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1.
Minerva Anestesiol ; 87(7): 766-773, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33591143

RESUMO

BACKGROUND: Fractured neck of femur (FNF) is a common cause of morbidity and mortality in elderly. Spinal catheter allows fractionation of local anesthetic dose which combined with intrathecal opioid leads to a dose reduction and better hemodynamic stability. The primary objective of this paper was to investigate the initial minimum local anesthetic dose (iMLAD) of 0.5% isobaric bupivacaine with 20 µg of fentanyl administered via spinal catheter in order to commence the operative fixation of FNF. METHODS: A prospective, single-blinded, adaptive clinical trial with patients undergoing dynamic hip screw implantation (DHS) or hemiarthroplasty (HEMI) due to FNF. The Dixon and Massey's up and down method was used to determine the ED50 of intrathecal bupivacaine. This figure was confirmed with Probit analysis, in addition to the ED95. RESULTS: Using the Dixon and Massey's approach, the iMLADED50 for DHS was 0.29 mL (1.45 mg) and the iMLADED50 for HEMI was 0.33 mL (1.65 mg) of 0.5% isobaric bupivacaine. The Probit analyses demonstrated that the iMLADED95 for DHS and HEMI were 0.32 mL (1.6 mg) and 0.34 mL (1.7 mg) respectively. The mean cumulative dose of 0.5% bupivacaine for the whole surgery was 0.67 mL (3.35 mg) and 0.87 mL (4.35 mg) in the DHS and HEMI groups, respectively. CONCLUSIONS: This study demonstrates that the placement of a spinal catheter allows for careful titration of local anesthetic, enabling a reduction of the initial intrathecal dose of 0.5% isobaric bupivacaine below 0.4 mL (2 mg) and leading to a significant reduction of a dose required for the whole surgery when combined with an intrathecal opioid.


Assuntos
Raquianestesia , Fraturas do Colo Femoral , Idoso , Anestésicos Locais , Bupivacaína , Método Duplo-Cego , Fraturas do Colo Femoral/cirurgia , Fentanila , Humanos , Injeções Espinhais , Estudos Prospectivos
2.
Crit Care Med ; 47(5): e403-e411, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30985462

RESUMO

OBJECTIVES: Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure. DESIGN: Randomized, controlled in vivo animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg). INTERVENTIONS: In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes. MEASUREMENTS AND MAIN RESULTS: Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson's r = 0.669 or r = 0.632, respectively). CONCLUSIONS: we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.


Assuntos
Isquemia Mesentérica , Metano , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Testes Respiratórios , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Isquemia Mesentérica/fisiopatologia , Metano/farmacologia , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Traumatismo por Reperfusão/fisiopatologia , Suínos
3.
Eur J Cardiothorac Surg ; 56(1): 135-142, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649294

RESUMO

OBJECTIVES: Extracorporeal circulation induces cellular and humoral inflammatory reactions, thus possibly leading to detrimental secondary inflammatory responses. Previous data have demonstrated the bioactive potential of methane and confirmed its anti-inflammatory effects in model experiments. Our goal was to investigate the in vivo consequences of exogenous methane administration on extracorporeal circulation-induced inflammation. METHODS: Two groups of anaesthetized Vietnamese minipigs (non-treated and methane treated, n = 5 each) were included. Standard central cannulation was performed, and extracorporeal circulation was maintained for 120 min without cardiac arrest or ischaemia, followed by an additional 120-min observation period with haemodynamic monitoring. In the methane-treated group, 2.5% v/v methane-normoxic air mixture was added to the oxygenator sweep gas. Blood samples through the central venous line and tissue biopsies from the heart, ileum and kidney were taken at the end point to determine the whole blood superoxide production (chemiluminometry) and the activity of xanthine-oxidoreductase and myeloperoxidase, with substrate-specific reactions. RESULTS: Methane treatment resulted in significantly higher renal blood flow during the extracorporeal circulation period compared to the non-treated group (63.9 ± 16.4 vs 29.0 ± 9.3 ml/min). Whole blood superoxide production (548 ± 179 vs 1283 ± 193 Relative Light Unit (RLU)), ileal myeloperoxidase (2.23 ± 0.2 vs 3.26 ± 0.6 mU/(mg protein)) and cardiac (1.5 ± 0.6 vs 4.7 ± 2.5 pmol/min/mg), ileal (2.2 ± 0.6 vs 7.0 ± 3.4 pmol/min/mg) and renal (1.2 ± 0.8 vs 13.3 ± 8.0 pmol/min/mg) xanthine-oxidoreductase activity were significantly lower in the treated group. CONCLUSIONS: The addition of bioactive gases, such as methane, through the oxygenator of the extracorporeal circuit represents a novel strategy to influence the inflammatory effects of extracorporeal perfusion in cardiac surgical procedures.


Assuntos
Anti-Inflamatórios , Circulação Extracorpórea/efeitos adversos , Inflamação , Metano , Administração por Inalação , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/prevenção & controle , Masculino , Metano/administração & dosagem , Metano/farmacologia , Metano/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Suínos , Porco Miniatura
4.
Turk J Surg ; 34(3): 205-211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30302425

RESUMO

OBJECTIVES: Pericardial tamponade is a life-threatening medical emergency, when the hemodynamic consequences of low cardiac output severely disturb the perfusion of the peripheral tissues. Our aim was to design a reliable large animal model to reproduce the clinical scenario with the relevant pathophysiological consequences of pericardial tamponade -induced cardiogenic shock. MATERIAL AND METHODS: Anesthetized Vietnamese mini pigs were used (n=12). Following laparotomy, a cannula was fixed into the pericardium through the diaphragm without thoracotomy. A sham-operated group (n=6) served as control, while in the second group (n=6) pericardial tamponade was induced by intra-pericardial injection of heparinized own blood. Throughout the 60-min pericardial tamponade and the 180-min reperfusion, macro hemodynamics, renal circulation and the mesenteric macro- and micro-circulatory parameters were monitored. Myeloperoxidase activity was measured to detect neutrophil leukocyte accumulation and in vivo histology was performed by confocal laser scanning endomicroscopy to observe the structural changes of the intestinal mucosa. RESULTS: PT increased the central venous pressure, heart rate, and decreased mean arterial pressure. The mesenteric artery flow (from 355.5±112.4 vs 182.0±59.1 mL/min) and renal arterial flow (from 159.63±50.7 vs 35.902±27.9 mL//min) and the micro-circulation of the ileum was reduced. The myeloperoxidase activity was elevated (from 3.66±1.6 to 7.01±1.44 mU/mg protein) and manifest injury of the ileal mucosa was present. CONCLUSION: This experimental model suitably mimics the hemodynamics and the pathology of clinical pericardial tamponade situations, and on this basis, it provides an opportunity to study the adverse macro- and micro-circulatory effects and biochemical consequences of human cardiogenic shock.

5.
Free Radic Biol Med ; 120: 160-169, 2018 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-29550332

RESUMO

Our aim was to characterize the main components of the nitrosative response with quantitative changes of the nitrergic myenteric neurons in adjacent intestinal segments after transient superior mesenteric artery occlusion. We also tested the hypothesis that exogenous methane may modulate the evolution of nitroxidation by influencing xanthine oxidoreductase (XOR) activity. The microcirculatory consequences of a 50 min ischemia or ischemia-reperfusion were investigated in anesthetized rats (n = 124) inhaling normoxic air with or without 2.2% methane. XOR activities, nitrogen monoxide (NO), nitrite/nitrate (NOx), and nitrotyrosine levels were measured, together with relative nitrergic neuron ratios from duodenum, ileum and colon samples. The effects of methane on XOR were also examined in vitro. The intramural flow stopped only in the ileum during ischemia. The highest baseline XOR activity was found in the duodenum, which increased further during ischemia. NO and nitrotyrosine levels rose, and the nNOS-immunopositive neuron ratio and NOx level both dropped. Reperfusion uniformly elevated XOR activity and nitrotyrosine formation, with the highest level attained in the duodenum, where the nitrergic neuron ratio remained depressed. These alterations were eliminated in methane-treated animals, XOR activity and nitrotyrosine formation decreased in all sites, and the duodenal nitrergic neuron ratio was re-established. The inhibitory effect of methane on XOR-linked nitrate reductase activity was also demonstrated in vitro. With segment-specific microcirculatory alterations, the risk for nitrosative stress is highest in transiently hypoxic tissues with high endogenous XOR activities. The XOR-inhibitory effect of methane can reduce nitroxidation and protects the nitrergic neuron population in such conditions.


Assuntos
Isquemia Mesentérica/enzimologia , Metano/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Nitrosativo/efeitos dos fármacos , Xantina Desidrogenase/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Masculino , Plexo Mientérico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/enzimologia
6.
Orv Hetil ; 159(5): 163-167, 2018 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-29376423

RESUMO

Acute pericardial tamponade is one of the most emergent clinical scenarios in cardiac surgery. With numerous causes in the background, pericardial tamponade can lead to cardiogenic shock and death. In modern diagnostic era, the recognition of pericardial tamponade is simple, but its management and the long-term effects can still be challenging. Without the detailed understanding of the pathophysiological pathways diagnostic and therapeutic management plans of pericardial tamponade is very difficult. The aim of this review was to give a complex picture of pericardial tamponade, from its role in medical history to pathophysiology and its significance in surgical experimental models. Orv Hetil. 2018; 159(5): 163-167.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Tamponamento Cardíaco/prevenção & controle , Tamponamento Cardíaco/fisiopatologia , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/etiologia , Ecocardiografia , Humanos , Derrame Pericárdico/etiologia
7.
Inflammopharmacology ; 26(1): 261-271, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28451776

RESUMO

BACKGROUND: We have developed a novel compound from acetylsalicylic acid (ASA) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors with ASA-like anti-inflammatory efficacy and reduced the mucosa-damaging side-effects. Our aim was to examine local and remote consequences of ASA-Tris administration in 2-,4-,6-trinitrobenzene-sulfonic acid (TNBS)-induced colitis as compared to ASA or mesalamine (5-aminosalicylate) treatment. METHODS: Sprague-Dawley rats were randomized to five groups (n = 6, each), and TNBS enemas were performed. Group 1 was the negative control; group 2 was the untreated colitis group. 12 hour after colitis induction repeated doses of ASA, ASA-Tris (both 0.55 mmol/kg) and mesalamine (0.77 mmol/kg) were given 3 times daily for 3 days to groups 3-5. On day 3 of colitis, the in vivo histology of the colon and stomach was investigated. Tissue xanthine-oxidoreductase, myeloperoxidase, nitrite/nitrate changes, and circulating TNF-alpha levels were measured. In addition, liver mitochondria were examined with high-resolution respirometry to analyze alterations in the electron transport chain. RESULTS: TNBS enema significantly elevated inflammatory enzyme activities, NO production, TNF-alpha concentration, and induced morphological damage in the colon. ASA-treatment reduced the inflammatory marker levels and mucosal injury in the colon, but gastric tissue damage was present. ASA-Tris- and mesalamine-treatments significantly reduced the cytokine levels, inflammatory enzyme activities, and colonic mucosal damage without inducing gastric injury. Also, ASA significantly reduced the Complex IV-linked respiration of liver mitochondria, which was not observed after ASA-Tris-treatment. CONCLUSION: As compared to ASA, ASA-Tris conjugation provides significant protection against the colonic injury and cytokine-mediated progression of inflammatory events in experimental colitis without influencing the gastric epithelial structure.


Assuntos
Aspirina/farmacologia , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Metilaminas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Colite/metabolismo , Colo/metabolismo , Modelos Animais de Doenças , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Mesalamina/farmacologia , Nitratos/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Ácido Trinitrobenzenossulfônico/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
8.
Magy Seb ; 70(4): 297-302, 2017 12.
Artigo em Húngaro | MEDLINE | ID: mdl-29183138

RESUMO

INTRODUCTION: Pericardial tamponade (PT) is a life-threatening condition, with low cardiac output. The hemodynamic consequences of PT can severely affect the circulation of all tissues, including the microcirculation of the kidneys and the intestinal mucosa. Our aim was to develop a hemodynamically stable and controllable large animal model of PT to study the consequences of cardiogenic shock. METHODS: Two groups of anesthetized vietnamese minipigs (n = 6, both groups) were used. Following laparotomy, a cannula was fixed into the pericardium through the diaphragm without thoracotomy. A sham-operated group served as control, in the second group 60-min PT was induced by intrapericardial injection of heparinised own blood. Throughout PT and 180-min reperfusion, macrohemodynamics, renal circulation and mesenteric macro- and microcirculation were monitored. Myeloperoxidase (MPO) activity was measured and in vivo histology was performed by confocal laser scanning endomicroscopy. RESULTS: The PT increased central venous pressure, heart rate and decreased mean arterial pressure, mesenteric flow (from 355.5 ± 112.4 vs 182.0 ± 59.1 ml/min) and renal arterial flow (from 159.63 ± 50.7 vs 35.902 ± 27.9 ml/min) and the microcirculation of the ileum. Elevated MPO activity (3.66 ± 1.6 vs 7.01 ± 1.44 mU/mg protein) and injury of the ileal mucosa were present also. SUMMARY: The reproducible large animal model is suitable for clinically relevant investigations of the hemodynamic and biochemical consequences of PT.


Assuntos
Tamponamento Cardíaco/fisiopatologia , Hemodinâmica/fisiologia , Microcirculação/fisiologia , Choque Cardiogênico/fisiopatologia , Animais , Modelos Animais de Doenças , Íleo/fisiopatologia , Mucosa Intestinal/fisiopatologia , Suínos , Porco Miniatura
9.
Magy Seb ; 70(3): 221-231, 2017 09.
Artigo em Húngaro | MEDLINE | ID: mdl-28876118

RESUMO

INTRODUCTION: Non-occlusive mesenteric ischemia (NOMI) develops without anatomical causes. Early diagnosis is challenging and treatments are of questionable effectiveness. We investigated the role of complement activation in the pathophysiology of NOMI in animal models through the inhibition of complement C5a. MATERIALS AND METHODS: 60-min partial aortic occlusion (PAO; abdominal aorta, proximal to celiac trunk; mean arterial pressure: 30-40 mmHg) was established in Sprague-Dawley rats (n = 28) and 60-min cardiac tamponade in minipigs (n = 19; mean arterial pressure: 40-50 mmHg) to observe short- and long-term circulatory and inflammatory consequences of NOMI. Macro- and microhemodynamics, leukocyte infiltration, plasma levels of inflammatory mediators (endothelin, HMGB-1) were measured. C5a inhibitor (Acetyl-Peptid-A; 4 mg/kg iv) was administered at the 45th min of PAO or tamponade, respectively. RESULTS: Twenty-four hours after PAO systemic inflammatory response increased cardiac output and superior mesenteric artery flow (SMAF). C5a inhibition reduced the elevated cardiac output (203.1 ± 5 vs 269.6 ± 8.1 ml/min/kg) and SMAF and increased ileal microcirculation (833.5 ± 33.8 vs 441.9 ± 22.4 µm/s). In pigs, after the tamponade, C5a inhibition reduced the immediate hemodynamic disturbances, temporarily increased SMAF and permanently the ileal microcirculation. The Acetyl-Peptid-A treatment reduced leukocyte infiltration and plasma levels of inflammatory mediators in both NOMI models. CONCLUSIONS: Complement activation plays central role in the macro- and microcirculatory disturbance during NOMI. C5a inhibition reduces the inflammatory activation and influences the hemodynamic consequences of experimental NOMI.


Assuntos
Hemodinâmica/efeitos dos fármacos , Isquemia Mesentérica/tratamento farmacológico , Serina Endopeptidases/farmacologia , Animais , Modelos Animais de Doenças , Hemodinâmica/fisiologia , Isquemia Mesentérica/fisiopatologia , Microcirculação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Suínos
10.
Surgery ; 161(6): 1696-1709, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28242089

RESUMO

BACKGROUND: Methane is part of the gaseous environment of the intestinal lumen. The purpose of this study was to elucidate the bioactivity of exogenous methane on the intestinal barrier function in an antigen-independent model of acute inflammation. METHODS: Anesthetized rats underwent sham operation or 45-min occlusion of the superior mesenteric artery. A normoxic methane (2.2%)-air mixture was inhaled for 15 min at the end of ischemia and at the beginning of a 60-min or 180-min reperfusion. The integrity of the epithelial barrier of the ileum was assessed by determining the lumen-to-blood clearance of fluorescent dextran, while microvascular permeability changes were detected by the Evans blue technique. Tissue levels of superoxide, nitrotyrosine, myeloperoxidase, and endothelin-1 were measured, the superficial mucosal damage was visualized and quantified, and the serosal microcirculation and mesenteric flow was recorded. Erythrocyte deformability and aggregation were tested in vitro. RESULTS: Reperfusion significantly increased epithelial permeability, worsened macro- and microcirculation, increased the production of proinflammatory mediators, and resulted in a rapid loss of the epithelium. Exogenous normoxic methane inhalation maintained the superficial mucosal structure, decreased epithelial permeability, and improved local microcirculation, with a decrease in reactive oxygen and nitrogen species generation. Both the deformability and aggregation of erythrocytes improved with incubation of methane. CONCLUSION: Normoxic methane decreases the signs of oxidative and nitrosative stress, improves tissue microcirculation, and thus appears to modulate the ischemia-reperfusion-induced epithelial permeability changes. These findings suggest that the administration of exogenous methane may be a useful strategy for maintaining the integrity of the mucosa sustaining an oxido-reductive attack.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Íleo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Metano/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Administração por Inalação , Animais , Modelos Animais de Doenças , Endotelina-1/efeitos dos fármacos , Endotelina-1/metabolismo , Íleo/metabolismo , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Masculino , Artéria Mesentérica Superior/cirurgia , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Valores de Referência , Traumatismo por Reperfusão/patologia
11.
BMC Anesthesiol ; 16(1): 79, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27658581

RESUMO

BACKGROUND: Fractured neck of femur is a common cause of hospital admission in the elderly and usually requires operative fixation. In a variety of clinical settings, preoperative glucocorticoid administration has improved analgesia and decreased opioid consumption. Our objective was to define the postoperative analgesic efficacy of single dose of dexamethasone administered preoperatively in patients undergoing operative fixation of fractured neck of femur. METHODS: Institutional ethical approval was granted and written informed consent was obtained from each patient. Patients awaiting for surgery at Cork University Hospital were recruited between July 2009 and August 2012. Participating patients, scheduled for surgery were randomly allocated to one of two groups (Dexamethasone or Placebo). Patients in the dexamethasone group received a single dose of intravenous dexamethasone 0.1 mg kg -1 immediately preoperatively. Patients in the placebo group received the same volume of normal saline. Patients underwent operative fixation of fractured neck of femur using standardised spinal anaesthesia and surgical techniques. The primary outcome was pain scores at rest 6 h after the surgery. RESULTS: Thirty seven patients were recruited and data from thirty patients were analysed. The groups were similar in terms of patient characteristics. Pain scores at rest 6 h after the surgery (the principal outcome) were lesser in the dexamethasone group compared with the placebo group [0.8(1.3) vs. 3.9(2.9), mean(SD) p = 0.0004]. Cumulative morphine consumption 24 h after the surgery was also lesser in the dexamethasone group [7.7(8.3) vs. 15.1(9.4), mean(SD) mg, p = 0.04]. CONCLUSIONS: A single dose of intravenous dexamethasone 0.1 mg kg -1 administered before operative fixation of fractured neck of femur improve significantly the early postoperative analgesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01550146 , date of registration: 07/03/2012.

12.
Surgery ; 159(3): 960-71, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26632492

RESUMO

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) can evolve in a variety of low-flow states. Although the mechanisms leading to NOMI-related intestinal necrosis are largely unknown, circumstantial evidence suggests that excessive vasoconstriction and complement activation both play important roles in this process. Because targeting of the circulatory malfunction of the splanchnic area could be of therapeutic relevance, we set out to investigate the long-term effects of treatment with a complement C5a antagonist in a rat model of partial aortic occlusion (PAO)-induced transient mesenteric hypoperfusion. METHODS: The mean arterial pressure of the splanchnic area was kept between 30 and 40 mm Hg by 60 minutes of PAO in anesthetized male Sprague-Dawley rats. C5a inhibitor acetyl-peptide-A (AcPepA; 4 mg kg(-1) intravenously) or vehicle administration was initiated at the 45th minute of PAO. After 24 hours, the animals were reanesthetized to record the macrohemodynamics and ileal microcirculation, and plasma and tissue samples were taken for determination of high-mobility group box protein-1 (HMGB-1), endothelin-1, tumor necrosis factor (TNF)-α levels, and small intestinal leukocyte infiltration. Epithelial structural changes were visualized by in vivo confocal laser scanning endomicroscopy. RESULTS: At 24 hours after PAO, mean arterial pressure, heart rate, and cardiac output were significantly greater, the intestinal intramural microcirculation was significantly impaired, and plasma HMGB-1, endothelin-1, TNF-α levels, the degree of epithelial damage and leukocyte infiltration was increased. The AcPepA treatment moderated the hemodynamic and microcirculatory changes, and decreased inflammatory activation and histologic signs of mucosal damage. CONCLUSION: C5a inhibition ameliorated the potentially harmful local mesenteric hypoperfusion and global long-term inflammatory consequences of PAO. This approach is of promise for use in NOMI-associated situations.


Assuntos
Hemodinâmica/efeitos dos fármacos , Íleo/irrigação sanguínea , Inflamação/sangue , Isquemia Mesentérica/tratamento farmacológico , Serina Endopeptidases/farmacologia , Análise de Variância , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Endotelina-1/sangue , Proteína HMGB1/sangue , Hemodinâmica/fisiologia , Inflamação/fisiopatologia , Masculino , Isquemia Mesentérica/patologia , Microcirculação/efeitos dos fármacos , Microscopia de Vídeo , Análise Multivariada , Projetos Piloto , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/sangue , Grau de Desobstrução Vascular/efeitos dos fármacos
13.
Eur J Anaesthesiol ; 32(11): 759-63, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25693137

RESUMO

BACKGROUND: Femoral neck fractures usually require operative fixation. Spinal anaesthesia is the preferred technique for many anaesthetists, although single-shot spinal anaesthesia may have severe haemodynamic side-effects. OBJECTIVE: To determine the initial minimum intrathecal dose of 0.5% isobaric bupivacaine required in order to achieve surgical anaesthesia within 15 min. DESIGN: Prospective controlled trial using the Dixon and Massey up-and-down method. SETTING: Patients awaiting surgery for proximal femoral fractures at Cork University Hospital were recruited between September 2012 and December 2012. PATIENTS: With institutional ethics approval and having obtained written informed consent from each, American Society of Anesthesiologists' physical status I to III patients aged more than 60 years were recruited. Twenty-three patients were recruited to the study, of which 22 were managed as per protocol. One patient was excluded because of the inability to insert an intrathecal catheter. INTERVENTION: A 22-guage spinal catheter was inserted between the L3 and L5 vertebral levels. An initial dose of 1 ml 0.5% isobaric bupivacaine was arbitrarily chosen as a starting point. The dose in subsequent patients was determined by the outcome of the preceding spinal block and adjusted by 0.1 ml until data on six independent pairs of patients with successful block/failed block were acquired. MAIN OUTCOME MEASURES: The minimum effective local anaesthetic dose of intrathecal 0.5% isobaric bupivacaine to achieve surgical anaesthesia was defined as the primary outcome. RESULTS: The minimum effective local anaesthetic dose of 0.5% bupivacaine was 0.24 ml (95% confidence interval 0.18 to 0.68). CONCLUSION: Our findings may influence clinicians' initial dose selection for spinal anaesthesia when a spinal catheter is used. The dose may be less than previously thought. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01680120.


Assuntos
Raquianestesia/métodos , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Fraturas do Colo Femoral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Hospitais Universitários , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
BMC Anesthesiol ; 14: 6, 2014 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-24460975

RESUMO

BACKGROUND: Fractured neck of femur generally requires operative fixation and is a common cause of admission to hospital. The combination of femoral nerve block and spinal anesthesia is a common anesthetic technique used to facilitate the surgical procedure. The optimal disposition of local anesthetic (LA) relative the femoral nerve (FN) has not been defined. Our hypothesis was: that the deposition of LA relative to the FN influences the quality of analgesia for positioning of the patient for performance of spinal anesthesia. The primary outcome was verbal rating (VRS) pain scores 0-10 assessed immediately after positioning the patient to perform spinal anesthesia. METHODS: With Institutional ethical approval and having obtained written informed consent from each, 52 patients were studied. The study was registered with ClinicalTrials.gov (NCT01527812). Patients were randomly allocated to undergo to one of three groups namely: intention to deposit lidocaine 2% (15 ml) i. above (Group A), ii. below (Group B), iii. circumferential (Group C) to the FN. A blinded observer assessed i. the sensory nerve block (cold) in the areas of the terminal branches of the FN and ii. VRS pain scores on passive movement from block completion at 5 minutes intervals for 30 minutes. Immediately after positioning the patient for spinal anesthesia, VRS pain scores were recorded. RESULTS: Pain VRS scores during positioning were similar in the three groups [Above group/Below group/Circumferential group: 2(0-9)/0(0-10)/3(0-10), median(range), p:0.32]. The block was deemed to have failed in 20%, 47% and 12% in the Above group, Below group and Circumferential group respectively. The median number of needle passes was greater in the Circumferential group compared with the Above group (p:0.009). Patient satisfaction was greatest in the Circumferential group [mean satisfaction scores were 83.5(19.8)/88.1(20.5)/93.8(12.3), [mean(SD), p=0.04] in the Above, Below and Circumferential groups respectively. CONCLUSIONS: We conclude that there is no clinical advantage to attempting to deposit LA circumferential to the femoral nerve (relative to depositing LA either above or below the nerve), during femoral nerve block in this setting.


Assuntos
Anestésicos Locais/administração & dosagem , Bloqueio Nervoso Autônomo/métodos , Nervo Femoral/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Idoso , Idoso de 80 Anos ou mais , Vias de Administração de Medicamentos , Feminino , Nervo Femoral/efeitos dos fármacos , Humanos , Masculino , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Método Simples-Cego
15.
Med Ultrason ; 15(3): 224-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23979618

RESUMO

Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.


Assuntos
Anestesia por Condução/métodos , Anestésicos Locais/administração & dosagem , Plexo Braquial/efeitos dos fármacos , Plexo Braquial/diagnóstico por imagem , Clavícula/diagnóstico por imagem , Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção/métodos , Humanos
16.
Perioper Med (Lond) ; 1: 4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-24764520

RESUMO

BACKGROUND: Peripheral nerve blocks are effective in treating acute pain, thereby minimizing the requirement for opiate analgesics. Fractured neck of femur (FNF) is a common, painful injury. The provision of effective analgesia to this cohort is challenging but an important determinant of their functional outcome. We investigated the analgesic efficacy of continuous femoral nerve block (CFNB) in patients with FNF. METHODS: Following institutional ethical approval and with informed consent, patients awaiting FNF surgery were randomly allocated to receive either standard opiate-based analgesia (Group 1) or a femoral perineural catheter (Group 2). Patients in Group 1 received parenteral morphine as required. Those in Group 2 received a CFNB comprising a bolus of local anaesthetic followed by a continuous infusion of 0.25% bupivacaine. For both Groups, rescue analgesia consisted of intramuscular morphine as required and all patients received paracetamol regularly. Pain was assessed using a visual analogue scale at rest and during passive movement (dynamic pain score) at 30 min following first analgesic intervention and six hourly thereafter for 72 hours. Patient satisfaction with the analgesic regimen received was recorded using verbal rating scores (0-10). The primary outcome measured was dynamic pain score from initial analgesic intervention to 72 hours later. RESULTS: Of 27 recruited, 24 patients successfully completed the study protocol and underwent per protocol analysis. The intervals from recruitment to the study until surgery were similar in both groups [31.4(17.7) vs 27.5(14.2) h, P = 0.57]. The groups were similar in terms of baseline clinical characteristics. For patients in Group 2, pain scores at rest were less than those reported by patients in Group 1 [9.5(9.4) vs 31(28), P = 0.031]. Dynamic pain scores reported by patients in Group 2 were less at each time point from 30 min up to 54 hours [e.g at 6 h 30.7(23.4) vs 67.0(32.0), P = 0.004]. Cumulative morphine consumption over 72 h was less in Group 2. Patient satisfaction scores were greater in Group 2 [9.4(1.1) vs 7.6(1.8), P = 0.014]. CONCLUSIONS: CFNB provides more effective perioperative analgesia than a standard opiate-based regimen for patients undergoing fixation of FNF. It is associated with lesser opiate use and greater patient satisfaction.

17.
Med Ultrason ; 12(2): 139-44, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21173942

RESUMO

Femoral nerve blockade is the most widely performed lower limb block. Methods of femoral nerve blockade are briefly reviewed with particular reference to ultrasound guidance.


Assuntos
Nervo Femoral/diagnóstico por imagem , Bloqueio Nervoso/métodos , Ultrassonografia de Intervenção/métodos , Nervo Femoral/anatomia & histologia , Humanos
18.
Med Ultrason ; 12(3): 223-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21203600

RESUMO

Thoracic paravertebral blockade is a simple and easy-to-learn technique with a low incidence of complications. It should be considered as a safe alternative to thoracic epidural analgesia/anaesthesia. We reviewed the techniques of thoracic paravertebral blockade with special interest to ultrasound guidance.


Assuntos
Bloqueio Nervoso/métodos , Vértebras Torácicas/anatomia & histologia , Tórax/anatomia & histologia , Ultrassonografia de Intervenção , Humanos , Vértebras Torácicas/inervação , Tórax/inervação
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