Editorial
What’s new in critical illness and injury science? State of the art in management of ARDS. In this issue of the International Journal of Critical Illness and Injury Science, Krishnamoorthy and Chung[1] put forth a call to arms for a renewed investigative push in search of a clinical solution for the grave clinical problem of the acute respiratory distress syndrome (ARDS).[2,3] On a spectrum of inflammatory‑mediated acute pulmonary disease, ARDS represents the most severe form of acute lung injury (ALI).[3,4] The development of ARDS has been associated with a number of heterogeneous medical and surgical conditions, including aspiration,[5,6] sepsis,[7] pancreatitis,[8] bacterial or viral pneumonia,[9] and trauma.[4,10] The syndrome itself can be characterized by a phasic nature, beginning with an acute presentation, a subacute stage, and finally the chronic or “burnout” phase.[11] Survivors of ARDS may face significant functional disability following recovery from this syndrome.[12,13] A number of therapeutic strategies have been tested for ARDS, without delivery of consistent or reliable results.[14‑18] Among the most prominent efforts to improve patient outcomes in ARDS are the use of exogenous surfactant,[19] prone positioning, [20] corticosteroids, [21] adjunctive inhaled agents,[19,22] paralytics,[23] advanced mechanical ventilation strategies, [2,24] perfluorocarbon‑based liquid ventilation, [25,26] and extracorporeal membrane oxygenation (ECMO) support for the refractory cases.[27] The advent and implementation of these therapies has allowed improved oxygenation of patients and guided more accurate discussions with families regarding prognosis. However, for patients suffering from ARDS, the attenuation of the inflammatory response, the ability to limit the associated tissue injury, and the improvement of subsequent functional disability, seem to be among the most urgent issues that need our immediate attention.[28] Prior research by Meduri et al.,[28] and Crandall et al.,[29] demonstrates the potential benefits of an attenuated inflammatory response in the setting of ARDS. However, Access this article online Website: www.ijciis.org DOI: 10.4103/2229-5151.134140
Quick Response Code:
the complications of glucocorticoid usage as described by Meduri [28] and the infeasibility of splenectomy as presented by Crandall [29] limit both the applicability and generalizability of these approaches across the inherently heterogeneous ARDS population. The concept of intratracheal administration of ropivacaine, lidocaine, or possibly another local anesthetic and the need for further translational research, as put forth by Krishnamoorthy and Chung, is timely and intriguing.[1,30] An increasing number of publications seem to support some degree of physiologic or clinical benefit associated with intravenous and/or intratracheal lidocaine administration. [31‑34] Ropivacaine administration has also been linked to attenuation of ALI in the experimental setting.[30] However, most of this preliminary evidence comes from studies involving animal models. Notably, as with any pharmacologic intervention, there is at least one reported case of local administration of lidocaine associated with ARDS[35] and one instance of seizures following aspiration of viscous lidocaine.[36] Krishnamoorthy and Chung [1] present a very timely request for further scientific evaluation, and their position is well‑supported by the evidence accumulated over the past 15 years. In 2000, Hollmann et al. raised the question of local anesthetics being used for new therapeutic indications, stressing the anti-inflammatory properties of these pharmacologic agents. [37] Their exhaustive review highlighted the evidence of in vitro and in vivo anti‑inflammatory effects of local anesthetics through the modulation of the release of polymorphonuclear cell (PMN) mediators, as well as the apparent facilitation of PMNs concentrating at the site of needed action.[37] Hollmann et al., also called for further clinical studies, in addition to the need to specifically identify the associated mechanisms of action. Several years later, Cassuto et al., in another review further extolled the potential virtue of local anesthetics through their effects on the cells of the immune system.[38] In this review, the authors admitted that there were relatively limited numbers of diseases that could be treated with local anesthetics but local anesthetics could be a platform to pursue future therapeutic interventions in regard to inflammation.[38] This is indeed coming to pass. In this decade, the non‑anesthetic lidocaine analogue JMF2‑1 was tested on mice and guinea pigs. [39,40] The
International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 2 | Apr-Jun 2014
95
Stawicki, et al.: New frontiers in ARDS management
first study demonstrated that JMF2‑1 prevented asthma symptoms by reduction of T H2 cytokine generation and pulmonary eosinophilia by inhibition of T‑cell function and survival. Here, the modification of the lidocaine aromatic ring led to this therapeutic novelty. This evidence supports the abovementioned postulate by Cassuto. [38] This same research team, in a second study, suggested that JMF2‑1 inhibits the contraction of respiratory smooth muscle and affects T-cell proliferation and survival through a cyclic adenosine monophosphate (cAMP) intracellular pathway [40]. This evidence, in turn, further highlights the possibilities of a modified local anesthetic platform from the pharmacological perspective. Research on the mechanism(s) of action of local anesthetics and their role as anti‑inflammatory modulators has also progressed nicely. Wang et al., enhanced our understanding of the mechanism of action of lidocaine by presenting evidence that lidocaine’s anti‑inflammatory effect occurred by inhibiting the expression of high mobility box group 1 (HMGB1) mRNA and translocating both HMGB1 and nuclear factor‑κB (NF‑κB) to the cytoplasm from the nucleus.[41] Sera et al., added to the evidence of lidocaine as an anti‑inflammatory in asthma by nebulizing it in a murine model and demonstrating that: (a) it prevented eosinophilic inflammation, (b) prevented overproduction of mucous, (c) decreased peribronchial fibrosis, and (d) decreased hyperreactivity of the bronchial tree by the inhibition of allergen‑evoked GATA3 expression.[42] A more recent work by Yuan et al., shows that use of lidocaine prophylactically inhibits lipopolysaccharide (LPS)‑induced release of mediators of inflammation from microglia, and these effects are enforced by blockade of the p38 mitogen‑activated protein kinase (MAPK) and NF‑κB pathways. [43] Additional recent work by Picardi et al., introduced the concept of local anesthetic inhibition of neutrophil priming. This occurred through the Gαq‑protein‑mediated priming that was facilitated by ester compounds.[44] In addition to Blumenthal’s work with ropivacaine,[30] Piegler et al., have produced several works of interest that involve ropivacaine (actually both ropivacaine and lidocaine).[45,46] In the former, Piegeler et al., studied the addition of ropivacaine, lidocaine, and chloroprocaine to NCI‑H838 lung cancer cells incubated with tumor necrosis factor‑α (TNFα). Ropivacaine and lidocaine significantly decreased Src‑activation and intercellular adhesion molecule‑1 phosphorylation. Chloroprocaine had no effect. Thus, amide‑linked but not ester‑linked local anesthetics may present anti‑metastatic effects. In the latter study, Piegeler et al., presented the ability of ropivacaine and lidocaine to stop TNF‑α signals in epithelial cells by lessening the p85 recruitment to TNF‑receptor‑1, causing a decrease in endothelial nitric oxide synthetase and Akt (also known as Protein Kinase 96
B). In addition, Src phosphorylation is known to decrease neutrophil adhesion. Thus, both these local anesthetics, again, may have value in management of inflammatory disease. This cumulative evidence provides a strong impetus of the investigational use of ropivacaine and lidocaine in the treatment of ARDS and further supports the push for bench-to-bedside multi-institutional trials. Thoughtful and safe protocols need to be considered and acted upon by the critical care community. Krishnamoorthy and Chung are to be commended for this timely call to arms. Without innovation and some risk‑taking, true progress in our quest to tame ARDS will only remain a dream. Galileo and Copernicus claimed the Earth orbited the Sun and now we have modern astronomy;[47] Fleming followed up on an unusual fungal metabolite, and now we have penicillin;[48] and if not for Warren and Marshal considering a bacterium as the causative agent of peptic ulcer, we would continue to perform invasive procedures for this medically treatable condition.[49] Therefore, we are now faced with the distinct and increasingly credible possibility, if not probability, that local anesthetics may indeed be helpful in the treatment of ARDS. Stanislaw P Stawicki, Mamta Swaroop1, Sagar C Galwankar2, Thomas J Papadimos3
Department of Research and Innovation, St. Luke’s University Health Network, Bethlehem, Philadelphia, 1Department of Surgery, Northwestern University School of Medicine, Chicago, Illinois, 2Department of Emergency Medicine, Winter Haven Hospital, University of Florida, Florida, 3Department of Anesthesiology, The Ohio State University College of Medicine, Columbus, Ohio, USA Address for correspondence: Dr. Stanislaw P. Stawicki Department of Research and Innovation, St. Luke’s University Health Network, 801 Ostrum Street, Bethlehem, 18015 Pennsylvania, USA. E‑mail: [email protected]
REFERENCES 1. 2. 3.
4. 5. 6.
Krishnamoorty V, Chung L. Bench‑to‑bedside: The use of local anesthetics to attenuate inflammation in acute respiratory distress syndrome. Int J Crit Illness and Injury Science, 2014. 4(2). Stawicki SP, Goyal M, Sarani B. High‑frequency oscillatory ventilation (HFOV) and airway pressure release ventilation (APRV): A practical guide. J Intensive Care Med 2009;24:215‑29. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. Report of the American‑European consensus conference on ARDS: Definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee. Intensive Care Med 1994;20:225‑32. Zilberberg MD, Epstein SK. Acute lung injury in the medical ICU: Comorbid conditions, age, etiology, and hospital outcome. Am J Respir Crit Care Med 1998;157(4 Pt 1):1159‑64. El Solh AA, Bhora M, Pineda L, Aquilina A, Abbetessa L, Berbary E. Alveolar plasminogen activator inhibitor‑1 predicts ARDS in aspiration pneumonitis. Intensive Care Med 2006;32:110‑5. Putzke C, Max M, Geldner G, Wulf H. Severe ARDS following perioperative aspiration of gastric content associated with the use of a “ProSeal” laryngeal mask airway. Anasthesiol Intensivmed Notfallmed Schmerzther 2005;40:487‑9.
International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 2 | Apr-Jun 2014
Stawicki, et al.: New frontiers in ARDS management 7. 8. 9. 10. 11. 12. 13. 14.
15. 16.
17. 18. 19. 20.
21. 22. 23. 24. 25. 26.
27. 28. 29. 30.
Sheu CC, Gong MN, Zhai R, Chen F, Bajwa EK, Clardy PF, et al. Clinical characteristics and outcomes of sepsis‑related vs non‑sepsis‑related ARDS. Chest 2010;138:559‑67. Guice KS, Oldham KT, Johnson KJ, Kunkel RG, Morganroth ML, Ward PA. Pancreatitis‑induced acute lung injury. An ARDS model. Ann Surg 1988;208:71‑7. Zangrillo A. ECMO, ARDS and AH1N1. HSR Proc Intensive Care Cardiovasc Anesth 2009;1:5‑7. Donnelly SC, Robertson C. Trauma, inflammatory cells and ARDS. Arch Emerg Med 1993;10:108‑11. Fein A, Wiener‑Kronish JP, Niederman M, Matthay MA. Pathophysiology of the adult respiratory distress syndrome. What have we learned from human studies? Crit Care Clin 1986;2:429‑53. Wise MP, Hart N. Functional disability 5 years after ARDS. N Engl J Med 2011;365:275. author reply 275‑6. Pearmain L, Herridge MS. Outcomes after ARDS: A distinct group in the spectrum of disability after complex and protracted critical illness. Minerva Anestesiol 2013;79:793‑803. Haitsma JJ, Uhlig S, Lachmann U, Verbrugge SJ, Poelma DL, Lachmann B. Exogenous surfactant reduces ventilator‑induced decompartmentalization of tumor necrosis factor alpha in absence of positive end‑expiratory pressure. Intensive Care Med 2002;28:1131‑7. Haitsma JJ, Lachmann U, Lachmann B. Exogenous surfactant as a drug delivery agent. Adv Drug Deliv Rev 2001;47:197‑207. Lindén VB, Lidegran MK, Frisén G, Dahlgren P, Frenckner BP, Larsen F. ECMO in ARDS: A long‑term follow‑up study regarding pulmonary morphology and function and health‑related quality of life. Acta Anaesthesiol Scand 2009;53:489‑95. Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A. Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: Meta‑analysis. BMJ 2008;336:1006‑9. Suchyta MR, Clemmer TP, Orme JF Jr, Morris AH, Elliott CG. Increased survival of ARDS patients with severe hypoxemia (ECMO criteria). Chest 1991;99:951‑5. Möller JC, Schaible TF, Reiss I, Artlich A, Gortner L. Treatment of severe non‑neonatal ARDS in children with surfactant and nitric oxide in a “pre‑ECMO”‑situation. Int J Artif Organs 1995;18:598‑602. Ullrich R, Lorber C, Röder G, Urak G, Faryniak B, Sladen RN, et al. Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS. Anesthesiology 1999;91:1577‑86. Luce JM. Corticosteroids in ARDS. An evidence‑based review. Crit Care Clin 2002;18: 79‑89, vii. Van Heerden PV, Blythe D, Webb SA. Inhaled aerosolized prostacyclin and nitric oxide as selective pulmonary vasodilators in ARDS‑‑a pilot study. Anaesth Intensive Care 1996;24:564‑8. Hraiech S, Forel JM, Papazian L. The role of neuromuscular blockers in ARDS: Benefits and risks. Curr Opin Crit Care 2012;18:495‑502. Slutsky AS, Ranieri VM. Mechanical ventilation: Lessons from the ARDSNet trial. Respir Res 2000;1:73‑7. Lozano JA, Castro JA, Rodrigo I. Partial liquid ventilation with perfluorocarbons for treatment of ARDS in burns. Burns 2001;27:635‑42. Papo M, Paczan P, Burak B, Holms B, Steinhorn D, Hernan L, et al. A medical grade perfluorocarbon used during PAGE improves oxygenation and ventilation in a model of ARDS. Crit Care Med 1993;21:S288. Pappert D, Rossaint R, Falke K. Treatment of ARDS with nitric oxide and ECMO. Int J Artif Organs 1995;18:611‑9. Meduri GU, Annane D, Chrousos GP, Marik PE, Sinclair SE. Activation and regulation of systemic inflammation in ARDS: Rationale for prolonged glucocorticoid therapy. Chest 2009;136:1631‑43. Crandall M, Shapiro MB, West MA. Does splenectomy protect against immune‑mediated complications in blunt trauma patients? Mol Med 2009;15:263‑7. Blumenthal S, Borgeat A, Pasch T, Reyes L, Booy C, Lambert M, et al.
31. 32. 33. 34. 35. 36. 37. 38. 39.
40.
41. 42.
43. 44.
45.
46.
47. 48. 49.
Ropivacaine decreases inflammation in experimental endotoxin‑induced lung injury. Anesthesiology 2006;104:961‑9. Meyanci G, Cosan F, Oz H. The effect of intratracheal and intravenous lidocaine in hydrochloric acid‑induced acute lung injury in rabbits. Crit Care 2001;5:29‑S30. Kiyonari Y, Nishina K, Mikawa K, Maekawa N, Obara H. Lidocaine attenuates acute lung injury induced by a combination of phospholipase A2 and trypsin. Crit Care Med 2000;28:484‑9. Nishina K, Mikawa K, Takao Y, Shiga M, Maekawa N, Obara H. Intravenous lidocaine attenuates acute lung injury induced by hydrochloric acid aspiration in rabbits. Anesthesiology 1998;88:1300‑9. Takao Y, Mikawa K, Nishina K, Maekawa N, Obara H. Lidocaine attenuates hyperoxic lung injury in rabbits. Acta Anaesthesiol Scand 1996;40:318‑25. Woelke BJ, Tucker RA. ARDS after local lidocaine administration. Chest 1983;83:933‑4. Garrettson LK, McGee EB. Rapid onset of seizures following aspiration of viscous lidocaine. J Toxicol Clin Toxicol 1992;30:413‑22. Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: A new therapeutic indication? Anesthesiology 2000;93:858‑75. Cassuto J, Sinclair R, Bonderovic M. Anti‑inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand 2006;50:265‑82. Olsen PC, Ferreira TP, Serra MF, Farias‑Filho FA, Fonseca BP, Viola JP, et al. Lidocaine‑derivative JMF2‑1 prevents ovalbumin‑induced airway inflammation by regulating the function and survival of T cells. Clin Exp Allergy 2011;41:250‑9. Olsen PC, Coelho LP, da Costa JC, Cordeiro RS, Silva PM, Martins MA. Two for one: Cyclic AMP mediates the anti‑inflammatory and anti‑spasmodic properties of the non‑anesthetic lidocaine analog JMF2‑1. Eur J Pharmacol 2012;680:102‑7. Wang HL, Zhang WH, Lei WF, Zhou CQ, Ye T. The inhibitory effect of lidocaine on the release of high mobility group box1 in lipopolysaccharide‑stimulated macrophages. Anesth Analg 2011;112:839‑44. Serra MF, Anjos‑Valotta EA, Olsen PC, Couto GC, Jurgilas PB, Cotias AC, et al. Nebulized lidocaine prevents airway inflammation, peribronchial fibrosis, and mucus production in a murine model of asthma. Anesthesiology 2012;117:580‑91. Yuan T, Li Z, Li X, Yu, G, Wang N, Yang X, et al. Lidocaine attenuates LPS‑induced inflammatory responses in microglia. J Surg Res 2014. [doi: 10.1016/j.jss.2014.05.023]. Picardi S, Cartellieri S, Groves D, Hahnenkamp K, Gerner P, Durieux ME, et al. Local anesthetic‑induced inhibition of human neutrophil priming: The influence of structure, lipophilicity, and charge. Reg Anesth Pain Med 2013;38:9‑15. Piegeler T, Votta‑Velis EG, Liu G, Place AT, Schwartz DE, Beck‑Schimmer B, et al. Antimetastatic potential of amide‑linked local anesthetics: Inhibition of lung adenocarcinoma cell migration and inflammatory Src signaling independent of sodium channel blockade. Anesthesiology 2012;117:548‑59. Piegeler T, Votta‑Velis EG, Bakhshi FR, Mao M, Carnegie G, Bonini MG, et al. Endothelial barrier protection by local anesthetics: Ropivacaine and lidocaine block tumor necrosis factor‑alpha‑induced endothelial cell src activation. Anesthesiology 2014;120:1414‑28. Streufert S. Complexity: An integration of theories. J Appl Soc Psychol 1997;27:2068‑95. Bennett JW, Chung KT. Alexander Fleming and the discovery of penicillin. Adv Appl Microbiol 2001;49:163‑84. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311‑5.
Cite this article as: Stawicki SP, Swaroop M, Galwankar SC, Papadimos TJ. What's new in critical illness and injury science? State of the art in management of ARDS. Int J Crit Illn Inj Sci 2014;4:95-7. Source of Support: Nil, Conflict of Interest: No.
International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 2 | Apr-Jun 2014
97
Copyright of International Journal of Critical Illness & Injury Science is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
What’s new in critical illness and injury science? State of the art in management of ARDS. In this issue of the International Journal of Critical Illness and Injury Science, Krishnamoorthy and Chung[1] put forth a call to arms for a renewed investigative push in search of a clinical solution for the grave clinical problem of the acute respiratory distress syndrome (ARDS).[2,3] On a spectrum of inflammatory‑mediated acute pulmonary disease, ARDS represents the most severe form of acute lung injury (ALI).[3,4] The development of ARDS has been associated with a number of heterogeneous medical and surgical conditions, including aspiration,[5,6] sepsis,[7] pancreatitis,[8] bacterial or viral pneumonia,[9] and trauma.[4,10] The syndrome itself can be characterized by a phasic nature, beginning with an acute presentation, a subacute stage, and finally the chronic or “burnout” phase.[11] Survivors of ARDS may face significant functional disability following recovery from this syndrome.[12,13] A number of therapeutic strategies have been tested for ARDS, without delivery of consistent or reliable results.[14‑18] Among the most prominent efforts to improve patient outcomes in ARDS are the use of exogenous surfactant,[19] prone positioning, [20] corticosteroids, [21] adjunctive inhaled agents,[19,22] paralytics,[23] advanced mechanical ventilation strategies, [2,24] perfluorocarbon‑based liquid ventilation, [25,26] and extracorporeal membrane oxygenation (ECMO) support for the refractory cases.[27] The advent and implementation of these therapies has allowed improved oxygenation of patients and guided more accurate discussions with families regarding prognosis. However, for patients suffering from ARDS, the attenuation of the inflammatory response, the ability to limit the associated tissue injury, and the improvement of subsequent functional disability, seem to be among the most urgent issues that need our immediate attention.[28] Prior research by Meduri et al.,[28] and Crandall et al.,[29] demonstrates the potential benefits of an attenuated inflammatory response in the setting of ARDS. However, Access this article online Website: www.ijciis.org DOI: 10.4103/2229-5151.134140
Quick Response Code:
the complications of glucocorticoid usage as described by Meduri [28] and the infeasibility of splenectomy as presented by Crandall [29] limit both the applicability and generalizability of these approaches across the inherently heterogeneous ARDS population. The concept of intratracheal administration of ropivacaine, lidocaine, or possibly another local anesthetic and the need for further translational research, as put forth by Krishnamoorthy and Chung, is timely and intriguing.[1,30] An increasing number of publications seem to support some degree of physiologic or clinical benefit associated with intravenous and/or intratracheal lidocaine administration. [31‑34] Ropivacaine administration has also been linked to attenuation of ALI in the experimental setting.[30] However, most of this preliminary evidence comes from studies involving animal models. Notably, as with any pharmacologic intervention, there is at least one reported case of local administration of lidocaine associated with ARDS[35] and one instance of seizures following aspiration of viscous lidocaine.[36] Krishnamoorthy and Chung [1] present a very timely request for further scientific evaluation, and their position is well‑supported by the evidence accumulated over the past 15 years. In 2000, Hollmann et al. raised the question of local anesthetics being used for new therapeutic indications, stressing the anti-inflammatory properties of these pharmacologic agents. [37] Their exhaustive review highlighted the evidence of in vitro and in vivo anti‑inflammatory effects of local anesthetics through the modulation of the release of polymorphonuclear cell (PMN) mediators, as well as the apparent facilitation of PMNs concentrating at the site of needed action.[37] Hollmann et al., also called for further clinical studies, in addition to the need to specifically identify the associated mechanisms of action. Several years later, Cassuto et al., in another review further extolled the potential virtue of local anesthetics through their effects on the cells of the immune system.[38] In this review, the authors admitted that there were relatively limited numbers of diseases that could be treated with local anesthetics but local anesthetics could be a platform to pursue future therapeutic interventions in regard to inflammation.[38] This is indeed coming to pass. In this decade, the non‑anesthetic lidocaine analogue JMF2‑1 was tested on mice and guinea pigs. [39,40] The
International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 2 | Apr-Jun 2014
95
Stawicki, et al.: New frontiers in ARDS management
first study demonstrated that JMF2‑1 prevented asthma symptoms by reduction of T H2 cytokine generation and pulmonary eosinophilia by inhibition of T‑cell function and survival. Here, the modification of the lidocaine aromatic ring led to this therapeutic novelty. This evidence supports the abovementioned postulate by Cassuto. [38] This same research team, in a second study, suggested that JMF2‑1 inhibits the contraction of respiratory smooth muscle and affects T-cell proliferation and survival through a cyclic adenosine monophosphate (cAMP) intracellular pathway [40]. This evidence, in turn, further highlights the possibilities of a modified local anesthetic platform from the pharmacological perspective. Research on the mechanism(s) of action of local anesthetics and their role as anti‑inflammatory modulators has also progressed nicely. Wang et al., enhanced our understanding of the mechanism of action of lidocaine by presenting evidence that lidocaine’s anti‑inflammatory effect occurred by inhibiting the expression of high mobility box group 1 (HMGB1) mRNA and translocating both HMGB1 and nuclear factor‑κB (NF‑κB) to the cytoplasm from the nucleus.[41] Sera et al., added to the evidence of lidocaine as an anti‑inflammatory in asthma by nebulizing it in a murine model and demonstrating that: (a) it prevented eosinophilic inflammation, (b) prevented overproduction of mucous, (c) decreased peribronchial fibrosis, and (d) decreased hyperreactivity of the bronchial tree by the inhibition of allergen‑evoked GATA3 expression.[42] A more recent work by Yuan et al., shows that use of lidocaine prophylactically inhibits lipopolysaccharide (LPS)‑induced release of mediators of inflammation from microglia, and these effects are enforced by blockade of the p38 mitogen‑activated protein kinase (MAPK) and NF‑κB pathways. [43] Additional recent work by Picardi et al., introduced the concept of local anesthetic inhibition of neutrophil priming. This occurred through the Gαq‑protein‑mediated priming that was facilitated by ester compounds.[44] In addition to Blumenthal’s work with ropivacaine,[30] Piegler et al., have produced several works of interest that involve ropivacaine (actually both ropivacaine and lidocaine).[45,46] In the former, Piegeler et al., studied the addition of ropivacaine, lidocaine, and chloroprocaine to NCI‑H838 lung cancer cells incubated with tumor necrosis factor‑α (TNFα). Ropivacaine and lidocaine significantly decreased Src‑activation and intercellular adhesion molecule‑1 phosphorylation. Chloroprocaine had no effect. Thus, amide‑linked but not ester‑linked local anesthetics may present anti‑metastatic effects. In the latter study, Piegeler et al., presented the ability of ropivacaine and lidocaine to stop TNF‑α signals in epithelial cells by lessening the p85 recruitment to TNF‑receptor‑1, causing a decrease in endothelial nitric oxide synthetase and Akt (also known as Protein Kinase 96
B). In addition, Src phosphorylation is known to decrease neutrophil adhesion. Thus, both these local anesthetics, again, may have value in management of inflammatory disease. This cumulative evidence provides a strong impetus of the investigational use of ropivacaine and lidocaine in the treatment of ARDS and further supports the push for bench-to-bedside multi-institutional trials. Thoughtful and safe protocols need to be considered and acted upon by the critical care community. Krishnamoorthy and Chung are to be commended for this timely call to arms. Without innovation and some risk‑taking, true progress in our quest to tame ARDS will only remain a dream. Galileo and Copernicus claimed the Earth orbited the Sun and now we have modern astronomy;[47] Fleming followed up on an unusual fungal metabolite, and now we have penicillin;[48] and if not for Warren and Marshal considering a bacterium as the causative agent of peptic ulcer, we would continue to perform invasive procedures for this medically treatable condition.[49] Therefore, we are now faced with the distinct and increasingly credible possibility, if not probability, that local anesthetics may indeed be helpful in the treatment of ARDS. Stanislaw P Stawicki, Mamta Swaroop1, Sagar C Galwankar2, Thomas J Papadimos3
Department of Research and Innovation, St. Luke’s University Health Network, Bethlehem, Philadelphia, 1Department of Surgery, Northwestern University School of Medicine, Chicago, Illinois, 2Department of Emergency Medicine, Winter Haven Hospital, University of Florida, Florida, 3Department of Anesthesiology, The Ohio State University College of Medicine, Columbus, Ohio, USA Address for correspondence: Dr. Stanislaw P. Stawicki Department of Research and Innovation, St. Luke’s University Health Network, 801 Ostrum Street, Bethlehem, 18015 Pennsylvania, USA. E‑mail: [email protected]
REFERENCES 1. 2. 3.
4. 5. 6.
Krishnamoorty V, Chung L. Bench‑to‑bedside: The use of local anesthetics to attenuate inflammation in acute respiratory distress syndrome. Int J Crit Illness and Injury Science, 2014. 4(2). Stawicki SP, Goyal M, Sarani B. High‑frequency oscillatory ventilation (HFOV) and airway pressure release ventilation (APRV): A practical guide. J Intensive Care Med 2009;24:215‑29. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. Report of the American‑European consensus conference on ARDS: Definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee. Intensive Care Med 1994;20:225‑32. Zilberberg MD, Epstein SK. Acute lung injury in the medical ICU: Comorbid conditions, age, etiology, and hospital outcome. Am J Respir Crit Care Med 1998;157(4 Pt 1):1159‑64. El Solh AA, Bhora M, Pineda L, Aquilina A, Abbetessa L, Berbary E. Alveolar plasminogen activator inhibitor‑1 predicts ARDS in aspiration pneumonitis. Intensive Care Med 2006;32:110‑5. Putzke C, Max M, Geldner G, Wulf H. Severe ARDS following perioperative aspiration of gastric content associated with the use of a “ProSeal” laryngeal mask airway. Anasthesiol Intensivmed Notfallmed Schmerzther 2005;40:487‑9.
International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 2 | Apr-Jun 2014
Stawicki, et al.: New frontiers in ARDS management 7. 8. 9. 10. 11. 12. 13. 14.
15. 16.
17. 18. 19. 20.
21. 22. 23. 24. 25. 26.
27. 28. 29. 30.
Sheu CC, Gong MN, Zhai R, Chen F, Bajwa EK, Clardy PF, et al. Clinical characteristics and outcomes of sepsis‑related vs non‑sepsis‑related ARDS. Chest 2010;138:559‑67. Guice KS, Oldham KT, Johnson KJ, Kunkel RG, Morganroth ML, Ward PA. Pancreatitis‑induced acute lung injury. An ARDS model. Ann Surg 1988;208:71‑7. Zangrillo A. ECMO, ARDS and AH1N1. HSR Proc Intensive Care Cardiovasc Anesth 2009;1:5‑7. Donnelly SC, Robertson C. Trauma, inflammatory cells and ARDS. Arch Emerg Med 1993;10:108‑11. Fein A, Wiener‑Kronish JP, Niederman M, Matthay MA. Pathophysiology of the adult respiratory distress syndrome. What have we learned from human studies? Crit Care Clin 1986;2:429‑53. Wise MP, Hart N. Functional disability 5 years after ARDS. N Engl J Med 2011;365:275. author reply 275‑6. Pearmain L, Herridge MS. Outcomes after ARDS: A distinct group in the spectrum of disability after complex and protracted critical illness. Minerva Anestesiol 2013;79:793‑803. Haitsma JJ, Uhlig S, Lachmann U, Verbrugge SJ, Poelma DL, Lachmann B. Exogenous surfactant reduces ventilator‑induced decompartmentalization of tumor necrosis factor alpha in absence of positive end‑expiratory pressure. Intensive Care Med 2002;28:1131‑7. Haitsma JJ, Lachmann U, Lachmann B. Exogenous surfactant as a drug delivery agent. Adv Drug Deliv Rev 2001;47:197‑207. Lindén VB, Lidegran MK, Frisén G, Dahlgren P, Frenckner BP, Larsen F. ECMO in ARDS: A long‑term follow‑up study regarding pulmonary morphology and function and health‑related quality of life. Acta Anaesthesiol Scand 2009;53:489‑95. Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A. Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: Meta‑analysis. BMJ 2008;336:1006‑9. Suchyta MR, Clemmer TP, Orme JF Jr, Morris AH, Elliott CG. Increased survival of ARDS patients with severe hypoxemia (ECMO criteria). Chest 1991;99:951‑5. Möller JC, Schaible TF, Reiss I, Artlich A, Gortner L. Treatment of severe non‑neonatal ARDS in children with surfactant and nitric oxide in a “pre‑ECMO”‑situation. Int J Artif Organs 1995;18:598‑602. Ullrich R, Lorber C, Röder G, Urak G, Faryniak B, Sladen RN, et al. Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS. Anesthesiology 1999;91:1577‑86. Luce JM. Corticosteroids in ARDS. An evidence‑based review. Crit Care Clin 2002;18: 79‑89, vii. Van Heerden PV, Blythe D, Webb SA. Inhaled aerosolized prostacyclin and nitric oxide as selective pulmonary vasodilators in ARDS‑‑a pilot study. Anaesth Intensive Care 1996;24:564‑8. Hraiech S, Forel JM, Papazian L. The role of neuromuscular blockers in ARDS: Benefits and risks. Curr Opin Crit Care 2012;18:495‑502. Slutsky AS, Ranieri VM. Mechanical ventilation: Lessons from the ARDSNet trial. Respir Res 2000;1:73‑7. Lozano JA, Castro JA, Rodrigo I. Partial liquid ventilation with perfluorocarbons for treatment of ARDS in burns. Burns 2001;27:635‑42. Papo M, Paczan P, Burak B, Holms B, Steinhorn D, Hernan L, et al. A medical grade perfluorocarbon used during PAGE improves oxygenation and ventilation in a model of ARDS. Crit Care Med 1993;21:S288. Pappert D, Rossaint R, Falke K. Treatment of ARDS with nitric oxide and ECMO. Int J Artif Organs 1995;18:611‑9. Meduri GU, Annane D, Chrousos GP, Marik PE, Sinclair SE. Activation and regulation of systemic inflammation in ARDS: Rationale for prolonged glucocorticoid therapy. Chest 2009;136:1631‑43. Crandall M, Shapiro MB, West MA. Does splenectomy protect against immune‑mediated complications in blunt trauma patients? Mol Med 2009;15:263‑7. Blumenthal S, Borgeat A, Pasch T, Reyes L, Booy C, Lambert M, et al.
31. 32. 33. 34. 35. 36. 37. 38. 39.
40.
41. 42.
43. 44.
45.
46.
47. 48. 49.
Ropivacaine decreases inflammation in experimental endotoxin‑induced lung injury. Anesthesiology 2006;104:961‑9. Meyanci G, Cosan F, Oz H. The effect of intratracheal and intravenous lidocaine in hydrochloric acid‑induced acute lung injury in rabbits. Crit Care 2001;5:29‑S30. Kiyonari Y, Nishina K, Mikawa K, Maekawa N, Obara H. Lidocaine attenuates acute lung injury induced by a combination of phospholipase A2 and trypsin. Crit Care Med 2000;28:484‑9. Nishina K, Mikawa K, Takao Y, Shiga M, Maekawa N, Obara H. Intravenous lidocaine attenuates acute lung injury induced by hydrochloric acid aspiration in rabbits. Anesthesiology 1998;88:1300‑9. Takao Y, Mikawa K, Nishina K, Maekawa N, Obara H. Lidocaine attenuates hyperoxic lung injury in rabbits. Acta Anaesthesiol Scand 1996;40:318‑25. Woelke BJ, Tucker RA. ARDS after local lidocaine administration. Chest 1983;83:933‑4. Garrettson LK, McGee EB. Rapid onset of seizures following aspiration of viscous lidocaine. J Toxicol Clin Toxicol 1992;30:413‑22. Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: A new therapeutic indication? Anesthesiology 2000;93:858‑75. Cassuto J, Sinclair R, Bonderovic M. Anti‑inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand 2006;50:265‑82. Olsen PC, Ferreira TP, Serra MF, Farias‑Filho FA, Fonseca BP, Viola JP, et al. Lidocaine‑derivative JMF2‑1 prevents ovalbumin‑induced airway inflammation by regulating the function and survival of T cells. Clin Exp Allergy 2011;41:250‑9. Olsen PC, Coelho LP, da Costa JC, Cordeiro RS, Silva PM, Martins MA. Two for one: Cyclic AMP mediates the anti‑inflammatory and anti‑spasmodic properties of the non‑anesthetic lidocaine analog JMF2‑1. Eur J Pharmacol 2012;680:102‑7. Wang HL, Zhang WH, Lei WF, Zhou CQ, Ye T. The inhibitory effect of lidocaine on the release of high mobility group box1 in lipopolysaccharide‑stimulated macrophages. Anesth Analg 2011;112:839‑44. Serra MF, Anjos‑Valotta EA, Olsen PC, Couto GC, Jurgilas PB, Cotias AC, et al. Nebulized lidocaine prevents airway inflammation, peribronchial fibrosis, and mucus production in a murine model of asthma. Anesthesiology 2012;117:580‑91. Yuan T, Li Z, Li X, Yu, G, Wang N, Yang X, et al. Lidocaine attenuates LPS‑induced inflammatory responses in microglia. J Surg Res 2014. [doi: 10.1016/j.jss.2014.05.023]. Picardi S, Cartellieri S, Groves D, Hahnenkamp K, Gerner P, Durieux ME, et al. Local anesthetic‑induced inhibition of human neutrophil priming: The influence of structure, lipophilicity, and charge. Reg Anesth Pain Med 2013;38:9‑15. Piegeler T, Votta‑Velis EG, Liu G, Place AT, Schwartz DE, Beck‑Schimmer B, et al. Antimetastatic potential of amide‑linked local anesthetics: Inhibition of lung adenocarcinoma cell migration and inflammatory Src signaling independent of sodium channel blockade. Anesthesiology 2012;117:548‑59. Piegeler T, Votta‑Velis EG, Bakhshi FR, Mao M, Carnegie G, Bonini MG, et al. Endothelial barrier protection by local anesthetics: Ropivacaine and lidocaine block tumor necrosis factor‑alpha‑induced endothelial cell src activation. Anesthesiology 2014;120:1414‑28. Streufert S. Complexity: An integration of theories. J Appl Soc Psychol 1997;27:2068‑95. Bennett JW, Chung KT. Alexander Fleming and the discovery of penicillin. Adv Appl Microbiol 2001;49:163‑84. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311‑5.
Cite this article as: Stawicki SP, Swaroop M, Galwankar SC, Papadimos TJ. What's new in critical illness and injury science? State of the art in management of ARDS. Int J Crit Illn Inj Sci 2014;4:95-7. Source of Support: Nil, Conflict of Interest: No.
International Journal of Critical Illness and Injury Science | Vol. 4 | Issue 2 | Apr-Jun 2014
97
Copyright of International Journal of Critical Illness & Injury Science is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
