Association of Hypercapnia in the First Week of Life with Severe Intraventricular Hemorrhage in the Ventilated Preterm Infants

기계적 환기 요법을 시행 받은 미숙아에서 고탄산혈증과 뇌실내 출혈의 발생과의 관계

  • Kim, Jeong-Eun (Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital) ;
  • Namgung, Ran (Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital) ;
  • Park, Min-Soo (Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital) ;
  • Park, Kook-In (Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital) ;
  • Lee, Chul (Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital) ;
  • Kim, Myung-Jun (Department of Diagnostic Radiology, Yonsei University College of Medicine, Severance Children's Hospital)
  • 김정은 (연세대학교 의과대학 세브란스 어린이병원 소아청소년과) ;
  • 남궁란 (연세대학교 의과대학 세브란스 어린이병원 소아청소년과) ;
  • 박민수 (연세대학교 의과대학 세브란스 어린이병원 소아청소년과) ;
  • 박국인 (연세대학교 의과대학 세브란스 어린이병원 소아청소년과) ;
  • 이철 (연세대학교 의과대학 세브란스 어린이병원 소아청소년과) ;
  • 김명준 (연세대학교 의과대학 세브란스 어린이병원 영상의학과교실)
  • Published : 2010.05.31

Abstract

Purpose : The aim of this study was to examine whether hypercapnia during the first seven days of life was associated with severe intraventricular hemorrhage (IVH) in preterm infants requiring mechanical ventilation. Methods : A matched pair analysis was performed for 19 preterm infants with severe IVH(grade$\geq$3) and 38 infants with no severe IVH (normal or grade 1), who required mechanical ventilation for more than seven days. The univariate and multivariate analysis of severe IVH with maximal and minimal $PaCO_2$, averag $PaCO_2$, SD of $PaCO_2$, and difference in the $PaCO_2$ were assessed. The major perinatal factors and maximal ventilator index (VI) were also compared. Results : Infants with severe IVH had a higher maximal $PaCO_2$ (86.1$\pm$18.4 mmHg vs. 60.1$\pm$ 11.6 mmHg, P <0.001) and mean $PaCO_2$ (47.5$\pm$5.6 mmHg vs. 41.2$\pm$6.3 mmHg, P=0.004) and a larger SD or difference in $PaCO_2$ (14.0$\pm$4.4 mmHg vs. 9.0$\pm$2.4 mmHg; 60.3$\pm$20.9 mmHg vs. 35.5$\pm$11.8 mmHg, P <0.001). However the minimal $PaCO_2$ values did not differ between the groups. Disseminated intravascular coagulation, pulmonary hemorrhage, and the air leak syndrome were more frequent in the IVH group than in the controls. The maximal VI on each day was higher in the IVH group. The multivariate logistic regression analysis after controlling for bleeding tendency showed that the air leak syndrome, maximal VI, and maximal $PaCO_2$ were independently associated with severe IVH [OR, 1.324 (95% CI, 1.011-1.733; P=0.041)]. Conclusion : Extreme hypercapnia was significantly associated with severe IVH in preterm infants, after adjustment for major perinatal risk factors. Frequent monitoring of the $PaCO_2$ may be important for early detection of inadvertent hypercapnia and prompt correction of high PaCOS levels.

목 적 : 기계적 환기요법을 시행 받은 미숙아에서 생후 첫 7일 동안 고탄산혈증과 중증 뇌실내 출혈의 발생과의 연관성을 알아보고자 본 연구를 시행하였다. 방 법:출생 후 7일 이상 기계적 환기 요법을 받은 재태주령 37주 미만의 미숙아를 대상으로 하여, 3단계 이상의 뇌실내 출혈로 진단받은 경우 IVH 군(n=19)으로, 정상 또는 1단계 뇌실내 출혈을 보인 경우, 출생 체중과 주수를 대응하여 대조군(n=38)으로 선정하였다. 두 군간의 생후 첫 7일 동안 혈중 이산화탄소 분압($PaCO_2$)의 최대값, 최소값, 평균값과 변화 정도(fluctuation)를 측정하기 위한 지표로 혈중 이산화탄소 분압의 최대값과 최소값의 차이(maximum-minimum)와 평균값의 표준편차를 비교 분석하였다. 결 과:재태주령과 출생체중은 IVH 군은 26.9$\pm$1.7주, 975.3$\pm$262.5g이었고, 대조군은 26.8$\pm$1.5주, 915.6$\pm$198.2 g이었다. IVH 군에서 생후 7일 동안 혈중 이산화탄소 분압의 최대값(IVH 군 vs. 대조군, 86.1$\pm$ 18.4 mmHg vs. 60.1$\pm$11.6mmHg, P <0.001), 평균값 (47.5$\pm$5.6 mmHg vs. 41.2$\pm$6.3mmHg, P=0.004), 최대값과 최소값의 차이(60.3$\pm$20.9 mmHg vs. 35.5$\pm$ 11.8 mmHg, P < 0.001), 평균값의 표준편차(14.0$\pm$4.4mmHg vs. 9.0$\pm$2.4 mmHg, P <0.001)는 유의하게 높았으나 최소값은 두 군 간의 차이가 없었다. 또한 IVH군에서 파종성혈관내응고[11 (57.9%):9 (23.7%), P=0.011], 폐출혈[12 (63.2%):10 (26.3%), P=0.007], 공기누출 증후군[4 (21.1%):1 (2.6%), P=0.021]의 빈도가 많았고, 생후 7일 동안 인공 호흡기 지수의 최대값이 통계적으로 유의하게 높았다. 출혈성 경향, 공기누출증후군, 인공 호흡기 지수의 영향력을 통제한 후에는 혈중 이산화탄소 분압의 최대값이 odds ratio 1.324 (95%CI: 1.011-1.733, P=0.041)로 중증 뇌실내 출혈과 통계적으로 유의한 연관성을 보였다. 결 론 : 기계적 환기 요법을 시행 받은 미숙아에서 출생 후 첫 7일 동안 극심한 고탄산혈증은 뇌출혈의 다른 위험 인자의 영향을 배제한 후에도 중증 뇌실내 출혈의 발생과 연관성을 보였다. 따라서 생후 초기에 호흡기 유발 폐손상을 막기 위해 고탄산혈증을 허용하는 시도는 중요하지만, 과도한 고탄산혈증과 심한 이산화탄소 분압의 변화를 피하고 적절한 이산화탄소 분압을 유지하는 노력이 필요할 것으로 생각된다.

Keywords

References

  1. Ambalavanan N, Nelson KG, Alexander G, Johnson SE, Biasini F, Carlo WA. Prediction of neurologic morbidity in extremely low birth weight infants. J Perinatol 2000;20:496-503. https://doi.org/10.1038/sj.jp.7200419
  2. Sherlock RL, Anderson PJ, Doyle LW. Neurodevelopmental sequelae of intraventricular haemorrhage at 8 years of age in a regional cohort of ELBW/very preterm infants. Early Hum Dev 2005;81:909-16. https://doi.org/10.1016/j.earlhumdev.2005.07.007
  3. Pryds O, Greisen G, Lou H, Friis-Hansen B. Heterogeneity of cerebral vasoreactivity in preterm infants supported by mechanical ventilation. J Pediatr 1989;115:638-45. https://doi.org/10.1016/S0022-3476(89)80301-4
  4. Tsuji M, Saul JP, du Plessis A, Eichenwald E, Sobh J, Crocker R, et al. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics 2000;106:625-32. https://doi.org/10.1542/peds.106.4.625
  5. Leahy FA, Cates D, MacCallum M, Rigatto H. Effect of CO2 and 100% O2 on cerebral blood flow in preterm infants. J Appl Physiol 1980;48:468-72. https://doi.org/10.1152/jappl.1980.48.3.468
  6. Pryds O, Greisen G. Effect of PaCO2 and haemoglobin concentration on day to day variation of CBF in preterm neonates. Acta Paediatr Scand Suppl 1989;360:33-6.
  7. Hansen NB, Brubakk AM, Bratlid D, Oh W, Stonestreet BS. The effects of variations in PaCO2 on brain blood flow and cardiac output in the newborn piglet. Pediatr Res 1984;18:1132-6. https://doi.org/10.1203/00006450-198411000-00015
  8. Wyatt J, Meek J. Commentary on cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics 2000;106:828. https://doi.org/10.1542/peds.106.4.828
  9. Wiswell TE, Graziani LJ, Kornhauser MS, Stanley C, Merton DA, McKee L, et al. Effects of hypocarbia on the development of cystic periventricular leukomalacia in premature infants treated with high-frequency jet ventilation. Pediatrics 1996;98:918-24.
  10. Gannon CM, Wiswell TE, Spitzer AR. Volutrauma, PaCO2 levels, and neurodevelopmental sequelae following assisted ventilation. Clin Perinatol 1998;25:159-75.
  11. Graziani LJ, Spitzer AR, Mitchell DG, Merton DA, Stanley C, Robinson N, et al. Mechanical ventilation in preterm infants: neurosonographic and developmental studies. Pediatrics 1992;90:515-22.
  12. Collins MP, Lorenz JM, Jetton JR, Paneth N. Hypocapnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants. Pediatr Res 2001;50:712-9. https://doi.org/10.1203/00006450-200112000-00014
  13. Wallin LA, Rosenfeld CR, Laptook AR, Maravilla AM, Strand C, Campbell N, et al. Neonatal intracranial hemorrhage: II. Risk factor analysis in an inborn population. Early Hum Dev 1990;23:129-37. https://doi.org/10.1016/0378-3782(90)90136-7
  14. Harper AM. Autoregulation of cerebral blood flow: influence of the arterial blood pressure on the blood flow through the cerebral cortex. J Neurol Neurosurg Psychiatry 1966;29:398-403. https://doi.org/10.1136/jnnp.29.5.398
  15. Haggendal E, Johansson B. Effects of arterial carbon dioxide tension and oxygen saturation on cerebral blood flow autoregulation in dogs. Acta Physiol Scand Suppl 1965;258:27-53.
  16. Kaiser JR, Gauss CH, Williams DK. The effects of hypercapnia on cerebral autoregulation in ventilated very low birth weight infants. Pediatr Res 2005;58:931-5. https://doi.org/10.1203/01.pdr.0000182180.80645.0c
  17. Kenny JD, Garcia-Prats JA, Hilliard JL, Corbet AJ, Rudolph AJ. Hypercarbia at birth: a possible role in the pathogenesis of intraventricular hemorrhage. Pediatrics 1978;62:465-7.
  18. Cooke RW. Autoregulation and intraventricular haemorrhage. Lancet 1980;1:1197-8.
  19. Van de Bor M, Van Bel F, Lineman R, Ruys JH. Perinatal factors and periventricular-intraventricular hemorrhage in preterm infants. Am J Dis Child 1986;140:1125-30.
  20. Erickson SJ, Grauaug A, Gurrin L, Swaminathan M. Hypocarbia in the ventilated preterm infant and its effect on intraventricular haemorrhage and bronchopulmonary dysplasia. J Paediatr Child Health 2002;38:560-2. https://doi.org/10.1046/j.1440-1754.2002.00041.x
  21. Kaiser JR, Gauss CH, Pont MM, Williams DK. Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J Perinatol 2006;26:279-85. https://doi.org/10.1038/sj.jp.7211492
  22. Fabres J, Carlo WA, Phillips V, Howard G, Ambalavanan N. Both extremes of arterial carbon dioxide pressure and the magnitude of fluctuations in arterial carbon dioxide pressure are associated with severe intraventricular hemorrhage in preterm infants. Pediatrics 2007;119:299-305. https://doi.org/10.1542/peds.2006-2434
  23. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92:529-34. https://doi.org/10.1016/S0022-3476(78)80282-0
  24. Volpe JJ. Intracranial hemorrhage: germix matrix-intraventricular hemorrhage. In: Volpe JJ, editor. Neurology of the newborn. 5th ed. Philadelphia : WB Saunders, 2008:539-41.
  25. Wilson DF, Pastuszko A, DiGiacomo JE, Pawlowski M, Schneiderman R, Delivoria-Papadopoulos M. Effect of hyperventilation on oxygenation of the brain cortex of newborn piglets. J Appl Physiol 1991;70:2691-6. https://doi.org/10.1152/jappl.1991.70.6.2691
  26. Wyatt JS, Edwards AD, Cope M, Delpy DT, McCormick DC, Potter A, et al. Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants. Pediatr Res 1991;29:553-7. https://doi.org/10.1203/00006450-199106010-00007
  27. Perlman JM, Goodman S, Kreusser KL, Volpe JJ. Reduction in intraventricular hemorrhage by elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome. N Engl J Med 1985;312:1353-7. https://doi.org/10.1056/NEJM198505233122104
  28. Lou HC, Lassen NA, Friis-Hansen B. Impaired autoregulation of cerebral blood flow in the distressed newborn infant. J Pediatr 1979;94:118-21. https://doi.org/10.1016/S0022-3476(79)80373-X
  29. Hauerberg J, Juhler M, Rasmussen G. Cerebral blood flow autoregulation after experimental subarachnoid hemorrhage during hyperventilation in rats. J Neurosurg Anesthesiol 1993;5:258-63. https://doi.org/10.1097/00008506-199310000-00006
  30. Skouteli HN, Kuban KC, Leviton A, Brown ER, Krishnamoorthy KS, Pagano M, et al. Arterial blood gas derangements associated with death and intracranial hemorrhage in premature babies. J Perinatol 1988;8:336-41.
  31. Linder N, Haskin O, Levit O, Klinger G, Prince T, Naor N, et al. Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study. Pediatrics 2003;111:e590-5. https://doi.org/10.1542/peds.111.5.e590
  32. Carlo WA, Stark AR, Wright LL, Tyson JE, Papile LA, Shankaran S, et al. Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants. J Pediatr 2002;141:370-4. https://doi.org/10.1067/mpd.2002.127507
  33. Mariani G, Cifuentes J, Carlo WA. Randomized trial of permissive hypercapnia in preterm infants. Pediatrics 1999;104:1082-8. https://doi.org/10.1542/peds.104.5.1082
  34. Woodgate PG, Davies MW. Permissive hypercapnia for the prevention of morbidity and mortality in mechanically ventilated newborn infants. Cochrane Database Syst Rev 2001;(2):CD002061.