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Effect of hyperbaric oxygen therapy (HBO) on implant-associated osteitis in a femur fracture model in mice.

ABSTRACT: Hyperbaric oxygen therapy (HBO) is applied very successfully in treatment of various diseases such as chronic wounds. It has been already suggested as adjunctive treatment option for osteitis by immune- and fracture modulating effects. This study evaluates the importance of HBO in an early implant-associated localized osteitis caused by Staphylococcus aureus (SA) compared to the standard therapy. In a standardized murine model the left femur of 120 BALB/c mice were osteotomized and fixed by a titanium locking plate. Osteitis has been induced with a defined amount of SA into the fracture gap. Debridément and lavages were progressed on day 7, 14, 28 and 56 to determine the local bacterial growth and the immune reaction. Hyperbaric oxygen (2 ATA, 90%) was applied for 90 minutes on day 7 to 21 for those mice allocated to HBO therapy. To evaluate the effect of HBO therapy the following groups were analyzed: Two sham-groups (12 mice / group) with and without HBO therapy, two osteotomy groups (24 mice / group) with plate osteosynthesis of the femur with and without HBO therapy, and two osteotomy SA infection groups (24 mice / group) with and without HBO therapy. Fracture healing was also quantified on day 7, 14, 28 and 56 by a.p. x-ray and bone healing markers from blood samples. Progression of infection was assessed by estimation of colony-forming units (CFU) and immune response was analyzed by determination of polymorphonuclear neutrophils (PMN), Interleukin (IL) - 6, and the circulating free DNA (cfDNA) in lavage samples. Osteitis induced significantly higher IL-6, cfDNA- and PMN-levels in the lavage samples (on day 7 and 14, each p < 0.05). HBO-therapy did not have a significant influence on the CFU and immune response compared to the standard therapy (each p > 0.05). At the same time HBO-therapy was associated with a delayed bone healing assessed by x-ray radiography and a higher rate of non-union until day 28. In conclusion, osteitis led to significantly higher bacterial count and infection parameters. HBO-therapy neither had a beneficial influence on local infection nor on immune response or fracture healing compared to the standard therapy in an osteitis mouse model.

SUBMITTER: Buren C

PROVIDER: S-EPMC5788341 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effect of hyperbaric oxygen therapy (HBO) on implant-associated osteitis in a femur fracture model in mice.

Büren Carina C Lögters Tim T Oezel Lisa L Rommelfanger Golnessa G Scholz Armin Olaf AO Windolf Joachim J Windolf Ceylan Daniela CD

PloS one 20180129 1

Hyperbaric oxygen therapy (HBO) is applied very successfully in treatment of various diseases such as chronic wounds. It has been already suggested as adjunctive treatment option for osteitis by immune- and fracture modulating effects. This study evaluates the importance of HBO in an early implant-associated localized osteitis caused by Staphylococcus aureus (SA) compared to the standard therapy. In a standardized murine model the left femur of 120 BALB/c mice were osteotomized and fixed by a ti ...[more]

PMID: 29377928

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Project description:Cerament (Bonesupport Holding, Lund, Sweden) is a bioresorbable synthetic bone substitute consisting of calcium sulfate and hydroxyapatite which is successfully used as a bone graft in bone defects or in delayed and non-unions after fractures. Besides, calcium sulfate/ hydroxyapatite (CAS/HA) could have, attributed to its composition and osteoinductive properties, have great importance in the treatment of bone infections with critical size defects (CSD). Aim of the study was to evaluate the effects of antibiotic infused CAS/HA on inflammation and bone healing in an implant-associated osteitis mice model. In a standardized murine model, the left femur of 72 BALB/c mice were osteotomized, generating a CSD (2,5 mm) with stabilization through a 6-hole titanium locking plate. Osteitis has been induced through inoculation of Staphylococcus aureus (SA) into the fracture gap. To analyze the effect of CAS/HA, following groups were generated with either CAS/HA, CAS/HA with gentamycin (CAS/ HA-G) or CAS/HA with vancomycin (CAS/HA-V) insets placed into the osteotomy. Debridément and lavages were progressed on day 7 and 42 to determine the local bacterial growth and the immune reaction. Fracture healing was quantified on day 7 and 42 by x-ray and bone healing markers from blood samples. Progression of infection was assessed by estimation of colony-forming units (CFU) and immune response was analyzed by determination of Interleukin (IL)- 6 and polymorphonuclear neutrophils (PMN) in lavage samples. Osteitis induced higher IL-6 and PMN-levels in the lavage samples on day 7. Both parameters showed a reduction in all groups on day 42. CAS/HA-V revealed a significant reduction of CFU and PMNs in lavage samples on day 42. A positive effect on bone healing could only be shown in non-infected mice. Whereas, application of mere CAS/HA in infected mice did show tendencies of bone destruction and lysis, independent of impregnation with antibiotics or not. Thus, application of CAS/HA in acute implant-associated infections is not recommended. In non-infectious environments or after infect-convalescence CAS/HA could albeit serve as a suggestive tool in trauma and orthopedic surgery.

Project description:BackgroundHyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than one atmosphere absolute (ATA) in a pressure vessel. This technology has been used to treat a variety of diseases and has been described as helping patients who have delayed healing or established non-union of bony fractures. This is an update of a Cochrane Review first published in 2005, and previously updated in 2008.ObjectivesThe aim of this review is to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of delayed bony healing and established non-union of bony fractures.Search methodsWe searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2012), the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1946 to July Week 1 2012), EMBASE (1974 to 2012 July 16), CINAHL (1937 to 17 July 2012), the Database of Randomised Controlled Trials in Hyperbaric Medicine (accessed July 2012), the WHO International Clinical Trials Registry Platform (17 July 2012) and reference lists of articles.Selection criteriaWe aimed to include all randomised controlled trials comparing the clinical effects of HBOT with no HBOT (no treatment or sham) for healing of bony fractures and fracture non-unions.Data collection and analysisTwo review authors independently screened electronic search results, and all three authors independently performed study selection. We planned independent data collection and risk of bias assessment by two authors using standardised forms.Main resultsNo trials met the inclusion criteria. In this update, we identified three ongoing randomised controlled trials. Among the eight excluded studies were three randomised trials comparing HBOT with no treatment that included patients with fractures. One of these trials had been abandoned and the other two did not report on fracture healing outcomes.Authors' conclusionsThis systematic review failed to locate any relevant clinical evidence to support or refute the effectiveness of HBOT for the management of delayed union or established non-union of bony fractures. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of these injuries. There are three randomised controlled trials underway and we anticipate these will help provide some relevant clinical evidence to address this issue in the future.

Project description:BACKGROUND:Chronic wounds are common and present a health problem with significant effect on quality of life. Various pathologies may cause tissue breakdown, including poor blood supply resulting in inadequate oxygenation of the wound bed. Hyperbaric oxygen therapy (HBOT) has been suggested to improve oxygen supply to wounds and therefore improve their healing. OBJECTIVES:To assess the benefits and harms of adjunctive HBOT for treating chronic ulcers of the lower limb. SEARCH METHODS:For this second update we searched the Cochrane Wounds Group Specialised Register (searched 18 February 2015); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 1); Ovid MEDLINE (1946 to 17 February 2015); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, 17 February 2015); Ovid EMBASE (1974 to 17 February 2015); and EBSCO CINAHL (1982 to 17 February 2015). SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing the effect on chronic wound healing of therapeutic regimens which include HBOT with those that exclude HBOT (with or without sham therapy). DATA COLLECTION AND ANALYSIS:Three review authors independently evaluated the risk of bias of the relevant trials using the Cochrane methodology and extracted the data from the included trials. We resolved any disagreement by discussion. MAIN RESULTS:We included twelve trials (577 participants). Ten trials (531 participants) enrolled people with a diabetic foot ulcer: pooled data of five trials with 205 participants showed an increase in the rate of ulcer healing (risk ratio (RR) 2.35, 95% confidence interval (CI) 1.19 to 4.62; P = 0.01) with HBOT at six weeks but this benefit was not evident at longer-term follow-up at one year. There was no statistically significant difference in major amputation rate (pooled data of five trials with 312 participants, RR 0.36, 95% CI 0.11 to 1.18). One trial (16 participants) considered venous ulcers and reported data at six weeks (wound size reduction) and 18 weeks (wound size reduction and number of ulcers healed) and suggested a significant benefit of HBOT in terms of reduction in ulcer area only at six weeks (mean difference (MD) 33.00%, 95% CI 18.97 to 47.03, P < 0.00001). We identified one trial (30 participants) which enrolled patients with non-healing diabetic ulcers as well as venous ulcers ("mixed ulcers types") and patients were treated for 30 days. For this "mixed ulcers" there was a significant benefit of HBOT in terms of reduction in ulcer area at the end of treatment (30 days) (MD 61.88%, 95% CI 41.91 to 81.85, P < 0.00001). We did not identify any trials that considered arterial and pressure ulcers. AUTHORS' CONCLUSIONS:In people with foot ulcers due to diabetes, HBOT significantly improved the ulcers healed in the short term but not the long term and the trials had various flaws in design and/or reporting that means we are not confident in the results. More trials are needed to properly evaluate HBOT in people with chronic wounds; these trials must be adequately powered and designed to minimise all kinds of bias.

Project description:BackgroundA few prospective trials and case series have suggested that hyperbaric oxygen therapy (HBOT) may be efficacious for the treatment of severe COVID-19, but safety is a concern for critically ill patients. We present an interim analysis of the safety of HBOT via a randomized controlled trial (COVID-19-HBO).MethodsA randomized controlled, open-label, clinical trial was conducted in compliance with good clinical practice to explore the safety and efficacy of HBOT for severe COVID-19 in critically ill patients with moderate acute respiratory distress syndrome (ARDS). Between 3 June 2020, and 17 May 2021, 31 patients with severe COVID-19 and moderate-to-severe ARDS, a ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) < 26.7 kPa (200 mmHg), and at least two defined risk factors for intensive care unit (ICU) admission and/or mortality were enrolled in the trial and randomized 1:1 to best practice, or HBOT in addition to best practice. The subjects allocated to HBOT received a maximum of five treatments at 2.4 atmospheres absolute (ATA) for 80 min over seven days. The subjects were followed up for 30 days. The safety endpoints were analyzed.ResultsAdverse events (AEs) were common. Hypoxia was the most common adverse event reported. There was no statistically significant difference between the groups. Numerically, serious adverse events (SAEs) and barotrauma were more frequent in the control group, and the differences between groups were in favor of the HBOT in PaO2/FiO2 (PFI) and the national early warning score (NEWS); statistically, however, the differences were not significant at day 7, and no difference was observed for the total oxygen burden and cumulative pulmonary oxygen toxicity dose (CPTD).ConclusionHBOT appears to be safe as an intervention for critically ill patients with moderate-to-severe ARDS induced by COVID-19.Clinical trial registrationNCT04327505 (31 March 2020) and EudraCT 2020-001349-37 (24 April 2020).

Project description:The disease burden from diabetic kidney disease is large and growing. Effective therapies are lacking, despite an urgent need. Hyperbaric oxygen therapy (HBOT) activates Nrf2 and cellular antioxidant defenses; therefore, it may be generally useful for treating conditions that feature chronic oxidative tissue damage. Herein, we determined how periodic exposure to oxygen at elevated pressure affected type 2 diabetes mellitus-related changes in the kidneys of db/db mice. Two groups of db/db mice, designated 2.4 ATA and 1.5 ATA, were treated four times per week with 100 % oxygen at either 1.5 or 2.4 ATA (atmospheres absolute) followed by tests to assess kidney damage and function. The sham group of db/db mice and the Hets group of db/+ mice were handled but did not receive HBOT. Several markers of kidney damage were reduced significantly in the HBOT groups including urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CyC) along with significantly lower levels of caspase-3 activity in kidney tissue extracts. Other stress biomarkers also showed trends to improvement in the HBOT groups, including urinary albumin levels. Expressions of the stress response genes NRF2, HMOX1, MT1, and HSPA1A were reduced in the HBOT groups at the end of the experiment, consistent with reduced kidney damage in treated mice. Urinary albumin/creatinine ratio (ACR), a measure of albuminuria, was significantly reduced in the db/db mice receiving HBOT. All of the db/db mouse groups had qualitatively similar changes in renal histopathology. Glycogenated nuclei, not previously reported in db/db mice, were observed in these three experimental groups but not in the control group of nondiabetic mice. Overall, our findings are consistent with therapeutic HBOT alleviating stress and damage in the diabetic kidney through cytoprotective responses. These findings support an emerging paradigm in which tissue oxygenation and cellular defenses effectively limit damage from chronic oxidative stress more effectively than chemical antioxidants.

Dataset Information

Effect of hyperbaric oxygen therapy (HBO) on implant-associated osteitis in a femur fracture model in mice.

Publications

Effect of hyperbaric oxygen therapy (HBO) on implant-associated osteitis in a femur fracture model in mice.

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