Relative Adrenal Insufficiency in Pediatric Septic Shock

Abstract

Sepsis and septic shock represent important causes of morbidity and mortality in children, and adrenal dysfunction may play a role in the cardiovascular and immunological response. According to existing reports, the incidence of adrenal dysfunction in critically ill children varies significantly between 4 and 52% of patients. This article reviews the concept of adrenal insufficiency and the role it may play in a pediatric septic shock. Also discussed are the diagnosis, prognosis, and treatment of adrenal insufficiency in septic shock in adults and children. Finally, the latest recommendations about steroid use in pediatric septic shock are summarized.

Keywords

sepsis - septic shock - pediatric septic shock - adrenal insufficiency - relative adrenal insufficiency

• References

• 1 Dellinger RP, Levy MM, Rhodes A , et al; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013; 39 (2) 165-228
• 2 Levy MM, Dellinger RP, Townsend SR , et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 2010; 36 (2) 222-231
• 3 Vila Pérez D, Jordan I, Esteban E , et al. Prognostic factors in pediatric sepsis study, from the Spanish Society of Pediatric Intensive Care. Pediatr Infect Dis J 2014; 33 (2) 152-157
• 4 Angus DC, Burgner D, Wunderink R , et al. The PIRO concept: P is for predisposition. Crit Care 2003; 7 (3) 248-251
• 5 Vincent JL, Opal S, Torres A, Bonten M, Cohen J, Wunderink R. The PIRO concept: I is for infection. Crit Care 2003; 7 (3) 252-255
• 6 Gerlach H, Dhainaut JF, Harbarth S, Reinhart K, Marshall JC, Levy M. The PIRO concept: R is for response. Crit Care 2003; 7 (3) 256-259
• 7 Vincent JL, Wendon J, Groeneveld J, Marshall JC, Streat S, Carlet J. The PIRO concept: O is for organ dysfunction. Crit Care 2003; 7 (3) 260-264
• 8 Opal SM. Concept of PIRO as a new conceptual framework to understand sepsis. Pediatr Crit Care Med 2005; 6 (3, Suppl): S55-S60
• 9 Siami S, Bailly-Salin J, Polito A , et al. Osmoregulation of vasopressin secretion is altered in the postacute phase of septic shock. Crit Care Med 2010; 38 (10) 1962-1969
• 10 Annane D, Sébille V, Charpentier C , et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288 (7) 862-871 Erratum in: JAMA 2008;300(14):1652. Chaumet-Riffaut, Philippe [corrected to Chaumet-Riffaud, Philippe]
• 11 Sprung CL, Annane D, Keh D , et al; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358 (2) 111-124
• 12 Toma A, Stone A, Green RS, Gray S. Steroids for patients in septic shock: the results of the CORTICUS trial. CJEM 2011; 13 (4) 273-276
• 13 Brierley J, Carcillo JA, Choong K , et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 2009; 37 (2) 666-688
• 14 Hollenberg SM, Weinberger C, Ong ES , et al. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 1985– 1986; 318 (6047) 635-641
• 15 Pilkis SJ, Granner DK. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Physiol 1992; 54: 885-909
• 16 Sam S, Corbridge TC, Mokhlesi B, Comellas AP, Molitch ME. Cortisol levels and mortality in severe sepsis. Clin Endocrinol (Oxf) 2004; 60 (1) 29-35
• 17 Carlet J. From mega to more reasonable doses of corticosteroids: a decade to recreate hope. Crit Care Med 1999; 27 (4) 672-674
• 18 Matot I, Sprung CL. Corticosteroids in septic shock: resurrection of the last rites?. Crit Care Med 1998; 26 (4) 627-630
• 19 Meduri GU, Kanangat S. Glucocorticoid treatment of sepsis and acute respiratory distress syndrome: time for a critical reappraisal. Crit Care Med 1998; 26 (4) 630-633
• 20 Schumer W. Controversy in shock research. Pro: The role of steroids in septic shock. Circ Shock 1981; 8 (6) 667-671
• 21 Sakaue M, Hoffman BB. Glucocorticoids induce transcription and expression of the alpha 1B adrenergic receptor gene in DTT1 MF-2 smooth muscle cells. J Clin Invest 1991; 88 (2) 385-389
• 22 Collins S, Caron MG, Lefkowitz RJ. Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids. J Biol Chem 1988; 263 (19) 9067-9070
• 23 Matsumura M, Kakishita H, Suzuki M, Banba N, Hattori Y. Dexamethasone suppresses iNOS gene expression by inhibiting NF-kappaB in vascular smooth muscle cells. Life Sci 2001; 69 (9) 1067-1077
• 24 Redington AE, Meng QH, Springall DR , et al. Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment. Thorax 2001; 56 (5) 351-357
• 25 Fujii E, Yoshioka T, Ishida H, Irie K, Muraki T. Evaluation of iNOS-dependent and independent mechanisms of the microvascular permeability change induced by lipopolysaccharide. Br J Pharmacol 2000; 130 (1) 90-94
• 26 Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995; 332 (20) 1351-1362
• 27 Barnes PJ. Beta-adrenergic receptors and their regulation. Am J Respir Crit Care Med 1995; 152 (3) 838-860
• 28 Saito T, Takanashi M, Gallagher E , et al. Corticosteroid effect on early beta-adrenergic down-regulation during circulatory shock: hemodynamic study and beta-adrenergic receptor assay. Intensive Care Med 1995; 21 (3) 204-210
• 29 Putterman C. Corticosteroids in sepsis and septic shock: has the jury reached a verdict?. Isr J Med Sci 1989; 25 (6) 332-338
• 30 Kawamura T, Inada K, Nara N, Wakusawa R, Endo S. Influence of methylprednisolone on cytokine balance during cardiac surgery. Crit Care Med 1999; 27 (3) 545-548 [Erratum in: Crit Care Med 1999;27(7):1404]
• 31 Shieh JH, Peterson RH, Moore MA. Cytokines and dexamethasone modulation of IL-1 receptors on human neutrophils in vitro. J Immunol 1993; 150 (8, Pt 1) 3515-3524
• 32 Wiegers GJ, Reul JM. Induction of cytokine receptors by glucocorticoids: functional and pathological significance. Trends Pharmacol Sci 1998; 19 (8) 317-321
• 33 Spriggs MK, Lioubin PJ, Slack J , et al. Induction of an interleukin-1 receptor (IL-1R) on monocytic cells. Evidence that the receptor is not encoded by a T cell-type IL-1R mRNA. J Biol Chem 1990; 265 (36) 22499-22505
• 34 Snyers L, De Wit L, Content J. Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells. Proc Natl Acad Sci U S A 1990; 87 (7) 2838-2842
• 35 Wiegers GJ, Labeur MS, Stec IE, Klinkert WE, Holsboer F, Reul JM. Glucocorticoids accelerate anti-T cell receptor-induced T cell growth. J Immunol 1995; 155 (4) 1893-1902
• 36 Paterson RL, Or R, Domenico JM, Delespesse G, Gelfand EW. Regulation of CD23 expression by IL-4 and corticosteroid in human B lymphocytes. Altered response after EBV infection. J Immunol 1994; 152 (5) 2139-2147
• 37 Pietzko D, Zohlnhöfer D, Graeve L , et al. The hepatic interleukin-6 receptor. Studies on its structure and regulation by phorbol 12-myristate 13-acetate-dexamethasone. J Biol Chem 1993; 268 (6) 4250-4258
• 38 Franchimont D, Galon J, Vacchio MS , et al. Positive effects of glucocorticoids on T cell function by up-regulation of IL-7 receptor alpha. J Immunol 2002; 168 (5) 2212-2218
• 39 Strickland RW, Wahl LM, Finbloom DS. Corticosteroids enhance the binding of recombinant interferon-gamma to cultured human monocytes. J Immunol 1986; 137 (5) 1577-1580
• 40 Hawrylowicz CM, Guida L, Paleolog E. Dexamethasone up-regulates granulocyte-macrophage colony-stimulating factor receptor expression on human monocytes. Immunology 1994; 83 (2) 274-280 [Erratum in: Immunology 1994;83(4):681]
• 41 van der Goes A, Hoekstra K, van den Berg TK, Dijkstra CD. Dexamethasone promotes phagocytosis and bacterial killing by human monocytes/macrophages in vitro. J Leukoc Biol 2000; 67 (6) 801-807
• 42 Freischlag JA, Colburn MD, Quiñones-Baldrich WJ, Moore WS. Alteration of neutrophil (PMN) function by heparin, dexamethasone, and enalapril. J Surg Res 1992; 52 (5) 523-529
• 43 Lloberas J, Soler C, Celada A. Dexamethasone enhances macrophage colony stimulating factor- and granulocyte macrophage colony stimulating factor-stimulated proliferation of bone marrow-derived macrophages. Int Immunol 1998; 10 (5) 593-599
• 44 Dinkel K, MacPherson A, Sapolsky RM. Novel glucocorticoid effects on acute inflammation in the CNS. J Neurochem 2003; 84 (4) 705-716
• 45 Yeager MP, Rassias AJ, Pioli PA , et al. Pretreatment with stress cortisol enhances the human systemic inflammatory response to bacterial endotoxin. Crit Care Med 2009; 37 (10) 2727-2732
• 46 Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther 2006; 8 (Suppl. 02) S3
• 47 Lauw FN, Pajkrt D, Hack CE, Kurimoto M, van Deventer SJ, van der Poll T. Proinflammatory effects of IL-10 during human endotoxemia. J Immunol 2000; 165 (5) 2783-2789
• 48 Pajkrt D, Camoglio L, Tiel-van Buul MC , et al. Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia: effect of timing of recombinant human IL-10 administration. J Immunol 1997; 158 (8) 3971-3977
• 49 Druce LA, Thorpe CM, Wilton A. Mineralocorticoid effects due to cortisol inactivation overload explain the beneficial use of hydrocortisone in septic shock. Med Hypotheses 2008; 70 (1) 56-60
• 50 Kaufmann I, Briegel J, Schliephake F , et al. Stress doses of hydrocortisone in septic shock: beneficial effects on opsonization-dependent neutrophil functions. Intensive Care Med 2008; 34 (2) 344-349
• 51 Lim HY, Müller N, Herold MJ, van den Brandt J, Reichardt HM. Glucocorticoids exert opposing effects on macrophage function dependent on their concentration. Immunology 2007; 122 (1) 47-53
• 52 Calandra T, Bucala R. Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator within the immune system. Crit Rev Immunol 1997; 17 (1) 77-88
• 53 Yeager MP, Pioli PA, Wardwell K , et al. In vivo exposure to high or low cortisol has biphasic effects on inflammatory response pathways of human monocytes. Anesth Analg 2008; 107 (5) 1726-1734
• 54 Warren MK, Vogel SN. Opposing effects of glucocorticoids on interferon-gamma-induced murine macrophage Fc receptor and Ia antigen expression. J Immunol 1985; 134 (4) 2462-2469
• 55 Eastman HB, Fawcett TW, Udelsman R, Holbrook NJ. Effects of perturbations of the hypothalamic-pituitary-adrenal axis on the acute phase response: altered C/EBP and acute phase response gene expression in lipopolysaccharide-treated rats. Shock 1996; 6 (4) 286-292
• 56 Dhabhar FS, McEwen BS. Enhancing versus suppressive effects of stress hormones on skin immune function. Proc Natl Acad Sci U S A 1999; 96 (3) 1059-1064
• 57 Matsusue S, Walser M. Healing of intestinal anastomoses in adrenalectomized rats given corticosterone. Am J Physiol 1992; 263 (1, Pt 2): R164-R168
• 58 Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003; 348 (8) 727-734
• 59 Mesotten D, Vanhorebeek I, Van den Berghe G. The altered adrenal axis and treatment with glucocorticoids during critical illness. Nat Clin Pract Endocrinol Metab 2008; 4 (9) 496-505
• 60 Widmer IE, Puder JJ, König C , et al. Cortisol response in relation to the severity of stress and illness. J Clin Endocrinol Metab 2005; 90 (8) 4579-4586
• 61 Vermes I, Beishuizen A. The hypothalamic-pituitary-adrenal response to critical illness. Best Pract Res Clin Endocrinol Metab 2001; 15 (4) 495-511
• 62 Selye H. The general adaptation syndrome and the diseases of adaptation. J Clin Endocrinol Metab 1946; 6: 117-230
• 63 Vermes I, Beishuizen A, Hampsink RM, Haanen C. Dissociation of plasma adrenocorticotropin and cortisol levels in critically ill patients: possible role of endothelin and atrial natriuretic hormone. J Clin Endocrinol Metab 1995; 80 (4) 1238-1242
• 64 Bornstein SR, Engeland WC, Ehrhart-Bornstein M, Herman JP. Dissociation of ACTH and glucocorticoids. Trends Endocrinol Metab 2008; 19 (5) 175-180
• 65 Bornstein SR, Chrousos GP. Clinical review 104: Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs. J Clin Endocrinol Metab 1999; 84 (5) 1729-1736
• 66 Aneja R, Carcillo JA. What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock?. Arch Dis Child 2007; 92 (2) 165-169
• 67 Aneja R, Carcillo JA. What is the rationale for hydrocortisone treatment in children with infection-related adrenal insufficiency and septic shock?. Arch Dis Child 2007; 92 (2) 165-169
• 68 Marik PE. Critical illness-related corticosteroid insufficiency. Chest 2009; 135 (1) 181-193
• 69 Marik PE, Zaloga GP. Adrenal insufficiency in the critically ill: a new look at an old problem. Chest 2002; 122 (5) 1784-1796
• 70 Hebbar K, Rigby MR, Felner EI, Easley KA, Fortenberry JD. Neuroendocrine dysfunction in pediatric critical illness. Pediatr Crit Care Med 2009; 10 (1) 35-40
• 71 Riordan FA, Thomson AP, Ratcliffe JM, Sills JA, Diver MJ, Hart CA. Admission cortisol and adrenocorticotrophic hormone levels in children with meningococcal disease: evidence of adrenal insufficiency?. Crit Care Med 1999; 27 (10) 2257-2261
• 72 Hatherill M, Tibby SM, Hilliard T, Turner C, Murdoch IA. Adrenal insufficiency in septic shock. Arch Dis Child 1999; 80 (1) 51-55
• 73 Bone M, Diver M, Selby A, Sharples A, Addison M, Clayton P. Assessment of adrenal function in the initial phase of meningococcal disease. Pediatrics 2002; 110 (3) 563-569
• 74 Menon K, Clarson C. Adrenal function in pediatric critical illness. Pediatr Crit Care Med 2002; 3 (2) 112-116
• 75 Pizarro CF, Troster EJ, Damiani D, Carcillo JA. Absolute and relative adrenal insufficiency in children with septic shock. Crit Care Med 2005; 33 (4) 855-859
• 76 Ando M, Park IS, Wada N, Takahashi Y. Steroid supplementation: a legitimate pharmacotherapy after neonatal open heart surgery. Ann Thorac Surg 2005; 80 (5) 1672-1678 , 1678
• 77 Cohen J, Ward G, Prins J, Jones M, Venkatesh B. Variability of cortisol assays can confound the diagnosis of adrenal insufficiency in the critically ill population. Intensive Care Med 2006; 32 (11) 1901-1905
• 78 Menon K, Lawson M. Identification of adrenal insufficiency in pediatric critical illness. Pediatr Crit Care Med 2007; 8 (3) 276-278
• 79 Menon K, Ward RE, Lawson ML, Gaboury I, Hutchison JS, Hébert PC ; Canadian Critical Care Trials Group. A prospective multicenter study of adrenal function in critically ill children. Am J Respir Crit Care Med 2010; 182 (2) 246-251
• 80 Briegel J, Schelling G, Haller M, Mraz W, Forst H, Peter K. A comparison of the adrenocortical response during septic shock and after complete recovery. Intensive Care Med 1996; 22 (9) 894-899
• 81 Zimmerman JJ, Donaldson A, Barker RM , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Real-time free cortisol quantification among critically ill children. Pediatr Crit Care Med 2011; 12 (5) 525-531
• 82 Naito Y, Fukata J, Tamai S , et al. Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period after major abdominal surgery. J Clin Endocrinol Metab 1991; 73 (1) 111-117
• 83 Schein RM, Sprung CL, Marcial E, Napolitano L, Chernow B. Plasma cortisol levels in patients with septic shock. Crit Care Med 1990; 18 (3) 259-263
• 84 Nickels DA, Moore DC. Serum cortisol responses in febrile children. Pediatr Infect Dis J 1989; 8 (1) 16-20
• 85 Singh UK, Jana UK. Serum prolactin and cortisol in children with some paroxysmal disorders. Indian J Pediatr 1994; 61 (1) 57-61
• 86 Joosten KF, de Kleijn ED, Westerterp M , et al. Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors. J Clin Endocrinol Metab 2000; 85 (10) 3746-3753
• 87 Bouachour G, Tirot P, Gouello JP, Mathieu E, Vincent JF, Alquier P. Adrenocortical function during septic shock. Intensive Care Med 1995; 21 (1) 57-62
• 88 Moran JL, Chapman MJ, O'Fathartaigh MS, Peisach AR, Pannall PR, Leppard P. Hypocortisolaemia and adrenocortical responsiveness at onset of septic shock. Intensive Care Med 1994; 20 (7) 489-495
• 89 McWhinney PH, Patel A, Walker E. Adrenal failure in fulminant meningococcal septicaemia: a clinical reality. Scand J Infect Dis 1990; 22 (6) 755-756
• 90 Streeten DH. What test for hypothalamic-pituitary-adrenocortical insufficiency?. Lancet 1999; 354 (9174) 179-180
• 91 Marik PE, Zaloga GP. Adrenal insufficiency during septic shock. Crit Care Med 2003; 31 (1) 141-145
• 92 Streeten DH, Anderson Jr GH, Bonaventura MM. The potential for serious consequences from misinterpreting normal responses to the rapid adrenocorticotropin test. J Clin Endocrinol Metab 1996; 81 (1) 285-290
• 93 Richards ML, Caplan RH, Wickus GG, Lambert PJ, Kisken WA. The rapid low-dose (1 microgram) cosyntropin test in the immediate postoperative period: results in elderly subjects after major abdominal surgery. Surgery 1999; 125 (4) 431-440
• 94 Broide J, Soferman R, Kivity S , et al. Low-dose adrenocorticotropin test reveals impaired adrenal function in patients taking inhaled corticosteroids. J Clin Endocrinol Metab 1995; 80 (4) 1243-1246
• 95 Mayenknecht J, Diederich S, Bähr V, Plöckinger U, Oelkers W. Comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease. J Clin Endocrinol Metab 1998; 83 (5) 1558-1562
• 96 Rasmuson S, Olsson T, Hagg E. A low dose ACTH test to assess the function of the hypothalamic-pituitary-adrenal axis. Clin Endocrinol (Oxf) 1996; 44 (2) 151-156
• 97 Tordjman K, Jaffe A, Grazas N, Apter C, Stern N. The role of the low dose (1 microgram) adrenocorticotropin test in the evaluation of patients with pituitary diseases. J Clin Endocrinol Metab 1995; 80 (4) 1301-1305
• 98 Abdu TA, Elhadd TA, Neary R, Clayton RN. Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J Clin Endocrinol Metab 1999; 84 (3) 838-843
• 99 Crowley S, Hindmarsh PC, Holownia P, Honour JW, Brook CG. The use of low doses of ACTH in the investigation of adrenal function in man. J Endocrinol 1991; 130 (3) 475-479
• 100 Crowley S, Hindmarsh PC, Honour JW, Brook CG. Reproducibility of the cortisol response to stimulation with a low dose of ACTH(1-24): the effect of basal cortisol levels and comparison of low-dose with high-dose secretory dynamics. J Endocrinol 1993; 136 (1) 167-172
• 101 Thaler LM, Blevins Jr LS. The low dose (1-microg) adrenocorticotropin stimulation test in the evaluation of patients with suspected central adrenal insufficiency. J Clin Endocrinol Metab 1998; 83 (8) 2726-2729
• 102 Agwu JC, Spoudeas H, Hindmarsh PC, Pringle PJ, Brook CG. Tests of adrenal insufficiency. Arch Dis Child 1999; 80 (4) 330-333
• 103 Beishuizen A, Thijs LG, Vermes I. Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma. Intensive Care Med 2001; 27 (10) 1584-1591
• 104 Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004; 350 (16) 1629-1638
• 105 Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab 2006; 91 (10) 3725-3745
• 106 Törnhage CJ. Salivary cortisol for assessment of hypothalamic-pituitary-adrenal axis function. Neuroimmunomodulation 2009; 16 (5) 284-289
• 107 Gozansky WS, Lynn JS, Laudenslager ML, Kohrt WM. Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic—pituitary—adrenal axis activity. Clin Endocrinol (Oxf) 2005; 63 (3) 336-341
• 108 Estrada-Y-Martin RM, Orlander PR. Salivary cortisol can replace free serum cortisol measurements in patients with septic shock. Chest 2011; 140 (5) 1216-1222
• 109 Loriaux L. Glucocorticoid therapy in the intensive care unit. N Engl J Med 2004; 350 (16) 1601-1602
• 110 Ho JT, Al-Musalhi H, Chapman MJ , et al. Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 2006; 91 (1) 105-114
• 111 Arafah BM, Nishiyama FJ, Tlaygeh H, Hejal R. Measurement of salivary cortisol concentration in the assessment of adrenal function in critically ill subjects: a surrogate marker of the circulating free cortisol. J Clin Endocrinol Metab 2007; 92 (8) 2965-2971
• 112 Patel RS, Shaw SR, Macintyre H, McGarry GW, Wallace AM. Production of gender-specific morning salivary cortisol reference intervals using internationally accepted procedures. Clin Chem Lab Med 2004; 42 (12) 1424-1429
• 113 Singh SN, Rathia SK, Awasthi S, Singh A, Bhatia V. Salivary cortisol estimation to assess adrenal status in children with fluid unresponsive septic shock. Indian Pediatr 2013; 50 (7) 681-684
• 114 de Jong MF, Beishuizen A, Spijkstra JJ, Groeneveld AB. Relative adrenal insufficiency as a predictor of disease severity, mortality, and beneficial effects of corticosteroid treatment in septic shock. Crit Care Med 2007; 35 (8) 1896-1903
• 115 Menon K, McNally JD, Choong K , et al. A survey of stated physician practices and beliefs on the use of steroids in pediatric fluid and/or vasoactive infusion-dependent shock. Pediatr Crit Care Med 2013; 14 (5) 462-466
• 116 Knighton JD, Woodock TE, Hough M. Adrenal failure in the critically ill. Br J Anaesth 1999; 82 (1) 152-153
• 117 Briegel J, Forst H, Haller M , et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 1999; 27 (4) 723-732
• 118 Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 1998; 26 (4) 645-650
• 119 Oppert M, Reinicke A, Gräf KJ, Barckow D, Frei U, Eckardt KU. Plasma cortisol levels before and during “low-dose” hydrocortisone therapy and their relationship to hemodynamic improvement in patients with septic shock. Intensive Care Med 2000; 26 (12) 1747-1755
• 120 Cronin L, Cook DJ, Carlet J , et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 1995; 23 (8) 1430-1439
• 121 Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ 2004; 329 (7464) 480
• 122 Annane D, Bellissant E, Bollaert PE , et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA 2009; 301 (22) 2362-2375
• 123 Wang C, Sun J, Zheng J , et al. Low-dose hydrocortisone therapy attenuates septic shock in adult patients but does not reduce 28-day mortality: a meta-analysis of randomized controlled trials. Anesth Analg 2014; 118 (2) 346-357
• 124 Menon K, McNally D, Choong K, Sampson M. A systematic review and meta-analysis on the effect of steroids in pediatric shock. Pediatr Crit Care Med 2013; 14 (5) 474-480
• 125 Yildiz O, Doganay M, Aygen B, Güven M, Keleştimur F, Tutuû A. Physiological-dose steroid therapy in sepsis [ISRCTN36253388]. Crit Care 2002; 6 (3) 251-259
• 126 Elsouri N, Bander J, Guzman JA. Relative adrenal insufficiency in patients with septic shock; a close look to practice patterns. J Crit Care 2006; 21 (1) 73-77
• 127 Guzman JA, Guzman CB. Adrenal exhaustion in septic patients with vasopressor dependency. J Crit Care 2007; 22 (4) 319-323
• 128 Bendel S, Karlsson S, Pettilä V, Loisa P, Varpula M, Ruokonen E ; Finnsepsis Study Group. Free cortisol in sepsis and septic shock. Anesth Analg 2008; 106 (6) 1813-1819
• 129 Llompart-Pou JA, Raurich JM, Ibáñez J, Riesco M, Ayestarán JI. Immediate hemodynamic response to steroid treatment in septic shock [in Spanish]. Med Intensiva 2008; 32 (8) 385-390
• 130 Ratanarat R, Promsin P, Srivijitkamol A, Leemingsawat C, Permpikul C. Diagnosis of corticosteroid insufficiency in Thai patients with septic shock. J Med Assoc Thai 2010; 93 (Suppl. 01) S187-S195
• 131 Slusher T, Gbadero D, Howard C , et al. Randomized, placebo-controlled, double blinded trial of dexamethasone in African children with sepsis. Pediatr Infect Dis J 1996; 15 (7) 579-583
• 132 Casartelli CH, Garcia PC, Branco RG, Piva JP, Einloft PR, Tasker RC. Adrenal response in children with septic shock. Intensive Care Med 2007; 33 (9) 1609-1613
• 133 Sarthi M, Lodha R, Vivekanandhan S, Arora NK. Adrenal status in children with septic shock using low-dose stimulation test. Pediatr Crit Care Med 2007; 8 (1) 23-28
• 134 Valoor HT, Singhi S, Jayashree M. Low-dose hydrocortisone in pediatric septic shock: an exploratory study in a third world setting. Pediatr Crit Care Med 2009; 10 (1) 121-125
• 135 Karagüzel G, Atay S, Değer O, İmamoğlu M, Ökten A, Karagüzel G. The effects of three specific conditions related to critical care on adrenal function in children. Intensive Care Med 2012; 38 (10) 1689-1696
• 136 Hermanides J, Vriesendorp TM, Bosman RJ, Zandstra DF, Hoekstra JB, Devries JH. Glucose variability is associated with intensive care unit mortality. Crit Care Med 2010; 38 (3) 838-842
• 137 Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology 2006; 105 (2) 244-252
• 138 Moghissi ES, Korytkowski MT, DiNardo M , et al; American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care 2009; 32 (6) 1119-1131
• 139 Hildebrandt T, Mansour M, Al Samsam R. The use of steroids in children with septicemia: review of the literature and assessment of current practice in PICUs in the UK. Paediatr Anaesth 2005; 15 (5) 358-365
• 140 Benken ST, Hutson TK, Gardiner RL, Wheeler DS. A single-center review of prescribing trends and outcomes of corticosteroid replacement therapy in critically ill children with septic shock. Open Crit Care Med J 2010; 3: 51-56
• 141 Marik PE, Pastores SM, Annane D , et al; American College of Critical Care Medicine. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008; 36 (6) 1937-1949
• 142 Bauer W, Ball J, Grounds M. Unanswered questions from Corticus and pragmatic suggestions. Crit Care 2008; 12 (4) 426 , discussion 426