A brain-dead pregnant woman with prolonged somatic support and successful neonatal outcome: A grand rounds case with a detailed review of literature and ethical considerations

Abstract

There are increased reports in the medical literature of brain death during pregnancy. In these rare cases, the decision was either to consider discontinuing homeostatic support and mechanical ventilation with an understanding that the fetus then will also die, or to continue full support in an attempt to prolong pregnancy for the purpose of maintaining the fetus alive until maturity. We report the first case in the United Arab Emirates and in literature of somatic support that extended up to 110 days with the successful delivery of a viable fetus. A 35-year-old woman suffered intracranial hemorrhage during the 16^th week of pregnancy that lead to brain death despite maximal surgical and medical management. Upon confirmation of this diagnosis, the patient received full ventilatory and homeostatic support required to prolong gestation and improve the survival prognosis of her fetus. The status of the patient was discussed in a multidisciplinary approach and with the full involvement of her family. Somatic support continued until the patient was 32 of weeks gestation. Obstetric complications of the patient were frequently assessed and managed. Lower segment cesarean section (LSCS) was then performed. A preterm male in breech presentation was delivered with an average weight of 750 gm, and an Apgar score of 6, 7, and 9 at 1, 5, and 10 minutes, respectively. Prolonging somatic support in a pregnant woman with brain death to allow fetal survival resulted in a successful outcome in terms of saving the life of the fetus. The results are consistent with previous published case reports in the literature on the appropriateness and safety of such a strategy that involved an intensive multidisciplinary approach. Despite being a tragedy, maternal death can represent an opportunity to save the life of the fetus and for organ donation. Consensus future recommendations that can guide the management of similar conditions may also be adapted, especially with the growing medical experience in this context.

INTRODUCTION

There are 30 cases reported in the literature between 1982 and 2010 on brain-dead pregnant women whose somatic non-neurological functions were maintained successfully to facilitate fetal maturation in the uterus. However, of the cases reported, 12 viable infants were born and survived the neonatal period.[1] Based on previous reports, the gestational age of the fetus was important in deciding to attempt somatic support following brain death.[2] However, this is no longer an important issue especially with the important advances in life-support technology and critical care that enables the maintenance of vital functions. Additionally, there are case reports that describe the successful prolongation of pregnancy without regard to gestational age at the time of brain death.[1] Spike[3] reported a case in which successful somatic support began at 16 weeks of gestational age. Likewise, Bernstein et al.[4] reported a similar neonatal outcome when somatic support began at 15 weeks gestation. Treatment of maternal physiologic changes and infectious complications due to brain death to maintain somatic survival and close surveillance of the fetus can lead to favorable neonatal outcomes. We report a case of maternal brain death at 16 weeks of gestation with somatic support provided for 110 days and a successful neonatal outcome.

CASE REPORT

Our patient was a 35-year-old woman, gravida 2 para 2, with no previous history of chronic medical illnesses except for gestational diabetes. She presented at 16 weeks of gestation to the emergency department with an acute-onset excruciating headache after waking up in the morning. The patient had tonic-clonic convulsions at home as witnessed by her husband. In the emergency department, the patient had low Glasgow Coma Scores (GCS) that required intubation. At the emergency department, a computed tomography (CT) scan revealed a left frontal hematoma measuring 5 × 2.6 × 3.5 cm with mild edema and mass effect causing a midline shift of 4 mm to the right. There was also bleeding that spread to the left lateral ventricle via the third ventricle into the fourth ventricle. Additionally, there was a left subdural hematoma that measured 4 mm in diameter. The basal cisterns were still open.

CT angiography (CTA) of the brain done on the same day revealed frontal lobe bleeding, carotid bifurcation aneurysm, and a small subarachnoidal bleeding. Especially relevant was the intraventricular bleeding that could lead to a later hydrocephalus. The patient was then sent to the operating room (OR) on the same day where a trial of coiling of the aneurysm failed. The patient was then admitted to the intensive care unit (ICU) for monitoring and supportive measures. She remained sedated on mechanical ventilation (MV). She was noted to have 2 mm size midposition pupils with sluggish reaction to light bilaterally. On the second day, a second trial of endovascular coiling failed.

On the third day in the ICU and upon physical examination, the patient had a sudden dilatation of the left pupil to 3 mm with a sluggish reaction to light, and the right pupil remained 1 to 2 mm in size. Additionally, her heart rate dropped to 55–59 beats/minute with a blood pressure of 110/60 mmHg that was managed with crystalloid and colloid therapy plus low doses of norepinephrine. Urgent CT of the brain was then performed and revealed modest subarachnoidal rebleeding with a spastic reaction of the vessels with extended ischemia in the middle cerebral artery (MCA). Moreover, there were signs of mesotemporal herniation on the left side. The third ventricle was well separated which indicated some flow problem at the aqueduct level.

On the fourth day, the patient was taken for another trial of coiling but that also was difficult; there was also an occlusion of the left carotid system by a thrombus. CT of the brain showed deterioration when compared to the previous examination; the ischemic areas were better demarcated corresponding to the left MCA and part from the left anterior cerebral artery with perforating branches to the basal ganglia. The midline shift had increased and there was an increase in the effacement of gyri and sulci.

Cerebral angiography revealed a thrombosis in the left internal cerebral artery (ICA) and MCA. Of note, there was no carotid artery aneurysm. Partial mechanical thrombectomy for MCA/ICA system was done.

After the last attempt of failed coiling, the pupils became fixed and dilated at 7 mm bilaterally. Therefore, the patient was shifted to the OR on the same day for decompressive craniotomy and placement of external ventricular drains (EVD) for monitoring intracranial pressure (ICP). The patient then came from OR ventilated and sedated with fixed dilated pupils (right pupil 4 mm in size, and left was 7 mm in size) with no cough or gag reflexes and an ICP monitor reading of less than 10 mmHg. On the fifth day, the ICP started rising and reached up to 50 mmHg. Medical management for high ICP was started and included muscle relaxants, mannitol, hypertonic saline infusions, and thiopental coma without success. As such, ICP remained elevated until removal of the monitor on the eighth day of admission.

Upon physical examination, the patients had a GCS of 3 with no gag or cough reflexes, while the pupils were 5 mm dilated in size and fixed. Consequently, sedation was stopped on the ninth day. Apnea test was not done due to a viable fetus and the use of vasopressors, whereas EEG was not done because of the local scalp and skull conditions as the brain tissue was visible.

Upon confirmation of this diagnosis, our patient received full ventilatory and nutritional support, vasoactive drugs, maintenance of normothermia, and other supportive measures required to prolong gestation and improve the survival prognosis of her fetus. The 110-day hospital course of the patient was complicated by medical problems that included severe hypotension managed with vasopressors, and hypertension treated with antihypertensives. Intranasal 1-deamino-8-d-arginine vasopressin (DDAVP, Rhone-Poulenc Rore Pharmaceutical Inc., Collegeville, PA) and water flushes through the nasogastric tube (NG) were initiated for the treatment of diabetes insipidus and hypernatremia. Additionally, the patient developed several episodes of sepsis due to pneumonia, urinary tract infection, and line infection that were treated successfully with antibiotics. Moreover, the patient developed meningitis that was treated with meropenem 2000 mg intravenously three times daily and vancomycin 1000 mg twice daily with a target trough level of 15 to 20 mg/L. Panhypopituitarism was also treated with thyroid hormone replacement and steroids. Hypothermia was managed with passive rewarming and blankets. A tracheostomy was performed on the 18^th hospital day. Early in the hospital course, feeding was initiated through an NG tube. All decisions regarding the treatment of the patient were taken with the consensus of her family. The current status of the patient was discussed with a multidisciplinary approach and involved the adult and infant ethics committees. The decision was to continue somatic support until the patient was 32 weeks gestation and a cesarean section (CS) could be done. An ultrasound scan after admission revealed intrauterine growth retardation (IUGR) with biometry corresponding to 25 weeks gestation, an estimated fetal weight of 650 gm, and oligohydramnios with no other fetal anomalies. Subsequently, intrauterine monitoring of the fetus was performed using serial ultrasounds, heart rate monitoring, and amniocentesis. Betamethasone therapy was also administered for fetal lung maturity and prophylaxis of fetal respiratory distress syndrome.

Lower segment CS was performed. A preterm male in breech presentation was delivered with an Apgar score of 6/7/9 at 1, 5, and 10 min, respectively, and an average weight of 750 gm. The baby was immediately transferred to the neonatal intensive care unit (NICU). Application of nasal continuous positive airway pressure (CPAP) was necessary owing to a mild respiratory distress syndrome.

Apnea test was done twice on the mother with positive results on both occasions. On the basis of the clinical examinations and these confirmatory technical tests, death was pronounced.

DISCUSSION

Brain death of a pregnant woman usually raises a dilemma whether to prolong the maternal homeostasis and ventilatory support to maintain the fetus alive until maturity, or to disconnect life-support measures and terminate life. According to the reported cases in the medical literature,[1] this is the second reported case where prolonged somatic support led to the delivery of a viable child in which the fetus was about 16 weeks of gestation.[3] Moreover, this is the first case reported in the United Arab Emirates. Furthermore, this is the first case in literature with the longest somatic support (110 days). Until this case report, the longest duration of somatic support was reported by Bernstein et al. (107 days).[4] As such, this supports the fact that the gestational age at the time of maternal brain death is not the main consideration in deciding whether to decide somatic support or not. However, gestational age of the fetus can predict the successful delivery of the fetus. Wood et al.[5] showed that the severity of the disability correlates with how extremely children were born as preterm infants. He also showed that at 22, 23, 24, and 25 weeks of gestation, a fetus has about 1%, 11%, 26%, and 44% likelihood of survival with a 0.7%, 5%, 12%, and 23% chances of survival without handicap at 30 months, respectively. Slattery et al.[6] also reported similar findings. Parry et al.[7] also showed that the probability of mortality increases in infants born before 32 weeks gestation. However, the improved outcome for preterm infants can be attributed to closer surveillance of the mother and preterm obstetric interventions and hence the decision of prolonged somatic support must be done on an individualized basis. Until now, the decision to support brain-dead patients and the duration of support have been controversial ethical issues, becoming more complex with the involvement of pregnancy. Moreover, only a few reported cases on managing a brain-dead woman are found in the literature; so ethical issues in this context remain relatively little publicized. Suddaby et al.[8] showed that of 252 brain-dead patients reported, only 5 (2.8%) involved pregnant women. Moreover, as very few women are prepared for such a devastating event with advanced directives or prior statements, the decision for prolonging pregnancy should be taken in collaboration with a surrogate decision maker from the family.[9] Field et al.[10] concluded that ethical considerations should support the decision of maintaining the brain-dead mother despite the technical difficulties and the economic costs incurred in such a case. Additionally, although maternal care during brain death incurs significant costs, increasing the intrauterine time where the brain-dead mother can serve as ‘a natural incubator’ can positively affect neonatal outcomes and therefore can reduce the duration of stay in the NICU and associated costs.[11] Hence, the closer the fetus is to viability, the more justifiable the provision of extended somatic support, especially when considering that the gestational age beyond which therapeutic abortion is permitted has been exceeded.[12] It is noteworthy to say that with extended somatic support, the pregnant mother will serve as an incubator. Therefore, this will violate her right to autonomy and bodily integrity, which are mostly cited issues in this context. However, these issues are not relevant as the patient is already dead.[13] Some professionals suggest that if the mother had a previous inclination to donate her organs, extended somatic support is justifiable to preserve the organs. Others argue that such support is still in the experimental stage with suboptimal knowledge about the adverse effects of the medications on the fetus. However, ethical justification for prolonging the vital functions of the mother can be supported better if she is a prospective organ donor as the fetus would be the first to benefit from receiving the organs of the mother. In the systematic review done by Esmaeilzadeh et al.,[1] organ donation from the brain-dead mother was carried out in 10 patients with an excellent one-year graft survival. For all of those patients, excellent patient and graft outcomes were reported. Of note, maternal somatic support in all the cases ended either after delivery or after organ donation. Also, the number of organs harvested was excellent. In the retrospective analysis of organ donors in brain-dead patients done by Suddaby et al.,[8] five of seven pregnant women were organ donors for 20 transplant recipients. Of 25 donated organs (5 hearts, 5 livers, 10 kidneys, 5 pancreases) in this analysis, only one liver and one pancreas graft were lost.

Consequently, supporting maternal vital functions may be ethically justifiable to support both the birth of a child and possible organ donation.

As events of brain death during pregnancy are infrequent, the wishes of the mother are mostly unknown. Hence, the family should be engaged in decisions made after extensive counseling regarding life-maintenance strategies, prognosis of the mother, and possible damages they may be caused to the fetus. Catlin et al.[14] performed an ethical analysis and suggested discussing issues of brain death during prenatal interviews, and incorporating the fate of the unborn child in the case of such an event in the form of a legal document.

From a medical point of view, somatic support should also involve a meticulous multidisciplinary approach from disciplines that can take care of the mother and the fetus until successful delivery as it is associated with many maternal medical complications. Feldman et al.[15] summarized complications and management when pregnancies with brain death were prolonged with the goal of achieving delivery of a viable infant. Furthermore, hemodynamic changes in the brain-dead mother can induce physiologic stress to the fetus.[16] Therefore, ensuring fetal intrauterine growth and maturation should be done through serial ultrasounds, heart rate monitoring, and amniocentesis due to a few reports on IUGR.[10,11] Fortunately, despite major complications noted in our case, prolonged somatic support was successful. In the systematic review done by Esmaeilzadeh et al.,[1] 12 (63%) of 19 reported cases led to the delivery of a viable child after extended somatic support. Of note, all of the 6 remaining cases were less than or equal to 20 weeks gestational age at the time of brain death. However, the true percentage at which the somatic support can lead to the delivery of a viable child cannot be successfully determined as not all cases with negative and positive neonatal outcomes are reported.

Apparently, special medical support and interventions from various clinical disciplines such as intensive care medicine, obstetrics, neonatology, anesthesiology, neurosurgery, and an ethics committee can lead to successful outcomes. Typically, brain-dead patients are prone to develop hypotension.[17] Adrenal insufficiency can add to hypotension and should be treated with methylprednisolone as it does not readily cross the placenta.[18] However, the initial treatment for hypotension consists of aggressive fluid replacement utilizing crystalloids followed by vasopressors for refractory cases. The endogenously produced vasopressors like norepinephrine and dopamine seem to be safe, whereas vasopressin has the potential to decrease uterine blood flow.[19] Powner et al.[11] reviewed case reports of brain-dead pregnant women with successful delivery of their infants after somatic support. From these reports, preservation of uterine/placental blood flow was the most important priority during somatic support due to the absence of autoregulation of the uterine vasculature. This can result in fetal hypoxia and neurological injury to the fetus during any episode of maternal hypotension. Maintaining normothermia is an important issue as hypothermia can result in IUGR as fetal energy will be directed away from normal growth and maturation. From an infectious point of view, ventilators, urinary catheters, and intravascular catheters are major sources of infection. This can lead to septicemia ultimately which represents the greatest risk for maternal somatic functions. Such infections should be treated aggressively regardless of safety to the fetus as bacteria can develop resistance to antibiotics over a prolonged period of time in the intensive care unit.[20]

Until now, due to the low number of cases that reported a successful somatic support in brain-dead pregnant women, there are no definitive guidelines or proven management strategies in this context and all the interventions are considered experimental.[21] Mallampalli et al.[22] reviewed the expected physiologic changes and highlighted specific recommendations regarding organ support of brain-dead pregnant women.

Prolongation of pregnancy until at least 28 weeks of gestation is preferred especially with stable pregnancy. According to current literature, there is no justification for prolonging pregnancy beyond 32 weeks of gestation especially when glucocorticoid-induced fetal lung maturity with cesarean section is the optimum method.

CONCLUSION

Maternal neurologic injury has a potential for fetal demise without intensive critical care support to the mother. The outcomes reported in our case are in accordance with previously published case reports on the appropriateness and safety of such a strategy that involved a multidisciplinary approach. Prolonging somatic support in a pregnant woman with brain death to allow fetal survival can have favorable outcomes. Despite being a tragedy, maternal death can represent an opportunity to save the life of the fetus and organ harvesting if decided by the surrogate decision maker. Consensus recommendations that can guide the management of similar conditions may also be adapted.