This case also highlights the potential problem of excessive bleeding in patients taking anti-platelet medication. Our patient suffered a serious and relatively hidden postoperative bleed with a drop in haemoglobin of around 5 g/dL. A recent paper states that aspirin and non-steroidal anti-inflammatory drugs moderately increase intra- and postoperative bleeding, but not transfusion requirements.26 Fewer data are available regarding clopidogrel.17–19 Whether we could have done anything other than maintain a high degree of suspicion in this case is debatable. The main issues of perioperative bleeding and neuraxial anaesthesia in this particular patient seem to relate to clopidogrel rather than aspirin and low-molecular-
weight heparin. Due to the widespread use of the latter two, experience has been gained and guidelines are in place for perioperative management. Both the above problems could have been solved by withdrawing some anti-platelet therapy at least one week before surgery. There is as yet no official guidance from the cardiologists regarding the management of patients who have stents in situ and present for non-cardiac surgery. Certainly, the risk of perioperative bleeding is high if medication is continued, but discontinuing medication can increases the risk of stent thrombosis. Both the CREDO13 and CURE12 trials have shown the significant benefit of continuing long-term clopidogrel with aspirin following stenting. A further case report published last year discussed a patient who presented for thoracic surgery six weeks after stenting of his left anterior descending and circumflex artery. Clopidogrel was stopped two weeks before surgery to allow epidural placement and he suffered a postoperative myocardial infarction due to total stent occlusion, which led to cardiogenic shock and death.27 In summary, providing safe obstetric anaesthesia for patients with severe coronary heart disease is challenging and there is still no general consensus as to the best way to manage these patients due to the relatively small number who present. The rapid increase in newer and more effective anti-thrombotic agents has allowed advances in percutaneous coronary intervention in the last few years, which has decreased the need for coronary artery bypass grafting, a procedure that would certainly carry a high risk in pregnancy, although it has been carried out successfully before.2 These techniques have produced problems of their own, namely the increased rate of surgical and post-surgical bleeding that occurs in those on anti-thrombotic medication. Specifically in obstetrics, it is not ideal to be precluded from using regional techniques that have dramatically decreased maternal mortality associated with anaesthesia.28 However, it remains uncertain whether a parturient with coronary artery disease is more stable and at less risk of complications from a spontaneous labour, regional anaesthesia or general anaesthesia, all of which cause significant and sometimes very rapid changes to maternal cardiovascular physiology. As percutaneous coronary intervention becomes more widespread, these patients are likely to present to obstetric anaesthetists with increasing frequency, resulting in further controversy about their management.
REFERENCES 1. Chestnut D H, Zlatnik F J, Pitkin R M, Varner M W. Pregnancy in a patient with a history of myocardial infarction and coronary artery bypass grafting. Am J Obstet Gynecol 1986; 155: 372–373.
Anaesthesia in coronary artery disease with a drug-eluting stent 171 2. Silberman S, Fink D, Berko R S, Mendzelevski B, Bitran D. Coronary artery bypass surgery during pregnancy. Eur J Cardiothorac Surg 1996; 10: 925–926. 3. Cowan N C, de Belder M A, Rothman M T. Coronary angioplasty in pregnancy. Br Heart J 1988; 59: 588–592. 4. Shalev A, Ben-Hur H, Hagay Z, et al. Successful delivery following myocardial ischemia during the second trimester of pregnancy. Clin Cardiol 1993; 16: 754–756. 5. Sheikh A U, Harper M A. Myocardial infarction during pregnancy:management and outcome of two pregnancies. Am J Obstet Gynecol 1993; 169: 279–284. 6. Hameed A B, Tummala P P, Goodwin T M, et al. Unstable angina during pregnancy in two patients with premature coronary atherosclerosis and aortic stenosis in association with familial hypercholesterolemia. Am J Obstet Gynecol 2000; 182: 1152–1155. 7. Crombie I K, Kenicer M B, Smith W C, Tunstall-Pedoe H D. Unemployment, socioenvironmental factors and coronary heart disease in Scotland. Br Heart J 1989; 61: 172–177. 8. Cannan C R. Antithrombotic therapy in cardiac stent patients. Curr Cardiol Rep 2001; 3: 78–84. 9. Thompson C A. First drug-eluting coronary stent approved. Am J Health Syst Pharm 2003; 60: 1210–1212. 10. Instructions for use:CYPHER Sirolimus-eluting coronary stent on RAPTOR Over-the-Wire Delivery System. Johnson and Johnson (UK), Cordis Corporation April 2003. 11. Kolansky D M, Klugherz B D, Curran S C, et al. Combination therapy with clopidogrel and aspirin after coronary stenting. Catheter Cardiovasc Interv 2000; 50: 276–279. 12. Mehta S R, Yusuf S, Peters R J, et al. CURE Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527–533. 13. Steinhubl S R, Berger P B, Mann J T, et al. CREDO Investigators. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2003; 289: 987. 14. Regar E, Serruys P W, Bode C, et al. Angiographic findings of the multicenter randomized study with the Sirolimus-Eluting Bx Velocity Balloon-Expandable stent (RAVEL): sirolimus-eluting stents inhibit restenosis irrespective of the vessel size. Circulation 2002; 106: 1949–1956.
15. Horlocker T T, Wedel D J, Schroeder D R, et al. Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg 1995; 80: 303–309. 16. Horlocker T T. Low molecular weight heparin and neuraxial anesthesia. Thromb Res 2001; 101: 141–154. 17. Horlocker T T, Wedel D J, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA consensus conference on neuraxial anesthesia and anticoagulation). Reg Anesth Pain Med 2003; 28: 172–197. 18. Payne D A, Hayes P D, Jones C L, Belham P, Naylor A R, Goodall A H. Combined therapy with clopidogrel and aspirin significantly increases the bleeding time through synergistic antiplatelet action. J Vasc Surg 2002; 35: 1204–1209. 19. Nikhil J Y, Radhakrishnan S, Paradiso-Hardy F L, Cohen E A. Clopidogrel in interventional cardiology: questions answered and questions remaining. Can J Cardiol 2002; 18: 739–748. 20. Yende S, Wunderink R G. Effect of clopidogrel on bleeding after coronary artery bypass surgery. Crit Care Med 2001; 29: 2271–2275. 21. Faccenda K A, Finucane B T. Complications of regional anaesthesia Incidence and prevention. Drug Saf 2001; 24: 413–442. 22. May L G. Effect of high spinal anesthesia on the cardiac output of normal and hypertensive patients. Am J Med 1949; 7: 251–252. 23. Graber E A. When an obstetric patient has coronary disease. Contemp Ob/Gyn 1989; 34: 56–62. 24. Lees M M, Scott D B, Kerr M G. Haemodynamic changes associated with labour. J Obstet Gynaecol Br Commonw 1970; 77: 29–36. 25. Volmanen P, Akural E I, Raudaskoski T, Alahuhta S. Remifentanil in obstetric analgesia:a dose finding study. Anesth Analg 2002; 94: 913–917. 26. Samama C M, Bastien O, et al. Antiplatelet agents in the perioperative period: expert recommendations of the French Society of Anesthesiology and Intensive Care (SFAR) 2001 – summary statement. Can J Anaesth 2002; 49: S26–S35. 27. Marcucci C, Chassot P G, Gardaz J P, et al. Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative coronary stenting. Br J Anaesth 2004; 92: 743–747. 28. Department of Health. Report on Confidential Enquiries into Maternal Deaths in the UK 1997–1999. London: RCOG, 2001.
CASE REPORT
Anaesthetic considerations in a parturient with critical coronary artery disease and a drug-eluting stent presenting for caesarean section J. A. Cuthill, S. Young, I. A. Greer, K. Oldroyd Department of Anaesthesia, Princess Royal Maternity Hospital, Department of Obstetrics & Gynaecology, University of Glasgow, and Department of Cardiology, Western Infirmary, Glasgow, UK SUMMARY. A parturient presented with her first symptoms of coronary artery disease at 18 weeks’ gestation. Following an angiogram, a drug-eluting stent was inserted, resulting in resolution of her symptoms. The patient was prescribed anti-platelet medication including clopidogrel. She was delivered by elective caesarean section at 35 weeks under general anaesthesia. The anaesthetic management is discussed and a review of the literature presented. 2004 Elsevier Ltd. All rights reserved. Keywords: Coronary stent; Drug-eluting; Coronary heart disease in pregnancy; Clopidogrel
pregnancies. There was no family history of coronary heart disease. She was taking no medication. Examination was unremarkable apart from a benign-sounding flow murmur at the left sternal edge. Her electrocardiogram (ECG) showed isolated T-wave inversion in lead aVL. She had good left ventricular systolic function on echocardiography with no ventricular hypertrophy and normal valves. A Bruce protocol exercise test was terminated after 4 min 8 s due to chest pain and widespread ischaemic ST-T wave changes. She was prescribed aspirin 75 mg daily, atenolol 25 mg daily and glyceryl trinitrate spray as required and referred both to the obstetric medicine clinic at the Princess Royal Maternity Hospital and to a cardiologist. Following discussion between the cardiologist and obstetricians, she underwent coronary angiography at 26 weeks. This showed severe ostial left main stem stenosis with moderate disease in the left anterior descending artery, its diagonal branches and the proximal segment of the left circumflex artery. The right coronary artery was also noted to have mild luminal irregularity. Four days later she was reviewed at the obstetric medicine clinic. She reported that her symptoms had worsened following angiography. At this point clopidogrel 75 mg daily and enoxaparin 40 mg daily were prescribed. The cardiothoracic surgeons did not consider her a candidate for coronary bypass surgery at this stage in her pregnancy and a decision was made to proceed to percutaneous coronary intervention. She remained on
INTRODUCTION Although uncommon in pregnancy, ischaemic heart disease can present the obstetric anaesthetist with major challenges. Recent advances in cardiological management further influence the decision-making process. The following case report illustrates some of these difficulties and reviews the current relevant literature.
CASE REPORT A 38-year-old woman, para 4 + 0, was referred to the chest pain clinic by her general practitioner at 18 weeks’ gestation complaining of a five-month history of chest discomfort, mainly on exertion. She smoked 20 cigarettes a day and had a past history of hypertension, which had worsened following each of her four previous Accepted October 2004 J.A. Cuthill, Senior House Officer in Anaesthesia; S. Young, Consultant Anaesthetist, Princess Royal Maternity Hospital, 16 Alexandra Parade, Glasgow, G31 2ER; I.A. Greer, Regius Professor of Obstetrics and Gynaecology, Wolfson Medical School Building, University of Glasgow, Glasgow G12 8QQ; K. Oldroyd, Consultant Cardiologist, Western Infirmary, Dumbarton Road, Glasgow, G12, UK. Correspondence to: S. Young, Consultant Anaesthetist, Department of Anaesthetics, Princess Royal Maternity Hospital, 16 Alexandra Parade, Glasgow G31 2ER. Tel.: +0141 211 4620. E-mail: [email protected]. 167
168 International Journal of Obstetric Anesthesia aspirin 75 mg, but labetalol 100 mg twice daily was substituted for atenolol on the advice of the obstetricians. At 28 weeks a 3 · 8 mm sirolimus eluting stent (Cyphere; Cordis, Johnson and Johnson) was inserted into the left main coronary artery. Further angiographic views confirmed the presence of moderately severe disease distal to the stent, in the mid-segment of the left anterior descending artery, a diagonal branch and the proximal segment of the left circumflex artery. It was considered, however, that no further revascularisation was required at this point. She was discharged on clopidogrel 75 mg and aspirin 75 mg daily as is standard cardiological practice, and additionally on labetalol 100 mg twice daily and enoxaparin 40 mg daily, to compensate for the relative hypercoagulable state of pregnancy as perceived by the obstetricians. At 35 weeks the patient was delivered by elective caesarean section. It was considered that in a patient who had residual widespread coronary atherosclerosis despite stent placement, caesarean section would be safer than spontaneous vaginal delivery from the standpoint of haemodynamics and myocardial oxygen delivery. It was also considered preferable to deliver her at 35 weeks in order to reduce any additional stress on the cardiovascular system in the last few weeks of pregnancy when there was relatively little potential gain for the fetus from continuing the pregnancy. In addition, although there is evidence to permit the use of neuraxial anaesthesia with both aspirin and low-molecular-weight heparin, there are few data regarding the risk of adding clopidogrel to this combination. The cardiologist considered it important that her anti-platelet medication was continued peri-operatively. Thus, her drug regime precluded regional anaesthesia due to the potential risk of spinal or epidural haematoma, and general anaesthesia was selected. She received enoxaparin 40 mg as a prophylactic dose on the evening before surgery and her aspirin and clopidogrel were withheld on the morning of surgery as she was fasting – the anti-platelet effect was not expected to be influenced by this short omission. Before induction of anaesthesia, large bore i.v. access and intra-arterial blood pressure monitoring were instituted and a glyceryl trinitrate patch applied. She required esmolol 10 mg to control transient hypertension of 180/95 mm Hg just before induction. Following preoxygenation for 3 min, we carried out a rapid sequence induction with left lateral tilt and cricoid pressure using etomidate 20 mg, suxamethonium 100 mg and a remifentanil infusion (initially 0.6 lgÆkg 1min 1). The pressor response to intubation was obtunded by lidocaine 1 mg/kg and alfentanil 1.5 mg. Induction was uncomplicated apart from a transient self-limiting bradycardia occurring during intubation. The lowest oxygen saturation was 95%. A right internal jugular central venous
line was inserted after induction to guide fluid replacement, as there was the potential for a larger blood loss than usual. Anaesthesia was maintained with isoflurane in oxygen and air. Remifentanil was infused at a rate of 0.2–0.3 lgÆkg 1min 1 to maintain the pulse rate around 75 to 80 beats/min. The caesarean section was uncomplicated surgically, a baby boy weighing 2.03 kg with Apgar scores of 5 at 1 min and 8 at 5 min was delivered 13 min after induction of anaesthesia. Remifentanil was continued after delivery, although she also received i.v. morphine boluses to a total of 17 mg during the remainder of the procedure. She remained haemodynamically stable intraoperatively, with a pulse rate of 70–85 beats/min, systolic pressure 110–150 mmHg and diastolic pressure 70–80 mm Hg. There were no ischaemic changes on ECG. To avoid any precipitous drop in blood pressure, an i.v. bolus dose of oxytocin was withheld and she received 20 units as an infusion in Hartmann’s solution 500 mL over one hour. The uterus was well contracted at the conclusion of surgery. Blood loss was estimated at 500 mL and 2500 mL crystalloid was infused perioperatively. Haemodynamic responses to extubation were obtunded by fentanyl and esmolol boluses. She was returned to the high dependency unit with a morphine patientcontrolled analgesia pump and was prescribed regular paracetamol. Non-steroidal anti-inflammatory drugs were withheld due to the increased risk of bleeding. Full invasive monitoring was continued postoperatively. In the first 2 h she required several i.v. boluses of labetalol 5–10 mg for hypertension. Four hours postoperatively she became oliguric and her blood pressure fell to 100/60 mm Hg. There was no obvious source of blood loss. Repeat full blood count showed a fall in haemoglobin from 11.3 g/dL pre-operatively to 6.3 g/dL. Coagulation remained normal. An ultrasound showed evidence of intra-abdominal clot with fluid in the paracolic gutter. She was transfused a total of four units of packed red cells which increased her haemoglobin to 9.0 g/dL and resolved her oliguria. She remained well for the next three days with no further bleeding or drop in haemoglobin and no anginal symptoms. Postoperative troponin levels were <0.2 lg/L and she had no new ECG changes. Six months post partum she has had no recurrence of her angina and a repeat Bruce protocol exercise test was negative at high workload. Accordingly no further coronary angiography or revascularisation is planned.
DISCUSSION Coronary artery disease in pregnancy has been uncommon in UK practice and there are few published case
Anaesthesia in coronary artery disease with a drug-eluting stent 169 reports.1–4 The prevalence of all cardiac lesions in women of reproductive age is estimated at 0.4% to 4.5%, while the incidence of myocardial infarction in pregnancy is estimated as 0.01%.5 The increased cardiovascular demands of pregnancy are well known and can worsen myocardial ischaemia in at-risk patients by altering the balance between myocardial oxygen supply and demand. A rise in blood volume, cardiac output and heart rate increases myocardial workload and oxygen consumption. In addition, myocardial oxygen supply may be reduced by the physiological anaemia of pregnancy and the lower diastolic pressure resulting from decreased systemic vascular resistance.6 The West of Scotland has one of the highest rates of coronary heart disease in the World, particularly in women7 and it is not unusual for patients to present with severe disease in their thirties. Pregnancy may be the final contributing factor that leads to symptoms in young women with prior asymptomatic disease. The development of coronary stenting coupled with improvements in adjunctive anti-platelet therapy has led to an increasing use of percutaneous intervention in the treatment of coronary artery disease.8 As far as we are aware, there is no published material on the use of coronary stents during pregnancy, although there is some experience of angioplasty.3 The sirolimus eluting stent used in this patient is the first drug-eluting coronary stent to be approved for clinical use, having received its CE (European Conformity) mark in April 2002 with FDA approval following in April 2003.9 It is coated with a formulation of sirolimus, a macrocytic lactone produced by Streptomyces hygroscopicus. Sirolimus is an immunosuppressant which inhibits both the activation of T lymphocytes and the proliferation of vascular smooth muscle and endothelial cells. It has been shown to decrease the rate of restenosis when compared to conventional bare metal stents,10 but there are no data on its use in pregnancy. Various trials have shown that the use of dual antiplatelet therapy, most commonly aspirin and clopidogrel, reduces the risk of subacute thrombosis following coronary stent implantation.11,12 In addition, continuing this therapy for up to one year after stenting has been shown to give a 26.9% relative reduction in the combined risk of death, myocardial infarction or stroke when compared to short-term therapy.13 All previous studies looking specifically at the Cyphere stent have used aspirin and clopidogrel in various dose regimes before and after stent placement.10,14 Discontinuation of clopidogrel is associated with a significant rate of stent thrombosis. 12 The fact that our patient was taking aspirin, clopidogrel and prophylactic enoxaparin decreased our options for anaesthetic management of this case. A rare complication of regional anaesthesia is epidural haematoma,
the consequences of which can be disastrous. Aspirin therapy does not increase this risk15 and most anaesthetists would probably still be willing to perform regional block in those patients taking aspirin. There are clear guidelines regarding the use of low-molecular-weight heparin in conjunction with central neuraxial block. These state that epidural anaesthesia is safest when performed 12 h after a prophylactic dose of low-molecularweight heparin.16,17 The estimated risk of haematoma following epidural block is 1:70 000 when heparin prophylaxis is prescribed. This increases to 1:8500 with the addition of aspirin.17 The addition of clopidogrel to aspirin, however, significantly increases the bleeding time.18 It has been shown that, in patients undergoing coronary bypass surgery while taking clopidogrel, there is an increase in the number of haemorrhagic complications with a greater need for surgical re-exploration, transfusion of packed red cells and the use of cryoprecipitate.19,20 No series has been performed to evaluate the risk of clopidogrel and neuraxial block and the safety of concurrent clopidogrel and aspirin has not been established. There have certainly been three reports of epidural haematoma attributed to clopidogrel and two cases of severe bleeding following lumbar sympathetic block.17 We felt that the risk of combining aspirin and clopidogrel with low-molecular-weight heparin was significant and in our view, regional anaesthesia was contraindicated. In addition, the cardiovascular responses to regional anaesthesia include hypotension secondary to sympathetic blockade, which is often more profound in hypertensive patients such as ours.21 It has been shown that a decline in blood pressure of greater than 30% is usually associated with a fall in cardiac output22 and this, combined with either bradycardia or reflex tachycardia – frequent occurrences, especially during spinal anaesthesia – results in major circulatory changes that could be life threatening in a patient with critical coronary artery disease. Our options were therefore spontaneous delivery with opioid analgesia if required or caesarean section under general anaesthesia. There is no general consensus as to the mode of delivery appropriate for patients with ischaemic heart disease. A previous case report of two pregnancies following myocardial infarction stated that the mode of delivery should be based solely on obstetric indications, allowing the mother to progress to spontaneous labour and deliver with no need for invasive haemodynamic monitoring, provided ventricular function was intact.5 Labour results in further increases in heart rate, cardiac output and systemic vascular resistance over and above those of pregnancy23 with an increase in central venous pressure and pre-load during contractions.24 These changes increase the myocardial oxygen demand
170 International Journal of Obstetric Anesthesia and may precipitate cardiac failure in some patients with poor ventricular function. Anxiety and pain, which may be difficult to control fully without epidural analgesia, act to increase cardiac work further due to catecholamine release. Our patient was known to have relatively widespread coronary artery disease distal to the stent placement. Had this not been the case, it could have been safer to allow her to progress to spontaneous labour with i.v. opioid analgesia if required. This would have almost completely removed the significant risk of general anaesthesia in pregnancy and of spinal or epidural haematoma resulting from neuraxial blockade. The patient had had four previous uncomplicated pregnancies and the risk of complications requiring operative or instrumental intervention was thought to be low. Despite this, it was felt that the benefits of a well prepared elective general anaesthetic carried out within normal office hours outweighed the physiological strain that would be placed on our patient if allowed to deliver spontaneously, particularly in the second stage of labour, and the small but significant risk of needing emergency intervention, possibly overnight and initiated by the most junior of the anaesthetic team. The aim of our general anaesthetic plan was to provide a stable blood pressure at all times and to avoid tachycardia, which would decrease myocardial oxygen supply. As far as possible, we attempted to provide this by using boluses of esmolol, alfentanil or lidocaine to obtund any pressor response. This proved successful. In caesarean sections under general anaesthesia, normal practice is to withhold opioid analgesia and use low minimal alveolar concentrations of volatile anaesthetic until after delivery of the baby to avoid the problems of neonatal sedation and respiratory depression. In our patient, this would probably have caused tachycardia and hypertension, both of which would have been detrimental to coronary oxygenation. Remifentanil was used as an infusion as it is quickly and easily titratable to both pain and cardiovascular parameters and has been shown to cause minimal neonatal depression.25 This case also highlights the potential problem of excessive bleeding in patients taking anti-platelet medication. Our patient suffered a serious and relatively hidden postoperative bleed with a drop in haemoglobin of around 5 g/dL. A recent paper states that aspirin and non-steroidal anti-inflammatory drugs moderately increase intra- and postoperative bleeding, but not transfusion requirements.26 Fewer data are available regarding clopidogrel.17–19 Whether we could have done anything other than maintain a high degree of suspicion in this case is debatable. The main issues of perioperative bleeding and neuraxial anaesthesia in this particular patient seem to relate to clopidogrel rather than aspirin and low-molecular-
weight heparin. Due to the widespread use of the latter two, experience has been gained and guidelines are in place for perioperative management. Both the above problems could have been solved by withdrawing some anti-platelet therapy at least one week before surgery. There is as yet no official guidance from the cardiologists regarding the management of patients who have stents in situ and present for non-cardiac surgery. Certainly, the risk of perioperative bleeding is high if medication is continued, but discontinuing medication can increases the risk of stent thrombosis. Both the CREDO13 and CURE12 trials have shown the significant benefit of continuing long-term clopidogrel with aspirin following stenting. A further case report published last year discussed a patient who presented for thoracic surgery six weeks after stenting of his left anterior descending and circumflex artery. Clopidogrel was stopped two weeks before surgery to allow epidural placement and he suffered a postoperative myocardial infarction due to total stent occlusion, which led to cardiogenic shock and death.27 In summary, providing safe obstetric anaesthesia for patients with severe coronary heart disease is challenging and there is still no general consensus as to the best way to manage these patients due to the relatively small number who present. The rapid increase in newer and more effective anti-thrombotic agents has allowed advances in percutaneous coronary intervention in the last few years, which has decreased the need for coronary artery bypass grafting, a procedure that would certainly carry a high risk in pregnancy, although it has been carried out successfully before.2 These techniques have produced problems of their own, namely the increased rate of surgical and post-surgical bleeding that occurs in those on anti-thrombotic medication. Specifically in obstetrics, it is not ideal to be precluded from using regional techniques that have dramatically decreased maternal mortality associated with anaesthesia.28 However, it remains uncertain whether a parturient with coronary artery disease is more stable and at less risk of complications from a spontaneous labour, regional anaesthesia or general anaesthesia, all of which cause significant and sometimes very rapid changes to maternal cardiovascular physiology. As percutaneous coronary intervention becomes more widespread, these patients are likely to present to obstetric anaesthetists with increasing frequency, resulting in further controversy about their management.
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