Anesthesia for fetal surgeryFrederik De Bucka, Jan Deprestb and Marc Van de Veldeaa Department of Anesthesiology and bDepa...
294 Obstetric and gynecological anesthesia  caval compression and uterine hypoperfusion due to           In the postoperat...
Anesthesia for fetal surgery De Buck et al.   295Pain perception involves multilayered networks, forming         products,...
296 Obstetric and gynecological anesthesia  resuscitation drugs, for example, atropine 0.2 mg/kg and       When a local or...
Anesthesia for fetal surgery De Buck et al.              297                                                              ...
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Anesthesia for fetal surgery

  1. 1. Anesthesia for fetal surgeryFrederik De Bucka, Jan Deprestb and Marc Van de Veldeaa Department of Anesthesiology and bDepartment of Purpose of reviewGynaecology and Obstetrics, University Clinics Leuven,Leuven, Belgium To look at different anesthetic approaches to different surgical techniques used in fetal procedures and the influence of maternal and fetal factors on anesthetic management.Correspondence to Frederik De Buck, MD, Departmentof Anesthesiology, University Clinics Leuven, Recent findingsHerestraat 49, B-3000 Leuven, Belgium Fetal surgery is evolving rapidly in the field of mainly ex-utero intrapartum treatmentTel: +32 16 344270;e-mail: procedures, where new indications are found and new anesthetic techniques are developed, enabling the use of locoregional anesthesia. Further development of anesthetic techniques focuses on minimizing the risks for the mother and preserving theCurrent Opinion in Anaesthesiology 2008,21:293–297 normal neurodevelopment of the fetus. Summary Open fetal surgery remains a major invasive procedure for mother and fetus both, requiring general anesthesia with adequate invasive monitoring. Minimal invasive fetal procedures can be performed with local anesthesia alone or, for the more complex fetoscopic procedures, with a neuraxial locoregional technique. Fetal anesthesia and analgesia can then be provided by different routes. Ex-utero intrapartum treatment procedures are open fetal procedures, but they can be performed with locoregional anesthesia, when uterine relaxation can be achieved without volatile anesthetics with the use of intravenous nitroglycerin. Keywords ex-utero intrapartum treatment procedures, fetal analgesia, fetal nociception, fetal surgery, fetoscopy Curr Opin Anaesthesiol 21:293–297 ß 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins 0952-7907 nancy [5,8,9], and most often these procedures areIntroduction performed in the second or third trimester of pregnancy.Fetal surgery is in rapid development. With the advancesin prenatal diagnosis, many abnormalities are identified Cardiac output rises by 50–100%, both by an increase inthat may benefit from antenatal treatment. Surgical tech- heart rate and an increase in stroke volume. The bloodniques range from minimal invasive to open fetal pro- pressure drops by 15% from vasodilation and the exist-cedures, with a trend towards less invasive fetoscopic ence of a low-resistance placental vascular bed [8].techniques [1–3]. Intravascular blood volume increases with change inAnother rising field in fetal surgery is the ex-utero intra- plasma composition and decrease in total protein andpartum (EXIT) surgery, also known as operations on albumin levels. The decreased oncotic pressure leads toplacental support (OOPS). In these procedures, the fetus an increased risk for fluid retention and pulmonaryis partially delivered and treated while the fetoplacental edema. Decreased plasma cholinesterase levels may leadcirculation is preserved, allowing for the management of to a prolonged effect of succinylcholine. Different drugsfetal airways before the oxygenation from the placenta is have changed distribution volumes, and drugs with a highdiscontinued [4,5,6,7]. degree of protein binding have a larger free fraction [8,9].Providing anesthesia for these different procedures is aclinical challenge, in which there are always two patients Increases in different coagulation factors, such as factorsto consider, both mother and fetus. VII, VIII, IX, X and fibrinogen, cause a hypercoagulable state, with an increased risk for thomboembolisms [8].Maternal considerations Patients presenting for fetal surgery often have a poly-Depending on the type of procedure, both general and hydramnios, where the second trimester uterus becomeslocoregional anesthesia can be performed. Different as large as near term in a normal pregnancy. Thischanges in anatomy and physiology occur during preg- increases the risk for the supine hypotension syndrome,0952-7907 ß 2008 Wolters Kluwer Health | Lippincott Williams WilkinsCopyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.
  2. 2. 294 Obstetric and gynecological anesthesia caval compression and uterine hypoperfusion due to In the postoperative phase, an adequate maternal analge- decreased venous return. Prevention by a left lateral sia results in decreased plasma oxytocin levels and tilted position is important in this case [5,9]. decreased uterine activity [12]. A 50% increase in minute ventilation is reflected by a decreased normal PaCO2 of 28–32 mmHg, with a normal Fetal considerations pH due to an increased renal excretion of bicarbonate. The fetus is at increased risk in fetal surgery due to its The tidal volumes increase, although the respiratory rate immature organ systems. Hypothermia occurs rapidly remains normal. Oxygen consumption increases by 20% from heat loss through the thin and easily bruised skin. and together with a 20% decrease in functional residual It suffers easily from hypovolemia, given its low total capacity, faster desaturation occurs should there be an blood volume, higher bleeding tendency with an imma- airway problem. The airway mucosa is swollen and bleeds ture coagulation system, and high evaporative fluid easily due to capillary engorgement, making pregnant losses. Hypovolemia leads to hypoperfusion, and the patients more difficult to intubate, especially combined decreased baroreceptor activity limits the ability for with weight gain and breast enlargement [8,9]. compensatory vasoconstriction. The decreased myo- cardial contractility also predisposes to hypoperfusion. The gastric acid content is elevated, with a decreased Fetal hypoperfusion, together with uteroplacental hypo- pH due to placental gastrine secretion. The tone of the perfusion, leads to fetal hypoxia [9]. gastroesophageal sphincter is reduced secondary to hor- monal changes and the upward shift by the gravid uterus. The issue whether or nor a fetus is capable of feeling pain The pyloric sphincter is displaced, resulting in slower is still controversial [13], and the controversy has been gastric emptying. It is wise to consider all pregnant renewed by the proposition of laws in different states patients to have full stomachs, at increased risk for of the United States requiring fetal pain relief during aspiration [5,8,9]. abortion [14]. Pain, by definition, is composed of two systems: a physiologic reaction towards a noxious Minimum alveolar concentration (MAC) values decrease stimulus, nociception and stress response, and an by approximately 40%, possibly by increased levels of emotional negative perception [14]. progesterone and b-endorphin. The autonomic and endocrine responses to noxious The epidural space is narrowed by epidural venous stimuli, the stress response, consist of the activation of engorgement, increasing the risk for intravascular the hypothalamic, pituitary, and adrenal axis [15]. Rises catheter placement. There is also a larger dermatomal in blood levels of noradrenaline, cortisol and b-endorphin spread of injected local anesthetics [8,9]. during invasive procedures in the human fetus are seen. Alterations in the brain blood flow have been seen as early as in the 18th week of pregnancy [15]. These autonomic Uterine relaxation effects of noxious stimulation can be suppressed by the For open fetal surgery and the EXIT/OOPS procedures, administration of analgesics [16]. a profound uterine relaxation is required for optimal surgical exposure and for optimal placental gas exchange The fetal stress response to noxious stimulation does not [4,5,6,10]. prove that the fetus has a conscious perception of pain. It is however very unlikely that there would be pain per- Volatile anesthetics at concentrations of minimal two ception without a stress response, so this is often used as a MAC are very potent uterine relaxants [9]. surrogate indicator for fetal pain [16]. With high concentrations of volatile anesthetics, the The neural structures involved in pain processing develop maternal cardiac output drops, leading to hypotension throughout the fetal life span, beginning very early with and decreased uteroplacental perfusion with fetal development of peripheral receptors (seventh to ninth hypoxia. Adequate monitoring of the maternal circulation gestational week), which are abundant by the 20th week. permits the timely administration of vasopressors, such as The afferent system in the substantia gelatinosa of the ephedrine or phenylephrine [5,9]. dorsal horn develops from the 10th to 13th week on, with connections between peripheral receptors and spinal cord As an alternative to a high concentration of volatiles, starting as early as eight weeks of gestation. Connections short-lasting profound uterine relaxation is possible with from the dorsal horn to the thalamus begin at 14 weeks and intravenous (i.v.) nitroglycerin. Although nitroglycerin are completed by 20 weeks. Thalamocortical connections crosses the placenta, fetal effects seem mild because of are present from 13 weeks and are more developed by a large placental metabolization [4,10,11]. 26–30 weeks [14].Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.
  3. 3. Anesthesia for fetal surgery De Buck et al. 295Pain perception involves multilayered networks, forming products, such as opioids, cross the placenta. When thediverse feedback and feed-forward loops. The neural mother is not under general anesthesia, an infusion ofelements in these networks are not inactive during their remifentanil provides both maternal and fetal sedation.development, and they mature through a process of This infusion was very successful in providing fetalplasticity that is impulse driven. Therefore pain percep- immobilization during fetoscopy [17]. Longer actingtion in the fetus does not involve the same structures as in opioids can also be used to provide fetal analgesia bythe adult. The immature pain system is capable of maternal administration. This route of administration ismounting behavioral responses to painful stimuli, as seen limited by the maternal side effects of the drug the movements of the fetus away from the stimulusduring fetal procedures [14]. When access to the fetus has been established, it is possible to administer opioids, muscle relaxants, vagoly-Pain is viewed as a homeostatic function, where the tics, or other drugs directly to the fetus i.v. through thethalamus plays a central role, regulating the different umbilical vein or i.m. Opioids given to the fetus have aspinal–brainstem loops. Fetal development of the slower metabolization than that in the adult and have athalamus occurs much earlier than the sensory cortex longer duration of action. Fentanyl , for example, can be[14]. given in a dose of 5–20 mg/kg. Atropine, 20 mg/kg, is frequently given to prevent bradycardic responses toEven if the sensory cortex itself is not fully developed, stimulation of the fetus [9].other structures in the developing brain can act as surro-gates for it. Neurons in the subplate zone form an earlyintrinsic synaptic network with inputs from the thalamus Open fetal surgeryand the neocortex. Subplate neurons serve as targets for As open fetal surgery involves a maternal laparotomy andcortical and thalamic afferents and as pathway pioneers a hysterotomy, these procedures are mostly performedfor corticothalamic efferents. They coordinate receptive under general anesthesia [18]. After a rapid sequencefields and are involved in gyrification. They are particu- induction (risks for aspiration), anesthesia is maintainedlarly susceptible to the preterm injuries that trigger by volatile anesthetics, increasing the concentrationcognitive and sensory deficits. The subplate zone is when the uterus is incised. At least two MAC is usedactive in the second-trimester human fetus [14]. for profound uterine relaxation [5]. If it is needed, i.v. nitroglycerin can also be used for short-lasting uterineAs fetal brain development is influenced by external relaxation [4,10,11]. The use of high concentrationsstimuli, strong and recurring stimuli may result in the of volatiles and nitroglycerin often necessitates vaso-formation of aberrant synapses, causing hyperactive pressor support for adequate uteroplacental perfusion.responses to later stimuli. In preterm infants, repetitive Ephedrine and phenylephrine can be given in smallnoxious stimulation in neonatal intensive care leads to boluses, and a drip of dopamine or dobutamine can beincreased cardiovascular responses, increased salivary started to support maternal circulation. Invasive monitor-cortisol response and altered pain thresholds and abnor- ing of the arterial blood pressure is required, and a centralmal pain-related behavior later in childhood [14]. venous line is useful for the measurement of filling status and the administration of inotropes or vasopressors. CareSo even if the fetus or premature newborn may not should be taken not to be too liberal with fluids, as theperceive pain on a cortical level, he or she may still be mother is at risk for postoperative pulmonary to process the information from nociceptive stimuli Only blood losses over 100 ml should be compensated,and model the developing nervous system in response and maintenance fluid should be restricted to 500 mlto pain. crystalloid [18].Therefore, one must consider providing analgesia or For postoperative pain control, the mother benefits fromanesthesia to the fetus during a fetal surgical procedure. an epidural catheter and patient-controlled analgesia.Ways of providing this are by transplacental passage, by Adequate postoperative pain control is necessary fordirect i.v., or i.m. administration of drugs to the fetus, or the prevention of uterine contractions and prematureby intraamniotic administration. delivery. Circulating oxytocin concentrations were lower in an animal model of open fetal surgery when adequateWhen the mother is under general inhalation anesthesia, postoperative analgesia was provided with morphinethe volatile anesthetics will pass into the fetus, with a infusions [12].somewhat slower uptake [9]. The fetus has lower MACvalues, and the concentration of volatile anesthetics is After exposure of the fetus, fetal analgesia and musclegenerally kept high for uterine relaxation, so the fetus will relaxation, for example, fentanyl 20 mg/kg and pancuro-be anesthetized during the procedure. Different i.v. nium or vecuronium 0.2 mg/kg can be given i.m. FetalCopyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.
  4. 4. 296 Obstetric and gynecological anesthesia resuscitation drugs, for example, atropine 0.2 mg/kg and When a local or locoregional technique is used, the fetus epinephrine 1 mg/kg should also be ready for the surgeon does not get any anesthesia or analgesia. It is possible to to administer if needed [9]. give the fetus some analgesia and sedation by adminis- tering remifentanil i.v. to the mother. Excellent results Perioperative fetal monitoring is possible with a sterile have been reported with this technique for the immo- pulse oximeter or by continuous fetal echocardiography. bilization of the fetus during lasering of connecting Fetal blood gas sampling from the umbilical artery is vessels in TTTS [17]. For more painful procedures also possible. on the fetus, direct fetal analgesia and muscle relaxation can be given either i.m. or through the umbilical vessels As fetal bleeding is frequent and the fetus has a very low [20]. blood volume, fetal transfusion blood , type O negative and leukocyte-free, should be available in aliquots of 50 ml. Ex-utero intrapartum procedure or operations Prophylactic tocolysis is already started preoperatively by on placental support rectal indomethacin 50 mg, and postoperative tocolysis can The ex-utero intrapartum procedure was originally devel- be provided, together with adequate analgesia, by mag- oped for the removing of a tracheal balloon and the nesium sulfate, loading dose of 6 g i.v., followed by an securing of the neonatal airways before the umbilical infusion of 3 g/h [9]. A careful monitoring of recovery of cord was cut, so that the neonate could remain oxyge- muscular function is needed, as magnesium sulfate poten- nated by the placental circulation [5]. Recently, many tates nondepolarizing neuromuscular blockers. Other other indications for this type of operation, on placental tocolytic drugs that can be used postoperatively are i.v. support (OOPS), have been selected. This operation is atosiban, oral nifedipine or subcutaneous terbutalin. now performed not only on children with a congenital malformation that poses a problem for the airways, such Frequent complications after open fetal surgery are pul- as large intraoral masses or cysts, cystic hygromas of the monary edema, premature labor, amniotic fluid leak and neck or other fetal neck masses, but also on children that fetal demise. Sometimes admission to ICU may be neces- have a congenital high airway obstruction syndrome sary [18]. (CHAOS), so that the airway can be secured by laryngo- scopy and intubation or tracheostomy before the separation from the placenta [4,5,7]. Treatment of Minimally invasive fetal surgery intrathoracic lesions with a compromised lung expansion Minimally invasive procedures can be ultrasound-guided is also described [6,23]. needling for fetal blood sampling, intrauterine transfu- sion, selective feticide, radiofrequency ablation of a non- The installation of an extracorporeal membrane oxyge- viable twin [19] or fetal cardiac punction for laser atrial nator (ECMO) prior to separation from the placental septostomy [20]. Fetoscopic procedures, intrauterine circulation (EXIT-to-ECMO procedure) allows the time endoscopic surgery, can be performed for laser coagu- on placental support to remain short, preventing major lation of connecting vessels in twin-to-twin transfusion maternal complications, especially bleeding. The neo- syndrome (TTTS), selective cord occlusion, or fetal nate can then be further treated while his oxygenation is endoscopic tracheal balloon occlusion (FETO), and for provided by the ECMO [23]. the subsequent removal of the tracheal balloon or the resection of urethral valves [1,3,12,21]. Most frequently, these procedures are performed while the mother is under general anesthesia, with a type of As these procedures are less invasive for the mother, a anesthesia comparable to open fetal surgery and with general anesthesia is not always necessary [18,19]. Many high concentrations of volatile anesthetics for uterine of the ultrasound-guided needling procedures can be relaxation [5,7,10]. This uterine relaxation is needed performed using local anesthesia of the maternal abdomi- for the prevention of placental separation and the nal wall alone [20]. For most of the fetoscopic procedures, preservation of the uteroplacental circulation. As the either a local anesthesia or a locoregional anesthesia such uteroplacental circulation is dependent on maternal as epidural or combined spinal epidural anesthesia is used hemodynamic stability, inotropes, vasopressors or fluids [19,21,22]. may be used for the treatment of maternal hypotension. Invasive monitoring is highly recommended [5,7]. If a general anesthesia is necessary, the same type of anesthesia as for an open fetal procedure can be used. Cases in which a general anesthesia is to be avoided (e.g. High concentrations of volatile anesthetics are less for patients at risk for malignant hyperthermia [11] or needed because the trauma to the uterus and the uterine with a known difficult airway [24]), a locoregional tech- activity is smaller [9,21]. nique such as a combined spinal epidural anesthesiaCopyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.
  5. 5. Anesthesia for fetal surgery De Buck et al. 297 5 Kuczkowski T, Krzysztof M. Advances in obstetric anesthesia: anesthesia for(CSE) is also possible, but with the use of nitroglycerin fetal intrapartum operations on placental support. J Anesth 2007; 21:243–i.v. to provide a rapid reversible profound uterine relaxa- 251.tion [4,6,10,11,24]. Recent review of the anesthetic approach for EXIT/OOPS procedures. The author works at the University of California, San Diego, a center that pioneered and has gained a large experience with these and other fetal inter- ventions.One of the major maternal complications after an EXIT 6 Kern C, Ange M, Morales. Ex utero intrapartum treatment (EXIT), a resuscita-procedure is major intraoperative and postoperative tion option for intra-thoracic foetal pathologies. Swiss Med Wkly 2007;blood loss. Intraoperative blood loss can be exaggerated 137:297–285. Case series and thorough discussion about the EXIT procedure for intrathoracicduring lengthy procedures. Postoperative blood loss is fetal lesions, requiring more or less invasive neonatal interventions.correlated with uterine atony, possibly from prolonged 7 Marwan A, Crombleholme TM. The EXIT procedure: principles, pitfalls, andeffects of tocolytics [5,6,7,23]. progress. Semin Pediatr Surg 2006; 15:107–115. 8 Goodman S. Anesthesia for nonobstetric surgery in the pregnant patient. Semin Perinatol 2002; 26:136–145.Fetal monitoring during the procedure is possible as for 9 Myers LB, Cohen D, Galinkin J, et al. Anaesthesia for fetal surgery. Paediatropen fetal surgery, with a fetal pulse oximeter, fetal Anaesth 2002; 12:569–578.echocardiography and fetal umbilical blood sampling 10 George RB, Melnick AH, Rose EC, Habib AS. Case series: combined spinalfor fetal blood gases and acid–base status [7]. epidural anesthesia for Cesarean delivery and ex utero intrapartum treatment procedure. Can J Anesth 2007; 54:218–222. This study shows that EXIT/OOPS procedures can be performed under LRA withFetal anesthesia is achieved either by transplacental the use of nitroglycerin for uterine relaxation.administration when the mother is under general 11 Rosen MA, Andreae MH, Cameron AG. Nitroglycerin for fetal surgery:anesthesia or by direct fetal i.v. or i.m. administration fetoscopy and ex utero intrapartum treatment procedure with malignant hyperthermia precautions. Anesth Analg 2003; 96:698–700.of opioids and muscle relaxants [7]. 12 Santolaya-Forgas J, Romero R, Mehendale R. The effect of continuous morphine administration on maternal plasma oxytocin concentration and uterine contractions after open fetal surgery. J Matern Fetal Neonatal Med 2006; 19:231–238.Conclusion 13 Lee SJ, Peter Ralston HJ, Drey EA, et al. Fetal pain: a systematicTo provide anesthesia for fetal surgery is a challenging multidisciplinary review of the evidence. JAMA 2005; 294:947 –task. There are always at least two patients that need to taken care of, mother and one or more fetuses. Both 14 Lowery CL, Hardman MP, Manning N, et al. Neurodevelopmental changes of fetal pain. Semin Perinatol 2007; 31:275–282.these patients have their specific needs and special Up-to-date overview of the evidence about fetal pain/nociception and its long-termconsiderations for anesthesia. The pregnant mother, with effects. This article puts the political and ethical debate around the issue of fetal pain in a more scientific perspective, focusing also on the long-term effects of fetalall the changes in physiology caused by pregnancy, is at nociceptive stimulation.increased overall risk when she needs to undergo a 15 Rychik J, Tian Z, Cohen MS, et al. Acute cardiovascular effects of fetal surgerygeneral anesthesia. In the event of maternal locoregional in the human. Circulation 2004; 110:1549–1556.or local anesthesia, the fetus is not anesthetized by 16 Smith RP, Gitau R, Glover V, Fisk NM. Pain and stress in the human fetus. Eurtransplacental passage, so it needs special attention to J Obstet Gynecol Reprod Biol 2000; 92:161–165.provide at least a form of analgesia. The discussion about 17 Van de Velde M, Van Schoubroeck D, Lewi LE, et al. Remifentanil for fetal immobilization and maternal sedation during fetoscopic surgery: a rando-the existence and the nature of fetal pain is not yet mized, double-blind comparison with diazepam. Anesth Analg 2005; 101:finished, but one should remain objective and choose 251–258.the anesthetic regimen that would best preserve the 18 Golombeck K, Ball RH, Lee H, et al. Maternal morbidity after maternal–fetal surgery. Am J Obstet Gynecol 2006; 194:834–839.normal fetal development. 19 Lee H, Wagner AJ, Sy E, et al. Efficacy of radiofrequency ablation for twin- reversed arterial perfusion sequence. Am JObstet Gynecol 2007; 196: 459e1–459e4. The anesthetic technique moved from general anesthesia to loco-regional anaes-References and recommended reading thesia as the experience of the team increased.Papers of particular interest, published within the annual period of review, havebeen highlighted as 20 Quintero RA, Huhta J, Suh E, et al. In utero cardiac fetal surgery: laser atrial of special interest septotomy in the treatment of hypoplastic left heart syndrome with intact atrial of outstanding interest septum. Am J Obstet Gynecol 2005; 193:1424–1428.Additional references related to this topic can also be found in the Current 21 Myers LB, Bulich LA, Hess P, Miller NM. Fetal endoscopic surgery: indicationsWorld Literature section in this issue (pp. 414–415). and anaesthetic management. Best Pract Res Clin Anaesthesiol 2004; 18:231–258.1 Deprest J, Jani J, Lewi L, et al. Fetoscopic surgery: encouraged by clinical 22 Myers LB, Watcha MF. Epidural versus general anesthesia for twin–twin experience and boosted by instrument innovation. Semin Fetal Neonatal Med transfusion syndrome requiring fetal surgery. Fetal Diagn Ther 2004; 19: 2006; 11:398–412. 286–291.2 Cass DL. Fetal surgery for congenital diaphragmatic hernia: the North 23 Kunisaki SM, Fauza DO, Barnewolt CE, et al. Ex utero intrapartum treatment American experience. Semin Perinatol 2005; 29:104–111. with placement on extracorporeal membrane oxygenation for fetal thoracic3 Deprest J, Gratacos E, Nicolaides KH, et al. Fetoscopic tracheal occlusion masses. J Pediatr Surg 2007; 42:420–425. (FETO) for severe congenital diaphragmatic hernia: evolution of a tech- A novel approach to the EXIT procedure for very difficult neonatal airway manage- nique and preliminary results. Ultrasound Obstet Gynecol 2004; 24:121– ment and reduction of maternal operative risks. 126. 24 Benonis JG, Habib AS. Ex utero intrapartum treatment procedure in a patient4 Okutomi T, Saito M, Kuczkowski KM. The use of potent inhalational agents for with arthrogryposis multiplex congenita, using continuous spinal anesthesia the ex-utero intrapartum treatment (exit) procedures: what concentrations? and intravenous nitroglycerin for uterine relaxation. Int J Obstet Anesth 2008; Acta Anaesthesiol Belg 2007; 58:97–99. 17:53–56.Case report on the use of i.v. nitroglycerin and a normal concentration of volatiles Case report on the use of LRA and IV nitroglycerin for an EXIT procedure in afor uterine relaxation. patient with a known difficult airway.Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.