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High-Dose Desflurane for Tocolysis During Intrapartum Myelomeningocele Repair in a Patient With Post-Adriamycin Cardiomyopathy

Ho, Jonathan T. MD, MA; Feldman, Jeffrey M. MD, MSE

doi: 10.1213/XAA.0000000000000341
Case Reports: Case Report
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High-dose desflurane is an uncommon need during general anesthesia. At our institution, open fetal surgery cases are managed with high desflurane concentrations to ensure uterine relaxation. We present a case of a 32-year-old parturient with a history of mild cardiomyopathy undergoing open fetal myelomeningocele repair. Phenylephrine and dopamine infusions helped maintain hemodynamic stability at 18% desflurane, while cardiac function was monitored with transthoracic echocardiography. This case is notable for the unknown risk of using high-dose desflurane with a preexisting cardiomyopathy and raises the question of the acceptable maternal risk in the setting of fetal surgery.

From the Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania.

Accepted for publication February 25, 2016.

Funding: None.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Address correspondence to Jonathan T. Ho, MD, MA, Johns Hopkins University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Bloomberg Children’s Center, 1800 Orleans St., Suite 6349-B, Baltimore, MD 21287. Address e-mail to jho29@jhmi.edu.

High-dose desflurane is an uncommon need during general anesthesia, except in the setting of open fetal surgery. At our institution, open fetal surgery cases are managed with desflurane at concentrations up to 18% to ensure uterine relaxation. This case highlights several issues: (1) the unknown risk of using high-dose desflurane on a parturient with a preexisting cardiomyopathy (CM); (2) the use of intraoperative maternal transthoracic echocardiography (TTE) monitoring during open fetal surgery; and (3) the question of acceptable maternal risk in the setting of fetal surgery. Written informed consent was obtained from the patient for publication of this case report.

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CASE DESCRIPTION

We present a case of a 32-year-old G4P3003 parturient at 23 weeks’ gestation with a history of mild CM who presented for open fetal myelomeningocele repair. Her medical history was significant for non-Hodgkin’s lymphoma 10 years earlier treated with field radiation therapy and chemotherapy including Adriamycin (Bedford Laboratories, Bedford, OH). She also had a remote history of depression but was otherwise healthy. Her surgical history included a port placement and removal without complications. Review of systems and physical examination were both unremarkable. When questioned about exercise tolerance, she described herself as an active runner with 3 children.

She admitted to prior tobacco and marijuana use and denied any heavy alcohol or other illicit drug use. There were no known drug allergies, and her only medications were prenatal vitamins.

A preoperative TTE was performed by a consulting cardiologist 3 days before surgery to identify any underlying CM. The left ventricle (LV) was found to be of normal size and thickness with a borderline normal ejection fraction of 51.8% (normal ≥54%). Regional wall motion abnormalities were noted with mild hypokinesis of the basal inferoseptum and basal anteroseptum.

On the morning of surgery, an epidural was placed preoperatively for postsurgical pain control, and Bicitra was given for aspiration prophylaxis before induction. A cardiologist was not available to obtain a bedside TTE; however, preinduction parasternal short-axis (Supplemental Digital Content 1, Supplemental Video 1, http://links.lww.com/AACR/A69) and long-axis (Supplemental Digital Content 2, Supplemental Video 2, http://links.lww.com/AACR/A70) views were obtained by the attending anesthesiologist who had received training in TTE.

Upon arrival into the operating room, the parturient was positioned supine with left uterine displacement. A modified rapid sequence induction was performed using fentanyl, lidocaine, propofol, and vecuronium, and the patient’s trachea was intubated. Vascular access included two 18-gauge peripheral IV lines and a radial artery catheter. Lactated Ringer’s solution was used for intravascular volume replacement, and blood was available. Urine output was monitored using a Foley catheter.

Desflurane was increased after intubation to evaluate hemodynamic stability before the start of surgery. Arterial blood pressure support required a combination of dopamine and phenylephrine infusions to achieve a mean arterial blood pressure (MAP) between 70 and 80 mm Hg. Postinduction parasternal short-axis (Supplemental Digital Content 3, Supplemental Video 3, http://links.lww.com/AACR/A71) and long-axis (Supplemental Digital Content 4, Supplemental Video 4, http://links.lww.com/AACR/A72) TTE views were obtained by the anesthesiologist and indicated similar LV function when compared with the preinduction images. At a later time, the original consulting cardiologist read the intraoperative examinations to confirm the impression.

Fetal anesthetic management consisted of an IM injection of fentanyl and vecuronium (estimated fetal weight 477 g) and maintenance desflurane from the placenta. Continuous fetal echocardiography served as the primary monitor used to assess fetal hemodynamics.

After hysterotomy closure, magnesium sulfate was administered IV for postoperative tocolysis. Desflurane levels were reduced, and the dopamine and phenylephrine infusions were weaned without difficulty. Neuromuscular blockade was reversed, and the patient’s trachea was extubated without incident. For pain control, the epidural was bolused with lidocaine and bupivacaine before extubation and maintained on a continuous infusion with good effect.

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DISCUSSION

This case is notable for the unknown risk of using high-dose desflurane with a preexisting Adriamycin-induced CM and raises the question of the acceptable maternal risk in the setting of fetal surgery.

Adriamycin’s toxic effects are secondary to dilation of sacrotubules and loss of myofibrils, with chronic effects leading to irreversible changes in the myocardium and possible heart failure.1 Fatal toxic reactions affect 2% to 7% of those given the drug and follow an insidious onset most frequently occurring 1 to 6 weeks after the last dose. Clinical appearances range from nonspecific dry cough to signs and symptoms of biventricular heart failure. Usually, a degree of LV dysfunction persists for years.2

The 2014 American College of Cardiology/American Heart Association Guideline for preoperative cardiac evaluations for nonischemic CM focuses on a thorough understanding of the pathophysiology, assessment, and management of the underlying process.3 Symptomatic heart failure is a well-established perioperative cardiovascular risk factor, but the effect of asymptomatic LV dysfunction on perioperative risk is unknown. The 2011 appropriate use criteria state that a preoperative echocardiography is not necessary for patients without signs or symptoms of cardiovascular disease.4 However, given the potential for hemodynamic instability with the use of high-dose desflurane during fetal surgery and the noninvasive nature of TTE imaging, it was deemed a reasonable indication for pre- and perioperative cardiovascular assessment and monitoring.

There are no data to guide the risk assessment in this patient. In healthy volunteers, desflurane causes a dose-related reduction in MAP due to reduced systemic vascular resistance (SVR) and mild myocardial depression. Cardiac output is well maintained up to 1.66 minimum alveolar concentration (MAC) with myocardial depression possibly being because of decreased contractility and decreased ventricular compliance.5 However, an in vitro study of desflurane’s effects on isolated rat papillary muscle showed a moderate positive inotropic effect from intramyocardial catecholamine release, which could participate in sympathetic activation in vivo.6 Swine studies have demonstrated that cardiovascular collapse occurs at desflurane doses of 2.45 ± 0.11 MAC7 in the absence of hemodynamic support, whereas canine studies show that desflurane depresses myocardial contractility in a dose-dependent manner comparable with that of isoflurane at up to 1.5 MAC.8 No data were obtained in the setting of underlying CM.

The typical approach to tocolysis for fetal surgery in our institution is to administer desflurane up to 18% for uterine incision and reduce the dose after hysterotomy if the uterus remains relaxed. Desflurane is chosen because it is an effective tocolytic,9 blood pressure can be managed with a vasopressor infusion, and the low blood gas solubility fosters rapid elimination. Physiologically, there are some disadvantages. Desflurane increases the heart rate especially at higher doses, while it substantially decreases SVR.5 High-dose desflurane typically causes arterial hypotension requiring a vasopressor to maintain an adequate MAP. In the setting of Adriamycin-induced CM, arterial hypotension is an even greater risk because the myocardium may not be able to increase cardiac output sufficiently to compensate for the decrease in SVR. When comparing desflurane with isoflurane or sevoflurane, desflurane does the best job of maintaining the cardiac index.5 In this case, we chose phenylephrine to decrease the heart rate and maintain SVR (countering desflurane’s cardiovascular effects) and combined it with dopamine to enhance contractility. Dobutamine was also considered for its ability to enhance contractility but not chosen because of its effects on decreasing SVR. Desflurane, dopamine, and phenylephrine can all cross the placenta, and while high-dose desflurane is known to cause direct fetal cardiovascular depression,10 fetal hemodynamics were reassuring as monitored by continuous fetal echocardiography.

Uterine relaxation during fetal surgery is typically accomplished using a volatile anesthetic with or without nitroglycerin.11 A nitroglycerin infusion could have been used to achieve adequate tocolysis while limiting the dose of desflurane. The advantage of this alternate approach is not obvious, however, because the use of nitroglycerin is associated with an increased risk of maternal pulmonary edema12 and can also decrease blood pressure although the effects are primarily on the vasculature and not the myocardium.

Another option for tocolysis would be magnesium sulfate that has an excellent safety profile and is a familiar drug used routinely by obstetricians. Its use during the entire course of general anesthesia, however, can significantly prolong neuromuscular blockade, depress sympathetic tone, decrease peripheral vascular tone, inhibit catecholamine release, and it has the potential to decrease myocardial contractile force.13

The ability to obtain both short- and long-axis views of the heart by TTE helped to confirm that contractility and filling volume were adequate. Fluid administration is challenging in these cases because it is important to limit the volume administered, given the need for postoperative magnesium and the attendant risk of pulmonary edema. A 2004 study evaluated the feasibility of intraoperative monitoring using an abbreviated TTE protocol. The protocol provided usable images, which impacted management in 97% of patients.14 The attending anesthesiologist in this case was experienced in both pediatric and obstetric anesthesia and had been trained in the use of TTE. Studies indicate that training to use TTE effectively for patient assessment can be accomplished without the need for echocardiography certification.15 Institutional credentialing is desirable however, and methods for credentialing are being developed.16

Risk assessment for patients undergoing fetal surgery can be difficult because of limited experience and the questionable applicability of typical risk indices to this patient population. In this case, the fetus had a Chiari II malformation with a slight hindbrain herniation and large myelomeningocele likely to result in incontinence and weakness of the lower extremities. Lower lumbosacral defects have an 80% chance of requiring a ventriculoperitoneal shunt in the first 1 to 2 years of life. Evidence shows that fetal surgery will improve neuromotor function in the lower extremities, increase ambulation rates, and significantly decrease the need for ventriculoperitoneal shunting.17 Well-known fetal and maternal risks include premature rupture of the membranes, preterm labor and delivery, and a 15% to 20% risk of future pregnancies having scar dehiscence, uterine rupture, or implantation abnormalities.

Maternal-fetal surgery exposes the mother to risks without any direct physical benefit. During the development of human maternal-fetal surgery, maternal risks focused on 3 areas: operative risk of general anesthesia and open hysterotomy, risk of premature labor after open hysterotomy, and the risk of compromising future reproductive potential.18 A 2006 review of short-term maternal morbidity risks showed that open hysterotomy techniques were associated with a greater risk of developing pulmonary edema, required intensive care unit stay, blood transfusion, premature rupture of membranes, and chorion amnion membrane separation while questions about compromised maternal fertility cannot yet be answered.19

The ethical principles of beneficence (medical decisions that promote the best interests of the patient) and respect for autonomy (the patient’s freedom to choose alternatives based on values and beliefs) provide a framework for considering the moral obligations of fetal surgery.20 The fetus is incapable of having its own perspective while the mother and physicians have beneficence-based obligations to protect and promote the interest of the fetus. A conflict between the best care for the fetus and the need to avoid maternal injury can occur in that the mother is due beneficence-based obligations by the physicians. Decision making can be further complicated when maternal instincts may cause some mothers to take what the medical care team may deem as undue risks in an effort to try to enhance fetal outcome. As a nascent field, outcomes from fetal surgery are still uncertain, and therefore, medical and ethical decision making is challenging.

If this patient had a more pronounced CM with lower ejection fraction or limited exercise tolerance, maternal risks of complications such as cardiac failure, pulmonary edema, or prolonged hospitalization would not warrant fetal intervention. In this particular instance, the potential for substantial benefits to the fetus outweighed the risk of harm to the mother. Both the surgical and the anesthetic teams were comfortable with the ability to manage the maternal risks for this patient but also agreed that the operation would not proceed if the patient did not tolerate the initial high-dose desflurane before incision, in accord with the ethical principle of maternal beneficence.

In summary, we report a case of successful use of high-dose desflurane for tocolysis in a patient with a preexisting Adriamycin-induced CM. This information is intended to provide evidence of the safety of this technique in the setting of a CM and to demonstrate the value of intraoperative TTE to help monitor the patient. This report also highlights the question of acceptable maternal risk in the setting of fetal surgery. The parturient and her family were given extensive counseling throughout this process and have now undergone successful delivery of their baby by elective cesarean section with a spinal anesthetic at full term without any significant complications.

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