Safe administration of hyperbaric oxygen after bleomycin: a case series of 15 patients.

INTRODUCTION: Supplemental oxygen has been reported to cause pulmonary complications after bleomycin. We describe the safe administration of hyperbaric oxygen (HBO2) after bleomycin in 15 patients. METHODS: Paper and electronic records were reviewed for bleomycin-exposed patients at the Duke Center for Hyperbaric Medicine and Environmental Physiology from 1979 to 2010. RESULTS: Fourteen bleomycin-exposed patients received HBO2 at Duke under a special-precautions protocol. One was treated for DCS elsewhere. The protocol included: pretreatment evaluation; chest radiograph; spirometry; blood gases; a single, 2-atmospheres absolute (atm abs), 120-minute HBO2 treatment; and a gradual acceleration over one week to a twice-daily schedule contingent on clinical and laboratory findings. Bleomycin indications were: head-and-neck squamous cell carcinomas (11), Hodgkin's lymphoma (2), other carcinomas (2). HBO2 indications were: osteoradionecrosis (10), soft-tissue radionecrosis (3), DCS (1) and a provocative oxygen toxicity test for a military aviator (1). Total bleomycin doses ranged from 40 to 225u/m2 (mean +/- SD, 105 +/- 57) given in conjunction with other chemotherapies and/or radiation. Radiation was 63.3 +/- 31.72 Gy (mean +/- SD), none to the chest with the exception of one patient treated for DCS elsewhere. Other chemotherapies included: vinblastine (11), methotrexate (11), CCNU (6) cisplatinum (7), dacarbazin (2), Adriamycin (1), and vincristine (1). Median age at time of HBO2 was 52 years (range 22-77). Median bleomycin-to-HBO2 latency was 34 months (range 1-279). Three patients received HBO2 within six months, and seven patients received HBO2 within two years of their last bleomycin exposure. There were no adverse pre-to-post HBO2 changes in: arterial blood gases, spirometry, chest radiograph findings or clinical reports. There were no persistent post-HBO2 pulmonary complications on follow-up. Post-HBO2 data were available for 40%, 53%, 87% and 100% of these parameters respectively. DISCUSSION: Bleomycin and oxygen can individually cause acute pulmonary toxicity. However, evidence for increased long-term susceptibility based on their synergy may be overstated.

What is the role of hyperbaric oxygen in the management of bisphosphonate-related osteonecrosis of the jaw: a randomized controlled trial of hyperbaric oxygen as an adjunct to surgery and antibiotics.

PURPOSE: This study tested hyperbaric oxygen (HBO) as an adjunct to surgery and antibiotics in the treatment of bisphosphonate-related osteonecrosis of the jaw (ONJ) and evaluated its effects on gingival healing, pain, and quality of life. MATERIALS AND METHODS: The investigators implemented a randomized controlled trial and enrolled a sample composed of patients with ONJ, where the predictor variable was HBO administered at 2 atm twice a day for 40 treatments as an adjunct to conventional therapy of surgery and antibiotics versus conventional therapy alone. Over the next 24 months, oral lesion size and number, pain, and quality of life were assessed. RESULTS: Forty-six patients (mean age, 66 yrs; 57% women) contributed data to the trial. There were no statistically significant differences in the distribution of variables used to assess randomization success between the HBO and standard treatment groups. Seventeen of 25 HBO-treated patients (68%) improved versus 8 of 21 controls (38.1%; P = .043, χ(2) test). Mean time to improvement was 39.7 weeks (95% confidence interval [CI], 22.4 to 57.0 weeks) for HBO-treated patients versus 67.9 weeks (95 CI, 48.4 to 87.5 weeks) for controls (P = .03, log-rank test). However, complete gingival healing occurred in only 14 of 25 HBO-treated patients (52%) versus 7 of 21 controls (33.3%; P = .203, χ(2) test), and time to healing was 59 weeks (95% CI, 42.8% to 75.8%) for HBO-treated patients versus 70 weeks (95 CI, 52.2% to 88.36%) for controls (P = .32, log-rank test). Pain decreased faster for HBO-treated subjects (P < .01, linear regression). Quality-of-life scores for physical health (P = .002) and perceived health (P = .043) decreased at 6 months for control group but for not the HBO group. CONCLUSIONS: ONJ is multifactorial and no single treatment modality is likely to reverse it; however, it is treatable and even advanced presentations can improve with intensive multimodal therapy. Clinically, HBO appears to be a useful adjunct to ONJ treatment, particularly for more severe cases, although this study was underpowered to fully support this claim.

Hyperbaric oxygen therapy in necrotising soft tissue infections: a study of patients in the United States Nationwide Inpatient Sample.

PURPOSE: Necrotising soft tissue infection (NSTI) is a deadly disease associated with a significant risk of mortality and long-term disability from limb and tissue loss. The aim of this study was to determine the effect of hyperbaric oxygen (HBO(2)) therapy on mortality, complication rate, discharge status/location, hospital length of stay and inflation-adjusted hospitalisation cost in patients with NSTI. METHODS: This was a retrospective study of 45,913 patients in the Nationwide Inpatient Sample (NIS) from 1988 to 2009. RESULTS: A total of 405 patients received HBO(2) therapy. The patients with NSTI who received HBO(2) therapy had a lower mortality (4.5 vs. 9.4 %, p = 0.001). After adjusting for predictors and confounders, patients who received HBO(2) therapy had a statistically significantly lower risk of dying (odds ratio (OR) 0.49, 95 % confidence interval (CI) 0.29-0.83), higher hospitalisation cost (US$52,205 vs. US$45,464, p = 0.02) and longer length of stay (LOS) (14.3 days vs. 10.7 days, p < 0.001). CONCLUSIONS: This retrospective analysis of HBO(2) therapy in NSTI showed that despite the higher hospitalisation cost and longer length of stay, the statistically significant reduction in mortality supports the use of HBO(2) therapy in NSTI.

Utility of hyperbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws.

Bisphosphonates suppress bone turnover by disrupting osteoclast signal transduction, maturation, and longevity. In some patients, it has been hypothesized that suppressed turnover can impair oral wound healing, leading to a distressing, osteopetrosis-like jaw necrosis called bisphosphonate-related osteonecrosis of the jaws (BRONJ). Hyperbaric oxygen (HBO), as an adjunct to surgery and antibiotics, might have utility in the treatment of BRONJ because it produces reactive oxygen and nitrogen species that positively modulate the redox-sensitive intracellular signaling molecules involved in bone turnover. The efficacy of HBO in the treatment of BRONJ is currently under investigation in randomized controlled trials at Duke University and the University of Minnesota, and the early results have been encouraging. This report discusses osteoclast biology, how HBO has the potential to augment bone turnover by way of the signaling effects on osteoclasts, the available clinical data on HBO in the treatment of BRONJ, the ongoing randomized controlled trials of HBO, and the study-associated efforts to find biomarkers to characterize an individual's risk of developing this disease.

Multimodality surgical and hyperbaric management of mandibular osteoradionecrosis.

PURPOSE: To elucidate long-term outcomes in 65 consecutive patients meeting a uniform definition of mandibular osteoradionecrosis (ORN) treated with multimodality therapy including hyperbaric oxygen (HBO). METHODS AND MATERIALS: Pretreatment, post-treatment and long-term follow-up of mandibular lesions with exposed bone were ranked by a systematic review of medical records and patient telephone calls. The ranking system was based on lesion diameter and number plus disease progression. Changes from pretreatment to post-treatment and follow-up were analyzed by Wilcoxon signed-rank tests. Improved wound survival, measured by time to relapse, defined as any less favorable rank after HBO treatment, was assessed by Kaplan-Meier analysis. RESULTS: In all, 57 cases (88%) resolved or improved by lesion grade or progression and evolution criteria after HBO (p < 0.001). Four patients healed before surgery after HBO alone. Of 57 patients who experienced improvement, 41 had failed previous nonmultimodality therapy for 3 months and 26 for 6 months or more. A total of 43 patients were eligible for time-to-relapse survival analysis. Healing or improvement lasted a mean duration of 86.1 months (95% confidence interval [95% CI], 64.0-108.2) in nonsmokers (n = 20) vs. 15.8 months (95% CI, 8.4-23.2) in smokers (n = 14) versus 24.2 months (95% CI, 15.2-33.2) in patients with recurrent cancer (n = 9) (p = 0.002 by the log-rank method). CONCLUSIONS: Multimodality therapy using HBO is effective for ORN when less intensive therapies have failed. Although the healing rate in similarly affected patients not treated with HBO is unknown, the improvements seen with peri-operative HBO were durable provided that the patients remained cancer free and abstained from smoking.

Hyperbaric oxygen treatment and bisphosphonate-induced osteonecrosis of the jaw: a case series.

PURPOSE: Bisphosphonate (BP)-associated osteonecrosis of the jaw (ONJ) is an emerging problem with few therapeutic options. Our pilot study of BP-ONJ investigated a possible role for hyperbaric oxygen (HBO(2)) therapy. PATIENTS AND METHODS: A total of 16 patients, ranging in age from 43 to 78 years, with BP-ONJ were treated with adjunctive HBO(2) between July 2003 and April 2006. Staging was based on the size and number of oral lesions. Clinical response after treatment and at distant follow-up; the odds of remission, stabilization, or relapse; and time to failure analysis were calculated. RESULTS: The median time on BP therapy before appearance of ONJ symptoms was 18 months, and that from symptom onset to HBO(2) therapy was 12 months. Fourteen of 16 patients (87.5%) improved in stage. The size and number of ONJ lesions were decreased after HBO(2) therapy (P < .001 and P = .008, respectively; Wilcoxon signed-rank test). Immediately after HBO(2) therapy, 7 of 16 patients (44%) were in remission and 8 (50%) had stabilized; however, stabilization without remission was sustained in only 2 patients. At follow-up, 10 of the patients (62.5%) were still in remission or had stabilized. The 7 patients who continued on BP treatment during HBO(2) therapy had a shorter time to failure (8.5 months; 95% confidence interval [CI] = 7.1 to 9.8) than those who discontinued the drug (20.1 months; 95% CI = 17.5 to 23.9; P = .006 by the log-rank test). Clinical response was not associated with cancer type or malignancy remission status. CONCLUSIONS: Adjunctive HBO(2) therapy may benefit patients with BP-ONJ; however, the outcome is improved with cessation of BP administration.

A comparison of hyperbaric oxygen versus hypoxic cerebral preconditioning in neonatal rats.

The potency of hyperbaric preconditioning (HBO-PC) is uncertain compared to well-validated ischemic or hypoxic models and no studies have directly compared HBO-PC to hypoxic preconditioning (HPC). We subjected rat pups to unilateral carotid cauterization followed by 90 min (min) of hypoxia using 8% O(2). Three HBO-PC regimes (maximum 2.5 atmospheres for 150 min) were compared to HPC (150 min of 8% O(2)) for changes in mortality and brain weight. Preconditioning-induced oxidative stress was assessed using aconitase activity and manganese superoxide dismutase (MnSOD) transcript levels. Initial brain weight data revealed a large coefficient of variation and compelled an examination of the temperature sensitivity of the model that revealed a narrow optimal range of 35 to 37 degrees C of variability in brain injury and mortality. With rigorous temperature control, high dose HBO-PC and HPC showed comparable anatomic (mean hemispheric weight decrease: control 42%, HPC 25% (P=0.01), HBO-PC 26% (P=0.01) and mortality protection (control 14.7%, HPC 5.9% HBO-PC 5.7%, P=0.001). High dose HBO-PC, but not HPC, suppressed aconitase activity by 65% at 24 h after the preconditioning stimulus (P=0.001). In contrast, MnSOD mRNA increased 2.5-fold at 24 h after HPC (P=0.007) but not after high dose HBO-PC. Thus, when temperature variability is eliminated, HBO-PC and HPC elicit similar preconditioning efficacy in neonatal brain but invoke different defenses against oxidative stress.