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

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.