Stress hyperglycaemia following trauma - a survival benefit or an outcome detriment?
Journal
Current opinion in anaesthesiology
ISSN: 1473-6500
Titre abrégé: Curr Opin Anaesthesiol
Pays: United States
ID NLM: 8813436
Informations de publication
Date de publication:
22 Jan 2024
22 Jan 2024
Historique:
medline:
23
2
2024
pubmed:
23
2
2024
entrez:
23
2
2024
Statut:
aheadofprint
Résumé
Stress hyperglycaemia occur often in critically injured patients. To gain new consideration about it, this review compile current as well as known immunological and biochemical findings about causes and emergence. Glucose is the preferred energy substrate for fending immune cells, reparative tissue and the cardiovascular system following trauma. To fulfil these energy needs, the liver is metabolically reprogrammed to rebuild glucose from lactate and glucogenic amino acids (hepatic insulin resistance) at the expenses of muscles mass and - to a less extent - fat tissue (proteolysis, lipolysis, peripheral insulin resistance). This inevitably leads to stress hyperglycaemia, which is evolutionary preserved and seems to be an essential and beneficial survival response. It is initiated by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), intensified by immune cells itself and mainly ruled by tumour necrosis factor (TNF)α and catecholamines with lactate and hypoxia inducible factor (HIF)-1α as intracellular signals and lactate as an energy shuttle. Important biochemical mechanisms involved in this response are the Warburg effect as an efficient metabolic shortcut and the extended Cori cycle. Stress hyperglycaemia is beneficial in an acute life-threatening situation, but further research is necessary, to prevent trauma patients from the detrimental effects of persisting hyperglycaemia.
Identifiants
pubmed: 38390910
doi: 10.1097/ACO.0000000000001350
pii: 00001503-990000000-00162
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Références
McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin 2001; 17:107–124.
Vanhorebeek I, van den Berghe G. Diabetes of injury: novel insights. Endocrinol Metab Clin North Am 2006; 35:859–872. x.
Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000; 355:773–778.
Christiansen C, Toft P, Jørgensen HS, et al. Hyperglycaemia and mortality in critically ill patients. A prospective study. Intensive Care Med 2004; 30:1685–1688.
Kreutziger J, Wenzel V, Kurz A, Constantinescu MA. Admission blood glucose is an independent predictive factor for hospital mortality in polytraumatised patients. Intensive Care Med 2009; 35:1234–1239.
Heldreth AC, Demissie S, Pandya S, et al. Stress-induced (not diabetic) hyperglycemia is associated with mortality in geriatric trauma patients. J Surg Res 2023; 289:247–252.
Rau C-S, Wu S-C, Chen Y-C, et al. Higher mortality in trauma patients is associated with stress-induced hyperglycemia, but not diabetic hyperglycemia: a cross-sectional analysis based on a propensity-score matching approach. Int J Environ Res Public Health 2017; 14:E1161.
Jeremitsky E, Omert L, Dunham CM, et al. Harbingers of poor outcome the day after severe brain injury: hypothermia, hypoxia, and hypoperfusion. J Trauma 2003; 54:312–319.
Tsai Y-C, Wu S-C, Hsieh T-M, et al. Association of stress-induced hyperglycemia and diabetic hyperglycemia with mortality in patients with traumatic brain injury: analysis of a propensity score-matched population. Int J Environ Res Public Health 2020; 17:4266–4276.
Bosarge PL, Shoultz TH, Griffin RL, Kerby JD. Stress-induced hyperglycemia is associated with higher mortality in severe traumatic brain injury. J Trauma Acute Care Surg 2015; 79:289–294.
Rosso C, Pires C, Corvol J-C, et al. Hyperglycaemia, insulin therapy and critical penumbral regions for prognosis in acute stroke: further insights from the INSULINFARCT trial. PLoS One 2015; 10:e0120230.
Nanas S, Kritikos K, Angelopoulos E, et al. Predisposing factors for critical illness polyneuromyopathy in a multidisciplinary intensive care unit. Acta Neurol Scand 2008; 118:175–181.
Mikaeili H, Yazdchi M, Barazandeh F, Ansarin K. Euglycemic state reduces the incidence of critical illness polyneuropathy and duration of ventilator dependency in medical intensive care unit. Bratisl Lek Listy 2012; 113:616–619.
Huang X, Shi Y, Chen H, et al. Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism. Cell Death Dis 2020; 11:1040.
Huang Y-F, Zhang Y, Liu C-X, et al. microRNA-125b contributes to high glucose-induced reactive oxygen species generation and apoptosis in HK-2 renal tubular epithelial cells by targeting angiotensin-converting enzyme 2. Eur Rev Med Pharmacol Sci 2016; 20:4055–4062.
van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345:1359–1367.
Liu H, Wang X, Liu S, et al. Effects and mechanism of miR-23b on glucose-mediated epithelial-to-mesenchymal transition in diabetic nephropathy. Int JBiochem Cell Biol 2016; 70:149–160.
Ishiguchi T, Tada H, Nakagawa K, et al. Hyperglycemia impairs antro-pyloric coordination and delays gastric emptying in conscious rats. Auton Neurosci Basic Clin 2002; 95:112–120.
Li Z, Zhang J, Ma Z, et al. Endothelial YAP mediates hyperglycemia-induced platelet hyperactivity and arterial thrombosis. Arterioscler Thromb Vasc Biol 2023; 44:254–270.
Giugliano D, Marfella R, Coppola L, et al. Vascular effects of acute hyperglycemia in humans are reversed by l-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation 1997; 95:1783–1790.
Tang WH, Cheng WT, Kravtsov GM, et al. Cardiac contractile dysfunction during acute hyperglycemia due to impairment of SERCA by polyol pathway-mediated oxidative stress. Am J Physiol Cell Physiol 2010; 299:C643–C653.
van Niekerk G, Davis T, Engelbrecht A-M. Hyperglycaemia in critically ill patients: the immune system's sweet tooth. Crit Care 2017; 21:202.
Czajka A, Ajaz S, Gnudi L, et al. Altered mitochondrial function, mitochondrial DNA and reduced metabolic flexibility in patients with diabetic nephropathy. EBioMedicine 2015; 2:499–512.
Souza Ferreira C de, Araújo TH, Ângelo ML, et al. Neutrophil dysfunction induced by hyperglycemia: modulation of myeloperoxidase activity. Cell Biochem Funct 2012; 30:604–610.
Otto NM, Schindler R, Lun A, et al. Hyperosmotic stress enhances cytokine production and decreases phagocytosis in vitro. Crit Care 2008; 12:R107.
Kreutziger J, Schlaepfer J, Wenzel V, Constantinescu MA. The role of admission blood glucose in outcome prediction of surviving patients with multiple injuries. J Trauma 2009; 67:704–708.
Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response!. Crit Care 2013; 17:305.
Chernow B, Rainey TG, Lake CR. Endogenous and exogenous catecholamines in critical care medicine. Crit Care Med 1982; 10:409–416.
Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol 2008; 8:279–289.
Jiang D, Liang J, Fan J, et al. Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med 2005; 11:1173–1179.
Shi H, Hua X, Kong D, et al. Role of Toll-like receptor mediated signaling in traumatic brain injury. Neuropharmacology 2019; 145:259–267.
Köhl J. The role of complement in danger sensing and transmission. Immunol Res 2006; 34:157–176.
Matzinger P. The danger model: a renewed sense of self. Science 2002; 296:301–305.
Burk A-M, Martin M, Flierl MA, et al. Early complementopathy after multiple injuries in humans. Shock 2012; 37:348–354.
Szczesny B, Marcatti M, Ahmad A, et al. Mitochondrial DNA damage and subsequent activation of Z-DNA binding protein 1 links oxidative stress to inflammation in epithelial cells. Sci Rep 2018; 8:914.
Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 2010; 464:104–107.
Aswani A, Manson J, Itagaki K, et al. Scavenging circulating mitochondrial DNA as a potential therapeutic option for multiple organ dysfunction in trauma hemorrhage. Front Immunol 2018; 9:891.
Fan J, Li Y, Levy RM, et al. Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1-TLR4 signaling. J Immunol 2007; 178:6573–6580.
Levy RM, Mollen KP, Prince JM, et al. Systemic inflammation and remote organ injury following trauma require HMGB1. American journal of physiology. Regul Integr Compar Physiol 2007; 293:R1538–R1544.
Vénéreau E, Ceriotti C, Bianchi ME. DAMPs from cell death to new life. Front Immunol 2015; 6:422.
Janeway C. Immunogenicity signals 1, 2, 3 … and 0. Immunol Today 1989; 10:283–286.
Rongvaux A. Innate immunity and tolerance toward mitochondria. Mitochondrion 2018; 41:14–20.
Wilkins HM, Weidling IW, Ji Y, Swerdlow RH. Mitochondria-derived damage-associated molecular patterns in neurodegeneration. Front Immunol 2017; 8:508.
Meylan E, Tschopp J, Karin M. Intracellular pattern recognition receptors in the host response. Nature 2006; 442:39–44.
Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004; 4:499–511.
Martinez I, Sveinbjørnsson B, Vidal-Vanaclocha F, et al. Differential cytokine-mediated modulation of endocytosis in rat liver endothelial cells. Biochem Biophys Res Commun 1995; 212:235–241.
McDonald B, Kubes P. Neutrophils and intravascular immunity in the liver during infection and sterile inflammation. Toxicol Pathol 2012; 40:157–165.
Campbell SJ, Zahid I, Losey P, et al. Liver Kupffer cells control the magnitude of the inflammatory response in the injured brain and spinal cord. Neuropharmacology 2008; 55:780–787.
Campbell SJ, Perry VH, Pitossi FJ, et al. Central nervous system injury triggers hepatic CC and CXC chemokine expression that is associated with leukocyte mobilization and recruitment to both the central nervous system and the liver. Am J Pathol 2005; 166:1487–1497.
Campbell SJ, Hughes PM, Iredale JP, et al. CINC-1 is an acute-phase protein induced by focal brain injury causing leukocyte mobilization and liver injury. FASEB J 2003; 17:1168–1170.
Chen X-L, Sun L, Guo F, et al. High-mobility group box-1 induces proinflammatory cytokines production of Kupffer cells through TLRs-dependent signaling pathway after burn injury. PLoS One 2012; 7:e50668.
Bamboat ZM, Balachandran VP, Ocuin LM, et al. Toll-like receptor 9 inhibition confers protection from liver ischemia-reperfusion injury. Hepatology 2010; 51:621–632.
Flierl MA, Rittirsch D, Nadeau BA, et al. Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature 2007; 449:721–725.
Bergquist J, Tarkowski A, Ekman R, Ewing A. Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop. Proc Natl Acad Sci USA 1994; 91:12912–12916.
Chu C an, Galassetti P, Igawa K, et al. Interaction of free fatty acids and epinephrine in regulating hepatic glucose production in conscious dogs. Am J Physiol Endocrinol Metab 2003; 284:E291–E301.
Chu CA, Sindelar DK, Neal DW, et al. Comparison of the direct and indirect effects of epinephrine on hepatic glucose production. J Clin Invest 1997; 99:1044–1056.
Miksa M, Wu R, Zhou M, Wang P. Sympathetic excitotoxicity in sepsis: pro-inflammatory priming of macrophages by norepinephrine. Front Biosci 2005; 10:2217–2229.
Frink M, Hsieh Y-C, Thobe BM, et al. TLR4 regulates Kupffer cell chemokine production, systemic inflammation and lung neutrophil infiltration following trauma-hemorrhage. Mol Immunol 2007; 44:2625–2630.
Yang S, Zhou M, Chaudry IH, Wang P. Norepinephrine-induced hepatocellular dysfunction in early sepsis is mediated by activation of alpha2-adrenoceptors. Am J Physiol Gastrointest Liver Physiol 2001; 281:G1014–G1021.
Schwabe RF, Brenner DA. Mechanisms of Liver Injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol 2006; 290:G583–G589.
Brenner C, Galluzzi L, Kepp O, Kroemer G. Decoding cell death signals in liver inflammation. J Hepatol 2013; 59:583–594.
Dufour S, Lebon V, Shulman GI, Petersen KF. Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans. Am J Physiol Endocrinol Metab 2009; 297:E231–E235.
Clarke C, Kuboki S, Sakai N, et al. CXC chemokine receptor-1 is expressed by hepatocytes and regulates liver recovery after hepatic ischemia/reperfusion injury. Hepatology 2011; 53:261–271.
Tsung A, Klune JR, Zhang X, et al. HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med 2007; 204:2913–2923.
Li L, Thompson LH, Zhao L, Messina JL. Tissue-specific difference in the molecular mechanisms for the development of acute insulin resistance after injury. Endocrinology 2009; 150:24–32.
Xu J, Kim HT, Ma Y, et al. Trauma and hemorrhage-induced acute hepatic insulin resistance: dominant role of tumor necrosis factor-alpha. Endocrinology 2008; 149:2369–2382.
Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2000; 106:171–176.
Nakae J, Accili D. The mechanism of insulin action. J Pediatr Endocrinol Metab 1999; 12: (Suppl 3): 721–731.
McCowen KC, Ling PR, Ciccarone A, et al. Sustained endotoxemia leads to marked down-regulation of early steps in the insulin-signaling cascade. Crit Care Med 2001; 29:839–846.
Wang X, Hu Z, Hu J, et al. Insulin resistance accelerates muscle protein degradation: activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology 2006; 147:4160–4168.
Thompson LH, Kim HT, Ma Y, et al. Acute, muscle-type specific insulin resistance following injury. Mol Med 2008; 14:715–723.
Holden CP, Storey KB. Second messenger and cAMP-dependent protein kinase responses to dehydration and anoxia stresses in frogs. J Compar Physiol B 1997; 167:305–312.
Heinrich PC, Müller M, Graeve L, Koch H-G (editors). Biochemie und Pathobiochemie: Mechanismen der Glucosehomöostase. Transkriptionelle Regulation von Glycolyse und Gluconeogenese. 10th ed.: Springer; 2022.
Hems R, Ross BD, Berry MN, Krebs HA. Gluconeogenesis in the perfused rat liver. Biochem J 1966; 101:284–292.
Berry MN. The liver and lactic acidosis. Proc Roy Soc Med 1967; 60:1260–1262.
Dahn MS, Lange P. Hormonal changes and their influence on metabolism and nutrition in the critically ill. Intensive Care Med 1982; 8:209–213.
Nourshargh S, Alon R. Leukocyte migration into inflamed tissues. Immunity 2014; 41:694–707.
Warburg O. Versuch an überlebenden Karzinom-Gewebe. Klin Wochenschr 1923; 2:776–777.
Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol 1927; 8:519–530.
Soeters PB, Shenkin A, Sobotka L, et al. The anabolic role of the Warburg, Cori-cycle and Crabtree effects in health and disease. Clin Nutr 2021; 40:2988–2998.
Palsson-McDermott EM, Curtis AM, Goel G, et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages. Cell Metab 2015; 21:65–80.
Cheng S-C, Quintin J, Cramer RA, et al. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 2014; 345:1250684.
Perrin-Cocon L, Aublin-Gex A, Diaz O, et al. Toll-like receptor 4-induced glycolytic burst in human monocyte-derived dendritic cells results from p38-dependent stabilization of HIF-1α and increased hexokinase II expression. J Immunol 2018; 201:1510–1521.
Morrison T, Watts ER, Sadiku P, Walmsley SR. The emerging role for metabolism in fueling neutrophilic inflammation. Immunol Rev 2023; 314:427–441.
Pearce EL, Poffenberger MC, Chang C-H, Jones RG. Fueling immunity: insights into metabolism and lymphocyte function. Science 2013; 342:1242454.
Kumar S, Dikshit M. Metabolic insight of neutrophils in health and disease. Front Immunol 2019; 10:2099.
Alarcón P, Manosalva C, Conejeros I, et al. d(-) Lactic acid-induced adhesion of bovine neutrophils onto endothelial cells is dependent on neutrophils extracellular traps formation and CD11b expression. Front Immunol 2017; 8:975.
Borregaard N, Herlin T. Energy metabolism of human neutrophils during phagocytosis. J Clin Invest 1982; 70:550–557.
Quiroga J, Alarcón P, Manosalva C, et al. Glycolysis and mitochondrial function regulate the radical oxygen species production induced by platelet-activating factor in bovine polymorphonuclear leukocytes. Vet Immunol Immunopathol 2020; 226:110074.
Rodríguez-Espinosa O, Rojas-Espinosa O, Moreno-Altamirano MMB, et al. Metabolic requirements for neutrophil extracellular traps formation. Immunology 2015; 145:213–224.
Kellum JA, Song M, Li J. Lactic and hydrochloric acids induce different patterns of inflammatory response in LPS-stimulated RAW 264.7 cells. Am J Physiol Regul Integr Comp Physiol 2004; 286:R686–R692.
Haas R, Smith J, Rocher-Ros V, et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol 2015; 13:e1002202.
Wagner S, Hussain MZ, Hunt TK, et al. Stimulation of fibroblast proliferation by lactate-mediated oxidants. Wound Repair Regen 2004; 12:368–373.
Paik J-Y, Jung K-H, Lee J-H, et al. Reactive oxygen species-driven HIF1α triggers accelerated glycolysis in endothelial cells exposed to low oxygen tension. Nuclear Med Biol 2017; 45:8–14.
Xu J, Li J, Yu Z, et al. HMGB1 promotes HLF-1 proliferation and ECM production through activating HIF1-α-regulated aerobic glycolysis. Pulmon Pharmacol Ther 2017; 45:136–141.
Textoris J, Beaufils N, Quintana G, et al. Hypoxia-inducible factor (HIF1α) gene expression in human shock states. Crit Care 2012; 16:R120.
Cori CF. The glucose-lactic acid cycle and gluconeogenesis. Curr Top Cell Regul 1981; 18:377–387.
Legouis D, Faivre A, Cippà PE, Seigneux S de. Renal gluconeogenesis: an underestimated role of the kidney in systemic glucose metabolism. Nephrol Dial Transplant 2022; 37:1417–1425.
Gerich JE, Meyer C, Woerle HJ, Stumvoll M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care 2001; 24:382–391.
Katic M, Kahn CR. The role of insulin and IGF-1 signaling in longevity. Cell Mol Life Sci 2005; 62:320–343.
Soeters MR, Soeters PB. The evolutionary benefit of insulin resistance. Clin Nutr 2012; 31:1002–1007.
Pijl JP, Londema M, Kwee TC, et al. FDG-PET/CT in intensive care patients with bloodstream infection. Crit Care 2021; 25:133.
Demers-Marcil S, Coles JP. Cerebral metabolic derangements following traumatic brain injury. Curr Opin Anaesthesiol 2022; 35:562–569.
O’Connell MT, Seal A, Nortje J, et al. Glucose metabolism in traumatic brain injury: a combined microdialysis and 18F-2-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) study. Acta Neurochir Suppl 2005; 95:165–168.
Hutchinson PJ, O’Connell MT, Seal A, et al. A combined microdialysis and FDG-PET study of glucose metabolism in head injury. Acta Neurochir 2009; 151:51–61.
Levin D, Lantsberg S, Giladi MR, et al. Post contusion breast hematoma mimicking malignancy on FDG PET/CT. Clin Nucl Med 2020; 45:552–554.
Shon IH, Fogelman I. F-18 FDG positron emission tomography and benign fractures. Clin Nucl Med 2003; 28:171–175.
Huang Y-T, Ravi Kumar AS. Classical skeletal injuries shown on 18F-FDG PET/CT following successful cardiopulmonary resuscitation. Clin Nucl Med 2013; 38:395–396.
Kreutziger J, Schmid S, Umlauf N, et al. Association between blood glucose and cardiac rhythms during prehospital care of trauma patients – a retrospective analysis. Scand J Trauma Resusc Emerg Med 2018; 26:58.
Lennmyr F, Molnar M, Basu S, Wiklund L. Cerebral effects of hyperglycemia in experimental cardiac arrest. Crit Care Med 2010; 38:1726–1732.
Raffay V, Chalkias A, Lelovas P, et al. Addition of glucagon to adrenaline improves hemodynamics in a porcine model of prolonged ventricular fibrillation. Am J Emerg Med 2014; 32:139–143.
Wang C-H, Huang C-H, Chang W-T, et al. Associations between blood glucose level and outcomes of adult in-hospital cardiac arrest: a retrospective cohort study. Cardiovasc Diabetol 2016; 15:118.
Ma G, Al-Shabrawey M, Johnson JA, et al. Protection against myocardial ischemia/reperfusion injury by short-term diabetes: enhancement of VEGF formation, capillary density, and activation of cell survival signaling. Naunyn-Schmiedebergs Arch Pharmacol 2006; 373:415–427.
Moro N, Ghavim S, Harris NG, et al. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury. Brain Res 2013; 1535:124–136.
Meier R, Béchir M, Ludwig S, et al. Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury. Crit Care 2008; 12:R98.
Khan RN, Saba F, Kausar SF, Siddiqui MH. Pattern of electrolyte imbalance in Type 2 diabetes patients: experience from a tertiary care hospital. Pak J Med Sci 2019; 35:797–801.
Kreutziger J, Fodor M, Morell-Hofert D, et al. Absence of stress hyperglycemia indicates the most severe form of blunt liver trauma. Diagnostics 2021; 11:1667–1681.
Jensen T, Sørensen MA, Nielsen EW. Turskiløper med kraftsvikt og nedsatt bevissthet. Tidsskrift for den Norske laegeforening: tidsskrift for praktisk medicin, ny raekke 2017; 137:289–291.
Vihonen H, Kuisma M, Nurmi J. Hypoglycaemia without diabetes encountered by emergency medical services: a retrospective cohort study. Scand J Trauma Resusc Emerg Med 2018; 26:12.
Kreutziger J, Lederer W, Schmid S, et al. Blood glucose concentrations in prehospital trauma patients with traumatic shock: a retrospective analysis. Eur J Anaesthesiol 2018; 35:33–42.
Kreutziger J, Rafetseder A, Mathis S, et al. Admission blood glucose predicted haemorrhagic shock in multiple trauma patients. Injury 2015; 46:15–20.
Hart BB, Stanford GG, Ziegler MG, et al. Catecholamines: study of interspecies variation. Crit Care Med 1989; 17:1203–1222.