Case Reports Anesthetic Considerations of an Infant with Be&with-Wiedemann Syndrome
Joseph D. Tobias, MD,* Sandra Lowe, MD,? George W. Holcomb III, MD+ Departments of Pediatrics, Anesthesiology, and Surgery, Vanderbilt University, Nashville, TN.
The case of a 3-day-old infant with Beckwith-Wiedemann syndrome who required anesthetic care during closure of an abo!ominal wall defect is presented. Beckwith-Wieo!emann syndrome comprises a constellation of clinical features, including macroglossia, macrosomia, omphalocele, visceromegaly, mild microcephaly, facial nevus Jammeus, horizontal earlobe creases, and renal medullary dysplasia. Due to the high rate of omphalocele in this syndrome, anesthetic care is frequently required during the neonatal period. Many of these infants (greater than 50%) are born prematurely. Therefore, their anesthetic care may be further complicated by associated diseases of prematurity, such as hyaline membrane disease. Additional anesthetic implications of this syndrome relate to the occurrence and management of hypoglycemia and polycythemia. Careful intraoperative management of glucose homeostasis is particularly important, since eventual neurologic outcome and intelligence will be normal provided prolonged neonatal hypoglycemia is avoided. Preoperative evaluation of the cardiac and genitourinary system, including echocardiography and renal ultrasound, are recommended because of the frequent occurrence of associated anomalies with omphalocele.
*Associate Professor
of Anesthesiology
TAssistant Professor
of Anesthesiology
SAssistant Professor
of Surgery
and Pediatrics
Received for publication March 17, 1992; revised manuscript cepted for publication May 8, 1992. 0 1992 Butterworth-Heinemann
Clin. Anesth. 4:484-486,
484
J. Clin. Anesth.,
1992.
vol. 4, November/December
syndrome;
Introduction Beckwith-Wiedemann syndrome, initially reported in 1963,*,’ comprises a constellation of clinical features, including macroglossia, macrosomia, visceromegaly, mild microcephaly, facial nevus flammeus, horizontal earlobe creases, and renal medullary dysplasia. Characteristic laboratory findings include hypoglycemia (due to hyperinsulinemia with islet cell hyperplasia) in approximately one-third of patients and polycythemia. Anesthetic care is frequently required during the neonatal period for repair of associated abdominal wall defects (omphalocele) or during placement of central venous catheters needed to deliver hypertonic glucose for the treatment of refractory hypoglycemia. Anesthetic care also may be required during the first decade of life related to the increased risk of intra-abdominal tumors (i.e., Wilms’ tumors, adrenocortical tumors, and hepatoblastoma). We present and discuss the anesthetic implications of a S-day-old infant with Beckwith-Wiedemann syndrome during primary closure of an omphalocele.
Case Report
Address reprint requests to Dr. Tobias at the Department of Pediatrics, Division of Pediatric Anesthesiology/Critical Care Medicine, Vanderbilt University, Medical Center North T-01 18, Nashville, TN 37232, USA.
J.
Keywords: Beckwith-Wiedemann hypoglycemia; polycythemia.
1992
ac-
A 3.16 kg male sarean section. phalocele were the diagnosis of
infant was delivered at 34 weeks by ceMacrosomia, macroglossia, and an omnoted in the delivery room, suggesting Beckwith-Wiedemann syndrome. As the
*Beckwith JB: Extreme cytomegaly of the adrenal fetal cortex, omphalocoele, hyperplasia of kidneys and pancreas and Leydigcell hyperplasia. Another syndrome? Paper presented at the Annual Meeting of Western Society for Pediatric Research, Los Angeles, November 11, 1,963.
Anesthesia
abdominal wall defect was small (4 cm), we decided to delay closure until treatment of the infant’s complicating medical conditions. During this time, the defect was kept covered with gauze moistened with saline. Polycythemia [hematocrit (Hct) 7 l%] was treated with a partial exchange transfusion, with the removal of 40 ml of blood and replacement with an equal volume of normal saline. During the child’s first 24 hours of life, hypoglycemia (glucose less than 30 mg/dl) developed, despite a glucose infusion of 3 mg/kg/min. The hypoglycemia was eventually controlled by increasing the glucose infusion to 6 mg/kg/min (D,, at 11.2 ml/hr). During the child’s second day of life, he developed hyaline membrane disease, which required endotracheal intubation and mechanical ventilation. Treatment also included two doses of exogenous surfactant. The infant was scheduled for primary closure of the omphalocele on the third day of life. Preoperative examination showed stable vital signs. Arterial blood gases were stable on ventilatory settings that included an inspired oxygen concentration of 0.6, ventilatory pressures of 29/5 cmH,O, and an intermittent mandatory ventilation rate of 40. Cardiovascular status was stable on dopamine at 5 kg/kg/min, the net Hct was 48%, and the remainder of the preoperative laboratory evaluation, including serum electrolytes, glucose, BUN, creatinine, and calcium, were within normal limits. The infant was brought to the operating room, and routine monitors were placed. Anesthesia was induced with midazolam 0.1 mg/kg, muscle relaxation was achieved with vecuronium 0.1 mg/kg, and intraoperative anesthesia consisted of fentanyl 12 pg/kg. Intraoperative fluids included D,, at 11.2 ml/hr, with third-space and evaporative losses replaced with lactated Ringer’s solution. Intraoperative serum glucose was measured every 30 to 45 minutes and remained 80 to 120 mg/dl throughout the procedure. The abdominal wall defect was closed without any noticeable effect on cardiorespiratory function. The infant was returned to the neonatal intensive care unit (ICU) and had an uneventful postoperative course.
Discussion We present the case of a neonate with Beckwith-Wiedemann syndrome who required anesthetic care during omphalocele repair. Our patient illustrates the various laboratory and physical features that may affect anesthetic care, as well as the need for preoperative preparation of such patients. As macroglossia is a key component of the syndrome, the immediate concern is its impact on airway management. This will depend on the degree of macroglossia and may vary from significant stridor and airway obstruction in the awake state to difficult intubation and bag/mask ventilation following the induction of anesthesia and muscle paralysis. Although our evaluation of this infant suggested that airway management would not be compromised by the macroglossia, awake endotracheal intubation should be considered if airway problems are anticipated. As with our patient, many of these infants (greater
and Beckwith-Wiedemann
syndrome:
Tobias et al.
than 50%) are born prematurely. Their anesthetic care is further complicated by associated diseases of prematurity, such as hyaline membrane disease. The preoperative assessment of respiratory function is particularly important, and the timing of surgical intervention may be difficult, since early closure of the omphalocele will lessen the likelihood of complications, while the development of severe hyaline membrane disease may affect the timing of the surgical procedure and intraoperative anesthetic care. The recent introduction of exogenous surfactant into clinical practice in many neonatal ICUs may lessen the severity of hyaline membrane disease. The characteristics of the omphalocele in infants with Beckwith-Wiedemann syndrome are similar to those occurring spontaneously. The size may vary from a small defect at the base of the umbilicus to a large sac containing the liver, spleen, and majority of the small and large intestine. Preoperative evaluation of the cardiac and genitourinary system, including echocardiography and renal ultrasound, are recommended due to the high incidence of associated anomalies with omphalocele. Early closure is necessary to prevent complications such as infection, dehydration, and hypothermia. Prior to surgical intervention, fluid balance must be closely monitored to avoid excessive evaporative losses of fluid, leading to preoperative hypovolemia. With large defects, intraoperative fluid requirements will be high (10 to 12 ml/ kg/hr) until closure of the defect is achieved. Small defects may be primarily closed, while larger defects may require a staged procedure with a synthetic silo or pouch. Attempted closure of larger defects may severely compromise cardiorespiratory function because of the sudden increase in intra-abdominal pressure. This increase may require unacceptably high inflating pressures to achieve adequate ventilation and oxygenation or even preclude effective gas exchange. Additionally, the increase in intra-abdominal pressure may compromise cardiovascular function by decreasing venous return. When primary closure of a large defect is contemplated, intraoperative monitoring of airway pressure, central venous pressure, and intragastric pressure may be helpful in differentiating those infants who will tolerate primary closure from those who will require a staged procedure.2 Aside from the fluid and electrolyte changes that may occur with large evaporative losses, the primary metabolic concern of these patients is glucose homeostasis. Symptomatic hypoglycemia occurs in roughly 50% of infants with Beckwith-Wiedemann syndrome. Hypoglycemia usually occurs within the first 24 hours of life but may be delayed for up to 72 hours. Early detection and ongoing treatment of hypoglycemia is particularly important, since eventual neurologic development and intelligence will be normal provided profound hypoglycemia does not occur. Hypoglycemia should be treated with a bolus dose of 200 mg/kg of glucose (2 ml/kg of 10% glucose) followed by a continuous infusion of glucose at 6 to 8 mg/kg/min.g Infants who remain hypoglycemic despite glucose administration of 12 to 16 mg/kg/min may require furJ. Clin. Anesth.,
vol. 4, November/December
1992
485
Case Reports
ther pharmacologic treatment, including steroids, diaor somatostatin. All of these zoxide, epinephrine, therapies may be associated with significant adverse effects. Glucose infusions of 16 to 18 mg/kg/min require large fluid volumes, resulting in hypervolemia. Side effects of epinephrine include lactic acidosis and cardiovascular effects, while diazoxide may result in hypotension and sodium retention. In addition to hypoglycemia, the other laboratory finding that frequently requires preoperative treatment in infants with Beckwith-Wiedemann syndrome is polycythemia. Treatment by partial exchange transfusion is recommended for all neonates with an Hct greater than 70% and in symptomatic infants with an Hct greater than 60%. Partial exchange transfusion is carried out by removing small aliquots of blood (10% of the estimated blood volume) and replacing it with either normal saline or 5% albumin, with the goal of reducing Hct to less than 55%. The total amount to be removed can be calculated from the following formula:4 volume exchange
blood of (ml) = volume
observed ’
- desired
observed
Hct
Hct
Following exchange transfusion, Hct should be monitored every 6 hours and the process repeated as needed. One other consideration in the care of these infants is the isolated report of the association of Beckwith-Wiedemann syndrome with immune deficiency.5 The report deals with one family with the immunologic defect characterized as a severe combined immune deficiency with thymic aplasia. Although the association may be coinci-
486
J. Clin.
Anesth.,
vol. 4, November/December
1992
dental, simple precautions, such as the irradiation of blood products to prevent the possibility of graft-verse-host disease, seem appropriate. In summary, we have presented the anesthetic management of a neonate with Beckwith-Wiedemann syndrome. The high rate of abdominal wall defects (omphalocele) as a component of this syndrome requires anesthetic care during the neonatal period for many of these infants. Of primary concern to the anesthesiologist are issues related to the perioperative occurrence and management of hypoglycemia and polycythemia. These concerns are further complicated by the frequent association of prematurity and its associated problems.
References 1. Wiedemann HR: Compiexe malformatif familial avec hernie ombilicale et macroglossie: Un “syndrome nouveau”? J Genet Hum 1964;13:223-32. DL, et al: Hemodynamic effects 2. Yaster M, Buck JR, Dudgeon of primary closure of omphalocele/gastroschisis in human newborns. Anesthesiology 1988;69:84-8. 3. Lilien LD, Pildes RS, Srinivasan G, Voora S, Yeh TF: Treatment of neonatal hypoglycemia with minibolus and intravenous glucose infusi0n.J. Pediatr 1980;97:295-8. 4. Gross S, Shurin SB, Gordon EM: The blood and hematopoietic system. In: Fanaroff AA, Martin RJ, Merkatz IR, eds. Behrman’s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. St. Louis: C.V. Mosby, 1988:741-2. 5. Greene RJ, Gilbert EF, Huang S, et al: Immunodeficiency associated with exomphalos-macroglossia-gigantism syndrome. J Pediatr 1973;82:814-20.
Joseph D. Tobias, MD,* Sandra Lowe, MD,? George W. Holcomb III, MD+ Departments of Pediatrics, Anesthesiology, and Surgery, Vanderbilt University, Nashville, TN.
The case of a 3-day-old infant with Beckwith-Wiedemann syndrome who required anesthetic care during closure of an abo!ominal wall defect is presented. Beckwith-Wieo!emann syndrome comprises a constellation of clinical features, including macroglossia, macrosomia, omphalocele, visceromegaly, mild microcephaly, facial nevus Jammeus, horizontal earlobe creases, and renal medullary dysplasia. Due to the high rate of omphalocele in this syndrome, anesthetic care is frequently required during the neonatal period. Many of these infants (greater than 50%) are born prematurely. Therefore, their anesthetic care may be further complicated by associated diseases of prematurity, such as hyaline membrane disease. Additional anesthetic implications of this syndrome relate to the occurrence and management of hypoglycemia and polycythemia. Careful intraoperative management of glucose homeostasis is particularly important, since eventual neurologic outcome and intelligence will be normal provided prolonged neonatal hypoglycemia is avoided. Preoperative evaluation of the cardiac and genitourinary system, including echocardiography and renal ultrasound, are recommended because of the frequent occurrence of associated anomalies with omphalocele.
*Associate Professor
of Anesthesiology
TAssistant Professor
of Anesthesiology
SAssistant Professor
of Surgery
and Pediatrics
Received for publication March 17, 1992; revised manuscript cepted for publication May 8, 1992. 0 1992 Butterworth-Heinemann
Clin. Anesth. 4:484-486,
484
J. Clin. Anesth.,
1992.
vol. 4, November/December
syndrome;
Introduction Beckwith-Wiedemann syndrome, initially reported in 1963,*,’ comprises a constellation of clinical features, including macroglossia, macrosomia, visceromegaly, mild microcephaly, facial nevus flammeus, horizontal earlobe creases, and renal medullary dysplasia. Characteristic laboratory findings include hypoglycemia (due to hyperinsulinemia with islet cell hyperplasia) in approximately one-third of patients and polycythemia. Anesthetic care is frequently required during the neonatal period for repair of associated abdominal wall defects (omphalocele) or during placement of central venous catheters needed to deliver hypertonic glucose for the treatment of refractory hypoglycemia. Anesthetic care also may be required during the first decade of life related to the increased risk of intra-abdominal tumors (i.e., Wilms’ tumors, adrenocortical tumors, and hepatoblastoma). We present and discuss the anesthetic implications of a S-day-old infant with Beckwith-Wiedemann syndrome during primary closure of an omphalocele.
Case Report
Address reprint requests to Dr. Tobias at the Department of Pediatrics, Division of Pediatric Anesthesiology/Critical Care Medicine, Vanderbilt University, Medical Center North T-01 18, Nashville, TN 37232, USA.
J.
Keywords: Beckwith-Wiedemann hypoglycemia; polycythemia.
1992
ac-
A 3.16 kg male sarean section. phalocele were the diagnosis of
infant was delivered at 34 weeks by ceMacrosomia, macroglossia, and an omnoted in the delivery room, suggesting Beckwith-Wiedemann syndrome. As the
*Beckwith JB: Extreme cytomegaly of the adrenal fetal cortex, omphalocoele, hyperplasia of kidneys and pancreas and Leydigcell hyperplasia. Another syndrome? Paper presented at the Annual Meeting of Western Society for Pediatric Research, Los Angeles, November 11, 1,963.
Anesthesia
abdominal wall defect was small (4 cm), we decided to delay closure until treatment of the infant’s complicating medical conditions. During this time, the defect was kept covered with gauze moistened with saline. Polycythemia [hematocrit (Hct) 7 l%] was treated with a partial exchange transfusion, with the removal of 40 ml of blood and replacement with an equal volume of normal saline. During the child’s first 24 hours of life, hypoglycemia (glucose less than 30 mg/dl) developed, despite a glucose infusion of 3 mg/kg/min. The hypoglycemia was eventually controlled by increasing the glucose infusion to 6 mg/kg/min (D,, at 11.2 ml/hr). During the child’s second day of life, he developed hyaline membrane disease, which required endotracheal intubation and mechanical ventilation. Treatment also included two doses of exogenous surfactant. The infant was scheduled for primary closure of the omphalocele on the third day of life. Preoperative examination showed stable vital signs. Arterial blood gases were stable on ventilatory settings that included an inspired oxygen concentration of 0.6, ventilatory pressures of 29/5 cmH,O, and an intermittent mandatory ventilation rate of 40. Cardiovascular status was stable on dopamine at 5 kg/kg/min, the net Hct was 48%, and the remainder of the preoperative laboratory evaluation, including serum electrolytes, glucose, BUN, creatinine, and calcium, were within normal limits. The infant was brought to the operating room, and routine monitors were placed. Anesthesia was induced with midazolam 0.1 mg/kg, muscle relaxation was achieved with vecuronium 0.1 mg/kg, and intraoperative anesthesia consisted of fentanyl 12 pg/kg. Intraoperative fluids included D,, at 11.2 ml/hr, with third-space and evaporative losses replaced with lactated Ringer’s solution. Intraoperative serum glucose was measured every 30 to 45 minutes and remained 80 to 120 mg/dl throughout the procedure. The abdominal wall defect was closed without any noticeable effect on cardiorespiratory function. The infant was returned to the neonatal intensive care unit (ICU) and had an uneventful postoperative course.
Discussion We present the case of a neonate with Beckwith-Wiedemann syndrome who required anesthetic care during omphalocele repair. Our patient illustrates the various laboratory and physical features that may affect anesthetic care, as well as the need for preoperative preparation of such patients. As macroglossia is a key component of the syndrome, the immediate concern is its impact on airway management. This will depend on the degree of macroglossia and may vary from significant stridor and airway obstruction in the awake state to difficult intubation and bag/mask ventilation following the induction of anesthesia and muscle paralysis. Although our evaluation of this infant suggested that airway management would not be compromised by the macroglossia, awake endotracheal intubation should be considered if airway problems are anticipated. As with our patient, many of these infants (greater
and Beckwith-Wiedemann
syndrome:
Tobias et al.
than 50%) are born prematurely. Their anesthetic care is further complicated by associated diseases of prematurity, such as hyaline membrane disease. The preoperative assessment of respiratory function is particularly important, and the timing of surgical intervention may be difficult, since early closure of the omphalocele will lessen the likelihood of complications, while the development of severe hyaline membrane disease may affect the timing of the surgical procedure and intraoperative anesthetic care. The recent introduction of exogenous surfactant into clinical practice in many neonatal ICUs may lessen the severity of hyaline membrane disease. The characteristics of the omphalocele in infants with Beckwith-Wiedemann syndrome are similar to those occurring spontaneously. The size may vary from a small defect at the base of the umbilicus to a large sac containing the liver, spleen, and majority of the small and large intestine. Preoperative evaluation of the cardiac and genitourinary system, including echocardiography and renal ultrasound, are recommended due to the high incidence of associated anomalies with omphalocele. Early closure is necessary to prevent complications such as infection, dehydration, and hypothermia. Prior to surgical intervention, fluid balance must be closely monitored to avoid excessive evaporative losses of fluid, leading to preoperative hypovolemia. With large defects, intraoperative fluid requirements will be high (10 to 12 ml/ kg/hr) until closure of the defect is achieved. Small defects may be primarily closed, while larger defects may require a staged procedure with a synthetic silo or pouch. Attempted closure of larger defects may severely compromise cardiorespiratory function because of the sudden increase in intra-abdominal pressure. This increase may require unacceptably high inflating pressures to achieve adequate ventilation and oxygenation or even preclude effective gas exchange. Additionally, the increase in intra-abdominal pressure may compromise cardiovascular function by decreasing venous return. When primary closure of a large defect is contemplated, intraoperative monitoring of airway pressure, central venous pressure, and intragastric pressure may be helpful in differentiating those infants who will tolerate primary closure from those who will require a staged procedure.2 Aside from the fluid and electrolyte changes that may occur with large evaporative losses, the primary metabolic concern of these patients is glucose homeostasis. Symptomatic hypoglycemia occurs in roughly 50% of infants with Beckwith-Wiedemann syndrome. Hypoglycemia usually occurs within the first 24 hours of life but may be delayed for up to 72 hours. Early detection and ongoing treatment of hypoglycemia is particularly important, since eventual neurologic development and intelligence will be normal provided profound hypoglycemia does not occur. Hypoglycemia should be treated with a bolus dose of 200 mg/kg of glucose (2 ml/kg of 10% glucose) followed by a continuous infusion of glucose at 6 to 8 mg/kg/min.g Infants who remain hypoglycemic despite glucose administration of 12 to 16 mg/kg/min may require furJ. Clin. Anesth.,
vol. 4, November/December
1992
485
Case Reports
ther pharmacologic treatment, including steroids, diaor somatostatin. All of these zoxide, epinephrine, therapies may be associated with significant adverse effects. Glucose infusions of 16 to 18 mg/kg/min require large fluid volumes, resulting in hypervolemia. Side effects of epinephrine include lactic acidosis and cardiovascular effects, while diazoxide may result in hypotension and sodium retention. In addition to hypoglycemia, the other laboratory finding that frequently requires preoperative treatment in infants with Beckwith-Wiedemann syndrome is polycythemia. Treatment by partial exchange transfusion is recommended for all neonates with an Hct greater than 70% and in symptomatic infants with an Hct greater than 60%. Partial exchange transfusion is carried out by removing small aliquots of blood (10% of the estimated blood volume) and replacing it with either normal saline or 5% albumin, with the goal of reducing Hct to less than 55%. The total amount to be removed can be calculated from the following formula:4 volume exchange
blood of (ml) = volume
observed ’
- desired
observed
Hct
Hct
Following exchange transfusion, Hct should be monitored every 6 hours and the process repeated as needed. One other consideration in the care of these infants is the isolated report of the association of Beckwith-Wiedemann syndrome with immune deficiency.5 The report deals with one family with the immunologic defect characterized as a severe combined immune deficiency with thymic aplasia. Although the association may be coinci-
486
J. Clin.
Anesth.,
vol. 4, November/December
1992
dental, simple precautions, such as the irradiation of blood products to prevent the possibility of graft-verse-host disease, seem appropriate. In summary, we have presented the anesthetic management of a neonate with Beckwith-Wiedemann syndrome. The high rate of abdominal wall defects (omphalocele) as a component of this syndrome requires anesthetic care during the neonatal period for many of these infants. Of primary concern to the anesthesiologist are issues related to the perioperative occurrence and management of hypoglycemia and polycythemia. These concerns are further complicated by the frequent association of prematurity and its associated problems.
References 1. Wiedemann HR: Compiexe malformatif familial avec hernie ombilicale et macroglossie: Un “syndrome nouveau”? J Genet Hum 1964;13:223-32. DL, et al: Hemodynamic effects 2. Yaster M, Buck JR, Dudgeon of primary closure of omphalocele/gastroschisis in human newborns. Anesthesiology 1988;69:84-8. 3. Lilien LD, Pildes RS, Srinivasan G, Voora S, Yeh TF: Treatment of neonatal hypoglycemia with minibolus and intravenous glucose infusi0n.J. Pediatr 1980;97:295-8. 4. Gross S, Shurin SB, Gordon EM: The blood and hematopoietic system. In: Fanaroff AA, Martin RJ, Merkatz IR, eds. Behrman’s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. St. Louis: C.V. Mosby, 1988:741-2. 5. Greene RJ, Gilbert EF, Huang S, et al: Immunodeficiency associated with exomphalos-macroglossia-gigantism syndrome. J Pediatr 1973;82:814-20.
