RESUMEN
BACKGROUND: Vasopressin is an alternative to epinephrine for vasopressor therapy during cardiopulmonary resuscitation, but clinical experience with this treatment has been limited. METHODS: We randomly assigned adults who had had an out-of-hospital cardiac arrest to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine, followed by additional treatment with epinephrine if needed. The primary end point was survival to hospital admission, and the secondary end point was survival to hospital discharge. RESULTS: A total of 1219 patients underwent randomization; 33 were excluded because of missing study-drug codes. Among the remaining 1186 patients, 589 were assigned to receive vasopressin and 597 to receive epinephrine. The two treatment groups had similar clinical profiles. There were no significant differences in the rates of hospital admission between the vasopressin group and the epinephrine group either among patients with ventricular fibrillation (46.2 percent vs. 43.0 percent, P=0.48) or among those with pulseless electrical activity (33.7 percent vs. 30.5 percent, P=0.65). Among patients with asystole, however, vasopressin use was associated with significantly higher rates of hospital admission (29.0 percent, vs. 20.3 percent in the epinephrine group; P=0.02) and hospital discharge (4.7 percent vs. 1.5 percent, P=0.04). Among 732 patients in whom spontaneous circulation was not restored with the two injections of the study drug, additional treatment with epinephrine resulted in significant improvement in the rates of survival to hospital admission and hospital discharge in the vasopressin group, but not in the epinephrine group (hospital admission rate, 25.7 percent vs. 16.4 percent; P=0.002; hospital discharge rate, 6.2 percent vs. 1.7 percent; P=0.002). Cerebral performance was similar in the two groups. CONCLUSIONS: The effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in the treatment of refractory cardiac arrest.
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Reanimación Cardiopulmonar , Epinefrina/uso terapéutico , Paro Cardíaco/tratamiento farmacológico , Simpatomiméticos/uso terapéutico , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéutico , Anciano , Quimioterapia Combinada , Servicios Médicos de Urgencia , Femenino , Paro Cardíaco/mortalidad , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tasa de Supervivencia , Fibrilación Ventricular/tratamiento farmacológicoRESUMEN
The effects of vasopressin on the gut in a porcine uncontrolled haemorrhagic shock model are described. In eight anaesthetised pigs, a liver laceration was performed; when haemorrhagic shock was decompensated, all animals received 0.4 IU/kg vasopressin, followed by 0.08 IU/kg min over 30 min, which maintained a mean arterial blood pressure >40 mmHg. Subsequent surgical intervention, infusion of whole blood and fluids resulted in a stable cardiocirculatory status. Three hours after stabilisation, all pigs developed non-bloody diarrhoea which converted into normal bowel movements within 24 h. All histological samples retained 7 days after the experiment revealed no histopathological changes. In conclusion, in this small observational study of uncontrolled porcine haemorrhagic shock, a resuscitation strategy that included high dose vasopressin was associated with transient diarrhoea and good long term survival.
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Intestinos/efectos de los fármacos , Intestinos/fisiopatología , Choque Hemorrágico/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéutico , Animales , Presión Sanguínea/efectos de los fármacos , Diarrea/fisiopatología , Modelos Animales de Enfermedad , Hígado/lesiones , Choque Hemorrágico/fisiopatología , Porcinos , Vasoconstrictores/farmacología , Vasopresinas/farmacologíaRESUMEN
UNLABELLED: We have shown previously that arginine vasopressin (AVP) given during sinus rhythm increases mean arterial blood pressure (MAP) and left anterior descending (LAD) coronary artery cross sectional area. AVP was assumed to result in vasodilatation via activation of the endothelial nitric oxide system. The purpose of the present study was to assess the effects of AVP before and after NO-inhibition. Nine domestic pigs were instrumented for measurement of haemodynamic variables using micromanometer-tipped catheters, and measurement of LAD coronary artery cross sectional area employing intravascular ultrasound (IVUS). Haemodynamic variables, LAD coronary artery cross sectional area and cardiac output were measured at baseline, 90 s and 5, 15, and 30 min after AVP (0.4 U kg (-1) IV) before and after blockade of nitric oxide synthase with N(G)-nitro L-arginine methyl ester (L-NAME). Compared with baseline, AVP significantly increased MAP after 90 s (89+/-4 versus 160+/-5 mm Hg), increased LAD coronary artery cross sectional area (11.3+/-1 versus 11.8+/-1 mm(2)) and decreased cardiac index (138+/-6 versus 53+/-6 mL/min kg(-1)). After blockade of nitric oxide synthase, AVP significantly increased MAP after 90 s (135+/-4 versus 151+/-3 mm Hg), increased LAD coronary artery cross sectional area (8.7+/-1 versus 8.9+/-1 mm(2)), and significantly decreased cardiac index (95+/-6 versus 29+/-4 mL/min kg (-1)). IMPLICATIONS: During sinus rhythm, AVP increased MAP and LAD coronary artery cross sectional area, but decreased cardiac index.
Asunto(s)
Arginina Vasopresina/farmacología , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/diagnóstico por imagen , Paro Cardíaco/fisiopatología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Vasoconstrictores/farmacología , Anatomía Transversal , Animales , Vasos Coronarios/metabolismo , Modelos Animales de Enfermedad , Paro Cardíaco/etiología , Paro Cardíaco/metabolismo , Inyecciones Intravenosas , Porcinos , Ultrasonografía Intervencional , Fibrilación Ventricular/complicaciones , Fibrilación Ventricular/fisiopatologíaRESUMEN
INTRODUCTION: We sought to determine and compare the effects of vasopressin, fluid resuscitation and saline placebo on haemodynamic variables and short-term survival in an abdominal vascular injury model with uncontrolled haemorrhagic shock in pigs. METHODS: During general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rate had declined progressively, experimental therapy was initiated. At that point, animals were randomly assigned to receive vasopressin (0.4 U/kg; n = 7), fluid resuscitation (25 ml/kg lactated Ringer's and 25 ml/kg 3% gelatine solution; n = 7), or a single injection of saline placebo (n = 5). Vasopressin-treated animals were then given a continuous infusion of 0.08 U/kg per min vasopressin, whereas the remaining two groups received saline placebo at an equal rate of infusion. After 30 min of experimental therapy bleeding was controlled by surgical intervention, and further fluid resuscitation was performed. Thereafter, the animals were observed for an additional hour. RESULTS: After 68 +/- 19 min (mean +/- standard deviation) of uncontrolled bleeding, experimental therapy was initiated; at that time total blood loss and mean arterial blood pressure were similar between groups (not significant). Mean arterial blood pressure increased in both vasopressin-treated and fluid-resuscitated animals from about 15 mmHg to about 55 mmHg within 5 min, but afterward it decreased more rapidly in the fluid resuscitation group; mean arterial blood pressure in the placebo group never increased. Seven out of seven vasopressin-treated animals survived, whereas six out of seven fluid-resuscitated and five out of five placebo pigs died before surgical intervention was initiated (P < 0.0001). CONCLUSION: Vasopressin, but not fluid resuscitation or saline placebo, ensured short-term survival in this vascular injury model with uncontrolled haemorrhagic shock in sedated pigs.
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Traumatismos Abdominales/tratamiento farmacológico , Hemostáticos/uso terapéutico , Choque Hemorrágico/tratamiento farmacológico , Vasopresinas/uso terapéutico , Traumatismos Abdominales/complicaciones , Animales , Modelos Animales de Enfermedad , Fluidoterapia , Mesenterio/lesiones , Distribución Aleatoria , Choque Hemorrágico/etiología , Cloruro de Sodio/uso terapéutico , Sus scrofa , Resultado del TratamientoRESUMEN
In this post hoc analysis, we assessed effects of thrombolysis during out-of-hospital cardiopulmonary resuscitation. The original study was designed as a double-blinded, prospective, multicenter, randomized, controlled clinical trial. In this report, 1,219 patients were randomized, but 33 patients were excluded due to missing study drug codes. Thus, 1,186 patients were analyzed based on receipt (n = 99) versus nonreceipt (n = 1,087) of thrombolysis; the primary end point was hospital admission, and the secondary end point was hospital discharge. Patients who received thrombolysis versus those who did not were significantly younger (mean +/- SD 62.7 +/- 13.3 vs 66.5 +/- 14.3 years of age, p = 0.01) and more likely to have had an acute myocardial infarction (75.3% vs 54.6%, p < 0.01) or pulmonary embolism (20.2% vs 12.0%, p = 0.03) as the suspected underlying cause for cardiac arrest. In patients who underwent thrombolysis versus those who did not, cardiac arrest was more often witnessed (86.9% vs 77.5%, p = 0.03), initial ventricular fibrillation was more likely (59.6% vs 38.0%, p < 0.01), and a short estimated interval (0 to 5 minutes) between collapse and initiation of basic life support was more likely (51.3% vs 29.2%, p < 0.01). In patients who received thrombolysis, sodium bicarbonate (45.5% vs 33.0%, p = 0.01), lidocaine (32.3% vs 18.1%, p < 0.01), and amiodarone (30.3% vs 12.2%, p < 0.01) were administered significantly more often. Hospital admission rates were significantly higher in patients who underwent thrombolysis than in patients who did not (45.5% vs 32.7%, p = 0.01), and there was a trend to higher hospital discharge rates (14.1% vs 9.5%, p = 0.14). In patients who had suspected myocardial infarction, hospital admission and discharge rates were significantly higher in patients who underwent thrombolysis than in patients who did not. In logistic regression models after adjusting for confounding variables (e.g., age, initial electrocardiographic rhythm, and initiation of basic life support), hospital admission and discharge rates did not differ significantly. In conclusion, even when being employed in patients with a potentially better chance to survive, thrombolysis in patients with cardiac arrest resulted in an increased hospital admission but not discharge rate in this post hoc analysis.
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Reanimación Cardiopulmonar/métodos , Fibrinolíticos/uso terapéutico , Paro Cardíaco/tratamiento farmacológico , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Servicios Médicos de Urgencia , Femenino , Paro Cardíaco/etiología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Embolia Pulmonar/complicaciones , Resultado del TratamientoRESUMEN
Vasopressin administration may be a promising therapy in the management of various shock states. In laboratory models of cardiac arrest, vasopressin improved vital organ blood flow, cerebral oxygen delivery, the rate of return of spontaneous circulation, and neurological recovery compared with epinephrine (adrenaline). In a study of 1219 adult patients with cardiac arrest, the effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity; however, vasopressin was superior to epinephrine in patients with asystole. Furthermore, vasopressin followed by epinephrine resulted in significantly higher rates of survival to hospital admission and hospital discharge. The current cardiopulmonary resuscitation guidelines recommend intravenous vasopressin 40 IU or epinephrine 1mg in adult patients refractory to electrical countershock. Several investigations have demonstrated that vasopressin can successfully stabilize hemodynamic variables in advanced vasodilatory shock. Use of vasopressin in vasodilatory shock should be guided by strict hemodynamic indications, such as hypotension despite norepinephrine (noradrenaline) dosages >0.5 mug/kg/min. Vasopressin must never be used as the sole vasopressor agent. In our institutional routine, a fixed vasopressin dosage of 0.067 IU/min (i.e. 100 IU/50 mL at 2 mL/h) is administered and mean arterial pressure is regulated by adjusting norepinephrine infusion. When norepinephrine dosages decrease to 0.2 microg/kg/min, vasopressin is withdrawn in small steps according to the response in mean arterial pressure. Vasopressin also improved short- and long-term survival in various porcine models of uncontrolled hemorrhagic shock. In the clinical setting, we observed positive effects of vasopressin in some patients with life-threatening hemorrhagic shock, which had no longer responded to adrenergic catecholamines and fluid resuscitation. Clinical employment of vasopressin during hemorrhagic shock is experimental at this point in time.
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Reanimación Cardiopulmonar , Choque/clasificación , Choque/terapia , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéutico , Animales , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Lipresina/análogos & derivados , Lipresina/uso terapéutico , Terlipresina , Vasoconstrictores/efectos adversos , Vasoconstrictores/farmacología , Vasopresinas/efectos adversos , Vasopresinas/farmacologíaRESUMEN
STUDY OBJECTIVE: Although a moderate positive end-expiratory pressure (PEEP) level is widely recommended, it is unknown whether moderate PEEP during mechanical ventilation has adverse effects during severe hemorrhagic shock. Therefore, the purpose of our study was to evaluate the effects of 0 cm H2O PEEP versus 5 cm H2O PEEP versus 10 cm H2O PEEP on short-term survival in a porcine model of severe hemorrhagic shock. Secondary study endpoints were hemodynamic variables and blood gases. METHODS: Twenty-four anesthetized pigs were bled approximately 45 mL/kg, randomized into 3 groups, and then ventilated with 0, 5, or 10 cm H2O PEEP. Survival rates were compared using Kaplan-Meier methods with log rank (Mantel Cox) comparison of cumulative survival by treatment group. RESULTS: Seven of 8 0 cm H2O PEEP animals survived the 120-minute study period, but 8 of 8 5 cm H2O PEEP animals died within 30 minutes, and 8 of 8 10 cm H2O PEEP animals were dead within 20 minutes (P<.0001). Ventilation with 0 cm H2O PEEP prevented a further reduction of mean arterial blood pressure and cardiac output. When compared with the 0 cm H2O PEEP group, end-tidal CO2 declined in the 5 cm H2O PEEP and 10 cm H2O PEEP animals. Compared with the 0 cm H2O PEEP animals, those ventilated with 5 or 10 cm H2O PEEP had higher lactate levels after 10 minutes. CONCLUSION: When compared with pigs ventilated with either 5 or 10 cm H2O PEEP, those ventilated with 0 cm H2O PEEP during untreated, severe hemorrhagic shock had significantly improved short-term survival.
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Respiración con Presión Positiva/métodos , Choque Hemorrágico/terapia , Animales , Análisis de los Gases de la Sangre , Modelos Animales de Enfermedad , Medicina de Emergencia/métodos , Hemodinámica , Distribución Aleatoria , Choque Hemorrágico/sangre , Choque Hemorrágico/fisiopatología , Análisis de Supervivencia , Porcinos , Resultado del TratamientoRESUMEN
Reducing inspiratory flow rate and peak airway pressure may be important in order to minimise the risk of stomach inflation when ventilating an unprotected airway with positive pressure ventilation. This study was designed to yield enough power to determine whether employing an inspiratory gas flow limiting bag-valve device (SMART BAG, O-Two Medical Technologies Inc., Ontario, Canada) would also decrease the likelihood of stomach inflation in an established bench model of a simulated unintubated respiratory arrest patient. The bench model consists of a training lung (lung compliance, 50 ml/cm H2O; airway resistance, 4 cm H2O/l/s) and a valve simulating lower oesophageal sphincter opening at a pressure of 19 cm H(2)O. One hundred and ninety-one emergency medicine physicians were requested to ventilate the manikin utilising a standard single-person technique for 1 min (respiratory rate, 12/min; Vt, 500 ml) with both a standard adult bag-valve-mask and the SMART BAG. The volunteers were blinded to the experimental design of the model until completion of the experimental protocol. The SMART BAG versus standard bag-valve-mask resulted in significantly (P < 0.001) lower (mean +/- S.D.) mean airway pressure (14 +/- 2 cm H2O versus 16 +/- 3 cm H2O), respiratory rates (13 +/- 3 breaths per min versus 14 +/- 4 breaths per min), incidence of stomach inflation (4.2% versus 38.7%) and median stomach inflation volumes (351 [range, 18-1211 ml] versus 1426 [20-5882 ml]); lung tidal volumes (538 +/- 97 ml versus 533 +/- 97 ml) were comparable. Inspiratory to expiratory ratios were significantly (P < 0.001) increased (1.7 +/- 0.5 versus 1.5 +/- 0.6). In conclusion, the SMART BAG reduced inspiratory flow, mean airway pressure and both the incidence and actual volume of stomach inflation compared with a standard bag-valve-mask device while maintaining delivered lung tidal volumes and increasing the inspiratory to expiratory ratio.
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Respiración Artificial/métodos , Diseño de Equipo , Humanos , Máscaras , Ápice del Flujo Espiratorio , Respiración Artificial/instrumentación , EstómagoRESUMEN
OBJECTIVE: HMR 1883 (the free acid form of HMR 1098) selectively inactivates myocardial ATP sensitive potassium channels, which may be a potential important therapeutic approach to prevent life-threatening arrhythmias. This study was designed to assess the effects of HMR 1883 combined with adrenaline on haemodynamic variables, blood gases, and cardiac arrhythmias in a porcine cardiac arrest model. METHODS: After 8 min of untreated cardiac arrest, followed by 1 min of cardiopulmonary resuscitation (CPR), 12 pigs weighing 30-40 kg were assigned randomly to receive either 45 microg/kg adrenaline alone (n=6), or 45 microg/kg adrenaline combined with 3 mg/kg HMR 1883 (n=6), followed by up to three defibrillation attempts 2 min later. Five minutes after return of spontaneous circulation, cardiac arrest was induced for 1 min, with the CPR protocol following as described above. All animals subsequently underwent four cardiac arrest intervals of 1, 2, 3, and 4 min duration which were separated by four episodes of 5 min of return of spontaneous circulation. RESULTS: Haemodynamic variables, cardiac arrhythmias in the acute resuscitation phase between termination of chest compressions and return of spontaneous circulation, and after return of spontaneous circulation in both groups were comparable throughout the experiment. Survival rates throughout the experiment were comparable between groups. Arterial blood gases, electrolyte, glucose, and lactate levels in both groups during the experiment indicated comparable severe metabolic acidosis, with increasing levels after each episode of simulated refibrillation, and subsequent return of spontaneous circulation. CONCLUSION: Combining HMR 1883 with adrenaline during CPR resulted in comparable haemodynamic variables, return of spontaneous circulation rates, cardiac arrhythmias, lactate and glucose levels compared with adrenaline alone. This indicates that injection of HMR 1883 was safe under these conditions.
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Reanimación Cardiopulmonar/métodos , Paro Cardíaco/complicaciones , Hemodinámica/fisiología , Bloqueadores de los Canales de Potasio , Sulfonamidas/uso terapéutico , Tiourea/análogos & derivados , Tiourea/uso terapéutico , Fibrilación Ventricular/prevención & control , Animales , Análisis de los Gases de la Sangre , Quimioterapia Combinada , Epinefrina/uso terapéutico , Paro Cardíaco/fisiopatología , Modelos Animales , Sulfonamidas/administración & dosificación , Porcinos , Tiourea/administración & dosificaciónRESUMEN
OBJECTIVE: Despite the important role of the adrenal gland during cardiac arrest, little is known about changes in the adrenal medullary or cortical blood flow in this setting. This study was designed to assess regional adrenal gland perfusion in the medulla and cortex during cardiopulmonary resuscitation (CPR), and after administration of adrenaline (epinephrine) versus vasopressin versus saline placebo. METHODS: After 4 min of untreated ventricular fibrillation, and 3 min of basic life support CPR, 19 animals were randomly assigned to receive either vasopressin (0.4 U/kg; n=7), adrenaline (45 microg/kg; n=6) or saline placebo (n=6), respectively. Haemodynamic variables, adrenal, and renal blood flow were measured after 90 s of CPR, and 90 s and 5 min after drug administration. RESULTS: All values are given as mean+/-S.E.M. Blood flow in the adrenal medulla was significantly higher 90 s after adrenaline when compared with saline placebo in the right adrenal medulla (210+/-14 vs. 102+/-5 ml/min per 100 mg), and in the left adrenal medulla (218+/-14 vs. 96+/-3 ml/min per 100 mg). Blood flow in the adrenal medulla was significantly higher 90 s and 5 min after vasopressin when compared with adrenaline in the right (326+/-22 mg vs. 210+/-14 ml/min per 100 mg, and 297+/-17 vs. 103+/-5 ml/min per 100 mg), and in the left medulla (333+/-25 vs. 218+/-14 ml/min per 100 mg, and 295+/-14 vs. 111+/-7 ml/min per 100 mg). Ninety seconds and five minutes after vasopressin, and 90 s after adrenaline, adrenal cortex blood flow was significantly higher when compared with saline placebo. After 12 min of cardiac arrest, including 8 min of CPR, seven of seven pigs in the vasopressin group, one of six pigs in the adrenaline group, but none of six placebo were successfully defibrillated. CONCLUSION: Both vasopressin and adrenaline produced significantly higher medullary and cortical adrenal gland perfusion during CPR than did a saline placebo; but vasopressin resulted in significantly higher medullary adrenal gland blood flow when compared with adrenaline.
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Glándulas Suprarrenales/irrigación sanguínea , Glándulas Suprarrenales/efectos de los fármacos , Reanimación Cardiopulmonar/métodos , Epinefrina/farmacología , Vasopresinas/farmacología , Fibrilación Ventricular/terapia , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Femenino , Hemodinámica/fisiología , Masculino , Probabilidad , Distribución Aleatoria , Valores de Referencia , Flujo Sanguíneo Regional , Sensibilidad y Especificidad , PorcinosRESUMEN
OBJECTIVE: Outcome after trauma with severe hemorrhagic shock is still dismal. Since the majority of blood is present in the venous vessels, it might be beneficial to perform venous recruiting via the airway during severe hemorrhagic shock. Therefore, the purpose of our study was to evaluate the effects of negative expiratory pressure ventilation on mean arterial blood pressure, cardiac output, and short-term survival during severe hemorrhagic shock. DESIGN: Prospective study in 21 laboratory animals. SETTING: University hospital research laboratory. SUBJECTS: : Tyrolean domestic pigs. INTERVENTIONS: After induction of controlled hemorrhagic shock (blood loss approximately 45 mL/kg), 21 pigs were randomly ventilated with either zero end-expiratory pressure (0 PEEP; n = 7), 5 cm H2O positive end-expiratory pressure (5 PEEP; n = 7), or negative expiratory pressure ventilation (up to -30 cm H2O at the endotracheal tube during expiration; n = 7). MEASUREMENTS AND MAIN RESULTS: Mean (+/-sd) arterial blood pressure was significantly higher in the negative expiratory pressure ventilation swine when compared with the 0 PEEP (38 +/- 5 vs. 27 +/- 3 mm Hg; p = .001) and the 5 PEEP animals (38 +/- 5 vs. 20 +/- 6 mm Hg; p < .001) after 5 mins of the experiment. Cardiac output was significantly higher in the negative expiratory pressure ventilation swine when compared with the 0 PEEP (3.1 +/- .4 vs. 1.9 +/- .9 L/min; p = .001) and 5 PEEP animals (3.1 +/- .4 vs. 1.2 +/- .8 L/min; p < .001) after 5 mins of the experiment. All seven negative expiratory pressure ventilation animals, but only three of seven 0 PEEP animals (p = .022), survived the 120-min study period, whereas all seven of seven 5 PEEP animals were dead within 35 mins (p < .001). Limitations include that blood loss was controlled and that the small sample size limits the evaluation of survival outcome. CONCLUSIONS: When compared with pigs ventilated with either 0 PEEP or 5 PEEP, negative expiratory pressure ventilation during severe hemorrhagic shock improved mean arterial blood pressure and cardiac output.
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Presión Sanguínea/fisiología , Gasto Cardíaco/fisiología , Respiración con Presión Positiva/métodos , Choque Hemorrágico/terapia , Animales , Función del Atrio Derecho/fisiología , Dióxido de Carbono/sangre , Modelos Animales de Enfermedad , Estudios Prospectivos , Distribución Aleatoria , Choque Hemorrágico/fisiopatología , Análisis de Supervivencia , PorcinosRESUMEN
Nerve stimulators are widely used to assist with peripheral nerve blocks but do not eliminate the risk of nerve injury. We evaluated the histologic findings 6 h after sciatic nerve block with bupivacaine in pigs. When a motor response was still obtained with a current <0.2 mA (n = 10), the postmortem microscopic evaluation revealed lymphocytes and granulocytes sub-, peri-, and intraneurally in 5 (50%) of 10 pigs. No signs of inflammation were observed when the muscle contraction was achieved with a current between 0.3 and 0.5 mA (P = 0.03). In conclusion, the current required to elicit a motor response, the position of the needle tip, and the subsequent likelihood of nerve damage merit further evaluation.
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Inflamación/patología , Bloqueo Nervioso , Nervio Ciático/patología , Animales , Estimulación Eléctrica , Nervio Ciático/fisiología , PorcinosRESUMEN
UNLABELLED: We estimated the predictive power with respect to defibrillation outcome of ventricular fibrillation (VF) mean frequency (FREQ), mean peak-to-trough amplitude (AMPL), and their combination. We examined VF electrocardiogram signals of 64 pigs from 4 different cardiac arrest models with different durations of untreated VF, different durations of cardiopulmonary resuscitation, and use of different drugs (epinephrine, vasopressin, N-nitro-L-arginine methyl ester, or saline placebo). The frequency domain was restricted to the range from 4.33 to 30 Hz. In the 10-s epoch between 20 and 10 s before the first defibrillation shock, FREQ and AMPL were estimated. We introduced the survival index (SI; 0.68 Hz(-1). FREQ + 12.69 mV(-1). AMPL) by use of multiple logistic regression. Kruskal-Wallis nonparametric one-way analysis was used to analyze the different porcine models for significant difference. The variables FREQ, AMPL, and SI were compared with defibrillation outcome by means of univariate logistic regression and receiver operating characteristic curves. SI increased predictive power compared with AMPL or FREQ alone, resulting in 89% sensitivity and 86% specificity. The probabilities of predicting defibrillation outcome for FREQ, AMPL, and SI were 0.85, 0.89 and 0.90, respectively. FREQ, AMPL, and SI values were not sensitive in regard to the four different cardiac arrest models but were significantly different for vasopressin and epinephrine animals. IMPLICATIONS: We present a retrospective data analysis to evaluate the predictive power of different ventricular fibrillation electrocardiogram variables in pigs with respect to defibrillation outcome. We showed that our combination of variables leads to an improved forecast, which may help to reduce harmful unsuccessful defibrillation attempts.
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Cardioversión Eléctrica , Paro Cardíaco/terapia , Algoritmos , Animales , Reanimación Cardiopulmonar , Inhibidores Enzimáticos/uso terapéutico , Epinefrina/uso terapéutico , Femenino , Masculino , NG-Nitroarginina Metil Éster/uso terapéutico , Valor Predictivo de las Pruebas , Análisis de Regresión , Análisis de Supervivencia , Porcinos , Resultado del Tratamiento , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéuticoRESUMEN
OBJECTIVE: In patients undergoing cardiopulmonary resuscitation, circulating endogenous vasopressin concentrations were significantly higher in successfully resuscitated patients than in patients who died. These observations have prompted several investigations to assess the role of vasopressin to improve cardiopulmonary resuscitation management. DESIGN: Literature review. RESULTS: In the cardiopulmonary resuscitation laboratory, vasopressin improved vital organ blood flow, cerebral oxygen delivery, the probability of restoring spontaneous circulation, and neurologic recovery better than epinephrine. In pediatric preparations with asphyxia, epinephrine was superior to vasopressin, whereas in both pediatric pigs with ventricular fibrillation and adult porcine models with asphyxia, combinations of vasopressin and epinephrine proved to be highly effective. In addition, vasopressin enabled short- and long-term survival in a porcine model of uncontrolled hemorrhagic shock. In a recently published European, multiple-center trial, 1,219 adult patients with out-of-hospital cardiac arrest were randomized to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine followed by additional epinephrine if needed. The clinical study did not confirm laboratory data showing vasopressin to be more effective than epinephrine in ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine was more effective than epinephrine alone in the treatment of refractory cardiac arrest. CONCLUSIONS: According to new data from the European vasopressin study, we suggest, first, the administration of 1 mg of epinephrine, followed alternately by 40 IU of vasopressin and 1 mg of epinephrine every 3 mins in adult cardiac arrest victims, regardless of the initial electrocardiographic rhythm.
Asunto(s)
Apoyo Vital Cardíaco Avanzado/métodos , Epinefrina/uso terapéutico , Paro Cardíaco/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéutico , Animales , Europa (Continente) , Paro Cardíaco/sangre , Paro Cardíaco/mortalidad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Porcinos , Vasoconstrictores/sangre , Vasoconstrictores/farmacología , Vasopresinas/sangre , Vasopresinas/farmacologíaRESUMEN
UNLABELLED: During normothermic cardiac arrest, a combination of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) with the inspiratory threshold valve (ITV) significantly improves vital organ blood flow, but this technique has not been studied during hypothermic cardiac arrest. Accordingly, we evaluated the hemodynamic effects of ACD + ITV CPR before, and after, the administration of vasopressin in a porcine model of hypothermic cardiac arrest. Pigs were surface-cooled until their body core temperature was 26 degrees C. After 10 min of untreated ventricular fibrillation, 14 animals were randomly assigned to either ACD CPR with the ITV (n = 7) or to standard (STD) CPR (n = 7). After 8 min of CPR, all animals received 0.4 U/kg vasopressin IV, and CPR was maintained for an additional 10 min in each group; defibrillation was attempted after 28 min of cardiac arrest, including 18 min of CPR. Before the administration of vasopressin, mean +/- SEM common carotid blood flow was significantly higher in the ACD + ITV group compared with STD CPR (67 +/- 13 versus 26 +/- 5 mL/min, respectively; P < 0.025). After vasopressin was given at minute 8 during CPR, mean +/- SEM coronary perfusion pressure was significantly higher in the ACD + ITV group, but did not increase in the STD group (29 +/- 3 versus 15 +/- 2 mm Hg, and 25 +/- 1 versus 14 +/- 1 mm Hg at minute 12 and 18, respectively; P < 0.001); mean +/- SEM common carotid blood flow remained higher at respective time points (33 +/- 8 versus 10 +/- 3 mL/min, and 31 +/- 7 versus 7 +/- 3 mL/min, respectively; P < 0.01). Without active rewarming, spontaneous circulation was restored and maintained for 1 h in three of seven animals in the ACD + ITV group versus none of seven animals in the STD CPR group (not significant). During hypothermic cardiac arrest, ACD CPR with the ITV improved common carotid blood flow compared with STD CPR alone. Moreover, after the administration of vasopressin, coronary perfusion pressure was significantly higher during ACD + ITV CPR, but not during STD CPR. IMPLICATIONS: New strategies are needed to improve the efficiency of cardiopulmonary resuscitation (CPR) in hypothermic cardiac arrest. Active compression-decompression CPR with the inspiratory threshold valve improved carotid blood flow (and coronary perfusion pressure with vasopressin) compared with standard CPR.
Asunto(s)
Reanimación Cardiopulmonar/métodos , Paro Cardíaco Inducido , Hemodinámica/efectos de los fármacos , Vasopresinas/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Arterias Carótidas/fisiología , Impedancia Eléctrica , Femenino , Masculino , Flujo Sanguíneo Regional/efectos de los fármacos , PorcinosRESUMEN
OBJECTIVE: Epinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation. DESIGN: Prospective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow. SETTING: University hospital laboratory. SUBJECTS: A total of 21 pigs weighing 32 +/- 3 kg. INTERVENTIONS: The anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean +/- sem loss of 40% +/- 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units.kg-1.min-1, n = 7), or epinephrine (45 microg/kg and 5 microg.kg(-1).min(-1), n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem arterial blood pressure at 2.5 and 10 mins was significantly (p <.001) higher after vasopressin vs. epinephrine vs. saline placebo (82 +/- 14 vs. 23 +/- 4 vs. 11 +/- 3 mm Hg, and 42 +/- 4 vs. 10 +/- 5 vs. 6 +/- 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p <.01) higher when compared with epinephrine or saline placebo (9 +/- 5 vs. 121 +/- 3 vs. 54 +/- 22 mL/min and 150 +/- 20 vs. 31 +/- 17 vs. 0 +/- 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo-treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p <.01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase. CONCLUSIONS: Vasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.
Asunto(s)
Arginina Vasopresina/uso terapéutico , Epinefrina/uso terapéutico , Hígado/lesiones , Choque Hemorrágico/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Animales , Velocidad del Flujo Sanguíneo , Frecuencia Cardíaca , Arteria Hepática , Vena Porta , Arteria Renal , Resucitación , Choque Hemorrágico/mortalidad , Choque Hemorrágico/fisiopatología , Choque Hemorrágico/terapia , Tasa de Supervivencia , PorcinosRESUMEN
UNLABELLED: In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of vasopressin versus an equal volume of saline placebo versus fluid resuscitation on hemodynamic variables and short-term survival. Twenty-one anesthetized pigs were subjected to severe liver injury. When mean arterial blood pressure was <20 mm Hg and heart rate decreased, pigs randomly received either vasopressin IV (0.4 U/kg; n = 7), an equal volume of saline placebo (n = 7), or fluid resuscitation (1000 mL each of lactated Ringer's solution and hetastarch; n = 7). Thirty minutes after intervention, surviving pigs were fluid resuscitated while bleeding was surgically controlled. Mean (+/- SEM) arterial blood pressure 5 min after the intervention was significantly (P < 0.05) higher after vasopressin than with saline placebo or fluid resuscitation (58 +/- 9 versus 7 +/- 3 versus 32 +/- 6 mm Hg, respectively). Vasopressin improved abdominal organ blood flow but did not cause further blood loss (vasopressin versus saline placebo versus fluid resuscitation 10 min after intervention, 1343 +/- 60 versus 1350 +/- 22 versus 2536 +/- 93 mL, respectively; P < 0.01). Seven of 7 vasopressin pigs survived until bleeding was controlled and 60 min thereafter, whereas 7 of 7 saline placebo and 7 of 7 fluid resuscitation pigs died (P < 0.01). We conclude that vasopressin, but not saline placebo or fluid resuscitation, significantly improves short-term survival during uncontrolled hemorrhagic shock. IMPLICATIONS: Although IV fluid administration is the mainstay of nonsurgical management of trauma patients with uncontrolled hemorrhagic shock, the efficacy of this strategy has been discussed controversially. In this animal model of severe liver trauma with uncontrolled hemorrhagic shock, vasopressin, but not saline placebo or fluid resuscitation, improved short-term survival.
Asunto(s)
Fluidoterapia/métodos , Hepatopatías/terapia , Resucitación/métodos , Choque Hemorrágico/terapia , Vasopresinas/uso terapéutico , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Hepatopatías/tratamiento farmacológico , Hepatopatías/fisiopatología , Masculino , Choque Hemorrágico/tratamiento farmacológico , Choque Hemorrágico/fisiopatología , Tasa de Supervivencia , Porcinos , Resultado del Tratamiento , Vasopresinas/farmacologíaRESUMEN
UNLABELLED: We assessed the effects of a calcium channel blocker versus saline placebo on ventricular fibrillation mean frequency and hemodynamic variables during prolonged cardiopulmonary resuscitation (CPR). Before cardiac arrest, 10 animals were randomly assigned to receive either nifedipine (0.64 mg/kg; n = 5) or saline placebo (n = 5) over 10 min. Immediately after drug administration, ventricular fibrillation was induced. After 4 min of cardiac arrest and 18 min of basic life support CPR, defibrillation was attempted. Ninety seconds after the induction of cardiac arrest, ventricular fibrillation mean frequency was significantly (P < 0.01) increased in nifedipine versus placebo pigs (mean +/- SD: 12.4 +/- 2.1 Hz versus 8 +/- 0.7 Hz). From 2 to 18.5 min after the induction of cardiac arrest, no differences in ventricular fibrillation mean frequency were detected between groups. Before defibrillation, ventricular fibrillation mean frequency was significantly (P < 0.05) increased in nifedipine versus placebo animals (9.7 +/- 1.2 Hz versus 7.1 +/- 1.3 Hz). Coronary perfusion pressure was significantly lower in the nifedipine than in the placebo group from the induction of ventricular fibrillation to 11.5 min of cardiac arrest; no animal had a return of spontaneous circulation after defibrillation. In conclusion, nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at approximately 10 Hz during prolonged CPR; this was nevertheless associated with no defibrillation success. IMPLICATIONS: This study evaluates the effects of a calcium channel blocker on ventricular fibrillation mean frequency, hemodynamic variables, and resuscitability during prolonged cardiopulmonary resuscitation (CPR) in pigs. Nifedipine, but not saline placebo, prevented a rapid decrease of ventricular fibrillation mean frequency after the induction of cardiac arrest and maintained ventricular fibrillation mean frequency at approximately 10 Hz during prolonged CPR but did not improve resuscitability.
Asunto(s)
Bloqueadores de los Canales de Calcio/uso terapéutico , Reanimación Cardiopulmonar , Nifedipino/uso terapéutico , Fibrilación Ventricular/prevención & control , Animales , Circulación Coronaria/efectos de los fármacos , Electrocardiografía , Paro Cardíaco/fisiopatología , Hemodinámica/efectos de los fármacos , Porcinos , Factores de TiempoRESUMEN
BACKGROUND: The authors compared the effects of vasopressin fluid resuscitation on survival in a liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs. METHODS: A midline laparotomy was performed on 23 domestic pigs, followed by an incision, and subsequent finger fraction across the right medial liver lobe. During hemorrhagic shock, animals were randomly assigned to receive either 0.4 U/kg vasopressin (n = 9), or fluid resuscitation (n = 7), or saline placebo (n = 7), respectively. A continuous infusion of 0.08 U x kg(-1) x min(-1) vasopressin in the vasopressin group, or normal saline was subsequently administered in the fluid resuscitation and saline placebo group, respectively. After 30 min of experimental therapy, bleeding was controlled by surgical intervention, and blood transfusion and rapid fluid infusion were subsequently performed. RESULTS: Maximum mean arterial blood pressure during experimental therapy in the vasopressin-treated animals was significantly higher than in the fluid resuscitation and saline placebo groups (mean +/- SD, 72 +/- 26 vs 38 +/- 16 vs 11 +/- 7 mmHg, respectively; P< 0.05). Subsequently, mean arterial blood pressure remained at approximately 40 mmHg in all vasopressin-treated animals, whereas mean arterial blood pressure in all fluid resuscitation and saline placebo pigs was close to aortic hydrostatic pressure (approximately 15 mmHg) within approximately 20 min of experimental therapy initiation. Total blood loss was significantly higher in the fluid resuscitation pigs compared with vasopressin or saline placebo after 10 min of experimental therapy (65 +/- 6 vs 42 +/- 4 vs 43 +/- 6 ml/kg, respectively; P< 0.05). Seven of seven fluid resuscitation, and seven of seven saline placebo pigs died within approximately 20 min of experimental therapy, while 8 of 9 vasopressin animals survived more than 7 days (P < 0.05). CONCLUSIONS: Vasopressin, but not fluid resuscitation or saline placebo, ensured survival with full recovery in this liver trauma model with uncontrolled and otherwise lethal hemorrhagic shock in pigs.
Asunto(s)
Fluidoterapia , Hígado/lesiones , Resucitación , Choque Hemorrágico/terapia , Vasopresinas/uso terapéutico , Animales , Hemodinámica/efectos de los fármacos , Choque Hemorrágico/mortalidad , Choque Hemorrágico/fisiopatología , PorcinosRESUMEN
UNLABELLED: We sought to determine the effects of a combination of vasopressin and epinephrine on neurologic recovery in comparison with epinephrine alone and saline placebo alone in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive, every 5 min, either a combination of vasopressin and epinephrine (vasopressin [IU/kg]/epinephrine [ micro g/kg]: 0.4/45, 0.4/45, and 0.8/45; n = 6), epinephrine alone (45, 45, and 200 micro g/kg; n = 6), or saline placebo alone (n = 5). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve the return of spontaneous circulation. Aortic diastolic pressure was significantly (P < 0.01) increased 90 s after each of 3 vasopressin/epinephrine injections versus epinephrine alone versus saline placebo alone (mean +/- SEM: 69 +/- 3 mm Hg versus 45 +/- 3 mm Hg versus 29 +/- 2 mm Hg, 63 +/- 4 mm Hg versus 27 +/- 3 mm Hg versus 23 +/- 1 mm Hg, and 52 +/- 4 mm Hg versus 21 +/- 3 mm Hg versus 16 +/- 3 mm Hg, respectively). Spontaneous circulation was restored in six of six vasopressin/epinephrine pigs, whereas six of six epinephrine and five of five saline placebo pigs died (P < 0.01). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait and was normal 5 days after the experiment in all vasopressin/epinephrine-treated animals. In conclusion, in this porcine model of prolonged CPR, repeated vasopressin/epinephrine administration, but not epinephrine or saline placebo alone, ensured long-term survival with full neurologic recovery. IMPLICATIONS: We present a study to evaluate the effects of a combination of vasopressin and epinephrine during prolonged cardiopulmonary resuscitation on neurological outcome in pigs. We found that all pigs treated with a combination of vasopressin and epinephrine could be resuscitated and had full neurologic recovery observed over an entire period of 5 days.