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• W1971894607 abstract "This is the first case report of two anesthetics administered to a patient potentially at risk for malignant hyperthermia (MH) undergoing fetal surgery and an ex utero intrapartum treatment (EXIT) procedure. The patient underwent laparotomy for fetoscopy and fetal tracheal occlusion under epidural anesthesia, and subsequently an EXIT procedure under general anesthesia. Large-dose volatile anesthetic concentrations, up to 2 or 3 minimum alveolar anesthetic concentration end-tidal, have been used since the inception of fetal surgery to provide intraoperative uterine atony (surgical tocolysis) (1,2). However, as triggering drugs for MH, anesthetic gases were contraindicated for this patient. Surgical and anesthetic management of patients undergoing surgery during pregnancy and fetal surgery have been reviewed recently (3–7), as have precautions for patients at risk for MH (8). We discuss the successful anesthetic and tocolytic management of a patient undergoing fetal surgery with IV nitroglycerin to avoid the use of volatile anesthetics. Case Report A 21-yr-old woman, gravida 2 SAB 1 (G2P0010), was referred at 25 wk gestation to the Fetal Treatment Center at the University of California San Francisco (9). Her fetus had severe left congenital diaphragmatic hernia with liver herniation into the hemithorax, with a normal karyotype and no other anomalies. The patient’s history revealed that the estranged brother of her paternal grandfather probably experienced an episode of MH and that her father had had an uneventful general anesthetic. MH susceptibility testing of the patient, her ancestors, or her unborn offspring could not be performed in time for surgery. Fetal Tracheal Occlusion The surgical plan for the first procedure was maternal mini-laparotomy, fetoscopy, and fetal tracheal occlusion. After premedication with indomethacin 100 mg by suppository for its tocolytic effect, a nonparticulate oral antacid, and IV midazolam 2 mg and fentanyl 50 μg, an epidural catheter was inserted at L3-4. After administering a test dose of 3 mL of 2% lidocaine with epinephrine 1:200,000, a further 20 mL was administered epidurally in divided doses. Standard American Society of Anesthesiologists monitors were used, supplemental oxygen was administered nasally, and maternal blood pressure maintained at >100/50 mm Hg with IV ephedrine, a total of 25 mg. Additional IV midazolam 2 mg, fentanyl 125 μg, and propofol 50–75 μg · kg−1 · min−1 were administered for intraoperative anxiolysis. Before hysterotomy, the surgeon medicated the fetus under sonographic guidance with fentanyl 25 μg and vecuronium 0.25 mg IM. Fetal heart rate was monitored by sonography. A small incision was made on the maternal abdomen to expose the uterus, and a small hysterotomy incision was made to accommodate the endoscope. Guided by sonography, the endoscope was first advanced into the fetal mouth, then further under direct vision into the trachea. Then, a small balloon (typically used to occlude intracranial arteries) was inflated to occlude the fetal trachea. During closure of the uterine incision, magnesium sulfate was administered IV as a 4-g loading dose, followed by a continuous infusion at 2 g/h. By inspection and palpation, we found no significant intraoperative contractions. Magnesium sulfate and terbutaline were used IV for continued postoperative tocolysis, and pain relief was provided with the use of epidural analgesia. Reestablishing Fetal Tracheal Patency At 31 3/7 wk gestation, the patient underwent a cesarean delivery and fetal EXIT procedure. Before the procedure, the anesthesia machine was flushed and the tubing and CO2 absorber were changed. An arterial line and standard American Society of Anesthesiologists monitors were used and after oral administration of a nonparticulate antacid, anesthesia was induced and tracheal intubation achieved with a modified rapid sequence technique using IV thiopental 375 mg, rocuronium 50 mg, fentanyl 50 μg, and midazolam 1 mg. Anesthesia was maintained with an IV propofol infusion at 150 μg · kg−1 · min−1, and an IV infusion of nitroglycerin 16 μg · kg−1 · min−1 was administered to achieve adequate uterine relaxation. Administering IV ephedrine (a total of 30 mg), we maintained the maternal mean arterial blood pressure at >65 mm Hg. Uterine incision was made with a stapling device to ensure hemostasis during the procedure (10). The baby was medicated with pancuronium 0.25 mg and morphine 0.25 mg IM. The fetal head, upper thorax, and left arm were delivered and a pulse oximeter was placed on the hand to monitor pulse and oxygen saturation. The fetal heart rate, initially 130 bpm, began to slow to approximately 90 bpm, which we attributed to umbilical cord compression. The surgeons were asked to completely deliver the baby, to keep the exposed umbilical cord wet (with saline), and to avoid stretching or touching it. The fetal heart rate immediately returned to a normal value. Under direct laryngoscopy, the surgeon pierced the balloon and removed it from the trachea. Then, the baby’s trachea was intubated, surfactant administered through the endotracheal tube, and the lungs were gently ventilated until the oxygen saturation (by pulse oximetry) increased from an initial value of 60% to >90%. The cord was then clamped, 30 min after uterine incision. During this time period, fetal gas exchange depends on normal placental function, and surgical tocolysis minimizes the risk of placental separation; in the case presented, nitroglycerin alone was sufficient to provide surgical tocolysis. After cord clamping, nitroglycerin was discontinued and the mother received IV Pitocin. The uterus was very firm within 3 min. Additional IV midazolam 1 mg, fentanyl 200 μg, and dolasetron 12.5 mg were administered. Neuromuscular blockade was antagonized and her trachea was extubated once she regained consciousness. We estimated her blood loss as 1000 mL. Per her request, she received postoperative analgesia by morphine patient-controlled analgesia, and had an uneventful recovery. The 1.7-kg baby boy was transferred to the neonatal intensive care unit after initial resuscitation in a resuscitation room connected to the obstetric operating room. Initial blood gases from the clamped umbilical cord revealed normal pH and Pco2 values with increased Po2 values. After a hospital course that included a trigger-free anesthetic for surgical repair of the diaphragmatic hernia, the child was discharged home on nasal O2 with a normal neurologic examination at 2 mo of age. Discussion Many of the anesthetic considerations for fetal procedures and surgery are identical to those for nonobstetric surgery during pregnancy. However, anesthesia for hysterotomy and fetal intervention pose unique challenges related to providing care and monitoring both mother and fetus, and providing surgical tocolysis (1–5). Fetal surgery is distinguished from other nonobstetric surgeries performed during pregnancy by concern about fetal anesthesia and fetal monitoring, and the significantly increased likelihood of intra- or postoperative preterm labor. Uterine atony during the procedure safely allows surgical exposure through a hysterotomy, avoiding the increased uterine tone or contractions associated with stimulation that could interfere with uteroplacental blood flow. The human uterine wall has a thick, muscular layer that is sensitive to stimulation or manipulation. After incision, strong uterine contractions can occur that have resulted in a frequent incidence of postoperative abortion in experimental preparations using nonhuman primates (11). Strong uterine contractions impede uteroplacental blood flow and can cause placental separation from the endometrium, compromising fetal well-being. For the minimally invasive endoscopic procedure, maternal anesthesia can be regional and/or general because the small incision or puncture of the uterine wall is a minimal stimulus to the uterus. For more invasive fetal surgical procedures that involve large uterine incisions, volatile anesthetics at relatively large concentrations, up to 3 minimum alveolar anesthetic concentration end-tidal, have been routinely used for surgical tocolysis since the inception of fetal surgery in 1981 (1,11,12). To supplement tocolysis, we administer indomethacin preoperatively by suppository. Intraoperatively, we use small boluses of IV nitroglycerin (100 μg) when contractions are palpable or visible to the eye or by sonography. Toward the end of the surgery, we administer a loading dose of IV magnesium sulfate, followed by an infusion that is continued postoperatively. Volatile anesthetics are the most potent for intraoperative uterine relaxation, but their triggering potential for MH precluded their use for our patient. Instead, we chose a regional technique for the fetoscopy and tracheal balloon placement. Based on our experience over the past two decades, and more recently reported by colleagues (13), we were confident that if increased uterine tone occurred during the fetoscopy, IV nitroglycerin boluses would have provided sufficient tocolysis, thus we easily avoided triggering drugs. The EXIT procedure, however, involves considerably more uterine stimulation than fetoscopy because of the larger uterine incision, and therefore required a potent tocolytic (14,15). With the patient’s family history of MH prohibiting the use of volatile anesthetics, we achieved adequate uterine relaxation with large-dose nitroglycerin alone. We selected this technique based on our successful experience using large-dose nitroglycerin, 20 μg · kg−1 · min−1, for in utero primary repair of diaphragmatic hernias in the late 1980s (3–5). More recently, there has been an emerging clinical experience of the tocolytic efficacy of nitroglycerin for obstetric indications such as uterine hyperstimulation (16). Nitroglycerin has the advantage of short duration of action, allowing rapid elimination upon discontinuation when the umbilical cord is clamped and Pitocin is administered to increase uterine tone to avoid postpartum hemorrhage. In addition, IV nitroglycerin is a more potent tocolytic than the more commonly used tocolytics, magnesium, and β-mimetic drugs such as terbutaline. However, great caution must be exercised when using large doses of nitroglycerin. We learned that it was important to eliminate the carrier agents present in commercially available glass bottles to avoid a phenomenon of a postoperative low-pressure pulmonary edema (17). MH susceptibility has an autosomal dominant inheritance with incomplete penetration and well established genetic heterogeneity and is often linked to the locus of the ryanodine receptor gene, encoding the skeletal muscle sarcoplasmic reticulum Ca2+ release channel (8). Hence, children and siblings of a susceptible patient have a 50% chance of inheriting MH susceptibility. However, not every susceptible gene carrier develops the MH episode upon each exposure to a triggering anesthetic. Genetic testing is being developed but is still flawed with frequent false negatives because of an incomplete understanding of MH genetics (18). Only a negative in vitro contracture test on a muscle biopsy from the patient or her highest level relative, e.g., the patient’s father, would have broken the genetic link to her presumed MH susceptible great-uncle and reduced the risk of MH susceptibility for her or her unborn offspring to normal. However, this could not be obtained in a timely manner. Had there been a triggering event, we were prepared to assess, diagnose, and treat the mother in the standard manner, including dantrolene administration. Intrauterine intervention has become a reasonable therapeutic alternative for certain correctable fetal abnormalities with predictable, life-threatening developmental consequences. Congenital diaphragmatic hernia occurs in approximately 1 of 2400 births and is characterized by herniation of abdominal contents into a hemithorax, usually the left. When this occurs early in gestation, it prevents normal lung development and leads to pulmonary hypoplasia, pulmonary hypertension, and hypoxia at birth, with a poor prognosis. The fetal lung produces fluid that normally passes out the trachea into the amniotic fluid. Experimental animal work demonstrated that draining the lung fluid resulted in pulmonary hypoplasia, whereas occluding the trachea led to fluid accumulation, accelerating lung growth and pulmonary hyperplasia (19–25). In summary, we performed two trigger-agent-free anesthetics for fetal surgery, one regional and one general, for a patient with a family history of MH. The first procedure was for fetoscopy and fetal tracheal balloon placement, the second for the EXIT procedure. Adequate surgical tocolysis was achieved with an IV infusion of nitroglycerin, without the use of volatile anesthetics." @default.
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• W1971894607 title "Nitroglycerin for Fetal Surgery: Fetoscopy and Ex Utero Intrapartum Treatment Procedure with Malignant Hyperthermia Precautions" @default.
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