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Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds

  1. Anne Eskes1,
  2. Hester Vermeulen2,
  3. Cees Lucas3,
  4. Dirk T Ubbink4,*

Editorial Group: Cochrane Wounds Group

Published Online: 16 DEC 2013

Assessed as up-to-date: 21 AUG 2013

DOI: 10.1002/14651858.CD008059.pub3


How to Cite

Eskes A, Vermeulen H, Lucas C, Ubbink DT. Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD008059. DOI: 10.1002/14651858.CD008059.pub3.

Author Information

  1. 1

    Academic Medical Centre, University of Amsterdam & Amsterdam School of Health Professions, Quality Assurance & Process Innovation, Amsterdam, Netherlands

  2. 2

    Academic Medical Centre, University of Amsterdam & Amsterdam School of Health Professions, Department of Quality Assurance & Process Innovation, Amsterdam, Noord-Holland, Netherlands

  3. 3

    Academic Medical Centre, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, Netherlands

  4. 4

    Academic Medical Centre, University of Amsterdam, Quality Assurance & Process Innovation, and Department of Surgery, Amsterdam, Netherlands

*Dirk T Ubbink, Quality Assurance & Process Innovation, and Department of Surgery, Academic Medical Centre, University of Amsterdam, J1b-215 Academic Medical Centre, Meibergdreef 9, PO Box 22700, Amsterdam, 1100 DE, Netherlands. d.ubbink@amc.uva.nl.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 16 DEC 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Bouachour 1996

MethodsRandomised clinical trial

Study period: not stated


ParticipantsInclusion criteria: acute crush injury of the limb classified as type 2 or 3 according to Gustillo; surgical management within 6 hours after injury; no history of peripheral arterial occlusive disease

Exclusion criteria: enrolment in any other trial; (suspected) pregnancy; neurologic, pulmonary or otorhinolaryngologic diseases contraindicating HBOT

Baseline wound size: not stated

Mean age (SD): HBOT 45.8 (16.1); Control 51.5 (20.9)
HBOT n = 18
Control n =18

Total number of patients: 36

Duration of follow-up: to complete wound healing


InterventionsIntervention Group 1: HBOT treatment in a multiplace chamber, sessions of 100% O2 at 2.5 atmosphere absolute (ATA) for 90 minutes, twice daily over 6 days
Comparison Group 2: sham HBOT, sessions of 21% O2 at 1.1 ATA for 90 minutes, twice daily over 6 days


OutcomesPrimary outcomes:
Complete wound healing without tissue necrosis requiring surgical excision
Time of healing (days)
Other outcomes:
Adverse effects; amputation; length of hospital stay


NotesLocation: Centre Hospitalier Universitaire, Angers, France France

Setting: university hospital

Financial support: research grants from the Centre of Hospitalier Universitaire of Angers


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were randomly assigned to receive HBO therapy or placebo".
Comment: insufficient information about the sequence generation process to permit judgement

Allocation concealment (selection bias)Unclear riskComment: the method of concealment is not described

Blinding (performance bias and detection bias)
Care provider blinding
Low riskQuote: "the surgeons and the patients were not informed of the treatment protocol performed during the study"
Comment: probably done; surgeons are blinded

Blinding (performance bias and detection bias)
Outcome assessor blinding
Unclear riskComment: it is not certain that the outcome assessor was unaware of the treatment. They did not describe clearly who did the outcome assessments (surgeon or someone else).

Blinding (performance bias and detection bias)
Participant blinding
Low riskQuote: "the surgeons and the patients were not informed of the treatment protocol performed during the study"
Comment: probably done; patients are blinded

Incomplete outcome data (attrition bias)
Was drop out rate described and acceptable
Low riskComment: there were no drop-outs and all patients were assessed at the 6-days follow-up time point

Incomplete outcome data (attrition bias)
ITT analysis
Low riskQuote: "A total of 36 patients were enrolled in the trial: 18 in the HBO group and 18 in the placebo group"
Comment: all patients were analysed in the groups to which they were originally randomly assigned. There were no patients excluded after randomisation.

Selective reporting (reporting bias)Low riskComment: no protocol available, but the trial report lists the outcomes of interest in both the methods and the results section

Other biasLow riskComment: co-interventions similar, groups comparable at baseline

Perrins 1967

MethodsRandomised clinical trial

Study period: not stated


ParticipantsInclusion criteria: every patient with split skin grafting

Exclusion criteria: infants

Baseline wound size: not stated

Mean age (SD): not stated
HBOT n = 24
Control n =24

Total number of patients = 48
Duration of follow-up: 7 days
Setting: Burns Unit, Queen Mary's Hospital, Roehampton, London, United Kingdom


InterventionsIntervention: HBOT treatment in a Vicker's clinical transparent pressure chamber, sessions of 100% O2 at 2 ATA for 2 hours, 1 day twice and the next 3 days once
Comparison: usual care, clarification of usual care was not stated
All cases had closed dressings of paraffin gauze, cotton wool and bandages applied to the operation and donor sites


OutcomesGraft survival (defined as at least 95% take) at day 7


NotesLocation: Queen Mary's Hospital, Roehampton, London, United Kingdom

Setting: Burns Unit

Financial support: not stated

Estimating patches is not a reliable and validated outcome measurement


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were allotted randomly to treatment or control groups"
Comment: insufficient information about the sequence generation process

Allocation concealment (selection bias)Unclear riskComment: the method of concealment is not described

Blinding (performance bias and detection bias)
Care provider blinding
Low riskQuote: "routine surgery was performed by the surgeon, who did not know if the case was subsequently to be treated".
Comment: probably done; surgeon is blinded

Blinding (performance bias and detection bias)
Outcome assessor blinding
Unclear riskComment: the surgeon who performed the operation was blinded, but it is not clear whether he was also the outcome assessor

Blinding (performance bias and detection bias)
Participant blinding
High riskComment: only the surgeon who performed the operation was blinded

Incomplete outcome data (attrition bias)
Was drop out rate described and acceptable
Low riskComment: there were no drop-outs and all patients were assessed at the 6-day follow-up time point.

Incomplete outcome data (attrition bias)
ITT analysis
High riskComment: 2 grafts failed completely in the treated group. These 2 cases were excluded from analysis, on the grounds that a successful 'take' could not be expected.

Selective reporting (reporting bias)High riskComment: no protocol available, but percentage wound healing was measured at day seven with multiple sub-endpoints. This increases the risk of a type 1 error.

Other biasUnclear riskComment: baseline comparability not stated; same treatment apart from intervention

Vishwanath 2011

MethodsRandomised clinical trial

Study period: not stated


ParticipantsInclusion criteria: (1) patients with a major defect requiring a free flap in which conventional techniques were considered as inapplicable or sub optimal and (2) fitness to undergo up to 12 hours of anaesthesia and surgery.

Exclusion criteria: none reported

Baseline wound size: not stated

Mean age (SD): not stated
HBOT n = 5
Control n = 5

Total number of participants = 10

Duration of follow-up: 14 days


InterventionsIntervention: HBOT treatment, sessions once a day for seven days (starting from the first postoperative day) at 2.5 ATA (type of chamber and duration not reported),
Comparison: "usual care", clarification of usual care was not stated.


OutcomesFlap loss (i.e. unviable segment of tissue of any size in the flap) (number);

Adverse effects; flap oedema and venous congestion.


NotesLocation: INHS Asvini, Mumbai, India

Setting: Department of surgery and reconstructive surgery, hospital

Financial support: Research grants from the office of DGAFMS


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were randomised into two groups by random chit method"

Comment: insufficient information about the sequence generation process to permit judgement

Allocation concealment (selection bias)Unclear riskComment: The method of concealment is not described

Blinding (performance bias and detection bias)
Care provider blinding
High riskComment: The treatment and control groups are distinguishable for the patients

Blinding (performance bias and detection bias)
Outcome assessor blinding
Unclear riskComment: Insufficient information to permit judgement

Blinding (performance bias and detection bias)
Participant blinding
High riskComment: The treatment and control groups are distinguishable for the patients

Incomplete outcome data (attrition bias)
Was drop out rate described and acceptable
Low riskComment: there were no drop-outs and all patients were assessed up to 14 days postoperatively

Incomplete outcome data (attrition bias)
ITT analysis
High riskQuote: "One flap each in groups 1 and 2 failed to survive beyond 24 hours of surgery. These patients were excluded from the analysis since flap loss had occurred even before HBO was exhibited to the case group"

Comment: No ITT-analysis was performed

Selective reporting (reporting bias)Low riskComment: no protocol available; but the trial report list the outcomes of interest in both the methods and the results section

Other biasUnclear riskComment: baseline comparable unclear; same treatment apart from intervention

Xie 2007

MethodsRandomised clinical trial

Study period: August 2002 to August 2006


ParticipantsInclusion criteria: patients with skin defects in the limbs who underwent flap grafting

Exclusion criteria: none stated

Baseline wound size: not stated, range 8 cm² to 40 cm²

Mean age (SD): not stated

HBOT = 45
Dexamethasone = 45
Local heparin = 45

Total number of patients = 135

Duration of follow-up: 7 days


InterventionsIntervention: HBOT treatment in a hyperbaric oxygen chamber made in China, sessions 2 times a day for 3 days and thereafter once a day resulting in a total of 6 to 12 treatments

Comparison 1: dexamethasone treatment started at the day of operation with a dose of 0.4 mg/kg per intravenous infusion; continued on day 1 with a single dose of 0.2 mg/kg; day 2 and 3 0.1 mg/kg; day 4 and 5 0.05 mg/kg; treatment stopped at day 6

Comparison 2: subcutaneous local heparin treatment (200 U/ml NS) was given for 6 days


OutcomesFlap survival at day 7, clinical assessment of skin colour, temperature of the skin, capillary refill test, arterial pulsations and bleeding


NotesLocation: Baoon People’s Hospital of Southern Medical University, Guangdong, China

Setting: Department of Orthopedics, hospital

Financial support: not stated


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "all patients were randomly divided"

Allocation concealment (selection bias)Unclear riskComment: not reported

Blinding (performance bias and detection bias)
Care provider blinding
High riskQuote: "blind evaluation methods has not been applied"
Comment: not done

Blinding (performance bias and detection bias)
Outcome assessor blinding
High riskQuote: "blind evaluation methods has not been applied"
Comment: not done

Blinding (performance bias and detection bias)
Participant blinding
High riskQuote: 'blind evaluation methods has not been applied'
Comment: not done

Incomplete outcome data (attrition bias)
Was drop out rate described and acceptable
Low riskComment: there were no drop-outs and all patients were assessed at the 7-day follow-up time point

Incomplete outcome data (attrition bias)
ITT analysis
Low riskComment: all patients were analysed in the groups to which they were originally randomly assigned. There were no patients excluded after randomisation.

Selective reporting (reporting bias)Unclear riskComment: no protocol available; they merely reported complete survival of the graft at day seven after the operation, but no other outcome measures.

Other biasUnclear riskComment: baseline comparability not stated

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Brannen 1997Included in Cochrane Review of thermal burns (Villanueva 2004)

Hart 1974Included in Cochrane Review of thermal burns (Villanueva 2004

Jian 2011Not RCT

Niezgoda 1997Included in Cochrane Review of thermal burns (Villanueva 2004

Xu N 1999Included in Cochrane Review of thermal burns (Villanueva 2004

 
Characteristics of ongoing studies [ordered by study ID]
Brismar

Trial name or titleNCT01002209

Postoperative Hyperbaric Oxygen Treatments to Reduce Complications in Diabetic Patients Undergoing Vascular Surgery (HODiVA)

MethodsRandomized controlled trial

ParticipantsInclusion Criteria: Patients are eligible for inclusion if the following criteria are fulfilled - informed consent obtained; scheduled for lower extremity open vascular surgery; diabetes treated with insulin or oral antidiabetic medicine; age ≥ 18 years

Exclusion Criteria: Contraindications to HBO therapy; pregnancy (women of childbearing potential will undergo pregnancy test before inclusion); patients already in HBO treatment; vascular reoperation; creatinine > 250 mmol/L; NYHA class IV heart failure or severe cardiopulmonary disease with desaturation judged to be incompatible with safe HBO/ placebo therapy in a monoplace chamber; clinically significant chronic obstructive pulmonary disease. Acute sepsis; malignancy or other serious medical condition where it is likely that the patient will significantly deteriorate or not survive within the two years of follow up. Simultaneous or previous (within 30 days prior to study entry participation in a clinical study using experimental drugs or devices. Mental condition making the subject unable to understand the concepts and risk of the study

InterventionsIntervention: HBO treatment will be given in a monoplace chamber and will start on first postoperative day (study day 1). The HBO group will be treated with 100% oxygen at 2.5 bar for 100 min with two 10 min air brakes (without mask).

HBO treatment will be given twice daily first three days (study day 1-3) and then once daily for up to three days (study day 4-6). The total number of treatments will be at least 6 and at most 9 treatments. Patients who have received at least three days HBO/placebo treatment and who have a clearly uncomplicated postoperative course will terminate HBO/placebo treatment on the day of discharge from hospital.

Comparison: HBO sham treatment will start on first postoperative day (study day 1). HBO sham treatment will be given twice daily first three days (study day 1-3) and then once daily for up to three days (study day 4-6). The total number of treatments will be at least 6 and at most 9 treatments. Patients who have received at least three days HBO sham treatments and who have a clearly uncomplicated postoperative course will terminate HBO sham treatment on the day of discharge from hospital.

For patient blinding purposes, the sham group will breathe air and will be given a brief compression to 1.5 bar at the beginning of each treatment after which the chamber is slowly decompressed to 1.1, 1.2, 1.3, or 1.4 bar corresponding to 0.23 ,0.25, 0.27, and 0.29 bar inspired oxygen. Two 10 min "airbrakes" will also be included.

OutcomesTime to complete healing of operative wounds (Time Frame: 7-365 days), HBO complications (confinement anxiety, barotrauma, oxygen convulsions) (Time Frame: During HBO treatment up to day 6) infections (numbers at 7 and 30 days assessed by ASEPSIS score), severity of infections (ASEPSIS score), a combination of any wound infection and/or unhealed wounds at 30 days (combined endpoint) (Time Frame: 30 days (plus minus 3 days), SF-36 score (Time Frame: 7, 14, 28, 365 days (plus minus 3 days), morbidity, major amputation (Time frame: 0-365 days), tissue perfusion and oxygenation on dorsum of foot on operated extremity as assessed by Transcutaneous oximetry during normobaric air breathing and after 6 min normobaric 100% oxygen challenge (Time Frame: day 3-5, 7 and 14, 28, 365 (plus minus 3 days)

Starting dateOctober 2009 - Anticipated end date: October 2014

Contact informationContact: Kerstin Brismar, MD, Prof (kerstin.brismar@ki.se)

Contact: Jonas Malmstedt, MD (jonas.malmstedt@karolinska.se), Karolinska University Hospital, Stockholm, Sweden, 17176

NotesLocation: Sweden

Source of funding: self-funded

Millar

Trial name or titleNCT00264511

Hyperbaric Oxygen in Lower Leg Trauma

MethodsRandomized controlled trial

ParticipantsInclusion Criteria: Acute fracture of the tibia with significant soft tissue injury of Gustilo Grade 3. Enrolment within 48 hours of injury with expectation of commencement of HBO therapy within 48 hours of injury. Valid consent

Exclusion Criteria: significant head injury, injuries incompatible with HBO, resuscitation requirements incompatible with HBO, follow up not possible, hyperbaric contra indications

InterventionsIntervention: Hyperbaric oxygenation (not further specified)

Comparison: No hyperbaric oxygenation. Patients randomised to this group will receive standard trauma care.

OutcomesAcute phase complication rate, soft tissue necrosis, infection (number), compartment syndrome, amputations, radiological union, quality of life score (method unclear), functional outcome scores.

Starting dateFebruary 2006 - Anticipated end date: December 2013

Contact informationContact: Ian L Millar, MBBS (I.millar@alfred.org.au), Bayside Health

NotesLocation: Worldwide

Source of funding: Bayside Health

Sires

Trial name or titleNCT01605110
Effects of Hyperbaric Oxygen Therapy on Surgical Wound Healing (BLEPH)

MethodsRandomized controlled trial

ParticipantsInclusion Criteria: Patients that are able to undergo surgery at the Allure Clinic are capable of undergoing exposure to HBOT, as the contraindications of HBOT are similar to eyelid surgery, with few exceptions.

Exclusion Criteria: Active smokers and those who have quit smoking in the last 12 months, those with known lung disease, seizure disorder, congestive heart failure, known active cancer, previous treatment with specific chemotherapy agents (Doxorubicin, Bleomycin, Disulfiram, Cis-platinum, Mafenide acetate), those who cannot undergo pressurization/ depressurization because of eustachian-tube dysfunction and confinement anxiety.

InterventionsIntervention: Hyperbaric oxygen therapy: two HBOT treatments (one before and one after surgery) with patients who have undergone upper eyelid surgery. Patients that volunteer to participate in this study will be exposed to two treatments of 100% oxygen at 2.0 atmospheres absolute (ATA)

Comparison: air (sham) 1.2 ATA inside mono-place chambers for 90 minutes.

OutcomesReduction of ecchymosis grade (Time Frame: 21 days) clinical signs, reduction of edema (Time Frame: 21 days)

Starting dateAugust 2011 - Anticipated end date: November 2013

Contact informationBryan Sires, MD, FACS (no email address given), Allure Laser Center & Medispa

NotesLocation: Washington, USA

Source of funding: Restorix Research Institute, LLLP

 
Comparison 1. HBOT compared with usual care

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Complete survival (defined as at least 95% take) at day 71Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 2. HBOT compared with sham HBOT

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Complete healing1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Time to healing (days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Adverse effects (additional surgical procedures)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Adverse effects (tissue necrosis)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Amputations1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Length of hospital stay1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 3. HBOT compared with dexamethasone or heparin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Complete healing HBOT vs dexamethasone1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Complete healing HBOT vs heparin1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected