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December 1984, Vol 119, No. 12 >
ARTICLE | December 1984

Evaluation of Naloxone for Therapy of Escherichia coli Shock: Title and subTitle BreakSpecies Differences FREE

Lerner B. Hinshaw, PhD; Beverly K. Beller; Alvin C. K. Chang; Dayl J. Flournoy, PhD; Robert A. Lahti, PhD; Richard B. Passey, PhD; Linda T. Archer, PhD
[+] Author Affiliations

Accepted for publication Aug 7, 1984.

Read before the Sixth Annual Conference on Shock, Grand Teton National Park, Wyo, June 7, 1983, and the Federation of American Societies for Experimental Biology, St Louis, April 2, 1984.

Reprint requests to Research 151-C, VA Medical Center, 921 NE 13th St, Oklahoma City, OK 73104 (Dr Hinshaw).


Arch Surg. 1984;119(12):1410-1418. doi:10.1001/archsurg.1984.01390240048009
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• Dogs and baboons were infused intravenously (IV) with Escherichia coli and treated with the opiate antagonist, naloxone hydrochloride, and the antibiotic, gentamicin sulfate, to determine the therapeutic efficacy of naloxone. Naloxone hydrochloride (2 mg/kg) was injected IV when one fourth of the E coli had been Infused and then infused at 2 mg/kg/hr (six hours for dogs and 12 hours for baboons). Four of five naloxone-treated dogs survived permanently (greater than seven days), while all dogs that were given only E coli died. Arterial BP, blood glucose levels, Pco2, and Po2 were supported at higher levels and lesions of the gastrointestinal tract were prevented In naloxone-treated dogs. A steady decline in blood glucose levels after an initial hyperglycemia was observed in naloxone-treated baboons, indications of peripheral vasoconstriction were noted, and all baboons died within 42 hours.

(Arch Surg 1984;119:1410-1418)

REFERENCES

1 +
Holaday JW, Faden AI:  Naloxone reverses the pathophysiology of shock through an antagonism of endorphine systems , in Martin JB, Reichlin S, Bick KL (eds): Neurosecretion and Brain Peptides . New York, Raven Press, 1981;, pp 421-434.
2 +
Holaday JW, Faden AI:  Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock . Nature 1978;;275:450-451.
3 +
Reynolds DG, Gurll NJ, Vargish T, et al:  Blockade of opiate receptors with naloxone improves survival and cardiac performance in canine endotoxin shock . Circ Shock 1980;;7:39-48.
4 +
Holaday JW:  Cardiovascular effects of endogenous opiate systems . Annu Rev Pharmacol Toxicol 1983;;23:541-594.
5 +
Holaday JW:  Cardiovascular consequences of endogenous opiate antagonism . Biochem Pharmacol 1983;;32:573-585.
6 +
Holaday JW, D'Amato RJ, Ruvio BA, et al:  Action of naloxone and TRH on the autonomic regulation of circulation . Adv Biochem Psychopharmacol 1982;;33:353-361.
7 +
Faden AI, Holaday JW:  Naloxone treatment of endotoxin shock: Stereospecificity of physiologic and pharmacologic effects in the rat . J Pharmacol Exp Ther 1980;;212:441-447.
8 +
Bone RC, Jacobs ER, Potter DM, et al:  Endorphins in endotoxin shock . Microcirculation 1981;;1:285-295.
9 +
Thijs LG, Balk E, Tuynman HARE, et al:  Effects of naloxone on hemodynamics, oxygen transport, and metabolic variables in canine endotoxin shock . Circ Shock 1983;;10:147-160.
10 +
Rees M, BowenJC, Payne JG, et al:  Plasma β-endorphin immunoreactivity in dogs during anesthesia, surgery, Escherichia coli sepsis, and naloxone therapy . Surgery 1983;;93:386-390.
11 +
Raymond RM, Harkema JM, Stoffs WV, et al:  Effects of naloxone therapy on hemodynamics and metabolism following a superlethal dosage of Escherichia coli endotoxin in dogs . Surg Gynecol Obstet 1981;;152:159-162.
12 +
Fettman M, Hand M, Chandrasena L, et al:  Effects of naloxone (N) therapy on lethality, hemodynamic, and metabolic parameters in awake endotoxemic yucatan minipigs . Circ Shock 1982;;9:185.
13 +
Szieberg L, Thomson P, Jinkins J, et al:  Effect of naloxone treatment on the cardiopulmonary response to endotoxin in sheep . Circ Shock 1982;;9:170.
14 +
Koyama S, Santiesteban HL, Ammons WS, et al:  The effects of naloxone on the peripheral sympathetics in cat endotoxin shock . Circ Shock 1983;;10:7-13.
15 +
Gahhos FN, Chiu RCJ, Hinchey EJ, et al:  Endorphins in septic shock . Arch Surg 1982;;117:1053-1057.
16 +
Weissglas IS, Hinchey EJ, Chiu RCJ:  Naloxone and methylprednisolone in the treatment of experimental septic shock . J Surg Res 1982;;33:131-135.
17 +
Adeleye GA, Furman BL, Parratt JR:  Possible involvement of opiate receptors in the response of conscious rats to Escherichia coli endotoxin: Protective effect of naloxone . J Physiol 1982;;329:31.
18 +
Groeger JS, Carlon GC, Howland WS:  Naloxone in septic shock . Crit Care Med 1983;;11:650-654.
19 +
Salerno TA, Milne B, Jhamandas KH:  Hemodynamic effects of naloxone in hemorrhagic shock in pigs . Surg Gynecol Obstet 1981;;152: 773-776.
20 +
Mannelli M, Maggi M, DeFeo ML, et al:  Naloxone administration releases catecholamines . N Engl J Med 1983;;308:654-655.
21 +
Peters WP, Johnson MW, Friedman PA, et al:  Pressor effect of naloxone in septic shock . Lancet 1981;;1:529-532.
22 +
Jacobs ER, Bone RC, Wilson FJ Jr, et al:  Naloxone blockade of endorphins in canine endotoxin shock . Microcirculation 1982;;2:19-27.
23 +
Janssen HF, Pugh JL, Lutherer LO:  Reduced ambient temperature blocks the ability of naloxone to prevent endotoxin-induced hypotension , in Reichard SM, Fletcher JR (eds): Advances in Shock Research . New York, Alan R Liss Inc, 1982;, vol 7, pp 117-124.
24 +
Patton ML, Gurll NJ, Reynolds DG, et al:  Adrenalectomy abolishes and cortisol restores naloxone's beneficial effects on cardiovascular function and survival in canine hemorrhagic shock . Circ Shock 1983;;10:317-327.
25 +
Hinshaw LB, Beller BK, Archer LT, et al:  Recovery from lethal Escherichia coli shock in dogs . Surg Gynecol Obstet 1979;;149:545-553.
26 +
Beller BK, Archer LT, Passey RB, et al:  Effectiveness of modified steroid-antibiotic therapies for lethal sepsis in the dog . Arch Surg 1983;;118:1293-1299.
27 +
Hinshaw LB, Archer LT, Beller-Todd BK, et al:  Survival of primates in LD100 septic shock following steroid/antibiotic therapy . J Surg Res 1980;;28:151-170.
28 +
Hinshaw LB, Beller-Todd BK, Archer LT:  Current management of the septic shock patient: Experimental basis for treatment . Circ Shock 1982;;9:543-553.
29 +
Beller BK, Archer LT, Lane MM, et al:  Preventing v delaying death in shock therapy studies: Evaluating 'Survival.' Circ Shock 1983;;11:351-358.
30 +
Rees M, Payne JG, Bowen JC:  Naloxone reverses tissue effects of live Escherichia coli sepsis . Surgery 1982;;91:81-86.
31 +
White GL, Archer LT, Beller BK, et al:  Increased survival with methylprednisolone treatment in canine endotoxin shock . J Surg Res 1978;;25:357-364.
32 +
Longnecker DE, Kettler DF:  Value of naloxone in the treatment of hemorrhagic shock . Anesthesiology 1983;;59:120.
33 +
Benedict CR, Grahame-Smith DG:  Plasma noradrenaline and adrenaline concentrations and dopamine-β-hydroxylase activity in patients with shock due to septicemia, trauma, and haemorrhage . Q J Med 1978;;47:1-20.
34 +
Bocking JK, Sibbald WJ, Holliday RL, et al:  Plasma catecholamine levels and pulmonary dysfunction in sepsis . Surg Gynecol Obstet 1979;;148: 715-719.
35 +
Taff RH:  Pulmonary edema following naloxone administration in a patient without heart disease . Anesthesiology 1983;;59:576-577.
36 +
Holaday JW, D'Amato RJ, Ruvio BA, et al:  Adrenalectomy blocks pressor responses to naloxone in endotoxic shock: Evidence for sympathomedullary involvement . Circ Shock 1983;;11:201-210.
37 +
Brake CM, Emerson TE Jr, Wittmers LE:  Alterations of vascular responses to endotoxin by adrenergic blockade . Am J Physiol 1964;;207: 149-151.
38 +
Masucci FD, Hinshaw LB:  Evaluation of protection with phenoxybenzamine against lethal endotoxin shock . Proc Soc Exp Biol Med 1964;;116:1057-1060.
39 +
Hinshaw LB, Brake CM, Emerson TE Jr, et al:  Participation of the sympathoadrenal system in endotoxin shock . Am J Physiol 1964;;207: 925-930.
40 +
Emerson TE Jr, Brake CM, Hinshaw LB:  Endotoxin shock in chronic splanchnic denervated dogs . J Trauma 1965;;5:737-740.

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1 +
Holaday JW, Faden AI:  Naloxone reverses the pathophysiology of shock through an antagonism of endorphine systems , in Martin JB, Reichlin S, Bick KL (eds): Neurosecretion and Brain Peptides . New York, Raven Press, 1981;, pp 421-434.
2 +
Holaday JW, Faden AI:  Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock . Nature 1978;;275:450-451.
3 +
Reynolds DG, Gurll NJ, Vargish T, et al:  Blockade of opiate receptors with naloxone improves survival and cardiac performance in canine endotoxin shock . Circ Shock 1980;;7:39-48.
4 +
Holaday JW:  Cardiovascular effects of endogenous opiate systems . Annu Rev Pharmacol Toxicol 1983;;23:541-594.
5 +
Holaday JW:  Cardiovascular consequences of endogenous opiate antagonism . Biochem Pharmacol 1983;;32:573-585.
6 +
Holaday JW, D'Amato RJ, Ruvio BA, et al:  Action of naloxone and TRH on the autonomic regulation of circulation . Adv Biochem Psychopharmacol 1982;;33:353-361.
7 +
Faden AI, Holaday JW:  Naloxone treatment of endotoxin shock: Stereospecificity of physiologic and pharmacologic effects in the rat . J Pharmacol Exp Ther 1980;;212:441-447.
8 +
Bone RC, Jacobs ER, Potter DM, et al:  Endorphins in endotoxin shock . Microcirculation 1981;;1:285-295.
9 +
Thijs LG, Balk E, Tuynman HARE, et al:  Effects of naloxone on hemodynamics, oxygen transport, and metabolic variables in canine endotoxin shock . Circ Shock 1983;;10:147-160.
10 +
Rees M, BowenJC, Payne JG, et al:  Plasma β-endorphin immunoreactivity in dogs during anesthesia, surgery, Escherichia coli sepsis, and naloxone therapy . Surgery 1983;;93:386-390.
11 +
Raymond RM, Harkema JM, Stoffs WV, et al:  Effects of naloxone therapy on hemodynamics and metabolism following a superlethal dosage of Escherichia coli endotoxin in dogs . Surg Gynecol Obstet 1981;;152:159-162.
12 +
Fettman M, Hand M, Chandrasena L, et al:  Effects of naloxone (N) therapy on lethality, hemodynamic, and metabolic parameters in awake endotoxemic yucatan minipigs . Circ Shock 1982;;9:185.
13 +
Szieberg L, Thomson P, Jinkins J, et al:  Effect of naloxone treatment on the cardiopulmonary response to endotoxin in sheep . Circ Shock 1982;;9:170.
14 +
Koyama S, Santiesteban HL, Ammons WS, et al:  The effects of naloxone on the peripheral sympathetics in cat endotoxin shock . Circ Shock 1983;;10:7-13.
15 +
Gahhos FN, Chiu RCJ, Hinchey EJ, et al:  Endorphins in septic shock . Arch Surg 1982;;117:1053-1057.
16 +
Weissglas IS, Hinchey EJ, Chiu RCJ:  Naloxone and methylprednisolone in the treatment of experimental septic shock . J Surg Res 1982;;33:131-135.
17 +
Adeleye GA, Furman BL, Parratt JR:  Possible involvement of opiate receptors in the response of conscious rats to Escherichia coli endotoxin: Protective effect of naloxone . J Physiol 1982;;329:31.
18 +
Groeger JS, Carlon GC, Howland WS:  Naloxone in septic shock . Crit Care Med 1983;;11:650-654.
19 +
Salerno TA, Milne B, Jhamandas KH:  Hemodynamic effects of naloxone in hemorrhagic shock in pigs . Surg Gynecol Obstet 1981;;152: 773-776.
20 +
Mannelli M, Maggi M, DeFeo ML, et al:  Naloxone administration releases catecholamines . N Engl J Med 1983;;308:654-655.
21 +
Peters WP, Johnson MW, Friedman PA, et al:  Pressor effect of naloxone in septic shock . Lancet 1981;;1:529-532.
22 +
Jacobs ER, Bone RC, Wilson FJ Jr, et al:  Naloxone blockade of endorphins in canine endotoxin shock . Microcirculation 1982;;2:19-27.
23 +
Janssen HF, Pugh JL, Lutherer LO:  Reduced ambient temperature blocks the ability of naloxone to prevent endotoxin-induced hypotension , in Reichard SM, Fletcher JR (eds): Advances in Shock Research . New York, Alan R Liss Inc, 1982;, vol 7, pp 117-124.
24 +
Patton ML, Gurll NJ, Reynolds DG, et al:  Adrenalectomy abolishes and cortisol restores naloxone's beneficial effects on cardiovascular function and survival in canine hemorrhagic shock . Circ Shock 1983;;10:317-327.
25 +
Hinshaw LB, Beller BK, Archer LT, et al:  Recovery from lethal Escherichia coli shock in dogs . Surg Gynecol Obstet 1979;;149:545-553.
26 +
Beller BK, Archer LT, Passey RB, et al:  Effectiveness of modified steroid-antibiotic therapies for lethal sepsis in the dog . Arch Surg 1983;;118:1293-1299.
27 +
Hinshaw LB, Archer LT, Beller-Todd BK, et al:  Survival of primates in LD100 septic shock following steroid/antibiotic therapy . J Surg Res 1980;;28:151-170.
28 +
Hinshaw LB, Beller-Todd BK, Archer LT:  Current management of the septic shock patient: Experimental basis for treatment . Circ Shock 1982;;9:543-553.
29 +
Beller BK, Archer LT, Lane MM, et al:  Preventing v delaying death in shock therapy studies: Evaluating 'Survival.' Circ Shock 1983;;11:351-358.
30 +
Rees M, Payne JG, Bowen JC:  Naloxone reverses tissue effects of live Escherichia coli sepsis . Surgery 1982;;91:81-86.
31 +
White GL, Archer LT, Beller BK, et al:  Increased survival with methylprednisolone treatment in canine endotoxin shock . J Surg Res 1978;;25:357-364.
32 +
Longnecker DE, Kettler DF:  Value of naloxone in the treatment of hemorrhagic shock . Anesthesiology 1983;;59:120.
33 +
Benedict CR, Grahame-Smith DG:  Plasma noradrenaline and adrenaline concentrations and dopamine-β-hydroxylase activity in patients with shock due to septicemia, trauma, and haemorrhage . Q J Med 1978;;47:1-20.
34 +
Bocking JK, Sibbald WJ, Holliday RL, et al:  Plasma catecholamine levels and pulmonary dysfunction in sepsis . Surg Gynecol Obstet 1979;;148: 715-719.
35 +
Taff RH:  Pulmonary edema following naloxone administration in a patient without heart disease . Anesthesiology 1983;;59:576-577.
36 +
Holaday JW, D'Amato RJ, Ruvio BA, et al:  Adrenalectomy blocks pressor responses to naloxone in endotoxic shock: Evidence for sympathomedullary involvement . Circ Shock 1983;;11:201-210.
37 +
Brake CM, Emerson TE Jr, Wittmers LE:  Alterations of vascular responses to endotoxin by adrenergic blockade . Am J Physiol 1964;;207: 149-151.
38 +
Masucci FD, Hinshaw LB:  Evaluation of protection with phenoxybenzamine against lethal endotoxin shock . Proc Soc Exp Biol Med 1964;;116:1057-1060.
39 +
Hinshaw LB, Brake CM, Emerson TE Jr, et al:  Participation of the sympathoadrenal system in endotoxin shock . Am J Physiol 1964;;207: 925-930.
40 +
Emerson TE Jr, Brake CM, Hinshaw LB:  Endotoxin shock in chronic splanchnic denervated dogs . J Trauma 1965;;5:737-740.

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