Early hyperbaric oxygen therapy improves survival in a model of severe sepsis

Abstract

Sepsis is a major clinical challenge, with therapy limited to supportive interventions. Therefore, the search for novel remedial approaches is of great importance. We addressed whether hyperbaric oxygen therapy (HBOT) could improve the outcome of sepsis using an acute experimental mouse model. Sepsis was induced in male CD-1 mice by cecal ligation and puncture (CLP) tailored to result in 80–90% mortality within 72 h of the insult. After CLP, mice were randomized into two groups receiving HBOT or not at different times after the initial insult or subjected to multiple HBOT treatments. HBOT conditions were 98% oxygen pressurized to 2.4 atmospheres for 1 h. HBOT within 1 h after CLP resulted in 52% survival in comparison with mice that did not receive the treatment (13% survival). Multiple HBOT at 1 and 6 h or 1, 6, and 21 h displayed an increase in survival of >50%, but they were not significantly different from a single treatment after 1 h of CLP. Treatments at 6 or 21 h after CLP, excluding the 1 h of treatment, did not show any protective effect. Early HBO treatment did not modify bacterial counts after CLP, but it was associated with decreased expression of TNF-α, IL-6, and IL-10 expression in the liver within 3 h after CLP. The decrease of cytokine expression was reproduced in cultured macrophages after exposure to HBOT. Early HBOT could be of benefit in the treatment of sepsis, and the protective mechanism may be related to a reduction in the systemic inflammatory response.

Effect of Hyperbaric Oxygen Therapy on Acute Liver Injury and Survival in a Rat Cecal Slurry Peritonitis Model

“…A recent study showed that the bacterial load within the peritoneal fluid and blood was not affected by HBOT in the CLP sepsis model. The authors concluded that, in that polymicrobial sepsis model, HBOT did not have a direct bactericidal effect [ 32 ]. However, our study results may not be affected by the presence or absence of a direct, HBOT-mediated bactericidal effect.…”

COVID-19, acute respiratory distress syndrome (ARDS), and hyperbaric oxygen therapy (HBOT): what is the link?

“…The absence of drug treatments to limit lethality and vaccines to curve down COVID-19 infections have left clinicians with the single option of using supportive therapy as the only intervention, such as the delivery of oxygen and fluids, and mechanical ventilation as the last resource. Experimental animal studies about the response to sepsis have suggested that early interventions are critical to ameliorate the condition, such as source control of the infection or injury (Cauvi et al 2012;Cauvi et al 2019), the use of antibiotics (Puskarich et al 2009), or a reduction in the inflammatory response (Halbach et al 2019). Indeed, the Surviving Sepsis Campaign calls for early administration of supportive therapy (e.g., antibiotics and fluids) to ameliorate the disease (http://www.…”

“…In this regard, hyperbaric oxygen therapy (HBOT) that consists of exposure to 100% oxygen under increased atmospheric pressure up to 2.4 atm could be a great resource to improve the outcome from the infection when it is administered at early stages as soon as a reduction of arterial oxygen concentration is detected. Indeed, experimental animal studies have shown that an initial HBOT improved dramatically the outcome from sepsis, which was correlated with a reduction of the inflammatory response triggered by the initial insult (Halbach et al 2019). The great advantage of HBOT is that it delivers oxygen at elevated partial pressure allowing this gas to penetrate tissues very rapidly and in higher concentration, which is more effective than hemoglobin oxygen delivery.…”

“…Moreover, HBOT alters the balance between glycolysis and mitochondrial respiration, possibly countering an effect of viral infection on cellular caloristasis networks (Tezgin et al 2020) and improving hypoxia in COVID-19 patients. An additional advantage of HBOT is its capacity to reduce the inflammatory response (Buras et al 2006;Halbach et al 2019). Several studies have shown that HBOT improves kidney function after infection (Edremitlioglu et al 2005) and reduces kidney damage in diabetic patients (Harrison et al 2018).…”

On barring the vascular gateway against severe COVID-19 disease

“…HBOT can directly reverse tissue hypoxia and is anti-inflammatory-both global pathologic features of COVID-19 disease. Most recently, HBOT reduced hepatic cytokine production in a rodent model of severe, polymicrobial sepsis (Halbach et al 2019). HBOT has been shown to reduce circulating cytokine levels in individuals with Crohn's disease (Weisz et al 1997).…”