Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair.

INTRODUCTION: The use of perioperative tocolytic agents in fetal surgery is imperative to prevent preterm labor. Indomethacin, a well-known tocolytic agent, can cause ductus arteriosus (DA) constriction. We sought to determine whether a relationship exists between preoperative indomethacin dosing and fetal DA constriction. MATERIALS AND METHODS: This is an IRB-approved, single-center retrospective observational case series of 42 pregnant mothers who underwent open fetal myelomeningocele repair. Preoperatively, mothers received either 1 (QD) or 2 (BID) indomethacin doses. Maternal anesthetic drug exposures and fetal cardiac dysfunction measures were collected from surgical and anesthesia records and intraoperative fetal echocardiography. Pulsatility Index was used to calculate DA constriction severity. Comparative testing between groups was performed using t- and chi-square testing. RESULTS: DA constriction was observed in all fetuses receiving BID indomethacin and in 71.4% of those receiving QD dosing (p = 0.0002). Severe DA constriction was observed only in the BID group (35.7%). QD indomethacin group received more intraoperative magnesium sulfate (p < 0.0001). Minimal fetal cardiac dysfunction (9.5%) and bradycardia (9.5%) were observed in all groups independent of indomethacin dosing. CONCLUSIONS: DA constriction was the most frequent and severe in the BID indomethacin group. QD indomethacin and greater magnesium sulfate dosing was associated with reduced DA constriction.

The effect of prenatal treatment with steroids and preterm delivery in a model of myelomeningocele on the rabbit foetus.

Damage of neural elements (spinal cord and encephalus) in myelomeningocele (MMC) seems to be progressive during gestation because of amniotic fluid chemical contact and continuous leakage of CSF. We studied the effect of preterm delivery and steroid treatment in a model of MMC in the rabbit foetus. Twelve New Zealand White rabbits underwent laparotomy and hysterotomy at 23 days of gestation. Fifty-nine out of 107 foetuses underwent lumbar laminectomy (three to four levels). Dura was opened to expose the neural elements to the amniotic fluid. Six rabbits underwent caesarean section on gestational day 31 for fetal harvest; three of them had no treatment (group T) and three received corticosteroid treatment (group TC). The other six rabbits underwent caesarean section on gestational day 29 for fetal harvest (preterm delivery); three of them had no treatment (group P) and three received corticosteroid treatment (group PC). Alive newborns were clinically, neurophysiologically and histologically analysed. None of mothers died during the procedure. After birth, animals in group preterm showed statistically significant less deformity than animals in group at term. Lower kyphosis was observed in group PC (preterm and steroids). Pain related and spontaneous mobility of lower extremities was higher in groups treated with corticosteroids (TC and PC). Only newborns at term (T and TC groups) showed response to evoked potentials (CMEPs). The response was earlier and higher in group treated with steroids (TC). Histologically, we observed progressive lesion of the spinal cord. Groups treated with steroids (TC and PC) show less inflammatory response. Arnold-Chiari malformation was present in all groups. Animals in group preterm with steroids show statistically significant less herniation than those group at term. Preterm delivery and prenatal steroid therapy seem to be an effective treatment to get less neural injury (spinal cord and encephalus) in myelomeningocele foetuses.

Discernment of adipose versus nervous tissue: a novel adjunct solution in lipomyelomeningocele surgery.

OBJECTIVE: To determine a solution capable of discerning adipose versus nervous tissue, to aid in surgical separation of the adipose tissue which appears to be visually indistinguishable from nervous tissue in lipomyelomeningoceles (LMMs). METHODS: The following solutes (in normal saline) were investigated, both at 25 and 37 degrees C: beta-carotene, vitamin D, vitamin E, lecithin, hydrogen peroxide, lipase, protease, hyaluronidase, partially purified collagenase, purified collagenase, trypsin, trypsin plus purified collagenase and non-solute-containing saline (control). Each solution was applied to a pediatric lipoma to determine gross effects over a period of approximately 30 min. If a solution appeared to affect the adipose tissue grossly, studies of functional in vivo sensory evoked and spontaneous potentials using that particular solution were conducted upon sheep spinal cord, nerve roots, dura and peripheral nerve. Additionally, histological studies were conducted to determine the effect of that solution upon adipose tissue, spinal cord, myelin, dura and nerve roots. RESULTS: Of all solutions investigated, partially purified collagenase type 1 (T1C; Lot M0M4322, Code CLS-1, Worthington Biochemical Corporation, Lakewood, N.J., USA) at 37 degrees C was the most successful in grossly altering the consistency and appearance of adipose tissue. This change was more apparent over 20-30 min following application of the solution to the adipose tissue. Solutions not containing T1C did not show appreciable results; purified collagenase plus trypsin did not appear comparable or superior to T1C. No significant histological or functional change was noted when comparing the spinal cord, nerve rootlets, myelin, dura or peripheral nerve from the T1C-treated group versus normal (untreated) control groups. CONCLUSION: T1C appears to be a potentially effective solution for application during LMM surgery in the acute setting, and such use of an adjunct solution may significantly aid in the safe surgical resection of LMMs. Pending further research, this technique may be applied for other indications which require discernment or alteration of adipose versus nervous tissue.

Use of hyaluronidase in the central nervous system.

Hyaluronidase, an enzyme which depolymerizes the mucopolysaccharide hyaluronic acid, appears to be tolerated by the human central nervous system and in the anterior chamber of the rabbit eye. Two patients with hydrocephalus and meningomyelocele had their condition curtailed by intraventricular injections of hyaluronidase, and in a third patient its use permitted delay of shunting. It was apparently effective in preventing a reaccumulation of cystic fluid in an intramedullary neurofibroma, and in reversing adverse effects of adhesive arachnoiditis of the spinal cord. Hylauronidase seems worthy of further investigation in disorders of the central nervous system.