A systematic review and meta-analysis of hyperbaric oxygen therapy for diabetic foot ulcers with arterial insufficiency.

BACKGROUND: Diabetic foot ulcers (DFUs) are frequently associated with peripheral arterial occlusive disease (PAOD) and may ultimately lead to amputations of the lower extremity. Adjuvant hyperbaric oxygen treatment (HBOT) might foster better wound healing and lower amputation rates in patients with DFU and PAOD. A systematic review was conducted to assess the effects of HBOT as an adjunctive therapy to standard treatment for patients with DFUs with PAOD. METHODS: Systematic review using the MEDLINE, EMBASE, and Cochrane CENTRAL databases (from inception to October 2018). All original, comparative studies on the effect of HBOT on DFUs with PAOD were eligible. The primary outcome measures were amputation rate, amputation-free survival, complete ulcer healing, and mortality. RESULTS: Eleven studies, totaling 729 patients, were included for analysis, including 7 randomized clinical trials, 2 controlled clinical trials, and 2 retrospective cohorts. Four were used for quantitative synthesis. Meta-analysis showed a significantly fewer major amputations in the HBOT group (10.7% vs 26.0%; risk difference, -15%; 95% confidence interval [CI], -25 to -6; P = .002; number needed to treat, 7; 95% CI, 4-20). No difference was found for minor amputations (risk difference, 8%; 95% CI, -13 to 30; P = .46). Three studies reporting on complete wound healing showed contrasting results. No significant difference was found for mortality or amputation-free survival. CONCLUSIONS: Current evidence shows that adjuvant HBOT improves major amputation rate, but not wound healing, in patients with DFUs and PAOD. Given the wide range of patients included in the trials, better patient selection may help define which patients with DFUs and PAOD benefit most from HBOT as standard adjunctive treatment.

Hyperbaric oxygen therapy for nonischemic diabetic ulcers: A systematic review.

Diabetic foot ulcers are a common complication of diabetes, which affects 25% of patients and may ultimately lead to amputation of affected limbs. Research suggests hyperbaric oxygen therapy improves healing of these ulcers. However, this has not been reflected in previous reviews, possibly because they did not differentiate between patients with and without peripheral arterial occlusive disease. Therefore, we performed a systematic review of published literature in the MEDLINE, Embase, and Cochrane CENTRAL databases on nonischemic diabetic foot ulcers with outcome measures including complete ulcer healing, amputation rate (major and minor), and mortality. Seven studies were included, of which two were randomized clinical trials. Two studies found no difference in major amputation rate, whereas one large retrospective study found 2% more major amputations in the hyperbaric oxygen group. However, this study did not correct for baseline differences. Two studies showed no significant difference in minor amputation rate. Five studies reporting on complete wound healing showed no significant differences. In conclusion, the current evidence suggests that hyperbaric oxygen therapy does not accelerate wound healing and does not prevent major or minor amputations in patients with a diabetic foot ulcer without peripheral arterial occlusive disease. Based on the available evidence, routine clinical use of this therapy cannot be recommended. However, the available research for this specific subgroup of patients is scarce, and physicians should counsel patients on expected risks and benefits. Additional research, focusing especially on patient selection criteria, is needed to better identify patients that might profit from this therapy modality.

Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower- Extremity Ulcers in Patients With Diabetes: Results of the DAMO2CLES Multicenter Randomized Clinical Trial.

OBJECTIVE: Conflicting evidence exists on the effects of hyperbaric oxygen therapy (HBOT) in the treatment of chronic ischemic leg ulcers. The aim of this trial was to investigate whether additional HBOT would benefit patients with diabetes and ischemic leg ulcers. RESEARCH DESIGN AND METHODS: Patients with diabetes with an ischemic wound (n = 120) were randomized to standard care (SC) without or with HBOT (SC+HBOT). Primary outcomes were limb salvage and wound healing after 12 months, as well as time to wound healing. Other end points were amputation-free survival (AFS) and mortality. RESULTS: Both groups contained 60 patients. Limb salvage was achieved in 47 patients in the SC group vs. 53 patients in the SC+HBOT group (risk difference [RD] 10% [95% CI -4 to 23]). After 12 months, 28 index wounds were healed in the SC group vs. 30 in the SC+HBOT group (RD 3% [95% CI -14 to 21]). AFS was achieved in 41 patients in the SC group and 49 patients in the SC+HBOT group (RD 13% [95% CI -2 to 28]). In the SC+HBOT group, 21 patients (35%) were unable to complete the HBOT protocol as planned. Those who did had significantly fewer major amputations and higher AFS (RD for AFS 26% [95% CI 10-38]). CONCLUSIONS: Additional HBOT did not significantly improve complete wound healing or limb salvage in patients with diabetes and lower-limb ischemia.

Economic outcomes in clinical studies assessing hyperbaric oxygen in the treatment of acute and chronic wounds.

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) is used to treat acute and chronic wounds. This systematic review was conducted to summarise and evaluate existing evidence on the costs associated with HBOT in the treatment of wounds. METHODS: We searched multiple electronic databases in March 2015 for cohort studies and randomised clinical trials (RCTs) that reported on the clinical effectiveness and treatment costs of HBOT in the treatment of acute or chronic wounds. RESULTS: One RCT and three cohort studies reported on economic as well as clinical outcomes. These studies comprised different disorders (ischaemic diabetic foot ulcers, thermal burns, Fournier's gangrene and necrotising soft tissue infections) and employed different clinical and economic outcome measures. Only the RCT had a good methodological quality. Three of the included studies reported that their primary clinical outcomes (wound healing, hospital stay, complications) improved in the HBOT group. The effects of HBOT on costs were variable. CONCLUSIONS: Currently, there is little direct evidence on the cost-effectiveness of HBOT in the treatment of acute and chronic wounds. Although there is some evidence suggesting effectiveness of HBOT, further studies should include economic outcomes in order to make recommendations on the cost-effectiveness of applying HBOT in wound care.

Is additional hyperbaric oxygen therapy cost-effective for treating ischemic diabetic ulcers? Study protocol for the Dutch DAMOCLES multicenter randomized clinical trial?

BACKGROUND: The value of hyperbaric oxygen therapy (HBOT) in the treatment of diabetic ulcers is still under debate. Available evidence suggests that HBOT may improve the healing of diabetic ulcers, but it comes from small trials with heterogeneous populations and interventions. The DAMOCLES-trial will assess the (cost-)effectiveness of HBOT for ischemic diabetic ulcers in addition to standard of care. METHODS: In a multicenter randomized clinical trial, including 30 hospitals and all 10 HBOT centers in the Netherlands, we plan to enroll 275 patients with Types 1 or 2 diabetes, a Wagner 2, 3 or 4 ulcer of the leg present for at least 4 weeks, and concomitant leg ischemia, defined as an ankle systolic blood pressure of <70 mmHg, a toe systolic blood pressure of <50 mmHg or a forefoot transcutaneous oxygen tension (TcpO2) of <40 mmHg. Eligible patients may be candidates for revascularization. Patients will be randomly assigned to standard care with or without 40 HBOT-sessions. RESULTS: Primary outcome measures are freedom from major amputation after 12 months and achievement of, and time to, complete wound healing. Secondary endpoints include freedom from minor amputations, ulcer recurrence, TcpO2 , quality of life, and safety. In addition, we will assess the cost-effectiveness of HBOT for this indication. CONCLUSION: The DAMOCLES trial will be the largest trial ever performed in the realm of HBOT for chronic ulcers, and it is unique for addressing patients with ischemic diabetic foot ulcers who may also receive vascular reconstructions. This matches the treatment dilemma in current clinical practice.

Systemic wound care: a meta-review of cochrane systematic reviews.

Wound care is a classic example of a surgical realm with a great variation in care. The diversity in wounds and wound treatments, the limited amount of convincing evidence, and the diverging opinions among doctors and nurses involved in wound care contribute to this undesirable variation in care. For chronic wounds, such as arterial or venous ulcers, pressure sores, and diabetic foot ulcers, but also for acute wounds after surgery or trauma, international and national guidelines provide recommendations on diagnostic procedures and treatment options, but rely mostly on expert opinion. We present the available evidence from Cochrane systematic reviews for the systemic treatment (i.e., not prevention) of patients with wounds, as opposed to topical wound treatments. This evidence shows: - Venous ulcers: High-compression therapy is the classic and evidence-based treatment for treating venous ulcers. Oral pentoxifylline promotes ulcer healing with and without compression therapy. Oral zinc is not effective to heal venous ulcers. - Acute wounds: Recombinant human growth hormone accelerates healing of large burn wounds and donor sites, while high-carbohydrate feeding might reduce the risk of pneumonia. Linezolid is more effective than vancomycin for treating skin and soft tissue infections. Hyperbaric oxygen may help heal crush wounds and skin grafts. Therapeutic touch does not heal acute wounds. - Pressure sores: Air-fluidized and some low-tech devices appear effective for treating existing pressure ulcers. Oral zinc, protein, or vitamin C supplements seem ineffective. Also, evidence is lacking on the effectiveness of repositioning regimes as a treatment option. - Diabetic ulcers: Hyperbaric oxygen therapy and pressure-relieving devices may improve healing rates. - Arterial ulcers: Prostanoids and spinal cord stimulation may be effective in healing ischemic ulcers. Thus, fortunately, some high-level evidence exists for various local and systemic interventions in wound care. Caregivers should be aware of, and apply, the strongest evidence available. Only when all stakeholders (patients, physicians, wound care nurses, but also manufacturers and buyers) implement this available evidence will optimum quality of care for patients with wounds be ensured.

Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is used as a treatment for acute wounds (such as those arising from surgery and trauma). However, the effects of HBOT on wound healing are unclear.  OBJECTIVES: To determine the effects of HBOT on the healing of acute surgical and traumatic wounds. SEARCH METHODS: We searched the Cochrane Wounds Group Specialised Register (searched 9 August 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12); Ovid MEDLINE (2010 to July Week 5 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, August 08, 2013); Ovid EMBASE (2010 to 2013 Week 31); EBSCO CINAHL (2010 to 8 August 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing HBOT with other interventions such as dressings, steroids, or sham HOBT or comparisons between alternative HBOT regimens. DATA COLLECTION AND ANALYSIS: Two review authors conducted selection of trials, risk of bias assessment, data extraction and data synthesis independently. Any disagreements were referred to a third review author.  MAIN RESULTS: Four trials involving 229 participants were included. The studies were clinically heterogeneous, which precluded a meta-analysis.One trial (48 participants with burn wounds undergoing split skin grafts) compared HBOT with usual care and reported a significantly higher complete graft survival associated with HBOT (95% healthy graft area risk ratio (RR) 3.50; 95% confidence interval (CI) 1.35 to 9.11). A second trial (10 participants in free flap surgery) reported no significant difference between graft survival (no data available). A third trial (36 participants with crush injuries) reported significantly more wounds healed (RR 1.70; 95% CI 1.11 to 2.61), and significantly less tissue necrosis (RR 0.13; 95% CI 0.02 to 0.90) with HBOT compared to sham HBOT. The fourth trial (135 people undergoing flap grafting) reported no significant differences in complete graft survival with HBOT compared with dexamethasone (RR 1.14; 95% CI 0.95 to 1.38) or heparin (RR 1.21; 95% CI 0.99 to 1.49).Many of the predefined secondary outcomes of the review were not reported. All four trials were at unclear or high risk of bias. AUTHORS' CONCLUSIONS: There is a lack of high quality, valid research evidence regarding the effects of HBOT on wound healing. Whilst two small trials suggested that HBOT may improve the outcomes of skin grafting and trauma, these trials were at risk of bias. Further evaluation by means of high quality RCTs is needed.

Hyperbaric oxygen therapy: solution for difficult to heal acute wounds? Systematic review.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is used to treat various wound types. However, the possible beneficial and harmful effects of HBOT for acute wounds are unclear. METHODS: We undertook a systematic review to evaluate the effectiveness of HBOT compared to other interventions on wound healing and adverse effects in patients with acute wounds. To detect all available randomized controlled trials (RCTs) we searched five relevant databases up to March 2010. Trial selection, quality assessment, data extraction, and data synthesis were conducted by two of the authors independently. RESULTS: We included five trials, totaling 360 patients. These trials, with some methodologic flaws, included different kinds of wound and focused on different outcome parameters, which prohibited meta-analysis. A French trial (n = 36 patients) reported that significantly more crush wounds healed with HBOT than with sham HBOT [relative risk (RR) 1.70, 95% confidence interval (CI) 1.11-2.61]. Moreover, there were significantly fewer additional surgical procedures required with HBOT (RR 1.60, 95% CI 1.03-2.50), and there was significantly less tissue necrosis (RR 1.70, 95% CI 1.11-2.61). In one of two American trials (n = 141) burn wounds healed significantly quicker with HBOT (P < 0.005) than with routine burn care. A British trial (n = 48) compared HBOT with usual care. HBOT resulted in a significantly higher percentage of healthy graft area in split skin grafts (RR 3.50, 95% CI 1.35-9.11). In a Chinese trial (n = 145) HBOT did not significantly improve flap survival in patients with limb skin defects. CONCLUSIONS: HBOT, if readily available, appears effective for the management of acute, difficult to heal wounds.

Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is used as a treatment for acute wounds (such as those arising from surgery and trauma) however the effects of HBOT on wound healing are unclear.  OBJECTIVES: To determine the effects of HBOT on the healing of acute surgical and traumatic wounds. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register (25 August 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), Ovid MEDLINE (1950 to August Week 2 2010 ), Ovid MEDLINE (In-Process & Other Non-Indexed Citations August 24, 2010), Ovid EMBASE (1980 to 2010, Week 33) and EBSCO CINAHL (1982 to 20 August 2010). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing HBOT with other interventions or comparisons between alternative HBOT regimens. DATA COLLECTION AND ANALYSIS: Two review authors conducted selection of trials, risk of bias assessment, data extraction and data synthesis independently. Any disagreements were referred to a third review author.  MAIN RESULTS: Three trials involving 219 participants were included. The studies were clinically heterogeneous, therefore a meta-analysis was inappropriate.One trial (48 participants with burn wounds undergoing split skin grafts) compared HBOT with usual care and reported a significantly higher complete graft survival associated with HBOT (95% healthy graft area risk ratio (RR) 3.50; 95% confidence interval (CI) 1.35 to 9.11). A second trial (36 participants with crush injuries) reported significantly more wounds healed with HBOT than with sham HBOT (RR 1.70; 95% CI 1.11 to 2.61) and fewer additional surgical procedures required with HBOT: RR 0.25; 95% CI 0.06 to 1.02 and significantly less tissue necrosis: RR 0.13; 95% CI 0.02 to 0.90). A third trial (135 people undergoing flap grafting) reported no significant differences in complete graft survival with HBOT compared with dexamethasone (RR 1.14; 95% CI 0.95 to 1.38) or heparin (RR 1.21; 95% CI 0.99 to 1.49).Many of the predefined secondary outcomes of the review, including mortality, pain scores, quality of life, patient satisfaction, activities daily living, increase in transcutaneous oxygen pressure (TcpO(2)), amputation, length of hospital stay and costs, were not reported. All three trials were at unclear or high risk of bias. AUTHORS' CONCLUSIONS: There is a lack of high quality, valid research evidence regarding the effects of HBOT on wound healing. Whilst two small trials suggested that HBOT may improve the outcomes of skin grafting and trauma these trials were at risk of bias. Further evaluation by means of high quality RCTs is needed.

Bipolar versus monopolar transurethral resection of the prostate: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Incorporation of bipolar technology in transurethral resection (TUR) of the prostate (TURP) potentially offers advantages over monopolar TURP (M-TURP). OBJECTIVE: To evaluate the evidence by a meta-analysis, based on randomized controlled trials (RCTs) comparing bipolar TURP (B-TURP) with M-TURP for benign prostatic obstruction. Primary end points included efficacy (maximum flow rate [Q(max)], International Prostate Symptom Score) and safety (adverse events). Secondary end points included operation time and duration of irrigation, catheterization, and hospitalization. EVIDENCE ACQUISITION: Based on a detailed, unrestricted strategy, the literature was searched up to February 19, 2009, using Medline, Embase, Science Citation Index, and the Cochrane Library to detect all relevant RCTs. Methodological quality assessment of the trials was based on the Dutch Cochrane Collaboration checklist. Meta-analysis was performed using Review Manager 5.0. EVIDENCE SYNTHESIS: Sixteen RCTs (1406 patients) were included. Overall trial quality was low (eg, allocation concealment and blinding of outcome assessors were poorly reported). No clinically relevant differences in short-term (12-mo) efficacy were detected (Q(max): weighted mean difference [WMD]: 0.72 ml/s; 95% confidence interval [CI], 0.08-1.35; p=0.03). Data on follow-up of >12 mo are scarce for B-TURP, precluding long-term efficacy evaluation. Treating 50 patients (95% CI, 33-111) and 20 patients (95% CI, 10-100) with B-TURP results in one fewer case of TUR syndrome (risk difference [RD]: 2.0%; 95% CI, 0.9-3.0%; p=0.01) and one fewer case of clot retention (RD: 5.0%; 95% CI, 1.0-10%; p=0.03), respectively. Operation times, transfusion rates, retention rates after catheter removal, and urethral complications did not differ significantly. Irrigation and catheterization duration was significantly longer with M-TURP (WMD: 8.75 h; 95% CI, 6.8-10.7 and WMD: 21.77 h; 95% CI, 19.22-24.32; p<0.00001, respectively). Inferences for hospitalization duration could not be made. PlasmaKinetic TURP showed an improved safety profile. Data on TUR in saline (TURis) are not yet mature to permit safe conclusions. CONCLUSIONS: No clinically relevant differences in short-term efficacy exist between the two techniques, but B-TURP is preferable due to a more favorable safety profile (lower TUR syndrome and clot retention rates) and shorter irrigation and catheterization duration. Well-designed multicentric/international RCTs with long-term follow-up and cost analysis are still needed.