The beneficial effects of inhaled nitric oxide in patients with severe traumatic brain injury complicated by acute respiratory distress syndrome: a hypothesis

Thomas J Papadimos, Thomas J Papadimos

Abstract

Background: The Iraq war has vividly brought the problem of traumatic brain injury to the foreground. The costs of death and morbidity in lost wages, lost taxes, and rehabilitative costs, let alone the emotional costs, are enormous. Military personnel with traumatic brain injury and acute respiratory distress syndrome may represent a substantial problem. Each of these entities, in and of itself, may cause a massive inflammatory response. Both presenting in one patient can precipitate an overwhelming physiological scenario. Inhaled nitric oxide has recently been demonstrated to have anti-inflammatory effects beyond the pulmonary system, in addition to its ability to improve arterial oxygenation. Furthermore, it is virtually without side effects, and can easily be applied to combat casualties or to civilian casualties.

Presentation of hypothesis: Use of inhaled nitric oxide in patients with severe traumatic brain injury and acute respiratory distress syndrome will show a benefit through improved physiological parameters, a decrease in biochemical markers of inflammation and brain injury, thus leading to better outcomes.

Testing of hypothesis: A prospective, randomized, non-blinded clinical trial may be performed in which patients meeting the case definition could be entered into the study. The hypothesis may be confirmed by: (1) demonstrating an improvement in physiologic parameters, intracranial pressure, and brain oxygenation with inhaled nitric oxide use in severely head injured patients, and (2) demonstrating a decrease in biochemical serum markers in such patients; specifically, glial fibrillary acidic protein, inflammatory cytokines, and biomarkers of the hypothalamic-pituitary-adrenal axis, and (3) documentation of outcomes.

Implications of hypothesis: Inhaled nitric oxide therapy in traumatic brain injury patients with acute respiratory distress syndrome could result in increased numbers of lives saved, decreased patient morbidity, decreased hospital costs, decreased insurance carrier and government rehabilitation costs, increased tax revenue secondary to occupational rehabilitation, and families could still have their loved ones among them.

References

    1. Murray CJ, Lopes AD, (eds) Global Health Statistics; Geneva. World Health Organization; 1996.
    1. Thurman D, Alverson C, Dunn K, Guerrero J, Sniezek J. Traumatic brain injury in the United States: a public health perspective. J Head Trauma Rehabil. 1999;14:602–615.
    1. Finkelstein E, Corso P, Miller T. The incidence and economic burden of injuries in the United States. New York: Oxford University Press; 2006.
    1. Warden D. Military TBI during the Iraq and Afghanistan Wars. J Head Trauma Rehabil. 2006;21:398–402.
    1. The economic costs of the Iraq war
    1. Wallsten S, Korsec K. The economic cost of the war in Iraq. The Brookings Institute Working Paper 2005. 2005. pp. 5–19.
    1. Zygun DA, Kortbeek JB, Fick GH, Laupland KB, Doig CJ. Non-neurologic organ dysfunction in severe traumatic brain injury. Crit Care Med. 2005;33:654–660. doi: 10.1097/01.CCM.0000155911.01844.54.
    1. Moranti-Kossman MC, Rancan M, Stahel PF, Kossman T. Inflammatory response in acute brain injury: a double-edged sword. Curr Opin Crit Care. 2002;8:101–105. doi: 10.1097/00075198-200204000-00002.
    1. Rall JM, Matslievich DA, Dash PK. Comparative analysis of mRNA levels in the frontal cortex and the hippocampus in the basal state and in response to experimental brain injury. Neuropathol Appl Neurobiol. 2003;29:18–131. doi: 10.1046/j.1365-2990.2003.00439.x.
    1. Lopes-Aguilar J, Villagra Ana, Bernabe F, Murias G, Piacentini E, Real J, Fernandez-Segoviano P, Romero PV, Hotchkiss JR, Blanch L. Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced injury. Crit Care Med. 2005;33:1077–1083. doi: 10.1097/01.CCM.0000162913.72479.F7.
    1. Zygun DA, Zuege DJ, Boiteau PJ, Laupland KB, Henderson EA, Kortbeek , Doig CJ. Ventilator-associated pneumonia in severe traumatic brain injury. Neurocrit Care. 2006;5:108–114. doi: 10.1385/NCC:5:2:108.
    1. Holland MC, Mackersie RC, Morabito D, Campbell AR, Kivett VA, Patel R, Erickson VR, Pittet JF. The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury. J Trauma. 2003;55:106–111.
    1. Yildirim E, Katanoglu E, ozsisik K, Beskonakli E, Ozer S, Mustafa F, Kamer K, Unal S. Ultrastructural changes in pneumatocyte type II cells following traumatic brain injury in rats. Eur J Cardiothorac Surg. 2004;25:523–529. doi: 10.1016/j.ejcts.2003.12.021.
    1. Strieter RM, Kunkel SL. Acute Lung Injury: the role of cytokines in the elicitation of neutrophils. J Investig Med. 1994;42:640–651.
    1. Griffiths MJD, Evans TW. Inhaled nitric oxide therapy in the adult. N Eng J Med. 2005;353:2683–2695. doi: 10.1056/NEJMra051884.
    1. Herridge MS, Cheung AM, Tansy CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS, Arthur S. One-year outcomes in survivors of acute respiratory distress syndrome. N Eng J Med. 2003;348:683–693. doi: 10.1056/NEJMoa022450.
    1. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Eng J Med. 2005;353:1685–1693. doi: 10.1056/NEJMoa050333.
    1. Herridge MS, Angus DC. Acute Lung Injury – affecting many lives. N Eng J Med. 2005;353:1736–1738. doi: 10.1056/NEJMe058205.
    1. Bennet D, (ed) Proceedings of the 9th European Congress in Intensive Care Medicine: 1996; Bologna Moduzzi Editore. 1996.
    1. Abman SH, Greibel JL, Parker DK, Schmidt JM, Swanton D, Kinsella JP. Acute effects of inhaled nitric oxide in children with severe hypoxemic respiratory failure. J Pediatr. 1994;124:881–888. doi: 10.1016/S0022-3476(05)83175-0.
    1. Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Crit Care Med. 1998;26:15–23. doi: 10.1097/00003246-199801000-00011.
    1. Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury: results of a European mulitcentre study. Intensive Care Med. 1999;25:911–919. doi: 10.1007/s001340050982.
    1. Rossaint R, Gerlach H, Schmidt-Ruhnke H, Pappert D, Lewandowski K, Steudel W, Falke K. Efficacy of inhaled nitric oxide in patients with severe ARDS. Chest. 1995;107:1107–1115. doi: 10.1378/chest.107.4.1107.
    1. Angus DC, Clermont G, Linde-Zwirble WT, Musthafa AA, Dremsizov TT, Lidicker J, Lave JR. Healthcare costs and long-term outcomes after acute respiratory distress syndrome: a phase III trial of inhaled nitric oxide. Crit Care Med. 2006;34:2883–2890.
    1. Peillon D, Jault V, Le Vavaseur O, Bellanger-Depagne JJ, Combe C. Effect du monoxyde d'azote inhale chez une patiente atteinte d'hypertension intracranienne. Ann Fr Anesth Reanim. 1999;18:225–229. doi: 10.1016/S0750-7658(99)80073-2.
    1. Vavilala MS, Roberts JS, Moore AE, Newell DW, Lam AM. The influence of inhaled nitric oxide on cerebral blood flow and metabolism in a child with traumatic brain injury. Anesth Analg. 2001;93:351–353. doi: 10.1097/00000539-200108000-00023.
    1. Cohen SM, Marion DW. Traumatic Brain Injury. In: Fink MP, Abraham E, Vincent J-L, Kochanek PM, editor. Textbook of Critical Care. 5. Philadelphia: Elsevier; 2005. pp. 377–385.
    1. Rosner MJ, Rosner SD. Cerebral perfusion in head injury. In: Avezaat CJJ, van Eijndhoven JHM, Maas AIR, editor. Intracranial Pressure VIII. Berlin: Springer-Verlag; 1993. pp. 540–545.
    1. Stocchetti N, Maas AIR, Chieregato A, van der Plas AA. Hyperventilation in head injury: a review. Chest. 2005;127:1812–1827. doi: 10.1378/chest.127.5.1812.
    1. Mathru M, Huda R, Solanki DR, Hays S, Lang JD. Inhaled nitric oxide attenuates reperfusion inflammatory responses in Humans. Anesthesiology. 2007;106:275–282. doi: 10.1097/00000542-200702000-00015.
    1. Gazoni LM, Tribble CG, Zhao MQ, Unger EB, Farrar RA, Ellman PI, Fernandez LG, Laubach VE, Kron IL. Pulmonary macrophage inhibition and inhaled nitric oxide attenuate lung ischemia-reperfusion injury. Ann Thorac Surg. 2007;84:247–253. doi: 10.1016/j.athoracsur.2007.02.036.
    1. Hu X, Guo C, Sun B. Inhaled nitric oxide attenuates hyperoxic and inflammatory injury without alteration of phosphatidylcholine synthesis in rat lungs. Pulm Pharmacol Ther. 2007;20:75–84. doi: 10.1016/j.pupt.2005.12.008.
    1. Aaltonen M, Soukka H, Halkila L, Kalimo H, Holopainen IE, Kaapa PO. Meconium aspiration induces neuronal injury in piglets. Acta Paediatr. 2005;94:1468–1475. doi: 10.1080/08035250510042816.
    1. Aaltonen M, Soukka H, Halkola L, Jalonen J, Kalimo H, Holopainen IE, Kaapa PO. Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets. Early Hum Dev. 2007;83:77–85. doi: 10.1016/j.earlhumdev.2006.05.003.
    1. Da J, Chen L, Hedenstierna G. Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis. Crit Care Med. 2006;35:26–32. doi: 10.1097/.
    1. Gow AJ. The biological chemistry of nitric oxide as it pertains to the extrapulmonary effects of inhaled nitric oxide. Proc Am Thorac Soc. 2006;3:150–152. doi: 10.1513/pats.200506-058BG.
    1. Luchsinger BP, Rich EN, Gow AJ, Williams EM, Stamler JS, Singel DJ. Routes to S-nitroso-hemoglobin formation with heme redox and preferential reactivity in the B subunits. Proc Nat Acad Sci USA. 2003;100:461–466. doi: 10.1073/pnas.0233287100.
    1. Robinson JM, Lancaster JR. Hemoglobin-mediated, hypoxia-induced vasodilation via nitric oxide: mechanism(s) and physiologic versus pathological relevance. Am J Respir Cell Mol Biol. 2005;32:257–261. doi: 10.1165/rcmb.F292.
    1. Kosaka H, Watanabe M, Yoshihara H, Shiga T. Detection of nitric oxide production in lipopolysaccharide-treated rats by ESR using carbon monoxide hemoglobin. Biochem Biophys Res Commun. 1992;184:1119–1124. doi: 10.1016/0006-291X(92)90708-S.
    1. Jourd'heuil D, Gray L, Grisham MB. S-nitrosothiol formation in blood of lipopolysaccharide-treated rats. Biochem Biophys Res Commun. 2000;273:22–26. doi: 10.1006/bbrc.2000.2892.
    1. Doctor A, Platt R, Sheram ML, Eisheid A, McMahon T, Doherty J, Axelrod M, Kline J, Gurka M, Gow A, Gaston B. Hemoglobin confirmation couples erythrocyte S-nitrosothiol content to O2 gradients. Proc Nat Acad Sci USA. 2005;102:5709–5714. doi: 10.1073/pnas.0407490102.
    1. Goldfarb RD, Cinel I. Inhaled nitric oxide therapy for sepsis: more than just lung. Crit Care Med. 2007;35:290–291. doi: 10.1097/01.CCM.0000251290.41866.2B.
    1. McCullers DL, Herman JP. Adrenocorticosteroid receptor blockade and excitotoxic challenge regulated adrenocorticosteroid receptor mRNA levels in the hippocampus. J Neurosci Res. 2001;64:277–283. doi: 10.1002/jnr.1076.
    1. McCullers DL, Sullivan PG, Scheff SW, Herman JP. Traumatic brain injury regulates adrenocorticosteroid receptor mRNA levels in rat hippocampus. Brain Res. 2002;947:41–49. doi: 10.1016/S0006-8993(02)02904-9.
    1. McCullers DL, Sullivan PG, Scheff SW, Herman JP. Mifepristone protects CA1 hippocampal neurons following traumatic brain injury in rat. Neuroscience. 2002;109:219–230. doi: 10.1016/S0306-4522(01)00477-8.
    1. Herman JP, Seroogy K. Hypothalamic-pituitary-adrenal axis, glucocorticoids, and neurologic disease. Neurol Clin. 2006;24:461–481. doi: 10.1016/j.ncl.2006.03.006.
    1. Bondanelli M, Ambrosio M, Zatelli MC, De Marinis L, Delgi U, Ettore C. Hypopituitarism after traumatic brain injury. Eur J Endocrinol. 2005;152:679–691. doi: 10.1530/eje.1.01895.
    1. Van den Berge G. Novel insights into the neuroendocrinology of critical illness. Eur J Endocrinol. 2000;143:1–13. doi: 10.1530/eje.0.1430001.
    1. Llompart-Pou JA, Raurich JM, Ibanez J, Burguera B, Barcelo A, Ayestaran JI, Prerezx-Barcena J. Relationship between plasma adrenocorticotropin hormone and intensive care unit survival in early traumatic brain injury. J Trauma. 2007;62:1457–1461.
    1. Koiv L, Merisalu E, Zilmer K, Tomberg T, Kaasik AE. Changes of sympatho-adrenal and hypothalamo-pituitary-adrenocortical system in patients with head injury. Acta Neurol Scand. 1997;96:52–58.
    1. Lee BH, Wen TC, Rogido M, Sola A. Glucocorticoid receptor expression in the cortex of the neonatal rat brain with and without focal ischemia. Neonatology. 2007;91:12–19. doi: 10.1159/000096966.
    1. Sokol J, Jacobs SE, Bohn D. Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults. Cochrane Database Syst Rev. 2003:CD002787. doi: 10.1002/14651858.
    1. Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma. 2004;21:1553–1561. doi: 10.1089/neu.2004.21.1553.
    1. Pelinka LE, Kroepfl A, Schmidhammer R, Krenn M, Buchinger W, Redl H, Raabe A. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma. 2004;57:1006–1012.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다