Lactate and base excess (BE) as markers of hypoperfusion and mortality in traumatic hemorrhagic shock in patients undergoing Damage Control: a historical cohort / Lactato e excesso de base (BE) como marcadores de hipoperfusão e mortalidade no choque hemorrágico traumático em pacientes submetidos à estratégia de controle de danos - Uma coorte histórica

ABSTRACT Introduction: hemorrhagic shock is a significant cause of trauma-related deaths in Brazil and worldwide. This study aims to compare BE and lactate values at ICU admission and twenty-four hours after in identifying tissue hypoperfusion and mortality. Methods: examines a historical cohort of trauma patients over eitheen years old submittet to damage control resuscitation approch upon hospital admission and were then admitted to the ICU. We collected and analyzed ISS, mechanism and type of trauma, need for renal replacement therapy, massive transfusion. BE, lactate, pH, bicarbonate at ICU admission and twenty-four hours later, and mortality data. The patients were grouped based on their BE values (≥-6 and <-6mmol/L), which were previously identified in the literature as predictors of severity. They were subsequently redivided using the most accurate values found in this sample. In addition to performing multivariate binary logistic regression. The data were compared using several statistical tests due to diversity and according to the indication for each variable. Results: there were significant changes in perfusion upon admission to the Intensive Care Unit. BE is a statistically significant value for predicting mortality, as determined by using values from previous literature and from this study. Conclusion: the results demonstrate the importance of monitoring BE levels in the prediction of ICU mortality. BE proves to be a valuable bedside marker with quick results and wide availability.

RESUMO Introdução: o choque hemorrágico é a principal causa reversível de morte no trauma no Brasil e no mundo. Objetivo: comparar o valor de BE ao do lactato na admissão da UTI e vinte e quatro horas após o internamento na identificação de hipoperfusão tecidual e predição de mortalidade Método: coorte histórica de pacientes traumatizados, maiores de dezoito anos, submetidos à estratégia de controle de danos na admissão hospitalar, seguido de internamento em UTI. Foram coletados e analisados ISS, mecanismo e tipo de trauma, necessidade de terapia de substituição renal e transfusão maciça; BE, lactato, pH e bicarbonato coletados na admissão da UTI e vinte e quatro horas após, e a mortalidade. Os pacientes foram divididos em grupos conforme valores de BE (≥-6 e <-6mmol/L) já descritos na literatura como preditores de gravidade, e após redivididos de acordo com os valores de melhor acurácia encontrados nesta amostra, além de realização de regressão logística binária multivariada. Os dados foram comparados através de diversos testes estatísticos devido a diversidade e conforme a indicação para cada variável. Resultados: houve alterações perfusionais impactantes já na admissão da UTI. BE manteve-se com valor estatisticamente significativo para predição de mortalidade tanto quando utilizado os valores já conhecidos da literatura como quando aplicados os valores neste estudo identificados. Conclusão: valores de BE e de lactato foram capazes de predizer hipoperfusão tecidual e mortalidade nos dois momentos estudados, quando comparados, o BE tem boa performance como preditor de mortalidade, com rápido resultado e ampla disponibilidade.

Modelo alternativo para o treinamento de técnicas de microssuturas em "patch" de pericárdio bovino / Alternative model for training microsuture techniques in bovine pericardium patches

Introdução: As técnicas microcirúrgicas caracterizam-se pela aplicação de manobras e suturas em estruturas milimétricas com o auxílio de lentes de aumento. São técnicas complexas, utilizadas em diversas especialidades médicas, que demandam grande habilidade e treinamento antes da aplicação em humanos. O objetivo é desenvolver um modelo de baixo custo e alta fidelidade, para o treinamento de técnicas de microcirurgia, utilizando um fragmento de patch de pericárdio bovino. Método: São utilizados para a confecção deste modelo segmentos remanescentes de uma placa de pericárdio bovino, previamente utilizado em reparos vasculares. O material é recortado em duas partes simétricas e suas extremidades fixadas aos campos cirúrgicos, com auxílio de clamps. A borda superior de cada uma das partes é, então, suturada à borda inferior com fio de Prolene 8-0, de maneira que cada uma forme uma estrutura tubular. Posteriormente, as extremidades tubulares livres passam pela dissecção da camada adventícia e são suturadas entre si, mimetizando uma anastomose vascular término-terminal. Resultados: Com o modelo, simulam-se os mesmos inconvenientes/ dificuldades presentes nas suturas vasculares humanas, como a delaminação de camadas, excesso da camada adventícia e risco de sutura inadvertida da parede posterior, provando sua utilidade na aquisição de habilidades microcirúrgicas básicas, sem necessidade de manipulação de tecidos humanos ou animais. A prática neste modelo pode ocorrer dentro do próprio centro cirúrgico e emprega materiais que seriam descartados. Conclusão: A utilização do pericárdio bovino para confecção de suturas milimétricas mimetiza o tecido vascular humano e é um procedimento de baixo custo, que possibilita o treinamento de habilidades microcirúrgicas.

Introduction: Microsurgical techniques are characterized by the application of maneuvers and sutures to millimetric structures with the aid of magnifying lenses. These are complex techniques, used in various medical specialties, which require great skill and training before applying them to humans. The objective is to develop a lowcost and high-fidelity model for training microsurgery techniques using a fragment of bovine pericardium patch. Method: Remaining segments of a bovine pericardium plate, previously used in vascular repairs, are used to create this model. The material is cut into two symmetrical parts, and its ends are fixed to the surgical drapes with the aid of clamps. The upper edge of each part is then sutured to the lower edge with 8-0 Prolene thread so that each one forms a tubular structure. Subsequently, the free tubular ends undergo dissection of the adventitial layer and are sutured together, mimicking an end-to-end vascular anastomosis. Results: With the model, the same inconveniences/ difficulties present in human vascular sutures are simulated, such as delamination of layers, excess of the adventitial layer, and risk of inadvertent suturing of the posterior wall, proving its usefulness in the acquisition of basic microsurgical skills, without need to manipulate human or animal tissues. Practice in this model can take place within the surgical center itself and uses materials that would otherwise be discarded. Conclusion: The use of bovine pericardium to create millimetric sutures mimics human vascular tissue and is a low-cost procedure that allows the training of microsurgical skills.

Left Nonrecurrent Laryngeal Nerve: A Very Unusual Finding during Thyroid Surgery.

Background: Identifying the inferior laryngeal nerve is one of the main concerns in thyroid surgery. The typical recurrent position occurs due the relative position between the vagus nerve and the larynx during the last 3 branchial arches development. In rare cases, this nerve does not loop under the right subclavian artery or the aortic arch. This abnormality is present in 0.7% of patients and is associated with the presence of anatomical vascular anomalies. The left non-recurrent inferior laryngeal nerve is an even rarer abnormality, with only six cases described in the literature to date. Method: A 46- years old female patient referred to total thyroidectomy for symptomatic multinodular benign goiter. Results: A left non-recurrent inferior laryngeal nerve was found with difficulty and then a partial thyroidectomy was performed. CT scan showed dextroposition of the vessels of the base of the heart and an aberrant left subclavian artery. Conclusion: An association of a right-sided aortic arch and aberrant left subclavian artery, or the presence of situs inversus, although rare anatomical variations, are associated to a non-recurrent inferior left laryngeal nerve. Proper identifying these abnormalities may help to properly identify and salvage this structure.

DO THE IMMUNOSUPPRESSIVE DRUGS AFFECT THE HYPOTHALAMIC NUCLEI INVOLVED IN THE REGULATION OF FOOD INTAKE? AN EXPERIMENTAL STUDY. / DROGAS IMUNOSSUPRESSORAS AFETAM OS NÚCLEOS HIPOTALÂMICOS ENVOLVIDOS NA INGESTÃO ALIMENTAR ? ESTUDO EXPERIMENTAL.

PURPOSE: Immunosuppressive drugs are essential for reducing the rejection risk in post-transplant patients, which is commonly associated with this procedure. However, side effects of those drugs on the hypothalamic nuclei involved in the food intake regulation, excessive weight gain, and also associated comorbidities are still unknown. The purpose of this study was to analyze possible changes in the neuronal morphology and cell density in the paraventricular nuclei, lateral hypothalamic area, dorsomedial nuclei, and ventromedial and arcuate nuclei in Wistar rats submitted to immunosuppressive treatment with tacrolimus (TAC) or mycophenolate mofetil (MMF). METHODS: Adult male Wistar rats were randomly assigned to the following groups according to the oral treatment administered for 14 weeks: control, sham (placebo), TAC (1 mg/kg of weight), and MMF (30 mg/kg of weight). After treatment, the animals were sacrificed and their brains fixed for later histological staining. Subsequently, the slides were photodocumented for stereological analysis of the hypothalamic nuclei. RESULTS: All experimental groups showed a weight gain throughout the study. There was no significant difference in neuronal density/number of cells in the hypothalamic nuclei between groups. Morphological changes were not detected in the hypothalamic neurons. CONCLUSION: Treatments with immunosuppressants could not modify the morphological and cell density aspects of the hypothalamic nuclei during this supplementation period.

OBJETIVO: Drogas imunossupressoras são indispensáveis para pacientes pós-transplante, diminuindo, significativamente, os riscos de rejeição inerentes a este tipo de procedimento. No entanto, seus efeitos colaterais sobre os núcleos hipotalâmicos envolvidos na regulação da ingestão de alimentos e o efeito no excessivo ganho de peso e suas comorbidades associadas são desconhecidos. Analisar a ocorrência de alterações morfológicas dos núcleos paraventricular, área hipotalâmica lateral, dorsomedial, ventromedial e arqueado em ratos Wistar submetidos ao tratamento imunossupressor com Tacrolimus (TAC) ou Micofenolato Mofetil (MMF). MÉTODOS: Foram utilizados Ratos Wistar machos adultos distribuídos, randomicamente, em quatro grupos de acordo com o tratamento oral utilizado por 14 semanas: Controle; Sham (Placebo); Tacrolimus (TAC 1mg/kg peso) e Micofenolato Mofetil (MMF 30mg/kg peso). Ao final do tratamento, os animais foram eutanasiados e seus encéfalos fixados para o processamento histológico. Posteriormente, as lâminas foram fotodocumentadas para o desenvolvimento da análise estereológica dos corpos celulares dos neurônios dos núcleos hipotalâmicos, tendo como parâmetros a densidade neuronal e no número de neurônios. RESULTADOS: Todos os grupos estudados mostraram curva de ganho de peso ponderal durante todo o período de experimento. Não houve diferença significativa na densidade neuronal e no número de neurônios hipotalâmicos dos núcleos hipotalâmicos entre os grupos estudados. Não foram detectadas alterações morfológicas dos corpos celulares dos neurônios hipotalâmicos capazes de serem imputadas ao uso dos imunossupressores envolvidos no estudo. CONCLUSÃO: O tratamento dos animais experimentais com os imunossupressores não evidenciou alterações no número e densidade dos corpos celulares dos neurônios dos núcleos hipotalâmicos estudados.

Liver transplantation for the treatment of iatrogenic bile duct injury / Transplante hepático no tratamento da lesão iatrogênica da via biliar

ABSTRACT Objective: to assess the outcomes of our patients who were subjected to LT for iatrogenic bile duct injury. Methods: all patients who underwent LT for treatment of complications of biliary duct injury were included in the study. Medical records and study protocols of these patients were retrospectively analyzed to determine demographic and clinical characteristics, treatment, and outcome of the patients. Results: of a total of 846 liver transplants performed, 12 (1.4%) were due to iatrogenic bile duct injury: 10 (83.3%) occurred during cholecystectomy, 1 (8.3%) following chemoembolization, and 1 (8.3%) during laparotomy to control abdominal bleeding. Cholecystectomy was performed by open access in 8 patients and by laparoscopic access in two . There were 8 female (66.7%) and 4 male (33.3%) with a mean age of 50.6 ± 13.1 years (range 23 to 70 years). All transplants were performed with livers from cadaveric donors. The mean operative time was 558.2 ± 105.2 minutes (range, 400-782 minutes). Biliary reconstruction was performed with Roux-en-Y hepaticojejunostomy in 11 patients and choledochocholedochostomy in one. Seven patients died (58.3%) and five (41.7%) were alive during a mean followed up of 100 months (range 18 to 118 months). Conclusion: liver transplantation in patients with iatrogenic bile duct injury is a complex procedure with elevated morbimortality.

RESUMO Objetivo: avaliar os resultados dos nossos pacientes que foram submetidos a transplante hepático por lesão iatrogênica do ducto biliar. Métodos: todos os pacientes que foram submetidos a transplante hepático para tratamento de complicações da lesão do ducto biliar foram incluídos no estudo. Os prontuários e protocolos de estudo desses pacientes foram analisados retrospectivamente para determinar características demográficas e clínicas, tratamento e desfecho dos pacientes. Resultados: de um total de 846 transplantes hepáticos realizados, 12 (1,4%) foram por lesão iatrogênica de via biliar: 10 (83,3%) ocorreram durante colecistectomia, 1 (8,3%) após quimioembolização e 1 (8,3%) durante laparotomia para controle de sangramento abdominal. A colecistectomia foi realizada por via aberta em 8 pacientes e por via laparoscópica em dois. Haviam 8 mulheres (66,7%) e 4 homens (33,3%), com média de idade de 50,6 ± 13,1 anos (variação de 23 a 70 anos). Todos os transplantes foram realizados com fígados de doadores cadavéricos. O tempo operatório médio foi de 565,2 ± 106,2 minutos (variação de 400-782 minutos). A reconstrução biliar foi realizada com hepaticojejunostomia em Y de Roux em 11 pacientes e coledococoledocostomia em um. Sete pacientes morreram (58,3%) e cinco (41,7%) estavam vivos durante um seguimento médio de 100 meses (variação de 18 a 118 meses). Conclusão: o transplante hepático em pacientes com lesão iatrogênica das vias biliares é um procedimento complexo com elevada morbimortalidade.

Liver regeneration after extensive hepatectomy in rats: effect of preoperative chemotherapy with intravenous 5-fluorouracil

Purpose: To evaluate the effect of preoperative intravenous chemotherapy with 5-fluorouracil on liver regeneration in an experimental model of major hepatectomy in rats. Methods: Wistar rats were divided into two groups of 20 animals each and submitted to 70% hepatectomy 24 h after intravenous injection of 5-fluorouracil 20 mg/kg (fluorouracil group, FG) or 0.9% saline (control group, CG). After hepatectomy, each group was subdivided into two subgroups of 10 animals each according to the day of sacrifice (24 h or 7 days). Liver weight during regeneration, liver regeneration rate using Kwon formula, and the immunohistochemical markers proliferating cell nuclear antigen (PCNA) and Ki-67 were used to assess liver regeneration. Results: At early phase (24 h after hepatectomy) it was demonstrated the negative effect of 5-fluorouracil on liver regeneration when assessed by Kwon formula (p < 0.0001), PCNA analysis (p = 0.02). With regeneration process complete (7 days), it was possible to demonstrate the sustained impairment of chemotherapy with 5-fluorouracil on hepatocytes regeneration phenomenon when measured by Kwon formula (p = 0.009), PCNA analysis (p = 0.0001) and Ki-67 analysis (0.001). Conclusions: Preoperative chemotherapy with intravenous 5-fluorouracil negatively affected the mechanisms of liver regeneration after major hepatectomy in rats.

Analysis of Surgical Recurrence after Larynx Microsurgery for Benign Lesions.

Introduction The study of larynx lesions is of great importance. More than 50% of people with vocal complaints have benign vocal fold alterations and some require surgery. Objective To determine which factors are related to surgical recurrence of benign laryngeal lesions and to determine which videolaryngoscopic diagnoses are related to the risk or protection of surgical relapses over time. Methods Observational, analytical, cross-sectional study with retrospective data collection of 1,383 surgeries in 1,301 patients. Results The mean age at the first surgery was 39.2 years old. The predominant gender was female (65.6%). There were 396 cases of polyps (25.34%), 349 cases of cysts (22.33%), 261 cases of Reinke edema (16.7%), 175 cases of nodules (11.2%), 153 cases of minor structural alterations (MSAs) (9.79%), 94 cases of leukoplakia (6.01%), 77 cases of granulomas (4.93%) and 58 cases of pseudocysts (3.71%). The age presented statistical significance with the risk of surgical relapses ( p = 0.016). Male gender was associated with the greatest chance of relapse. Diagnosis of granuloma ( p < 0.001) and of leukoplakia ( p < 0.001) were associated with a higher risk of surgical recurrence. Cyst diagnosis was associated with protection ( p = 0.015) in relation to the chance of further surgeries. Patients with associated lesions, bilaterals or voice professionals did not present a statistically significant association with surgical recurrence. Conclusion Age and gender are statistically related to the increase of surgical relapses. Leukoplakia and granuloma are associated with increased surgical relapses. Patients submitted to cyst microsurgery appear to be protected against surgical recurrence.

Boa qualidade de vida após mais de uma década de transplante hepático inter-vivos / Good quality of life after more than a decade of living donor liver transplantation

ABSTRACT BACKGROUND: Receptors of living donor liver transplantation (LDLT) have higher rate of postoperative biliary and vascular complications that may reduce posttransplant quality of life (QOL) due to the need of invasive and repetitive treatments. OBJECTIVE: The purpose of our study is to assess the various aspects of QOL of receptors undergoing LDLT after 10 years of transplantation and to identify potential factors that might be associated with impaired QOL. METHODS: Data of all patients with more than 10 years of LDLT were retrospectively evaluated. Patients were interviewed through a quality of life questionnaire (SF-36). RESULTS: From a total of 440 LT performed in 17 years (from September 1991 through December 2008), 78 patients underwent LDLT, of which 27 were alive and 25 answered completely the questionnaire. There were 17 (68%) men and 8 (32%) women, with a mean age of 38.6±18.5 years at the time of transplantation and mean follow up time of 15.1±1.9 years. The average MELD was 16.4±4.9 and the main indication for LT was hepatic cirrhosis caused by hepatitis B virus (32%). When compared to the general po­pulation, LDLT patients had lower mental health score (66.4 vs 74.5, P=0.0093) and higher vitality score (87.8 vs 71.9, P<0.001), functional aspects (94.6 vs 75.5, P=0.002), social aspects (93 vs 83.9, P=0.005), physical aspects (92 vs 77.5, P=0.006), and emotional aspects (97.33 vs 81.7, P<0.001). General health status (73.28 vs 70.2, P=0.074) and pain (78.72 vs 76.7, P=0.672) scores were similar in both groups. CONCLUSION: It is concluded that the various aspects LDLT recipients' QOF are similar to those of the general population more than a decade after the transplant, except for the mental health domain which is lower.

RESUMO CONTEXTO: Receptores de transplante hepático inter-vivo (THIV) apresentam elevada taxa de complicações biliares e vasculares pós-operatórias que podem reduzir a qualidade de vida (QV) devido à necessidade de tratamentos invasivos e repetitivos. OBJETIVO: O objetivo deste estudo é avaliar os vários aspectos da qualidade de vida dos pacientes submetidos a THIV após 10 anos de transplante e identificar possíveis fatores que possam estar associados à diminuição da QV. MÉTODOS: Os dados de todos os pacientes com mais de 10 anos de THIV foram avaliados retrospectivamente. Os pacientes foram entrevistados por meio de um questionário de qualidade de vida (SF-36). RESULTADOS: Do total de 440 transplantes hepáticos realizados em 17 anos (setembro de 1991 a dezembro de 2008), 78 pacientes foram submetidos a THIV, dos quais 27 estavam vivos e 25 responderam completamente ao questionário. Destes, 17 (68%) homens e 8 (32%) mulheres, com idade média de 38,6±18,5 anos no momento do transplante e tempo médio de acompanhamento de 15,1±1,9 anos. O MELD médio foi de 16,4±4,9 e a principal indicação para o transplante hepático foi cirrose hepática causada pelo vírus da hepatite B, 32%. Quando comparado com a população geral, os pacientes submetidos a THIV apresentaram menor escore de saúde mental (66,4 vs 74,5; P=0,0093) e escores mais altos de vitalidade (87,8 vs 71,9; P<0,001), aspectos funcionais (94,6 vs 75,5; P=0,002), aspectos sociais (93 vs 83,9; P=0,005), aspectos físicos (92 vs 77,5; P=0,006), e aspectos emocionais (97,33 vs 81,7; P<0,001). Os escores do estado geral de saúde (73,28 vs 70,2; P=0,074) e de dor (78,72 vs 76,7; P=0,672) eram similares nos dois grupos. CONCLUSÃO: Conclui-se que os vários aspectos da QV dos receptores de transplante hepático inter-vivo são semelhantes aos da população geral mais de uma década após o transplante, exceto o domínio da saúde mental que é menor.

DOES THE ASSOCIATION OF TACROLIMUS AND MYCOPHENOLATE MOFETIL CHANGE THE HEALING OF THE ABDOMINAL WALL? STUDY IN RATS SUBMITTED TO ISCHEMIA AND KIDNEY REPERFUSION.

BACKGROUND: Tacrolimus and mycophenolate mofetil are immunosuppressive agents widely used on the postoperative period of the transplants. AIM: To evaluate the influence of the association of them on the abdominal wall healing in rats. METHODS: Thirty-six Wistar rats were randomly assigned in three groups of 12. On the early postoperative period, four of the control group and three of the experimental groups died. The three groups were nominated as follow: control group (GC, n=8); group I (GI, n=11, standard operation, mycophenolate mofetil and tacrolimus); group II (GII, n=10, standard operation, mycophenolate mofetil and tacrolimus). The standard operation consisted of right total nephrectomy and 20 min ischemia of the left kidney followed by reperfusion. Both NaCl 0.9% and the immunosuppressive agents were administered starting on the first postoperative day and continuing daily until the day of death on the 14th day. On the day of their deaths, two strips of the anterior abdominal wall were collected and submitted to breaking strength measurement and histological examination. RESULTS: There were no significant differences in wound infection rates (p=0,175), in the breaking strength measurement and in the histological examination among the three groups. CONCLUSION: The combination of the immunosuppressive agents used in the study associated with renal ischemia and reperfusion does not interfere in the abdominal wall healing of rats.

Drogas imunossupressoras afetam os núcleos hipotalâmicos envolvidos na ingestão alimentar ? estudo experimental / Do the immunosuppressive drugs affect the hypothalamic nuclei involved in the regulation of food intake? an experimental study

RESUMO - RACIONAL: Drogas imunossupressoras são indispensáveis para pacientes pós-transplante, diminuindo, significativamente, os riscos de rejeição inerentes a este tipo de procedimento. No entanto, seus efeitos colaterais sobre os núcleos hipotalâmicos envolvidos na regulação da ingestão de alimentos e o efeito no excessivo ganho de peso e suas comorbidades associadas são desconhecidos. OBJETIVO: Analisar a ocorrência de alterações morfológicas dos núcleos paraventricular, área hipotalâmica lateral, dorsomedial, ventromedial e arqueado em ratos Wistar submetidos ao tratamento imunossupressor com Tacrolimus (TAC) ou Micofenolato Mofetil (MMF). MÉTODOS: Foram utilizados Ratos Wistar machos adultos distribuídos, randomicamente, em quatro grupos de acordo com o tratamento oral utilizado por 14 semanas: Controle; Sham (Placebo); Tacrolimus (TAC 1mg/kg peso) e Micofenolato Mofetil (MMF 30mg/kg peso). Ao final do tratamento, os animais foram eutanasiados e seus encéfalos fixados para o processamento histológico. Posteriormente, as lâminas foram fotodocumentadas para o desenvolvimento da análise estereológica dos corpos celulares dos neurônios dos núcleos hipotalâmicos, tendo como parâmetros a densidade neuronal e no número de neurônios. RESULTADOS: Todos os grupos estudados mostraram curva de ganho de peso ponderal durante todo o período de experimento. Não houve diferença significativa na densidade neuronal e no número de neurônios hipotalâmicos dos núcleos hipotalâmicos entre os grupos estudados. Não foram detectadas alterações morfológicas dos corpos celulares dos neurônios hipotalâmicos capazes de serem imputadas ao uso dos imunossupressores envolvidos no estudo. CONCLUSÃO: O tratamento dos animais experimentais com os imunossupressores não evidenciou alterações no número e densidade dos corpos celulares dos neurônios dos núcleos hipotalâmicos estudados.

ABSTRACT - BACKGROUND: Immunosuppressive drugs are essential for reducing the rejection risk in post-transplant patients, which is commonly associated with this procedure. However, side effects of those drugs on the hypothalamic nuclei involved in the food intake regulation, excessive weight gain, and also associated comorbidities are still unknown. PURPOSE: The purpose of this study was to analyze possible changes in the neuronal morphology and cell density in the paraventricular nuclei, lateral hypothalamic area, dorsomedial nuclei, and ventromedial and arcuate nuclei in Wistar rats submitted to immunosuppressive treatment with tacrolimus (TAC) or mycophenolate mofetil (MMF). METHODS: Adult male Wistar rats were randomly assigned to the following groups according to the oral treatment administered for 14 weeks: control, sham (placebo), TAC (1 mg/kg of weight), and MMF (30 mg/kg of weight). After treatment, the animals were sacrificed and their brains fixed for later histological staining. Subsequently, the slides were photodocumented for stereological analysis of the hypothalamic nuclei. RESULTS: All experimental groups showed a weight gain throughout the study. There was no significant difference in neuronal density/number of cells in the hypothalamic nuclei between groups. Morphological changes were not detected in the hypothalamic neurons. CONCLUSION: Treatments with immunosuppressants could not modify the morphological and cell density aspects of the hypothalamic nuclei during this supplementation period.

Cerebrospinal Fluid Infection with External Ventricular Drainage: Analysis of the Risk Factors in 110 Patients of a Single Institution

Objectives External ventricular drainage (EVD) is extensively used in the neurosurgical practice with the purpose of monitoring the intracranial pressure and draining the cerebrospinal fluid (CSF). Despite its remarkable benefits, the technique is not devoid of risks, notably infections, which have been reported in up to 45% of the cases. Methods A retrospective analysis of the main risk factors for CSF infection in neurosurgical patients submitted to EVD at a single institution. We recorded and submitted to statistical comparison every risk factor for CSF infection present or absent in each of the 110 EVD patients enrolled, 53 males and 57 females, with an average age of 52.9 years, with different underlying neurosurgical conditions. Results Infection of the CSF occurred in 32 patients (29%). The rate of mortality related to CSF infection was of 18.7% (6 of 32). The risk factors that showed statistical significance for CSF infection in this series were: emergency surgery; length of stay at the intensive care unit (UCI); duration of the EVD; parenchymal and/or intraventricular hemorrhage; simultaneous infections; time of bladder catheterization; and the use of non-disposable adhesive drapes as part of the preparation of the wound area. Conclusions Infection of the CSF in patients submitted to EVD is multifactorial and a challenge in terms of prevention. Further studies proposing scores with blended risk factors may be useful to prevent and reduce the morbidity and mortality associated with CSF infection.

EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS.

BACKGROUND: Example of wound contraction area at: A) day of surgery in the control group; B) 7PO in the control group; C) day of surgery in the probiotic group; D) 7PO in probiotic group. Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions. AIM: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats. METHODS: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E. RESULTS: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001). CONCLUSIONS: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.

Conservation of both hematocrit and liver regeneration in hepatectomies: a vascular occlusion approach in rats.

BACKGROUND: Hepatectomies promote considerable amount of blood loss and the need to administrate blood products, which are directly linked to higher morbimortality rates. The blood-conserving hepatectomy (BCH) is a modification of the selective vascular occlusion technique. It could be a surgical maneuver in order to avoid or to reduce the blood products utilization in the perioperative period. AIM: To evaluate in rats the BCH effects on the hematocrit (HT) variation, hemoglobin serum concentration (HB), and on liver regeneration. METHODS: Twelve Wistar rats were divided into two groups: control (n=6) and intervention (n=6). The ones in the control group had their livers partially removed according to the Higgins and Anderson technique, while the rats in the treatment group were submitted to BCH technique. HT and HB levels were measured at day D0, D1 and D7. The rate between the liver and rat weights was calculated in D0 and D7. Liver regeneration was quantitatively and qualitatively evaluated. RESULTS: The HT and HB levels were lower in the control group as of D1 onwards, reaching an 18% gap at D7 (p=0.01 and p=0.008, respectively); BCH resulted in the preservation of HT and HB levels to the intervention group rats. BCH did not alter liver regeneration in rats. CONCLUSION: The BCH led to beneficial effects over the postoperative HT and serum HB levels with no setbacks to liver regeneration. These data are the necessary proof of evidence for translational research into the surgical practice. A) Unresected liver; B) liver appearance after the partial hepatectomy (1=vena cava; 2=portal vein; 3=hepatic vein; 4=biliary drainage; 5=hepatic artery).

Does the association of tacrolimus and mycophenolate mofetil change the healing of the abdominal wall? study in rats submitted to ischemia and kidney reperfusion / A associação de tacrolimus e micofenolato mofetil altera a cicatrização da parede abdominal? estudo em ratos submetidos à isquemia e reperfusão renal

ABSTRACT Background: Tacrolimus and mycophenolate mofetil are immunosuppressive agents widely used on the postoperative period of the transplants. Aim: To evaluate the influence of the association of them on the abdominal wall healing in rats. Methods: Thirty-six Wistar rats were randomly assigned in three groups of 12. On the early postoperative period, four of the control group and three of the experimental groups died. The three groups were nominated as follow: control group (GC, n=8); group I (GI, n=11, standard operation, mycophenolate mofetil and tacrolimus); group II (GII, n=10, standard operation, mycophenolate mofetil and tacrolimus). The standard operation consisted of right total nephrectomy and 20 min ischemia of the left kidney followed by reperfusion. Both NaCl 0.9% and the immunosuppressive agents were administered starting on the first postoperative day and continuing daily until the day of death on the 14th day. On the day of their deaths, two strips of the anterior abdominal wall were collected and submitted to breaking strength measurement and histological examination. Results: There were no significant differences in wound infection rates (p=0,175), in the breaking strength measurement and in the histological examination among the three groups. Conclusion: The combination of the immunosuppressive agents used in the study associated with renal ischemia and reperfusion does not interfere in the abdominal wall healing of rats.

RESUMO Racional: O tacrolimus e o micofenolato mofetil são imunossupressores amplamente utilizados no pós-operatório dos transplantes de órgãos. Objetivo: Avaliar os efeitos deles sobre a cicatrização da parede abdominal em ratos. Métodos: Foram utilizados 36 ratos Wistar, distribuídos aleatoriamente em três grupos de 12. No pós-operatório imediato, quatro do grupo controle e três do grupo experimentação morreram. Os três grupos receberam as seguintes denominações: grupo controle (GC, n=8); grupo I (GI, n=11, operação-padrão, micofenolato mofetil e tacrolimus); grupo II (GII, n=10, operação-padrão, micofenolato mofetil e tacrolimus). A operação-padrão consistiu de nefrectomia total à direita, isquemia durante 20 min seguida de reperfusão do rim esquerdo. Solução de NaCl 0,9% e micofenolato mofetil + tracolimus foram administradas a partir do 1° dia do pós-operatório e mantidas até o dia do sacrifício dos animais, no 14° dia. Na data do sacrifício, foram retirados dois fragmentos da parede abdominal para análise da resistência à ruptura e exame histológico. Resultados: Não houve diferença estatisticamente significativa no índice de infecção de ferida operatória (p=0,175), nos valores de resistência de ruptura e nos achados histopatológicos entre os três grupos de animais. Conclusão: Os esquemas de imunossupressão empregados associados ao fenômeno da isquemia-reperfusão renal não induzem fraqueza significativa da cicatriz da parede abdominal em ratos no 14° dia de pós-operatório.

Conservation of both hematocrit and liver regeneration in hepatectomies: a vascular occlusion approach in rats / Hepatectomia hemoconservadora no rato: preservação do hematócrito e da regeneração hepática

ABSTRACT Background: Hepatectomies promote considerable amount of blood loss and the need to administrate blood products, which are directly linked to higher morbimortality rates. The blood-conserving hepatectomy (BCH) is a modification of the selective vascular occlusion technique. It could be a surgical maneuver in order to avoid or to reduce the blood products utilization in the perioperative period. Aim: To evaluate in rats the BCH effects on the hematocrit (HT) variation, hemoglobin serum concentration (HB), and on liver regeneration. Methods: Twelve Wistar rats were divided into two groups: control (n=6) and intervention (n=6). The ones in the control group had their livers partially removed according to the Higgins and Anderson technique, while the rats in the treatment group were submitted to BCH technique. HT and HB levels were measured at day D0, D1 and D7. The rate between the liver and rat weights was calculated in D0 and D7. Liver regeneration was quantitatively and qualitatively evaluated. Results: The HT and HB levels were lower in the control group as of D1 onwards, reaching an 18% gap at D7 (p=0.01 and p=0.008, respectively); BCH resulted in the preservation of HT and HB levels to the intervention group rats. BCH did not alter liver regeneration in rats. Conclusion: The BCH led to beneficial effects over the postoperative HT and serum HB levels with no setbacks to liver regeneration. These data are the necessary proof of evidence for translational research into the surgical practice.

RESUMO Racional: As hepatectomias compreendem considerável perda sanguínea e utilização de hemoderivados, o que diretamente estão relacionados com maior morbimortalidade. A hepatectomia hemoconservadora (HH) é modificação da técnica de oclusão vascular seletiva em hepatectomia. Ela pode ser alternativa cirúrgica para evitar ou diminuir o uso de hemoderivados no perioperatório. Objetivo: Avaliar os efeitos da HH sobre o volume globular (VG), concentração de hemoglobina (HB) e sobre a regeneração hepática em ratos. Métodos: Dois grupos de ratos Wistar foram constituídos: controle (n=6) e intervenção (n=6). Os do grupo controle foram submetidos à hepatectomia parcial de Higgins e Anderson e os do grupo Intervenção à HH. VG e HB foram medidos nos dias D0, D1 e D7. A relação peso do fígado/peso do rato foi calculada em D0 e D7. A regeneração hepática foi analisada qualitativamente e quantitativamente. Resultados: Houve diminuição dos níveis de VG e HB nos ratos do grupo controle a partir de D1, atingindo decréscimo de 18% em D7 (p=0,01 e p=0,008 respectivamente); a HH permitiu a manutenção dos níveis de VG e HB nos ratos do grupo intervenção. A HH não alterou a regeneração hepática. Conclusão: HH resultou em níveis maiores de VG e HB pós-operatórios sem alterar a regeneração hepática. Pode-se considerar estes dados como a prova necessária para a translação à pesquisa clinicocirúrgica.

Effects of probiotics supplementation on skin wound healing in diabetic rats / Suplementação perioperatória com probióticos na cicatrização de feridas cutâneas em ratos diabéticos

ABSTRACT Background: Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions. Aim: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats. Methods: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E. Results: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001). Conclusions: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.

RESUMO Racional: Feridas crônicas em pacientes diabéticos muitas vezes se tornam incuráveis devido à produção prolongada e excessiva de citocinas inflamatórias. A utilização de probióticos modifica a microbiota intestinal e modula reações inflamatórias. Objetivo: Avaliar a influência da suplementação perioperatória com probióticos no processo de cicatrização cutânea em ratos diabéticos. Método: Quarenta e seis ratos foram divididos em quatro grupos (C3, P3, C10, P10) conforme tratamento (P=probiótico ou C=controle, via oral) e dia de eutanásia: 3o ou 10o dia de pós-operatório. Todos os ratos foram induzidos ao diabete melito 72 h antes de iniciar o experimento com aloxana. A suplementação foi iniciada cinco dias antes da operação e mantida até a eutanásia. Foi realizada incisão com bisturi guiada por molde de 2x2 cm e a ferida foi deixada para cicatrizar por segunda intenção. As feridas foram medidas digitalmente. A densitometria de colágeno foi determinada com coloração picrosirius red. A histologia foi avaliada por coloração com H&E. Resultados: A contração da ferida foi maior no grupo P10, o que resultou em menor área cruenta (p=0,011). Houve aumento do colágeno tipo I do 3o para o 10o dia de pós-operatório no grupo P10 (p=0,016), o que não ocorreu no grupo controle (p=0,487). A análise histológica mostrou melhor grau de cicatrização no grupo P10 (p=0,005), com menos polimorfonucleares (p<0,001) e mais neovasos (p=0,001). Conclusões: A suplementação perioperatória de probióticos promove aceleração da cicatrização cutânea em ratos diabéticos, possivelmente por atenuar a resposta inflamatória e aumentar a neovascularização e a deposição de colágeno tipo I.

Postoperative aesthetic and healing features of postectomy using three different surgical techniques: a randomized, prospective, and interdisciplinary analysis / Aspectos estético e cicatricial pós-operatórios da postectomia por três diferentes técnicas cirúrgicas: análise randomizada, prospectiva e interdisciplinar

ABSTRACT Objective: to compare the postoperative esthetic and healing aspects of postectomy performed by different surgical techniques, based on the evaluation of different specialty expert professionals. Methods: prospective and randomized clinical trial enrolling 149 preschool children with a medical indication for circumcision, divided into three groups: postectomy with the hemostatic device Plastibell® (PB group), conventional technique (CV group) and conventional with subcuticular stitches (SC group). Pictures were taken from patients at pre-defined angles on the 30th and 60th postoperative days. Photos were evaluated by three specialists (dermatologist, pediatrician and plastic surgeon), who assigned scores from 1 to 5 regarding the esthetic and healing features at each moment. Grades 4 or 5 from all specialists characterized "best result". Data were analysed to compare the used surgical techniques, the judgments from specialties and postoperative complications. Results: most of the patients obtained the "best result" regarding healing (70%) and esthetics (56%). The final overall result showed the PB group as the best for healing (p=0.028) and the SC group as the best for esthetics (p=0.002). For the dermatologist, on the 60th postoperative day, the CV group presented the worst aesthetic result, whereas for the pediatrician and the plastic surgeon, the PB group presented the best healing result and the SC group had the best esthetic result. There was no difference between the groups regarding the presence of complications. Conclusion: the most common surgical techniques used to perform postectomy in children were differently assessed regarding healing and esthetic features by distinct medical professionals. The analysis of these two parameters among experts from related areas diverged among them and over time.

RESUMO Objetivo: analisar os aspectos estético e cicatricial pós-operatórios (PO) de pacientes submetidos a postectomia por diferentes técnicas cirúrgicas a partir da avaliação de profissionais experientes de áreas afins. Método: ensaio clínico prospectivo e randomizado, incluindo 149 meninos em idade pré-escolar com indicação médica de postectomia, divididos em três grupos: postectomia com dispositivo hemostático Plastibell® (grupo PB), técnica convencional (grupo CV) e convencional com pontos subcuticulares (grupo SC). Os pacientes foram fotografados em ângulos predefinidos no 30º e 60º dias de PO e as fotos avaliadas por três especialistas (dermatologista, pediatra e cirurgião plástico) que atribuíram notas entre 1 e 5, quanto aos aspectos estético e cicatricial em cada momento. Notas 4 ou 5 de todos os especialistas caracterizaram o "melhor resultado". Os dados foram submetidos à análise estatística para comparar as técnicas cirúrgicas, as avaliações dos especialistas e as complicações pós-operatórias. Resultados: a maioria dos pacientes obteve "melhor resultado" cicatricial (70%) e estético (56%). O resultado geral final apontou o grupo PB como superior quanto à cicatrização (p=0,028) e o grupo SC quanto ao aspecto estético (p=0,002). Para o dermatologista, na segunda avaliação, o grupo CV apresentou o pior resultado estético, enquanto para o pediatra e o cirurgião plástico, o grupo PB apresentou o melhor resultado cicatricial e o grupo SC o melhor resultado estético. Não houve diferença entre os grupos quanto à presença de complicações. Conclusão: as técnicas cirúrgicas mais empregadas para realizar postectomia em crianças foram avaliadas quanto aos resultados cicatricial e estético de distintas maneiras. A análise desses dois parâmetros entre especialistas de áreas afins divergiu entre eles e ao longo do tempo.

Risk factors associated with hospital mortality in mitral valve reoperation. / Fatores de risco associados à mortalidade hospitalar em reoperação valvar mitral.

OBJECTIVE: to identify the factors associated with mortality in mitral valve reoperation, to create a predictive model of mortality and to evaluate the EuroSCORE. METHODS: a total of 65 patients were evaluated from January 2008 to December 2017. It was verified the association of variables with death and a multiple logistic regression model was used to stratify patients. RESULTS: hospital mortality was 13.8% and in the Death Group: EuroSCORE was 12.33±8.87 (p=0.017), the left ventricular ejection fraction (LVEF) was 45.33±5.10 (p=0.000), the creatinine was 1.56±0.29 (p=0.002), the prothrombin time (TAP) was 1.64 (p=0.001), pulmonary artery systolic pressure (PSAP): 66.1±13.6 (p=0.002), female: 88% (p=0.000), malnutrition: 77.7% (p=0.007), associated tricuspid disease: 44,4% (p=0.048), presence of ventricular arrhythmia: 77.7% (p=0.005), implantation of a biological prosthesis: 55.5% (p=0.034), bronchopneumonia and sepsis: 33,3% (p=0.048), systemic inflammatory response syndrome (SIRS): 55.5% (p=0.001), low cardiac output syndrome (LCOS): 88.8% (p=0.000). CONCLUSION: the factors associated with mortality were: EuroSCORE, LVEF, creatinine, TAP, PSAP, female, malnutrition, tricuspid disease, ventricular arrhythmia, implantation of biological prosthesis, SIRS, SBDC, bronchopneumonia and sepsis. The explanatory variables of death of the model were: EuroSCORE, creatinine, TAP, LVEF, length of stay in the intensive care unit (ICU), interval between surgeries and presence of ventricular arrhythmia. The high EuroSCORE is related to higher mortality.

OBJETIVO: identificar os fatores associados à mortalidade em reoperação valvar mitral, criar um modelo preditivo de mortalidade e avaliar o EuroSCORE. MÉTODOS: foram avaliados 65 pacientes submetidos à reoperação de valva mitral no período de janeiro de 2008 a dezembro de 2017. Foi verificada a associação das variáveis com o óbito e criado um modelo de regressão logística múltiplo para estratificar os pacientes. RESULTADOS: a mortalidade hospitalar foi de 13,8% e, neste grupo, o EuroSCORE foi de 12,33±8,87 (p=0,017), a fração de ejeção do ventrículo esquerdo (FEVE) foi de 45,33±5,10 (p=0,000), a creatinina foi 1,56±0,29 (p=0,002), o tempo de atividade da protrombina (TAP): 1,64±0,15 (p=0,001), pressão sistólica da artéria pulmonar (PSAP): 66,1±13,6 (p=0,002), sexo feminino: 88% (p=0,000), desnutrição: 77,7% (p=0,007), doença tricúspide associada: 44,4% (p=0,048), presença de arritmia ventricular: 77,7% (p=0,005), implante de prótese biológica: 55,5% (p=0,034), broncopneumonia e sepse: 33,3% (p=0,048), síndrome da resposta inflamatória sistêmica (SIRS): 55,5% (p=0,001), síndrome do baixo débito cardíaco: 88,8% (p=0,000). CONCLUSÃO: os fatores associados à mortalidade foram: EuroSCORE, FEVE, creatinina, TAP, PSAP, sexo feminino, desnutrição, doença tricúspide, arritmia ventricular, implante de prótese biológica, SIRS, SBDC, broncopneumonia e sepse. As variáveis explicativas de óbito do modelo foram: EuroSCORE, creatinina, TAP, FEVE, tempo de internamento na unidade de terapia intensiva (UTI), intervalo entre cirurgias e presença de arritmia ventricular. O EuroSCORE elevado está relacionado à maior mortalidade.

Diferenciação de miofibroblastos em feridas após uso tópico do metronidazol: estudo experimental / Differentiation of myofibroblasts in wounds after topical use of metronidazole: an experimental study

RESUMO Objetivo: avaliar os efeitos da administração tópica do metronidazol na diferenciação de fibroblastos e na contração da ferida durante cicatrização experimental por segunda intenção em ratos. Métodos: cento e oito animais foram submetidos a uma ferida circular no dorso, com 2cm de diâmetro e divididos em seis grupos: grupo controle, com aplicação de solução salina sobre a ferida e cinco grupos experimentais divididos de acordo com a concentração da solução do metronidazol utilizada (4%, 6%, 8%,10% e 12%). Curativos foram realizados diariamente durante todo o período do experimento, que foi subdividido em três momentos de análise: três, sete e 14 dias. A contração da ferida foi avaliada por planimetria digital e os miofibroblastos e protomiofibroblastos foram identificados usando técnicas de imuno-histoquímica CD34 e a-SMA. Resultados: a contração da ferida não apresentou diferença entre os grupos e o controle. Os protomiofibroblastos foram significativamente mais numerosos aos sete dias (p=0,022) nos grupos metronidazol de 4%, 6% e 8%. Após 14 dias, nos mesmos grupos, os miofibroblastos predominaram significativamente (p=0,01). Conclusão: a administração tópica de solução de metronidazol em feridas de pele com cicatrização por segunda intenção foi capaz de melhorar a diferenciação de fibroblastos. A fase de contração da cicatrização de feridas permaneceu inalterada, sem redução significativa da contração avaliada pela planimetria digital. Estes resultados podem ser utilizados em favor do processo de cicatrização de feridas.

ABSTRACT Objective: to assess the effects of topical administration of metronidazole on fibroblast differentiation and on wound contraction during experimental secondary intention wound healing in rats. Methods: we submitted 108 rats to a circular wound on the back, 2cm in diameter, and divided them into six groups: control group, with application of saline solution on the wound and five experimental groups, divided according to the concentration of metronidazole solution used (4%, 6%, 8%, 10% and 12%). We changed the dressings daily throughout the trial period, which comprised three stages of analysis: three, seven and 14 days. We evaluated wound contraction by digital planimetry, and identified myofibroblasts and protomyofibroblasts using CD34 and α-SMA immunohistochemistry techniques. Results: wound contraction was not different between the experimental and the control groups. Protomyofibroblasts were significantly more numerous at seven days (p=0.022) in the 4%, 6% and 8% metronidazole groups. After 14 days, in the same groups, myofibroblasts predominated significantly (p=0.01). Conclusion: the topical administration of metronidazole solution in skin wounds healing by secondary intention was able to improve the differentiation of fibroblasts. The contraction phase of wound healing remained unchanged, without significant reduction of the contraction evaluated by digital planimetry. These results can be used in favor of the wound healing process.

Metronidazole concentration in the bloodstream following its topical application, at different concentration levels, on experimental skin wounds during healing by secondary intention

Abstract Purpose: To characterize qualitatively and quantitatively the absorption of metronidazole solution, in greater concentrations and for longer periods, when applied topically to an experimental open skin wound model. Methods: An open skin wound, 2 cm in diameter and total skin thickness was prepared, under anesthetic, in the dorsal region of 108 Wistar rats weighing between 300 and 350 grams. The animals were allocated to groups of 18 animals in accordance with the concentration of metronidazole in the solution to be applied daily to the wound. In the control group (CG), 0.9% sodium chloride solution was used for application, and in the experimental groups (GI, GII, GIII, GIV and GV) metronidazole solution at 4%, 6%, 8%, 10% and 12%, respectively, was applied. After 3, 7 and 14 days of treatment. Blood samples collected through cardiac puncture were examined for the existence or non-existence of metronidazole, using high performance liquid chromatography (HPLC). Detected metronidazole values were compared statistically within each group (temporal analysis 3 days X 7 days X 14 days) and between the groups that used topical metronidazole (4% X 6% X 8% X 10% and 12%) using the Kruskal-Wallis test, considering a statistical significance of 95% (p<0.05). Results: Metronidazole was detected in all the samples at all times in all the groups in which topical metronidazole was applied to the wounds. Characteristically, there was no significant difference between the doses obtained within each group over time (3 days X 7 days X 14 days) GI=0.461; GII=0.154; GIII=0.888; GIV= 0.264 and GV=0.152. In the evaluation between groups, a similar degree of absorption was found after 3 days (p=0.829) and 14 days (p=0.751). Conclusion: The serum concentration of metronidazole that was achieved was not influenced by the concentration of the solution applied to the skin wound, with similar extend, or by the duration of the application.