Agenesis of the Left Lung and Total Anomalous Pulmonary Venous Connection

drop remained unchanged, but with no new symptom developing. Administration of cyclophosphamide was discontinued in January, 1974. In January of 1976, the patient developed cough, dyspnea, and fever. Antibiotic therapy was ineffective, and a chest x-ray film in February 1976 showed a diffuse infiltrate involving the entire right lung. Bronchoscopic examination revealed necrotic tissue to be partially obstructing the right upper lobe orifice and bronchus intermedius. A biopsy showed changes of lymphomatoid granulomatosis. On Feb 24, 1976, therapy with cyclophosphamide was restarted, in a dosage producing lymphopenia. Respiratory symptoms worsened, and the chest x-ray 6Im showed further consolidation in the right lung by April 1, 1976 (Fig 1). Levels of arterial blood gases deteriorated to an arterial oxygen pressure (Pa0 2 ) of 40 DUD Hg and an arterial carbon dioxide tension (Pa~) of 24 DUD Hg with the patient receiving therapy with 2 L of supplemental oxygen by nasal cannula. Radiotherapy in a dosage of 1,800 rads to the right hemithorax and an additional 2,250 rads to the right middle lobe was administered in April and May 1976. Within two weeks of therapy, the patient was afebrile and DO longer required therapy with supplemental oxygen. When he was seen in December of 1976, the patient was asymptomatic, except for mild dyspnea on moderate exertion. Levels of arterial blood gases showed a Pa02 of 17 DUD Hg and a PaC02 of 34 DUD Hg with the patient breathing room air. Pulmonary function showed a reduced carbon monoxide diffusing capacity of 14.7 ml/min/mm Hg (predicted normal, 25 to 42 ml/min/mm Hg). The patient's chest x-ray film also showed marked clearing (Fig 2). The patient was then well until February 1977, when he developed signs of hepatic failure. Biopsy of the liver con&rmed extensive involvement with the disease. Despite a course of radiotherapy with 3,000 rads to the liver, the patient died in the middle of April 1977 from progressive hepatic failure. Postmortem examination revealed extensive involvement of the liver, spleen, and abdominal lymph nodes with lymphomatoid granulomatosis. The right lung showed &brosis, particularly of the right upper lobe, but no evidence of lymphomatoid granulomatosis. DlSCUSSION

Although the involvement of lungs, skin, and CNS

in our patient are all commonly seen in lymphomatoid granulomatosis, the development of the subcutaneous mass in the thigh was unique. Therapy with irradiation was effective in resolving this lesion after therapeutic failures with surgical excision and treatment with corticosteroids and chlorambucil. Our patient's life-threatening Pulmonary involvement is not uncommon in this condition; 14 of the 26 deaths in the series of Liebow et all were a result of this complication. AD of these patients bad received therapy with corticosteroids and one bad received treabnent with azathioprine without response.' Our patient's disease lilcewise failed to respond to therapy with cyclophosphamide in dosages producing lymphopenia; however, following therapy with irradiation, dramatic improvement occurred in his clinical status and blood gas levels, along with partial clearing on the chest x-ray film. The absence of lymphomatoid granulomatosis in the irradiated lung at autopsy further supports the eflieacy of this treatment, One can only speculate as to why the hepatic involvement did not respond to radiotherapy, but

10& 10m ET AL

the reason may relate to the volume of tumor and the limitation of dosage that can be given to that organ. Polymorphic reticulosis has been known for years to be radiosensitive, and its nasopharyngeal manifestations often are controlled with radiotherapy. Since some investigators believe this disease to be similar (if not identical) to lymphomatoid granulomatosis," this lends further support to our belief that therapy with irradiation may be of value in localized lesions of lymphomatoid granulomatosis.

REFERENCES 1 Liebow AA, Carrington CRB, Friedman PJ: Lymphomatoid granulomatosis. Hum Patho13:457-558, 1972 2 Liebow AA: The J. Burns Amberson lecture: Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 181:1-18, 1973 3 McDonald TJ, DeRemee RA, Harrison EG, et al: The protean clinical features of polymorphic reticulosis (lethal midline granuloma). Laryngoscope 86:936-945, 1976

Agenesis of the Left Lung and Total Anomalous Pulmonary Venous Connection• Hemodynamic Studies before and after Complete Surgical Correction Robert A Boxer, M.D.;·· Consttmce ]. Hayes, M.D.;t Allan ]. Honlo/, M.D.;t and Robert B. MelUns, M.D.§ A fe.-le InfaDt with DDII8tenI puImoDary apaesJs dec:o.....e . . . . failure do....... by symptoms of oIIstnic:tIve ditIe8Ie of the llirways at 31h moDths of ap. Cardiae ca8leterlzatioa revealed total anomalous .........,. veD01I8 c:onoedloa to the right atrium. DespIte • ....n-e Ieft-............. ODe puImoDaI'y IIdery veloped

wi.

the entire rIPt v~ _ ..... since bIr1II, the patient'. nstiDI pabaoaary ftICIIIar resilbuice was DOrIIUII. Open heart IIUJ'I'9'Y to re..... the c.di8c Iesloo was performed when the infaDt was foar months of aceSullllequent studies revealed _ excellent .......uc _d functioDaI re"", witII normal puImoDary . . . . pressures. ODe year following 1III'geI'y, the chBd is asyDIptomade and has normal arowtIa and developmellt. ~

experiment of nature in which two rare congenital A ndefects coexisted (namely, total anomalous pulmonary venous connection and unilateral pulmonary agene·From the Cardiac and Pulmonary Divisions Department of Pediatrics, Columbia University College ;t Physicians and Surgeons, and Babies Hospital, the Children's Medical and Surgical Center, New York. in part by National Institutes of Health grant IlL

=rted

••Assistant in Clinical Pediabics. t Assistant Professor of Clinical Pediatrics. tAssistant Professor of Pediatrics. §Professor of Pediabics. Reprint requests: Dr. Mellin8, Deptlrimer&t of Pediatrics, Columbia Unioenity Colle.Ee of P & S, 630 West 168th St1'eet, New York City 10032 CHES~

74: 1, JULY, 1978

F'JctmB 1. Chest x-ray film tabn when patient was 31 months of age demonstrates large right lung. mediastinal shift to left, and increased pulmonary vascular markings on right.

sis} was documented in a four-month-old infant. Since

birth the pulmonary blood flow had been markedly increased as the result of "the 1eft-to-right shunt and diversion of the entire right ventricular output to one lung. This case provided a unique opportunity to study the changes in pulmonary hemodynamic data before and after correction of the cardiovascular malformation. CASE REPoRT A female infant weighing 6 Ib 8 oz (2.950 gin) who was delivered at term was noted at two days of age to have Intermittent duskiness and tachypnea. She was in no acute distress and had a respiratory rate of 84/min. The chest was symmetric, with good aeration bilaterally. The results of cardiovascular examination were normal. The electrocardiogram demonstrated right axis deviation and right ventricular

hypertrophy. The chest x-ray film showed absence of the left lung, with a large right lung and mediuHnal shift . to the left. The cardiac silhouette was difBcult to define. Arterial blood gas levels with the patient breathing room air consistently revealed an arterial oxygen saturation (Sa02) of 75 to 80 percent and an arterial carbon dioxide tension of :n mm Hg. An intravenous pyelogram was normal. The infant remaiDed asymptomatic and was discharged with the clinical diagJ!O'N of agenesis of the left lung. At 31 months of age, the infant was readmitted to the hospital in moderately IeYeI'rJ respiratory dJstrea, with a biItory and 8Ddinp suggestive of brondliolitil There was a grade 3/6 panIYItoIic murmur at the upper left ItemaI border and a grade 2/6 diastolic murmur at the left lower ItemaI border. The liver was palpable 3 em below the right COIta1 margin. The chest x-ray film ,( Fig 1) revealed overcircu1ation of a large right lung. The dramatic but transient respoDIe to therapy with diuretic drugs suggested the preseoce of interstitial pulmonary edema. Sublequent cardiac catheterization revealed total anomalouB pulmonary venous connection to the right atrium (Fig 2A) and an absent left pulmonary artery ( Fig 2B); there was also a small patent ductus artIlriosuI. The pnlmonary arterial pJ"eSlUl'e was two-thirds of the systemic pJ"eSlUl'e, the SaO I was 84 percent, and the pulmonary vascular resistance was 2.IS mm Hg/L/min/Iq m (Table 1). Open heart surgery to repair the cardiovucu1ar anomaly was performed under deep hypothermia, at which time no left lung could be Jdentifted. The infant IuId an UDeWlDtful postoperative coune and hal been uymptomatic subequently, with normal growth and development. A chest x-ray film at one year of age showed a marked decreue In the pulmooary vascularity compared to the preoperative chest x-ray film. Repeat cardiac catheterization revealed a pulmonary arterial pressure of 16/4 mm Hg and an SaC>, of 97 percent (Table 1 ); angiographic studies demonstrated unobstructed pulmonary veins returning to a left atrium that was of normal size. OJscussION

Unilateral pulmonary agenesis is a rare congenital anomaly that has been found in only O.()07 pen:ent of

F'JctmB 2. Preoperative angIocardiograms following Injection of contrast material Into right ventricle. A (lefC), Total anoma1ous puImooary venous CODDeCtion to right atrium; and B (right), singlepulmooary artery.

CHEST, 74: 1, JULY, 1978

AGENESIS Of LEfT LUllS 101

Table 1-0. . from Cardioc Cadaeteriaalioa Data Age of patient

Pressure, mm Hg Right pulmonary artery. Systemic systolic arterial Mean pulmonary venous Pulmonary arterial wedge

Systemic

Sao" percent

Ratio of pulmonary /systemlc flow

Before Surgery

Mter Surgery

4mo

lyr

55/20 (27) 80

16/4 (8) 87

5

4

84

97

4.9/1

1/1

Pulmonary vascular resistance, mm Hg/L/min/sq m··

2.5

1.2

*N umbers within parentheses are means.

··Based on assumed oxygen consumption of 150 ml/min/ sq m. 1I

postmortem specimens," Patent ductus arteriosus and septal defects 2, S are commonly associated. In several instances, partial anomalous pulmonary venous connection has been reported in association with unilateral pulmonary agenesisr' however, there is only one report in the literature of the coexistence of total anomalous pulmonary venous connection and absence of a lung; this occurred in a five-week-old infant who initially had severe respiratory distress and died without surgical intervention. 5 Total anomalous pulmonary venous connection is likewise a rare congenital malformation, with a reported incidence of 1.6 to 2 percent6,7 of all congenital cardiac defects. The simultaneous occurrence of pulmonary agenesis and total anomalous pulmonary venous connection may be traced to an abnormality in the embryologic development of the lung and its vascular supply. By the fourth week of embryonic life, the pulmonary venous system is in transition £rom its. primitive association with the systemic venous circulation to its final connection to the left atrium. 8 While these events are OCCUlTing, the primitive lung buds are forming. 8 Theoretically, any insult during this dynamic stage could simultaneously arrest pulmonary development and interfere with the establishment of normal pulmonary venous return. Signs of. increased airway resistance were initially prominent and indistinguishable from those associated with severe bronchiolitis. Hordof and co-workersw attributed the signs of obstructive pulmonary disease in infants with pulmonary vascular engorgement and edema resulting from large left-to-right shunts to (1) extrinsic compression of the larger airways by enlarged pulmonary arteries and cardiac chambers, (2) elevated resistance in smaller airways due to accumulation of peribronchial fluid, and (3) reflex bronchoconstriction. The disappearance of signs of the airways obstruction after surgery supports the premise that the pulmonary symptoms were secondary to pulmonary vascular engorgement and edema and not to intrinsic pulmonary

disease. The pulmonary arterial hypertension in this infant

1.

BOXER, ET AL

resulted from high How of blood, since pulmonary vaseular resistance was low and pulmonary venous pressures were normal. The ·low pulmonary vascular resistance implies that normal regression of the high pulmonary vascular resistance present in the newborn's pulmonary circulation occurred in spite of the increased pulmonary flow of blood through the single lung. The normal postoperative pulmonary vascular pressures and resistance also support this conclusion. The data from postoperative catheterization (Table 1) demonstrated an excellent surgical repair. The normal postoperative pulmonary arterial pressure is consistent with the observation that pulmonary arterial pressure does not rise appreciably until cardiac output more than doubles.'! In a patient with one pulmonary artery, the solitary lung under resting conditions receives approximately twice the normal pulmonary blood flow. Although exercise testing was not feasible in this one-year-old patient, it is possible that mild pulmonary hypertension occurs with physical stress. A solitary lung that is larger than normal is associated with unilateral pulmonary agenesis. 1 •5 •12, 1 8 If agenesis of one lung resulted in marked hyperinflation of the contralateral lung, this could lead to an increase in vascular resistance; however, if there is simply a larger right lung (ie. more alveoli and more blood vessels), overall vascular resistance might remain normal. Thus, the normal vascular resistance recorded at rest in our patient may reflect compensatory growth of the solitary lung. The long-term follow-up of infants who have undergone surgical correction of total anomalous pulmonary . venous connection has indicated normal cardiovascular function. U Since the cardiovascular malformation has been corrected in our patient and the pulmonary vascular pressures are normal, we expect that the clinical course will be the same as in other patients with is0lated agenesis of the lung. Maltz and Nadass reported a mortality of 41 percent (18 patients) among 44 patients with unilateral pulmonary agenesis who were followed for a maximum of 40 years. Fifteen of these 18 deaths occurred during the first year of life and were attributed to severe respiratory disease and associated extrapulmonary anomalies. The absence of additional congenital malformations in our patient who has survived the critical first year of life suggests a favorable long-term prognosis.

REFERENCES 1 Smart J: Complete congenital absence of a lung. Q J Med 15:125-139, 1946 2 Spencer H: Pathology of the Lung. London, Pergamon Press. 1968, p 70 3 VaDe AR: Agenesis of the lung. Am J Surg 89:90-100. 1955 4 Maltz DL, Nadas AS: Agenesis of the lung: Presentation of eight new cases and review of the literature. Pediatrics 42: 175-188, 1968 5 Clark H, Scott RB, Johnson JB: Pulmonary agenesis: Roentgenographic and postmortem findiDgs in one patient; hemodynamic and angiographic &ndings in another.

CHEST, 74: 1, JULY, 1978

Pediatrics 15:761-767, 1955 6 DuShane JW: Total anomalous puImouary veDOUI c0nnection: Clinical aspects. Proc Staff Meetings Mayo CJin 31:167-172, 1956 7 Mehrizi A, Hirsh MS. Taussig HB: Congenital heart disease in the neonatal period: Autopsy study of 170 cases. J Pediatr 65:721-726. 1964 ~ l.angman J: Medical Embryology. Baltimore. Williams and WiIJdDs, 1975. pp 201-223 ~ Thurlbedc W: PostDatal growth and development of the lung. Am Rev Respir Dis 111:803-844, 1975 10 Hordof AI. MeDins RB. Genony WM. et a1: Reversibility of chronic obstructive lung disease in infants following repair of ventricular septal defect. I Pediatr 90:187-191. 1977 11 Coumand A. Riley RL. Himmelstein A, et al: Pulmonary circaJation aod alveolar ventilatioo-perfusion relationships after pneumonectomy. J Thorac Surg 19:80-116. 1950 12 Massumi R. Ta1eghani M. Ellis I: Cardiorespiratory studies in congenital ab8ence of ODe lung. J Tborac Cardiovasc Surg 51:561-568. 1968 13 Warner AL, Paladino NM. Schwartz W. et a1: The relationship of agenesis of the lung to emphysema and cor pulmooaIe. J Pediatr 46:200-209. 1955 14 Hayes CI. Gersony WM. Griftltbs SP. et al: Results of correction of total anomalous pulmonary venous connections in infancy. Adv Cardiol, 2:36-40. 1974 15 Rudolph AM: Congenital Disease of the Heart. OUcago. Year Book MedkaI Publishers, 1974, p 1!0

Unsuspected Cerebral Perfusion· A Comphcation of the Use of a Central Venous Pressure Catheter

by rapidly perproceda- ee.u.J pr'l &Ie •..c' etla.., lie ., tile ......... jIIpIIII' . . . . . , . . of 1JIoaIc ..... tbrouP lUCIa • cadle. . may lead to poteDtIaIIy . . . eoIBJIiIa........... detedIoa of COla1.1 lehdoII .. ~

,....

..................

Several authon have pointed out the hazards

ass0-

ciated with the use of central venous pressure catheters. 1" The "ear-gurgling" sign has recently been described as a benign annoyance encountered when the catheter has entered the internal jugular vein.· We encountered a potentially serious problem produced by infusion of pharmacologic agents into a central venous pressure catheter located deep in the internal jugular vein. Since this problem bas not been emphasized in the literature, We feel compelled to call attention to it. -From the Department of Cardiology. Meir General H~tal. Kfar-Saba. tinel, and the ~ School of Medfclne. Tel-Aviv University, Tel-Aviv, Ia'aeL lIspriftI f'fICItIM8: Dr. K~ II_ H ~ K/- StJba, lmwl

CHEST, 74: 1, JULY, 1978

A 48-year-old fema1e

DUJ'Ie

experienced sudden crushing

chest while at work. An electrocardiogra revealed an acute extensive anterior wall myocardial infarction. Within seconds, ventricular &brillation occurred. De&brillation was successfuJly performed, and normal sinus rhythm was reestablished. The patient became fully conscious; however. the systolic blood pressure was 40 mm Hg. Because of a total lade of peripheral veins, a catheter was quickly inserted through the subclavian vein, and a solution of norepinephrine was rapidly infused without waiting for a portable unit to obtain a chest x-ray &1m. Two events were then noticed. First, the blood pressure did not change. despite the rapid rate of infusion, but the patient, who all this time was fuDy conscious, complained of an excruciating headache of sudden onset. The blood pressure began to rise after several minutes. and when it reached a systolic level of 100 mm Hg, its rate decreased. The beadpains in the

ache persisted. although attenuated in intensity. Secondly. because wntricular premature beats were frequent, its rate was decreased with lidocaine instituted through the same central veD0U8 pressure line. with a bolus of 100 mg followed by a continuous drip infusion of 4 mg/min. The patient was then noted to become gradual1y more and more obtunded. There were DO convulsions; however. the ventricular premature beats did not respond readily to treatment, and several doses of 25 mg of lidocaine were given at 2O-minute intervals. A chest x-ray &1m revealed that the central venous pressure catheter was oriented cephalad in the iDtemaI jugular vein. The tip of the catheter was well within the neck. Infusions of norepinephrine and lidocaine were therefore relocated to a peripheral vein by a venous cutdown, and the central venous pressure cathemr was removed. Over the next hour the patient regained full consciousness and became free of headaches. From then OD, her recovery was uneventful.

DIscussIoN

HematIft O. KlIrira, M.D.; ElIo DI Segrai. M.D.; ontl ElIaer K"",Un.1cv, MD.

c.nu.

CASE REPoBT

There is no doubt that the events are directly traceable to the location of the catheter in the internal jugular vein. The mean pressure in the internal jugular vein does not exceed 10 mm Hg; it is easy to overcome this pressure by raising the height of the infusion bottle and to thus obtain retrograde perfusion of the intracranial venous sinuses and their ttibutary cerebral veins, especially when the forward driving force (arterial pressure) is reduced to 40 IDOl Hg. Headache is a well-known side effect when blood pressure is raised by the intravenous infusion of catecholamines. The intense headache of our patient in the absence of a rise in blood pressure is explained only by the large quantity of the solution of norepinephrine in the intracranial venous sinuses and ttibutary veins. Peripheral blood pressure rose only gradually and after much delay as the solution of norepinephrine "melded down" around the catheter in the left jugular vein and probably by way of the contralateral jugular vein after mixing with arterial blood and after stasis in the venous sinuses. The second event, although less dramatic than the first, is also well accounted for by this explanation; the patient rapidly became obtunded, but ventricular premature beats were not adequately suppressed in spite

UIISUSP£CTED CEREBRAL PERfUSION 1.