Marfan syndrome (MFS) is a rare autosomal dominant connective tissue disorder with an incidence of 0.02–0.03%. Aortic dissection is a common complication and is the cause of death for 90% of MFS patients. Pregnancy is associated with an increased risk of aortic dissection caused by hemodynamic and hormonal changes [1]. In addition, 63–92% of MFS patients have dural ectasia (DE). DE involves widening of the dural sac or spinal nerve root sleeves with increased cerebrospinal fluid volume, which is associated with an increased risk of accidental dural puncture and inadequate anesthesia during neuraxial anesthesia [2]. Perioperative management is multidisciplinary and challenging.

MFS is often unexpectedly diagnosed during pregnancy. Anesthesiologists not only focus on their own major but are also familiar with the overall algorithms. Current guidelines focus on the management of MFS patients with aortic diseases during pregnancy and rarely focus on perioperative management [1, 3], especially from the anesthesiologist’s perspective, including cardiac and obstetric anesthesia. Therefore, we propose an algorithm for the perioperative management of MFS pregnant women according to the experience of our center and the literatures (Fig. 1). A case of a patient with successful management is attached (Annex 1).

Fig. 1
figure 1

Algorithm for the perioperative management of Marfan syndrome during pregnancy

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1 Preoperative counseling and evaluation

According to the latest guidelines from the 2018 European Society of Cardiology and the 2022 American College of Cardiology/American Heart Association [1, 3], multidisciplinary management is recommended once MFS is diagnosed. Pregnant women should be informed about potential pregnancy-related complications, prenatal diagnosis, and genetic risk for offspring to choose abortion or continuing pregnancy. Anesthesia is an important part of multidisciplinary management, and anesthesia counseling and evaluation is essential for facilitating informed choices, which should be throughout pregnancy. The focus should be on cardiac and obstetric anesthesia during pregnancy.

For pregnant women who were evaluated before the third trimester (< 28 weeks), those with an aortic root diameter (ARD) ≥ 45 mm or between 40 and 45 mm with progressive aortic dilation (growth ≥ 0.3 cm/year) or a family history of aortic dissection are at high risk of aortic dissection, and prophylactic aortic surgery during pregnancy should be considered [3]. The second trimester (14–27 weeks) is the optimum time for surgery. The outcome of pregnant women during cardiopulmonary bypass (CPB) is the same as that of nonpregnant women, with a mortality rate ranging from 3 to 15%; however, there is a potential adverse effect on fetal outcomes, with a mortality rate ranging from 20 to 33% [4]. One of the most important influencing factors is CPB. CPB has adverse effects on uteroplacental blood flow, and fetuses may be affected by the activation of inflammation, hypotension, hypothermia and nonpulsatile perfusion (NP). Dysfunction of fetal vascular endothelial function and an increase in catecholamine levels also occur, which causes fetal vessel contraction and fetal acidosis. Therefore, perioperative hemodynamic optimization, favorable CPB and fetal monitoring can improve fetal outcomes [5]. Importantly, the mother must be prioritized when there is an irreconcilable contradiction between maternal and fetal safety, which needs to be supported by the pregnant woman and her family. Moreover, there is no clear evidence of fetal teratogenicity associated with common general anesthesia drugs, which can reduce her psychological burden. For pregnant women who were evaluated after the third trimester (≥ 28 weeks), cesarean section (CS) should be considered before cardiac surgery if aortic surgery is needed. The greatest risk is postpartum hemorrhage, and two-stage surgery is recommended for asymptomatic pregnant women to reduce the risk of bleeding. One-stage surgery should be chosen when acute aortic dissection occurs. Patients without indications for surgery should be closely follow-up under transthoracic echocardiography (TTE) surveillance.

Standard preoperative evaluation, including a detailed history, physical exam, laboratory tests, electrocardiogram, TTE and functional status should be performed. It is necessary to evaluate the key points of routine non-obstetric surgery during pregnancy, including difficult intubation, aspiration, and the well-being of the fetus. Importantly, we should focus on functional status because MFS often involves the aortic and mitral regurgitation. The functional status is often described using the New York Heart Association Functional Classification. Pregnant women have strong cardiac compensatory capacity and tolerance to regurgitant valvular disease. The symptoms of heart failure appear, this indicates that the disease is serious; it may be challenging to differentiate between the normal signs and symptoms of pregnancy and those that result from the progression of the patient's underlying heart disease. Therefore, we should focus on objective cardiac index and TTE evaluation of reflux severity, left ventricular size and function. An N-terminal pro-B-type natriuretic peptide concentration > 128 pg/mL at 20 weeks’ gestation is predictive of events later in pregnancy [1]. Physical examination and magnetic resonance imaging should be performed to evaluate the presence of DE if possible.

2 The perioperative management of aortic surgery

The greatest difference in cardiac surgery between pregnant and nonpregnant patients is that CPB and fetal heart rate (FHR) monitoring need to be optimized during pregnancy. The strategies include maintaining normothermia or mild hypothermia (> 32 °C if possible), a high pump flow rate (2.5–6 L/min/m2), a high perfusion pressure (mean blood pressure > 70 mmHg), a stable hematocrit (> 28%), short CPB (< 120 min if possible) and aortic cross-clamping times, avoidance of circulatory arrest and personalized FHR monitoring [5].

Some also recommend pulsating perfusion (PP), although the debate over the superiority of either NP or PP during CPB remains controversial. PP is more natural than NP because it mimics physiological blood flow and improves microcirculation and tissue oxygen saturation; however, its clinical use is limited since there are no standard criteria for what constitutes and how to quantify it. NP triggers an abnormal foeto-placental response accompanied by increased placental vascular resistance and dysfunction, while PP has advantages in maintaining foeto-placental blood flow and preventing fetal acidosis. PP may reduce uterine contractions by releasing endothelial-derived growth factors, decreasing the activation of the fetal renin-angiotensin system, and decreasing the dilution of progesterone [6]. Moreover, the PP is noninferior to the NP based on the current evidence, especially in high-risk patients [7]. Therefore, PP is worth trying and recommending, especially in cardiac centers experienced in CPB. The heparin target during CPB remains empirical. The coagulation time should be maintained above 480 s, and pregnant women are in a hypercoagulable state and need to be tested regularly (every 30 min).

Doppler transducers are available for monitoring the abdominal wall, but it is difficult to fix the probe during surgery, and fetal echocardiography can reveal fetal cardiac reactions and FHR changes. We recommend maintaining an FHR ≥ 110 bpm. Importantly, fetal bradycardia occurs during CPB. Fetal bradycardia can resolve with the removal of the aortic cross-clamp, increased perfusion, increased temperature, etc. [8]. If not fully recognized, inappropriate clinical decisions may be made. The risk of intrauterine hypoxia and death is considered if a low FHR (< 70 bpm) persists, and there is little benefit from urgent CS unless the gestational week is close to 28 weeks.

CS followed by aortic surgery should be performed after the third trimester (≥ 28 weeks). The greatest risk of one-stage surgery is postpartum hemorrhage, which is suitable for patients with acute aortic dissection. Early surgery involves hysterectomy to prevent bleeding, while balloon compression or artery embolization is used to preserve fertility; these procedures are also important for anesthesiologists. Two-stage surgery significantly reduces the risk of bleeding.

3 Postoperative management

Postoperative monitoring is necessary along with FHR and uterine contraction monitoring, which may assist in maternal positioning and cardiorespiratory management and influence the decision to deliver the fetus. We recommend that obstetricians make a monitoring plan based on the surgical approach, gestational age, and available resources for cesarean delivery. Continued close follow-up for at least 12 weeks postpartum is of extreme importance given the continued risk of developing cardiac and obstetric complications, the frequency depends on the aortic diameter, aortic growth rate, and underlying condition. Furthermore, postoperative analgesia can reduce the risk of premature labor. Opioids and paracetamol are the most common treatment regimens. Neuraxial analgesia is not recommended because of spinal-epidural hematoma (SEH), and nonsteroidal anti-inflammatory drugs are not used routinely because of potential fetal effects.

The antithrombotic regimen involved anticoagulation therapy, antiplatelet therapy, or combination therapy after cardiac surgery. Mechanical valve replacement requires lifelong anticoagulation, while biological valves or valvuloplasty require only short-term anticoagulants (3–6 months) followed by antiplatelet drugs. Among the antiplatelet agents, aspirin is still the first-line treatment. The anticoagulant agents commonly used include low-molecular-weight heparin, heparin, and warfarin. The timing of anesthesia and antithrombotic administration should be coordinated to optimize the safety of both agents [9].

4 Delivery and anesthesia

Delivery is the high-risk stage for adverse cardiac events; the anesthetic goal is sufficient analgesia to avoid sympathetic stimulation. Anesthesiologists pay attention to the following issues: delivery mode, monitoring method, and anesthesia selection.

For women with an ARD ≥ 45 mm or a history of aortic surgery, CS is preferred; for women with an ARD between 40 and 45 mm, CS is still preferred, and vaginal delivery (VD) can also be attempted with epidural anesthesia (EA) and an expedited second stage. For women with an ARD < 40 mm, VD can be chosen. Standard noninvasive monitoring is required during delivery, and invasive arterial monitoring is recommended for patients at high risk of aortic dissection [1].

Although DE is not a contraindication for neuraxial procedures, the risk of accidental dural puncture and inadequate anesthesia is greater. However, there are only case reports on anesthesia management, including general and neuraxial anesthesia, in pregnant women with MFS complicated with DE. Neuraxial anesthesia involved spinal anesthesia (SA), EA, or combined spinal-epidural anesthesia. SA is not limited by inadequate anesthesia, but its incidence is still high [10]. Theoretically, DE may lead to a reduction in the epidural space, and accidental dural puncture can easily occur during EA; however, Weinstein reported that anesthetic complications due to DE were not encountered during neuraxial anesthesia, outweighing the potential risk of accidental dural puncture in MFS patients [2]. The most likely reason is that DE commonly occurs in the lumbosacral region, where the puncture interspace is greater than that in the DE location. Therefore, we chose neuraxial anesthesia as the first choice because it may cause accidental dural puncture and inadequate anesthesia during neuraxial anesthesia.

In summary, multidisciplinary management is recommended for perioperative management. Anesthesia is a key part of multidisciplinary management. It is critical that the practice of anesthesia not only provides safe analgesia and anesthesia but also involves team-based coordinated care.