Inhibition of Autonomic Storm by Epidural Anesthesia Does Not Influence Cardiac Inflammatory Response After Brain Death in Rats

Background. After brain death (BD) donors usually experience cardiac dysfunction, which is responsible for a considerable number of unused organs. Causes of this cardiac dysfunction are not fully understood. Some authors argue that autonomic storm with severe hemodynamic instability leads to inflammatory activation and myocardial dysfunction. Objectives. To investigate the hypothesis that thoracic epidural anesthesia blocks autonomic storm and improves graft condition by reducing the inflammatory response. Methods. Twenty-eight male Wistar rats (250-350 g) allocated to four groups received saline or bupivacaine via an epidural catheter at various times in relation to brain-death induction. Brain death was induced by a sudden increase in intracranial pressure by rapid inflation of a ballon catheter in the extradural space. Blood gases, electrolytes, and lactate analyses were performed at time zero, and 3 and 6 hours. Blood leukocytes were counted at 0 and 6 hours. After 6 hours of BD, we performed euthanasia to measure vascular adhesion molecule (VCAM)-1, intracellular adhesion molecule (ICAM)-1, interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, Bcl-2 and caspase-3 on cardiac tissue. Results. Thoracic epidural anesthesia was effective to block the autonomic storm with a significant difference in mean arterial pressure between the untreated (saline) and the bupivacaine group before BD (P < .05). However, no significant difference was observed for the expressions of VCAM-1, ICAM-1, TNF-alpha, IL-1 beta, Bcl-2, and caspase-3 (P > .05). Conclusion. Autonomic storm did not seem to be responsible for the inflammatory changes associated with BD; thoracic epidural anesthesia did not modify the expression of inflammatory mediators although it effectively blocked the autonomic storm.

Effects of thoracic epidural anesthesia on hemodynamics and global oxygen transport in ovine endotoxemia

Besides providing effective analgesia, thoracic epidural anesthesia (TEA) has been shown to decrease perioperative morbidity and mortality. Because of its vasodilatory properties in association with the sympathetic blockade, however, TEA may potentially aggravate cardiovascular dysfunctions resulting from sepsis and systemic inflammatory response syndrome. The objective of the present study was to assess the effects of TEA on hemodynamics, global oxygen transport, and renal function in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 18), Salmonella typhosa endotoxin was centrally infused at incremental doses to induce and maintain a hypotensive-hypodynamic circulation using an established protocol. The animals were then randomly assigned to one of two groups. In the treatment group, continuous TEA was initiated with 0.1 mL.kg of 0.125% bupivacaine at the onset of endotoxemia and maintained with 0.1 mL.kg.h. In the control group, the same amount of isotonic sodium chloride solution was injected through the epidural catheter. In the animals surviving the entire experiment (n = 7 per group), cardiac index and mean arterial pressure decreased in a dose-dependent manner during endotoxin infusion. In the TEA group, neither systemic hemodynamics nor global oxygen transport were impaired beyond the changes caused by endotoxemia itself. Urinary output was increased in the TEA group as compared with the control group (P < 0.05). In this model of endotoxic shock, TEA improved renal perfusion without affecting cardiopulmonary hemodynamics and global oxygen transport.

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair

OBJECTIVE: To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. STUDY DESIGN: Blind, randomized clinical study. ANIMALS: Dogs with femoral (n=18) or pelvic (27) fractures. METHODS: Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. RESULTS: Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. CONCLUSIONS: Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. CLINICAL RELEVANCE: Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.

Continuous thoracic epidural anesthesia improves gut mucosal microcirculation in rats with sepsis

Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. The present study was designed as a prospective and controlled laboratory experiment to assess the effects of continuous TEA on the mucosal microcirculation in a cecal ligation and perforation model of sepsis in rats. Anesthetized Sprague-Dawley rats underwent laparotomy and cecal ligation and perforation to induce sepsis. Subsequently, either bupivacaine 0.125% (n = 10) or isotonic sodium chloride solution (n = 9) was continuously infused via the thoracic epidural catheter for 24 h. In addition, a sham laparotomy was carried out in eight animals. Intravital videomicroscopy was then performed on six to ten villi of ileum mucosa. The capillary density was measured as areas encircled by perfused capillaries, that is, intercapillary areas. The TEA accomplished recruitment of microcirculatory units in the intestinal mucosa by decreasing total intercapillary areas (1,317 +/- 403 vs. 1,001 +/- 236 microm2) and continuously perfused intercapillary areas (1,937 +/- 512 vs. 1,311 +/- 678 microm2, each P < 0.05). Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.

Effects of Local Anesthetic on the Time Between Analgesic Boluses and the Duration of Labor in Patient-Controlled Epidural Analgesia: Prospective Study of Two Ultra-Low Dose Regimens of Ropivacaine and Sufentanil

BACKGROUND: Patient-controlled epidural analgesia with low concentrations of anesthetics is effective in reducing labor pain. The aim of this study was to assess and compare two ultra-low dose regimens of ropivacaine and sufentanil (0.1% ropivacaine plus 0.5 μg.ml-1 sufentanil vs. 0.06% ropivacaine plus 0.5 μg.ml-1 sufentanil) on the intervals between boluses and the duration of labor. MATERIAL AND METHODS: In this non-randomized prospective study, conducted between January and July 2010, two groups of parturients received patient-controlled epidural analgesia: Group I (n = 58; 1 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil) and Group II (n = 57; 0.6 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil). Rescue doses of ropivacaine at the concentration of the assigned group without sufentanil were administered as necessary. Pain, local anesthetic requirements, neuraxial blockade characteristics, labor and neonatal outcomes, and maternal satisfaction were recorded. RESULTS: The ropivacaine dose was greater in Group I (9.5 [7.7-12.7] mg.h-1 vs. 6.1 [5.1-9.8 mg.h-1], p < 0.001). A time increase between each bolus was observed in Group I (beta = 32.61 min, 95% CI [25.39; 39.82], p < 0.001), whereas a time decrease was observed in Group II (beta = -1.40 min, 95% CI [-2.44; -0.36], p = 0.009). The duration of the second stage of labor in Group I was significantly longer than that in Group II (78 min vs. 65 min, p < 0.001). CONCLUSIONS: Parturients receiving 0.06% ropivacaine exhibited less evidence of cumulative effects and exhibited faster second stage progression than those who received 0.1% ropivacaine.

Comparación entre analgesia epidural continua vs bloqueo nervio periférico en niños llevados a cirugía múltiple de miembros inferiores

Las cirugías reconstructivas múltiples de miembros inferiores son intervenciones quirúrgicas que implican un difícil manejo analgésico en el postoperatorio, actualmente la técnica analgésica usada es la analgesia peridural; sin embargo los efectos adversos asociados a esta no la hacen una técnica ideal para manejo de dolor. Los bloqueos de nervio periférico han aparecido como una alternativa para el manejo del dolor; pero no se ha difundido ampliamente su uso. Se pretende evaluar la disminución de efectos adversos con el uso de bloqueos de nervio periférico sobre la analgesia epidural. Este estudio piloto inicial se realizo para verificar efectividad técnicas a usar y problemas que se pudieran presentar. Se aplico el protocolo en 23 pacientes que fueron llevados a cirugía de miembros inferiores, se dividieron en 2 grupos 11 recibieron bloqueos de nervio periférico y 12 analgesia epidural. Se les realizo seguimiento por 48 horas y se evaluó el control del dolor, consumo de opioides y efectos adversos. El tiempo de colocación del bloqueo fue similar en ambos grupos, el grupo de bloqueos presento menos episodios de dolor y menos episodios de dolor severo. No se presento retención urinaria en ningún paciente pero en el grupo de epidural se presento mayor incidencia de nausea y vomito (60% vs 45%). Se encontró que los bloqueos de nervio periférico son una adecuada opción para el manejo del dolor en este tipo de cirugías; y al parecer disminuye la incidencia de eventos adversos asociados a la analgesia epidural.

Pre-emptive epidural ketamine or S(+)-ketamine in post-incisional pain in dogs: A comparative study

Objective-To compare the pre-emptive analgesic effects of epidural ketamine or S(+)-ketamine on post-incisional hyperalgesia.Study Design-Prospective randomized study.Animals-Twenty-four mongrel dogs (1-5 years, weighing 11.9 +/- 1.8 kg).Methods-Dogs were anesthetized with propofol (5 mg/kg intravenously) and a lumbosacral epidural catheter was placed. Dogs were randomly allocated to 3 groups, each with 8 dogs. The control group (CG) was administered saline solution (0.3 mL/kg); the ketamine group (KG) ketamine (0.6 mg/kg); and the S(+)-ketamine group (SG) S(+)-ketamine (0.6 mg/kg). The final volume was adjusted to 0.3 mL/kg in all groups. Five minutes after the epidural injection a surgical incision was made in the common pad of the right hind limb and was immediately closed with simple interrupted nylon suture. Respiratory (RR) and heart (HR) rates, rectal temperature (7, sedation (S), lameness score, and mechanical nociceptive threshold by von Frey filaments were evaluated before the propofol anesthesia and at 15, 30, 45, 60, 75, and 90 minutes and then at 2, 4, 6, 8, 12, and 24 hours after epidural injection.Results-There were no differences in RR, HR, T, or S between groups. Motor blockade of the hind limbs was observed during 20 +/- 3.6 minutes in KG and during 30.6 +/- 7.5 minutes in SG (mean SD). Mechanical force applied to obtain an aversive response was higher from 45 minutes to 12 hours in KG and from 60 to 90 minutes in SG, when compared with CG.Conclusions-Pre-emptive epidural ketamine induced no alterations in RR and FIR, and reduced post-incisional hyperalgesia for a longer time than did S(+) ketamine.Clinical Relevance-Although anesthetic and analgesic potency of S(+) ketamine is twice that of ketamine, the racemic form is seemingly better for post-incisional hyperalgesia. (C) Copyright 2004 by the American College of Veterinary Surgeons.

Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in ovariohysterectomized dogs

Objective-To evaluate analgesic effects of epidurally administered neostigmine alone or in combination with morphine in dogs after ovariohysterectomy.Animals-40 healthy bitches.Procedures-After acepromazine premedication, anesthesia was induced. Dogs randomly received 1 of the following 4 epidural treatments 30 minutes before ovariohysterectomy (n = 10/group): saline (0.9% NaCl) solution (control), morphine (0.1 mg/kg), neostigmine (10 pg/kg), or morphine-neostigmine (0.1 mg/kg and 10 pg/kg, respectively). Analgesia was assessed for 24 hours after surgery by use of a visual analogue.scale (VAS; scale of 0 to 10) or numeric descriptive scale (NDS; scale of 0 to 24) and by the need for supplemental analgesia (morphine [0.5 mg/kg, IM] administered when VAS was >= 4 or NDS was >= 8).Results-Significantly more control dogs (n = 8) received supplemental analgesia, compared with the number of neostigmine-treated dogs (1); no dogs in the remaining groups received supplemental analgesia. Compared with values for the control dogs, the NDS scores were lower for morphine-neostigmine-treated dogs (from 2 to 6 hours and at 12 hours) and for morphine-treated dogs (all time points). The NDS scores were lower for morphine-treated dogs at 3, 12, and 24 hours, compared with values for neostigmine-treated dogs. The VAS was less sensitive than the NDS for detecting differences among groups.Conclusions and Clinical Relevance-Epidurally administered neostigmine reduced the use of supplemental analgesia after ovariohysterectorny in dogs. However, analgesic effects were less pronounced than for epidurally administered morphine or morphine-neostigmine. Adding neostigmine to epidurally administered morphine did not potentiate opioid-induced analgesia.

Effects on mother and fetus of epidural and combined spinal-epidural techniques for labor analgesia

OBJETIVO: A peridural (AP) e a técnica de duplo bloqueio (DB) são utilizadas em analgesia para o trabalho de parto. Este estudo comparou os efeitos na mãe e no feto de ambas as técnicas em analgesia e anestesia para o parto. MÉTODOS: Quarenta parturientes ASA I e II receberam por via peridural 15 ml de ropivacaína a 0,125% (grupo AP) e 5 µg de sufentanil com 2,5 mg bupivacaína por via subaracnóidea (grupo DB). Foram avaliados: intensidade de dor, altura do bloqueio sensitivo, tempo de latência, bloqueio motor, duração da analgesia de parto, tempo para a resolução do parto, hipotensão materna e presença de prurido. Os recém-nascidos foram avaliados pelo índice de Apgar e escore da capacidade adaptativa e neurológica (ECAN), método de Amiel-Tison. RESULTADOS: Não houve diferenças significativas entre os grupos na intensidade da dor, no tempo de latência, no nível do bloqueio sensitivo e no índice de Apgar. O bloqueio motor, a duração da analgesia e o tempo para resolução do parto foram maiores no grupo DB, do qual sete parturientes apresentaram prurido leve. ECAN foi maior no grupo AP após meia hora, duas horas e 24 horas. Noventa e cinco por cento dos recém-nascidos do grupo AP e 60% do grupo DB foram considerados neurologicamente vigorosos ao exame de 24 horas. CONCLUSÃO: As duas técnicas mostraram-se eficazes para analgesia do trabalho de parto. As parturientes do grupo DB apresentaram prurido e trabalho de parto mais prolongado. Recém-nascidos de mães que receberam analgesia de parto via peridural apresentaram melhor ECAN.

Efeitos da metadona ou do neostigmine, associados à lidocaína administrados pela via epidural em cães

Seis cães adultos, de raças e sexos variados, com peso de 13,3±3,4kg (média±DP), foram utilizados no estudo. Os animais foram tranqüilizados com acepromazina (0,1mg/kg, IV) e, após 30 minutos, foram aleatoriamente submetidos à anestesia epidural com um dos seguintes tratamentos: lidocaína 2% 0,25ml/kg (controle); neostigmine 0,01mg/kg+lidocaína (NEO); metadona 0,3mg/kg+lidocaína (MET). Todos os animais foram submetidos aos três tratamentos com intervalo mínimo de uma semana. Foram mensuradas as freqüências cardíaca (FC) e respiratória (FR), a pressão arterial sistólica (PAS), o tempo para a perda do reflexo interdigital, a duração e a altura do bloqueio sensitivo, durante um período de 90 minutos. Não houve diferença significativa entre os tratamentos nos valores de FC, PAS e FR, bem como na duração do bloqueio sensitivo e no tempo para a perda do reflexo interdigital. No grupo MET, houve diminuição de FC dos 30 aos 90 minutos em relação ao valor basal. Bloqueio sensitivo mais cranial também foi observado em MET. A associação de neostigmine ou metadona não prolongou o período hábil de anestesia epidural produzido pela lidocaína em cães. A metadona, mas não o neostigmine, parece estender mais cranialmente o bloqueio epidural pela lidocaína.

Anestesia epidural cranial com lidocaína e morfina para campanhas de castração em cães

A castração de machos e fêmeas tem sido preconizada como a principal técnica para redução do grande número de cães errantes. No entanto, vários são os entraves com relação à escolha do melhor protocolo anestésico, em relação à eficácia, segurança e redução de custos. Objetivou-se, com este trabalho, avaliar os efeitos cardiorrespiratórios, hemogasométricos e analgésicos da utilização de lidocaína em um volume maior, associada à morfina, pela via epidural em cadelas submetidas à ovariosalpingohisterectomia (OSH), com ou sem suplementação de oxigênio. Utilizaram-se 12 cadelas, com peso médio de 11,5±3,7kg e idade de um a quatro anos. Os animais receberam como medicação pré-anestésica (MPA) acepromazina (0,1mg kg-1) e meperidina (5mg kg-1), pela via intramuscular. Após 15 minutos, administrou-se tiopental (10mg kg-1), por via intravenosa, seguido de intubação endotraqueal. Nesse momento, os animais foram alocados em dois grupos: o grupo GCO (com oxigênio, n=06) recebeu suplementação de oxigênio 100% e o grupo GSO (sem oxigênio, n=06) permaneceu intubado sem suplementação de oxigênio. Após a intubação, foi administrada, pela via epidural, em ambos os grupos, morfina (0,1mg kg-1) em volume final ajustado para 1mL 3,0kg-1 de peso com lidocaína 2% sem vasoconstritor. Imediatamente após a anestesia epidural, os animais foram posicionados em decúbito dorsal com a cabeça no mesmo plano do corpo, e iniciou-se o procedimento cirúrgico, o qual foi padronizado em 30 minutos. em ambos os grupos, foi possível realizar a cirurgia sem a necessidade de complementação analgésica e sem resposta de dor. A pressão arterial média (PAM) foi menor no GSO em todos os momentos em comparação ao basal. No GCO, a PAM foi menor após MPA e após epidural. Houve redução da f de M1 até M6 no GSO. A SaO2 e PaO2 foram maiores no GCO em comparação ao GSO. O pH foi menor no GCO 15 minutos após MPA até 40 minutos após epidural, em comparação ao GSO. Conclui-se que a anestesia epidural lombossacra com morfina e lidocaína na dose e no volume propostos é efetiva para realização de OSH em cadelas, com mínimas alterações cardiovasculares e hemogasométricas, as quais são bem toleradas em animais hígidos. Essa prática é exequível em campanhas de castração em que não há possibilidade de oxigenação dos animais.

Anestesia epidural em cutias (Dasyprocta azarae) submetidas à ovariossalpingohisterectomia

In this research, the epidural anesthesia technique in nulliparous and non non-nulliparous submitted to ovarysalpingohysterectomy was studied. These are rodents belonging to the Missina Palmeira Zancaner municipal zoo of catanduva in São Paulo. The tranquilization was achieved using azaperone (4mg/kg) and meperidine (4mg/kg) followed by injection of cetamine (20mg/kg) and xylazine (0.4mg/kg), intramuscularly from the same syringe. Subsequently, lidocaine (5mg/kg) was injected into the lumbosacral space. The time of latency of the anesthesic association (4.0[plus or minus]1.51min), time of latency of epidural lidocaine (6.87[plus or minus]2.35min) and time of analgesia (115.0[plus or minus]12.49min) were analyzed, in addition to rectal temperature, which decreased 2.12[plus or minus]0.86[degree]C on average from the beginning of the anesthesia to the end of its effective time. All animals recovered satisfactorily without presenting signs of excitation or complications due to the epidural tecnique. It was concluded that the balanced anesthesia tecnique provided adequate analgesia during a time considered sufficient for several procedures, by means of low doses of xylazine and ketamine.

Injeção epidural de cetamina ou cetamina levógira no controle da dor pós-incisional, em eqüinos

The aim of this study was to evaluate the pre-emptive effect of epidural ketamine S (+) (SK) or racemic ketamine (RK) administration, in post-incisional pain in horses. Were used in a blinded, randomized experimental study, sixteen mixed breed mares, 6±2 years old, weighting 273.2±42.0 kg. An epidural catheter was inserted 24 hours before the trials. The thigh region was shaved bilaterally, and mechanical cutaneous sensibility was measured using von Frey filaments (T-30). Using the left side as the control one, local anesthesia was performed at the right side. Twenty-five minutes later, SK was injected in G1 or RK in G2 through the epidural catheter. Five minutes after the ketamine injection, a 10 cm skin incision was made on the right side, and then sutured. Mechanical post-incisional pain was measured using von Frey filaments, at 1, 3 and 5 cm around the incision at 15 minutes intervals, for 2 hours, then 4, 6 and 8 hours after suturing. No changes were observed in the heart and respiratory rate and rectal temperature among groups or times of each group. Hind limb ataxia was observed in 62.5% and 12.5% of G1 and G2 respectively. SK and RK reduced cutaneous sensibility in the right and the left sides to mechanical postincisional pain during all time of experiment. Epidural SK and RK produce similar post-incisional analgesic effects, did not interfere in the cardio-respiratory parameters. The SK induces more intense ataxia in mares and presents a larger analgesic potency in the first 60 minutes after the administration.

Uso da lidocaína isolada ou associada à quetamina ou ao butorfanol, em anestesia epidural em cães: avaliação cardiorrespiratória e analgésica

Pós-graduação em Anestesiologia - FMB

Longer immediate recovery time after anesthesia increases risk of respiratory complications after laparotomy for bariatric surgery: a randomized clinical trial and a cohort study

We compared the effects of two anesthesia protocols in both immediate recovery time (IRT) and postoperative respiratory complications (PRCs) after laparotomy for bariatric surgery, and we determined the association between the longer IRT and the increase of PRC incidence. We conducted the study in two stages: (i) in a randomized controlled trial (RCT), patients received either intervention (sevoflurane-remifentanil-rocuronium-ropivacaine) or control protocol (isoflurane-sufentanil-atracurium-levobupivacaine). All patients received general anesthesia plus continuous epidural anesthesia and analgesia. Treatment was masked for all, except the provider anesthesiologist. We defined IRT as time since anesthetics discontinuation until tracheal extubation. Primary outcomes were IRT and PRCs incidence within 15 days after surgery. We also analyzed post-anesthesia care unit (PACU) and hospital length of stays; (ii) after the end of the RCT, we used the available data in an extension cohort study to investigate IRT > 20 min as exposure factor for PRCs. Control protocol (n = 152) resulted in longer IRT (30.4 ± 7.9 vs 18.2 ± 9.6 min; p < 0.0001), higher incidence of PRCs (6.58 vs 2.5 %; p = 0.048), and longer PACU and hospital stays than intervention protocol (n = 200); PRC relative risk (RR) = 2.6. Patients with IRT > 20 min (n = 190) presented higher incidence of PRCs (7.37 vs 0.62 %; p < 0.0001); RR = 12.06. Intervention protocol, with short-acting anesthetics, was more beneficial and safe compared to control protocol, with long-acting drugs, regarding the reduction of IRT, PRCs, and PACU and hospital stays for laparotomy in bariatric patients. We identified a 4.5-fold increase in the relative risk of PRCs when morbid obese patients are exposed to an IRT > 20 min.