Background Endotoxemia from lipopolysaccharide (LPS) induces systemic cytokine production, whereas traumatic brain injury (TBI) increases intracerebral cytokine production. In anesthetic doses, ketamine has potent anti-inflammatory properties. However, its anti-inflammatory effects at sub-anesthetic doses and its effects upon TBI induced inflammation have not been fully investigated. We hypothesized that ketamine would attenuate both LPS and TBI induced inflammatory responses. Methods Male rats received intraperitoneal ketamine (70, 7, or 1 mg/kg IP) or saline one hour before LPS (20 mg/kg IP) or saline. Five hours after LPS, rats were sacrificed. Serum was collected for cytokine analysis. In other experiments, male rats were given ketamine (7 mg/kg IP) or saline one hour prior to induction of TBI with controlled cortical impact (or sham). One and six hours following injury, brain was extracted for analysis of cerebral edema and cytokine production. Results LPS increased the serum concentrations of IL-1α, IL-1β, IL-6, IL-10, TNF-α, and IFN-γ. Ketamine dose dependently attenuated these changes. TBI caused cerebral edema and increased concentrations of cerebral IL-1α, IL-1β, IL-6, IL-10, and TNF-α. However, ketamine had minimal effect on TBI induced inflammation. Conclusions While ketamine did not appear to exert any beneficial effects against TBI in the rat, it did not exacerbate cytokine production or enhance cerebral edema as some studies have suggested.

No abstract

No abstract

IntroductionInfection control in patients with perforated peptic ulcers (PPU) commonly includes empiric antifungals (AF). We investigated the variation in the use of empiric AF and explored the association between their use and the subsequent development of organ space infection (OSI).MethodsThis was a secondary analysis of a multicenter, case–control study of patients treated for PPU at nine institutions between 2011 and 2018. Microbiology and utilization of empiric AF, defined as AF administered within 24 hours from the index surgery, were recorded. Patients who received empiric AF were compared with those who did not. The primary outcome was OSI and secondary outcome was OSI with growth of Candida spp. A logistic regression was used to adjust for differences between the two cohorts.ResultsA total of 554 patients underwent a surgical procedure for PPU and had available timing of AF administration. The median age was 57 years and 61% were male. Laparoscopy was used in 24% and omental patch was the most common procedure performed (78%). Overall, 239 (43%) received empiric AF. There was a large variation in the use of empiric AF among participating centers, ranging from 25% to 68%. The overall incidence of OSI was 14% (77/554) and was similar for patients who did or did not receive empiric AF. The adjusted OR for development of OSI for patients who received empiric AF was 1.04 (95% CI 0.64 to 1.70), adjusted p=0.86. The overall incidence of OSI with growth of Candida spp was 5% and was similar for both groups (adjusted OR 1.29, 95% CI 0.59 to 2.84, adjusted p=0.53).ConclusionFor patients undergoing surgery for PPU, the use of empiric AF did not yield any significant clinical advantage in preventing OSI, even those due to Candida spp. Use of empiric AF in this setting is unnecessary.Study typeOriginal article, case series.Level of evidenceIII.