Purpose Animal studies have demonstrated anti-inflammatory, and anti-nociceptive properties of hyperbaric oxygen therapy (HBOT). However, physiological data are scarce in humans. In a recent experimental study, the authors used the burn injury (BI) model observing a decrease in secondary hyperalgesia areas (SHA) in the HBOT-group compared to a control-group. Surprisingly, a long-lasting neuroplasticity effect mitigating the BI-induced SHA-response was seen in the HBOT-preconditioned group. The objective of the present study, therefore, was to confirm our previous findings using an examiner-blinded, block-randomized, controlled, crossover study design. Patients and methods Nineteen healthy subjects attended two BI-sessions with an inter-session interval of ≥28 days. The BIs were induced on the lower legs by a contact thermode (12.5 cm 2 , 47C°, 420 s). The subjects were block-randomized to receive HBOT (2.4 ATA, 100% O 2 , 90 min) or ambient conditions ([AC]; 1 ATA, 21% O 2 ), dividing cohorts equally into two sequence allocations: HBOT-AC or AC-HBOT. All sensory assessments performed during baseline, BI, and post-intervention phases were at homologous time points irrespective of sequence allocation. The primary outcome was SHA, comparing interventions and sequence allocations. Results Data are mean (95% CI). During HBOT-sessions a mitigating effect on SHA was demonstrated compared to AC-sessions, ie, 18.8 (10.5–27.0) cm 2 vs 32.0 (20.1–43.9) cm 2 ( P =0.021), respectively. In subjects allocated to the sequence AC-HBOT a significantly larger mean difference in SHA in the AC-session vs the HBOT-session was seen 25.0 (5.4–44.7) cm 2 ( P =0.019). In subjects allocated to the reverse sequence, HBOT-AC, no difference in SHA between sessions was observed ( P =0.55), confirming a preconditioning, long-lasting (≥28 days) effect of HBOT. Conclusion Our data demonstrate that a single HBOT-session compared to control is associated with both acute and long-lasting mitigating effects on BI-induced SHA, confirming central anti-inflammatory, neuroplasticity effects of hyperbaric oxygen therapy.

BackgroundSeptic shock remains a leading cause of death worldwide. Hyperbaric oxygen treatment (HBO2) has been shown to alter the inflammatory response during sepsis and to reduce mortality. A therapeutic window of HBO2 treatment has been demonstrated experimentally, but optimal timing remains uncertain. We investigated the effects of 24 h delayed normobaric oxygen (NBO2) and HBO2 treatment on the endogenous production of the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10, and on mortality in rats with cecal ligation and puncture (CLP) induced sepsis.MethodFifty-five male Sprague-Dawley rats underwent CLP and were randomized to the following groups: 1) HBO2 2.5 bar absolute pressure (pabs); 2) NBO2 1.0 bar pabs; 3) Control (no-treatment), and they were individually monitored for 72 h with intermittent blood sampling.ResultsIL-6, TNF-α, and IL-10 were increased 24 h after the procedure, and IL-6 was significantly higher in non-survivors than in survivors. The level of IL-10 was significantly higher at hour 48 in the HBO2 group compared to control (p = 0.01), but this was not the case at other time points. No other significant differences in cytokine levels were found for any group comparisons. Delayed NBO2 and HBO2 treatment failed to change the mortality in the animals.ConclusionHigh levels of IL-6 in non-surviving animals with sepsis suggest that IL-6 is a potential biomarker. We found a significantly higher concentration of IL-10 in the HBO2 group at hour 48 vs. control animals. However, 24 h–delayed treatment with HBO2 did not change the levels of pro-inflammatory cytokines and survival, suggesting that earlier intervention may be required to obtain an anti-inflammatory effect.

Background:The nitric oxide system could play an important role in the pathophysiology related to necrotizing soft tissue infection (NSTI). Accordingly, we investigated the association between plasma nitrite level at admission and the presence of septic shock in patients with NSTI. We also evaluated the association between nitrite, asymmetric dimethylarginine (ADMA), l-arginine, l-arginine/ADMA ratio, and outcome.Methods:We analyzed plasma from 141 NSTI patients taken upon hospital admission. The severity of NSTI was assessed by the presence of septic shock, Simplified Acute Physiology Score (SAPS) II, Sepsis-Related Organ Failure Assessment (SOFA) score, use of renal replacement therapy (RRT), amputation, and 28-day mortality.Results:No difference in nitrite levels was found between patients with and without septic shock (median 0.82 μmol/L [interquartile range (IQR) 0.41–1.21] vs. 0.87 μmol/L (0.62–1.24), P = 0.25). ADMA level was higher in patients in need of RRT (0.64 μmol/L (IQR 0.47–0.90) vs. (0.52 μmol/L (0.34–0.70), P = 0.028), and ADMA levels correlated positively with SAPS II (rho = 0.32, P = 0.0002) and SOFA scores (rho = 0.22, P = 0.01). In a logistic regression analysis, an l-arginine/ADMA ratio below 101.59 was independently associated with 28-day mortality, odds ratio 6.03 (95% confidence interval, 1.41–25.84), P = 0.016. None of the other analyses indicated differences in the NO system based on differences in disease severity.Conclusions:In patients with NSTI, we found no difference in baseline nitrite levels according to septic shock. High baseline ADMA level was associated with the use of RRT and patients with a low baseline l-arginine/ADMA ratio were at higher risk of dying within 28 days after hospital admission.