Effects of Indomethacin on Hepatogenic Pulmonary Angiodysplasia

Effects of Indomethacin on Hepatogenic Pulmonary Angiodysplasia

Effects of Indomethacin on Hepatogenic Pulmonary Angiodysplasia* Hiro.~lli Shijo. M.D.; Haruka Sasllki. M.D.; K.ouichi lull, M.D.; Sdgo Sakaf!.uchi...

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Effects of Indomethacin on Hepatogenic Pulmonary Angiodysplasia* Hiro.~lli

Shijo. M.D.; Haruka Sasllki. M.D.; K.ouichi lull, M.D.;

Sdgo Sakaf!.uchi. M.D.; and Makoto Okumura. M.D.

A patient had liver cirrhosis associa ted with marked hypoxemia. With administration of indomethacin (75 mglday for six days), PaO. was elevated u p to 50 m m Hg from 44 m m Hg. At that time, dynamic pulmonary perfusion imaging revealed a p la teau time course curve of MAA uptake in the lungs, as compared with findings obtained during the state of severe hypoxemia without indomethacin. These observations suggest that part of hepatogenic pulmonary angiodysplasia is a f unctional vasodilatation that is presumably modulated by vasoactive substances, such as prostaglandins a nd/or other eicosano ids.

(Chest 1991; 99:1027-29) PC= prostaglandin; RA =radioimmunoassay; P(A-a)O, = alveolar-arterial oxygen pressure difference; MAA = macro-aggregated albumin

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he pathogt•m•tic mechanism of hepatogenic pulmonary angiodysplasia is still unknown. Dilated alveolar capillaries and small arteriovenous shunts seem to be the major cause of st>vere hypoxemia in these patients. Clinical evidence of resolution of tlw intrapulmonary arteriovenous shunt ratio has been noted following liver transplantation in a patient with primary biliary cirrhosis' and during a period of improved hepatic function in cirrhotic patients.' ·' In view of thest' findings. venous admixtures in the pulmonary circulation may be caused by a functional vasodilatation rather than an anatomically fixed a r te riovenous shunt in patients with hepatogenic pulmonary angiodysplasia. Abnormal production of various circulating vasoactive substances such as prostaglandins, atrial natriuretic polypeptide, renin-angiotensin system. and some other substances have been linked to the pathophysiologic conditions in the patients with liver cirrhosis. As these vasoactive substances could affect the pulmonar y circulation and gas exchange,'·$ development of hepatogenic pulmonary angiodysplasia may be influenced by these vasoactive substances. We report herein comparative findings c:oncerning serial dynamic pulmonary perfusion imaging before and after the administration of prostaglandin synthesis inhibitor, indomethacin, in a patient with hepatogenic pulmonary angiodysplasia.

prnthrnmbin time of 13.3 s with C.'(mtrol of 11.0 s, and plasma retentinn rate of indocyanine g,reen of 15 minutes, 46 percent. Serum hepatitis B surface anti)!en was negative. On a laparoscopic observation, the liver was nodular. and histologic findings revealed an established cirrhosis. Arterial blood ~as analysis revealed Pa01 of 44 mm llg, arterial oxygen saturation (SaOJ of 82 percent, PaCO, of 25 mm llg, alveolar-arterial oxygen pressure difference (P[A-a)O,} of 81 mm Hg, a pH of7.45, and IICO, of20 mmoVL. The 7 mm Hg nf decrease in PaO, was noted in the standing position. The "true" shunt ratio (QS/QT} was 18 percent, when the standard shunt equation was used under C.'(mditinns of 100 percent oxygen inhalation (PaO, was elevated to 317 mm Hg). Chest roentgenograms, elcctmcardiogr.lm, echocardiogram, and cardiopulmnnary function were "~thin normal limits except for low diffusion capacity (35 percent). Contrast-enhanced cchocardiography disclosed delayed opacifica· tion of the left ventricle. The pulmonary perfusion imaging hy technetium 99m MAA revealed a significant uptake in hoth lunJ(s and in the liver. splee n. and both kidneys (Fig 1}. The shunt ratio was 61 percent, as estimated hy the quantitative radionuclide method.• The dynamic pulmonary perfusion imaging hy -Tc MA.A revealed that the MAA particles passed through the lun)!s in ahmrt 15 s {Fi)! 2A}. The PaO, was elevated to 49 mm Hg from 43 mm llg hy intravenous infusiun nf prosta)!landin (PC) F,a (0.4 IJ.!iminlkw for 30 minutes. The PaO, was returned to 43 mm Hg 30 minutes after termination of PC F,a infusion. The urinary excretion of PCs and arterial hlood ~ases were measured before and after indomethacin (75 mwday for six days). which was reported tn potentiate hypoxic pulmonary vas
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CASE REPORT A 62-year-old cyanotic man was admitted to the hospital with exact'rhatin~ clysprwa. Physkal examinations disclosed cyanosis of mouth. lips. and nail beds. and marked clubbing of the fingers. Routine laboratory data Wt're as follows: red hlnod <:ell <."unt, 566X 10'; hemo~lohin , 12. 7 )!!d); white hlnod cell count, 1.900/cu mm; platelet <."unt . 6.6X 10'; serum total bilirubin, 2.0 m,.Vdl; st·rum albumin, 3.2 ,.Vdl; serum SCOT. 28 IU; serum SGPT. 13 IU; and LDH. 396 IU. Additional studies revealed a •From the First Department of Internal Medicine, School of Medicine. Fnkuoka Unin•rsity. Fukuoka. Japan. 1ktlrint requests: Dr. Shijo, 1-'irst Department of Internal Medicirw , Fukrwka Unirx•rsity School of M<•dicirw. 45-1 , 7-clwme. NanakunUJ, jorwn-ku , Fukuoka 81-1-01, japm1

FJC:URE

I. Pulmonary perfusion imaging with -Tc MAA reveals a

si~nificant radinisotope uptake in the lungs. liver, spleen, and both

kidneys.

CHEST I 99 I 4 I APRIL, 1991

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100 ·-.

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sec Ft<:URE 2. lime <.~JUrse of uptake of MAA particles in lun~o:s hef<>re (A) and after (B) indomethacin. Values of PaO,, PaCO,, and P(A-a)O, are 44 mm li$(, 25 mm llf,:. and Ill rnm Ill-(. respectively. hefore indomethadn. Values of PaO,. PaCO,. and P(A-a)O, after indomethacin are 50 mm ll~o:. 24 mm 11$(, and 76 rnrn ll~o:. respedively. Note the more ~o:entle slopt• (arrows) after the resolution of hypoxemia ";th indomethacin. a.~ mmpared with the steep slope ohtained in the period of severe hypoxemia without indomethadn. daily diet <.•mtaining i ).(of sodium chloride. Urinary 6-keto-P(; F,a and PGE were reduced from 865 nw'day and 405 nwday to 650 nwday and 334 nwday. respectively. after indomethacin. Urinary ex<.·retion of thromhox;me B, was also decreased to 270 nwday from 1,425 nwdaF On the other hand, PaO, was elevated to 50 mm ll~o: from 44 mm ll~o:. and P(A-a)O, was reduced to 76 mm llg fmmlll rnm Ill-( after indomethacin. AI that time. dynamic pulmonary perfusion ima).(ing wa.~ perfcmned, and the time <.'ltuse curve of uptake in lun).(s revealed a plateau curve after the peak activity as compared with time murse curve obtained in the period of severe h~·p<1xemia without indomethacin (Fi~o: 2B). The shunt ratio wa.~ sli).(htly de<.·reased to 55 percent from 61 pereent. Liver function (SCOT. SGPT. LOll. hilinthin, and prothrombin time) was basically nnchan~ed. Because of mild deterioration of renal function. indomethacin themp,· was dis<.'lnlinued. Dts<:tiSSJON

In the present case, tlw pulmonary perfusion imaging by ,_Tc MAA revealed a significant uptakt· in tlw lungs, liver, spleen, and both kidneys. and discrepancy was noted hetween physiologic shunt ratio and percentage of right-toleft shunt as estimated hy the quantitative radionuclide method. Moreover, PaO, worsened in the standing position. 1028

and contrast-enhanced echO<:ardiography disclosed delayed opacification of the left ventricle. These results are consistent with hepatogt·nic pulmonary angiodysplasia.• Recently, Stoller et al' reported that the reversibility of intrapulmonary right-to-left shunt ratio became evident fi>llowing liver transplantation. Other investigators have shown similar results!·' These findings su~t'st that hepatogenic pulmonary angiodysplasia is a functional vasodilatation rather than pathoanatomic change. Impaired hypoxic pulmonary vasoconstriction was noted in patients with liver cirrhosis.'"·" Indomethacin recovered the vascular sensitivity to vas<><.~mst rictor such as angiotensin II in patients with liver cirrhosis. •~ In addition, indomethacin potentiates hypoxic pulmonary vas<><.·onstriction and improves the pulmonary gas exchange.'·' From this evidence. we speculated that one of the pathogenetic factors of hepatogenic pulmonary angiodysplasia would be associated with the predominance of vasodilatative eicosanoids that could interfere with pulmonary gas t'xchange.'·' Thus, we gave PGF,a, vas<><.~mstrictor on pulmonary vascular channel,'3 intravenously and indomt'thacin orally to a patient with hepatogenic pulmonary angiodysplasia. As expected. PGF2 and indomethacin e lt·vatt'd the arterial oxygen pressure and indomt'thacin supprt'ssed urinary excretion of PGs. Dynamic pulmonary perfusion imaging depicts the passage of MAA particles through tht> pulmonary te leangiectasia6 and the time courst> curve of lung uptake of MAA tends toward a plateau aftt•r resolution of hypoxemia in patients with ht'patogenic pulmonary angiodysplasia." In the present case, the time course curve of the lung uptake of MAA was significantly changed, and the down slope was more gentle and tt•nded toward the plateau after therapy with indomethacin and some resolution of the hypoxemia (Fig 28, arrows). Thest• observations suggest that. in the state of some resolution of hypoxemia with indomethacin, pulmonary capillaries would bt• more narrowed. The MAA particles would pass through tlw pulmonary vasculature more slowly and more MAA particles would be captured by pulmonary capillary heds. The degree of resolution of hypoxemia in this case was mild and not always complete after administration of indomethacin. Various pulmonary \'asaoactive substances are speculated to be the causal factors of hepatogenic angiodysplasia" and otht•r mort• dfective factors may affect the pulmonary circulation. Although further studies are needed to arrive at a definite conclusion, we believe that our findings on dynamic pulmonary perfusion imaging before and after indomethacin therapy are interpreted as suggesting that predominance of vasodilatative PGs and/or other eicosanoids is one of the pathogenic factors of hepatogenic pulmonary angiodysplasia. ACKNOWLEDGMf.j'I;T: The authors thank M. Ohara of K\'ushu · University for l'lllllllt'llts un the manuscript. REFEREN CES

Stoller JK. Moodie D. Sthiavone \VA, vhw, D. Brou,::han T. Winkelman E. el al. Reductiun of intrapulmonary shunt and resolution of di,::ital duhhin~ associated "ith primary hiliary t:irrhosis after liwr transplantation. Hepatology 1990; 11:54-8 2 Stanley NN. Wood).(ale Dj. Mottled chest radio~raph and ,::as transfer defet'l in thronic liver disease. Thora.' 1972: 27:315-23 Indomethacin lor Hepatogenic Pulmonary Angiodysplasia (Shijo eta/)

3 Chen NS, Barnet CA, Farrer PA. Reversibility of intrapulmonary arteriovenous shunts in liver cirrhosis documented by serial radionuclide perfusion lung scans. Clin Nucl Med 1984; 9:27982 4 Goto F, Otani E , Kato S , Fujita T. Prostaglandin E, as a hypotensive drug during general anesthesia. Anesthesia 1982; 37:S».35 5 Raj JS , Chen P. Role of eicosanoids in hypoxic vasoconstriction in isolated lamb lungs. Am J Physiol 1987; 253:H626-H33 6 Shijo H , Hisano S, Sasalci H , Yuh IC, Kusuhara H , Sakaguchi S, et al. Detection of pulmonary telangiectasia using dynamic pulmonary perfusion imaging in patients with liver cirrhosis. Clin Nucl Med 1989; 14:179-82 7 Alexander JM , Nyby MD, Jasberg ICA. Prostaglandin synthesis inhibition restores hypoxemic pulmonary vasoconstriction. J Appl Physiol 1977; 42:903-()8 8 Light RB. Indomethacin and acetylsalicylic acid reduce intrapulmonary shunt in experimental pneumococcal pneumonia. Am Rev Respir Dis 1986; 134:500.25 9 Krowka MJ. Hepatopulmonary syndrome: an evolving perspective in the era of liver transplantation. Hepatology 1990; 11:138-

42 10 Daoud FS, Reevesff, Schaefer JW. Failureofhypoxicpulmonary vasoconstriction in patients with liver cirrhosis. J Clin Invest 1972; 51:1076-80 11 Rodriguetz-Roisin R. Roca J, Agusti AGN , Mastai R, Wagner PD, Bosch J. Gas exchange and pulmonary vascular reactivity in patients with liver cirrhosis. Am Rev Respir Dis 1987; 135:1085-92 12 Zipser RD . Hoefs JC, Speckart PF, Zia PK, Horton R. Prostaglandins: modulato rs of renal function and pressor resistance in chronic live r disease. J Clin Endocrinol Metab 1979; 48:895-900 13 Scherer Rw, Vigfusson G , Hultsch E . Vanaken H. Lawin P. Prostaglandin F. improves oxygen tension and reduces venous admixture during one-lung ventilation in anesthetized paralyzed dogs. Anesthesiology 1985; 62:23-8 14 Shijo H . Nakayama K, Sasalci H , Ueki T, Sakaguchi S, Sakata H, et al. Reversibility of pulmonary telangiectasia in liver cirrhosis evidenced by serial dynamic pulmonary perfusion imaging. Clin Nucl Med 1989; 14:909-11

Benign Thyroid Hyperplasia Presenting As Bilateral Vocal Cord Paralysis* Complete Remission Following Surgery jeffrey E. Godwin, M.D.;t K. Srott Miller; M.D., F.C.C.P.;t Khanh-Cien C. Hoang, M.D.;§ and StevenA. Sahn, M.D., F.C.C.P.II

A 52-year-old woman developed respiratory arrest on two separate occasions that required mechanical ventilation. Fibe.r optic bronchoscopy demonstrated bilateral vocal cord paralysis, and a cr scan of the nedc demonstrated a right oeclc mass. On surgical exploration, the mass was found • From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, Medical University of South Carolina, Charleston. tPulmonary Fellow. tAssistant Professor of Medicine. §Assistant Professor of Otorhinolaryngology. II Professor of Medicine. Reprint requen1: Dr. Sahn, fulmonary and Critical Care Medicine, 171 Ashley Auenue, Charleston, SC 29425

extending from the thyroid gland and was identified as benign thyroid tissue. Thyroid hyperplasia should be considered i.o the differential diagnosis of bilateral vocal cord paralysis. (Cheat 1991; 99:1029-30) rauma, most often iatrogenically-induced, and maligT nancy are the major causes of bilateral vocal cord

paralysis. To our lcnowledge, a patient with bilateral vocal cord paralysis caused by benign thyroid gland hyperplasia has not as yet been reported. CASE REPORT

A 52-yeaN>Id black woman with a history of hypertension, obesity, and previous alcohol abuse presented to a local hospital with increasing dyspnea and stridor requiring endotracheal intubation. She had no history of respiratory problems and had not previously been intubated. After successful weaning from the ventilator, she was discharged well, but two weeks later, experienced respiratory arrest. Once again, she was weaned from the ventilator and transferred to our unit for further evaluation. On presentation, she admitted to inspiratory stridor, but experienced no difficulty in phonation. She was in no distress with a respiratory rate of 20 per minute. The temperature was 37.0"C; pulse, 72; and blood pressure was 130182 mm Hg. The neck was supple without adenopathy or masses. Chest examination revealed minimal diffuse expiratory wheezing. Cardiac examina.tion was normal. The abdomen was distended without palpable organomegaly. Ne urologic examination results were normal. Laboratory evaluation i.n c.l uded the following: hemoglobin, 11.9 gldl; hematocrit, 37.7 percent; white blood cell count, 18,4001 cumm; platelet count, 133,0001cumm; normal levels for blood urea nitrogen, creatinine , electrolytes, and liver functions. A thyroid pro61e revealed: T., 6.07 11g/dl (4.5 to ll.S j.Lg/dl}; T3 resin uptake 51.4 percent (35 to 45 percent}; T, index 3. 12 (1.6 to 5.2}; and TSH 1.11 mcufml (< 10 mcufml}. The Westergren erythrocyte sedimentation rate was 50 mmlhour. The serum antinuclear antibody and rheumatoid factor were negative. Amorning cortisol level was 10.5 J.Lg/dl. The rapid plasma reagin was nonreactive. Arterial blood gas values on room air showed a pH, 7.45; Pc o •• 36 mm Hg; and Po., 60 mm Hg. Pulmonary function studies demonstrated FVC of 1.53 L (57 percent of predicted}; FEV., 1.40 L (69 percent of predicted}; FEV/FVC, .91; and a Battened inspiratory Row loop. Roentgenographic examination of the chest was normal. With the patient's history of inspiratory stridor, bronchoscopy was performed t.h at showed paramedian vocal cords. A tracheotomy was performed. ACT scan of the neck showed a retrotracheal and paraesophageal mass on the right side at the C.-C, level. Needle aspiration of the mass showed atypical cells with scattered clusters ofcytologically benign epithelial cells consistent with thyroid origin. Right neck exploration was performed. The mass identi6ed on CT scan was found to be extending from the thyroid gland. Aright hemithyroidectomy was performed. The postope.rative course was uneventful, and she was discharged with a tracheostomy tube in

place.

Histologic examination of the neclc mass revealed normal thyroid tissue. Eight weeks postoperation, aRexible 6beroptic laryngoscopic examination revealed normally functioning vocal cords permitting tracheostomy tube removal at that time. The patient was examined 11 months following the operation and was doing well without recurrence of stridor. DISCUSSION

The differential diagnosis of vocal cord paralysis is broad, encompassing causes of peripheral neuritis such as alcoholism, influenza, syphilis, diphtheria, typhoid fever, and drug CHEST I 99 I 4 I APRIL, 1991

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