Recent advances in anaesthesia for intrauterine and foetal surgery : Indian Journal of Anaesthesia

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Recent advances in anaesthesia for intrauterine and foetal surgery

Nath, Gita; Subrahmanyam, M; Jayanthi, R1; Singh, Ranju2; Ramesh, S1; Ahuja, Vanita3

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Indian Journal of Anaesthesia 67(1):p 11-18, January 2023. | DOI: 10.4103/ija.ija_964_22
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Abstract

INTRODUCTION

Progressive technological advances in prenatal diagnostic techniques have enabled the early detection of potentially correctable foetal anomalies. Timely treatment by intrauterine intervention can prevent irreversible organ damage and post-natal morbidity. In this narrative review, we aim to look at recent developments in anaesthesia for these procedures.

Historical background: Intraperitoneal blood transfusion for hydrops foetalis by Sir William Liley in 1963 was the first successful foetal procedure.[1] As late as 2002, most foetal surgeries in the United States were being done in only three centres.[2] The whole situation changed in 2011 when the landmark Management of Myelomeningocoele Study (MOMS) was published, which showed the dramatic improvement in clinical course after prenatal versus post-natal surgery.[3]

Indications for foetal surgery: In essence, foetal surgery is for those malformations which would impede organ development irreversibly, but would allow normal development if corrected. Recent changes in the criteria for foetal surgery include the following:[2]

  • Goals have expanded from just foetal survival to reduction of morbidity.
  • It is no longer required to be a singleton pregnancy.
  • Women themselves are now willing to accept risk to themselves to ensure foetal survival. Hence, the importance of careful risk-benefit analysis and counselling to ensure realistic expectations.
  • A multidisciplinary team-based approach, ethics oversight and participation in registries are encouraged.
  • Should be done in centres with expertise, experience and credentialling; and appropriate infrastructure and facilities.

TYPES OF FOETAL SURGICAL PROCEDURES

Minimally invasive foetal procedures [Figure 1], performed in the early or mid-gestation period of pregnancy, include needle-based and foetoscopic procedures. Examples of needle-based procedures are percutaneous umbilical blood sampling, balloon valvuloplasty for aortic stenosis, and radiofrequency ablation for selective foetal reduction.

F1
Figure 1:
Minimally invasive surgery. (a) Laser photocoagulation for twin–twin transfusion syndrome (Reproduced with permission from the Colorado Foetal Care Centre, Aurora, Colorado). (b) Tracheal balloon insertion for CDH. (c) CO2 insufflation for improved visibility. CDH: Congenital diaphragmatic hernia; CO2: Carbon dioxide

Foetoscopy (FETENDO) initially done via laparotomy[4] is now done percutaneously under ultrasound guidance.[2] Examples of foetoscopic interventions include foetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH), laser photocoagulation for twin–twin transfusion syndrome, release of amniotic bands, placement of vesico-amniotic and peritoneo-amniotic shunts; and myelomeningocoele (MMC) repair in some centres.[2,4-6] Foetoscopic surgery avoids the need for a hysterotomy, preserving the possibility of vaginal delivery during subsequent pregnancies.

Open mid-gestational foetal procedures are performed through a uterine incision, under regional or general anaesthesia. These procedures include repair of MMC, excision of lesions such as sacrococcygeal teratoma, congenital cystic adenomatoid/pulmonary malformation (CCAM/CPAM)[2] and temporary tracheal occlusion for CDH.[7]

Open procedures preclude vaginal birth in the current as well as subsequent pregnancies. Hence, there are continuing attempts to do as many of these surgeries foetoscopically as possible.

Ex-Utero Intrapartum Treatment (EXIT) procedure is done for a foetal life-threatening lesion, maintaining foetal oxygenation via the placental circulation. It is mainly for lesions in the upper airway which make it difficult or impossible to breathe after delivery. Originally performed for CDH foetuses with tracheal plugging, it is now performed for other causes of airway obstruction.[4,7] The head and upper chest of the foetus are delivered, and airway is secured before clamping the cord. EXIT procedure can also facilitate transition to extracorporeal membrane oxygenation (ECMO).

It is important to understand the management concerns in specific congenital defects [Table 1].

T1
Table 1:
Specific conditions amenable to foetal interventions

ANAESTHESIA CONSIDERATIONS FOR FOETAL SURGERY

Maternal safety concerns: Foetal surgery is primarily directed at improving outcomes in the foetus; the mother is only a bystander in the process and derives no direct benefit. Ensuring maternal safety is of prime importance. The various anatomical and physiological changes of pregnancy should be kept in mind [Table 2].[8] Left uterine displacement should be strictly maintained till the end of the procedure or delivery of the foetus. Invasive monitoring and additional intravenous access will be necessary during EXIT procedure. Use of tocolytic agents such as nitroglycerine increases cardiovascular instability and necessitates the use of vasopressor agents. Considering the risk of haemorrhage in the setting of uterine hypotonia, adequate blood products should be arranged beforehand for open foetal and EXIT procedures.[9]

T2
Table 2:
Anatomical and physiological changes of pregnancy

Foetal physiology: The foetal cardiovascular system has a parallel circuit with a blood volume 110–160 ml/kg, over 50% of which is in the placenta. Since the output of right and left ventricles is not equal, the combined cardiac output is described and is normally 425–550 ml/kg/min.[10] Cardiac output is mainly determined by the heart rate, since the stroke volume is limited. Foetal bradycardia (<100 beats per minute) is a strong indicator of distress; and hypoxia, hypothermia and noxious stimuli are common stressors for the foetus.[11]

Thalamocortical connections mediating pain perception only develop at 23–30 weeks gestation, but even before this time, noxious stimuli cause increased catecholamine and cortisol secretion. This stress response causes placental vasoconstriction and bradycardia and can also induce premature labour.[11] Specific foetal analgesia is not required if non-innervated tissue is involved, such as placenta or umbilical vessels.[2]

A common misconception is that maternal analgesic drugs suffice to produce adequate foetal analgesia. However, extraction index (foetal/maternal ratio of drug concentration) depends on biophysical properties of the drug molecules (molecular weight, lipid solubility, ionisation) and acid–base differences across the placental membrane. Hence, it is advisable to directly administer analgesics to the foetus.[11]

Management of uterine tone: Any foetal intervention necessitates tocolysis to prevent premature labour. For minimally invasive procedures, oral non-steroidal anti-inflammatory drugs (NSAIDs) [indomethacin 50–100 mg per oral (PO)/per rectal (PR)] and calcium channel blockers (nifedipine 10–20 mg PO q 6-8 h) can be used. When general anaesthesia is given, maintaining an end-tidal volatile anaesthetic concentration of 1.5–2 minimum alveolar concentration (MAC) is effective at relaxing the uterus. Nitroglycerine (50–100 mg intravenous boluses, 0.5–1 mg/kg/min infusion) or terbutaline (250 mg intravenous bolus, 5–10 mg/min) can be used for open and EXIT procedures. Magnesium sulphate and atosiban infusions given during and after the procedure prevent premature onset of labour.[1,12]

Loss of amniotic fluid when the uterus is opened can stimulate uterine contraction as well as placental separation. Hence, the foetus is only delivered partially, and warm crystalloid is infused into the amniotic cavity to keep the intrauterine pressure up.

After baby delivery in EXIT procedure, all uterine relaxants should be stopped and uterotonic agents should be given to promote uterine contraction and retraction. It should be noted that magnesium sulphate or atosiban should not be used in EXIT procedures as they are long acting. For open mid-gestational procedures, uterine relaxants are continued post-operatively.[2,4]

Maintenance of utero-placental blood flow: Since autoregulation is absent in the utero-placental circulation, maternal blood pressure should be maintained at or above baseline with vasopressors and intravenous fluids, especially in the presence of sympathetic block or effect of tocolytic agents. Left uterine displacement of 15° should be applied after 18 weeks gestation, or even earlier in the case of multiple pregnancies. Uterine contraction and umbilical cord compression should be minimised as they can both decrease the utero-placental blood flow.[1]

Foetal monitoring: Doppler ultrasonography is used to monitor the foetal heart rate during minimally invasive and open surgery, and pulse oximetry may be used during EXIT procedure. Continuous echocardiography is done during foetal cardiac interventions.[13]

Resuscitation for foetal bradycardia:

  1. Increase oxygen delivery to foetus
    1. Optimise maternal fraction of inspired oxygen (FiO2) and ventilation
    2. Maintain maternal blood pressure – Left uterine displacement, vasopressors, fluids
    3. Improve uterine relaxation
    4. Check for placental abruption

  2. Post-placental measures
    1. Relieve cord compression, reposition foetus
    2. Increase uterine volume – infuse warm fluid
    3. Improve foetal cardiac function – injection of adrenaline or atropine into the foetal heart (cardiocentesis) or into umbilical cord (cordocentesis), foetal blood transfusion, foetal chest compressions[14]

Foetal anaesthesia: Analgesia and immobility are essential during foetal surgery to block the stressful noxious stimuli and to facilitate safe performance of the foetal intervention, respectively. Extraction ratios of anaesthetic agents range from 0.38 to 0.8 (sevoflurane – 0.38, propofol – 0.5–0.8, fentanyl – 0.5). The time required for foetal concentrations to build up also needs to be considered. Hence, a combination of opioid (fentanyl 20 mg/kg), muscle relaxant (rocuronium 2 mg/kg) and anticholinergic (atropine 20 mg/kg) should be administered to the foetus as an intramuscular injection [Table 3].[1,11]

T3
Table 3:
Drugs and equipment for foetal anaesthesia and resuscitation

ANAESTHETIC MANAGEMENT

Preoperative assessment and planning: A multidisciplinary team approach is needed to discuss the risks versus benefits for both the mother and baby. The anaesthesiologist is a critical member of this team and will evaluate the anaesthetic risks in the mother. Blood grouping and screening should be done for all patients, and cross-matching should be done for open foetal surgery and EXIT procedures. In addition, O-negative leuco-reduced irradiated cytomegalovirus (CMV)-negative blood should be arranged for the foetus. Important foetal information for the anaesthesiologist is gestational age, foetal lesion needing correction, cardiac function, estimated weight for drug dosing and location of the placenta which determines patient positioning and the need to exteriorise the uterus. Contingency planning must also be done for events like maternal or foetal cardiac arrest, haemorrhage and need for unplanned caesarean delivery.[9]

Minimally invasive foetal surgery: Less invasive procedures (examples are amnioreduction and umbilical blood sampling) can be performed under local anaesthesia in the ultrasound room without involving the anaesthesiologist. Others are done under neuraxial anaesthesia with minimal to moderate sedation so that airway reflexes are preserved and the mother can be repositioned if necessary. General anaesthesia may be necessary if the procedure is prolonged.

Maternal blood pressure is maintained at baseline or higher with fluids and vasopressors (phenylephrine). Profound uterine relaxation is not considered necessary now, and NSAIDs such as indomethacin (PO or PR) and oral calcium channel blockers such as nifedipine are sufficient. Pulmonary oedema has been reported during foetoscopic surgery when 8 L excess fluid was infused; hence, inflow and outflow of irrigation fluids should be strictly audited.[15] Foetal analgesia and immobility are ensured with an intramuscular injection of the cocktail described above.

Open mid-gestational procedures: These can be done under regional, but general anaesthesia is preferred. Epidural for post-operative pain management reduces stress and thus preterm labour. Invasive arterial monitoring and two large bore lines are inserted for volume replacement. Tocolysis is achieved with volatile anaesthesia at 1.5 to 2 MAC and/or nitroglycerin infusion. Supplementation with intravenous anaesthesia reduces foetal cardiac dysfunction. Arterial pressure is maintained at or above baseline. To prevent premature labour, magnesium sulphate 4 g intravenous bolus is followed by an infusion of 1–2 g/h for 24–48 hours. Fluid administration should be judicious, to prevent pulmonary oedema, and neuromuscular function should be monitored.

Ex-utero intrapartum treatment procedures: There are case reports of EXIT procedures done under regional anaesthesia,[16] but more commonly they are done under general anaesthesia. Invasive monitoring, access for volume replacement, tocolysis and maintenance of uterine pressure by amniotic infusion are the components of anaesthetic care. Tocolysis is achieved with volatile anaesthesia at 1.5 to 2 MAC and/or nitroglycerine infusion. Unlike open surgery, EXIT patients need the uterine tone to increase rapidly after delivery, to prevent excessive blood loss. The volatile agent concentration is reduced, nitroglycerine infusion stopped, and uterotonic agents are given.

Airway management during ex-utero intrapartum treatment surgery: This requires meticulous preoperative multidisciplinary planning. The airway team consists of paediatric anaesthesiologist, neonatologist, paediatric surgeon and otorhinolaryn gologist. The mother is in the lithotomy position so that the airway team can access the baby’s airway from between the legs. A mock drill should be conducted beforehand, planning where each member of the team will be positioned and where each section of equipment will be placed [Figure 2]. There should be a separate monitor for the foetus; airway and monitoring equipment should be sterilised and arranged on a separate trolley [Table 3].

F2
Figure 2:
Arrangement of personnel and equipment for EXIT procedure. ENT: Ear, nose, throat; EXIT: Ex-utero intrapartum treatment

Based on prenatal imaging, an airway strategy is formulated in advance consisting of Plan A, Plan B and so on. Finite time is allotted for each approach, for example 5 minutes each for direct/video laryngoscopy, rigid bronchoscopy and tracheostomy. Other options are to use a laryngeal mask as a conduit for fibre-optic intubation, or as a rescue device to maintain the airway till a tracheostomy is done.[17] In the case of large neck masses, partial decompression of the mass may allow access to the trachea. The last option, if all these techniques are unsuccessful, is ECMO. If the airway is not secured by the time the placenta separates, the foetus will go on to bradycardia and cardiac arrest, for which standard guidelines should be followed; but this situation is likely to end in foetal demise. Team members should leave the surgical field promptly once their tasks are completed, to facilitate the role of the next team.

Various algorithms with essential elements have been proposed for airway management during EXIT.[18-20] They include various essential elements [Figure 3].

F3
Figure 3:
Airway management in EXIT procedure. MRI: Magnetic resonance imaging; FOI: Fibre-optic intubation; ECMO: Extracorporeal membrane oxygenation; EXIT: Ex-utero intrapartum treatment, LMA: Laryngeal mask airway

OUTCOMES FROM FOETAL SURGERY

A systematic review and meta-analysis concluded that the FETO procedure for CDH increased the neonatal survival at 30 days and 6 months with a relative risk of 5.8 and 10.5, respectively. However, the rates of premature rupture of membrane and preterm birth were higher, and the gestational age at delivery decreased by 2 weeks.[21]

The MOMS of 2011 found a reduced incidence of hydrocephalus and improved mental and motor development after prenatal surgery compared to correction after birth, when patients were assessed at 30 months. Obstetric complications included preterm birth, placental abruption and pulmonary oedema related to tocolysis; and over 1/3 of the women had thinning or an area of dehiscence at the hysterotomy site.[3]

In a recent systematic review of 235 cases of EXIT surgery, there were 13 adverse maternal events; 11 of them were post-partum haemorrhage (4.7%). There were 29 adverse foetal events (12.2%), with failure of securing the airway in 8 (3.4%). In 40 cases out of 235 (17%), foetal or neonatal death occurred.[22]

Maternal complications: In a meta-analysis of 10,596 foetal surgeries, open surgery had a complication rate of about 21% compared to 6% in foetoscopic surgery. Serious complications occurred in 4.5% of open and 1.7% of foetoscopic procedures.[23]

Mirror syndrome is the development of maternal pulmonary oedema when there is foetal hydrops. The features are very similar to preeclampsia, such as weight gain, hypertension, proteinuria, elevated uric acid, creatinine and liver enzymes, and even headache and visual disturbances. Treating the foetal hydrops, for instance, by inserting a peritoneo-amniotic shunt, relieves these symptoms.[24,25]

SUMMARY

Outcomes of foetal surgery have greatly improved with advances in imaging technology, better understanding of foetal and maternal physiology and refinements in surgical and anaesthetic techniques. The anaesthesiologist plays a crucial role in risk assessment, multidisciplinary coordination, maintaining maternal and foetal homeostasis and optimising surgical conditions. A clear understanding of the type of foetal defect and the foetal surgery planned helps to formulate a suitable management plan.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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Keywords:

EXIT procedure; foetal resuscitation; foetal surgery; foetal therapy; maternal anaesthesia; uteroplacental perfusion

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