Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

Effect of enriched oxygen inhalation on lower limb skin temperatures in diabetic and healthy humans: a pilot study.

INTRODUCTION: Measurement of skin temperature with infrared thermometry has been utilised for assessing metabolic activity and may be useful in identifying patients with ulcers suitable for hyperbaric oxygen treatment and monitoring their treatment progress. Since oxygen promotes vasoconstriction in the peripheral circulation, we hypothesised that oxygen administration may lower skin temperature and complicate the interpretation of temperatures obtained. This pilot study investigated the effect of oxygen administration on lower limb skin temperature in healthy subjects and diabetic patients. METHODS: Volunteers were recruited from healthy staff members (n = 10) and from patients with diabetic foot ulcers (n = 10) at our facility. Foot skin surface temperatures were measured by infra-red thermometry while breathing three different concentrations of oxygen (21%, 50% and 100%). RESULTS: Skin temperature changes were observed with increasing partial pressure of oxygen in both groups. The mean (SD) foot temperatures of diabetic patients and healthy controls at air-breathing baseline were 30.1°C (3.6) versus 29.0°C (3.7) respectively, at FiO2 0.5 were 30.1°C (3.6) versus 28.5°C (4.1) and at FiO2 1.0 were 28.3°C (3.2) versus 29.2°C (4.3). None of these differences between groups were statistically significant. CONCLUSIONS: Data from this small study may indicate a difference in thermal responses between healthy subjects and diabetic patients when inhaling oxygen; however, none of the results were statistically significant. Further investigations on a larger scale are warranted in order to draw firm conclusions.

Adjunctive hyperbaric oxygen treatment for necrotising soft-tissue infections: A systematic review and meta-analysis.

INTRODUCTION: Surgical intervention, broad-spectrum antibiotics and intensive care support are the standard of care in the treatment of necrotising soft-tissue infections (NSTI). Hyperbaric oxygen treatment (HBOT) may be a useful adjunctive treatment and has been used for almost 60 years, but its efficacy remains unknown and has not been systematically appraised. The aim was to systematically review and synthesise the highest level of clinical evidence available to support or refute the use of HBOT in the treatment of NSTI. METHODS: The review was prospectively registered (PROSPERO; CRD42020148706). MEDLINE, EMBASE, CENTRAL and CINAHL were searched for eligible studies that reported outcomes in both HBOT treated and non-HBOT treated individuals with NSTI. In-hospital mortality was the primary outcome. Odds ratio (ORs) were pooled using random-effects models. RESULTS: The search identified 486 papers of which 31 were included in the qualitative synthesis and 21 in the meta-analyses. Meta-analysis on 48,744 patients with NSTI (1,237 (2.5%) HBOT versus 47,507 (97.5%) non-HBOT) showed in-hospital mortality was 4,770 of 48,744 patients overall (9.8%) and the pooled OR was 0.44 (95% CI 0.33-0.58) in favour of HBOT. For major amputation the pooled OR was 0.60 (95% CI 0.28-1.28) in favour of HBOT. The dose of oxygen in these studies was incompletely reported. CONCLUSIONS: Meta-analysis of the non-random comparative data indicates patients with NSTI treated with HBOT have reduced odds of dying during the sentinel event and may be less likely to require a major amputation. The most effective dose of oxygen remains unclear.

Hyperbaric oxygen for sudden hearing loss: Influence of international guidelines on practice in Australia and New Zealand.

INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSHL) is an otolaryngologic emergency. The Undersea and Hyperbaric Medicine Society (UHMS) revised practice guidelines in 2014 adding ISSHL to approved indications. This study investigated whether the UHMS guidelines influenced referral and practice in Australia and New Zealand. METHODS: Retrospective review of 319 patient referrals in two time periods (five years prior to addition of ISSHL to indications (T-PRE) and three years post (T-POST)). RESULTS: Seven of eight participating hyperbaric facilities provided data down to the level of the indication for HBOT for analysis. In T-PRE 136 patients were treated with HBOT for ISSHL, representing between 0% and 18% of the total cases to each facility. In the T-POST period 183 patients were treated for ISSHL, representing from 0.35% to 24.8% of the total patients in each facility. Comparison between the two periods shows the proportion of patients treated with ISSHL among all indications increased from 3.2% to 12.1% (P < 0.0009). One facility accounted for 74% (101/136) of ISSHL patients receiving HBOT in T-PRE and 63% (116/183) in T-POST. ISSHL case load at that facility increased from 18% to 24.8% (P = 0.009) after the UHMS guideline publication. Three of the seven units had a significant increase in referrals after the guideline change. CONCLUSION: There remains equipoise regarding HBOT in the management of ISSHL. Only three out of seven units had a significant increase in ISSHL patients after the UHMS guidelines publication. Without well controlled RCTs to develop guidelines based on good evidence this is unlikely to change and practice variation will continue.

An observational trial to establish the effect of hyperbaric oxygen treatment on pelvic late radiation tissue injury due to radiotherapy.

INTRODUCTION: Rates of pelvic cancer are growing globally with around half of these patients receiving radiotherapy. In a small proportion, radiotherapy results in significant late radiation tissue injury (LRTI) to surrounding tissue, most commonly affecting the bladder and bowel mucosa. We conducted a combined prospective and retrospective observational trial to establish the effectiveness of hyperbaric oxygen treatment (HBOT) in improving the symptoms and signs of LRTI in these patients. METHODS: Fifty-two patients were included after receiving radiotherapy for cancers of the bowel, bladder, cervix, prostate or vulva. They received HBOT at 203-243 kPa (2.0-2.4 atmospheres absolute (atm abs)) for 90 minutes with the median number of treatments being 30 (IQR 1). Late effects normal tissues - subjective, objective, management, analytic (LENT-SOMA) scores were recorded before and after treatment. RESULTS: The mean LENT-SOMA scores before and after HBOT were 11.7 (SD 5.3) and 8.1 (5.1) respectively. This reduction in score of 3.7 (95% CI 2.6 to 4.8) was statistically significant (P < 0.001). For radiation cystitis the mean reduction was 3.7 (95% CI 2.4 to 5.0, P < 0.001) and for radiation proctitis was 3.8 (95% CI 1.4 to 6.1, P = 0.004). There were no significant adverse effects recorded. CONCLUSIONS: Hyperbaric oxygen treatment may be an effective and safe treatment for pelvic late tissue radiation injury.

South Pacific Underwater Medicine Society guidelines for cardiovascular risk assessment of divers.

The South Pacific Underwater Medicine Society (SPUMS) diving medical for recreational scuba divers was last reviewed in 2011. From 2011 to 2019, considerable advancements have occurred in cardiovascular risk assessment relevant to divers. The SPUMS 48th (2019) Annual Scientific Meeting theme was cardiovascular risk assessment in diving. The meeting had multiple presentations updating scientific information about assessing cardiovascular risk. These were distilled into a new set of guidelines at the final conference workshop. SPUMS guidelines for medical risk assessment in recreational diving have subsequently been updated and modified including a new Appendix C: Suggested evaluation of the cardiovascular system for divers. The revised evaluation of the cardiovascular system for divers covers the following topics: 1. Background information on the relevance of cardiovascular risk and diving; 2. Defining which divers with cardiovascular problems should not dive, or whom require treatment interventions before further review; 3. Recommended screening procedures (flowchart) for divers aged 45 and over; 4. Assessment of divers with known or symptomatic cardiovascular disease, including guidance on assessing divers with specific diagnoses such as hypertension, atrial fibrillation, cardiac pacemaker, immersion pulmonary oedema, takotsubo cardiomyopathy, hypertrophic cardiomyopathy and persistent (patent) foramen ovale; 5. Additional cardiovascular health questions included in the SPUMS guidelines for medical risk assessment in recreational diving; 6. Updated general cardiovascular medical risk assessment advice; 7. Referencing of relevant literature. The essential elements of this guideline are presented in this paper.

The myopic shift associated with hyperbaric oxygen administration is reduced when using a mask delivery system compared to a hood - a randomised controlled trial.

INTRODUCTION: A temporary myopic shift is a well-recognized complication of hyperbaric oxygen treatment (HBOT). Oxidation of proteins in the crystalline lens is the likely cause. Direct exposure of the eye to hyperbaric oxygen may exacerbate the effect. Our aim was to measure the magnitude of the myopic shift over a course of HBOT when using two different methods of oxygen delivery. METHODS: We conducted a randomised trial of oxygen delivery via hood versus oronasal mask during a course of 20 and 30 HBOT sessions. Subjective refraction was performed at baseline and after 20 and 30 sessions. We repeated these measurements at four and 12 weeks after completion of the course in those available for assessment. RESULTS: We enrolled 120 patients (mean age 57.6 (SD 11.2) years; 81% male). The myopic shift was significantly greater after both 20 and 30 sessions in those patients using the hood. At 20 treatments: refractory change was -0.92 D with hood versus -0.52 D with mask, difference 0.40 D (95% CI 0.22 to 0.57, P < 0.0001); at 30 treatments: -1.25 D with hood versus -0.63 with mask, difference 0.62 D (95% CI 0.39 to 0.84, P < 0.0001). Recovery was slower and less complete in the hood group at both four and 12 weeks. CONCLUSIONS: Myopic shift is common following HBOT and more pronounced using a hood system than an oronasal mask. Recovery may be slower and less complete using a hood. Our data support the use of an oronasal mask in an air environment when possible.

Is there a role for hyperbaric oxygen therapy in the treatment of refractory wounds of rare etiology?

INTRODUCTION: Delayed wound healing indicates wounds that have failed to respond to more than 4-6 weeks of comprehensive wound care. Wounds with delayed healing are a major source of morbidity and a major cost to hospital and community healthcare providers. Hyperbaric oxygen therapy (HBOT) is a treatment designed to increase the supply of oxygen to wounds and has been applied to a variety of wound types. This article reviews the place of HBOT in the treatment of non-healing vasculitic, calcific uremic arteriolopathy (CUA), livedoid vasculopathy (LV), pyoderma gangrenosum (PG) ulcers. METHODS: We searched electronic databases for research and review studies focused on HBOT for the treatment of delayed healing ulcers with rare etiologies. We excluded HBOT for ulcers reviewed elsewhere. RESULTS: We included a total of three case series and four case reports including 63 participants. Most were related to severe, non-healing ulcers in patients with vasculitis, CUA, LV, and PG. There was some evidence that HBOT may improve the healing rate of wounds by increasing nitric oxide (NO) levels and the number of endothelial progenitor cells in the wounds. HBOT may also improve pain in these ulcers. CONCLUSION: We recommend the establishment of comprehensive and detailed wound care registries to rapidly collect prospective data on the use of HBOT for these problem wounds. There is a strong case for appropriately powered, multi-centre randomized trials to establish the true efficacy and cost-effectiveness of HBOT especially for vasculitis ulcers that have not improved following immunosuppressive therapy.

Mortality After Paclitaxel-Coated Device Use in Dialysis Access: A Systematic Review and Meta-Analysis.

Purpose: To report the risk of all-cause mortality in patients who underwent dialysis access treatment using paclitaxel-coated devices compared with percutaneous transluminal angioplasty (PTA) with an uncoated balloon. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials were performed to investigate the mortality outcomes associated with paclitaxel-coated devices in the treatment of patients with a failing dialysis access (last search date February 28, 2019). The primary endpoint was all-cause mortality. This analysis included 8 studies comparing paclitaxel-coated balloon (PCB) angioplasty (n=327) and PTA (n=331) in the treatment of failing dialysis access. None investigated paclitaxel-coated stents. Mortality data were pooled using a random effects model. Statistical heterogeneity was evaluated with a chi-square test and the I2 statistic. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI). Results: At the pooled mean follow-up of 13.5 months (median 12, range 6-24) all-cause mortality was similar in the PCB group (13.8%) compared with PTA (11.2%; RR 1.26, 95% CI 0.85 to 1.89, p=0.25; I2=0%). Subgroup analysis, stratified according to length of follow-up, confirmed that there were no statistically significant differences in mortality at short- and midterm follow-up [6-month (8 studies): 5.2% vs 4.8%, RR 1.24, 95% CI 0.62 to 2.47, p=0.55; 12-month (6 studies): 6.3% vs 6.0%, RR 1.06, 95% CI 0.43 to 2.63, p=0.90; and 24-month (3 studies): 19.0% vs 13.5%, RR 1.38, 95% CI 0.90 to 2.12, p=0.14). Conclusion: The analysis found no difference in short- to midterm mortality among patients treated with a drug-coated balloon compared with PTA. With proven benefit and no evidence of harm, the authors recommend ongoing use of PCB for the failing dialysis access.

Emerging indications for hyperbaric oxygen.

PURPOSE OF REVIEW: To identify and discuss emerging trends in the therapeutic use of hyperbaric oxygen. RECENT FINDINGS: There has been a maturing of the clinical evidence to support the treatment of sudden hearing loss, a wide range of problematic chronic wound states and the prevention and treatment of end-organ damage associated with diabetes mellitus. On the other hand, the controversy continues concerning the use of hyperbaric oxygen therapy (HBOT) to treat sequelae of mild traumatic brain injury. HBOT remains poorly understood by many medical practitioners despite more than 50 years of clinical practice. Pharmacological actions arise from increased pressures of oxygen in the blood and tissues. Most therapeutic mechanisms identified are not the simple result of the reoxygenation of hypoxic tissue, but specific effects on immunological and metabolic pathways by this highly reactive element. HBOT remains controversial despite biological plausibility and a solid clinical evidence base in several disease states. SUMMARY: Multiple proposals for new indications for HBOT continue to emerge. Although many of these will likely prove of limited clinical importance, some show significant promise. Responsible practitioners remain acutely aware of the need for high-quality clinical evidence before introducing emerging indications into routine practice.

The use of drug-eluting stents in infrapopliteal arteries: an updated systematic review and meta-analysis of randomized trials.

INTRODUCTION: Endovascular treatment below-the-knee is safe and effective but limited by poor patency. Coronary drug-eluting stents (DES) may play a role in providing mechanical scaffolding and deliver anti-proliferative drug to the site of vascular barotrauma to reduce the incidence of restenosis. Our aim was to evaluate and compare the use of contemporary DES with standard endovascular-therapies for atherosclerotic disease of infrapopliteal arteries. EVIDENCE ACQUISITION: We performed a meta-analysis of randomized controlled trials comparing DES with conventional treatment for symptomatic peripheral artery disease (search date 30 August 2017). The primary endpoint was primary patency. Secondary endpoints were freedom from target lesion revascularization (TLR), major amputation, sustained Rutherford class improvement and mortality. EVIDENCE SYNTHESIS: We identified 7 trials enrolling 801 randomly assigned patients (392 DES, 409 control). At the median follow-up of 12-months DES improved rates of primary patency (OR 3.49, 95%CI 2.38-5.12, I2=0%, P<0.00001), freedom from TLR (OR 2.19, 95%CI 1.30-3.69, I2=38%, P=0.003), major amputation (OR 0.56, 95%CI 0.31-0.99, I2=0%, P=0.049), and Rutherford class improvement (OR 1.62, 95%CI 1.01-2.59, I2=65%, P=0.046), but not mortality (OR 1.05, 95%CI 0.68-1.62; I2 =0%, P=0.91) compared to control. Subgroup analysis of primary patency favoured DES coated in sirolimus analogues compared to paclitaxel (Test for subgroup differences, Chi2=6.51, df=1, P=0.01, I2=84.6%). CONCLUSIONS: At midterm follow-up DES significantly improved rates of primary patency, re-intervention, Rutherford class improvement and major amputation for the treatment of atherosclerotic disease of infrapopliteal arteries compared to control therapy, with no effect on patient survival. Stents coated in sirolimus analogues were more effective than paclitaxel.

Assessment of hyperbaric patients at risk of malnutrition using the Malnutrition Screening Tool - a pilot study.

BACKGROUND: Nutritional assessment and support is essential for wound management. The hyperbaric oxygen clinic is a unique outpatient service where chronically unwell patients present daily for hyperbaric oxygen treatment (HBOT) over several weeks, allowing time for effective nutritional intervention. This is the first study to examine the prevalence of those at risk of malnutrition in a cohort of hyperbaric medical patients. METHODS: A prospective study was undertaken over six months. Following consent, 39 enrolled patients had the Malnutrition Screening Tool and Baseline Characteristic Collection Form completed. Those at risk of malnutrition were given an option to be assessed by a dietitian to complete a Subjective Global Assessment (SGA). At the completion of treatment, the patients completed a questionnaire. RESULTS: Twelve of the 39 patients screened were at risk of malnutrition using our screening process. Of these, all the patients with available SGA results were diagnosed with moderate to severe malnutrition. Patients receiving HBOT for non-healing wounds and osteoradionecrosis were most at risk of malnutrition. CONCLUSION: The prevalence of patients being at risk of malnutrition in our hyperbaric medical service was about one in three. Malnutrition screening should be part of routine patient assessment in order to ensure patients receive timely nutritional intervention. This may improve wound healing.

Epidural analgesia versus patient-controlled intravenous analgesia for pain following intra-abdominal surgery in adults.

BACKGROUND: Intravenous patient-controlled analgesia (IVPCA) with opioids and epidural analgesia (EA) using either continuous epidural administration (CEA) or patient-controlled (PCEA) techniques are popular approaches for analgesia following intra-abdominal surgery. Despite several attempts to compare the risks and benefits, the optimal form of analgesia for these procedures remains the subject of debate. OBJECTIVES: The objective of this review was to update and expand a previously published Cochrane Review on IVPCA versus CEA for pain after intra-abdominal surgery with the addition of the comparator PCEA. We have compared both forms of EA to IVPCA. Where appropriate we have performed subgroup analysis for CEA versus PCEA. SEARCH METHODS: We searched the following electronic databases for relevant studies: Cochrane Central Register of Controlled Trials (CENTRAL) (2017; Issue 8), MEDLINE (OvidSP) (1966 to September 2017), and Embase (OvidSP) (1988 to September 2017) using a combination of MeSH and text words. We searched the following trial registries: Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, and the EU Clinical Trials Register in September 2017, together with reference checking and citation searching to identify additional studies.We included only randomized controlled trials and used no language restrictions. SELECTION CRITERIA: We included all parallel and cross-over randomized controlled trials (RCTs) comparing CEA or PCEA (or both) with IVPCA for postoperative pain relief in adults following intra-abdominal surgery. DATA COLLECTION AND ANALYSIS: Two review authors (JS and EY) independently identified studies for eligibility and performed data extraction using a data extraction form. In cases of disagreement (three occasions) a third review author (MB) was consulted. We appraised each included study to assess the risk of bias as outlined in Section 8.5 of the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included 32 studies (1716 participants) in our review. There are 10 studies awaiting classification and one ongoing study. A total of 869 participants (51%) received EA and 847 (49%) received IVPCA. The EA trials included 16 trials with CEA (418 participants) and 16 trials with PCEA (451 participants). The studies included a broad range of surgical procedures (including hysterectomies, radical prostatectomies, Caesarean sections, colorectal and upper gastrointestinal procedures), a wide range of adult ages, and were performed in several different countries.Our pooled analyses suggested a benefit with regard to pain scores (using a visual analogue scale between 0 and 100) in favour of EA techniques at rest. The mean pain reduction at rest from waking to six hours after operation was 5.7 points (95% confidence interval (CI) 1.9 to 9.5; 7 trials, 384 participants; moderate-quality evidence). From seven to 24 hours, the mean pain reduction was 9.0 points (95% CI 4.6 to 13.4; 11 trials, 558 participants; moderate-quality evidence). From 24 hours the mean pain reduction was 5.1 points (95% CI 0.9 to 9.4; 7 trials, 393 participants; moderate-quality evidence). Due to high statistical heterogeneity, no pooled analysis was possible for the estimation of pain on movement at any time. Two single studies (one using CEA and one PCEA) reported lower pain scores with EA compared to IVPCA at 0 to 6 hours and 7 to 24 hours. At > 24 hours the results from 2 studies (both CEA) were conflicting.We found no difference in mortality between EA and IVPCA, although the only deaths reported were in the EA group (5/287, 1.7%). The risk ratio (RR) of death with EA compared to using IVPCA was 3.37 (95% CI 0.72 to 15.88; 9 trials, 560 participants; low-quality evidence).A single study suggested that the use of EA may result in fewer episodes of respiratory depression, with an RR of 0.47 (95% CI 0.04 to 5.69; 1 trial; low-quality evidence). The successful placement of an epidural catheter can be technically challenging. The improvements in pain scores above were accompanied by an increase in the risk of failure of the analgesic technique with EA (RR 2.48, 95% CI 1.13 to 5.45; 10 trials, 678 participants; moderate-quality evidence); the occurrence of pruritus (RR 2.36, 95% CI 1.67 to 3.35; 8 trials, 492 participants; moderate-quality evidence); and episodes of hypotension requiring intervention (RR 7.13, 95% CI 2.87 to 17.75; 6 trials, 479 participants; moderate-quality evidence). There was no clear evidence of an advantage of one technique over another for other adverse effects considered in this review (Venous thromboembolism with EA (RR 0.32, 95% CI 0.03 to 2.95; 2 trials, 101 participants; low-quality evidence); nausea and vomiting (RR 0.94, 95% CI 0.69 to 1.27; 10 trials, 645 participants; moderate-quality evidence); sedation requiring intervention (RR 0.87, 95% CI 0.40 to 1.87; 4 trials, 223 participants; moderate-quality evidence); or episodes of desaturation to less than 90% (RR 1.29, 95% CI 0.71 to 2.37; 5 trials, 328 participants; moderate-quality evidence)). AUTHORS' CONCLUSIONS: The additional pain reduction at rest associated with the use of EA rather than IVPCA is modest and unlikely to be clinically important. Single-trial estimates provide low-quality evidence that there may be an additional reduction in pain on movement, which is clinically important. Any improvement needs to be interpreted with the understanding that the use of EA is also associated with an increased chance of failure to successfully institute analgesia, and an increased likelihood of episodes of hypotension requiring intervention and pruritus. We have rated the evidence as of moderate quality given study limitations in most of the contributing studies. Further large RCTs are required to determine the ideal analgesic technique. The 10 studies awaiting classification may alter the conclusions of the review once assessed.

The effectiveness of hyperbaric oxygen therapy for healing chronic venous leg ulcers: A randomized, double-blind, placebo-controlled trial.

Over 30% of venous leg ulcers do not heal despite evidence-based treatment. This study aimed to determine the effectiveness of Hyperbaric Oxygen Therapy (HBOT) as an adjunct treatment for nonhealing venous leg ulcers. A randomized, double-blind, parallel group, placebo-controlled trial was undertaken in three hyperbaric medicine units. Adults with a venous leg ulcer, Transcutaneous Oxygen Measurement indicative of a hypoxic wound responsive to oxygen challenge, and without contraindications for HBOT; were eligible. Of 84 eligible patients, 10 refused and 74 enrolled. 43 participants achieved over 50% ulcer Percent Area Reduction (PAR) after four weeks of evidence-based care and were thus excluded from the intervention phase. Thirty-one participants were randomized to either 30 HBOT treatments (100% oxygen at 2.4 atmospheres absolute (ATA) for 80 minutes), or 30 "placebo" treatments, receiving a validated "sham" air protocol, initially pressurized to 1.2ATA, then cycled between 1.05-1.2ATA for eight minutes before settling at 1.05ATA. The primary outcome was numbers in each group completely healed. Secondary outcomes were ulcer PAR, pain and quality of life, 12 weeks after commencing interventions. The participants' mean age was 70 years (standard deviation (SD) 12.9) and median ulcer duration at enrolment was 62 weeks (range 4-3120). At 12 weeks, there was no significant difference between groups in the numbers completely healed. The HBOT intervention group had a mean of 95 (SD 6.53) ulcer PAR, compared to 54 (SD 67.8) mean PAR for the placebo group (t = -2.24, p = 0.042, mean difference -40.8, SE 18.2) at 12 weeks. HBOT may improve refractory healing in venous leg ulcers, however patient selection is important. In this study, HBOT as an adjunct treatment for nonhealing patients returned indolent ulcers to a healing trajectory.

Consensus guideline: Pre-hospital management of decompression illness: expert review of key principles and controversies.

(Mitchell SJ, Bennett MH, Bryson P, Butler FK, Doolette DJ, Holm JR, Kot J, Lafère P. Pre-hospital management of decompression illness: expert review of key principles and controversies. Diving and Hyperbaric Medicine. 2018 March;48(1):45е.doi.10.28920/dhm48.1.45-55.) Guidelines for the pre-hospital management of decompression illness (DCI) had not been formally revised since the 2004 Divers Alert Network/Undersea and Hyperbaric Medical Society workshop held in Sydney, entitled "Management of mild or marginal decompression illness in remote locations." A contemporary review was initiated by the Divers Alert Network and undertaken by a multinational committee with members from Australasia, the USA and Europe. The process began with literature reviews by designated committee members on: the diagnosis of DCI; first aid strategies for DCI; remote triage of possible DCI victims by diving medicine experts; evacuation of DCI victims; effect of delay to recompression in DCI; pitfalls in management when DCI victims present at hospitals without diving medicine expertise and in-water recompression. This was followed by presentation of those reviews at a dedicated workshop at the 2017 UHMS Annual Scientific Meeting, discussion by registrants at that workshop and, finally, several committee meetings to formulate statements addressing points considered of prime importance to the management of DCI in the field. The committee placed particular emphasis on resolving controversies around the definition of "mild DCI" arising over 12 years of practical application of the 2004 workshop's findings, and on the controversial issue of in-water recompression. The guideline statements are promulgated in this paper. The full workshop proceedings are in preparation for publication.

Evidence brief: hyperbaric oxygen therapy (HBOT) for traumatic brain injury and/or post-traumatic stress disorder.

This report is a product of the VA Evidence-based Synthesis Program. The purpose is to provide "timely and accurate syntheses of targeted healthcare topics …. to improve the health and healthcare of Veterans". The authors have made a comprehensive search and analysis of the literature and make recommendations to assist clinicians in dealing with veterans suffering from either traumatic brain injury (TBI) or post-traumatic stress disorder (PTSD). The report is timely and of great potential impact given the vigorous and lengthy debate among hyperbaric physicians and lay people determined to find an answer for the large numbers of veterans deeply affected with some combination of PTSD and post-concussion dysfunction. The authors lament the evidence on using hyperbaric oxygen treatment (HBOT) for TBI/PTSD has been "controversial, widely debated, and potentially confusing." Unfortunately, this report will not improve that situation. The report is as much a political document as it is evidence-based. That politics are involved is apparent from the outset with the statement "The ESP Coordinating Center is responding to a request from the Center for Compassionate Innovation (CCI)…" The report fails to further illuminate the situation than the many thousands of words already spent on summarising the evidence. Let me save you some time and get to the quick of this report. The authors (rightly) highlight the fact that uncontrolled case series and a randomised, controlled trial (RCT) without blinding or a sham control all suggest HBOT may be of benefit for these Veterans. Somewhat disappointingly, well-controlled, blinded RCTs using a sham exposure to 1.2 or 1.3 ATA breathing air fail to confirm any such benefit. While the conventional interpretation of these data is that there is no reliable evidence of an effect of HBOT, proponents have responded by postulating these control exposures are not 'sham' because they are clinically active. Any putative mechanism remains unknown and unproven outside the context of this clinical area. These exposures just happen to be about equipotent with true HBOT. With this accurate summary, the authors conclude that any effect of HBOT is as yet unclear. They suggest that in Veterans who have not responded to other therapeutic options, the use of HBOT is "reasonable". This conclusion allows for a similar recommendation for any unproven therapeutic option where there is no clearly effective treatment available and is, to this reviewer, unacceptable. While any putative mechanism for low-pressure air exposure owes more to magical thinking than physics, physiology or therapeutics, this is an argument the authors of this report seem to have accepted at some level. The proponents of HBOT have an obligation to both show the greater effectiveness of HBOT than a functional sham and to demonstrate a plausible mechanism. Until then, the strongest recommendation that should be made is that the 'sham' therapy can be used until the case is proven. It is not clear why the proponents of HBOT do not advocate this, given the 'efficacy' seems roughly equal with HBOT. Logic determines one cannot prove a negative. This reviewer agrees it is not possible to definitively prove trivial pressure exposures breathing air may have a comparable effectiveness in treating TBI/PTSD as true HBOT. Using the principle of Occam's razor it seems far more likely any apparent effectiveness is the result of a participation effect in both groups. In my view, the authors of this report have taken an easy option in allowing that HBOT use is reasonable. The tragedy is potentially the waste of time, money and hope this may bring to the very Veterans the authors are charged to serve. I have discussed this issue in more detail previously in the pages of this journal.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of administering radiotherapy for the treatment of malignant tumours while breathing HBO. SEARCH METHODS: In September 2017 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library Issue 8, 2017, MEDLINE, Embase, and the Database of Randomised Trials in Hyperbaric Medicine using the same strategies used in 2011 and 2015, and examined the reference lists of included articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air or an alternative sensitising agent. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of and extracted data from the included trials. MAIN RESULTS: We included 19 trials in this review (2286 participants: 1103 allocated to HBOT and 1153 to control).For head and neck cancer, there was an overall reduction in the risk of dying at both one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and some evidence of improved local tumour control immediately following irradiation (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to imprecision). There was a lower incidence of local recurrence of tumour when using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78, high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate-quality evidence due to inconsistency between trials). There was also some evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45 95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No trials reported a quality of life assessment. Any benefits come at the cost of an increased risk of severe local radiation reactions with HBOT (severe radiation reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the available evidence failed to clearly demonstrate an increased risk of seizures from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality evidence).For carcinoma of the uterine cervix, there was no clear benefit in terms of mortality at either one year or five years (RR with HBOT at one year 0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI 0.80 to 1.14, moderate-quality evidence due to inconsistency between trials). Similarly, there was no clear evidence of a benefit of HBOT in the reported rate of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high-quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality evidence due to inconsistency between trials). We also found no clear evidence for any effect of HBOT on the rate of development of metastases at both two years and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due to inconsistency). There were, however, increased adverse effects with HBOT. The risk of a severe radiation injury at the time of treatment with HBOT was 2.05, 95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of local tumour control, quality of life assessments, or the risk of seizures during treatment.With regard to the treatment of urinary bladder cancer, there was no clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97, 95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality evidence due to imprecision). No trial reported on failure of local control, local recurrence, quality of life, or adverse effects.When all cancer types were combined, there was evidence for an increased risk of severe radiation tissue injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33, high-quality evidence) and of oxygen toxic seizures during treatment (RR with HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision). AUTHORS' CONCLUSIONS: We found evidence that HBOT improves local tumour control, mortality, and local tumour recurrence for cancers of the head and neck. These benefits may only occur with unusual fractionation schemes. Hyperbaric oxygenation therapy is associated with severe tissue radiation injury. Given the methodological and reporting inadequacies of the included studies, our results demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for uterine cervical or bladder cancer. There is little evidence available concerning malignancies at other anatomical sites.