Immunomodulation by extracorporeal ozone-based bactericide system in porcine Pseudomonas aeruginosa septic shock

Rundgren H, Sjöholm J, Juric S, et al. Scientific Reports, 2025.

View the abstract on PubMed

Study type
Animal study
Animals studied
13 animals
Population
13 swine with P. aeruginosa septic shock, allocated to extracorporeal ozone treatment (7) or no ozone treatment (6)
Published
2025, Scientific Reports
Identifiers
PMID 40562794, DOI 10.1038/s41598-025-07408-5
Group
Background science and mechanism studies

What the authors reported

In pigs with P. aeruginosa septic shock (7 ozone, 6 none), one pass through the system cut viable bacteria by 53%, but bacteria in peripheral blood and survival (median 134 vs 159 min) did not differ. IL-1β, IL-4, IL-6, IL-8 and IFN-γ fell with ozonation, complement did not; hemoglobin, hematocrit, noradrenaline doses, breathing rate and peak airway pressure were lower with ozone.

What limits this result

Not the EBOO procedure: a prototype that cools blood and mixes it with oxygen-ozone gas, at about 50 mL/min (about 2 L over 4 hours), in pigs. Small 4-hour feasibility study; groups were allocated, not stated as randomized, and with no ozone-free control circuit ozone is not separated from cooling or circuit effects. Funded by Sangair; two authors own or work for Sangair.

How ozone acts on blood and cells, how blood filters work, the laboratory and device-development studies behind the EBOO circuit, and studies that measure markers in the blood rather than how patients fare. None of these shows whether EBO2 helps patients. One study rarely settles a medical question; our guides weigh each paper against the rest of the evidence.

How the study was done

Design
4-hour swine sepsis model: P. aeruginosa infusion with or without extracorporeal ozone treatment (groups allocated)
Setting
Section for Experimental Traumatology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden (corresponding author's affiliation)
Read from
Read from the full text of the paper. Read on October 2, 2026.

Source: Abstract on PubMed

Study arms

Each group as the paper describes it.
GroupParticipantsWhat they received
P. aeruginosa infusion and ozone treatment7P. aeruginosa infusion with extracorporeal ozone treatment
P. aeruginosa infusion, no ozone treatment6P. aeruginosa infusion without ozone treatment

Source: Abstract on PubMed

Procedure as reported

Ozone concentration
Below 100 g/m3 (gas flow 15 mL/min)The ozone concentration was maintained below 100 g/m 3 , with a gas flow rate of 15 mL/min.
Blood volume
Approximately 2 L of blood over the 4-h experimental periodthe extracorporeal ozone treatment was administered at a flow rate of 50 mL/min, treating approximately 2 L of blood over the 4-h experimental period
Session length
Mean (SD) 134 (67) min
Blood flow
Average 50 mL/minblood was drawn from the venous circulation of the swine at an average flow rate of 50 mL/min
Anticoagulant
Heparin: 4000 IU IV 15 min before ozone therapy, then 33 IU/kg/h throughout the treatment period4000 IU of heparin was administered intravenously 15 min before ozone therapy began, followed by a continuous infusion of 33 IU/kg/h throughout the treatment period.
Filter
SangAsept blood ozonation prototype (patent no. WO2016/043649)

In the paper's own units, not converted.

Sources: Full text on PubMed Central, Abstract on PubMed

What it measured

Viable P. aeruginosa after a single pass through the system
Decreased by 53%, mean 2193 to 1023 CFU/mL; mean of differences -1170 (95% CI -1689 to -651, P < 0.0001)
Viable bacteria in peripheral venous blood, ozone vs no ozone
No difference between groups (P = 0.68)
Cytokines
IL-1β, IL-4, IL-6, IL-8 and IFN-γ decreased by ozonation; TNFa, IL-2 and IL-10 were not affected
Classical and alternative complement pathways
Not affected
Hemoglobin, hematocrit, and noradrenaline doses
Decreased in the ozone treatment group
Breathing frequency and pulmonary peak airway pressure
Decreased in the ozone treatment group
Survival
Median 134 min with ozone treatment and 159 min without; no statistical difference
Methemoglobin
Did not increaseMethemoglobin levels did not increase, consistent with findings from our previous investigation

Sources: Abstract on PubMed, Full text on PubMed Central

Safety as reported

The authors state the system was compatible with an intensive care environment and did not induce any observable physiological adverse effects

Source: Full text on PubMed Central

Follow-up

Animals euthanized at the end of the experiment or at the time of circulatory collapseAt the end of the experiment, or at the time of circulatory collapse, the animals were euthanized with 40 mL pentobarbital sodium (Alfatal Vet 100 mg/mL)

Source: Full text on PubMed Central

Funding and conflicts

Funded by an unrestricted grant from Sangair AB (Sweden)

Source: Full text on PubMed Central

Where we cite this study

All studies we track · How the studies compare