Effect of protective solutions and hydroxyethyl starch in the attenuation of the injuries of ischemia and reperfusion of splanchnic organs

PURPOSE: Vogt´s antioxidant solution (red blood cells, Ringer's solution, sodium bicarbonate, mannitol, allopurinol and 50% glucose) or its modification including hydroxyethyl starch (HES) were tested for the prevention of splanchnic artery occlusion shock. METHODS: Seventy rats were distributed in treatment (3), control (1), and sham (3) groups. Ischemia and reperfusion were induced by celiac, superior mesenteric and inferior mesenteric arteries occlusion for 40 min, followed by 60 min reperfusion or sham procedures. Controls received saline, both treatment and sham groups received the Vogt's solution, modified Vogt's solution (replacing Ringer's solution by HES), or HES. Mean arterial blood pressure (MABP), ileal malondialdehyde (MDA) and plasmatic MDA were determined, and a histologic grading system was used. RESULTS: At reperfusion, MABP dropped in all I/R groups. Only HES treatment was able to restore final MABP to the levels of sham groups. Plasmatic MDA did not show differences between groups. Ileum MDA was significantly higher in the control and treatment groups as compared to the sham group. Histology ranking was higher in the only in control group. CONCLUSIONS: Hydroxyethyl starch was able to prevent hemodynamic shock but not intestinal lesions. Both treatments with Vogt's solutions did not show any improvement. .

A randomized prospective analysis of alteration of hemostatic function in patients receiving tranexamic acid and hydroxyethyl starch (130/0.4) undergoing off pump coronary artery bypass surgery.

Postoperative hemorrhagic complications is still one of the major problems in cardiac surgeries. It may be caused by surgical issues, coagulopathy caused by the side effects of the intravenous fluids administered to produce plasma volume expansion such as hydroxyl ethyl starch (HES). In order to thwart this hemorrhagic issue, few agents are available. Fibrinolytic inhibitors like tranexamic acid (TA) may be effective modes to promote blood conservation; but the possible complications of thrombosis of coronary artery graft, precludes their generous use in coronary artery bypass graft surgery. The issue is a balance between agents that promote coagulation and those which oppose it. Therefore, in this study we have assessed the effects of concomitant use of HES and TA. Thromboelastogram (TEG) was used to assess the effect of the combination of HES and TA. With ethical committee approval and patient's consent, 100 consecutive patients were recruited for the study. Surgical and anesthetic techniques were standardized. Patients fulfilling our inclusion criteria were randomly allocated into 4 groups of 25 each. The patients in group A received 20 ml/kg of HES (130/0.4), 10 mg/kg of T.A over 30 minutes followed by infusion of 1 mg/kg/hr over the next 12 hrs. The patients in group B received Ringer's lactate + TA at same dose. The patients in the Group C received 20 ml/kg of HES. Group D patients received RL. Fluid therapy was goal directed. Total blood loss was assessed. Reaction time (r), α angle, maximum amplitude (MA) values of TEG were assessed at baseline, 12, 36 hrs. The possible perioperative myocardial infraction (MI) was assessed by electrocardiogram (ECG) and troponin T values at the baseline, postoperative day 1. Duration on ventilator, length of stay (LOS) in the intensive care unit (ICU) were also assessed. The demographical profile was similar among the groups. Use of HES increased blood loss significantly (P < 0.05). Concomitant use of TA reduced blood loss when used along with HES. r value was prolonged at 12 hours in all the groups and α angle was reduced at 12 hours in all the groups, where as MA value was reduced at 12 th hour in the HES group compared to the baseline and increased in TA + HES group. These findings were statistically significant. No significant change in Troponin T values/ ECG, duration of ventilation and LOS ICU was observed. No adverse events was noticed in any of the four groups. HES (130/0.4) used at a dose of 20 ml/kg seems to produce coagulopathy causing increased blood loss perioperatively. Hemodilution produced by fluid therapy seems to produce Coagulopathy as observed by TEG parameters. Concomitant use of TA with HES appears to reverse these changes without causing any adverse effects in patients undergoing OPCAB surgery.

Hidroxietilalmidón (Hextend®) en solución electrolítica balanceada en el choque hipovolémico hemorrágico / Use of hetastarch in a balanced electrolyte solution - Hextend®- in the resuscitation of the patient in hypovolemic hemmorrhagic shock: review of the international literature

Hextend® is a preparation of hetilstarch in a balanced electrolyte solution that contains 143 mEq/L of sodium, 124mEq/L of chloride, 5 mEq/L of calcium 3 mEq/L of potassium 0.9 mEq/L of magnesium, 0.99 g/L of glucose and 24 mEq/L of lactate. It has a volume of distribution similar to blood volume which enables it to stay in the intravascular compartment until it is renally cleared or absorbed by the reticuloendothelial system. It shows a bimodal pattern of clearance with a half life during the first 8 hrs of its infusion of 4.2 hrs and during the 7 days following of 38.2 hrs. Hextend® is currently one of the preferred resuscitation solutions in the hypovolemic patient showing a better profile of effects over hemostasis and acid base status and conferring a better survival over similar patients resuscitated with crystalloids or other synthetic colloids. Hextend® provides an adequate fluid that is effective in the resuscitation of the trauma patient in hypovolemic hemorrhagic shock and promises to become the fluid of choice in the routine management of these patients. There is a need of more randomized prospective studies in the field of trauma using Hextend ® and its combination with the inflammatory cascade modifiers such as ethyl pyruvate among others.

Hextend® es una combinación de hetilalmidón balanceada en una solución de electrolitos que contiene 143 mEq/L de sodio, 124 mEq/L de cloro, 5 mEq/L de calcio, 3 mEq/L de potasio, 0,9 mEq/L de magnesio, 0,99 g/L de glucosa y 24 mEq/L de lactato. Posee un volumen de distribución equivalente al volumen sanguíneo manteniéndose en el compartimento vascular hasta ser excretado vía renal o absorbido por el sistema retículo-endotelial. Estas características le confieren un patrón farmacocinético bimodal con una vida media de 4,2 horas durante las primeras 8 hrs de infusión y de 38,2 h durante los primeros 7 días. Hextend® es actualmente una de las soluciones de reanimación con mejor perfil de efectos sobre la hemostasia y el equilibrio ácido base del paciente en choque hipovolémico y confiere un aumento de la sobrevida, comparado con controles resucitados con cristaloides u otros coloides sintéticos. Esta combinación de hetilalmidón en una solución amortiguadora electrolítica posee mínimos efectos sobre la función hemostática y plaquetaria por lo que actualmente es preferido frente a soluciones cristaloides y otros coloides utilizados en el pasado en la reanimación de pacientes politraumatizados en estado de choque hipovolémico hemorrágico. A su vez, promete transformarse en el fluido de elección en el manejo rutinario de estos pacientes. En relación al uso de este producto es imperativo realizar un mayor número de estudios prospectivos randomizados. La literatura internacional augura un esplendoroso futuro al uso de Hextend®, como también a su posible combinación con modificadores de la cascada inflamatoria, entre otros con el etil piruvato.

Modulación inflamatoria en el shock traumático: [revisión] / Inflammatory modulation in traumatic shock: [review]

Hemorrhagic hypovolemic shock secondary to trauma is an important cause of morbidity and mortality worldwide. During the last few years, new concepts have emerged and the guidelines of fluid resuscitation in these patients have been redefined. The concept of hypotensive resuscitation has been established and new colloid solutions based on starch have been manufactured, been hydroxyethyl starch in a balanced electrolytic solution, the most studied and successful one. It has been reported, as well, the positive effects of the pharmacologic modulation of the inflammatory pathways in experimental model subjects submitted to hypovolemic shock. Products such as, ethyl pyruvate and the Na+/H+ type 1 inhibitor, BIIB513, have been Studies only experimentally in rodent models using colloids as the primary resuscitation fluid. The significant improvement in the hemodinamyc, pattern and the cardiac and inflammatory indexes and mediators, has created the basis for their use in clinical trials in the near future. The systemic inflammatory response is an important cause of multiple organ failure that increases the late mortality of patients surviving the initial early phases of hypovolemic traumatic shock and its experimental modulation in rodent models with products such as ethyl pyruvate and BIIB513 has produced excellent in vivo and in vitro results.

Universalmente se considera el Shock hipovolémico de origen hemorrágico como una importante causa de morbi-mortalidad. Durante los últimos años se ha redefinido los conceptos de la reanimación con líquidos intravenosos en los pacientes con choque hipovolémico y establecido los conceptos de reanimación hipotensa con el uso de nuevos coloides derivados del almidón, tales como el hidroxietil-almidón en solución electrolítica balanceada (Hextend®). Así mismo, se ha reportado el beneficio que conlleva el uso de modificadores de la cascada inflamatoria en modelos experimentales de sujetos sometidos a choque hipovolémico hemorrágico. Productos como el etil piruvato y la BIIB513, un inhibidor selectivo del intercambiador Na+/H+ tipo 1, han sido estudiados sólo experimentalmente en modelos roedores, empleando coloides como principal elemento de reanimación. Al mejorar el perfil hemodinámico, parámetros cardíacos y niveles de mediadores inflamatorios, estos compuestos constituyen una base cierta para ser incluidos en estudios clínicos en un futuro próximo. La respuesta inflamatoria sistémica está íntimamente implicada en la patogénesis de la Falla Orgánica Múltiple, aumentando la mortalidad tardía de pacientes que sobreviven las etapas tempranas del shock hipovolémico hemorrágico traumático. Su modulación experimental con el etil piruvato o bien la BIIB513 ha dado excelente resultado tanto en modelos experimentales in vivo como in vitro.

Hemodynamic effects of volume replacement with saline solution and hypertonic hydroxyethyl starch in dogs / Efeitos hemodinâmicos da reposição volêmica com solução salina e hidroxi-etil amido hipertônico em cães

PURPOSE: To investigate hemodynamic response to volume replacement with saline solution and hypertonic hydroxyethyl starch in hypovolemic dogs. METHODS: Forty dogs under general anesthesia and hemodynamic monitoring, following measurements at baseline, were bled 20 ml.Kg-1 and parameters were measured again after 10 minutes. The animals were randomly divided in two groups and volume replacement was performed with saline solution twice the volume removed or 4 ml.Kg-1 of hypertonic hydroxyethyl starch. Hemodynamic data were again measured after 5, 15, 30, 45 and 60 minutes. RESULTS: With both solutions values returned to satisfactory hemodynamic levels. With saline solution, there was a greater amplitude in variations that tended to decrease progressively. With hypertonic hydroxyethyl starch, the parameters studied returned more rapidly to levels similar to those at baseline and varied less. CONCLUSION: Both solutions proved to be efficient at replacing volume in the short period studied, although hypertonic hydroxyethyl starch produced more stable results.

OBJETIVO: Avaliar em cães hipovolêmicos as respostas hemodinâmicas da reposição volêmica com solução salina e hidroxi-etil amido hipertônico. MÉTODOS: Quarenta cães sob anestesia geral e monitorização hemodinâmica, após medidas em repouso foram sangrados 20 ml.Kg-1 e tiveram os parâmetros novamente medidos após 10 minutos. Os animais foram aleatoriamente divididos em dois grupos nos quais foi realizada reposição volêmica com solução fisiológica duas vezes o volume retirado ou 4 ml.Kg-1 de hidroxi-etil amido hipertônico e os dados hemodinâmicos medidos novamente após 5, 15, 30, 45 e 60 minutos. RESULTADOS: A reposição volêmica com as duas soluções fez os valores retornarem a níveis hemodinâmicos satisfatórios, a amplitude das variações com solução fisiológica foi maior, mas tendeu a diminuir progressivamente, com o hidroxi-etil amido hipertônico os parâmetros estudados retornaram a semelhantes ao repouso mais rapidamente e variaram menos. CONCLUSÃO: Ambas soluções se mostraram eficientes na reposição volêmica, o hidroxi-etil amido hipertônico proporcionou resultados mais estáveis.

Substitutos do plasma / Plasma substitutes

A preocupaçao constante com as complicaçoes advindas da transfusao indiscriminada de sangue, notadamente as doenças transmissíveis e também a falta de uma reserva sangüínea razoável para uma reposiçao emergencial, fizeram com que houvesse um grande impulso no sentido de se buscar uma soluçao alternativa para as perdas sangüíneas e plasmáticas. O objetivo do presente estudo é fazer uma revisao sobre as soluçoes em uso com esta finalidade, seus aspectos fisiopatológicos, complicaçoes e restriçoes ao seu emprego.

Dispositivo de assistência circulatória em contrapulsaçäo / Counterpulsation circulatory assist device

Objetivo: Testar um dispositivo de assistência circulatória (DAC) que trabalha em contrapulsação e sem válvulas. Material e Métodos: O DAC desenvolvido consta de carcaça de policarbonato, contendo em seu interior bolsa de poliuretano com volume màximo de 110 ml, acionada alternadamente por vàcuo e pressão gerados por propulsor eletropneumàtico sincronizado com o ECG. O dispositivo foi mantido em funcionamento em simulador do sistema circulatório por 300 horas ininterruptas para testar a resistência e segurança dos materiais empregados com relação ao esforços e fadiga. O DAC foi implantado na raiz de aorta de 5 cães, em falência cardíaca induzida através do uso de propranolol e ministração de expansores plasmàticos. Acionou-se o dispositivo por 5 períodos de 2 minutos separados por pausas de igual duração, registrando-se a variação dos parametros hemodinâmicos nesses tempos...

Purpose: To test a circulatory assist device (CAD) developd in the University of São Paulo. Heart Institute, Bioengineering Division. It is a valveless chamber working through the counterpulsation principle, aiming at assistance to temporary the left ventricle. Patients and Methods: The CAD consists of a rigid policarbonate shell, which houses in its interior a poliurethane bag with a maximum volume of 110 cm3, driven alternately by pressure and vaccum from an external electropneumatic device synchronized with the ECG. The device worked for 300 hours in a test bench simulating the cardiovascular system in order to verify its resistance to wear and fatigue. The CAD was implanted near the aortic root of five dogs, in whom cardiac failure was induced through the use of propranolol and plasma expanders. The CAD was driven for five periods of 2 minutes separated by pauses of equal duration. The hemodynamic parameters were measured during the mentioned periods.