Gut lavage with antiendotoxin antibodies impedes bacterial translocation in hemorrhage/resuscitation

Dennis Gore, George Sutherland

Research output: Contribution to journalArticle

Abstract

Introduction: Bacterial/endotoxin translocation has been theorized to propagate cytokine liberation and promote sepsis syndrome following hemorrhage. Neither selective gut decontamination with antibiotics or intravenous administration of antiendotoxin antibodies have been encouraging in their ability to improve outcome in critically ill patients. The purpose of this study is to assess any efficacy in gut cleansing with lavage and gastric installation of monoclonal antiendotoxin antibodies in hemorrhage/resuscitation. Methods: Rats (group A) were given via a gastrostomy tube a 4 hour lavage of Golytely at 10cc per hour prior to a 30% blood volume hemorrhage and subsequent resuscitation with shed blood and normal saline. Rats were also given E5 (murine IgM antiendotoxin monoclonal antibody) in two doses (group B: E5 at 0.2 mg/100gm body wt; group C: E5 at 2 mg/100 gm body wt) during the final hour of the Golytely lavage and then subjected to 30% blood volume hemorrhage/ resuscitation. For sham controls (group D) instrumented rats were subjected to standard hemorrhage/resuscitation without either gut lavage or antibody therapy. All animals were sacrificed 300 minutes following hemorrhage. Results: Plasma Plasma TNFα (pg/ml) Group (n) mBP@300 mins lactate (mmol/l) 0 mins 120 mins 300 mins A (6) 94 ± 4 1.9 ± 0.5*4.9 ± 2.5 54.4 ± 29.4 2.0 ± 1.1*B (6) 95 ± 3 2.1 ± 0.4*6.7 ± 1.6 23.1 ± 11.5 5.6 ± 1.2 C (6) 111 ± 6*1.7 ± 0.2*8.3 ± 1.1 15.9 ± 4.7*3.7 ± 0.9*D (8) 87 ± 8 4.8 ± 1.9 9.2 ± 5.5 65.9 ± 37.0 9.3 ± 4.7 Mean ± SEM,*p<0.05 comparison to group D by Student's independent t test. mBP (mean blood pressure) These findings demonstrate that reducing the quantity of gut bacteria by lavage may reduce cytokine liberation and improve systemic perfusion, as indexed by plasma lactate, associated with severe hemorrhage/resuscitation. Furthermore, the addition of monoclonal antiendotoxin antibodies via gut lavage may have a slight adjunctive effect. Conclusion: These results support the concept of bacterial/endotoxin translocation following hemorrhage/resuscitation and suggest a possible therapeutic benefit to gut lavage and gastric administration of monoclonal antiendotoxin antibodies in patients likely to suffer ongoing or recurrent severe hemorrhage.

Original languageEnglish (US)
JournalCritical Care Medicine
Volume27
Issue number1 SUPPL.
StatePublished - 1999

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Bacterial Translocation
Therapeutic Irrigation
Resuscitation
Hemorrhage
Monoclonal Antibodies
Gastric Lavage
Blood Volume
Endotoxins
Lactic Acid
Cytokines
Blood Pressure
antilipopolysaccharide antibodies
Systemic Inflammatory Response Syndrome
Gastrostomy
Decontamination
Critical Illness
Intravenous Administration
Immunoglobulin M
Perfusion
Students

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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Gut lavage with antiendotoxin antibodies impedes bacterial translocation in hemorrhage/resuscitation. / Gore, Dennis; Sutherland, George.

In: Critical Care Medicine, Vol. 27, No. 1 SUPPL., 1999.

Research output: Contribution to journalArticle

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title = "Gut lavage with antiendotoxin antibodies impedes bacterial translocation in hemorrhage/resuscitation",
abstract = "Introduction: Bacterial/endotoxin translocation has been theorized to propagate cytokine liberation and promote sepsis syndrome following hemorrhage. Neither selective gut decontamination with antibiotics or intravenous administration of antiendotoxin antibodies have been encouraging in their ability to improve outcome in critically ill patients. The purpose of this study is to assess any efficacy in gut cleansing with lavage and gastric installation of monoclonal antiendotoxin antibodies in hemorrhage/resuscitation. Methods: Rats (group A) were given via a gastrostomy tube a 4 hour lavage of Golytely at 10cc per hour prior to a 30{\%} blood volume hemorrhage and subsequent resuscitation with shed blood and normal saline. Rats were also given E5 (murine IgM antiendotoxin monoclonal antibody) in two doses (group B: E5 at 0.2 mg/100gm body wt; group C: E5 at 2 mg/100 gm body wt) during the final hour of the Golytely lavage and then subjected to 30{\%} blood volume hemorrhage/ resuscitation. For sham controls (group D) instrumented rats were subjected to standard hemorrhage/resuscitation without either gut lavage or antibody therapy. All animals were sacrificed 300 minutes following hemorrhage. Results: Plasma Plasma TNFα (pg/ml) Group (n) mBP@300 mins lactate (mmol/l) 0 mins 120 mins 300 mins A (6) 94 ± 4 1.9 ± 0.5*4.9 ± 2.5 54.4 ± 29.4 2.0 ± 1.1*B (6) 95 ± 3 2.1 ± 0.4*6.7 ± 1.6 23.1 ± 11.5 5.6 ± 1.2 C (6) 111 ± 6*1.7 ± 0.2*8.3 ± 1.1 15.9 ± 4.7*3.7 ± 0.9*D (8) 87 ± 8 4.8 ± 1.9 9.2 ± 5.5 65.9 ± 37.0 9.3 ± 4.7 Mean ± SEM,*p<0.05 comparison to group D by Student's independent t test. mBP (mean blood pressure) These findings demonstrate that reducing the quantity of gut bacteria by lavage may reduce cytokine liberation and improve systemic perfusion, as indexed by plasma lactate, associated with severe hemorrhage/resuscitation. Furthermore, the addition of monoclonal antiendotoxin antibodies via gut lavage may have a slight adjunctive effect. Conclusion: These results support the concept of bacterial/endotoxin translocation following hemorrhage/resuscitation and suggest a possible therapeutic benefit to gut lavage and gastric administration of monoclonal antiendotoxin antibodies in patients likely to suffer ongoing or recurrent severe hemorrhage.",
author = "Dennis Gore and George Sutherland",
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AU - Sutherland, George

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N2 - Introduction: Bacterial/endotoxin translocation has been theorized to propagate cytokine liberation and promote sepsis syndrome following hemorrhage. Neither selective gut decontamination with antibiotics or intravenous administration of antiendotoxin antibodies have been encouraging in their ability to improve outcome in critically ill patients. The purpose of this study is to assess any efficacy in gut cleansing with lavage and gastric installation of monoclonal antiendotoxin antibodies in hemorrhage/resuscitation. Methods: Rats (group A) were given via a gastrostomy tube a 4 hour lavage of Golytely at 10cc per hour prior to a 30% blood volume hemorrhage and subsequent resuscitation with shed blood and normal saline. Rats were also given E5 (murine IgM antiendotoxin monoclonal antibody) in two doses (group B: E5 at 0.2 mg/100gm body wt; group C: E5 at 2 mg/100 gm body wt) during the final hour of the Golytely lavage and then subjected to 30% blood volume hemorrhage/ resuscitation. For sham controls (group D) instrumented rats were subjected to standard hemorrhage/resuscitation without either gut lavage or antibody therapy. All animals were sacrificed 300 minutes following hemorrhage. Results: Plasma Plasma TNFα (pg/ml) Group (n) mBP@300 mins lactate (mmol/l) 0 mins 120 mins 300 mins A (6) 94 ± 4 1.9 ± 0.5*4.9 ± 2.5 54.4 ± 29.4 2.0 ± 1.1*B (6) 95 ± 3 2.1 ± 0.4*6.7 ± 1.6 23.1 ± 11.5 5.6 ± 1.2 C (6) 111 ± 6*1.7 ± 0.2*8.3 ± 1.1 15.9 ± 4.7*3.7 ± 0.9*D (8) 87 ± 8 4.8 ± 1.9 9.2 ± 5.5 65.9 ± 37.0 9.3 ± 4.7 Mean ± SEM,*p<0.05 comparison to group D by Student's independent t test. mBP (mean blood pressure) These findings demonstrate that reducing the quantity of gut bacteria by lavage may reduce cytokine liberation and improve systemic perfusion, as indexed by plasma lactate, associated with severe hemorrhage/resuscitation. Furthermore, the addition of monoclonal antiendotoxin antibodies via gut lavage may have a slight adjunctive effect. Conclusion: These results support the concept of bacterial/endotoxin translocation following hemorrhage/resuscitation and suggest a possible therapeutic benefit to gut lavage and gastric administration of monoclonal antiendotoxin antibodies in patients likely to suffer ongoing or recurrent severe hemorrhage.

AB - Introduction: Bacterial/endotoxin translocation has been theorized to propagate cytokine liberation and promote sepsis syndrome following hemorrhage. Neither selective gut decontamination with antibiotics or intravenous administration of antiendotoxin antibodies have been encouraging in their ability to improve outcome in critically ill patients. The purpose of this study is to assess any efficacy in gut cleansing with lavage and gastric installation of monoclonal antiendotoxin antibodies in hemorrhage/resuscitation. Methods: Rats (group A) were given via a gastrostomy tube a 4 hour lavage of Golytely at 10cc per hour prior to a 30% blood volume hemorrhage and subsequent resuscitation with shed blood and normal saline. Rats were also given E5 (murine IgM antiendotoxin monoclonal antibody) in two doses (group B: E5 at 0.2 mg/100gm body wt; group C: E5 at 2 mg/100 gm body wt) during the final hour of the Golytely lavage and then subjected to 30% blood volume hemorrhage/ resuscitation. For sham controls (group D) instrumented rats were subjected to standard hemorrhage/resuscitation without either gut lavage or antibody therapy. All animals were sacrificed 300 minutes following hemorrhage. Results: Plasma Plasma TNFα (pg/ml) Group (n) mBP@300 mins lactate (mmol/l) 0 mins 120 mins 300 mins A (6) 94 ± 4 1.9 ± 0.5*4.9 ± 2.5 54.4 ± 29.4 2.0 ± 1.1*B (6) 95 ± 3 2.1 ± 0.4*6.7 ± 1.6 23.1 ± 11.5 5.6 ± 1.2 C (6) 111 ± 6*1.7 ± 0.2*8.3 ± 1.1 15.9 ± 4.7*3.7 ± 0.9*D (8) 87 ± 8 4.8 ± 1.9 9.2 ± 5.5 65.9 ± 37.0 9.3 ± 4.7 Mean ± SEM,*p<0.05 comparison to group D by Student's independent t test. mBP (mean blood pressure) These findings demonstrate that reducing the quantity of gut bacteria by lavage may reduce cytokine liberation and improve systemic perfusion, as indexed by plasma lactate, associated with severe hemorrhage/resuscitation. Furthermore, the addition of monoclonal antiendotoxin antibodies via gut lavage may have a slight adjunctive effect. Conclusion: These results support the concept of bacterial/endotoxin translocation following hemorrhage/resuscitation and suggest a possible therapeutic benefit to gut lavage and gastric administration of monoclonal antiendotoxin antibodies in patients likely to suffer ongoing or recurrent severe hemorrhage.

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