The safety of hyperbaric oxygen treatment--retrospective analysis in 2,334 patients.

INTRODUCTION: Hyperbaric oxygen (HBO2) therapy is applied in a growing number of cases for patients with different comorbidities and is considered a generally safe therapy. The main side effects related to HBO2 therapy are barotrauma, central nervous system- and pulmonary oxygen toxicity, claustrophobia, anxiety and visual disturbances. The aim of this study was to evaluate the incidence of side effects associated with HBO2 therapy and risk factors in a large cohort of patients treated for different indications. METHODS: We conducted a retrospective analysis of 2,334 patients treated in the Sagol Center of Hyperbaric Medicine and Research, Assaf Harofeh, Israel, between June 2010 and December 2014. Patients were classified to one of three categories of indications: Category A--non-neurological indications; Category B--neurotherapeutic indications; and Category C--acute indications. RESULTS: From a total of 2,334 patients, 406 (17.4%) experienced adverse event(s) (one or more) during HBO2 therapy sessions. The overall per-session incidence was 721:100,000 events:sessions (0.72%). The main complication was middle ear barotrauma, which occurred in 9.2% of patients and in 0.04% of sessions. Females and children under the age of 16 years had increased risk for barotrauma. Other complications--hypoglycemia, oxygen toxicity, dizziness, anxiety reactions, dyspnea and chest pain--occurred in 0.5-1.5% of patients. CONCLUSIONS: Strict operational protocols, including pre-HBO2 therapy evaluations and in-chamber monitoring, are essential and improve patient safety. When applied, HBO2 therapy can be considered one of the safest medical treatments available today.

Seizures during hyperbaric oxygen therapy: retrospective analysis of 62,614 treatment sessions.

INTRODUCTION: Hyperbaric oxygen (HBO2) therapy is considered to be a generally safe therapy. However, data regarding seizure incidence during HBO2 therapy as a clinical presentation of central nervous system- (CNS) related oxygen toxicity are conflicting (ranging from 1:10,000 to 1:600 seizures:hyperbaric sessions). The risk for seizures is of significant importance for the growing population of patients suffering from chronic neurological disorders such as traumatic brain injury and stroke who are treated with HBO2. The aim of this study was to evaluate the incidence of seizures during HBO2 therapy in a large cohort of patients and determine whether patients with known chronic neurological disorders are at increased risk. METHODS: Retrospective analysis of 2,334 patients treated at the Sagol Center of Hyperbaric Medicine and Research, Assaf Harofeh Medical Center, Israel, between June 2010 and December 2014. Patients were grouped into one of three categories according to indication for HBO2 therapy: Category A--non- neurological indications; Category B--neurological indications; and Category C--acute indications. RESULTS: A total of 62,614 hyperbaric sessions, administered to 2,334 patients, were included in the analysis. The overall incidence of seizures during hyperbaric sessions was 0.011% (1:8,945), occurring in seven (0.3%) patients. Only one patient had a clear oxygen toxicity-induced seizure, with an overall incidence of 1:62,614. CONCLUSIONS: Seizures induced by oxygen toxicity during HBO2 therapy are extremely rare. Moreover, in relation to oxygen-induced seizures, HBO2therapy can be considered safe for patients suffering with chronic neurological disorders except for uncontrolled epilepsy.

Diagnosis and treatment of primary lymphedema. Consensus document of the International Union of Phlebology (IUP)-2009.

Primary lymphedema can be managed safely as one of the chronic lymphedemas by a proper combination of DLT with compression therapy. Treatment in the maintenance phase should include compression garments, self management including the compression therapy, self massage and meticulous personal hygiene and skin care in addition to lymph-transport promoting excercises. The management of primary lymphedema can be further improved with proper addition of surgical therapy either reconstructive or ablative. These two surgical therapies can be effective only when fully integrated with MLD-based DLT postoperatively. Compliance with a long-term commitment of DLT postoperatively is the most critical factor determining the success of any new treatment strategy with either reconstructive or palliative surgery. The future of management of primary lymphedema caused by truncular lymphatic malformation has never been brighter with the new prospect of gene-oriented management.

Hyperbaric oxygen, oxidative stress, NO bioavailability and ulcer oxygenation in diabetic patients.

BACKGROUND: Hyperbaric oxygen therapy (HBO2) increases tissue oxygenation, thus serving as an adjunct therapy for diabetic wounds. However, in some patients there is insufficient increase in tissue O2. AIMS: To investigate the pathophysiology of insufficient HBO2 and the possible role of N-acetylcysteine (NAC). METHODS: Prospective, randomized, cross-over trial included 50 diabetic patients with non-healing ulcers. Each patient received two treatments with 100% oxygen/2ATA. NAC was administered i.v. at one of the two treatments. Basal and post-treatment peri-wound transcutaneous O2 (TcPO2) pressure, malondialdehyde (MDA), total anti-oxidant status (TAOS) and nitric oxide (NO) were assessed. An ulcer oxygenation increase above 200 mmHg was accepted as sufficient. RESULTS: During HBO2, 17 patients (34%) demonstrated insufficient increase in TcPO2. Concomitantly, their TAOS and NO decreased, while MDA increased. NAC administration attenuated these parameters, thus improving the HBO2 outcome. In those affected by NAC, the cure rate was 75%. By contrast, in 66% of patients with sufficient increase in TcPO2 TAOS was increased and MDA decreased irrespective of NAC administration. The cure rate in this subgroup was 82%. CONCLUSIONS: Insufficient increase of ulcer oxygenation during HBO2 results from exaggerated oxidative stress and decreased NO bioavailability. NAC administration-induced modulation of both parameters and may improve ulcer oxygenation during HBO2.

Mechanisms in experimental venous valve failure and their modification by Daflon 500 mg.

OBJECTIVES: To characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon 500), on this response. MATERIAL AND METHODS: A femoral arteriovenous fistula was created in Wistar rats (n=48). A cohort of 24 rats received oral treatment with MPFF (100 mg/kg/day body weight), 24 rats underwent the arteriovenous fistula procedure and received no treatment. At days 1, 7 and 21 the animals (n=8 at each time point) were killed. Experimental parameters measured included limb circumference, blood flow at the sapheno-femoral junction, leukocyte infiltration and gelatinase activity (matrix metalloproteinase, MMP). RESULTS: The acute rise in venous hypertension was accompanied by limb edema and venous reflux together with an eventual loss of valve leaflets in the saphenous vein. There was an increase in granulocyte and macrophage infiltration into the venous wall and the surrounding tissue, and a lesser increase in T- and B-lymphocyte infiltration. These changes were accompanied by a local increase in the proteolytic enzymes, MMP-2 and MMP-9. Administration of MPFF reduced the edema and lessened the venous reflux produced by the acute arteriovenous fistula. Decreased levels of granulocyte and macrophage infiltration into the valves were also observed compared with untreated animals. CONCLUSIONS: Venous hypertension caused by an arteriovenous fistula resulted in the development of venous reflux and an inflammatory reaction in venous valves culminating in their destruction. MPFF was able to delay the development of reflux and suppress damage to the valve structures in this rat model of venous hypertension.

Hyperbaric oxygen therapy for nonhealing vasculitic ulcers.

BACKGROUND: Cutaneous nonhealing ulceration is a threatening manifestation of vasculitis. Hyperbaric oxygen (HBO), frequently used as adjuvant therapy for patients with ischaemic ulcers, exerts additional beneficial effects on the vascular inflammatory response. AIM: To evaluate the effect of HBO on vasculitis-induced nonhealing skin ulcers. METHODS: The study population comprised 35 patients aged >or= 18 years with severe, nonhealing, vasculitis-induced ulcers that had not improved following immunosuppressive therapy. Baseline ulcer tissue oxygenation was evaluated at room air concentration (21% O2), at 1 atmosphere absolute (ATA) breathing 100% O2, and at 2 ATA breathing 100% O2. The baseline treatment protocol consisted of a 4-week course of 100% O2 for 90 min at 2 ATA, five times/week. RESULTS: The mean baseline ulcer tissue oxygenation (3.1 +/- 2.4 kPa at room air concentration), was significantly increased to 13.9 +/- 11.9 kPa at 1 ATA breathing 100% O2 (P < 0.001), and subsequently increased further to 59.1 +/- 29.8 kPa at 2 ATA breathing 100% O2 (P < 0.001). At the end of the hyperbaric therapy, 28 patients (80%) demonstrated complete healing, 4 (11.4%) had partial healing and 3 (8.6%) had no improvement. None of the patients had any side-effects related to the HBO therapy. CONCLUSION: HBO therapy may serve as an effective safe treatment for patients with vasculitis having nonhealing skin ulcers. Further studies are needed to evaluate its role as primary therapy for this group of patients.

Foam sclerotherapy of venous malformations.

Venous malformations may occur either as localized or segmental lesions. Radiologic imaging defines the extent of involvement but magnetic resonance imaging is the best modality: it gives a bright hypersignal on T2-weighted spin-echo sequences. During a 30-month period, 1427 patients were investigated for venous disorders and 1% were found to have venous angiomata (9 women and 5 men). The age range was 15 to 76 years (mean 30.8+/-18.6 years). Foam was produced by the Tessari technique using 1% or 2% concentration of polidocanol. The duplex Doppler was used for ultrasound guidance to insure intravenous flow of foam and to monitor effects of treatment. A goal of pain-free healing of ulcers or cosmetic improvement was set for each patient. The mean number of treatments was 3.6+/-2.8 (range 1-10). Pain-free healing was achieved in patients with non-healing ulcerations and cosmetically, all of the patients were improved. Sclerosant foam is useful in treating low-flow venous malformations.

Venous disorders: treatment with sclerosant foam.

AIM: Treatment of venous insufficiency has been revolutionized by introduction of less invasive endovenous procedures. Foam sclerotherapy competes with these for truly minimal less invasive care. The idea of using air and drug in combination is quite old. Orbach described an air block technique using froth in 1944 and in 1993 Cabrera proposed use of a true foam of sodium tetradecyl sulfate or polidocanol to treat varicose veins. When Tessari presented a three-way tap technique in 2000, very good microfoam could be made at a very low cost. Foam can be used in classical sclerotherapy but it is the new indications that excite interest. This report documents experience in treating severe chronic venous insufficiency (CVI), venous angiomata and varicose veins using foam sclerotherapy. METHODS: This report describes initial experience in treating 332 patients: 261 patients with varicose veins, 56 patients (77 limbs) with severe CVI, 6 patients with venous angiomata and 9 patients with Klippel-Trenaunay (KT) syndrome. Patients with telangiectasias were also treated but are not a part of this report. A compounding pharmacy supplied the 1-3% polidocanol that was prescribed for each patient according to guidelines on the Food and Drug Administration (FDA) website. Foam was produced by the Tessari technique. Ultrasound guidance was used. Venous access was obtained percutaneously through varices for saphenous vein and variceal closure and through specific targeted veins for treatment of CVI, angiomata and KT syndrome. Deep venous thrombosis (DVT) surveillance was done at 1, 7, 30, and 60 days. Specific perforating vein injection was done only occasionally. Foam volumes varied from 1 to 16 mL for each treatment. RESULTS: Obliteration of varicose and saphenous veins was entirely satisfactory (2.89 treatments/limb). There was no disability down time, no need for analgesics or sedation. Trapped thrombus in large varices required evacuation and caused local pain and cutaneous staining. Treatment goals but not cure were achieved in limbs with angiomata and KT syndrome. Treatment of CVI resulted in rapid, 2-6 weeks, ulcer healing, relief of painful lipodermatosclerosis and dermatitis and some decrease in skin hyperpigmentation. There was one failure in 77 limbs treated for CVI and one case of cutaneous necrosis in one limb treated for CVI and another in a limb treated for angiomata. Other adverse events (5.4%) lasting 3 to 20 min included dry cough (4), occular migraine (2), true migraine (2), other visual disturbances (3), chest tightness (2), panic attack (2), paresthesias (2) myoclonus (1) and cutaneous necrosis (2). DVT (1.8%) was limited to gastrocnemius veins (3 cases) and posterior tibial veins (3 veins). No pulmonary emboli or lung complications occurred. CONCLUSIONS: Treatment of a variety of venous disorders can be accomplished using foam sclerotherapy with results comparable to surgery and with an acceptably low rate of adverse events. These results, however, must be confirmed by larger experience in other institutions.

New clinical and laboratory staging systems to improve management of chronic lymphedema.

We have developed new clinical (C) and laboratory (L) staging systems to improve the clinical management of chronic lymphedema. These systems were retrospectively assessed in 220 chronic lymphedema patients followed up for 4 years. Clinical evaluation of the treatment response/disease progression was performed at 6 month intervals and laboratory evaluation at a yearly interval except for recurrent sepsis cases. The reliability of C-stage and L-stage for the progression of disease were analyzed separately. The C-staging was based on the subjective and objective findings of local and systemic conditions, while L-staging was based on lymphoscintigraphicfindings. Clinical implementation of this new staging system facilitated interpretation of the progress/deterioration of the clinical response to CDT treatment, and it was found to be a useful guideline for the decision/selection of further surgical treatment. We propose that these two separate staging systems could now become a new guideline for improved management of lymphedema with a better prediction of treatment outcome and decision point for additional medical/surgical therapy. Further clinical implementation and evaluation is necessary to demonstrate clinical usefulness especially to guide surgical therapy and L-staging in followup.

Venous hypertension, inflammation and valve remodeling.

OBJECTIVES: To identify possible mechanisms for destruction of valves in chronic venous hypertension and the results of treatment with an anti-inflammatory micronized purified flavonoid fraction. MATERIAL AND METHODS: The saphenous vein valves in a rat model of venous hypertension caused by a femoral arterial-venous fistula were studied. Studies included femoral venous pressure, valve morphology, femoral venous reflux and selected molecular inflammatory markers as examined by immunohistochemistry. The effects of treatment with the anti-inflammatory micronized purified flavonoid fraction (S 5628, Servier, 50 and 100 mg/kg/day) were investigated. RESULTS: The femoral venous pressure was elevated close to arterial values for a period of 3 weeks. We then examined the morphology of the veins and selected molecular inflammatory markers were assessed. The results show that in this model venous reflux develops in response to venous hypertension. This can be inhibited by the administration of the anti-inflammatory micronized purified flavonoid fraction (S 5628, Servier, 50 and 100 mg/kg/day). The valve becomes incompetent by a combination of venous dilation and shortening of the valve leaflets. This is not inhibited by treatment with S 5628. The valve leaflets are infiltrated with granulocytes, monocytes and T-lymphocytes, and the endothelial cells express enhanced levels of P-selectin and ICAM-1. Cells in the valves are subject to extensive apoptosis although no enhancement of MMP 2,9 expression could be detected at the three-week time point examined in this study. CONCLUSIONS: These results indicate that in this model chronic elevation of venous pressure is associated with an inflammatory reaction in venous valves, a process that may lead to their dysfunction, reflux, and upstream elevation of venous pressure. These effects are mitigated by the anti-inflammatory micronized purified flavonoid fraction in a dose dependent manner.

Treatment of varicose veins: proximal saphenofemoral ligation comparing adjunctive varicose phlebectomy with sclerotherapy at a military medical center.

There is no consensus as to the single best approach to the treatment of varicose veins. There has been a trend toward less invasive procedures to reduce the number of incisions and provide more selective ablation of varicosities. Ultimately, therapeutic decisions have depended on surgeon preference and the patient population. The active duty military population presents a unique challenge in the treatment of varicose veins. This mobile and active population requires a treatment method that provides maximum relief with the lowest possible morbidity and rapid recovery. The authors previously reported their experience with 104 patients who underwent saphenofemoral ligation combined with perforator point ligation and staged sclerotherapy. This group was compared to 103 patients who underwent saphenofemoral ligation, point perforator ligation, and stab avulsion phlebectomy as a single procedure. Follow-up for the sclerotherapy group included patient satisfaction surveys and documentation of recurrent varicosities. All ambulatory phlebectomy patients responded positively with respect to symptomatic and cosmetic results. Overall satisfaction was favorable and there was no significant difference in patient satisfaction between the ambulatory phlebectomy and sclerotherapy groups. Twelve per cent of the sclerotherapy patients developed true recurrences or new varicosities compared to 11% in the ambulatory phlebectomy group. The most common complication was superficial thrombophlebitis (20% ambulatory phlebectomy, 16% sclerotherapy) which was mild in all cases. All but three patients in the ambulatory phlebectomy group returned to work within 7 days and 75% returned to full duty within 72 hours. Completion of therapy was accomplished in a much shorter period for the ambulatory phlebectomy group. Overall patient satisfaction was achieved for both ambulatory phlebectomy and sclerotherapy patients. Completion of therapy was achieved in a shorter period with fewer clinic visits in the ambulatory phlebectomy group and this has become our procedure of choice for active duty military patients.

New advances in the understanding of the pathophysiology of chronic venous insufficiency.

Chronic venous insufficiency (CVI) is inseparably linked to elevated venous pressure and is accompanied by vascular, dermal, and subcutaneous tissue damage and restructuring. Abundant evidence exists both in humans and in experimental models to suggest that the tissue damage may be initiated by generation of an inflammatory reaction. Inflammatory indicators include elevation of endothelial permeability; attachment of circulating leukocytes to the endothelium; infiltration of monocytes, lymphocytes, and mast cells into the connective tissue; and development of fibrotic tissue infiltrates and several molecular markers, such as growth factor or membrane adhesion molecule generation. Indicators of an inflammatory reaction are already detectable at early stages of CVI and may be involved in the development of primary venous valve dysfunction. One of the important questions is to identify trigger mechanisms for the inflammatory reaction in CVI. Current evidence suggests that, among several possible mechanisms (hypoxia, humoral stimulation), a shift in fluid shear stress from normal physiological levels and endothelial distension under the influence of elevated venous pressure may serve as trigger mechanisms for inflammation.

Therapeutic approach to chronic venous insufficiency and its complications: place of Daflon 500 mg.

Early manifestations of chronic venous insufficiency (CVI) are edema, hyperpigmentation, and lipodermatosclerosis. Late complications are cutaneous ulceration and delayed healing. The specific hallmarks of this inflammation include CD68-positive infiltration into the dermal tissue, monocytes, and lymphocytes and enhanced endothelial permeability. This may lead to "fibrin cuff" formation. In addition, membrane adhesion molecules are present and cytokine expression is seen. In one experimental model of mesenteric venous hypertension, the inflammatory process was detected in its earliest stages. This was evident in the form of neutrophilic leukocyte adhesion to venular endothelium as well as migration of cells across the endothelium and basement membrane into the interstitial space. Simultaneously, parenchymal cell death was detected. This suggests that the mechanism that triggers the inflammatory reaction is venous hypertension. This may cause venous distension and a shift in fluid shear stress. Our observations suggest that patients with venous insufficiency demonstrate circulatory humoral stimulators for leukocyte activation. Otherwise, there is evidence that the inflammatory reaction is limited to the region of the venous ulceration or at least to the skin areas with severe microangiopathy. It may be that activated leukocytes traverse perivascular cuffs and release active transforming growth factor-beta1 (TGF-beta1) which has been found to be elevated exclusively in areas of clinically active CVI. Surgical intervention markedly decreases the number of dysfunctional vein segments and allows pharmacologic agents to protect normal structures from continuing damage. Daflon 500 mg, the purified micronized flavonoid fraction containing 90% diosmin and 10% hesperidin, acts favorably in venous ulcer treatment by inhibiting the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and may act favorably to inhibit leukocyte activation, trapping, and migration. Clinically, edema is reduced, ulcer healing is accelerated, and leukocyte trapping diminished. The action of micronized purified flavonoid fraction is beginning to be better understood, and as further knowledge is gained, better pharmacologic control of CVI is a tantalizing promise.

Growing the vascular surgical practice: venous disorders.

For the 48th meeting of the International Society for Cardiovascular Surgery, North American Chapter in June 2000, we were asked to organize a presentation with the title displayed above. We welcomed this opportunity because the phrase 'growing the practice' literally means giving greater service to underserved patients with vascular disorders. Underserved individuals with vascular disorders include those with nonatherosclerotic arterial disorders, patients with lymphedema, and individuals with a variety of venous disorders including venous insufficiency. The majority of these conditions are not surgical, but venous insufficiency commands attention because its treatments are interventional. Therefore, this presentation will discuss prevalence of venous insufficiency, a unifying concept of its pathophysiology, how treatment may be selected, what the new technology provides, and then a description of coding issues and whether or not interventions are actually worthwhile from the point of view of the patient.

Internal to external carotid artery transposition to repair recurrent stenosis after carotid artery stenting.

Recently, carotid artery stenting (CAS) has emerged as a treatment option for carotid artery stenosis. Since the procedure is new, management of its complications is not standardized. This case report describes one method of arterial reconstruction after failed CAS. A 64-year-old male underwent CAS of his right internal carotid artery (ICA) for an asymptomatic 65% stenosis. Seven months later the stented area had narrowed to 95%. Arteriography revealed that the common and external carotid arteries (ECA) were free of disease so we elected to perform a transposition of the distal ICA onto the proximal ECA. The ECA and its branches were completely mobilized and the ascending pharyngeal and lingual arteries divided. The ICA was divided distal to the stent. Transection of the occipital artery provided an arteriotomy for an end ICA to side ECA anastamosis, thus preserving ECA flow. Postoperative surveillance after 8 months has revealed no recurrent stenosis. Operative repair of restenosis after CAS may be challenging if standard endarterectomy is not possible. Other options for reconstruction are feasible but if the common and external carotid arteries are disease-free, an ICA to ECA transposition provides a simple all-arterial repair that avoids bypass and prosthetic material.