Anesthesia Considerations for Cesarean Delivery in a Patient with Loeys-Dietz Syndrome Jessica Cronin, MD, MBA, Heidi Bazick Cuschieri, MD, Xiaobo Dong, MD, Gretchen Oswald, MS, Melissa Russo, MD, Hal Dietz, MD, and Jamie Murphy, MD A 28-year-old primigravida female with Loeys-Dietz syndrome presented at 36 weeks’ gestation for scheduled primary elective cesarean delivery. The patient had clinical findings consistent with this diagnosis, including mild aortic root dilation, chronic right vertebral artery dissection with 2 intracerebral aneurysms, and small ectasias of the thecal sac in the lumbar region. Pregnant patients with Loeys-Dietz syndrome have significant risks, including aneurysm rupture, new aneurysm formation, and uterine rupture. After a thorough preoperative evaluation, the patient underwent successful general anesthesia focused on maintenance of intraoperative hemodynamic stability and minimal intraoperative blood loss. (A&A Case Reports. 2015;4:47–8.)
L
oeys-Dietz syndrome (LDS) is a rare autosomal dominant genetic syndrome affecting connective tissue. It has been associated with aortic dissection, cerebrovascular bleeding, and in pregnancy, catastrophic vascular and uterine rupture. Two previous case reports have addressed LDS in pregnancy. One case described the successful surgical replacement of the aortic valve and arch of a pregnant woman with type A aortic dissection and severe aortic regurgitation at 16 weeks, followed by an uneventful cesarean delivery.1 The second case described a woman with LDS who underwent cesarean delivery at 34 weeks’ gestation without complications.2 However, there is little discussion in the literature regarding the anesthetic implications of LDS in the parturient. The following case illustrates the multiple anesthetic considerations in the care of a pregnant patient with LDS and associated neurovascular comorbidities, including the risks and benefits of general versus neuraxial anesthesia in her management. Consent was obtained from the patient allowing publication.
CASE DESCRIPTION
A 28-year-old primigravida with LDS presented at 36 weeks’ gestation for scheduled primary elective cesarean delivery. The patient had a confirmed mutation in the TGFBR2 gene as well as clinical findings consistent with the diagnosis, including widely spaced eyes, joint hypermobility, translucent skin, aortic root dilation of 3.45 cm, and diffuse vascular tortuosity, including chronic right vertebral artery dissection and aneurysmal dilation of the right internal carotid and left superior cerebellar arteries. Her medical history was significant for a self-contained pulmonary From the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland. Accepted for publication August 5, 2014. Funding: No external or internal funding required. The authors declare no conflicts of interest. This report was previously presented, in part, at the ASA 2013. Address correspondence to Jessica Cronin, MD, MBA, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, 600 N. Wolfe St., Blalock 1415, Baltimore, MD 21287. Address e-mail to [email protected]. Copyright © 2015 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000114
February 15, 2015 • Volume 4 • Number 4
artery branch rupture in 2008 requiring no intervention. Her family history was notable for a maternal aunt who died as a complication of vascular dissection immediately after parturition and her mother who experienced sudden cardiac death after multiple dissections and surgeries for vascular aneurysm. Before becoming pregnant, she had been receiving propranolol, which was continued throughout gestation. The patient’s pregnancy progressed uneventfully, and her aortic root diameter remained unchanged. An interdisciplinary team including a genetic specialist, cardiac surgeon, cardiac anesthesiologist, obstetric anesthesiologist, and obstetricians decided that the patient would undergo elective cesarean delivery at 36 weeks’ gestation to mitigate the hemodynamic perturbations associated with term pregnancy, labor, and vaginal delivery. Because a prior magnetic resonance image of the lumbar spine had revealed ectasias of the thecal sac between the L5 and S2 levels, the decision was made after a lengthy discussion with the patient to proceed with general anesthesia because of concern that dural ectasia could complicate neuraxial anesthetic placement. In anticipation of potential hemodynamic instability and need for intravascular volume resuscitation, large-bore IV access and intraarterial monitoring were established before induction of anesthesia. General anesthesia was induced with remifentanil, propofol, and succinylcholine in an attempt to maintain hemodynamic stability. Video laryngoscopy using a Glidescope (Verathon, Bothell, WA) was performed to maximize vocal cord visualization while minimizing manipulation of the cervical spine. General anesthesia was maintained with a total IV anesthetic technique consisting of propofol and remifentanil to both blunt the sympathetic response to stimulation while avoiding anesthetic drugs associated with uterine relaxation. After delivery of the infant, uterine massage was performed and myometrial and intramuscular Hemabate (carboprost tromethamine) were administered to increase uterine tone. Hemodynamic stability was maintained intraoperatively without need for vasopressors or blood product transfusion. At the conclusion of surgery, labetalol and hydromorphone were administered to blunt hemodynamic responses to emergence and the trachea was extubated smoothly. After initial recovery in the postoperative care unit, the patient was transferred to the labor and delivery unit for cases-anesthesia-analgesia.org
47
telemetry and hemodynamic monitoring in addition to standard postpartum care. Her maintenance dose of propranolol was continued postpartum. Postoperative pain was well controlled with IV hydromorphone and oxycodone. A repeat echocardiogram performed on postoperative day 1 showed no significant change in the aortic root diameter. Her postpartum course was uneventful, and she was discharged home on postoperative day 5 without complications.
DISCUSSION
LDS is an autosomal dominant systemic disorder of connective tissue that is most commonly caused by heterozygous missense mutations in either of the genes (TGFBR1 or TGFBR2) that encode either subunit of the transforming growth factor-beta (TGFβ) receptor, leading to increased output of TGFβ-responsive gene products including types I and III collagen and connective tissue growth factor.3 The prevalence of LDS is unknown. Clinical manifestations of LDS vary greatly, and those of special interest for anesthesiologists include atrial septal defect, arterial/aortic aneurysms and dissections, cerebrovascular aneurysms, scoliosis, pectus deformity, and predisposition to cervical spine malformation. It may therefore be prudent to obtain antepartum, radiographic imaging of the brain and spine to assess for cervical instability, dural ectasia, scoliosis, or vascular malformations that might complicate anesthetic care. The median survival of patients with LDS is approximately 37 years, with death commonly occurring after thoracic aortic dissection, abdominal aortic dissection, and hemorrhagic stroke. Accordingly, experts have recommended early surgical intervention in the setting of a lower aortic root diameter threshold (4 cm) in patients with LDS as compared with other connective tissue disorders such as Marfan syndrome. Most patients receive medications including β blockers and/or angiotensin receptor blockers to reduce hemodynamic lability even in the absence of preexisting hypertension. The physiologic changes associated with pregnancy and the puerperium may pose additional risks to the patient with LDS. While some state that patients with LDS can tolerate pregnancy and delivery without any adverse effects, 1 study showed that of 21 pregnancies in patients with LDS, 6 had a major complication during pregnancy or immediately postpartum including uterine rupture in 2 patients and aortic dissection in 4 patients.4 Anomalous vascularity is common, increasing the risk of significant surgical bleeding, complications with vascular access, and inadvertent intravascular placement of an epidural catheter. Connective tissue laxity may be associated with an increased risk of premature rupture of membranes, uterine atony, and uterine rupture. Postpartum uterine involution can be facilitated by nonpharmacologic methods (e.g., fundal massage) and the avoidance
48 cases-anesthesia-analgesia.org
of inhaled anesthetics; it may be prudent to avoid uterotonic medications due to the increased risk of uterine rupture. Dural ectasias in the lumbosacral region are very common in this population,5 and while spinal and epidural anesthesia have been successfully performed,6 there is an increased likelihood of failed spinal anesthesia.7 There is also increased theoretic risk of inadvertent dural puncture8 because of increased hydrostatic pressure in the setting of weakened dura.8 Dural puncture may cause decreased intracranial pressure and subsequent risk of intracerebral aneurysmal bleeding.9,10 In the setting of a dural ectasia in the L5-S2 region, a reasonable alternative is for an experienced provider to place an epidural catheter above L4-5 with slow, controlled dosing with the patient in the lateral position. Though LDS is a rare disorder, the anesthesiologist should be alert to characteristic physical features common to patients with LDS and other connective tissue disorders because they may herald the presence of occult cardiovascular, neurologic, and musculoskeletal concerns. E REFERENCES 1. Kunishige H, Ishibashi Y, Kawasaki M, Yamakawa T, Morimoto K, Inoue N. Surgical treatment for acute type A aortic dissection during pregnancy (16 weeks) with Loeys-Dietz syndrome. Gen Thorac Cardiovasc Surg 2012;60:764–7 2. Gutman G, Baris HN, Hirsch R, Mandel D, Yaron Y, Lessing JB, Kuperminc MJ. Loeys-Dietz syndrome in pregnancy: a case description and report of a novel mutation. Fetal Diagn Ther 2009;26:35–7 3. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 2005;37:275–81 4. Van Hemelrijk C, Renard M, Loeys B. The Loeys-Dietz syndrome: an update for the clinician. Curr Opin Cardiol 2010;25:546–51 5. Rodrigues VJ, Elsayed S, Loeys BL, Dietz HC, Yousem DM. Neuroradiologic manifestations of Loeys-Dietz syndrome type 1. AJNR Am J Neuroradiol 2009;30:1614–9 6. Buser RT, Mordecai MM, Brull SJ. Combined spinal-epidural analgesia for labor in a patient with Marfan’s syndrome. Int J Obstet Anesth 2007;16:274–6 7. Lacassie HJ, Millar S, Leithe LG, Muir HA, Montaña R, Poblete A, Habib AS. Dural ectasia: a likely cause of inadequate spinal anaesthesia in two parturients with Marfan’s syndrome. Br J Anaesth 2005;94:500–4 8. Jones KB, Myers L, Judge DP, Kirby PA, Dietz HC, Sponseller PD. Toward an understanding of dural ectasia: a light microscopy study in a murine model of Marfan syndrome. Spine (Phila Pa 1976) 2005;30:291–3 9. Rocchi R, Lombardi C, Marradi I, Di Paolo M, Cerase A. Intracranial and intraspinal hemorrhage following spinal anesthesia. Neurol Sci 2009;30:393–6 10. Eggert SM, Eggers KA. Subarachnoid haemorrhage follow ing spinal anaesthesia in an obstetric patient. Br J Anaesth 2001;86:442–4
A & A case reports
L
oeys-Dietz syndrome (LDS) is a rare autosomal dominant genetic syndrome affecting connective tissue. It has been associated with aortic dissection, cerebrovascular bleeding, and in pregnancy, catastrophic vascular and uterine rupture. Two previous case reports have addressed LDS in pregnancy. One case described the successful surgical replacement of the aortic valve and arch of a pregnant woman with type A aortic dissection and severe aortic regurgitation at 16 weeks, followed by an uneventful cesarean delivery.1 The second case described a woman with LDS who underwent cesarean delivery at 34 weeks’ gestation without complications.2 However, there is little discussion in the literature regarding the anesthetic implications of LDS in the parturient. The following case illustrates the multiple anesthetic considerations in the care of a pregnant patient with LDS and associated neurovascular comorbidities, including the risks and benefits of general versus neuraxial anesthesia in her management. Consent was obtained from the patient allowing publication.
CASE DESCRIPTION
A 28-year-old primigravida with LDS presented at 36 weeks’ gestation for scheduled primary elective cesarean delivery. The patient had a confirmed mutation in the TGFBR2 gene as well as clinical findings consistent with the diagnosis, including widely spaced eyes, joint hypermobility, translucent skin, aortic root dilation of 3.45 cm, and diffuse vascular tortuosity, including chronic right vertebral artery dissection and aneurysmal dilation of the right internal carotid and left superior cerebellar arteries. Her medical history was significant for a self-contained pulmonary From the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, Baltimore, Maryland. Accepted for publication August 5, 2014. Funding: No external or internal funding required. The authors declare no conflicts of interest. This report was previously presented, in part, at the ASA 2013. Address correspondence to Jessica Cronin, MD, MBA, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Hospital, 600 N. Wolfe St., Blalock 1415, Baltimore, MD 21287. Address e-mail to [email protected]. Copyright © 2015 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000114
February 15, 2015 • Volume 4 • Number 4
artery branch rupture in 2008 requiring no intervention. Her family history was notable for a maternal aunt who died as a complication of vascular dissection immediately after parturition and her mother who experienced sudden cardiac death after multiple dissections and surgeries for vascular aneurysm. Before becoming pregnant, she had been receiving propranolol, which was continued throughout gestation. The patient’s pregnancy progressed uneventfully, and her aortic root diameter remained unchanged. An interdisciplinary team including a genetic specialist, cardiac surgeon, cardiac anesthesiologist, obstetric anesthesiologist, and obstetricians decided that the patient would undergo elective cesarean delivery at 36 weeks’ gestation to mitigate the hemodynamic perturbations associated with term pregnancy, labor, and vaginal delivery. Because a prior magnetic resonance image of the lumbar spine had revealed ectasias of the thecal sac between the L5 and S2 levels, the decision was made after a lengthy discussion with the patient to proceed with general anesthesia because of concern that dural ectasia could complicate neuraxial anesthetic placement. In anticipation of potential hemodynamic instability and need for intravascular volume resuscitation, large-bore IV access and intraarterial monitoring were established before induction of anesthesia. General anesthesia was induced with remifentanil, propofol, and succinylcholine in an attempt to maintain hemodynamic stability. Video laryngoscopy using a Glidescope (Verathon, Bothell, WA) was performed to maximize vocal cord visualization while minimizing manipulation of the cervical spine. General anesthesia was maintained with a total IV anesthetic technique consisting of propofol and remifentanil to both blunt the sympathetic response to stimulation while avoiding anesthetic drugs associated with uterine relaxation. After delivery of the infant, uterine massage was performed and myometrial and intramuscular Hemabate (carboprost tromethamine) were administered to increase uterine tone. Hemodynamic stability was maintained intraoperatively without need for vasopressors or blood product transfusion. At the conclusion of surgery, labetalol and hydromorphone were administered to blunt hemodynamic responses to emergence and the trachea was extubated smoothly. After initial recovery in the postoperative care unit, the patient was transferred to the labor and delivery unit for cases-anesthesia-analgesia.org
47
telemetry and hemodynamic monitoring in addition to standard postpartum care. Her maintenance dose of propranolol was continued postpartum. Postoperative pain was well controlled with IV hydromorphone and oxycodone. A repeat echocardiogram performed on postoperative day 1 showed no significant change in the aortic root diameter. Her postpartum course was uneventful, and she was discharged home on postoperative day 5 without complications.
DISCUSSION
LDS is an autosomal dominant systemic disorder of connective tissue that is most commonly caused by heterozygous missense mutations in either of the genes (TGFBR1 or TGFBR2) that encode either subunit of the transforming growth factor-beta (TGFβ) receptor, leading to increased output of TGFβ-responsive gene products including types I and III collagen and connective tissue growth factor.3 The prevalence of LDS is unknown. Clinical manifestations of LDS vary greatly, and those of special interest for anesthesiologists include atrial septal defect, arterial/aortic aneurysms and dissections, cerebrovascular aneurysms, scoliosis, pectus deformity, and predisposition to cervical spine malformation. It may therefore be prudent to obtain antepartum, radiographic imaging of the brain and spine to assess for cervical instability, dural ectasia, scoliosis, or vascular malformations that might complicate anesthetic care. The median survival of patients with LDS is approximately 37 years, with death commonly occurring after thoracic aortic dissection, abdominal aortic dissection, and hemorrhagic stroke. Accordingly, experts have recommended early surgical intervention in the setting of a lower aortic root diameter threshold (4 cm) in patients with LDS as compared with other connective tissue disorders such as Marfan syndrome. Most patients receive medications including β blockers and/or angiotensin receptor blockers to reduce hemodynamic lability even in the absence of preexisting hypertension. The physiologic changes associated with pregnancy and the puerperium may pose additional risks to the patient with LDS. While some state that patients with LDS can tolerate pregnancy and delivery without any adverse effects, 1 study showed that of 21 pregnancies in patients with LDS, 6 had a major complication during pregnancy or immediately postpartum including uterine rupture in 2 patients and aortic dissection in 4 patients.4 Anomalous vascularity is common, increasing the risk of significant surgical bleeding, complications with vascular access, and inadvertent intravascular placement of an epidural catheter. Connective tissue laxity may be associated with an increased risk of premature rupture of membranes, uterine atony, and uterine rupture. Postpartum uterine involution can be facilitated by nonpharmacologic methods (e.g., fundal massage) and the avoidance
48 cases-anesthesia-analgesia.org
of inhaled anesthetics; it may be prudent to avoid uterotonic medications due to the increased risk of uterine rupture. Dural ectasias in the lumbosacral region are very common in this population,5 and while spinal and epidural anesthesia have been successfully performed,6 there is an increased likelihood of failed spinal anesthesia.7 There is also increased theoretic risk of inadvertent dural puncture8 because of increased hydrostatic pressure in the setting of weakened dura.8 Dural puncture may cause decreased intracranial pressure and subsequent risk of intracerebral aneurysmal bleeding.9,10 In the setting of a dural ectasia in the L5-S2 region, a reasonable alternative is for an experienced provider to place an epidural catheter above L4-5 with slow, controlled dosing with the patient in the lateral position. Though LDS is a rare disorder, the anesthesiologist should be alert to characteristic physical features common to patients with LDS and other connective tissue disorders because they may herald the presence of occult cardiovascular, neurologic, and musculoskeletal concerns. E REFERENCES 1. Kunishige H, Ishibashi Y, Kawasaki M, Yamakawa T, Morimoto K, Inoue N. Surgical treatment for acute type A aortic dissection during pregnancy (16 weeks) with Loeys-Dietz syndrome. Gen Thorac Cardiovasc Surg 2012;60:764–7 2. Gutman G, Baris HN, Hirsch R, Mandel D, Yaron Y, Lessing JB, Kuperminc MJ. Loeys-Dietz syndrome in pregnancy: a case description and report of a novel mutation. Fetal Diagn Ther 2009;26:35–7 3. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak PJ, Cameron DE, De Backer J, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 2005;37:275–81 4. Van Hemelrijk C, Renard M, Loeys B. The Loeys-Dietz syndrome: an update for the clinician. Curr Opin Cardiol 2010;25:546–51 5. Rodrigues VJ, Elsayed S, Loeys BL, Dietz HC, Yousem DM. Neuroradiologic manifestations of Loeys-Dietz syndrome type 1. AJNR Am J Neuroradiol 2009;30:1614–9 6. Buser RT, Mordecai MM, Brull SJ. Combined spinal-epidural analgesia for labor in a patient with Marfan’s syndrome. Int J Obstet Anesth 2007;16:274–6 7. Lacassie HJ, Millar S, Leithe LG, Muir HA, Montaña R, Poblete A, Habib AS. Dural ectasia: a likely cause of inadequate spinal anaesthesia in two parturients with Marfan’s syndrome. Br J Anaesth 2005;94:500–4 8. Jones KB, Myers L, Judge DP, Kirby PA, Dietz HC, Sponseller PD. Toward an understanding of dural ectasia: a light microscopy study in a murine model of Marfan syndrome. Spine (Phila Pa 1976) 2005;30:291–3 9. Rocchi R, Lombardi C, Marradi I, Di Paolo M, Cerase A. Intracranial and intraspinal hemorrhage following spinal anesthesia. Neurol Sci 2009;30:393–6 10. Eggert SM, Eggers KA. Subarachnoid haemorrhage follow ing spinal anaesthesia in an obstetric patient. Br J Anaesth 2001;86:442–4
A & A case reports
