Anesthesia for intrauterine myelomeningocele correction: case report

Abstracts

JUSTIFICATIVA E OBJETIVOS: A cirurgia fetal constitui tratamento de malformações no período pré-natal, que não são adequadamente corrigidas após o nascimento e tem como objetivo tratar ou evitar a progressão das anomalias. O objetivo deste relato é apresentar um caso de anestesia para correção intra-útero de mielomeningocele. RELATO DO CASO: Paciente com 19 anos, 23 semanas de idade gestacional, sem antecedentes anestésicos, estado físico ASA I, submetida à cirurgia fetal intra-uterina, sob anestesia geral associada à peridural contínua. No pré-operatório utilizaram-se indometacina (50 mg por via retal), metoclopramida (10 mg por via venosa), cimetidina (50 mg por via venosa), e como medicação pré-anestésica midazolam (2 mg por via venosa). No espaço peridural injetou-se bupivacaína a 0,25% com adrenalina (25 mg) associada à fentanil (100 µg), seguida de passagem de cateter cefálico, para analgesia pós-operatória. O útero foi mantido deslocado para esquerda com auxílio da cunha de Crawford. Indução anestésica em seqüência rápida, com fentanil, propofol e rocurônio e manutenção com isoflurano em concentração de 2,5% a 3% veiculado em O2 e N2O (50%). Após histerotomia, realizada com staplin (grampeadores) para promover hemostasia, a região fetal a ser operada foi exposta e a analgesia e imobilidade fetal, foram obtidas com a associação fentanil (10 µg.kg-1) e pancurônio (0,1 mg.kg-1) administrada na região glútea fetal. A pressão arterial sistólica materna foi mantida acima de 100 mmHg, com efedrina em bolus (5 mg), colóides e cristalóides. O líquido amniótico perdido foi substituído por solução fisiológica aquecida. Após correção do defeito fetal, procedeu-se ao fechamento uterino e da membrana amniótica em dois planos, com fio de vicryl e cola de fibrina. Seguiu-se a diminuição gradativa da concentração do isoflurano, e para a manutenção do relaxamento uterino utilizou-se sulfato de magnésio (4 g/20minutos), seguido de infusão contínua (2 g/hora). Ao final da cirurgia injetou-se morfina (2 mg) pelo cateter peridural para analgesia pós-operatória. CONCLUSÕES: A anestesia para cirurgia fetal envolve dois seres, mãe e feto, e o manuseio anestésico exige segurança materno-fetal, anestesia e imobilidade fetal, relaxamento uterino, prevenção do trabalho de parto prematuro e analgesia pós-operatória.

CIRURGIA, Fetal; TÉCNICAS ANESTÉSICAS, Geral

CLINICAL REPORT

Anesthesia for intrauterine myelomeningocele correction. Case report^*

Anestesia para corrección intra-útero de mielomeningocele. Relato de caso

Angélica de Fátima de Assunção Braga, TSA, M.D.^I; Monique Sampaio Rousselet, M.D.^II; Helder Zambelli, M.D.^III; Lourenço Sbragia, M.D.^IV; Ricardo Barini, M.D.^V

^IProfessora Associada do Departamento de Anestesiologia da Faculdade de Ciências Médicas da UNICAMP

^IIAnestesiologista do Centro de Atenção Integral à Saúde da Mulher - CAISM

^IIIProfessor Doutor do Departamento de Neurologia da FCM da UNICAMP

^IVProfessor Doutor do Departamento de Cirurgia da FCM da UNICAMP

^VProfessor Associado do Departamento de Ginecologia da FCM da UNICAMP

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: Fetal surgery is the treatment of choices for prenatal malformations that are not adequately corrected after birth and aims at treating or preventing the progression of the abnormalities. This report describes a case of anesthesia for intrauterine correction of a myelomeningocele.

CASE REPORT: Pregnant patient, 19 years old, 23 weeks of gestational age, without previous anesthetic history, physical status ASA I, submitted to intrauterine fetal surgery under general anesthesia associated to continuous epidural continuous anesthesia. The patient was premedicated with rectal indomethacin (50 mg), intravenous metoclopramide (10 mg) and cimetidine (50 mg), in addition to intravenous midazolam (2 mg). The patient received 0.25% bupivacaine with epinephrine (25 mg) associated to fentanyl (100 µg) epidurally, followed by cephalic catheter insertion for postoperative analgesia. The uterus was left-displace with a Crawford's wedge. Rapid sequence anesthesia was induced with fentanyl, propofol and rocuronium, and was maintained with 2.5% - 3% isoflurane in O₂ and N₂O. After stapling hysterectomy to promote homeostasis, fetal operative site was exposed and fetal analgesia and immobility was obtained with the association of fentanyl (10 µg.kg^-1) and pancuronium (0.1 mg.kg^-1) administered on fetal gluteus muscle. Maternal systolic blood pressure was maintained above 100 mmHg with bolus ephedrine (5 mg), colloids and crystalloids. Lost amniotic fluid was replaced with warm saline. After correction of the fetal defect, both uterus and amniotic membrane were closed in two planes with vicryl suture and fibrin glue. Afterwards, isoflurane concentration was gradually decreased and bolus magnesium sulfate (4 g/20 minutes) followed by continuous infusion was administered to maintain uterine relaxation (2 g/hour). Morphine (2 mg) was administered via epidural catheter at the end of surgery for postoperative analgesia.

CONCLUSIONS: Anesthesia for fetal surgery involves two individuals the mother and the fetus, an anesthetic management requires: maternal-fetal safety, fetal anesthesia and immobility, uterine relaxation, prevention of premature labor and postoperative analgesia.

Key words: ANESTHETIC TECHNIQUES, General: combined; SURGERY, Fetal: myelomeningocele

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La cirugía fetal constituye tratamiento de malformaciones en el período prenatal, que no son adecuadamente corregidas después del nacimiento y tiene como objetivo tratar o evitar la progresión de las anomalías. El objetivo de este relato es presentar un caso de anestesia para corrección intra-útero de mielomeningocele.

RELATO DEL CASO: Paciente con 19 años, 23 semanas de edad gestacional, sin antecedentes anestésicos, estado físico ASA I, sometida a cirugía fetal intrauterina, bajo anestesia general asociada a la peridural continuada. En el pre-operatorio se utilizaron indometacina (50 mg por vía rectal), metoclopramida (10 mg por vía venosa), cimetidina (50 mg por vía venosa), y como medicación pre-anestésica midazolam (2 mg por vía venosa). En el espacio peridural se inyectó bupivacaína a 0,25% con adrenalina (25 mg) asociada al fentanil (100 µg), seguida del pasaje de catéter cefálico, para analgesia postoperatoria. El útero fue mantenido dislocado para la izquierda con auxilio de la cuña de Crawford. Inducción anestésica en secuencia rápida, con fentanil, propofol y rocuronio y mantenimiento con isoflurano en concentración del 2,5% a 3% vehiculado en O₂ y N₂O (50%). Después de la histerotomía, realizada con staplin (grapadoras) para promover hemostasia, la región fetal a ser operada fue expuesta y la analgesia e inmovilidad fetal, fue lograda con la asociación fentanil (10 µg.kg^-1) y pancuronio (0,1 mg.kg^-1) administrada en la región glútea fetal. La presión arterial sistólica materna fue mantenida arriba de 100 mmHg, con efedrina en bolus (5 mg), coloides y cristalóides. El líquido amniótico perdido fue sustituido por solución fisiológica entibiada. Después de la corrección del defecto fetal, se procedió al encerramiento uterino y de la membrana amniótica en dos planos, con hilo de vicryl y cola de fibrina. Se siguió la disminución gradativa de la concentración del isoflurano, y para el mantenimiento del relajamiento uterino se utilizó sulfato de magnesio (4 g/20minutos), seguido de infusión continuada (2 g/hora). Al final de la cirugía se inyectó morfina (2 mg) por el catéter peridural para la analgesia postoperatoria.

CONCLUSIONES: La anestesia para cirugía fetal envuelve dos seres, madre y feto, y el manoseo anestésico requiere: seguridad materno-fetal, anestesia e inmovilidad fetal, relajamiento uterino, prevención del trabajo de alumbramiento prematuro y analgesia postoperatoria.

INTRODUCTION

The first fetal procedure in humans was performed in 1963 by Liley ¹ and consisted of intraperitoneal blood transfusion to treat fetal erythroblastosis.

Advances in prenatal diagnostic tools, such as high-resolution ultrasound, biochemical and cytogenetic analysis of amniotic fluid and fetal blood, have increasingly allowed for early diagnosis and correction of fetal defects thereby delaying their evolution and preventing them to become irreversible ². Although different abnormalities might be corrected intra-uterus, mother and fetus are only candidates to surgery when the risk of fetal mortality or severe inability will be higher if no intervention is performed and when maternal risk remains low ². Optimal gestational age for fetal correction is 21 to 27 weeks, however the earlier the surgery the better its outcomes ^3,4.

Anesthesia for fetal surgery involves two patients, the mother and the fetus. Thus maternal-fetal safety should be taken into consideration. Maternal management includes uterine relaxation, prevention of premature labor, pre, intra and postoperative tocolytic agents and postoperative analgesia, in addition to those related to inherent pregnancy changes. Fetal management includes anesthesia, immobility and prevention of fetal asphyxia ^2,5. This report aimed at describing a case of anesthesia for intrauterine correction of fetal myelomeningocele.

CASE REPORT

After being informed about the anesthetic procedure, a pregnant patient, 19 years old, 56 kg, 155 cm, gestation 1 to 2, 23 weeks of gestational age, without previous anesthetic history, physical status ASA I, was submitted to intrauterine fetal surgery for myelomeningocele correction under general anesthesia with mechanically controlled ventilation associated to continuous epidural anesthesia. Monitoring consisted of cardioscopy at D_II, noninvasive blood pressure, pulse oximetry, capnography and acceleromyography to evaluate neuromuscular block. Preoperative medication consisted of rectal indomethacin (50 mg), intravenous metoclopramide (10 mg) and cimetidine (50 mg). Preanesthetic medication was intravenous midazolam (2 mg) 10 minutes before anesthesia.

In the operating theater, at room temperature, venoclysis on the upper limb was achieved with 14G catheter for volume replacement and drugs administration. The L₃-L₄ intervertebral space was punctured with disposable 16G Tuohy needle having the patient in the sitting position. After epidural space identification by the loss of resistance to air technique, 0.25% bupivacaine with 1:200,000 epinephrine (25 mg) associated to fentanyl (100 µg) were injected and a catheter was inserted cephalically for postoperative analgesia.

With patient in the supine position and left uterine displacement with a Crawford's wedge, general anesthesia was induced in rapid sequence: oxygenation with 100 oxygen under mask, intravenous fentanyl (250 µg), propofol (150 mg) and rocuronium (50 mg) Sellick maneuver and tracheal intubation. Anesthesia was maintained with 2.5% - 3% isoflurane through a calibrated vaporizer in a 50% mixture of O₂/N₂O. After stapling hysterectomy to promote homeostasis, the fetal operative site was exposed and, to assure fetal analgesia and immobility, intramuscular fentanyl (10 µg.kg^-1) and pancuronium (0.1 mg.kg^-1) were administered into the fetal gluteus muscle.

Fetal heart rate was continuously monitored by ultrasound and maintained between 127 to 139 bpm throughout the procedure. Maternal systolic blood pressure was maintained above 100 mmHg with bolus ephedrine (5 mg), colloids (500 mL) and crystalloids (1000 mL). Lost amniotic fluid was replaced with warmed 0.9% saline until normal AFI (Amniotic Fluid Index) was reached. After correction of the fetal defect, both uterus and amniotic membranes were closed in two planes with vicryl suture and fibrin glue.

Isoflurane concentration was gradually decreased and bolus magnesium sulfate (4 g/20 minutes) followed by continuous infusion (2 g.h^-1) was started to maintain uterine relaxation. There were no maternal-fetal intercurrences. Morphine (2 mg) was injected via epidural catheter at the end of surgery. After neuromuscular block recovery, the patient was extubated when T₄:T₁ > 0,8 (acceleromyography), and hemoglobin saturation was 98% in room air. Fetal procedure lasted 17 minutes with total surgery time of 150 minutes. Patient was transferred to the intensive care unit conscious and hemodynamically stable.

DISCUSSION

Fetal surgery aims at treating or preventing progression and irreversibility of abnormalities. Among fetal diseases, prenatal myelomeningocele correction has received special attention and aims at restoring CSF flow after spinal defect closure, thus preventing hydrocephalus and loss of spinal cord function ².

Intrauterine procedures to correct fetal abnormalities may be performed under regional anesthesia or sedation (minimally invasive procedures), however when hysterectomy is needed, they should be performed under general anesthesia to control tone and assure uterine atonia needed for fetal perfusion and adequate for fetal exposure. Epidural anesthesia does not promote uterine relaxation, however it may be useful in preventing premature labor ^2,3,6,7.

Important anesthetic maternal-fetal risk factors are maternal physiological changes, especially respiratory, cardiocirculatory and gastrointestinal changes. Among respiratory changes, decreased functional residual capacity associated to increased oxygen consumption contribute to higher risk of hypoxia which may be minimized by 100% oxygen before anesthetic induction and tracheal intubation ^3,8. Decreased oncotic pressure and increased capillary patency may also increase the risk of postoperative pulmonary edema, especially when magnesium sulfate is used as tocolytic agent ⁷. Positive pressure hyperventilation leads to hypocapnia with oxyhemoglobin curve shift to the left and decreased fetal oxygen availability ³. Additionally, there is decreased venous return, maternal cardiac output and uterine blood flow, which is the primary determinant of placental flow ^2,3.

Gastrointestinal changes increase the risk of gastric content aspiration, and preventive measures, such as oral non-particulate antacids, intravenous metoclopramide (10 mg), induction and tracheal intubation in rapid sequence, should be considered ^2,5,7. Although there were no counterindications for succinylcholine due to its numerous undesirable effects, we decided for rocuronium to obtain adequate muscle relaxation for laryngoscopy and tracheal intubation. It is an nondepolarizing neuromuscular blockers with fast onset, which can be used when rapid sequence induction is needed without maternal-fetal repercussions, such as in obstetric procedures ⁹.

Increased uterine tone, hypotension, hypertension and noradrenergic activity with myometrial vasoconstriction are among factors to be avoided during fetal surgery since they promote decreased uterine blood flow with resultant fetal wellbeing impairment. Inferior vena cava compression by the pregnant uterus during supine position decreases venous return and triggers maternal hypotension, making mandatory left uterine displacement to prevent maternal hypotension and fetal asphyxia ^3,5,10.

To assure placental perfusion and prevent fetal asphyxia during anesthesia, maternal systolic blood pressure should be maintained above 100 mmHg and hypotension should be promptly corrected by decreasing volatile agent concentration and administering colloids and crystalloids or vasopressors. In fetal procedures, however, due to aggressive tocolytic therapy, patients tend to develop acute postoperative pulmonary edema, so care must be taken with fluid replacement.

On the other hand, decreased anesthetic concentration may lead to increased uterine activity. Although there are controversies about vasopressors to treat maternal hypotension following spinal block, ephedrine, which effects are primarily beta-adrenergic with minor uterine blood flow repercussions, has remained for a long time as the drug of choice to treat maternal hypotension ^2,11. However, recent studies comparing ephedrine and phenylephrine to treat maternal hypotension have shown that ephedrine may promote further fetal acidosis ¹¹.

Studies in pregnant ewes have shown that high doses of vasoconstrictors have deleterious effects on uterine blood flow. Phenylephrine, even in high doses (1000 µg), does not promote clinically significant vasoconstriction and decreased placental perfusion. Although high doses are needed to maintain homeostasis, they do not increase blood pressure above normal values. So, they may be considered adequate to correct vasodilation secondary to spinal anesthesia ¹¹.

Different from other surgical procedures performed during pregnancy, fetal surgery needs fetal anesthesia and immobility, which are critical for surgical success. Fetal movements should be prevented and this is relevant for fetal surgery since they make the procedure technically more difficult and may increase the risk of umbilical vessels or fetal trauma ^6,12,13. Fetal activity, although being related to gestational age and maternal glycemic levels, is primarily due to surgical stimulation ⁷.

Studies have shown that surgical manipulation of non-anesthetized fetuses results in autonomic nervous system stimulation with repercussions in heart rate, increased hormone levels and fetal motor activity, which may be abolished with adequate fetal anesthesia ^3,13. Notwithstanding the rapid transfer of volatile agents through placental barrier, fetal concentration remains lower as compared to maternal concentration, even after long exposure time, and does not assure fetal anesthesia and immobility to provide safe intrauterine therapy ¹⁴.

Fetal response to surgical stimulation may be blocked by muscular or intravenous opioids, such as fentanyl (5 to 20 µg.kg^-1) with our without atropine (20 µg.kg^-1), directly administered to fetus. Fentanyl is chosen due to efficacy and safety for premature neonates submitted to anesthesia ^5,6,12,14. Fetal movements have been safely controlled with pancuronium (intravenous 0.05 to 0.1 mg.kg^-1 or muscular 0.2 to 0.3 mg.kg^-1), pipecuronium (muscular 0.2 mg.kg^-1) or vecuronium (intravenous 0.1 mg.kg^-1 or muscular 0.2 mg.kg^-1) ^2,3,7,12,14. Due to its vagolytic activity, pancuronium increases heart rate, which is desirable to maintain fetal cardiac output ³.

Intraoperative volatile agents for anesthetic maintenance inhibit uterine contraction providing enough relaxation for fetal exposure through minor hysterectomy. However, in addition to decreasing myometrial tone, these potent vasodilating drugs tend to promote maternal hypotension with uterine-placental low flow, resulting in decreased fetal oxygenation ^2,7. In addition, uterine relaxation promoted by these agents significantly increases risk of intraoperative hemorrhage, which may be decreased by limiting surgical incision size and by special surgical techniques with hemostatic stapling, also useful for amniotic membrane sealing ^2,5.

Although halothane is considered the volatile agent with highest uterine relaxing property, it has not been recommended as anesthetic agent for fetal interventions due to its negative effects on fetal heart rate, which are not observed with isoflurane and sevoflurane. Similar to other authors, low opioid doses were used to optimize the use of high isoflurane concentrations (2.5% to 3%) needed for adequate uterine relaxation and fetal defect correction ^3,5,15. These concentrations, however, decrease maternal blood pressure, uterine-placental perfusion and, as a consequence, fetal cardiac output and oxygenation, which may be prevented by moderate fluids and beta-adrenergic drugs infusion ^2,5,7,14.

A major drawback for the success of fetal surgery is the possibility of premature labor resulting from uterine stimulation and contraction caused by uterine manipulation and incision. This manipulation may induce abruption placenta with decreased placental blood flow and fetal anoxia. Prevention of premature labor and its treatment are critical for surgical success and include pre, intra and postoperative tocolytic drugs ¹⁴.

Although there are controversies about the efficacy of preventive tocolytics, these have been recommended by some authors ⁶. They have also been associated to maternal complications such as hypotension, arrhythmias, pulmonary edema and metabolic changes ⁶. Tocolytics, prostaglandin synthesis inhibitors and beta-adrenergics, such as indomethacin and terbutaline, are among the most commonly used preoperative agents.

Magnesium sulfate has been used both intra and postoperatively to maintain uterine relaxation. The mechanism of its tocolytic effect is unknown and 4 to 8 mEq.L^-1 concentrations are needed to decrease myometrial activity ⁵. Due to the interaction between magnesium sulfate and neuromuscular blockers, manifested by increased sensitivity especially to nondepolarizing NMB, and increased neuromuscular block duration, lower doses and neuromuscular transmission monitoring are recommended ⁵. Intravenous nitroglycerin may also be used to maintain uterine relaxation, however its use as tocolytic agent may be associated to acute pulmonary edema ^2,5.

Our patient was given preoperative indomethacin and after correction of the fetal defect and hysterorrhaphy, postoperative uterine relaxation was maintained with bolus magnesium sulfate (4 g in 20 minutes) followed by continuous infusion (2 g.h^-1). It should be stressed that relaxation induced by these drugs significantly increases the risk of maternal hemorrhage.

Postoperative pain control is critical for the success of fetal surgery, due to its importance in preventing premature labor. Adequate postoperative analgesia was obtained with local anesthetics and morphine administered through an epidural catheter ².

In our case, pregnancy has evolved until the 35^th week and time elapsed between fetal surgery (23^rd week) and birth could be considered a record, since most fetuses submitted to this procedure are delivered before 32 weeks of gestational age. Further studies, however, are needed to determine the best anesthetic technique for the binomial mother-fetus. It should assure maternal cardiovascular stability, excellent uterine-placental perfusion, total uterine relaxation, adequate fetal immobility and anesthesia with blockade of fetal response to stress and minor fetal cardiac depression.

REFERENCES

Submitted for publication September 27, 2004

Accepted for publication February 1, 2005

• 01. Liley AW - Intrauterine transfusion of foetus in haemolytic disease. Br Med J, 1963;2:1107-1109.
• 02. Myers LB, Cohen D, Galinkin J et al - Anaesthesia for fetal surgery. Paediatr Anaesth, 2002;12: 569-578.
• 03. Cauldwell CB - Anesthesia for fetal surgery. Anesthesiol Clin North America, 2002;20:211-226.
• 04. Simpson JL - Fetal surgery for myelomeningocele: promise, progress, and problems. JAMA, 1999;282:1873-1874.
• 05. Gaiser RR, Kurth CD - Anesthetic considerations for fetal surgery. Semin Perinatol, 1999;23: 507-514.
• 06. Spielman FJ, Seeds JW, Corke BC - Anaesthesia for fetal surgery. Anaesthesia, 1984;39:756-759.
• 07. Schwarz U, Galinkin JL - Anesthesia for fetal surgery. Semin Pediatr Surg, 2003;12:196-201.
• 08. Archer WA Jr, Marx GF - Arterial oxygen tension during apnoea in parturient women. Br J Anaesth, 1974;46:358-360.
• 09. Abouleish E, Abboud T, Lechevalier T et al - Rocuronium (Org 9426) for caesarean section. Br J Anaesth, 1994;73:336-341.
• 10. Rychik J, Tian ZY, Cohen DE et al - Hemodynamic changes during human fetal surgery. Circulation, 1998;98:1481.
• 11. Riley ET - Spinal anaesthesia for Caesarean delivery: keep the pressure up and don't spare the vasoconstrictors. Br J Anaesth, 2004;92:459-461.
• 12. Fan SZ, Susetio L, Tsai MC - Neuromuscular blockade of the fetus with pancuronium or pipecuronium for intra-uterine procedures. Anaesthesia, 1994;49:284-286.
• 13. Anand KJ, Hickey PR - Pain and its effects in the human neonate and fetus. N Engl J Med, 1987;317:1321-1329.
• 14. Rosen MA - Anesthesia for Fetal Surgery, em Chestnut DH - Obstetric Anesthesia. Principles and Practice. 2^st Ed, Philadelphia. Mosby, 1999;110-121.
• 15. Sabik JF, Assad RS, Hanley FL - Halothane as an anesthetic for fetal surgery. J Pediatr Surg, 1993;28:542-546.

Correspondence to

Dra. Angélica de Fátima de Assunção Braga

Address: Rua Luciano Venere Decourt, 245 - Cidade Universitária

ZIP: 13084-040 City: Campinas, Brazil

*

Received from Centro de Atenção Integral à Saúde da Mulher - CAISM - UNICAMP, Campinas, SP

Publication Dates

• Publication in this collection
  28 June 2005
• Date of issue
  June 2005

History

• Received
  27 Sept 2004
• Accepted
  01 Feb 2005