Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats.

Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1α, IL-1ß, IL-6, IL-10, and TNF-α). Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH); parecoxib/no hemorrhage (Pcx/NH); placebo/hemorrhage (Plc/H); and parecoxib/hemorrhage (Pcx/H). Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline). Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

Cyclosporine A attenuates apoptosis and necrosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic rats.

PURPOSE:: To investigate the effects of cyclosporine A on renal ischemia-reperfusion injury during transient hyperglycemia in rats. METHODS:: In a model of ischemia-reperfusion-induced renal injury and transiently induced hyperglycemia by intraperitoneal injection of glucose, 2.5 g.kg-1, Wistar rats were anesthetized with either isoflurane or propofol and received intravenous cyclosporine A, 5 mg.kg-1, five minutes before reperfusion. Comparison groups were isoflurane and propofol sham groups and isoflurane and propofol ischemia-reperfusion-induced renal injury. Renal tubular cell viability was quantitatively assessed by flow cytometry after cell culture and classified as early apoptosis, necrotic cells, and intact cells. RESULTS:: Early apoptosis was significantly higher in isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury when compared to both cyclosporine A treated and sham groups. Necrosis percentage was significantly higher in propofol-anesthetized animals subjected to renal ischemia-reperfusion injury. The percentage of intact cells was lower in both, isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury. CONCLUSION:: In a model of ischemia-reperfusion-induced renal injury, cyclosporine A, 5 m.kg-1, administered five minutes before renal reperfusion in rats with acute-induced hyperglycemia under either isoflurano or propofol anesthesia, attenuated early apoptosis and preserved viability in renal tubular cells, regardless of the anesthetic used.

Cyclosporine A attenuates apoptosis and necrosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic rats

Abstract Purpose: To investigate the effects of cyclosporine A on renal ischemia-reperfusion injury during transient hyperglycemia in rats. Methods: In a model of ischemia-reperfusion-induced renal injury and transiently induced hyperglycemia by intraperitoneal injection of glucose, 2.5 g.kg-1, Wistar rats were anesthetized with either isoflurane or propofol and received intravenous cyclosporine A, 5 mg.kg-1, five minutes before reperfusion. Comparison groups were isoflurane and propofol sham groups and isoflurane and propofol ischemia-reperfusion-induced renal injury. Renal tubular cell viability was quantitatively assessed by flow cytometry after cell culture and classified as early apoptosis, necrotic cells, and intact cells. Results: Early apoptosis was significantly higher in isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury when compared to both cyclosporine A treated and sham groups. Necrosis percentage was significantly higher in propofol-anesthetized animals subjected to renal ischemia-reperfusion injury. The percentage of intact cells was lower in both, isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury. Conclusion: In a model of ischemia-reperfusion-induced renal injury, cyclosporine A, 5 m.kg-1, administered five minutes before renal reperfusion in rats with acute-induced hyperglycemia under either isoflurano or propofol anesthesia, attenuated early apoptosis and preserved viability in renal tubular cells, regardless of the anesthetic used.

Does Spinal Block Through Tattooed Skin Cause Histological Changes in Nervous Tissue and Meninges?: An Experimental Model in Rabbits.

BACKGROUND AND OBJECTIVES: Although there is no documented evidence that tattoo pigments can cause neurological complications, the implications of performing neuraxial anesthesia through tattooed skin are unknown. In this study, we aimed to assess whether spinal puncture performed through tattooed skin of rabbits determines changes over the spinal cord and meninges. In addition, we sought to evaluate the presence of ink fragments entrapped in spinal needles. METHODS: Thirty-six young male adult rabbits, each weighing between 3400 and 3900 g and having a spine length between 38.5 and 39 cm, were divided by lot into 3 groups as follows: GI, spinal puncture through tattooed skin; GII, spinal puncture through tattooed skin and saline injection; and GIII, spinal puncture through skin free of tattoo and saline injection. After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance with a 22-gauge 2½ Quincke needle. Animals in GII and GIII received 5 µL/cm of spinal length (0.2 mL) of saline intrathecally. In GI, the needle tip was placed into the yellow ligament, and no solution was injected into the intrathecal space; after tattooed skin puncture, 1 mL of saline was injected through the needle over a histological slide to prepare a smear that was dyed by the Giemsa method to enable tissue identification if present. All animals remained in captivity for 21 days under medical observation and were killed by decapitation. The lumbosacral spinal cord portion was removed for histological analysis using hematoxylin-eosin stain. RESULTS: None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group (GIII) showed signs of injuries to meninges. In GII, however, 4 animals presented with signs of meningeal injury. The main histological changes observed were focal areas of perivascular lymphoplasmacyte infiltration in the pia mater and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. Tissue coring containing ink pigments was noted in all GI smears from the spinal needles used to puncture the tattooed skin. CONCLUSIONS: On the basis of the present results, intrathecal injection of saline through a needle inserted through tattooed skin is capable of producing histological changes over the meninges of rabbits. Ink fragments were entrapped inside the spinal needles, despite the presence of a stylet.

Do propofol and isoflurane protect the kidney against ischemia/reperfusion injury during transient hyperglycemia?

PURPOSE: To study the effect of isoflurane (Iso) or propofol (Prop) anesthesia on renal ischemia/reperfusion injury (IRI) during transient hyperglycemia. METHODS: Thirty six rats were randomly assigned into six groups of six animals each: PHS (Sham-Prop=1mg.kg-1.min-1 + Hyperglycemia=2.5g.kg-1 of glucose solution administered intraperitoneally); HIS (Sham-Iso + Hyperglycemia); PHI (Prop + Hyperglycemia + Ischemia); IHI (Iso + Hyperglycemia + Ischemia); PI (Prop + Ischemia), and II (Iso + Ischemia). After 30 minutes of anesthesia induction, right nephrectomy was performed (all animals) and the left renal artery was clamped during 25 minutes (ischemia). The animals were sacrificed after 24 hours and blood collection (to dose creatinine) and left kidney removal were performed for histological analysis, and flow cytometry (FCM): percentage of initial apoptosis (APTi) and viable cells (VC). RESULTS: Serum creatinine (mg/dL) was statistically different in groups PHI (3.60±0.40) and IHI (3.23±1.08), p<0.05. Histological analysis was statistically different in groups PHI (4.0[4.0;5.0]) and IHI (4.5[4.0;5.0]), p<0.05. APTi percentage was statistically different in groups PHI (73.2±7.1), and IHI (48.1±14). VC percentage was statistically different in groups PHI (25.8±6.9) and IHI (38.5±9.2), p<0.05. CONCLUSIONS: Propofol and isoflurane showed the same level of protection against ischemia/reperfusion injury in the normoglycemic groups. Transient hyperglycemia is associated with an increase in IRI.

Does propofol and isoflurane protect the kidney against ischemia/reperfusion injury during transient hyperglycemia?

PURPOSE: To study the effect of isoflurane (Iso) or propofol (Prop) anesthesia on renal ischemia/reperfusion injury (IRI) during transient hyperglycemia. METHODS: Thirty six rats were randomly assigned into six groups of six animals each: PHS (Sham-Prop=1mg.kg-1.min-1 + Hyperglycemia=2.5g.kg-1 of glucose solution administered intraperitoneally); HIS (Sham-Iso + Hyperglycemia); PHI (Prop + Hyperglycemia + Ischemia); IHI (Iso + Hyperglycemia + Ischemia); PI (Prop + Ischemia), and II (Iso + Ischemia). After 30 minutes of anesthesia induction, right nephrectomy was performed (all animals) and the left renal artery was clamped during 25 minutes (ischemia). The animals were sacrificed after 24 hours and blood collection (to dose creatinine) and left kidney removal were performed for histological analysis, and flow cytometry (FCM): percentage of initial apoptosis (APTi) and viable cells (VC). RESULTS: Serum creatinine (mg/dL) was statistically different in groups PHI (3.60±0.40) and IHI (3.23±1.08), p<0.05. Histological analysis was statistically different in groups PHI (4.0[4.0;5.0]) and IHI (4.5[4.0;5.0]), p<0.05. APTi percentage was statistically different in groups PHI (73.2±7.1), and IHI (48.1±14). VC percentage was statistically different in groups PHI (25.8±6.9) and IHI (38.5±9.2), p<0.05. CONCLUSIONS: Propofol and isoflurane showed the same level of protection against ischemia/reperfusion injury in the normoglycemic groups. Transient hyperglycemia is associated with an increase in IRI.

The effect of 6% Hydroxyethyl starch vs. Ringer's lactate on acute kidney injury after renal ischemia in rats.

PURPOSE: To compare fluid replacement therapy with Hydroxyethyl starch 6% (HES) versus Ringer's lactate (RL) in a rodent model of non-septic renal ischemia. METHODS: Forty male Wistar rats were randomized to receive HES 2 ml.kg(-1).hr(-1) or RL 5 ml.kg(-1).hr(-1) that underwent 30 minutes of renal ischemia followed by reperfusion. Twelve hours after kidney ischemia, the kidneys were evaluated for histological changes. Serum NGAL levels were obtained at different times of the experimental protocol. RESULTS: Rodents in the HES group had a median (IQR) grade of renal injury 3 (3 to 5) compared to 2 (2 to 4) in the RL group (p=0.03). NGAL levels were not associated with the severity of kidney injury. CONCLUSION: Hydroxyethyl starch administration caused more kidney injury than Ringer's lactate in a non-infectious model of renal hypoperfusion.

The effect of 6% Hydroxyethyl starch vs. Ringer's lactate on acute kidney injury after renal ischemia in rats

PURPOSE: To compare fluid replacement therapy with Hydroxyethyl starch 6% (HES) versus Ringer's lactate (RL) in a rodent model of non-septic renal ischemia. METHODS: Forty male Wistar rats were randomized to receive HES 2 ml.kg-1.hr-1or RL 5 ml. kg-1.hr-1 that underwent 30 minutes of renal ischemia followed by reperfusion. Twelve hours after kidney ischemia, the kidneys were evaluated for histological changes. Serum NGAL levels were obtained at different times of the experimental protocol. RESULTS: Rodents in the HES group had a median (IQR) grade of renal injury 3 (3 to 5) compared to 2 (2 to 4) in the RL group (p=0.03). NGAL levels were not associated with the severity of kidney injury. CONCLUSION: Hydroxyethyl starch administration caused more kidney injury than Ringer's lactate in a non-infectious model of renal hypoperfusion.

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane.

PURPOSE: To evaluate the effect of N-acetylcysteine, as a renoprotective agent, when administered early after anesthesia induction, against ischemia/reperfusion injury in rats anesthetized with isoflurane. METHODS: Eighteen male Wistar rats weighing > 300 g were anesthetized with isoflurane. The internal jugular vein and the left carotid artery were dissected and cannulated. The animals were randomly divided into GAcetyl, receiving intravenous N-acetylcysteine, 300 mg/kg, and GIsot, isotonic saline. After 30 minutes, right nephrectomy was performed and the left renal artery was clamped during 45 minutes. The animals were sacrificed after 48 hours and blood samples were taken after anesthetic induction and upon sacrificing of the animals to evaluate blood creatinine. The kidneys were sent for histological analysis. RESULTS: The variation in serum creatinine was 2.33 mg/dL ± 2.21 in GAcetyl and 4.38 mg/dL ± 2.13 in GIsot (p=0.074). Two animals presented intense tubular necrosis in GAcetyl, compared to 5 in GIsot. Only GAcetyl presented animals free of tubular necrosis (two) and tubular degeneration (one). CONCLUSION: After renal ischemia/reperfusion, the rats which were given N-acetylcysteine presented less variation in serum creatinine and milder kidney injuries than the control group.

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane / Prevenção de lesão de isquemia/reperfusão em ratos com acetilcisteína após anestesia com isoflurano

PURPOSE: To evaluate the effect of N-acetylcysteine, as a renoprotective agent, when administered early after anesthesia induction, against ischemia/reperfusion injury in rats anesthetized with isoflurane. METHODS: Eighteen male Wistar rats weighing > 300g were anesthetized with isoflurane. The internal jugular vein and the left carotid artery were dissected and cannulated. The animals were randomly divided into GAcetyl, receiving intravenous N-acetylcysteine, 300mg/kg, and GIsot, isotonic saline. After 30 minutes, right nephrectomy was performed and the left renal artery was clamped during 45 minutes. The animals were sacrificed after 48 hours and blood samples were taken after anesthetic induction and upon sacrificing of the animals to evaluate blood creatinine. The kidneys were sent for histological analysis. RESULTS: The variation in serum creatinine was 2.33mg/dL ± 2.21 in GAcetyl and 4.38mg/dL ± 2.13 in GIsot (p=0.074). Two animals presented intense tubular necrosis in GAcetyl, compared to 5 in GIsot. Only GAcetyl presented animals free of tubular necrosis (two) and tubular degeneration (one). CONCLUSION: After renal ischemia/reperfusion, the rats which were given N-acetylcysteine presented less variation in serum creatinine and milder kidney injuries than the control group.

OBJETIVO: Avaliar o efeito da N-acetilcisteína na proteção renal contra lesão de isquemia/reperfusão, quando administrada logo após a indução anestésica, em ratos anestesiados com isoflurano. MÉTODOS: Dezoito ratos Wistar machos pesando mais que 300g foram anestesiados com isoflurano. A jugular interna direita e a carótida esquerda foram dissecadas e canuladas. Os animais foram distribuídos aleatoriamente em GAcetil, recebendo N-acetilcisteína por via intravenosa, 300mg/kg, e GIsot, solução salina. Foi realizada nefrectomia direita e clampeamento da artéria renal esquerda por 45 min. Os animais foram sacrificados após 48h, sendo colhidas amostras sanguíneas após a indução anestésica e ao sacrifício dos mesmos para avaliar a creatinina sérica. Realizou-se histologia renal. RESULTADOS: A variação da creatinina foi 2,33mg/dL ± 2,21 no GAcetil e 4,38mg/dL ± 2,13 no GIsot (p=0,074). Dois animais apresentaram necrose tubular intensa no GAcetil, comparados a cinco no GIsot. Apenas GAcetil apresentou animais livres de necrose tubular (dois) e degeneração tubular (um). CONCLUSÃO: Após isquemia/reperfusão renais, os ratos aos quais se administrou N-acetilcisteína apresentaram menor variação na creatinina sérica e lesões renais mais leves que o grupo controle.

Renal histology and immunohistochemistry after acute hemorrhage in rats under sevoflurane and ketoprofen effect / Histologia e imuno-histoquímica renais após hemorragia aguda em ratos sob efeito do sevoflurano e cetoprofeno

PURPOSE: To investigate the influence of intravenous nonselective cyclooxygenase inhibitor, ketoprofen (keto), on kidney histological changes and kidney cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), levels after hemorrhage of 30 percent of volemia (three times 10 percent, intervals of 10 min) in rats. METHODS: Under sevoflurane (sevo) anesthesia, sevo and sevo+keto groups (10 rats each) were instrumented for Ringer solution (5mL/kg/h) administration and mean arterial pressure (MAP) evaluation, plus keto (1.5mg/kg) administration in sevo+keto group in the beginning of anesthesia. Rectal temperature was continuously measured. The baseline data of temperature and MAP were collected at the first hemorrhage (T1), the third hemorrhage (T2) and 30min after T2 (T3). Bilateral nephrectomy was achieved for histology and immunohistochemistry. RESULTS: In both groups, temperature and MAP diminished from initial values. Hypothermia was greater in sevo group (p=0.0002). Tubular necrosis was more frequent in sevo group (p=0.02). The studied cytokines were equally present in the kidneys of both groups. CONCLUSION: Ketoprofen was more protective to the rat kidney in condition of anesthesia with sevoflurane and hypovolemia, but it seems that TNF-α and IL-1 were not involved in that protection.

OBJETIVO: Investigar a influência do inibidor não-seletivo da ciclooxigenase, cetoprofeno (ceto) intravenoso, em alterações histológicas e dos níveis das citocinas renais - fator α de necrose tumoral (TNF- α) e interleucina 1 (IL-1) - após hemorragia de 30 por cento da volemia (10 por cento, três vezes, em intervalos de 10 min). MÉTODOS: Sob anestesia com sevoflurano (sevo), os grupos sevo e sevo+ceto (10 ratos cada) foram preparados cirurgicamente para leitura de pressão arterial média (PAM) e administração de solução de Ringer (5 mL/kg/h) e de cetoprofeno (1,5 mg/kg), no início da anestesia, no grupo sevo+ceto. Mediu-se temperatura retal continuamente. Os valores de temperatura e PAM foram observados antes da primeira hemorragia (T1), após a terceira hemorragia (T2) e 30 min após T2 (T3). Realizada nefrectomia bilateral nos dois grupos para análise histológica e imuno-histoquímica. RESULTADOS: Nos dois grupos, temperatura e PAM diminuíram com relação aos valores basais. Hipotermia foi mais acentuada no grupo sevo (p=0,0002). Necrose tubular foi mais frequente no grupo sevo (p=0,02). As citocinas estiveram igualmente presentes nos rins dos dois grupos. CONCLUSÃO: Cetoprofeno foi mais protetor no rim de rato durante anestesia com sevoflurano e hipovolemia, porém parece que TNF- α e IL-1 não estão envolvidas nessa proteção.

Renal histology and immunohistochemistry after acute hemorrhage in rats under sevoflurane and ketoprofen effect.

PURPOSE: To investigate the influence of intravenous nonselective cyclooxygenase inhibitor, ketoprofen (keto), on kidney histological changes and kidney cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), levels after hemorrhage of 30% of volemia (three times 10%, intervals of 10 min) in rats. METHODS: Under sevoflurane (sevo) anesthesia, sevo and sevo+keto groups (10 rats each) were instrumented for Ringer solution (5 mL/kg/h) administration and mean arterial pressure (MAP) evaluation, plus keto (1.5mg/kg) administration in sevo+keto group in the beginning of anesthesia. Rectal temperature was continuously measured. The baseline data of temperature and MAP were collected at the first hemorrhage (T1), the third hemorrhage (T2) and 30 min after T2 (T3). Bilateral nephrectomy was achieved for histology and immunohistochemistry. RESULTS: In both groups, temperature and MAP diminished from initial values. Hypothermia was greater in sevo group (p=0.0002). Tubular necrosis was more frequent in sevo group (p=0.02). The studied cytokines were equally present in the kidneys of both groups. CONCLUSION: Ketoprofen was more protective to the rat kidney in condition of anesthesia with sevoflurane and hypovolemia, but it seems that TNF-α and IL-1 were not involved in that protection.

Análise retrospectiva de fatores de risco e preditores de complicações intraoperatórias dos bloqueios do neuroeixo realizados na Faculdade de Medicina de Botucatu-UNESP / Retrospective analysis of risk factors and predictors of intraoperative complications in neuraxial blocks at Faculdade de Medicina de Botucatu-UNESP

JUSTIFICATIVA E OBJETIVOS: As alterações cardiovasculares associadas aos bloqueios do neuroeixo apresentam interesse pela frequência com que ocorrem e porque algumas delas podem ser consideradas efeitos fisiológicos desencadeados pelo bloqueio do sistema nervoso simpático. O objetivo desta pesquisa foi avaliar as complicações cardiovasculares intraoperatórias e os fatores preditores associados aos bloqueios do neuroeixo em pacientes com idades > 18 anos submetidos a procedimentos não obstétricos, em um período de 18 anos, em hospital universitário de atendimento terciário-HCFMB-UNESP. MÉTODO: Foi realizada análise retrospectiva das seguintes complicações: hipertensão arterial, hipotensão arterial, bradicardia sinusal e taquicardia sinusal. Tais complicações foram correlacionadas com técnica anestésica, estado físico (ASA), idade, sexo e comorbidades pré-operatórias. Para a análise estatística, foram utilizadas o teste de Tukey para comparações entre proporções e regressão logística. RESULTADOS: Foram avaliados 32.554 pacientes submetidos a bloqueios do neuroeixo e houve 4.109 citações de hipotensão arterial, 1.107 de bradicardia sinusal, 601 de taquicardia sinusal e 466 de hipertensão arterial no período intraoperatório. Hipotensão foi mais frequente nos pacientes submetidos à anestesia subaracnoidea contínua (29,4 por cento, OR = 2,39), com idades > 61 anos e do sexo feminino (OR = 1,27). CONCLUSÕES: Hipotensão e bradicardia intraoperatórias foram complicações mais frequentes, sendo que a hipotensão arterial esteve relacionada à técnica anestésica (ASC), faixa etária elevada e sexo feminino. Taquicardia e hipertensão arterial podem não ter sido diretamente relacionadas aos bloqueios do neuroeixo.

BACKGROUND AND OBJECTIVES: Cardiovascular changes associated with neuraxial blocks are a cause of concern due to their frequency and because some of them can be considered physiological effects triggered by the sympathetic nervous system blockade. The objective of this study was to evaluate intraoperative cardiovascular complications and predictive factors associated with neuraxial blocks in patients > 18 years of age undergoing non-obstetric procedures over an 18-year period in a tertiary university hospital - HCFMB-UNESP. METHODS: A retrospective analysis of the following complications was undertaken: hypertension, hypotension, sinus bradycardia, and sinus tachycardia. These complications were correlated with anesthetic technique, physical status (ASA), age, gender, and preoperative co-morbidities. The Tukey test for comparisons among proportions and logistic regression was used for statistical analysis. RESULTS: 32,554 patients underwent neuraxial blocks. Intraoperative complications mentioned included hypotension (n = 4,109), sinus bradycardia (n = 1,107), sinus tachycardia (n = 601), and hypertension (n = 466). Hypotension was seen more often in patients undergoing continuous subarachnoid anesthesia (29.4 percent, OR = 2.39), > 61 years of age, and female (OR = 1.27). CONCLUSIONS: Intraoperative hypotension and bradycardia were the complications observed more often. Hypotension was related to anesthetic technique (CSA), increased age, and female. Tachycardia and hypertension may not have been directly related to neuraxial blocks.

JUSTIFICATIVA Y OBJETIVOS: Las alteraciones cardiovasculares asociadas a los bloqueos del neuro eje son de interés por la frecuencia con que ocurren y porque algunas de ellas pueden ser consideradas como efectos fisiológicos desencadenados por el bloqueo del sistema nervioso simpático. El objetivo de esta investigación, fue evaluar las complicaciones cardiovasculares intraoperatorias y los factores predictores asociados a los bloqueos del neuro eje, en pacientes con edades > 18 años, sometidos a procedimientos no obstétricos, en un período de 18 años, en un hospital universitario de atención terciario-HCFMB-UNESP. MÉTODO: Fue realizado un análisis retrospectivo de las siguientes complicaciones: hipertensión arterial, hipotensión arterial, bradicardia sinusal y taquicardia sinusal. Esas complicaciones se correlacionaron con la técnica anestésica, estado físico (ASA), edad, sexo y comorbilidades preoperatorias. Para el análisis estadístico, se usó el test de Tukey para las comparaciones entre las proporciones y la regresión logística. RESULTADOS: Fueron evaluados 32.554 pacientes sometidos a bloqueos del neuro eje y hubo 4.109 apariciones de hipotensión arterial, 1.107 de bradicardia sinusal, 601 de taquicardia sinusal y 466 de hipertensión arterial en el período intraoperatorio. La hipotensión fue más frecuente en los pacientes sometidos a la anestesia subaracnoidea continua (29,4 por ciento, OR = 2,39), con edades > 61 años y pertenecientes al sexo femenino (OR =1,27). CONCLUSIONES: La hipotensión y la bradicardia intraoperatorias fueron las complicaciones más frecuentes, siendo que la hipotensión arterial se relacionó con la técnica anestésica (ASC), franja etaria elevada y sexo femenino. La taquicardia y la hipertensión arterial pueden no haber sido directamente relacionadas con los bloqueos del neuro eje.

Retrospective analysis of risk factors and predictors of intraoperative complications in neuraxial blocks at Faculdade de Medicina de Botucatu-UNESP.

BACKGROUND AND OBJECTIVES: Cardiovascular changes associated with neuraxial blocks are a cause of concern due to their frequency and because some of them can be considered physiological effects triggered by the sympathetic nervous system blockade. The objective of this study was to evaluate intraoperative cardiovascular complications and predictive factors associated with neuraxial blocks in patients ≥ 18 years of age undergoing non-obstetric procedures over an 18-year period in a tertiary university hospital--HCFMB-UNESP. METHODS: A retrospective analysis of the following complications was undertaken: hypertension, hypotension, sinus bradycardia, and sinus tachycardia. These complications were correlated with anesthetic technique, physical status (ASA), age, gender, and preoperative co-morbidities. The Tukey test for comparisons among proportions and logistic regression was used for statistical analysis. RESULTS: 32,554 patients underwent neuraxial blocks. Intraoperative complications mentioned included hypotension (n=4,109), sinus bradycardia (n=1,107), sinus tachycardia (n=601), and hypertension (n=466). Hypotension was seen more often in patients undergoing continuous subarachnoid anesthesia (29.4%, OR=2.39), ≥ 61 years of age, and female (OR=1.27). CONCLUSIONS: Intraoperative hypotension and bradycardia were the complications observed more often. Hypotension was related to anesthetic technique (CSA), increased age, and female. Tachycardia and hypertension may not have been directly related to neuraxial blocks.

Avaliação clínica de duas ke0 no mesmo modelo farmacocinético de propofol: estudo da perda e recuperação da consciência / Clinical evaluation of two ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness / Evaluación clínica de dos ke0 en el mismo modelo farmacocinético de propofol: estudio de la pérdida y de la recuperación de la conciencia

JUSTIFICATIVA E OBJETIVOS: A constante de equilíbrio entre o plasma e o sítio efetor (ke0) é utilizada pelos modelos farmacocinéticos para prever a concentração do fármaco em seu local de ação (Ce). Seria interessante que a Ce de propofol fosse semelhante na perda e na recuperação da consciência. O objetivo deste estudo foi avaliar o desempenho clínico de duas diferentes ke0 (rápida = 1,21 min-1 e lenta = 0,26 min-1) com relação à Ce durante a perda e a recuperação da consciência, usando o modelo farmacocinético de Marsh. MÉTODO: Participaram deste estudo 20 voluntários adultos sadios do sexo masculino. Em todos os voluntários, administrou-se propofol em regime de infusão alvo-controlada, modelo farmacocinético de Marsh ke0 rápida e, em outra oportunidade, usou-se o mesmo modelo farmacocinético com a ke0 lenta. Inicialmente, o propofol foi infundido em concentração-alvo plasmática de 3,0µg.mL-1. A perda de consciência e a recuperação de consciência basearam-se na resposta ao estímulo verbal. A Ce foi anotada no momento da perda e da recuperação da consciência. RESULTADOS: Na perda e na recuperação da consciência a Ce pela ke0 rápida foi diferente (3,64 ± 0,78 e 1,47 ± 0,29µg.mL-1, respectivamente, p < 0,0001), enquanto com a ke0 lenta a Ce foi semelhante (2,20 ± 0,70 e 2,13 ± 0,43µg.mL-1, respectivamente, p = 0,5425). CONCLUSÕES: Do ponto de vista clínico, a ke0 lenta (0,26 min-1) incorporada ao modelo farmacocinético de Marsh apresentou melhor desempenho que a ke0 rápida (1,21 min-1), uma vez que a concentração de propofol prevista em seu local de ação na perda e recuperação da consciência foi semelhante.

BACKGROUND AND OBJECTIVE: The constant equilibrium between the plasma and effect site (ke0) is used by pharmacokinetic models to calculate a drug concentration in its site of action (Ce). It would be interesting if Ce of propofol was similar at loss and recovery of consciousness. The objective of this study was to evaluate the clinical performance of two different ke0 (fast = 1.21 min-1, and slow = 0.26 min-1) in relation to Ce during loss and recovery of consciousness using Marsh pharmacokinetic model. METHODS: Twenty healthy adult male volunteers participated in this study. In all volunteers propofol was administered as target-controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol was infused with a serum target-controlled infusion of 3.0 µg.mL-1. Loss of consciousness and recovery of consciousness were based on response to verbal stimulus. Ce was recorded at the moment of loss and recovery of consciousness. RESULTS: On loss and recovery of consciousness, the Ce for fast ke0 was different (3.64 ± 0.78 and 1.47 ± 0.29 µg.mL-1, respectively, p < 0.0001), while with slow ke0 the Ce was similar (2.20 ± 0.70 and 2.14 ± 0.43 µg.mL-1, respectively, p = 0.5425). CONCLUSIONS: Clinically, the slow ke0 (0.26 min-1) incorporated in the Marsh pharmacokinetic model showed better performance than the fast ke0 (1.21 min-1), since the calculated concentration of propofol at the effect site on loss and recovery of consciousness was similar.

JUSTIFICATIVA Y OBJETIVOS: La constante de equilibrio entre el plasma y el sitio efector (ke0), se usa por los modelos farmacocinéticos para prever la concentración del fármaco en su región de acción (Ce). Sería interesante que el Ce de propofol fuese similar en la pérdida y en la recuperación de la conciencia. El objetivo de este estudio, fue evaluar el desempeño clínico de dos diferentes ke0 (rápida = 1,21 min-1 y lenta = 0,26 min-1), con relación a la Ce durante la pérdida y la recuperación de la conciencia, usando el modelo farmacocinético de Marsh. MéTODO: Participaron en este estudio, 20 voluntarios adultos sanos del sexo masculino. A todos los voluntarios se les administró propofol en régimen de infusión objeto controlada, modelo farmacocinético de Marsh ke0 rápida y en otro momento, se usó el mismo modelo farmacocinético con a ke0 lenta. Inicialmente, el propofol se infundió en concentración-objeto plasmática de 3,0 µg.mL-1. La pérdida de la conciencia y la recuperación de la conciencia estuvieron basadas en la respuesta al estímulo verbal. La Ce fue anotada en el momento de la pérdida y de la recuperación de la conciencia. RESULTADOS: En la pérdida y en la recuperación de la conciencia, la Ce por la ke0 rápida, fue diferente (3,64 ± 0,78 y 1,47 ± 0,29 µg.mL-1, respectivamente, p < 0,0001), mientras que con la ke0 lenta la Ce fue parecida (2,20 ± 0,70 y 2,13 ± 0,43 µg.mL-1, respectivamente, p = 0,5425). CONCLUSIONES: Desde el punto de vista clínico, la ke0 lenta (0,26 min-1) incorporada al modelo farmacocinético de Marsh, presentó un mejor desempeño que la ke0 rápida (1,21 min-1), pues la concentración de propofol prevista en su región de acción en la pérdida y en la recuperación de la conciencia fue similar.

Clinical evaluation of two Ke0 in the same pharmacokinetic propofol model: study on loss and recovery of consciousness.

BACKGROUND AND OBJECTIVE: The constant equilibrium between the plasma and effect site (ke0) is used by pharmacokinetic models to calculate a drug concentration in its site of action (Ce). It would be interesting if Ce of propofol was similar at loss and recovery of consciousness. The objective of this study was to evaluate the clinical performance of two different ke0 (fast = 1.21 min(-1), and slow = 0.26 min(-1)) in relation to Ce during loss and recovery of consciousness using Marsh pharmacokinetic model. METHODS: Twenty healthy adult male volunteers participated in this study. In all volunteers propofol was administered as target-controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol was infused with a serum target-controlled infusion of 3.0 µg.mL(-1). Loss of consciousness and recovery of consciousness were based on response to verbal stimulus. Ce was recorded at the moment of loss and recovery of consciousness. RESULTS: On loss and recovery of consciousness, the Ce for fast ke0 was different (3.64 ± 0.78 and 1.47 ± 0.29 µg.mL(-1), respectively, p < 0.0001), while with slow ke0 the Ce was similar (2.20 ± 0.70 and 2.14 ± 0.43 µg.mL(-1), respectively, p = 0.5425). CONCLUSIONS: Clinically, the slow ke0 (0.26 min(-1)) incorporated in the Marsh pharmacokinetic model showed better performance than the fast ke0 (1.21 min(-1)), since the calculated concentration of propofol at the effect site on loss and recovery of consciousness was similar.

Dexmedetomidina e S(+)-cetamina em lesão de isquemia e reperfusão no rim de rato / Dexmedetomidine and S(+)-ketamine in ischemia and reperfusion injury in the rat kidney

PURPOSE: To investigate blood creatinine and renal histology in rats anesthetized with S(+)-ketamine (keta) or dexmedetomidine (dex) and submitted to kidney ischemia/reperfusion injury (IRI). METHODS: Under intraperitoneal (ip) S(+)-ketamine, 20 male Wistar rats were divided into two groups (n=10): maintenance with iv S(+)-ketamine or dex (keta and dex groups), and submitted to right (R) nephrectomy and left (L) renal artery clamping for 45 min. Blood creatinine was measured before ischemia (T1) and 48h after reperfusion (T2), when L nephrectomy was performed. Histological analysis was performed in all kidneys. RESULTS: Blood creatinine was significantly higher at T2 in both groups, but dex group results were lower than those of keta group. Histological changes: between groups, R kidneys did not differ; there were significant high scores for vascular dilation: keta L kidneys; for vascular congestion, tubular dilation, and necrosis: L kidneys from both groups; for tubular degeneration: keta R kidneys. CONCLUSION: S(+)-ketamine plus IRI were aggressive to rat kidneys, according to histological changes, and dexmedetomidine may have not totally protected the kidneys from these injuries, despite the better results of blood creatinine.

OBJETIVO: Investigar a creatinina sanguínea e histologia renal em ratos anestesiados com S(+)-cetamina (ceta) ou dexmedetomidina (dex) e submetidos à lesão de isquemia/reperfusão renal (IR). MÉTODOS: Sob S(+)-cetamina intraperitoneal (ip), 20 ratos Wistar machos foram distribuídos em dois grupos (n=10): manutenção com S(+)-cetamina ou dexmedetomidina, iv, (grupos ceta e dex), e submetidos à nefrectomia direita (D) e clampeamento da artéria renal esquerda (E) por 45 min. A creatinina sanguínea foi dosada antes da isquemia (T1) e 48h após a reperfusão (T2), quando foi realizada nefrectomia E. Houve análise histológica de todos os rins. RESULTADOS: A creatinina foi significativamente maior em T2 em ambos os grupos, porém menor com a dexmedetomidina. Alterações histológicas: entre grupos, os rins Ds não diferiram; houve escores altos significativos para dilatação vascular: rins Es do grupo ceta; para congestão vascular, dilatação tubular, necrose: rins Es de ambos os grupos; para degeneração tubular: rins Ds do grupo ceta. CONCLUSÃO: S(+)-cetamina e IR foram agressivas histologicamente para rins de ratos e a dexmedetomidina pode não ter protegido totalmente os rins dessas lesões, apesar dos melhores resultados de creatinina.

Dexmedetomidine and S(+)-ketamine in ischemia and reperfusion injury in the rat kidney.

PURPOSE: To investigate blood creatinine and renal histology in rats anesthetized with S(+)-ketamine (keta) or dexmedetomidine (dex) and submitted to kidney ischemia/reperfusion injury (IRI). METHODS: Under intraperitoneal (ip) S(+)-ketamine, 20 male Wistar rats were divided into two groups (n=10): maintenance with iv S(+)-ketamine or dex (keta and dex groups), and submitted to right (R) nephrectomy and left (L) renal artery clamping for 45 min. Blood creatinine was measured before ischemia (T1) and 48h after reperfusion (T2), when L nephrectomy was performed. Histological analysis was performed in all kidneys. RESULTS: Blood creatinine was significantly higher at T2 in both groups, but dex group results were lower than those of keta group. Histological changes: between groups, R kidneys did not differ; there were significant high scores for vascular dilation: keta L kidneys; for vascular congestion, tubular dilation, and necrosis: L kidneys from both groups; for tubular degeneration: keta R kidneys. CONCLUSION: S(+)-ketamine plus IRI were aggressive to rat kidneys, according to histological changes, and dexmedetomidine may have not totally protected the kidneys from these injuries, despite the better results of blood creatinine.

Enzyme biomarkers of renal tubular injury in arterial surgery patients.

OBJECTIVE: The aim of this study was to verify whether preoperative diabetes, hypertension, and renal function had any relationship with postoperative tubule function in patients submitted to anesthesia for arterial surgery. METHODS: Prospective observational study. One hundred and forty-four patients submitted to anesthesia for arterial surgery enrolled consecutively and divided into four groups: G1--diabetes and hypertension; G2--diabetes; G3--hypertension; and G4--without hypertension or diabetes. Urine was obtained for laboratory analysis of urinary creatinine (Ucr), alkaline phosphatase (AP), γ-glutamyltransferase (γGT), and blood for cystatin C and creatinine before the surgery (M1) and 24 h after the surgery (M2). RESULTS: Values of γGT, γGT/Ucr, and AP × Î³GT/Ucr increased at M2 in G4. Patients without renal function compromise (GFR ≥90 mL/min/1.73 m(2)) presented increased γGT/Ucr and AP × Î³GT/Ucr values at M2 and those with slightly compromised renal function (60-89 mL/min/1.73 m(2)) presented increased γGT values at M2. There was no correlation between deltaCystatin C and deltaAP, deltaγGT, deltaγGT/Ucr, deltaAP/Ucr, and deltaAP × Î³GT/Ucr. CONCLUSIONS: Diabetes, hypertension, and preoperative renal function seem to interfere in tubular enzymuria immediately after surgery in arteriopathic patients. However, when these markers do not increase in postoperative period, renal dysfunction cannot be discarded.

Cystatin C and glomerular filtration rate in the cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: The aim of this study was to compare cystatin C versus creatinine as a marker for acute kidney injury in patients submitted to cardiac surgery with cardiopulmonary bypass. METHODS: Fifty consecutive patients submitted to coronary artery bypass grafting were studied. Renal function was evaluated by serum cystatin C and creatinine. Blood samples were obtained from each patient at three time points: before operation, and on the first and fifth postoperative days. Glomerular filtration rate (GFR) was calculated by Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Larsson (Cys-GFR) formulas. RESULTS: Creatinine and GFR by CG and MDRD formulas did not show statistical difference between study times. After renal injury from surgery, there was an increase in cystatin C on the 1st and 5th day after surgery, being significantly different on the 5th postoperative (P<0.01). The GFR by Larson formula was higher in the preoperative time (105.2 +/- 41.0 ml/min) than in the 5th postoperative day (89.5+/- 31.5 ml/min; P<0.012). CONCLUSION: The cystatin C and the Cys-GFR showed significant changes after cardiac surgery when compared with the creatinine and respective GFR calculated by the Cockcroft-Gault and MDRD formulas.