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.

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.

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.

Comparative nitrogen balance study between young and aged adults using three levels of protein intake from a combination wheat-soy-milk mixture.

The protein requirement and the efficiency of protein used were studied in young and old adult human subjects. Protein intake levels (N X 6.25) of 0.4, 0.8, and 1.6 g/kg body weight per day from a combination wheat-soy-milk mixture were fed. Caloric intake was held constant at 40 kcal/kg body weight per day throughout the 11-day study of each dietary period. No significant differences were observed in their protein requirement, efficiency of protein use or the ability to adapt to changes of protein intake levels. Protein digestibility was not impaired in the aged. It is concluded that the protein requirement and the efficiency of protein use are not affected by the aging process.

Donor HL-A incompatibility and lymphocytotoxic antibody response in human renal allotransplantation.

When 81 recipients of primary renal allografts were examined for the influence of donor HL-A incompatibilities (DIC) on the survival of allografts, an association was found between greater DIC and not only an increased loss of allografts in the 1st year, but also a decreased survival of transplants in the subsequent years. However, three allografts with no DIC were rejected, whereas nine others with three to four imcompatibilities have functioned well for 1-5 years. A surprisingly high proportion (52%) of 81 renal allograft recipients produced lymphocytotoxic antibodies which lack HL-A specificity but apparently detect a polymorphic antigenic system on normal human lymphocytes. Only three patients who rejected the allografts made detectable circulating antibodies specific to DIC. However, when patients received grafts with fewer DIC, there was a greater number of no antibody or low frequency antibody producers, whereas with a greater number of DIC there was an increased occurrence of high frequency antibody producers. These results suggest that HL-A as well as non-HL-A systems may play a significant role in the success of allotransplantation. Although the presence of non-HL-A antibodies was not always associated with allograft loss, further characterization of these antibodies may reveal a new genetic system(s).

Extended treatment with antithymocyte globulin (ATGAM) in renal allograft recipients.

Twenty renal allograft recipients were treated with antithymocyte globulin (ATGAM; ATG) for up to 16 weeks in addition to azathioprine and prednisone, while 20 controls received no ATG. The ATG group showed a lower incidence of first rejection episodes during the first month after transplantation, and also a better functional graft survival rate up to 2 years after transplantation. The results in this early ATG trial were better than those in subsequent trials which used 14-day treatment regimens. Longer treatment deserves another look.

Nociceptive responsiveness during slow-wave sleep and waking in the rat.

Brainstem neurons that are thought to modulate pain are reported to have state-dependent discharge rates. Yet, the effect of behavioral state upon nociceptive transmission has not been well studied. Therefore, we examined responses to noxious thermal stimulation of the rat hindpaw presented during different behavioral states. Noxious thermal stimuli were applied to rats as they spontaneously cycled through waking and sleeping states. Two different methods of heating the paw - a focused light bulb ("radiant heat") and a CO2 laser ("laser heat")-were employed. Regardless of the heating method used, rats withdrew from noxious thermal stimulation when it was applied in each behavioral state tested. When rats were tested with radiant heat, the withdrawal latency from noxious heat was shorter during slow-wave sleep than during waking. In contrast, when tested with laser heat, there was no difference in either the response latency or magnitude evoked by noxious heat across sleep/wake states. Despite the fact that rats withdrew from noxious heat (using either method of application) applied during sleep, the rats quickly returned to sleep afterwards. The latency to sleep after noxious stimulation was significantly greater during waking than during sleeping. The behavioral response to noxious thermal stimulation includes both an initial motor withdrawal which is enhanced during sleep and arousal or alerting which is suppressed during sleep. Therefore, pain evokes at least two distinct reactions that are differentially modulated across sleep/wake cycles.

Use of the axillary artery in complex cerebral revascularization.

Two cases of complex common carotid and innominate artery disease managed by axillocarotid autogenous saphenous vein bypass are presented, including a detailed description of the operative technique. The results in each case were gratifying. Although the concept of extra-anatomic repair is not new, this modification in operative technique expands the surgeon's armamentarium. The ease and safety of exposure and anastomosis of the axillary artery combine to make it the preferable donor vessel for extra-anatomic cerebral revascularization in the poor-risk, elderly patient population.

Abdominal aortic salmonellosis.

A recent example of Salmonella mycotic abdominal aortic aneurysm is presented together with a review of the 24 other cases in the literature. Emphasis is placed on common modes of presentation, diagnosis, and surgical management. A review of current theories of etiology is presented along with a new, more descriptive classification of mycotic aneurysms.

Assessment of donor limb hemodynamics in femorofemoral bypass for claudication.

During a 5-year period (1975 to 1980), 44 patients underwent femorofemoral bypass for unilateral disabling claudication caused by iliac atheroocclusive disease. All patients had complete Doppler arterial examination performed pre- and postoperatively, including segmental thigh and ankle pressure and calculation of an ankle/brachial (A/B) index for each limb. In 37 patients, standard treadmill exercise testing was performed before and after femorofemoral grafting. Hemodynamic improvement in the symptomatic limb was evidenced by an increase in resting A/B index from a mean of 0.54 +/- 0.14 before to 0.76 +/- 0.22 after operation (P less than 0.001). Exercise tests which were abnormal in all 37 recipient limbs preoperatively were improved. Six of the seven unimproved recipient limbs had associated femoropopliteal occlusion. Donor limb mean resting ankle/brachial index fell from 0.93 +/- 0.22 before to 0.83 +/- 0.22 after surgery (P less than 0.05). However, in 13 of 23 donor limbs, exercise response which had been normal before surgery became abnormal. Additionally, in 14 patients with abnormal donor limb exercise response before grafting, seven limbs had a significantly worsening of the exercise response postoperatively. These findings were not related to the patency of the superficial femoral artery in the donor limb. Deterioration in donor limb hemodynamics noted in 20 (45%) of the 44 patients in this series suggests that strict patient selection criteria should be maintained. Unlike in healthy subjects, an arteriographically patent atherosclerosis iliac artery may not support flow requirements of bilateral lower limb exercise.

Sequential femoral-tibial bypass for severe limb ischemia.

Sequential femoral-popliteal-tibial bypass has been recommended for surgical treatment of severe lower limb ischemia in patients with complex multisegmental arterial occlusion. To evaluate this alternative technique critically, sequential grafting was performed in 40 limbs with severe ischemia manifest by rest pain (20), nonhealing ulceration (eight), or gangrene (12). Measurement of segmental Doppler arterial pressure revealed a significant increase in ankle brachial index from 0.29 +/- 0.15 before operation to 0.93 +/- 0.12 after operation, confirming the hemodynamic improvement among these patients. In the early postoperative period occlusion of the distal graft segment was recognized in 12 patients by a characteristic reduction of the ankle/brachial index (0.50 +/- 0.14), while the low thigh pressures remained unchanged. Recurrent severe ischemia was prevented in most by persistent patency of the proximal graft segment. Overall, significant hemodynamic improvement was achieved in 29 of 38 limbs, a limb salvage rate (76%) comparable to that reported for femoral-distal bypass or femoral-popliteal bypass to an isolated popliteal segment. Early graft failure in this series resulted in major amputation in eight of 16 limbs, a significantly lower rate than for these other techniques. Sequential bypass grafting is a useful alternative method for limb salvage. The preservation of the proximal graft patency after distal segmental occlusion may be an important characteristic of this type of reconstruction.

Ankle pressure changes in distal bypass grafts during knee flexion.

Systolic ankle blood pressure was measured with the limb extended and then acutely flexed in four study groups. These included 11 normal individuals, 11 patients with below-knee autologous saphenous vein bypass grafts, 11 patients with polytetrafluoroethylene (PTFE) prosthetic below-knee bypass grafts, and 11 patients with femoropopliteal arterial occclusion who had not undergone bypass grafting. This study shows that normal limbs, limbs with saphenous vein bypass grafts, arteriosclerotic limbs, and those with PTFE bypass grafts all tolerate acute knee flexion without significant decrease in distal blood pressure.

Correlation of immune and nutritional status with wound complications in patients undergoing vascular operations.

The acquired failure of host immunocompetence that may result from significant protein and caloric malnutrition has been associated with an increased incidence of septic complications in patients undergoing operation. Wound infection in patients undergoing vascular surgical procedures may lead to exposure or contamination of a vascular graft, with the subsequent risk of hemorrhage, limb loss, or death. The present study was undertaken to correlate the immune and nutritional status of patients undergoing vascular surgical procedures with the development of significant wound complications. Seventy-nine patients undergoing a variety of vascular operations were subjected to comprehensive nutritional assessment, including anthropometric measurements (height, weight, midarm circumference, triceps skin fold), serologic testing (albumin, transferrin, lymphocyte count, serum zinc), cutaneous assessment of delayed hypersensitivity (anergy battery), and neutrophil functional analysis. After operation the patients were observed for the development of delayed wound healing or wound infection. Statistical analysis of measured variables was performed to identify immune and nutritional markers with prognostic value. Patients with serum albumin levels above 3 gm/dl were much more likely to have uncomplicated wound healing (P less than 0.001). Similarly, patients with serum transferrin levels above 150 mg/dl had significantly fewer wound problems (P less than 0.01). Only 29% of patients with cutaneous anergy had normal wound healing, while 56% of those with intact cutaneous reactivity healed primarily; this difference, however, was not statistically significant. Diabetics in this series were more likely to develop wound problems (P less than 0.05). Anthropometric measurements provided no predictive information regarding the likelihood of uncomplicated healing. Similarly, measurement of total lymphocyte count and serum zinc yielded no significant prognostic information. The urgent nature of many vascular surgical procedures may preclude preoperative immune and nutritional assessment; however, the outcome of these procedures may ultimately depend upon intact host defense. The contribution of protein and caloric malnutrition to immunocompromise can be easily assessed in these patients. The detection and subsequent reversal of immunoincompetence through the use of enteral or parenteral alimentation should provide a significant reduction in operative morbidity and mortality.

Management of infection of major amputation stumps after failed femorodistal grafts.

A retrospective review was performed of 174 patients who underwent 199 lower-extremity amputations for unreconstructable vascular insufficiency from 1976 to 1983 at the Northwestern University Medical Center. This study was initiated to identify the cause of amputation wound healing complications and secondary ascending prosthetic graft infection, as well as to propose a plan of management for the failed prosthetic grafts at the time of major limb amputation. Ninety-eight amputations were performed primarily, 12 were performed secondary to graft infection, and 89 were performed in patients who had previously undergone infrainguinal arterial bypass procedures. At the time of amputation, graft management consisted of high transection and suture ligation, allowing the graft to retract into the substance of the stump and away from the skin suture line and weight-bearing area of the limb. Delayed stump healing was noted to occur more commonly in the group who had undergone previous bypasses as opposed to those who had undergone primary amputation (34.8% versus 14.3%). Fourteen graft infections developed in 89 patients after amputation (15.7%), which is significantly higher than the overall 1.4% incidence of lower-extremity bypass infections that occurred during the same interval in patients with intact extremities. In addition, it was found that when infected grafts in amputated limbs were completely removed, stump healing without recurrent wound and graft sepsis was better than when treated locally or with partial graft removal. We therefore recommend removal of a thrombosed graft with an infected wound or an infected graft at the time of major limb amputation to decrease the incidence of wound complications and graft infection.

A systematic approach to severe hand ischemia.

Because severely symptomatic hand ischemia is not common and because there are a wide variety of clinical conditions which can cause arterial insufficiency of the upper extremity, a retrospective study has been done to determine the efficacy of various diagnostic manipulations used in managing 65 patients with severe hand ischemia at the Northwestern University McGaw Medical Center, Traumatic, thermal, and iatrogenic causes of hand ischemia were diagnosed by simple history taking, as was advanced uremic arteritis. Doppler ultrasound and digital arterial pressure recording were confirmative, rather than diagnostic. These aided in defining precise degrees of ischemia and identifying proximal arterial occlusions. Invasive total extremity angiography clarified atherosclerotic, atheroembolic, and other chronic occlusive lesions while serum electrophoresis and immunoelectrophoresis defined the polyclonal and monoclonal gammopathies. When digital necrosis was present, organic arterial occlusions usually were found. These responded best to direct arterial reconstruction down to the mid-palm level. Transpleural, transthoracic sympathectomy was useful as an adjuvant or as definitive treatment for distal digital arterial occlusions. Selective vasodilator therapy was used as dictated by the cause of ischemia and its eventual outcome.

Correlation of foot arterial anatomy with early tibial bypass patency.

The detailed arterial anatomy of the foot in severe limb ischemia is not well known. This study was undertaken to define foot arterial anatomy and correlate these findings with the early results (6 months) of femoral-distal bypass. After completion of the bypass, operative arteriography was performed by direct injection of contrast media into the graft. A lateral view of the distal limb and foot was obtained. Foot vessel anatomy was classified into primary and secondary pedal arches, analogous to the superficial and deep volar arches of the hand. For peroneal bypass, special attention was paid to perforating branches and their communications with these two pedal arches. A total of 56 distal bypass operations was analyzed. Femoral--anterior tibial bypass was performed in 26 cases. When either a primary or a secondary pedal arch was intact, early graft patency (6 months) was achieved in 20 of 21 patients. When neither pathway was present, graft failure occurred in four of five cases. Similarly, of 10 femoral--posterior tibial grafts, seven remained patent with at least one pedal arch intact, whereas six of seven grafts failed when neither arch was patent. Bypass to the peroneal artery was successful in eight of nine limbs when a patent primary or secondary arch was reconstituted via either the anterior or posterior perforating branches. None of four peroneal grafts remained patent when both arches were occluded. As a whole, in 40 limbs with either a patent primary or secondary pedal arch, early graft success was achieved in 35 limbs (87.5%). In contrast, in 16 limbs with no patent arch, only two (12.5%) were successfully reconstructed (P less than 0.001). Analysis of the results of femoral-distal bypass based on a single plantar arch as the sole determining anatomic factor in graft patency is not adequate. The secondary pedal arch and communicating branches of the peroneal artery are also of surgical significance. Operative arteriography can define runoff in the foot, and this information has prognostic significance. It may allow rational judgment regarding reintervention in patients with failed grafts.

Use of a temporary shunt for renal transplant protection during aortic aneurysm repair.

Broader indications for renal transplantation and improved allograft survival suggest that aortic aneurysms will be encountered more commonly in kidney transplant recipients. This report describes the use of a temporary heparin-bonded shunt placed from the proximal abdominal aorta to the femoral artery for perfusion of a renal allograft during simultaneous repair of an aortic aneurysm and correction of transplant renal artery stenosis. Renal function was satisfactorily maintained intraoperatively and has continued to be excellent during 2 1/2 years of follow-up. Methods of renal transplant protection during aortic reconstruction are reviewed, and principles of temporary shunting for allograft protection are proposed.