A Systematic Review of the Quality of Clinical Practice Guidelines for Chronic Limb-Threatening Ischemia.

BACKGROUND: To assess the quality of clinical practice guidelines (CPGs) for chronic limb-threatening ischemia (CLTI) using the Appraisal of Guidelines for Research and Evaluation II instrument. METHODS: A systematic review of Medline, Embase, and online CPG databases was carried out. Four CPGs on CLTI were identified: Global Vascular Guidelines (GVG), European Society of Cardiology (ESC), American College of Cardiology, and National Institute for Health and Care Excellence guidelines on lower limb peripheral arterial disease. Two independent appraisers analyzed the 4 CPGs using the Appraisal of Guidelines for Research and Evaluation II instrument. CPGs were ranked across 6 domains with 23 items that ranged from 1 (strongly disagree) to 7 (strongly agree). A scaled domain score was calculated as a percentage of the maximum possible score achievable. A domain score of ≥50% and an overall average domain score of ≥80% reflected a CPG of adequate quality recommended for use. RESULTS: GVG had the highest overall score (82.9%), as an average of all domains, and ESC had the lowest score (50.2%). GVG and National Institute for Health and Care Excellence guidelines had all domains scoring >50%, while American College of Cardiology had 5 and ESC had 3. Two domains, rigor of development and applicability, scored the lowest among the CPGs. There was a lack of detail in describing systematic methods used in the literature review, how guidelines were formulated with minimal bias, and the planned procedure for updating the guidelines. Implications of guideline application and monitoring of outcomes after implementations were not explicitly discussed. CONCLUSIONS: The GVG guideline published in 2019 discussing CLTI is assessed to be of high quality and recommended for use. This review helps to improve clinical decision-making and quality of future CPGs for CLTI.

Impact of renal insufficiency on clinical outcomes in patients with critical limb ischemia undergoing endovascular revascularization.

BACKGROUND: Patients with renal insufficiency (RI) are frequently excluded from trials assessing various endovascular revascularization concepts in critical limb ischemia (CLI) although information on clinical outcomes is scarce. METHODS: Consecutive patients with CLI undergoing endovascular lower limb revascularization during a 4.5-year time interval at a tertiary referral center were prospectively followed over a 12-month period. Patients were grouped according to renal function defined as normal (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2); n = 108, 49.5%), moderate RI (eGFR ≥ 30-59 mL/min/1.73 m(2); n = 86, 39.5%) and severe RI, including dialysis (eGFR < 30 mL/min/1.73 m(2); n = 24, 11%). Clinical endpoints assessed were sustained clinical success, peri- and postprocedural mortality and major, above-the-ankle amputation. Sustained clinical improvement was defined as an upward shift of at least one category on the Rutherford classification compared with baseline to a level of claudication without repeated revascularization or unplanned amputation in surviving patients. Survival analysis was performed using the Kaplan-Meier method. Multivariate regression analysis was conducted in separate models for all above-mentioned clinical endpoints. RESULTS: A total of 208 patients (218 limbs, mean age 77.1 ± 9.5, 131 men) underwent endovascular revascularization. Technical success rate was 95.2%, 92.5%, and 100% in patients without, moderate or severe RI. Sustained clinical success was 81.7%, 74.1%, and 51.5% in patients with normal renal function, 87.8%, 67.0%, and 63.3% with moderate, and 81.0%, 64.6%, and 50.2% with severe RI (P = .87 by log-rank) at 2, 6, and 12 months. Accordingly, major amputation rates were 9.9%, 18.2%, and 20.8% vs 9.9%, 22.6%, and 24% vs 12.5%, 16.7%, and 21.1% (P = .83, by log-rank). Mortality rates were 8.4%, 17.6%, and 26.5% in patients with normal renal function, 9.6%, 17.6%, and 30.1% with moderate and 17.5%, 26.6%, and 31.9% in patients with severe RI (P = .77, by log-rank) at corresponding intervals. Multivariate analysis revealed eGFR (hazard ratio [HR], 1.016; 95% confidence interval [CI], 1.001-1.031; P = .036), age (HR, 1.12; 95% CI, 1.061-1.189; P < .0001) and cigarette smoking (HR, 3.14; 95% CI, 1.153-8.55; P = .026) to be predictors for increased mortality within 1 year of follow-up. CONCLUSION: While functional lower limb outcomes were not influenced by renal function in this study, presence of RI was an independent predictor for higher mortality in CLI patients undergoing endovascular revascularization.

Critical limb ischemia in a patient with systemic lupus erythematosus: a case report.

BACKGROUND: Peripheral vascular disease is the rarest vascular complication in systemic lupus erythematosus. Some theories propose that immune complexes may promote inflammation in the vessel, and disrupt it in a manner that may cause ischemia. CASE PRESENTATION: A 14-year-old Asian girl presented with intermittent claudication as the chief complaint followed by discoloration of her left big toe for 2 weeks prior to admission. Her medical history showed that 1 month prior to admission she had photosensitivity, rash, and arthralgia, with positive antinuclear antibody test, positive anti-double-stranded DNA test, positive anti-ribosomal protein P, and complement C4 (7.4 mg/dL); she was diagnosed as having systemic lupus erythematosus and started therapy. A local examination of her left toe showed black discoloration, low pulsation, localized tenderness, and decreased sensation. Laboratory results showed C-reactive protein of 1.16 mg/dL and D-dimer of 2.28 uG/mL. A computed tomography angiogram showed near total occlusion of her popliteal artery; critical limb ischemia was confirmed. Peripheral arteriography was performed with invasive strategy. After the procedure, the flow was improved to distal, but there was inflammation in the vessel, so we decided to stop the procedure because of the risk of dissection. Our patient was given atorvastatin and warfarin, and we maximized her systemic lupus erythematosus therapy with prednisone. There were two follow-ups. The first follow-up was 1 week after the procedure. Our patient attended her first follow-up at our out-patient department with no symptoms and improvement in her toe's discoloration; warfarin was stopped, and clopidogrel and cilostazol were added for thrombus prevention therapy, she was then scheduled for debridement. The second follow-up was done 2 months after the first follow-up and discoloration was improved. The third follow-up, 5 months after the second follow-up, showed improvement. CONCLUSION: Critical limb ischemia is a rare complication of systemic lupus erythematosus that requires immediate treatment. Due to our limited resources, we improvised a strategy to achieve the best possible outcome in our patient by using a combination of invasive treatment and medication.

The Impact of Walking Exercises and Resistance Training upon the Walking Distance in Patients with Chronic Lower Limb Ischaemia.

Objective. The objective of this paper is to compare the impact of supervised walking and resistance training upon the walking distance in PAD patients. Materials and Methods. The examination involved 50 PAD patients at the 2nd stage of the disease according to Fontaine's scale. The participants were randomly allocated to two groups: one exercising on the treadmill (n = 24) and one performing resistance exercises of lower limbs (n = 26). Results. The 12-week program of supervised rehabilitation led to a significant increase in the intermittent claudication distance measured both on the treadmill and during the 6-minute walking test. The group training on the treadmill showed a statistically significant increase of the initial claudication distance (ICD) and the absolute claudication distance (ACD) measured on the treadmill, as well as of ICD and the total walking distance (TWD) measured during the 6-minute walking test. Within the group performing resistance exercises, a statistically significant improvement was observed in the case of parameters measured on the treadmill: ICD and ACD. Conclusions. The supervised rehabilitation program, in the form of both walking and resistance exercises, contributes to the increase in the intermittent claudication distance. The results obtained in both groups were similar.

Mechanisms of postischemic injury in skeletal muscle: intervention strategies.

Reperfusion of ischemic skeletal muscle leads to adverse local and systemic effects. These detrimental effects may be attenuated by interfering with or modulating the pathophysiological processes that are set in motion during ischemia and/or reperfusion. The purpose of this paper is to review the different intervention strategies that have been employed in an attempt to elucidate the mechanisms involved in the pathogenesis of skeletal muscle ischemia-reperfusion injury. The results of these studies indicate that the postischemic injury processes that lead to cell dysfunction and death are multifactorial in nature and include oxidant generation, elaboration of proinflammatory mediators, infiltration of leukocytes, Ca2+ overload, phospholipid peroxidation and depletion, impaired nitric oxide metabolism, and reduced ATP production. Although the etiopathogenesis of skeletal muscle ischemia-reperfusion is complex, careful delineation of the mechanisms that contribute to postischemic microvascular dysfunction and muscle necrosis has progressed to the point where rational intervention strategies may be proposed and implemented as potential treatments for skeletal muscle dysfunction associated with ischemia-reperfusion.

Idosos vítimas de trauma: doenças preexistentes, medicamentos em uso no domicílio e índices de trauma / Elderly victims of trauma: preexisting conditions, medications taken at home and indexes of trauma / Ancianos víctimas de trauma: condiciones preexistentes, medicamentos tomados en el hogar e índices de trauma

Objetivou-se identificar o perfil sociodemográfico de idosos vítimas de trauma, caracterizar doenças preexistentes e medicamentos utilizados no domicílio; calcular índices de trauma e desfecho clínico. Estudo retrospectivo e exploratório, com a análise de dados secundários de um banco de dados de um hospital geral terciário, entre 2008 e 2010. Foram estudados 131 idosos, média de idade 69,9 anos, 73,3% homens, 55,1% casados, 54,7% aposentados; 65,6% possuíam doenças preexistentes e 48,9% usavam medicamentos no domicílio. Houve representatividade de quedas (31,3%), seguidas por atropelamento (28,2%), com cabeça/pescoço sendo a região mais acometida (59,5%). Prevaleceu o trauma moderado (44,3%), com condições de sobrevida após o evento (80,2%). Houve associação entre mecanismo do trauma e doença preexistente (p=0,01) e entre mecanismo do trauma e sexo (p=0,03). O conhecimento das variáveis envolvidas com idosos vítimas de trauma possibilita aos profissionais de saúde o planejamento de medidas preventivas, visando aprimorar sua assistência.

The objective was to identify the sociodemographic profile of the elderly victims of trauma, to characterize preexisting conditions and medications taken at home, and to calculate indices of trauma and clinical outcomes. This is a retrospective and exploratory analysis from a database of a general hospital between 2008 and 2010. There were studied 131 elderly, mean age 69.9 years, 73.3% male, 55.1% married, 54.7% retired, 65.6% had preexisting conditions and 48.9% used drugs at home. There was a representative number of falls (31.3%), followed by running over (28.2%), with the head/neck region being the most affected (59.5%). Moderate trauma prevailed (44.3%), with conditions of survival after the event (80.2%). There was an association between mechanism of trauma and preexisting disease (p=0.01) and between mechanism of trauma and sex (p=0.03). The knowledge of the variables involved with the elderly victims of trauma enables healthcare professionals to plan preventive measures aimed at improving the assistance. Key words: Aged; Wounds and Injuries; Disease; Drug Utilization.

Se objetivó identificar el perfil sociodemográfico de ancianos víctimas de trauma, caracterizar condiciones preexistentes y medicamentos tomados en casa, y calcular índices de trauma y evolución clínica. Se realizó un análisis retrospectivo y exploratorio de una base de datos de un hospital general terciario entre 2008 y 2010. Se estudiaron 131 ancianos, media of 69,9 años, 73,3% hombres, 55,1% casados, 54,7% jubilados, 65,6% tienen condiciones preexistentes y 48,9% estaban tomando medicación en casa. Hubo representación de las caídas (31,3%), seguido de atropello (28,2%). La región cabeza/cuello fue el más afectado (59,5%). Prevaleció trauma moderado (44,3%), con condiciones de supervivencia después del evento (80,2%). Se observó una asociación entre mecanismo de lo trauma y enfermedad previa (p=0,01) y entre mecanismo de lo trauma y sexo (p=0,03). El conocimiento de las variables que intervienen con ancianos víctimas de trauma permite a los profesionales de la salud planificar medidas preventivas para mejorar su asistencia.

[Adenosine for treatment of ischemic pain in thromboangiitis obliterans. A case report]. / Adenosin zur Behandlung von Ischämieschmerzen bei Thrombangiitis obliterans. Ein Fallbericht.

Treating ischemic pain is often unsatisfactory. Current findings demonstrate that patients with chronic ischemia may develop sensory neuropathy and signs of central sensitization. This issue makes is reasonable treating with conventional analgesics and drugs against neuropathic pain. Adenosine has also a pain reducing effect in neuropathic pain which makes it a possible therapeutic option in ischemic pain.We report of a patient with thromboangiitis obliterans. We treated his pain with a broad analgesic therapy and administered adenosine intravenously, which resulted in a reduction of pain for several hours. Afterwards the patient received buflomedil to increase adenosine plasma levels. A long term pain reduction could be achieved. Modulation of adenosine demonstrates an experimental approach in the therapy of ischemic pain in thromboangiitis obliterans.

Ischemic conditioning of the stomach may reduce the incidence of esophagogastric anastomotic leaks complicating esophagectomy: a hypothesis.

Esophagogastric anastomotic leaks are a major cause of morbidity and mortality after esophagectomy. Occult ischemia of the mobilized and partially devascularized gastric fundus is an important cause of esophagogastric leaks. The author hypothesizes that the vascularity of the gastric fundus can be improved, and anastomotic leaks reduced, by a process of ischemic conditioning (delay phenomenon). Laparoscopic partial gastric devascularization could be performed 2-3 weeks before esophagectomy. The gastric fundus would have time to re-establish an abundant blood supply before being mobilized and anastomosed to the esophagus. Since laparoscopic partial devascularization could be done at the time of laparoscopic cancer staging, gastric ischemic conditioning would not necessarily add cost or morbidity to the overall treatment of esophageal cancer. Laboratory and clinical evidence are presented to support this hypothesis.

The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review.

There are two components to the reperfusion syndrome, which follows extremity ischemia. The local response, which follows reperfusion, consists of limb swelling with its potential for aggravating tissue injury and the systemic response, which results in multiple organ failure and death. It is apparent that skeletal muscle is the predominant tissue in the limb but also the tissue that is most vulnerable to ischemia. Physiological and anatomical studies show that irreversible muscle cell damage starts after 3 h of ischemia and is nearly complete at 6 h. These muscle changes are paralleled by progressive microvascular damage. Microvascular changes appear to follow rather than precede skeletal muscle damage as the tolerance of capillaries to ischemia vary with the tissue being reperfused. The more severe the cellular damage the greater the microvascular changes and with death of tissue microvascular flow ceases within a few hours-the no reflow phenomenon. At this point tissue swelling ceases. The inflammatory responses following reperfusion varies greatly. When muscle tissue death is uniform, as would follow tourniquet ischemia or limb replantation, little inflammatory response results. In most instances of reperfusion, which follows thrombotic or embolic occlusion, there will be a variable degree of ischemic damage in the zone where collateral blood flow is possible. The extent of this region will determine the magnitude of the inflammatory response, whether local or systemic. Only in this region will therapy be of any benefit, whether fasciotomy to prevent pressure occlusion of the microcirculation, or anticoagulation to prevent further microvascular thrombosis. Since many of the inflammatory mediators are generated by the act of clotting, anticoagulation will have additional benefit by decreasing the inflammatory response. In instances in which the process involves the bulk of the lower extremity, amputation rather than attempts at revascularization may be the most prudent course to prevent the toxic product in the ischemic limb from entering the systemic circulation.

Effect of lung allograft ischaemia duration on postreperfusion graft function and postoperative course.

Lung transplantation is limited by the effects of ischaemia. Previous clinical studies related graft ischaemia duration to post-operative pulmonary function in the ICU, morbidity, and overall survival. This report describes the intraoperative pulmonary allograft function immediately after reperfusion. 23 lung transplantations (15 bilateral, 8 single) were analysed. Donor selection and organ procurement were identical. After pulmonary vasodilation with prostacyclin, allografts were flush-perfused with cold modified Euro-Collins solution. Mean duration of lung ischaemia was 255.1 +/- 35.1 min (190-314 min). Ischaemia times did not differ with respect to the recipient's disease or the use of extracorporeal circulation. After reperfusion, oxygenation indices deteriorated in 73.9% of patients compared with the native lungs (313.4 +/- 163.5 vs 427.2 +/- 96.1, p = 0.006). Linear regression analysis and subgroup analysis both revealed a significant influence of the duration of allograft ischaemia on early transplant function. Ischaemia of more than 4 hours resulted in an acceptable but significantly lower PaO2 (254.9 +/- 143.3 mmHg vs 463.0 +/- 149.2 mmHg, p = 0.011). However, mean time until extubation and time spent in the ICU were not affected. It is concluded that flush-perfusion of the lung with modified Euro-Collins solution provides reliable preservation of lung function up to four hours. Longer ischaemia, up to six hours, is followed by an acceptable but progressively reduced early transplant function.

[Oxygen radicals and postischemic organ damage--pathophysiology, clinical relevance and therapy]. / Sauerstoffradikale und postischämische Organschäden--Pathophysiologie, klinische Relevanz und Therapie.

Postischemic damages after ischemia and reperfusion are of growing clinical relevance. It was assumed that these damages were due to hypoxia. It has been shown that during reperfusion oxygen radicals are generated in high concentrations adding significantly to the damage. These oxygen radicals are generated by the hypoxanthine-xanthine oxidase system. They do not only damage directly but trigger the accumulation and migration of PMN-leukocytes within the inflicted tissue. PMN-leukocytes induce a non-specific postischemic inflammatory reaction which is responsible for the severe reperfusion damages. Oxygen radicals can be treated successfully by so-called radical scavengers. Thereby, it is essential to initiate the therapy during the so-called "therapeutic window", a time interval in which reperfusion aggravates the ischemic lesions. Only few clinical studies have been performed. The results concerning scavenger treatment after myocardial infarction have been disappointing. In transplantation surgery, however, antioxidative therapy has proven to be beneficial. Well-defined double blind randomized well-stratified clinical studies are now essential in order to assess the possibilities of antioxidative therapy after time-limited ischemia and reperfusion.

Monitoring for spinal cord ischemia by use of the evoked spinal cord potentials during aortic aneurysm surgery.

PURPOSE: This clinical study was to evaluate changes of evoked spinal cord potentials (ESCPs) elicited by direct spinal cord stimulation and to determine their relation to spinal cord ischemia during aortic aneurysm surgery. METHODS: We monitored descending ESCPs from the thoracic spinal cord and lumbar enlargement after cervical spinal cord stimulation (thoracic descending ESCP and lumbar descending ESCP), and segmental ESCP at lumbar enlargement elicited by bilateral tibial nerve stimulation in 22 aortic aneurysm surgical operations. RESULTS: ESCP changes were classified into three types: (1) decrease of amplitude in lumbar descending ESCP and segmental ESCP; (2) decrease of amplitude in segmental ESCP alone; (3) decrease of amplitude in all ESCPs. The late negative waves of both lumbar descending ESCP and segmental ESCP were more sensitive than other components of ESCPs. Postoperative paraplegia occurred in the two cases that showed persistent diminution of amplitude in the late negative waves. Segmental ESCP was less reliable than lumbar descending ESCP, because it depended entirely on the adequate perfusion of the lower extremities. CONCLUSIONS: Lumbar descending ESCP was the best method for the spinal cord ischemia during aortic aneurysm surgery. Spinal cord ischemia could be detected by diminution in the amplitude of the late negative wave of lumbar descending ESCP. The recovery amplitude of the late negative wave after declamping correlated with the neurologic outcome.

Splanchnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfunction syndrome.

The incidence of multiple organ failure syndrome (MOFS) has increased dramatically in most intensive care units (ICU) in the United States and is now the leading cause of death after sepsis, trauma, and burns (1). Despite advances in resuscitation, availability of potent antibiotics, and modern techniques of organ support (2), the survival of critically ill patients with MOFS has not significantly improved since the syndrome was first described over 2 decades ago (3). In the ICU, the monitoring and management of critically ill patients with MOFS has relied, in large part, on readily available measurements of global hemodynamics and oxygen transport. Given the increased understanding of the special role of splanchnic hypoperfusion in the pathophysiology of sepsis and MOFS (4-5), investigators have focused more recently on regional blood flow and oxygen metabolism in these patients (6). In this article, we first present a clinical overview of sepsis and MOFS. Current concepts of the pathogenesis and pathophysiology of MOFS are discussed, with particular emphasis on the roles of splanchnic ischemia and gut barrier failure in the development of both sepsis and the maintenance of the systemic inflammatory response that leads to MOFS. Alterations in both global and regional oxygen transport in septic shock are described to emphasize the limitations of global monitoring in the assessment of splanchnic tissue oxygenation. The role of gastric tonometry in the monitoring of splanchnic oxygenation and its utility in critically ill patients is then analyzed. In addition, the effects and clinical implications of commonly used vasoactive agents on intestinal oxygenation are discussed. Finally, novel therapeutic strategies based on the "gut-origin hypothesis" of MOFS are reviewed.

Proteçäo farmacológica da medula espinal isquêmica / Pharmacological protection of the ischemic spinal cord

Estudou-se a açao protetora da quetamina (30mg/Kg, EV) e da clorpromazina (2mg/Kg,EV), sobre a medula espinal de ratos Wistar, submetida à isquemia de 30 min, por oclusao da aorta torácica, seguida de reperfusao. Em 70 animais, com peso médio de 380g, divididos em 7 grupos iguais, obtiveram-se os seguintes resultados porcentuais referentes à integral recuperaçao sensitivo-motora: 1) "Sham-operation": 100 por cento; 2) isquemia-reperfusao: 0 por cento; 3) quetamina, 1 min antes da isquemia: 30 por cento; 4) quetamina, 10 min. antes da isquemia: 50 por cento; 5) clorpromazina, 1 min antes da isquemia: 50 por cento; 6) clorpromazina, 1 min. antes da reperfusao: 10 por cento; 7) quetamina+clorpromazina, 1 min antes da isquemia: 60 por cento. Tanto a quetamina quanto a clorpromazina protegeram parte dos animais cuja medula espinal fora submetida à isquemia-reperfusao. Contudo, ao se comparar os animais protegidos, as diferenças de resultados só alcançaram significância estatística entre os grupos 6 e 7. O estudo histológico, por microscopia óptica, confirmou a açao protetora de ambos os agentes farmacológicos. A perfusao do espaço subaracnóideo dos animais cuja medula espinal fora submetida à isquemia-reperfusao demonstrou quantidade excessiva dos aminoácidos neuroexcitadores, L-aspartato e L-glutamato.