E. J. Charles1, A. Y. Zhang1, D. Wu1, R. G. Sawyer2, Z. Yang1 1University Of Virginia,Surgery,Charlottesville, VA, USA 2Western Michigan University,Surgery,Kalamazoo, MI, USA
Introduction: Septic shock often results in end-organ damage and high mortality. We have previously demonstrated that systemic hypothermia prolongs survival of rats with septic shock by inhibiting inflammatory responses. In the present study, we hypothesized that topical neck cooling would inhibit systemic inflammation and thus prolong survival of rats with septic shock.
Methods: Septic shock was induced by cecal ligation and incision (CLI) in Sprague Dawley rats. One hour after CLI, rats were randomized to no further treatment (control, N=12) or topical neck cooling for two hours by wrapping an ice-filled Penrose drain around the neck (N=10). An additional group of rats (N=5) underwent bilateral cervical vagotomy just prior to CLI, followed by topical neck cooling. Primary endpoint was survival duration (hours). Parallel groups of rats (N=4-5 per group) were euthanized three hours after CLI for evaluation of inflammatory markers.
Results: Topical neck cooling prolonged survival after CLI, with a median [IQR] of 10.4 [7.7-11.4] hours for neck cooling rats compared with 6.3 [5.1-7] hours for control (p=0.001). Kaplan-Meier survival analysis is shown in the figure (hazard ratio 0.14, 95% confidence interval 0.05-0.44). Median survival for vagotomy plus neck cooling group was significantly less than both other groups (2.8 [2.4-3] hours). Neck skin temperature was significantly lower in the neck cooling group than control group (16.7±1.4 vs. 30.5±0.6?C, p<0.0001), but the rectal core temperatures were maintained similar between control and neck cooling groups for up to 3 hours (36±0.2 vs. 36.4±0.3?C, p=0.3). Neck cooling rats awoke from anesthesia 71 minutes earlier than control (109±9 vs. 180±7 minutes, p=0.0004). None of the vagotomy plus neck cooling rats awoke prior to death. Significantly more splenic contraction (decreased weight) and fewer circulating leukocytes were found in control rats. Splenic tissue IL-1β and TNF-α protein and mRNA levels were significantly higher in control and vagotomy plus neck cooling groups compared to neck cooling alone (p<0.05). Plasma IL-1β and TNF-α levels were significantly higher in control and vagotomy plus neck cooling animals compared to neck cooling alone (p<0.05).
Conclusion: Topical neck cooling significantly prolonged survival of rats with septic shock and was associated with decreased splenic and systemic pro-inflammatory mediator expression, an effect abrogated by vagotomy. Neck cooling may be effective by activating the vagus nerve, leading to a reduced systemic inflammatory response. Topical cooling to target the vagus nerve is a non-invasive treatment that may provide a clinical benefit for septic patients.
