Role of Oxygen and Its Radicals in Peripheral Nerve Regeneration: From Hypoxia to Physoxia to Hyperoxia.

Oxygen is compulsory for mitochondrial function and energy supply, but it has numerous more nuanced roles. The different roles of oxygen in peripheral nerve regeneration range from energy supply, inflammation, phagocytosis, and oxidative cell destruction in the context of reperfusion injury to crucial redox signaling cascades that are necessary for effective axonal outgrowth. A fine balance between reactive oxygen species production and antioxidant activity draws the line between physiological and pathological nerve regeneration. There is compelling evidence that redox signaling mediated by the Nox family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases plays an important role in peripheral nerve regeneration. Further research is needed to better characterize the role of Nox in physiological and pathological circumstances, but the available data suggest that the modulation of Nox activity fosters great therapeutic potential. One of the promising approaches to enhance nerve regeneration by modulating the redox environment is hyperbaric oxygen therapy. In this review, we highlight the influence of various oxygenation states, i.e., hypoxia, physoxia, and hyperoxia, on peripheral nerve repair and regeneration. We summarize the currently available data and knowledge on the effectiveness of using hyperbaric oxygen therapy to treat nerve injuries and discuss future directions.

Validation of sham treatment in hyperbaric medicine: a randomised trial.

INTRODUCTION: This study aimed to determine the lowest possible atmospheric pressure in the 111-152 kPa (1.1-1.5 atmospheres absolute [atm abs]) range that would require the patients to equalise their ears, allowing an effective sham for a 203 kPa (2.0 atm abs) hyperbaric exposure. METHODS: We performed a randomised controlled study on 60 volunteers divided into 3 groups (compression to 111, 132 and 152 kPa (1.1, 1.3, 1.5 atm abs) to determine the minimum pressure to obtain blinding. Secondly, we applied additional blinding strategies (faster compression with ventilation during the fictitious compression time, heating at compression, cooling at decompression) on 25 new volunteers in order to enhance blinding. RESULTS: The number of participants who did not believe they had been compressed to 203 kPa was significantly higher in the 111 kPa compressed arm than in the other two arms (11/18 vs 5/19 and 4/18 respectively; P = 0.049 and P = 0.041, Fisher's exact test). There was no difference between compressions to 132 and 152 kPa. By applying additional blinding strategies, the number of participants who believed they had been compressed to 203 kPa increased to 86.5 %. CONCLUSIONS: A compression to 132 kPa, (1.3 atm abs, 3 metres of seawater equivalent) combined with the additional blinding strategies of forced ventilation, enclosure heating and compression in five minutes, simulates a therapeutic compression table and can be used as a hyperbaric placebo.

Successful Delayed Hyperbaric Oxygen Therapy and Iloprost Treatment on Severe Frostbite at High Altitude.

Magnan, Dre Marie-Anne, Marco Gelsomino, Pierre Louge, and Rodrigue Pignel. Successful delayed hyperbaric oxygen therapy and iloprost treatment on severe frostbite at high altitude. High Alt Med Biol. 23:294-297, 2022.-Frostbite is an injury caused when tissues freeze. Severe frostbite can result in amputation. Hyperbaric oxygen therapy (HBO) may improve frostbite outcome. The patient, a 36-year-old man, was climbing above 6,000 m in Kyrgystan when he fell into a crevasse and lost his gloves. The outside temperature was -30°C. He sustained grade 3 frostbite of both hands, which carries a high amputation risk. He was rescued by local responders and transported to the local hospital: neither rapid rewarming in warm water nor other specific frostbite treatment was given. The patient was repatriated to Geneva (day 2). On day 3, he received medical care including iloprost infusion for 7 days and daily HBO for 3 weeks. His hands healed in <1 month. He suffered no amputation. At 6-month follow-up, no early arthritis was found. Three years later he was able to climb again and play volleyball. He still does not have any clinical arthritis at 4-year follow-up. Iloprost is less effective when initiated longer than 48 hours after frostbite injury. Despite the delay, the patient did not require amputation, as might have been predicted by the injury. The combination of HBO and iloprost may have contributed to this favorable outcome.

Fatal diving: could it be an immersion pulmonary edema? Case report.

Immersion pulmonary edema is a rare, underrecognized, and potentially lethal pathology developing during scuba diving and other immersion-related activities (swimming or apnoea). Physiopathology is complex and not fully understood, but its mechanisms involve an alteration of the alveolo-capillary barrier caused by transcapillary pressure elevation during immersion, leading to an accumulation of fluid and blood in the alveolar space. Diagnosis remains a challenge for clinicians and forensic practionner. The symptoms begin during ascent, with cough, frothy sputum, and hemoptysis. Auscultation reveals signs of pulmonary edema. Pulmonary CT scan, which is the radiological exam of choice, shows ground glass opacities and interlobular thickening, eventually demonstrating a patterned distribution, likely in the anterior segments of both lungs. Apart from the support of vital functions, there is no specific treatment and hyperbaric oxygen therapy is not systematically recommended. We present a case of fatal IPE occurring in a recreational diver who unfortunately died shortly after his last dive. Diagnosis was made after complete forensic investigations including post-mortem-computed tomography, complete forensic autopsy, histological examination, and toxicological analysis.

A Delphi study to identify relevant scenarios as the first step toward an international hyperbaric medicine simulation curriculum.

INTRODUCTION: Evidence across healthcare specialties suggests that simulation-based education improves practices and patient outcomes. However, simulation has yet to be widely used in hyperbaric medicine education. We aimed to identify the most relevant clinical scenarios for inclusion in a simulation-based curriculum for hyperbaric medicine. METHODS: After ethics approval, we used a modified Delphi consensus method. We assembled an initial questionnaire and distributed it online in English and French to an international group of hyperbaric physicians and operators using a snowball recruitment technique. Participants rated the list of scenarios using a 5-point scale ranging from 1 (least relevant) to 5 (most relevant). Scenarios judged by at least 80% of participants to be relevant (score 4 or 5) were automatically included. Scenarios that did not meet this threshold and new scenarios suggested by participants during the first round were included in a second round. RESULTS: Seventy-one participants from nine countries, including both physicians and non-physicians, completed the first round and 34 completed the second. Five scenarios were identified as relevant: seizure, fire, cardiac arrest, pneumothorax, and technical deficiency such as power loss while operating the chamber. CONCLUSIONS: Five scenarios relevant for inclusion in the simulation-based curriculum in hyperbaric medicine were identified by expert consensus.

Hyperbaric Oxygen Therapy with Iloprost Improves Digit Salvage in Severe Frostbite Compared to Iloprost Alone.

Background and Objectives: Frostbite is a freezing injury that can lead to amputation. Current treatments include tissue rewarming followed by thrombolytic or vasodilators. Hyperbaric oxygen (HBO) therapy might decrease the rate of amputation by increasing cellular oxygen availability to the damaged tissues. The SOS-Frostbite study was implemented in a cross-border program among the hyperbaric centers of Geneva, Lyon, and the Mont-Blanc hospitals. The objective was to assess the efficacy of HBO + iloprost among patients with severe frostbite. Materials and Methods: We conducted a multicenter prospective single-arm study from 2013 to 2019. All patients received early HBO in addition to standard care with iloprost. Outcomes were compared to a historical cohort in which all patients received iloprost alone between 2000 and 2012. Inclusion criteria were stage 3 or 4 frostbite and initiation of medical care <72 h from frostbite injury. Outcomes were the number of preserved segments and the rate of amputated segments. Results: Thirty patients from the historical cohort were eligible and satisfied the inclusion criteria, and 28 patients were prospectively included. The number of preserved segments per patient was significantly higher in the prospective cohort (mean 13 ± SD, 10) compared to the historical group (6 ± 5, p = 0.006); the odds ratio was significantly higher by 45-fold (95%CI: 6-335, p < 0.001) in the prospective cohort compared to the historical cohort after adjustment for age and delay between signs of freezing and treatment start. Conclusions: This study demonstrates that the combination of HBO and iloprost was associated with higher benefit in patients with severe frostbite. The number of preserved segments was two-fold higher in the prospective cohort compared to the historical group (mean of 13 preserved segments vs. 6), and the reduction of amputation was greater in patients treated by HBO + iloprost compared with the iloprost only.

Decompression illness treated at the Geneva hyperbaric facility 2010-2016: A retrospective analysis of local cases.

INTRODUCTION: The Geneva hyperbaric chamber is the main treatment centre for decompression illness (DCI) in Switzerland. The characteristics, symptomatology, treatment and short-term outcome of divers treated at this chamber have not previously been investigated. METHODS: This was a retrospective study of patients treated with hyperbaric oxygen (HBO) for DCI from 2010 to 2016. Data were analysed to provide a description of the cases and statistical analysis for possible factors associated with an unfavourable outcome. RESULTS: One hundred and thirty-five patients were treated for DCI. Ninety-two were included in the study. Sixty-four presented with neurological and 28 with mild DCI. One hundred and thirty-five patients were treated for DCI. Ninety-two were included in the study. Sixty-four presented with neurological and 28 with mild DCI. Patients with mild DCI mainly had musculoskeletal symptoms (79%). Patients with neurological DCI mainly had spinal (55%), followed by vestibular (36%) symptoms. Arterial gas embolism was diagnosed in 30% of cases. Diving depths ranged between 15 and 142 metres, and dive times between two and 241 min. Median time to treatment was 6 h. Patients with neurological DCI had a high rate (25%) of persisting deficits after treatment. Older age was associated with an unfavourable outcome in univariate but not in multivariate analysis. No adverse effects of HBO were observed. For spinal DCI, a high Boussuges score was associated with persisting deficits after treatment. CONCLUSIONS: Our findings are consistent with other series. Severe DCI was associated with a high rate of persisting deficits. No single factor was associated with a negative outcome. A Boussuges score > 7 had sensitivity of 90% and positive predictive value 53% for predicting an unfavourable outcome in spinal DCI.

[Management of a foot ulcer in a patient with diabetes]. / Ulcère du pied chez un patient avec un diabète : quelle prise en charge médico-chirurgicale ?

Despite a benign appearance, any foot injury occurring in a patient with diabetes requires multidisciplinary management if dreaded complications such as amputation are to be avoided. From a pathophysiological point of view, foot ulcer generally results from the combination of lower extremity neuropathy, mechanical overload, immunopathy and vascular insufficiency. The treatment associates in all cases an offloading and one or more debridements. Depending on the grade of the ulcer, adjuvant treatments, such as antibiotic therapy, revascularization, and hyperbaric oxygen therapy may be indicated.

En dépit d'un aspect bénin, toute plaie au niveau d'un pied survenant chez un patient avec un diabète nécessite une prise en charge multidisciplinaire si l'on veut éviter des complications redoutables comme une amputation. D'un point de vue physiopathologique, l'ulcère du pied résulte généralement de la combinaison entre une neuropathie des membres inférieurs, une surcharge mécanique, une immunopathie et une insuffisance vasculaire. La prise en charge associe dans tous les cas une décharge et un ou plusieurs débridements. Selon la gravité de l'ulcère, des traitements adjuvants sont indiqués, tels qu'une antibiothérapie, une revascularisation et une oxygénothérapie hyperbare.

Urgent hyperbaric oxygen therapy for suicidal carbon monoxide poisoning: from a preliminary survey to a proposal for an integrated somatic-psychiatric protocol.

A considerable number of patients who made a carbon monoxide (CO) suicidal attempt are treated with urgent hyperbaric oxygen therapy (HBOT). For these patients at potential persistent risk of suicide, the hyperbaric chamber is a dangerous environment and their management a complex challenge for the Emergency Department (ED) and Hyperbaric Medicine Unit (UMH) teams. We aimed to (1) identify cases of intentional CO poisoning treated with urgent HBOT in the UMH of the University Hospitals of Geneva (HUG) during 2011-2018 and (2) test a proposed operational and integrated somatic-psychiatric protocol based on acquired experience. A total of 311 patients with CO poisoning were treated using urgent HBOT, for which poisoning was assumed suicidal in 40 patients (12.9%). This percentage appears greater than in other European countries. Both the excess of cases of intentional CO poisonings and difficulties encountered in their management resulted in the implementation of an operational and integrated somatic-psychiatric protocol addressing the entire patient's clinical trajectory, from the admission at ED-HUG to the treatment at the UMH-HUG. The established institutional protocol includes (1) clinical evaluation, (2) suicide risk assessment, and (3) safety measures. This is the first report-at our best knowledge-of a protocol detailing a practical procedure algorithm and focusing on multidisciplinary and mutual collaboration between the medical-nursing teams at the ED, psychiatric ED, and UMH. Improvements in patient's safety and care team's sense of security were observed. In conclusion, the opportunity to refer to a standardized protocol was beneficial in that it offers both reduced risks for suicidal patients and reduced stress for care teams operating in very acute and complex situations. Further studies are needed.

Can preventive hyperbaric oxygen therapy optimise surgical outcome?: A systematic review of randomised controlled trials.

BACKGROUND: A primary underlying cause of postoperative complications is related to the surgical stress response, which may be mitigated by hyperbaric oxygen therapy (HBOT), the intermittent administration of oxygen at a pressure higher than the atmospheric pressure at sea level. Promising clinical studies have emerged suggesting HBOT's efficacy for reducing some postoperative complications. Notwithstanding, the effectiveness (if any) of HBOT across a range of procedures and postoperative outcomes has yet to be clearly quantified. OBJECTIVE: This systematic review aimed to summarise the existing literature on peri-operative HBOT to investigate its potential to optimise surgical patient outcome. DESIGN: A systematic review of randomised controlled trials (RCTs) with narrative summary of results. DATA SOURCES: MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials were searched without language restrictions through to 19 June 2018. ELIGIBILITY CRITERIA: Studies were included if they involved patients of any age undergoing any surgical procedure and provided with at least one HBOT session in the peri-operative period. Two independent reviewers screened the initial identified trials and determined those to be included. Risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. RESULTS: The search retrieved 775 references, of which 13 RCTs were included (627 patients). Ten RCTs (546 patients) reported treatment was effective for improving at least one of the patient outcomes assessed, while two studies (55 patients) did not find any benefit and one study (26 patients) found a negative effect. A wide range of patient outcomes were reported, and several other methodological limitations were observed among the included studies, such as limited use of sham comparator and lack of blinding. CONCLUSION: Peri-operative preventive HBOT may be a promising intervention to improve surgical patient outcome. However, future work should consider addressing the methodological weaknesses identified in this review. TRIAL REGISTRATION: The protocol (CRD42018102737) was registered with the International ProspectiveRegister of Systematic Reviews (PROSPERO).

Mass Casualty Triage in the Case of Carbon Monoxide Poisoning: Lessons Learned.

ABSTRACTCarbon monoxide (CO) can cause mass intoxication, but no standard triage algorithm specifically addresses CO poisoning. The roles of some recent diagnostic tools in triage as well as treatment with hyperbaric oxygen are controversial. We describe a mass casualty case of CO poisoning involving 77 patients, with a focus on the triage and treatment options decided on-site. The reasons for choosing these options are reviewed, and the pitfalls that occurred and the lessons learned from this major incident are described. We discuss the potential to improve the management of such an event and strategies to accomplish this, including simplifying triage and administering oxygen to all exposed persons for 6 h. (Disaster Med Public Health Preparedness. 2018; 12: 373-378).

Delayed hyperbaric oxygen therapy for air emboli after open heart surgery: case report and review of a success story.

BACKGROUND: The current case describes a rare diagnosis of iatrogenic air emboli after elective cardiopulmonary bypass that was successfully treated with delayed hyperbaric oxygen therapy, with good clinical evolution in spite of rare complications. CASE PRESENTATION: A 35 years old male was admitted to the intensive care unit (ICU) for post-operative management after being placed on cardiopulmonary bypass (CPB) for an elective ventricular septal defect closure and aortic valvuloplasty. The patient initially presented with pathologically late awakening and was extubated 17 h after admission. Neurologic clinical status after extubation showed global aphasia, mental slowness and spatio-temporal disorientation. The injected cerebral CT scan was normal; the EEG was inconclusive (it showed metabolic encephalopathy without epileptic activity); and the cerebral MRI done 48 h after surgery showed multiple small subcortical acute ischemic lesions, mainly on the left fronto- parieto- temporo-occipital lobes. He was taken for hyperbaric oxygen therapy (HOT) over 54 h after cardiac surgery. The first session ended abruptly after 20 min when the patient suffered a generalised tonico-clonic seizure, necessitating a moderately rapid decompression, airway management, and antiepileptic treatment. In total, the patient received 7 HOT sessions over 6 days. He demonstrated full neurological recovery at 4 weeks and GOS (Glasgow Outcome Scale) of 5 out of 5 even after a long delay in initial management. Convulsions are a rare complication of HOT either due to reperfusion syndrome or hyperoxic toxicity and can be managed. Prior imaging by MRI or tympanic paracentesis (myringotomy) should not add further delay of treatment. CONCLUSION: HOT should be initiated upon late awakening and/or neurologic symptoms after CPB heart surgery, after exclusion of formal counter-indications, even if the delay exceeds 48 h.

Hyperbaric oxygen therapy promotes wound repair in ischemic and hyperglycemic conditions, increasing tissue perfusion and collagen deposition.

The treatment of chronic wounds remains inconsistent and empirical. Hyperbaric oxygen therapy (HBOT) is a promising method to improve wound repair but there is still a lack of understanding of its mechanisms of action and its indications are not yet clearly defined. We studied the effects of HBOT in four different wound conditions by inflicting bilateral wounds on the dorsal aspect of the feet of nonischemic or ischemic limbs in normoglycemic or hyperglycemic rats. To create an ischemic condition, arterial resection was performed unilaterally. Forty-four animals received HBOT five times a week until complete wound closure. Wound repair was compared with 44 rats receiving standard dressing only. HBOT increased blood flow and accelerated wound closure in ischemic and hyperglycemic wounds, most significantly when the two conditions were combined. Wound contraction and reepithelialization were similarly stimulated by HBOT. The acceleration of wound contraction was not associated with increased myofibroblasts expression, nor fibroblast recruitment or higher cell count in the granulation tissue. Of note, we observed a significant increase in collagen deposition in early time points in ischemic wounds receiving HBOT. This data emphasizes that an early application of HBOT might be crucial to its efficacy. We concluded that wounds where ischemia and hyperglycemia are combined, as it is often the case in diabetic patients, have the best chance to benefit from HBOT.