Avi Shupak

Necrotizing fasciitis : an indication for hyperbaric oxygenation therapy ?

BACKGROUND The accepted treatment protocol for necrotizing fasciitis (NF) consists of extensive surgery and wide spectrum antibiotics. Hyperbaric oxygenation (HBO) has been recommended as adjuvant therapy for NF, improving patient mortality and outcome. However, the beneficial effect of HBO for NF remains controversial. METHODS A retrospective evaluation of treatment outcome in 37 patients treated for NF between 1984 and 1993 was carried out. The mortality rate, morbidity criteria, and risk factors for grave prognosis were compared between a group of 25 patients who received HBO as part of their treatment protocol and a group of the remaining 12 patients treated by surgical excision and antibiotics alone. RESULTS The two groups were found to be similar with regard to age, gender, the incidence of individual risk factors for ominous prognosis, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score for diseases severity on presentation. The mortality rate among the HBO-treated patients was 36%, as opposed to 25% in the non-HBO group. The mean number of surgical débridements required per patient was significantly higher in the HBO group: 3.3 compared with 1.5 in the non-HBO-treated patients. Although the average length of hospitalization for survivors was shorter for the HBO group, the difference between the groups did not reach statistical significance. CONCLUSIONS The results of this study cast doubt on the suggested advantage of HBO in reducing patient mortality and morbidity when used as adjuvant therapy for NF.

Hyperbaric oxygen therapy as a treatment for stage-I avascular necrosis of the femoral head.

Avascular necrosis (AVN) of the head of the femur is a potentially crippling disease which mainly affects young adults. Although treatment by exposure to hyperbaric oxygen (HBO) is reported as being beneficial, there has been no study of its use in treated compared with untreated patients. We selected 12 patients who suffered from Steinberg stage-I AVN of the head of the femur (four bilateral) whose lesions were 4 mm or more thick and/or 12.5 mm or more long on MRI. Daily HBO therapy was given for 100 days to each patient. All smaller stage-I lesions and more advanced stages of AVN were excluded. These size criteria were chosen in order to compare outcomes with an identical size of lesion in an untreated group described earlier. Overall, 81% of patients who received HBO therapy showed a return to normal on MRI as compared with 17% in the untreated group. We therefore conclude that hyperbaric oxygen is effective in the treatment of stage-I AVN of the head of the femur.

Transdermal scopolamine for prevention of motion sickness : clinical pharmacokinetics and therapeutic applications.

A transdermal therapeutic system for scopolamine (TTS-S) was developed to counter the adverse effects and short duration of action that has restricted the usefulness of scopolamine when administered orally or parenterally. The plaster contains a reservoir of 1.5mg of scopolamine programmed to deliver 0.5mg over a 3-day period. A priming dose (140μg) is incorporated into the adhesive layer to saturate certain binding sites within the skin and to accelerate the achievement of steady-state blood levels. The remainder is released at a constant rate of approximately 5 μg/hour. The protective plasma concentration of scopolamine is estimated to be 50 pg/mL. TTS-S attains that concentration after 6 hours; a steady state of about 100 pg/mL is achieved 8–12 hours after application. Yet 20–30% of subjects failed to attain the estimated protective concentration, and plasma concentrations measured in subjects who failed to respond to TTS-S were lower than in responders. These findings may explain some of the treatment failures. Overall, the product appears to be the approximate functional equivalent of a 72-hour slow intravenous infusion. A combination of transdermal and oral scopolamine (0.3 or 0.6mg) was effective and well tolerated in producing desired plasma concentrations 1-hour post-treatment.TTS-S has proved to be significantly superior to placebo in reducing the incidence and severity of motion sickness by 60–80%. It was more effective than oral meclizine or cinnarizine, similar to oral scopolamine 0.6mg or promethazine plus ephedrine, and the same as or superior to dimenhydrinate. The addition of ephedrine or the use of two patches did not improve its efficacy, but rather increased the rate of adverse effects. TTS-S was most effective against motion sickness 8–12 hours after application. Despite previous evidence to the contrary, a recent bioavailability study demonstrated similar intraindividual absorption and sustained clinical efficacy with long-term use of the drug.The adverse effects produced by TTS-S, although less frequent, are qualitatively typical of those reported for the oral and parenteral formulations of this agent. Dry mouth occurs in about 50–60% of subjects, drowsiness in up to 20%, and allergic contact dermatitis in 10%. Transient impairment of ocular accommodation has also been observed, in some cases possibly the result of finger-to-eye contamination. Low-dose pyridostigmine was found effective in preventing cycloplegia but not mydriasis. Adverse CNS effects, including toxic psychosis (mainly in elderly and paediatric patients), have been reported only occasionally, as have difficulty in urinating, headache, rashes and erythema. Adverse effects were not correlated with plasma scopolamine concentrations. TTS-S produced only about half the incidence of drowsiness caused by oral dimenhydrinate or cinnarizine, and a level of adverse effects similar to that found with oral meclizine. Performance is not affected by short-term use. Prolonged or repeated application may cause some impairment of memory storage for new information. However, sea studies revealed significantly less reports of a decrement in performance or drowsiness due to prevention of sea sickness.The recommended dosage is a single TTS-S patch applied to the postauricular area at least 6–8 hours before the anti-motion sickness effect is required. For faster protection, the patch may be applied 1 hour before the journey in combination with oral scopolamine (0.3 or 0.6mg). After 72 hours, the patch should be removed and a new one applied behind the opposite ear. Its place in therapy is mainly on long journeys (6–12 hours or longer), to avoid repeated oral doses, or when oral therapy is ineffective or intolerable.

The Effect of Interleukin-8 on the Viability of Injected Adipose Tissue in Nude Mice

Adipose tissue injection as a free graft for the correction of soft-tissue defects is a widespread procedure in plastic surgery. The main problem in achieving long-term soft-tissue augmentation is partial absorption of the injected fat and hence the need for overcorrection and re-injection. The purpose of this study was to improve the viability of the injected fat by the use of interleukin-8. The rationale for the use of interleukin-8 was its abilities to accelerate angiogenesis and attract inflammatory cells and fibroblasts, providing the injected adipocytes more feeding vessels and a well-established graft bed to enhance their viability. Human adipose tissue, obtained by suction-assisted lipectomy, was re-injected into the subcutis in the scalp of nude mice. Interleukin-8 (0.25 ng) was injected subcutaneously to the scalp as a preparation of the recipient site 24 hours before the fat injection and was added to the fat graft itself (25 ng per 1 cc of injected fat). In the control group, pure fat without interleukin-8 was injected and no interleukin-8 was added for the preparation of the recipient site. One cubic centimeter of fat was injected in each animal in both the study and control groups. There were 10 animals in each group. The animals were euthanized 15 weeks after the procedure. Graft weight and volume were measured and histologic evaluation was performed. In addition, triglyceride content and adipose cell sizes were measured as parameters for fat cells viability. Histologic analysis demonstrated significantly less cyst formation in the group treated with interleukin-8. No significant differences were found between the groups with regard to graft weight and volume or the other histologic parameters investigated. No significant differences were demonstrated in adipose cell sizes and their triglyceride content. In conclusion, less cyst formation, indicating improved quality of the injected fat, can be obtained by the addition of interleukin-8. Further studies of various dosages of interleukin-8 and their long-term effect are required before these encouraging results could be applied clinically.

Hyperbaric Oxygen Therapy in the Pediatric Patient: The Experience of the Israel Naval Medical Institute

The pediatric patient is to be found in hyperbaric facilities throughout the world, receiving hyperbaric oxygen (HBO) therapy for both life-threatening and chronic diseases. Objective. To review the experience accumulated at the Israel Naval Medical Institute in the treatment of pediatric patients. Design. A retrospective analysis and review of all records of patients younger than age 18 years. Results. Between 1980 and 1997, 139 pediatric patients age 2 months to 18 years (mean, 7.7 years) received HBO treatment at the Israel Naval Medical Institute. Of the children, 111 (79%) suffered from acute carbon monoxide (CO) poisoning; 13 (9.2%) were treated after crush injury, traumatic ischemia, or compartment syndrome; 4 (2.8%) had clostridial myonecrosis; 1 (0.7%) had necrotizing fasciitis; 5 (3.6%) had refractory osteomyelitis; 2 (1.4%) had suffered massive air embolism; 2 (1.4%) had purpura fulminans; and 1 (0.7%) suffered from decompression sickness. Outcome, judged by neurologic sequelae, mortality, and extent of soft tissue loss and limb amputation, was favorable in 129 patients (93%). Two patients (1.4%) died, 1 as a result of CO poisoning and the other, gas gangrene; 2 of the patients in the CO group (1.4%) remained with neurologic sequelae, and 6 patients in the acute traumatic ischemia group (4.3%) underwent limb amputation. Conclusions. We had a favorable experience with 129 of a total 139 pediatric patients treated at our facility for the indications listed. A basic knowledge of HBO therapy is needed to refer the pediatric patient for treatment when indicated. The needs of the pediatric patient, especially the critically ill, require specific skills and equipment inside the hyperbaric chamber. Close collaboration between the pediatrician and the hyperbaric medicine physician is essential to ensure adequate care for infants and children.

Prednisone Treatment for Vestibular Neuritis

Objective: To evaluate the value of corticosteroids in the treatment of vestibular neuritis (VN). Design: Prospective controlled randomized. Methods: Thirty VN patients, 15 in the study and 15 in the control group, were the subjects of the study. The study group was treated by 1 mg/kg prednisone for 5 days, followed by gradually reduced doses of prednisone for an additional 15 days, and vestibular sedatives for symptomatic relief during the first 5 days after presentation. The control group received a placebo and similar vestibular sedatives. The patients had a baseline evaluation and follow-up examinations after 1, 3, 6, and 12 months. The groups were compared for the presence of symptoms and signs, caloric lateralization on the electronystagmography (ENG), the presence of other pathologic findings in the ENG, and Dizziness Handicap Inventory scores. Results: No differences were found between the groups in the occurrence of symptoms and signs, degree of caloric lateralization, presence of other ENG pathologic findings, and Dizziness Handicap Inventory scores at the end of the study. Complete resolution was observed in 64% of the study and in 80% of the control group. The study group showed earlier recovery of ENG lateralization at the 1- and 3-month follow-up evaluations and higher rates of complete resolution at the 3- and 6-month follow-up points. Conclusion: Prednisone therapy might enhance earlier recovery but does not improve the long-term prognosis of VN. The clinical and laboratory parameters in VN are not correlated, and both are required for complete patient evaluation.

Mal de Debarquement and Posture: Reduced Reliance on Vestibular and Visual Cues

Objective The neural mismatch theory assumes that the intersensory conflicts leading to motion sickness are resolved by changes in the relative weighting of the various senses that contribute to orientation. If this sensory rearrangement persists after disembarkment, it might result in mal de debarquement (MD): ataxia and a rocking sensation sometimes felt after landing. The objective of the present study was to examine possible changes in sensory organization in naval crew members with differing susceptibility to MD with computerized dynamic posturography (CDP).

Hyperbaric oxygen therapy for cutaneous/soft-tissue zygomycosis complicating diabetes mellitus.

A 24-year-old female diabetic patient was hospitalized because of ketoacidosis and a necrotic wound on the hand. Debridement and antibiotic therapy failed to halt the process. After demonstration of Mucor in cultures from the wound, the patient underwent extensive surgery and amphotericin B was administered. When the necrotic process continued despite these measures, adjunctive hyperbaric oxygen (100% O2 at 2.5 ATA for 90 minutes) was administered daily for a total of 21 treatment sessions. She gradually improved, and at 2 months follow-up most of the wound had healed. Although the mortality rate of cutaneous/soft-tissue zygomycosis is markedly lower than that of the rhinocerebral form, morbidity is still considerably high. Successful use of hyperbaric oxygen has been reported in rhinocerebral zygomycosis, and it may have been of benefit in this high-risk patient by preventing local and systemic spreading of the fungus. This report is the first case of the use of hyperbaric oxygen for cutaneous/soft-tissue zygomycosis. It is suggested that hyperbaric oxygen be considered for this indication in diabetic patients as an adjunct to surgery and amphotericin B.

The effects of dimenhydrinate, cinnarizine and transdermal scopolamine on performance

We assessed the influence of dimenhydrinate, cinnarizine and transdermal scopolamine on the ability to perform simulated naval crew tasks. The effect of single doses of dimenhydrinate, 100 mg, cinnarizine, 50 mg, and one transdermal scopolamine patch on psychomotor performance was evaluated using a double-blind, placebo-controlled, randomized, crossover design in three separate studies. A total of 60 young naval crew (20 for dimenhydrinate, 15 for cinnarizine and 25 for transdermal scopolamine) underwent a battery of computerized and paper and pencil performance tests, and filled out a questionnaire on side-effects and well-being self-assessment. Dimenhydrinate significantly impaired decision reaction time and auditory digit span. Most of the subjects who took dimenhydrinate also reported a subjective decrease in well-being and general performance abilities. Cinnarizine and transdermal scopolamine did not affect performance abilities. Cinnarizine was free of significant side-effects. Dry mouth was the only significant side-effect of transdermal scopolamine. These findings could be explained by the well-known sedative properties of dimenhydrinate and not by a specific effect on any particular cognitive or motor function. Our results suggest that dimenhydrinate, 100 mg, adversely affects psychomotor function, whereas single doses of cinnarizine, 50 mg, and transdermal scopolamine appear to be free of side-effects on performance and seem to be a preferable anti-seasickness drug for use by a naval crew.

Hyperbaric oxygen therapy for massive arterial air embolism during cardiac operations

BACKGROUND Massive arterial air embolism is a rare but devastating complication of cardiac operations. Several treatment modalities have been proposed, but hyperbaric oxygen is the specific therapy. METHODS The Israel Naval Medical Institute is the only referral hyperbaric center in this country for acute care patients. We reviewed our experience in the hyperbaric oxygen treatment of massive arterial air embolism during cardiac operations. RESULTS Seventeen patients were treated between 1985 and 1998. Eight patients (47.1%) experienced a complete neurologic recovery; 6 patients (35.3%) remained unconscious at discharge, and 3 patients (17.6%) died. Mean (+/- SD) delay from the end of the operation to hyperbaric therapy was 9.6 +/- 7.4 hours (range, 1-20 hours). This delay was 4.0 +/- 3.4 hours (1-12 hours) for patients who had a full neurologic recovery, 12.8 +/- 7.1 hours (5-20 hours) for patients with severe neurologic disability, and 18.0 +/- 2.0 hours (16-20 hours) for patients who died (1-way analysis of variance; P =.002). The source of variance among the groups mainly resulted from the short delay for patients who experienced complete recovery compared with the other 2 groups (Tukey test). All 5 patients who were treated within 3 hours from the operation and 50% (2 of 4 patients) of those patients treated 3 to 5 hours from operation experienced a full neurologic recovery. With a delay of 9 to 20 hours, only 1 of 8 patients had a full neurologic recovery. The association between outcome and treatment delay was found to be statistically significant (tau = 0.65 with exact 2-sided P value =.0007). CONCLUSION Hyperbaric oxygen therapy should be administered as soon as possible after massive arterial air embolism during cardiac operations.