Milton A MeierI; Waldir JazbikII; Joaquim H CoutinhoII; João Carlos JazbikII; José Aldrovando de OliveiraIII; José Caetano SilvaIII; Rosa Célia BarbosaIII; Helder PaupérioIII; Astolfo Serra JrIII
DOI: 10.1590/S0102-76381989000100002
RESUMO
A presença de canal arterial patente (PCA) com grande shunt sistêmico -pulmonar no prematuro com síndrome de angústia respiratória (SAR) está quase sempre associada a insuficiência cardíaca, displasia broncopulmonar, enterocolite necrotizante, hemorragia intracraniana e morte. A ligadura do canal melhora a complacência pulmonar, reduz, significativamente, o tempo de assistência ventilatória e melhora 0 estado geral do paciente. Depois da introdução, nesta última década, da indometacina para a interrupção do PCA, no prematuro, vários estudos vêm procurando estabelecer as vantagens de uma forma de tratamento sobre a outra. O propósito do nosso estudo é comparar os resultados obtidos em 48 pacientes (pts.) (Grupo 1) submetidos a ligadura cirúrgica, nos últimos 8 anos, com 28 pts. (Grupo 2) nos quais a indometacina foi, preferentemente, utilizada. A idade gestacional média do Grupo 1 foi de 29,13 ± 2,33 semanas (24-34) e de 28,39 ± 2,30 semanas (25-32) no Grupo 2. O peso médio foi de 954,17 ± 220,68 g (540-1750 g) no Grupo 1 e de 923,21 ± 191,74 g (550-1400 g) no Grupo 2. Trinta e três (60,75%) dos pts. do Grupo 1 eram menores do que 1000 g (prematuros extremos), enquanto que 21 do Grupo 2 (75,0%) estavam nessa condição. Nove pacientes (32,1%) do Grupo 2 foram transferidos para o Grupo 1, devido ao insucesso da terapêutica com a indometacina, ou pela intolerância às doses indicadas. A ligadura foi realizada na própria unidade de terapia intensiva em 31 pts. (64,5%). A técnica empregada tem sido a de uma toracotomia póstero-lateral pequena, com preservação dos músculos do tórax e abertura pelo 3º ou 4º espaço intercostal. Por via extrapleural, o canal é alcançado e ligado com dois clips metálicos. Inicialmente, o tórax era rotineiramente drenado, apenas quando havia abertura da pleura. Mais recentemente, mesmo com a pleura aberta, somente são drenados os casos que apresentam pneumotórax prévio, ou então sangramento excessivo. A mortalidade no Grupo 1 foi de 18,75% (9 pts.) e, no Grupo 2, de 25,0% (7 pts.). Quatro pacientes do Grupo 2 transferidos para o Grupo 1 faleceram. As causas de óbito no Grupo 1 foram sépsis e hemorragia intracraniana; no Grupo 2, sépsis, enterocolite necrotizante com perfuração localizada, hemorragia intracraniana e penumotórax. Nos dois grupos, a mortalidade foi significantemente maior nos prematuros extremos. A despeito dos problemas de comparação entre os 2 grupos e das conclusões limitadas que podem ser retiradas de um estudo retrospectivo e não randomizado, acreditamos que os resultados da ligadura cirúrgica são nitidamente superiores aos obtidos com o uso da indometacina.ABSTRACT
Patent ductus arteriosus (PDA) in low-birth-weight premature infants has been associated with congestive heart failure, bronchopulmonary dysplasia, necrotizing enterocolitis, intracranial hemorrhage, and death. Surgical ligation of the PDA in these infants has improved lung compliance, decreased the duration of assisted ventilation, and increased nutritional utilization. After the introduction of indomethacin for the pharmacological interruption of the PDA in the last decade, several studies have been reported which attempted to establish advantages of the pharmacological treatment over the surgical ligature. The purpose of our study is to compare the results obtained in 48 consecutive patients (Group 1) who underwent surgical ligature of the PDA in the last 8 years, with 28 patients (Group 2), who underwent indomethacin therapy. The mean gestational age of Group 1 was 29.13 ± 2.33 weeks (range, 24-34 weeks), and 28.39 ± 2.30 weeks (range, 25-32 weeks) in Group 2. The mean birth weight was 954.17 ± 220.86 g (range, 540-1750 g) in Group 1, and 923.21 ± 191.74 g (range 550-1400 g) in Group 2. Thirty three (60.75%) pts. from Group 1 weighed 1,000 g or less, and 21 pts. from Group 2 (75.0%) weighed less than 1,000 g. Nine pts. (32.1%) from Group 2 received indomethacin previously and were transferred to Group 1, due to failure to close the PDA or due to drug intolerance. Ligation of the PDA was performed in the neonatology intensive care unit, in 31 pts. (64.5%). Usually a small postero-lateral thoracotomy, with preservation of the latissimus dorsi and anterior serratus muscles, with thorax access through the 3rd or 4th intercostal spaces. The ductus is isolated by an extrapleural path, and ligated with two or three a medium hemoclips. In our early experience pleural drainage was employed routinely in all patients. Later, it was used only when the pleura was inadvertently opened, and more recently pleural drainage was used only in patients who had preexisting pneumothorax or excessive bleeding. The overall mortality in Group 1 was 18.75% (9 pts.) and in Group 2 was 25.0% (7 pts.). Four patients from Group 2 who were transferred to Group 1, died. Causes of death in Group 1, included sepsis, intraventricular hemorrhage, necrotizing enterocolitis and focal perforations, and pneumothorax. Patients who weighed more than 1,000 g had a better survival and a shorter period of assisted ventilation than patients weighing less than 1,000 g. Despite the problems of comparison between the two groups, and limited conclusions that can be drawn from a retrospective and non randomized study, we believe that surgical ligature for PDA was associated with significant less morbidity and mortality, than patients treated with indomethacin.REFERÊNCIAS
1. ALPERT, B. S.; LEWINS, M. J.; ROWLAND, D. W.; GRANT. M. J.; OLLEY, P. M.; SOLDIN, S. J.; SWYER, P. R.; COCEANI, F.; ROWE, R. D. - Plasma indometacin levels in preterm newborn infants with symptomatic patent ductus arteriosus: clinical and echocardiography assessment of response. J. Pediatr., 95: 578-582, 1979. [MedLine]
2. BAYLEN, B. G.; OKATA, H.; IKEGAMI, M.; JACOBS, H. C.; HOBE, A. H.; EMMANOUILIDES, G. C. - Left ventricular performance and regional blood flow before and after ductus arteriosus occlusion in premature lambs treated with surfactant. Circulation, 67: 837-842, 1983.
3. BELL, E. F.; WARBURTON, D.; STONESTREET, B. S.; OH, W. - Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive hart failure in premature infants. N. Engl. J. Med., 302: 598-601, 1980.
4. BETHENCOURT, D. M. & HOLMES, E. C. - Musclesparing posterolateral thoracotomy. Ann. Thorac. Surg., 45: 337-339, 1988. [MedLine]
5. BRANDT III, B.; MARVIN, W. J.; EHRENHAT, J. L.; HEINTZ, S.; DOTY, D. B. - Ligation of patent ductus arteriosus in premature infants. Ann. Thorac. Surg., 32: 167-172, 1981.
6. BROWN, E. R. - Increased risk of bronchopulmonary displasia in infants with patent ductus arteriosus. J. Pediatr., 95: 865-866, 1979. [MedLine]
7. CLYMAN, R. I. - The role of the patent ductus arteriosus in respiratory distress syndrome. Semin. Perinatol., 8: 293-297, 1984.
8. CLYMAN, R. I. ; CAMPBELL, D.; HEYMANN, M. A.; MAURAY, F. - Persistent responsiveness of the neonatal ductus arteriosus in immature lambs: a possible for reopening of patent ductus arteriosus after indomethacin-induced closure. Circulation, 71: 141-145, 1985. [MedLine]
9. CLYMAN, R. I. & HEYMAN, M. A. - Pharmacology of the ductus arteriosus. Pediatr. Clin. N. Am., 28: 77-82, 1981.
10. COCEANI, F. & OLLEY, P. M. - Role of prostaglandins, prostacyclin, and thromboxanes in the control of prenatal patency and postnatal closure of the ductus arteriosus. Semin. Perinatol., 4: 109-113, 1980. [MedLine]
11. COOKE, R. W. I. & PICKERING, D. - Poor response to oral indomethacin therapy for persistent ductus arteriosus in very low birth weight infants. Br. Heart J., 41: 301-303, 1979. [MedLine]
12. COTTON, R. B.; STAHLMAN, M. T.; BENDER, H. W.; GRAHAM T, P.; CATTERTON, W. Z.; ROVAR, I. - Randomized trial of early closure of symptomatic patent ductus arteriosus in small preterm infants. J. Pediatr/. 93: 647-651, 1978.
13. COTTON, R. B.; STHALMAN, M. T.; KOVAR, I.; CATTERTON, W. Z. - Medical management of small infants with symptomatic patent ductus arteriosus. J. Pediatr., 92: 467-474, 1978.
14. EDMUNDS Jr., L. H. - Operation or indomethacin for the premature ductus. Ann. Thorac. Surg., 26: 586-569, 1978.
15. EDMUNDS Jr., L. H.; GREGORY, G. A.; HEYMANN, M. A.; KITTERMAN, J. A.; RUDOLPH, A. M.; TOLLEY, W. H. - Surgical closure of the ductus arteriosus in premature infants. Circulation, 48: 856-862, 1973.
16. EGGERT, L. D.; JUNG, A. L.; McGOUGH, E. C.; RUTTENBERG, H. D. - Surgical treatment of patent ductus arteriosus in preterm infants: four-year experience with ligation in the newborn intensive care unit. Pediatr. Cardiol., 2: 15-19, 1982.
17. ELLISON, R. C.; PECKHAM, G. J.; LANG, P.; TALNER, N. S.; LERER, T. J.; LIN, L.; DOOLEY, K. J.; NADAS, A. S. - Evaluation of the preterm infant for patent ductus arteriosus. Pediatrics, 71: 364-370, 1983.
18. FLOWER, R. W. & BLAKE, D. A. - Retrolental fibroplasia: evidence for a role of the prostaglandin cascade in the pathogenesis of oxygen-induced retinopathy in the newborn beagle. Pediatr. Res., 15: 660-668, 1981.
19. FRIEDMAN, W. F.; HIRSCHKLAU, M. J.; PRINTZ, M. P.; PITLICK, P. T.; KIRKPATRICK, S. E. - Pharmacologic closure of patent ductus arteriosus in the premature infant. N. Engl. J. Med., 295: 526, 1976. [MedLine]
20. FRIEDMAN, W. F.; HIRSCHKLAU, M. J.; PRINTZ, M. P.; PITLICK, P. T.; KIRKPATRICK, S. E. - Pharmacologic closure of patent ductus arteriosus in hyaline membrane disease. J. Pediatr.. 93: 682-689, 1978.
21. FRIEDMAN, W. F.; KURLINSKI, J.; JACOB, J.; DISESSA, T. G.; CLUCK, L.; MERRIT, T. A.; FELDMAN, B. H. - The inhibition of prostaglandin and prostacyclin synthesis in the clinical management of patent ductus arteriosus. Semin. Perinatol., 4: 125-133, 1980. [MedLine]
22. GAY, J. H.; DAILY, W. J. R.; MEYER, B. H. P.; TRUMP, D. S.; CLOUD, D. T.; MOLTHAN, M. E. - Ligation of the patent ductus arteriosus in premature infants: report of 45 cases. J. Pediatr. Surg., 8: 677-683, 1973. [MedLine]
23. GERSONY, W. M.; PECKHAM, G. J.; ELLISON, R. C.; MIETTINEN, O. S.; NADAS, A. S. - Effects of indomethacin in premature infants with patent ductus arteriosus: results of a national collaborative study. J. Pediatr., 102: 895-906, 1983. [MedLine]
24. GUNNING, A. J. - A simple, safe, surgical technique for closing the persistent ductus arteriosus in the preterm neonate. Ann. R. Coll. Surg. Eng., 65: 214-216, 1983.
25. HARINCK, E.; VAN ERTBRUGGEN, L.; SENDERS, R. C. H.; MOULAERT, A. J. - Problems with indomethacin for ductus closure. Lancet., 2: 245, 1977. [MedLine]
26. HEYMANN, M. A. & HOFFMAN, J. I. E. - Problems of patent ductus arteriosus in premature infants. Paediatrician, 7: 3-17, 1978. [MedLine]
27. HEYMANN, M. A.; RUDOLPH, A. M.; SILVERMAN, N. H. - Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N. Engl. J. Med., 295: 530-536, 1976.
28. HOAFFMAN, J. I. E.; HEYMANN, M. A.; CLYMAN, R. I.; RUDOLPH, A. M. - Patent ductus arteriosus in premature infants. Rev. Latina Cardiol. Infant., 4: 293-306, 1986.
29. IVEY, H.H.; KATTIWINKEL, J.; PARK, T. S.; KROVETZ, L. J. - Failure of indomethacin to close persistent ductus arteriosus in infants weighing under 1000 grams. Br. Heart. J., 41: 305-307, 1979.
30. JACOB, J.; GLUCK, L.; DI SESSA, T.; EDWARDS, D.; KULOVICH, M.; KURLINSKI, J.; MERRIT, T. A.; FRIEDMAN, W. F. - The contribution of PDA in the neonate with severe RDS. J. Pediatr., 96: 79-85, 1980.
31. JOHNSON, G. L.; BREART, G. L.; GEWITZ, M. H.; BRENNER, J. I.; LANG, P.; DOOLEY, K. J.; ELLISON, R. C. - Echocardiography characteristics of premature infants with patent ductus arteriosus. Pediatrics., 72: 846-849, 1983.
32. KITTERMAN, J. A.; EDMUNDS Jr., L. H.; GREGORY, G. A.: HEYMANN, M. A.; TOOLEY, W. H.; RUDOLPH, A. M. - Patent ductus arteriosus in premature infants: incidence, relation to pulmonary disease and management. J. Engl. J. Med., 287: 473-477, 1972.
33. KRON, I. L.; MANTZER Jr., R. M.; RHEUBAN, K. S.; NOLAN, S. P. - A simple rapid technique for operative closure of patent ductus arteriosus in the premature infant. Ann. Thorac. Surg., 37: 422-427, 1984.
34. LEWIS, A. B.; HEYMANN, M. A.; RUDOLPH, A. M. - Gestational changes in pulmonary vascular response in fetal lamb in utero. Circ. Res., 39: 536-542, 1976.
35. MAHER, P.; LANE, B.; BALLARD, R.; PIECUCH, R.; CLYMAN, R. I. - Does indomethacin cause extensions of intracranial hemorrhages: a preliminary study. Pediatrics, 75: 497-504, 1985.
36. MAHONEY, L.; CARNERO, V.; BRETT, C.; HEYMANN, M. A.; CLYMAN, R. A. - Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth: weight infants. N. Engl. J. Med., 306: 506-511, 1982.
37. MAVROUDIS, C.; COOK, L. N.; FLEISCHAKER, J. W.; NAGARAJ, H. S.; SHOTT, R. J.; HOWE, W. R.; GRAY Jr., L. A. - Management of patent ductus arteriosus in the premature infant: indomethacin versus ligation. Ann. Thorac. Surg., 36: 561-566, 1983. [MedLine]
38. McCARTHY J. S.; ZIES, L. G.; GELBAND, H. - Age-dependent closure of the patent ductus arteriosus by indomethacin. Pediatrics, 62: 706-712, 1978. [MedLine]
39. MELLANDER, M.; LEHEUP, B.; LINDSTROM, D. R.; PALME, C.; GRAHAM Jr., T. P.; STAHLMAN, M. T.; COTTON, R. B. - Recurrence of symptomatic patent ductus arteriosus in extremely premature infants, treated with indomethacin. J. Pediatr., 105: 138-146, 1984.
40. MERRITT, T. A.; HARRIS, J. P .; ROGHMANN, K.; WOOD, B.; CAMPANELLA, V.; ALEXSON, C.; MANNING, J.; SHAPIRO, D. L. - Early closure of the patent ductus arteriosus in very low-birth-weight infants: a controled trial. J. Pediatr., 99: 281-288, 1981.
41. MERRITT, T. A.; WHITE, C. L.; JACOB, J.; KURLINSKI, J.; MARTIN, J.; DI SESSA, T. G.; EDWARDS, D.; FRIEDMAN, W. F.; GLUCK, L. - Patent ductus arteriosus treated with ligation or indomethacin: a follow-up study. J. Pediatr., 95: 588-594, 1979.
42. MIKHAIL, M.; LEE, W.; TOEWS, W.; SYNHORST, D. P.; HAWES, C. R.; HERNANDEZ, J.; LOCKHART, C.; WHITFIELD, J.; PAPPAS, G. - Surgical and medical experience with 734 premature infants with patent ductus arteriosus. J. Thorac. Cardiovasc. Surg., 83: 349-357, 1982. [MedLine]
43. MOMMA, K.; KONISHI, T.; HAGIWARA, H. - Characteristic morphology of the constricted fetal ductus arteriosus following maternal administration of indomethacin. Pediatr. Res., 19: 493-499, 1985.
44. NADAS, A. S. - Patent ductus revisited. N. Engl. J. Med., 295: 563, 1976. [MedLine]
45. NAGARAJ, H. S.; SANDHU, A. S.; COOK, L. - Gastrointestinal perforation following indomethacin therapy in very low birth weight infants. J. Pediatr. Surg., 16: 1003-1009, 1981.
46. NAULTI, C. M; HORN, S.; CONRY, J.; AVERY, G. B. - Improved lung compliance after ligation of patent ductus arteriosus in hyaline membrane disease. J. Pediatr., 93: 682-689, 1978.
47. NEAL, W. A.; BESSINGER Jr., F. B.; HUNT, C. E.; LUCAS Jr., R. V. - Patent ductus arteriosus complicating respiratory distress syndrome. J. Pediatr., 86: 127-136, 1975.
48. NEAL, W. A.; LYLE, J. M.; MULLET, M. D. - Failure of indomethacin therapy to induce closure of patent ductus arteriosus in premature infants with respiratory distress syndrome. J. Pediatr., 91: 621-623, 1977. [MedLine]
49. NEU, J.; ARIAGNO, R. L.; JOHNSON, J. B. - A double-blind study of the effects of oral indomethacin in preterm infants with patent ductus arteriosus who failed medical management. Pediatr. Pharmacol., 1: 245-250, 1981.
50. OLLEY, P. M.; COCEANI, F.; FREEDOM, R. M.; IZUKAWA, T.; SWYER, P. R.; ROWE, R. D. - Pharmacological manipulations of the ductus arteriosus. In: GODMAN, M. J. (ed.) Paediatric cardiology. Edinburgh, Churchill Livingstone, 1981. Vol. 4, p. 259-266.
51. OXNARD, S. C.; McGOUCH, E. C.; JUNG, A. L.; RUTTENBERG, H. D. - Ligation of the patent ductus arteriosus in the newborn intensive care unit. Ann. Thorac. Surg., 23: 564-570, 1977.
52. SALOMON, N. W.; ANDERSON, R. M.; COPELAN, J. G. - A rational approach to ligation of patent ductus arteriosus in the neonate. Chest, 75: 671-678, 1979.
53. SIASSI, B.; BLANCO, C.; CABAL, L. A.; CORAN, A. G. - Incidence and clinical features of patent ductus arteriosus in low-birth-weight infants: a prospective analysis of 150 consecutively born infants. Pediatrics, 57: 347-361, 1976.
54. STRANGE, M.; MYERS, G.; KIRKLIN, J. K.; PACIFICO, A. D.; CASSADY, G. - Lack of effect of patent ductus arteriosus ligations on intraventricular hemorrhage in preterm infants. Clin. Res., 31: 913, 1983. [MedLine]
55. THALJI, A. A.; CARR, I.; YEH, T. F.; RAVAL, D.; LUKEN, J. A.; PILDES, R. S. - Pharmacokinetics of intravenously administered indomethacin in premature infants. J. Pediatr., 87: 995-1001, 1980.
56. THIBEAULT, D. W.; EMMANOUILIDES, G. C.; NELSON, R. J.; LACHMAN, R. S.; ROSENGARDT, R. M.; OH, W. - Patent ductus arteriosus complicating the respiratory distress syndrome in preterm infants. J. Pediatr., 86: 120-129, 1975.
57. TRAUGOTT, R. C.; WILL, R. J.; SCHUCHMANN, G. F.; TREASURE, R. L. - A simplified method of ligation of patent ductus arteriosus in premature infants. Ann. Thorac. Surg., 29: 263-267, 1980.
58. WAGNER, H. R.; ELLISON, R. C.; ZIERLER, S.; LANG, P.; PUROHIT, D. M.; BEHRENDT, D.; WALDHAUSEN, J. A. - Surgical closure of patent ductus arteriosus in 268 preterm infants. J. Thorac. Cardiovasc. Surg., 87: 870-878, 1984.
59. WAY, G. L.; PIERCE, J. R.; WOLFE, R. R.: McGRATH, R.; WIGGINS, J.; MERENSTEIN, J. B. - ST depression suggesting subendocardial ischemia in neonates with respiratory distress syndrome and patent ductus arteriosus. J. Pediatr., 95: 609-614, 1978.
60. YANAGI, R. M.; WILSON, A.; NEWFELD, E. A.; AZIZ, K. V.; HUNT, C. E. - Indomethacin treatment for symptomatic patent ductus arteriosus: a double-blind control study. Pediatrics, 67: 647-656, 1981.
61. YEH, T. F.; LUKEN, J. A.; THALJI, A.; RAVAL, D.; CARR, I.; PILDES, R. S. Intravenous indomethacin therapy in premature infants with persistent ductus arteriosus: a double-blind study. J. Pediatr., 98: 137-146, 1981.
62. YEH, T. F.; THALJI, A.; LUKEN, J.; RAVAL, D.; CARR, I.; PILDES, R. S. - Intravenous indomethacin therapy in premature infants with PDA: a double blind control study. Pediatr. Res., 13: 354-360, 1979.
63. ZACHMAN, R. D.; STEINMETZ, G. P.; BOTHAM, R. J.; GRAVEN, S. N.; LEDBETTER, M. K. - Indicence and treatment of the patent ductus arteriosus in the ill premature neonate. Am. Heart J., 87: 697-702, 1974.