Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1.

PURPOSE: Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. METHODS AND MATERIALS: Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. RESULTS: In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. CONCLUSION: Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error.

Only minor stem cell mobilization in head and neck irradiated patients treated with hyperbaric oxygen.

INTRODUCTION: Hyperbaric oxygen, (HBO) is used to treat several conditions including late radiation tissue injury. Previous studies have suggested that HBO mobilizes bone marrow derived stem/progenitor cells (SPC) to the peripheral blood, however possible cumulative effects were highly variable. METHODS: We have investigated a possible HBO-induced mobilization of SPCs by determining CD34+CD45dim cell numbers, as well as SPCs in general. The latter were characterized by high aldehyde dehydrogenase (ALDH) activity by use of the Aldefluor® assay. We included ten patients admitted for HBO treatment of radiation tissue injury. Six patients completed the 29-30 HBO treatment exposures. We also investigated possible HBO-induced effects on platelet activation as measured by flow cytometry and functional analyses. RESULTS: We found a weak and insignificant tendency toward mobilization of CD34+CD45dim cells after a single HBO exposure versus before. Additionally, we found an additive effect of 15 HBO exposures on the increase in CD34+CD45dim cells relative to the pre-1st-HBO values. These changes were significantly more than zero but less than a doubling. We could not demonstrate a significant effect of HBO on the content of Aldefluor® positive SPCs in peripheral blood. There was no significant effect on platelet activation overall. However, in patients with increased expression of activation markers at baseline, we found a decrease after one exposure although this was not reflected in functional tests. CONCLUSION: We found a minor statistically significant mobilizing effect of HBO treatment on the bone marrow derived stem/progenitor cell content in peripheral blood after 15 treatments (n = 10 patients), but no effect after 30 treatments (n = 6 patients). However, because of the low number of patients we cannot confidentially prove or disprove the null hypothesis. The possibility that HBO treatment reduces the number of activated platelets could not be demonstrated nor excluded.

Patient's perspective on hyperbaric oxygen treatment of osteoradionecrosis.

Osteoradionecrosis (ORN) is a known complication to radiation therapy for head and neck cancer with a prevalence of 5-7% among radiated patients. Treatment might include dental surgery and reconstruction of the jawbone as well as hyperbaric oxygen treatment (HBOT). HBOT takes place in a closed compartment where patients are breathing 100% oxygen under pressure for 90 minutes once a day every weekday for 6 weeks. In Denmark, HBOT is available at two facilities with very different organizational set-ups.

Chamber personnel's use of Nitrox 50 during hyperbaric oxygen treatment: a quality study--research report.

OBJECTIVE: We aimed to evaluate the feasibility and safety of using Nitrox 50 as breathing gas during attendance in a multiplace hyperbaric chamber. METHODS: Paper logs between Jan.-Dec. 2011 were reviewed to analyze nitrogen gas-loading, actual bottom time, total bottom time and surface interval time. With the use of the Norwegian Diving Tables nitrogen gas-loading was converted to Repetitive Group Letters. Symptoms of decompression sickness and health problems related to hyperbaric exposures were registered at weekly staff meetings. The chamber personnel breathed chamber air or Nitrox 50. RESULTS: 1,207 hyperbaric exposures were distributed to five chamber attendants and technicians, 14 doctors, and six nurses. Nitrox 50 was inhaled on 978 occasions (81.0%). Median nitrogen gas-loading after first pressurization complied with Repetitive Group Letter A (range A-E), second to C (range A-F), third to D (range A-F), fourth to E (range C-H), fifth to F (range C-H), and sixth to E (range B-G). No symptoms of decompression sickness were reported (95% CI 0.00-0.33%). CONCLUSION: Breathing Nitrox 50 during repetitive hyperbaric sessions seems to be feasible and safe while meeting high demands in number of treatment sessions and patient flow and with fewer people employed in the hyperbaric unit.

Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study.

Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO in irradiated head and neck cancer patients. Eighty patients eligible for HBO treatment on the indication of prevention/treatment of osteoradionecrosis or soft tissue radiation injury were consecutively sampled, of whom 45 had hyposalivation (i.e. unstimulated whole saliva (UWS) flow rate <0.1ml/min), and 69 complained of xerostomia. UWS and stimulated whole saliva (SWS) were collected prior to and after 30 sessions of hyperbaric oxygen treatment over 6weeks. Xerostomia was assessed using the visual analogue scale (VAS). Each HBO session involved compression to 243kPa (2.4 ATA) for 90min while breathing 100% oxygen from a facemask or hood. There was a significant decrease in xerostomia (p<0.001) and slight increase in UWS (p<0.001) and SWS (p<0.001) flow rate, from before HBO as compared to after. Twenty-five of 45 patients with hyposalivation achieved an increased UWS flow rate after HBO. In 12 of these, the flow rates increased to levels not associated with hyposalivation. Patient-assessed improvement of xerostomia and slightly increased UWS and SWS secretion after HBO treatment suggest that HBO may have a beneficial effect on radiation-induced salivary gland damage.

Cyanide intoxication as part of smoke inhalation--a review on diagnosis and treatment from the emergency perspective.

This paper reviews the current literature on smoke inhalation injuries with special attention to the effects of hydrogen cyanide. It is assumed that cyanide poisoning is still an overlooked diagnosis in fire victims. Treatment against cyanide poisoning in the emergency setting should be given based on the clinical diagnosis only. Oxygen in combination with a recommended antidote should be given immediately, the first to reduce cellular hypoxia and the second to eliminate cyanide. A specific antidote is hydroxycobalamin, which can be given iv. and has few side effects.

Delayed response of the retina after hyperbaric oxygen exposure.

PURPOSE: To examine retinal electrophysiological function and retinal thickness in healthy eyes before and after hyperbaric oxygen (HBO) exposure. METHODS: The healthy eye in each of six subjects who underwent experimental HBO treatment for branch retinal vein occlusion in the fellow eye was examined using multifocal electroretinography (mfERG) and optical coherence tomography (OCT) at baseline and following a course of five consecutive daily sessions of exposure to HBO at 2.4 atmospheres of absolute pressure lasting 90 min each. RESULTS: After HBO, P1 implicit times of the mfERG were significantly shorter than at baseline. The response was delayed, being undetectable on the day treatment concluded, whereas a 2.65% reduction in implicit time was seen 1 week later (p = 0.032). The P1 implicit time remained 2.49% shorter than at baseline 1 month after the end of the HBO sessions (p = 0.020). The bulk of the response to HBO was found in the foveal and parafoveal regions. No detectable change was seen in mfERG amplitudes or in the volume or thickness of the retina. CONCLUSION: A mfERG component related to bipolar and Müller cell function was accelerated by a short intermittent exposure to HBO. The response developed after the end of the HBO exposure and lasted for at least 3 weeks, suggesting that it was prompted by the withdrawal of HBO rather than the onset and subsequent brief exposure to HBO.

Effect of hyperbaric oxygen therapy on whole blood cyanide concentrations in carbon monoxide intoxicated patients from fire accidents.

BACKGROUND: Hydrogen cyanide (HCN) and carbon monoxide (CO) may be important components of smoke from fire accidents. Accordingly, patients admitted to hospital from fire accidents may have been exposed to both HCN and CO. Cyanide (CN) intoxication results in cytotoxic hypoxia leading to organ dysfunction and possibly death. While several reports support the use of hyperbaric oxygen therapy (HBO) for the treatment of severe CO poisoning, limited data exist on the effect of HBO during CN poisoning. HBO increases the elimination rate of CO haemoglobin in proportion to the increased oxygen partial pressure and animal experiments have shown that in rats exposed to CN intoxication, HBO can increase the concentration of CN in whole blood. OBJECTIVE: The purpose of the present study was to determine whole blood CN concentrations in fire victims before and after HBO treatment. MATERIALS AND METHODS: The patients included were those admitted to the hospital because of CO intoxication, either as fire victims with smoke inhalation injuries or from other exposures to CO. In thirty-seven of these patients we measured CN concentrations in blood samples, using a Conway/microdiffusion technique, before and after HBO. The blood samples consisted of the remaining 2 mL from the arterial blood gas analysis. CN concentration in blood from fire victims was compared to 12 patients from non-fire accidents but otherwise also exposed to CO intoxication. RESULTS: The mean WB-CN concentration before patients received HBO did not differ significantly between the two groups of patients (p = 0.42). The difference between WB-CN before and after HBO did not differ significantly between the two groups of patients (p = 0.7). Lactate in plasma before and after did not differ significantly between the two groups of patients. Twelve of the 25 fire patients and one of the non-fire patients had been given a dose of hydroxycobalamin before HBO. DISCUSSION AND CONCLUSION: CN concentrations in blood from patients admitted to hospital with CO intoxication and smoke inhalation exposure did not differ significantly from controls. Accordingly, we were not able to detect any changes in CN concentrations in blood after treatment with HBO. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00280579.

[Necrotizing fasciitis]. / Nekrotiserende fasciitis.

INTRODUCTION: Necrotizing fasciitis (NF) is an acute soft-tissue infection, associated with a high mortality and morbidity. To reduce the mortality, an early diagnosis and treatment is essential. Our study aims to identify the number of patients, the microorganisms involved, and NF treatment outcomes among patients admitted to our unit. MATERIAL AND METHODS: This retrospective cohort study enrolled 85 patients admitted to the multidisciplinary, tertiary Intensive Care Unit, Abdominal Center, Rigshospitalet, Denmark in 2005-2007. All received the same protocolled treatment of intensive care, extensive surgical débridements, broad-spectrum antibiotics, intravenous immunoglobulin and hyperbaric oxygen. RESULTS: The microbiological analyses of specimens demonstrated that 51% were positive for polymicrobial infection, 40% for a single pathogen, 74% of these caused by beta-hemolytic streptococci, and 9% of the analyses were inconclusive. Of the patients, 91% required treatment in a respirator, 67.5% presented with septic shock and 25.3% developed acute renal failure needing dialysis. Intensive care unit mortality was 6% and 30-day mortality was 9.5%. Expected mortality based on SAPS II and APACHE II scoring was 38%. Our patients had a significantly higher body mass index than other patients admitted to the unit. CONCLUSION: NF is a complex disease, often associated with multi-organ failure. A protocolled treatment plan with close cooperation between the intensive care, clinical microbiology, medical and surgical specialties seems to reduce mortality considerably in this vulnerable group of patients.

1H MR spectroscopy of gray and white matter in carbon monoxide poisoning.

Carbon monoxide (CO) intoxication leads to acute and chronic neurological deficits, but little is known about the specific noxious mechanisms. (1)H magnetic resonance spectroscopy (MRS) may allow insight into the pathophysiology of CO poisoning by monitoring neurochemical disturbances, yet only limited information is available to date on the use of this protocol in determining the neurological effects of CO poisoning. To further examine the short-term and long-term effects of CO on the central nervous system, we have studied seven patients with CO poisoning assessed by gray and white matter MRS, magnetic resonance imaging (MRI) and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1-6 days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline (Cho) and decreased N-acetyl aspartate (NAA) ratios to creatine (Cr), predominantly in the white matter. Lactate peaks were detected in two patients during the early phase of high-dose CO poisoning. Two patients with chronic low-dose CO exposure and without loss of consciousness had normal MRI and MRS scans. On follow-up. five of our seven patients had long-lasting intellectual impairment, including one individual with low-dose CO exposure. The MRS results showed persisting biochemical alterations despite the MRI scan showing normalization of morphological changes. In conclusion, the MRS was normal in patients suffering from chronic low-dose CO exposure; in contrast, patients with high-dose exposure showed abnormal gray and white matter levels of NAA/Cr, Cho/Cr and lactate, as detected by (1)H MRS, suggesting disturbances of neuronal function, membrane metabolism and anaerobic energy metabolism, respectively. Early increases in Cho/Cr and decreases of NAA/Cr may be related to a poor long-term outcome, but confirmation by future studies is needed.

Pressure-equalizing earplugs do not prevent barotrauma on descent from 8000 ft cabin altitude.

INTRODUCTION: The aim of this study was to evaluate the effect of pressure-equalizing earplugs available in major airports and drugstores. No previous study has focused on preventing barotrauma using these earplugs. METHODS: Blinded and double-blinded, one type of pressure-equalizing earplugs (JetEars) was studied in 27 volunteers disposed to ear barotrauma. They acted as their own controls with an active earplug in one ear and a placebo earplug in the other ear at random. All were exposed to the same well-defined pressure profile for 1 h at 8000 ft, comparable to the environment in civil commercial air travel in a pressurized cabin. Satisfaction was assessed by questionnaire and objective results were evaluated prior to and after the pressure exposure by tympanometry and otoscopy using the Teed classification. RESULTS: The majority of the volunteers (78%) reported a pleasant noise-reducing feeling using the earplugs. However, 75% also experienced ear pain during descent. In comparing the middle ear pressure before and after pressurization, a decrease was found in ears with both active earplugs and placebo earplugs. No difference between the active and the placebo earplugs were found. Furthermore, after evaluation of the two groups of ears using otoscopy, no prevention of barotrauma was found. In fact, the ears using an active pressure-equalizing earplug scored significantly worse (p = 0.033). CONCLUSIONS: Feelings of noise reduction were reported, but no prevention of barotrauma could be demonstrated with the use of pressure-equalizing earplugs. Pressure-equalizing earplugs cannot be recommended in air travel for preventing ear barotrauma.

Hyperbaric oxygen and radiotherapy.

BACKGROUND: Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure of at least 1.5 atmospheres absolute (150 kPa). It uses oxygen as a drug by dissolving it in the plasma and delivering it to the tissues independent of hemoglobin. For a variety of organ systems, HBO is known to promote new vessel growth into areas with reduced oxygen tension due to poor vascularity, and therewith promotes wound healing and recovery of radiation-injured tissue. Furthermore, tumors may be sensitized to irradiation by raising intratumoral oxygen tensions. METHOD: A network of hyperbaric facilities exists in Europe, and a number of clinical studies are ongoing. The intergovernmental framework COST B14 action "Hyperbaric Oxygen Therapy" started in 1999. The main goal of the Working Group Oncology is preparation and actual implementation of prospective study protocols in the field of HBO and radiation oncology in Europe. RESULTS: In this paper a short overview on HBO is given and the following randomized clinical studies are presented: a) reirradiation of recurrent squamous cell carcinoma of the head and neck after HBO sensitization; b) role of HBO in enhancing radiosensitivity on glioblastoma multiforme; c) osseointegration in irradiated patients; adjunctive HBO to prevent implant failures; d) the role of HBO in the treatment of late irradiation sequelae in the pelvic region. The two radiosensitization protocols (a, b) allow a time interval between HBO and subsequent irradiation of 10-20 min. CONCLUSION: Recruitment of centers and patients is being strongly encouraged, detailed information is given on www.oxynet.org.

Refractive change during hyperbaric oxygen therapy. A clinical trial including ultrasound oculometry.

PURPOSE: To record changes in refraction and refractive parameters associated with a standard hyperbaric oxygen treatment protocol consisting of a 95 min session at > 95% oxygen at 2.5 atmospheres (ATA) given daily Monday to Friday, to a total of 30 sessions. PATIENTS AND METHODS: Seventeen of the 26 patients included were able to attend for ophthalmic assessment at time zero (to) and after 20 treatments (t20). Thirteen patients also had a post-treatment follow-up. Most patients were being treated for osteoradionecrosis after radiotherapy of ENT cancers, and drop-outs for the eye exam were common. Refraction was determined subjectively and by refractometry, before and after tropicamide 1% eyedrops. Refractive parameters were assessed by keratometry and by A-scan axial ultrasound measurement. RESULTS: Results are given for the 17 patients with to and t20 assessments. The induced refractive change ranged from 0 to 1.5 D. When observed, refractive changes were myopic in nature. The shift averaged 0.58 D according to the refractometer and 0.49 D as subjectively assessed, with corresponding median change values being 0.62 and 0.39 D. The differences between 0 D and these values, although small, were statistically highly significant. CONCLUSIONS: The refractive changes associated with hyperbaric oxygen therapy were smaller than the literature had led us to expect. No significant change in axial eye length measurements was found, and keratometry readings reflected only minimal change, although this was statistically significant on a 0.05 level. Therefore it is most likely that lens changes, whether in internal refractive indices or curvatures, accounted for the transitory shift towards more myopic/less hyperopic values.