In any case the exact percentage risk is of little importance since we would never deny antenatal amniocentesis to persons within these pedigrees who were known by systematic family studies to be carriers and who requested that the test be performed. The finding of a (13;8) translocation in one of the sons of family D (0,53) was unexpected and very interesting. Perhaps his mother's (21 ;22) translocation-carrier constitution predisposed her to meiotic breakage as has been suggested in other reports.69 It appears to have been to his great disadvantage, as his wife had four miscarriages before producing one phenotypically normal child. The miscarriages were presumably due to unbalanced chromosome strLlcture leading to nonviable fetuses. The investigation of this large kin-
ship is being continued. We urge family physicians to have karyotyping done in all newborn children with Down's syndrome, even those born to older mothers. It is true that only about 1% of all cases of Down's syndrome are caused by a familial translocation, but when a translocation is found, investigation of the parents and other relevant family members should be undertaken without delay. Limitation of family size to control the number of carrier children might be an acceptable suggestion to parents at risk. We thank Dr. Louis Dallaire, Montreal, for the karyotyping in one of the family members; Dr. George Fraser and Mrs. Joan Sampson, Ottawa, for their advice; Dr. Henri A. Bertrand, Maniwaki, PQ, for sending blood specimens from one of the branches of the family; and the family members for their helpful cooperation.
References 1. JACOBS PA, BUCKTON KE, CUNNINGHAM C,
et al: An analysis of the break points of structural rearrangements in man. I Med Genet 11: 50, 1974 2. Paris Conference (1971): Standardization in human cytogenetics. Birth Defects Orig Art Ser 8 (7): 1, 1972 3. CHAPMAN CJ, GARDNER RJM, VEALE AMO: Segregation analysis of a large t(21q22q)
family. I Med Genet 10: 362, 1973 4. STENE J: A statistical segregation analysis of (21 q22q) translocations. Hum Hered 20: 465, 1970 5. HAMERTON IL: Rohertsonian translocations in man: evidence for prezygotic selection.
Cytogenetics 7: 260, 1968
6. KOHN G, ARONsON M, MELLMAN WI: Spon-
taneous D/G translocation in fibrohiasts derived from a patient with trisomy 21 mosaicism. Clin Genet 5: 113, 1974 7. Witiss L, WOLF CB: Familial C :G translocation causing mitotic non-disjunction. Am I Dis Child 116: 609, 1968 8. ArKINS L, BARTsoCAs CS, PORTER P3: Diverse
chromosomal anomalies in a family. I Med Genet 5: 314, 1968 9. THOMAS GH, BIAS WB: Occurrence of a presumptive C-B translocation carrier 46,XY,t(?Cp-;Bp) in a family of D;G translocation carriers 45,D-,G-,t(DqGq). I Med
Genet 6: 382, 1969
General anesthesia in Elsenmenger's syndrome R.K. WEBER,* MD; A.J. BUDA,f MD; D.L. LEVENE,* MD
The anesthetic management of a woman with Elsenmenger's syndrome undergoing abdominal hysterectomy with general anesthesia is described. Proper anesthetic management of patients with this syndrome depends on a knowledge of the pathophysiologic process and associated complications. The potential problems of systemic hypotension, pulmonary embolism and infective endocarditis are outlined. Sudden death is common and pregnancy is a major hazard. On decrit les soins requis lors de l'anesthesie d'une femme souffrant d'un syndrome de Eisenmenger qui subit une hysterectomie abdominale sous anesthesie generale. Chez les patients ayant ce syndrome une anesthesie adequate depend de Ia connaissance de cette entite pathophysiologique et des complications qui lui sont reliees. On discute les problemes causes par l'hypotension generale, l'embolie pulmonaire, l'endocardite infectieuse et Ia grossesse qui sont associ6es. Une mort subite est frequente et Ia grossesse constitue un risque majeur. In patients with intracardiac left-toright shunts at any level the development of permanent pulmonary vascular changes and pulmonary hypertension may cause reversal of the shunt. Eisenmenger's complex was defined by Wood1 as "pulmonary hypertension at From the department of *anesthesia and .the division of cardiology, 4department of medicine, Sunnybrook Medical Centre, University of Toronto Reprint requests to: Dr. DL. Levene, Department of medicine, Sunnybrook Medical Centre, 2075 Bayview Ave., Toronto, Ont. M4N 3M5
systemic level, due to a high pulmonary vascular resistance (over 800 dynes sec./cm.5), with reversed or bidirectional shunt through a large ventricular septal defect". The term Eisenmenger's syndrome includes the above complex and a number of intracardiac defects associated with the development of pulmonary hypertension to systemic levels. The term Eisenmenger's reaction has been used synonymously with Eisenmenger's syndrome.2 Young and Mark3 stated that "although the presence of the Eisenmenger's Syndrome renders the underlying defect inoperable... the natural history, longevity, capacity for activity and ability to withstand stress compare relatively favorably with patients with similar congenital cardiac malformations and lesser increase in pulmonary vascular resistance". A number of patients in their series lived comfortably into the 3rd decade; there were progressively fewer survivors in the 4th, 5th and 6th decades. Presumably some persons with this syndrome on occasion must undergo a noncardiac surgical procedure. Although the risks of such procedures are generally believed to be high, there are few reports in the literature addressing the problem of providing anesthesia and perioperative care for this group of patients. In this paper we describe the management of a 30-year-old woman with Eisenmenger's syndrome who underwent abdominal hysterectomy with general anesthesia. Case report Eisenmenger's syndrome was first sus-
pected at the time of appendectomy when the patient was 16 years old. Five years later exertional syncope appeared, followed 18 months later by episodes of recurrent pulmonary embolism, which forced the discontinuation of oral contraceptives. Tubal ligation was performed and oral anticoagulants were prescribed for ongoing prophylaxis of pulmonary embolism. At age 28 the patient complained of dyspnea and fatigue, presyncope and chest pain, all associated with exertion; she could negotiate two flights of stairs at slow speed. She was holding one full-time job and two part-time jobs and seemed well motivated. Her drug program consisted of digoxin, 0.25 mg once daily, furosemide, 40 mg once daily, and a potassium supplement. Cyanosis at rest and clubbing of fingers and toes were noted. The right ventricle was clinically enlarged and the intensity of the pulmonic component of the second heart sound was greatly increased. A grade 3 ejection systolic murmur with a soft early diastolic blow was audible at the left sternal border. There were no signs of right heart failure and no other abnormal findings in the chest. The electrocardiogram showed right ventricular overload and the chest roentgenogram showed enlargement of the right ventricle and central pulmonary vessels. The presumptive diagnosis of Eisenmenger's syndrome was confirmed by the results of cardiac catheterization: nortic pressure, 125/80 mm Hg (mean, 85 mm Hg); pulmonary artery pressure, 125/60 mm Hg (mean, 86 mm Hg); left ventricular pressure, 125/7 to 10 mm Hg; right ventricular pressure, 125/9 mm Hg; and systemic and pulmonary vascular resistance, 1075 and 1044 dynes/sec .cm5 respectively. The shunt was bidirectional,
CMA JOURNAL/DECEMBER 17, 1977/VOL. 117 1413
with a net flow (right to left) of 1.4 L/min. Ventriculography revealed a large membranous ventricular septal defect. Primary dysmenorrhea became uncontrollable, even with potent analgesics, when the patient was 30 years old. Oral contraceptives were contraindicated and narcotics were refused. Hysterectomy seemed the only solution. The preoperative arterial blood gas values with a fractional intake of oxygen of 0.21 were as follows: pH, 7.47; Paco2, 31 mm Hg; and Pao2, 50 mm Hg; actual bicarbonate concentration was 23 mmol/L. Pulmonary function studies showed only a 50% decrease in gas-exchange parameters. Her weight was 45 kg and her blood pressure 90 to 100/60 mm Hg. Heparin in low dosage and antibiotics (erythromycin and streptomycin) were given preoperatively as prophylaxis of pulmonary embolism and infective endocarditis respectively. Morphine, 10 mg, given 1 hour preoperatively, had optimal sedative effect. Continuous electrocardiographic monitoring was arranged and anesthesia was induced, beginning with inhalation of 100% oxygen and intravenous administration of d-tubocurarine, 6 mg. Three minutes later sodium thiopental, 125 mg, was administered slowly, followed by succinylcholine, 80 mg, for intubation. Anesthesia was maintained by the use of a Bain circuit with a fresh gas flow of nitrous oxide, 4 L/min, and oxygen, 1.5 L/min. Ventilation was controlled with a tidal volume of 600 mL, a respiratory rate of 1 1/mm and an airway pressure of 15 cm H20. A single dose of pancuronium bromide, 2 mg, produced excellent relaxation. One dose of fentanyl citrate, 25 .g, was given 20 minutes after induction of anesthesia. Blood pressure was monitored meticulously by cuff; the systolic pressure was allowed to be 20 to 30 mm Hg above the preoperative level and it did not vary throughout the procedure. The patient's skin remained pink. The head was tilted down by 150; this was well tolerated and caused no change in ventilatory parameters. Measured blood loss was 100 mL, and 500 mL of lactated Ringer's solution was infused. Total operating time was 1 hour and 25 minutes. Following administration of atropine and prostigmine at the end of the procedure the patient awakened and was cooperative. She was transferred to the surgical intensive care unit with oxygen given by mask. Arterial blood gas values 1 hour later, while the patient was breathing 28% oxygen, were as follows: pH, 7.36; Paco2, 39 mm Hg; and Pao2, 64 mm Hg; actual bicarbonate concentration was 25 mmol/L. The patient was out of bed within 2 hours. Anticoagulant and antibiotic therapy was continued throughout the postoperative period and aggressive physiotherapy was given to prevent pulmonary complications.
Discussion There is little information in the literature directly pertaining to the anesthetic and perioperative manage-
of a patient with Eisenmenger's syndrome undergoing a noncardiac surgical procedure. Crawford, Mills and Pentecost4 discussed the considerations relative to pregnancy and the management of vaginal delivery with the use of continuous epidural anesthesia, and Ashling and Fung3 recently described the successful management of a patient undergoing abdominal tubal ligation also with epidural anesthesia. Knowledge of the pathophysiologic aspects of this syndrome is mandatory in selecting the appropriate anesthetic technique. Fixed pulmonary hypertension at the systemic level produces a relatively fixed cardiac output that cannot respond to a decrease in systemic pressure. Systemic hypotension increases the right-to-left shunt, with a resultant increase in arterial hypoxemia that can be life-threatening. Volume overload may increase shunting or lead to right heart failure or both. Therefore, particular attention to volume replacement and careful choice of anesthetic agents and technique are necessary to minimize cardiac and vascular depression. Profound systemic hypotension due to vascular depression is an indication for the prompt use of an a-adrenergic vasopressor. In our patient anesthesia was maintained with inhalation of oxygen in a concentration of 27% to 30%, which produced clinically better oxygenation than normal for her. Reasonably applied intermittent positive pressure breathing did not appear to affect cardiovascular status. Sudden death is relatively common in patients with Eisenmenger's syndrome, the usual explanation being arrhythmias, sudden circulatory collapse or right heart failure in children and heart failure in adults.2 Many sudden deaths thought to be due to pulmonary embolism are, however, unexplained at autopsy.6 Accordingly, because of the risk of pulmonary thromboembolism and paradoxic systemic embolism, heparm was given in low dosage (5000 U subcutaneously every 12 hours) beginning 1½ hours preopetatively and continued postoperatively. Particular attention was paid to the hazard of paradoxic air embolism by the anesthetist in relation to infusion lines and by the surgeon in relation to the opening of large veins or venous sinuses with the patient in a position where vascular air entrapment was possible. Postoperative pulmonary infection with or without atelectasis decreases oxygenation and increases shunting, a critical factor in a patient with borderline oxygenation. Our patient was out of bed within 2 .hours of the end of her operation, and aggressive postoperative physiotherapy was directed to the chest. Knowledge of preoperative arterial blood gas tensions in the pres-
1414 CMA JOURNAL/DECEMBER 17, 1977/VOL. 117
ence of cyanosis can assist in the clinical evaluation of oxygen therapy postoperatively and reduce the number of arterial punctures required. The risk of infective endocarditis was reduced in our case by the administration of appropriate antibiotics before and after the procedure. Jones and Howitt6 reviewed documented pregnancies in patients with proven Eisenmenger's syndrome. Pregnancy is a major threat to these patients whether or not they are symptomatic or cyanotic prior to conception. Maternal mortality was quoted by Jones and Howitt as 27%, far higher than in pregnancy associated with any other form of congenital heart disease, and sudden death in the postpartum period was common. Important risk factors appear to be the increased blood volume due to pregnancy, a high hematocrit, a possible sudden decrease in systemic vascular resistance post partum and perhaps an unexplained rapid increase in pulmonary vascular resistance. Large pulmonary emboli were not shown to be a major factor, but small emboli may initiate a sudden increase in pulmonary vascular resistance. The choice of general or regional anesthesia, especially in surgical procedures in the lower abdomen, usually arises. Inadvertent hypotension may occur with both techniques, as can respiratory complications pre- and postoperatively. An overcautious regional technique may yield an inadequate block, and with general anesthesia that is too light the patient may be aware or the operative conditions may be inadequate. Some individuals will refuse spinal or epidural anesthesia. Careful general anesthesia with the technique described seemed reasonable in our case: cardiac and vascular depression was minimal, and ventilation and oxygenation were well controlled. Judicious use of narcotics yielded good postoperative analgesia and minimal respiratory depression. In addition, general anesthesia allowed the prophylactic use of heparin, a point of some concern if one were planning to penetrate the epidural space. References 1. wOOD P: The Eisenmenger syndrome or pulmonary hypertension with reversed central shunt. Br Med J 2: 701, 755; 1958 2. BRAMMELL HL, VOGEL JHK, PRIOR R, Ct al:
The Eisenmenger syndrome: physiologic reappraisal. Am 679, 1971 3. YOUNG D, MARK H: Fate of Eisenmenger syndrome. Ibid,
a clinical and J Cardiol 28:
the patient with p 658
4. CRAWFORD J5, MILLS WG, PENTECOST BL: A
pregnant patient with Eisenmenger's syndrome - case report. Br J Anaesth 43: 1091, 1971 5. ASHLING 311, FUNG DL: Epidural anesthesia in Eisenmenger's syndrome - a case report. Anesth Anaig (Cleve) 53: 965, 1974 6. JONES AM, Howsrr G: Eisenmenger's syndrome in pregnancy. Br Med J 1: 1627, 1965