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.

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 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.

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.

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.

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.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon 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 problems following surgery. OBJECTIVES: To assess the benefits and harms of HBOT for treating or preventing LRTI. SEARCH METHODS: We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE, EMBASE, DORCTIHM and reference lists of articles in December 2015. We also searched for ongoing trials at clinicaltrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials. MAIN RESULTS: Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P value = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events. AUTHORS' CONCLUSIONS: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.

Hyperbaric oxygen therapy for acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS), includes acute myocardial infarction and unstable angina, is common and may prove fatal. Hyperbaric oxygen therapy (HBOT) will improve oxygen supply to the threatened heart and may reduce the volume of heart muscle that perishes. The addition of HBOT to standard treatment may reduce death rate and other major adverse outcomes.This an update of a review previously published in May 2004 and June 2010. OBJECTIVES: The aim of this review was to assess the evidence for the effects of adjunctive HBOT in the treatment of ACS. We compared treatment regimens including adjunctive HBOT against similar regimens excluding HBOT. Where regimens differed significantly between studies this is clearly stated and the implications discussed. All comparisons were made using an intention to treat analysis where this was possible. Efficacy was estimated from randomised trial comparisons but no attempt was made to evaluate the likely effectiveness that might be achieved in routine clinical practice. Specifically, we addressed:Does the adjunctive administration of HBOT to people with acute coronary syndrome (unstable angina or infarction) result in a reduction in the risk of death?Does the adjunctive administration of HBOT to people with acute coronary syndrome result in a reduction in the risk of major adverse cardiac events (MACE), that is: cardiac death, myocardial infarction, and target vessel revascularization by operative or percutaneous intervention?Is the administration of HBOT safe in both the short and long term? SEARCH METHODS: We updated the search of the following sources in September 2014, but found no additional relevant citations since the previous search in June 2010 (CENTRAL), MEDLINE, EMBASE, CINAHL and DORCTHIM. Relevant journals were handsearched and researchers in the field contacted. We applied no language restrictions. SELECTION CRITERIA: Randomised studies comparing the effect on ACS of regimens that include HBOT with those that exclude HBOT. DATA COLLECTION AND ANALYSIS: Three authors independently evaluated the quality of trials using the guidelines of the Cochrane Handbook and extracted data from included trials. Binary outcomes were analysed using risk ratios (RR) and continuous outcomes using the mean difference (MD) and both are presented with 95% confidence intervals. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: No new trials were located in our most recent search in September 2014. Six trials with 665 participants contributed to this review. These trials were small and subject to potential bias. Only two reported randomisation procedures in detail and in only one trial was allocation concealed. While only modest numbers of participants were lost to follow-up, in general there is little information on the longer-term outcome for participants. Patients with acute coronary syndrome allocated to HBOT were associated with a reduction in the risk of death by around 42% (RR: 0.58, (95% CI 0.36 to 0.92), 5 trials, 614 participants; low quality evidence).In general, HBOT was well-tolerated. No patients were reported as suffering neurological oxygen toxicity and only a single patient was reported to have significant barotrauma to the tympanic membrane. One trial suggested a significant incidence of claustrophobia in single occupancy chambers of 15% (RR of claustrophobia with HBOT 31.6, 95% CI 1.92 to 521). AUTHORS' CONCLUSIONS: For people with ACS, there is some evidence from small trials to suggest that HBOT is associated with a reduction in the risk of death, the volume of damaged muscle, the risk of MACE and time to relief from ischaemic pain. In view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigour is justified to define those patients (if any) who can be expected to derive most benefit from HBOT. The routine application of HBOT to these patients cannot be justified from this review.

Adjunctive hyperbaric oxygen for necrotizing fasciitis.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) involves the therapeutic administration of 100% oxygen in a pressure chamber at pressures above one atmosphere absolute. This therapy has been used as an adjunct to surgery and antibiotics in the treatment of patients with necrotizing fasciitis with the aim of reducing morbidity and mortality. OBJECTIVES: To review the evidence concerning the use of HBOT as an adjunctive treatment for patients with necrotizing fasciitis (NF). Specifically, we wish to address the following questions.1. Does administration of HBOT reduce mortality or morbidity associated with NF?2. What adverse effects are associated with use of HBOT in the treatment of individuals with NF? SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE Ovid (1966 to September 2014); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ovid (1982 to September 2014); EMBASE Ovid (1980 to September 2014); and the Database of Randomised Controlled Trials in Hyperbaric Medicine (DORCTHIM, M Bennett) (from inception to September 2014). In addition, we performed a systematic search of specific hyperbaric literature sources. This included handsearching of relevant hyperbaric textbooks; hyperbaric journals (Hyperbaric Medicine Review, South Pacific Underwater Medicine Society Journal, European Journal of Underwater and Hyperbaric Medicine, Aviation Space and Environmental Medicine Journal); and conference proceedings of the major hyperbaric societies (Undersea and Hyperbaric Medical Society, South Pacific Underwater Medicine Society, European Underwater and Baromedical Society, International Congress of Hyperbaric Medicine). SELECTION CRITERIA: We included all randomized and pseudo-randomized trials (trials in which an attempt at randomization has been made but the method was inappropriate, for example, alternate allocation) that compared the effects of HBOT with the effects of no HBOT (no treatment or sham) in the treatment of children and adults with necrotizing fasciitis. DATA COLLECTION AND ANALYSIS: We planned independent data collection by two review authors using standardized forms. MAIN RESULTS: We found no trials that met the inclusion criteria. AUTHORS' CONCLUSIONS: This systematic review failed to locate relevant clinical evidence to support or refute the effectiveness of HBOT in the management of necrotizing fasciitis. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of individuals with necrotizing fasciitis.

Normobaric and hyperbaric oxygen therapy for the treatment and prevention of migraine and cluster headache.

BACKGROUND: Migraine and cluster headaches are severe and disabling. Migraine affects up to 18% of women, while cluster headaches are much less common (0.2% of the population). A number of acute and prophylactic therapies are available. Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than one atmosphere, while normobaric oxygen therapy (NBOT) is oxygen administered at one atmosphere. This is an updated version of the original Cochrane review published in Issue 3, 2008 under the title 'Normobaric and hyperbaric oxygen for migraine and cluster headache'. OBJECTIVES: To examine the efficacy and safety of normobaric oxygen therapy (NBOT) and hyperbaric oxygen therapy (HBOT) in the treatment and prevention of migraine and cluster headache. SEARCH METHODS: We updated searches of the following databases up to 15 June 2015: CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and CINAHL. For the original review we searched the following databases up to May 2008: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM, and reference lists from relevant articles. We handsearched relevant journals and contacted researchers to identify trials. SELECTION CRITERIA: Randomised controlled trials comparing HBOT or NBOT with one another, other active therapies, placebo (sham) interventions, or no treatment in participants with migraine or cluster headache. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: In this update, we included 11 trials with 209 participants. Five trials (103 participants) compared HBOT versus sham therapy for acute migraine, three trials compared NBOT to sham therapy or ergotamine tartrate for cluster headache (145 participants), two trials evaluated HBOT for cluster headache (29 participants), and one trial (56 participants) compared NBOT to sham for a mixed group of headache. The risk of bias varied considerably across these trials but in general trial quality was poor to moderate. One trial may not have been truly randomised and two included studies were reported as abstracts only. Seven trials did not indicate allocation concealment or randomisation method. Notably, 10 of the 11 trials used a sham comparator therapy and masked the outcome assessor to allocation.We pooled data from three trials, which suggested that HBOT was effective in relieving migraine headaches compared to sham therapy (risk ratio (RR) 6.21, 95% CI 2.41 to 16.00; 58 participants, three trials). The quality of evidence was low, having been downgraded for small crossover studies with incomplete reporting. There was no evidence that HBOT could prevent migraine episodes, reduce the incidence of nausea and vomiting, or reduce the requirement for rescue medication. There was no evidence that HBOT was effective for the termination of cluster headache (RR 11.38, 95% CI 0.77 to 167.85; P = 0.08) (one trial), but this trial had low power.NBOT was effective in terminating cluster headache compared to sham in a single small study (RR 7.88, 95% CI 1.13 to 54.66), but not superior to ergotamine administration in another small trial (RR 1.17, 95% CI 0.94 to 1.46; P = 0.16). A third trial reported a statistically significant difference in the proportion of attacks successfully treated with oxygen (117 of 150 attacks were successfully treated with NBOT (78%) versus 30 of 148 attacks treated with NBOT (20%)). The proportion of responders was consistent across these three trials, and suggested more than 75% of headaches were likely to respond to NBOT.No serious adverse events during HBOT or NBOT were reported. AUTHORS' CONCLUSIONS: Since the last version of this review, two new included studies have provided additional information to change the conclusions. There was some evidence that HBOT was effective for the termination of acute migraine in an unselected population, and some evidence that NBOT was similarly effective in cluster headache. Given the cost and poor availability of HBOT, more research should be done on patients unresponsive to standard therapy. NBOT is cheap, safe, and easy to apply, so will probably continue to be used despite the limited evidence in this review.

Hyperbaric oxygen therapy for chronic wounds.

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.

Hyperbaric oxygen therapy for acute ischaemic stroke.

Background Most cases of stroke are caused by impairment of blood flow to the brain (ischaemia), which results in a reduction in available oxygen and subsequent cell death. It has been postulated that hyperbaric oxygen therapy (HBOT) may reduce the volume of brain that will die by greatly increasing available oxygen, and it may further improve outcomes by reducing brain swelling. Some centres are using HBOT routinely to treat people with stroke. This is an update of a Cochrane Review first published in 2005.Objectives To assess the effectiveness and safety of adjunctive HBOT in the treatment of people with acute ischaemic stroke.Search methods We searched the Cochrane Stroke Group Trials Register (last searched April 2014), the Cochrane Central Register of Controlled Trials(CENTRAL) (April 2014), MEDLINE (1966 to April 2014), EMBASE (1980 to April 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to April 2014), the Database of Randomised Controlled Trials in Hyperbaric Medicine(DORCTIHM) (searched April 2014) and the reference lists of articles.We handsearched relevant publications and contacted researchers to identify additional published and unpublished studies.Selection criteria Randomised controlled trials (RCTs) that compared the effects of adjunctive HBOT versus those of no HBOT (no treatment or sham).Data collection and analysis Three review authors independently extracted data, assessed each trial for internal validity and resolved differences by discussion.Main results We included 11 RCTs involving 705 participants. The methodological quality of the trials varied. We could pool data only for case fatalities. No significant differences were noted in the case fatality rate at six months in those receiving HBOT compared with the control group (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.34 to 2.75, P value 0.96). Four of 14 scale measures of disability and functional performance indicated improvement following HBOT, for example, the mean Trouillas Disability Scale score was lower with HBOT (mean difference (MD) 2.2 point reduction with HBOT, 95% CI 0.15 to 4.3, P value 0.04), and the mean Orgogozo Scale score was higher (MD 27.9 points, 95% CI 4.0 to 51.8, P value 0.02).Authors' conclusions We found no good evidence to show that HBOT improves clinical outcomes when applied during acute presentation of ischaemic stroke. Although evidence from the 11 RCTs is insufficient to provide clear guidelines for practice, the possibility of clinical benefit has not been excluded. Further research is required to better define the role of HBOT in this condition.

Randomized controlled trials in diving and hyperbaric medicine.

Randomized controlled trials (RCTs) are widely accepted as the most appropriate methodology available for the investigation of health interventions. This is because of the low potential for systematic bias and the ability to assume causality. Well-designed RCTs, often modified by the addition of blinding participants to the treatment allocated, greatly assist physicians and funding agencies in deciding on the most effective and cost-efficient methods available to prevent and treat ill health. One of the problems for hyperbaric physicians is the widely scattered nature of the evidence, making retrieval and appraisal problematic. This review assembles the randomized evidence in order to assist practitioners, discusses the nature of randomized trials and explores approaches to designing and performing powerful and convincing trials in this area. It is extracted from the UHMS Report Hyperbaric Oxygen Therapy Indications.

WITHDRAWN: Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union.

BACKGROUND: Hyperbaric 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. OBJECTIVES: The aim of this review was 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 METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (April 2008), the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2008), MEDLINE (OVID 1966 to April week 3, 2008), CINAHL (OVID 1982 to April week 3, 2008), EMBASE (OVID 1980 to week 17 2008), the locally developed Database of Randomised Controlled Trials in Hyperbaric Medicine (available at www.hboevidence.com) from inception to May 2008, and reference lists of articles. SELECTION CRITERIA: We aimed to include all randomised controlled trials that compared the effect of HBOT with no HBOT (no treatment or sham). DATA COLLECTION AND ANALYSIS: We planned independent data collection by two authors using standardised forms. MAIN RESULTS: No trials met the inclusion criteria. We excluded one trial that compared HBOT with no treatment because no clinical outcomes were reported. AUTHORS' CONCLUSIONS: This 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.

Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury.

BACKGROUND: Traumatic brain injury is a common health problem with significant effect on quality of life. Each year in the USA approximately 0.56% of the population suffer a head injury, with a case fatality rate of about 40% for severe injuries. These account for a high proportion of deaths in young adults. In the USA, 2% of the population live with long-term disabilities following head injuries. The major causes are motor vehicle crashes, falls, and violence (including attempted suicide). Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than 1 atmosphere absolute (ATA). This involves placing the patient in an airtight vessel, increasing the pressure within that vessel, and administering 100% oxygen for respiration. In this way, it is possible to deliver a greatly increased partial pressure of oxygen to the tissues. HBOT can improve oxygen supply to the injured brain, reduce the swelling associated with low oxygen levels and reduce the volume of brain that will ultimately perish. It is, therefore, possible that adding HBOT to the standard intensive care regimen may reduce patient death and disability. However, a concern for patients and families is that using HBOT may result in preventing a patient from dying only to leave them in a vegetative state, entirely dependent on medical care. There are also some potential adverse effects of the therapy, including damage to the ears, sinuses and lungs from the effects of the pressure and oxygen poisoning, so the benefits and risks of the therapy need to be carefully evaluated. OBJECTIVES: To assess the effects of adjunctive HBOT for traumatic brain injury. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and DORCTHIM electronic databases. We also searched the reference lists of eligible articles, handsearched relevant journals and contacted researchers. All searches were updated to March 2012. SELECTION CRITERIA: Randomised studies comparing the effect of therapeutic regimens which included HBOT with those that did not, for people with traumatic brain injury. DATA COLLECTION AND ANALYSIS: Three authors independently evaluated trial quality and extracted data. MAIN RESULTS: Seven studies are included in this review, involving 571 people (285 receiving HBOT and 286 in the control group). The results of two studies indicate use of HBOT results in a statistically significant decrease in the proportion of people with an unfavourable outcome one month after treatment using the Glasgow Outcome Scale (GOS) (relative risk (RR) for unfavourable outcome with HBOT 0.74, 95% CI 0.61 to 0.88, P = 0.001). This five-point scale rates the outcome from one (dead) to five (good recovery); an 'unfavourable' outcome was considered as a score of one, two or three. Pooled data from final follow-up showed a significant reduction in the risk of dying when HBOT was used (RR 0.69, 95% CI 0.54 to 0.88, P = 0.003) and suggests we would have to treat seven patients to avoid one extra death (number needed to treat (NNT) 7, 95% CI 4 to 22). Two trials suggested favourably lower intracranial pressure in people receiving HBOT and in whom myringotomies had been performed. The results from one study suggested a mean difference (MD) with myringotomy of -8.2 mmHg (95% CI -14.7 to -1.7 mmHg, P = 0.01). The Glasgow Coma Scale (GCS) has a total of 15 points, and two small trials reported a significant improvement in GCS for patients treated with HBOT (MD 2.68 points, 95%CI 1.84 to 3.52, P < 0.0001), although these two trials showed considerable heterogeneity (I(2) = 83%). Two studies reported an incidence of 13% for significant pulmonary impairment in the HBOT group versus 0% in the non-HBOT group (P = 0.007).In general, the studies were small and carried a significant risk of bias. None described adequate randomisation procedures or allocation concealment, and none of the patients or treating staff were blinded to treatment. AUTHORS' CONCLUSIONS: In people with traumatic brain injury, while the addition of HBOT may reduce the risk of death and improve the final GCS, there is little evidence that the survivors have a good outcome. The improvement of 2.68 points in GCS is difficult to interpret. This scale runs from three (deeply comatose and unresponsive) to 15 (fully conscious), and the clinical importance of an improvement of approximately three points will vary dramatically with the starting value (for example an improvement from 12 to 15 would represent an important clinical benefit, but an improvement from three to six would leave the patient with severe and highly dependent impairment). The routine application of HBOT to these patients cannot be justified from this review. Given the modest number of patients, methodological shortcomings of included trials and poor reporting, the results should be interpreted cautiously. An appropriately powered trial of high methodological rigour is required to define which patients, if any, can be expected to benefit most from HBOT.

Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union.

BACKGROUND: Hyperbaric 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. OBJECTIVES: The 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 METHODS: We 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 CRITERIA: We 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 ANALYSIS: Two 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 RESULTS: No 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' CONCLUSIONS: This 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.