Impact of colloids or crystalloids in renal function assessed by NGAL and KIM-1 after hysterectomy: randomized controlled trial

Abstract Background Hydroxyethyl starches are colloids used in fluid therapy that may reduce volume infusion compared with crystalloids, but they can affect renal function in critical care patients. This study aims to assess renal effects of starches using renal biomarkers in the perioperative setting. Methods This prospective, controlled, randomized study compared Hydroxyethyl starch 6% (HES) with Ringer's lactate (RL) in hysterectomy. Each episode of mean arterial pressure (MAP) below 60 mmHg guided the fluid replacement protocol. The RL group received 300 mL bolus of RL solution while the HES group received 150 mL of HES solution. All patients received RL (2 mL.kg−1.h−1) intraoperatively to replace insensible losses. Blood and urine samples were collected at three time points (preoperatively, 24 hours, and 40 days postoperatively) to assess urinary NGAL and KIM-1, as primary outcome, and other markers of renal function. Results Seventy patients were randomized and 60 completed the study. The RL group received a higher crystalloid volume (1,277 ± 812.7 mL vs. 630.4 ± 310.2 mL; p= 0.0002) with a higher fluid balance (780 ± 720 mL vs. 430 ± 440 mL; p= 0.03) and fluid overload (11.7% ± 10.4% vs. 7.0% ± 6.3%; p= 0.04) compared to the HES group. NGAL and KIM-1 did not differ between groups at each time point, however both biomarkers increased 24 hours postoperatively and returned to preoperative levels after 40 days in both groups. Conclusion HES did not increase renal biomarkers following open hysterectomy compared to RL. Moreover, HES provided better hemodynamic parameters using less volume, and reduced postoperative fluid balance and fluid overload.

Rotational thromboelastometry assessment of ballanced crystalloid, hydroxyethyl starch and gelatin effects on coagulation: a randomized trial / Tromboelastometria rotacional na avaliação dos efeitos de cristaloides balanceados, hidroxietilamido e gelatina na coagulação: estudo randômico

Abstract Background and objectives Modern crystalloid and colloid solutions are balanced solutions which are increasingly used in perioperative period. However, studies investigating their negative effect on whole blood coagulation are missing, and vivid debate is going on about which solution has the minimal coagulopathy effect. The aim of our study was to assess the effect of modern fluid solutions on whole blood coagulation using rotational thromboelastometry. Methods Blood samples were obtained from 30 patients during knee arthroscopy before and after administration of 500 mL of crystalloid, Hydroxyethyl Starch and gelatin according to the randomization. Rotational thromboelastometry (Extem, Intem and Fibtem tests) was used to assess negative effect of fluid solutions on whole blood coagulation. Results In Extem test, the initiation phase of fibrin clot formation represented by CT parameter was not influenced by any fluid solution (p > 0.05). The speed of clot formation represented by CFT and α angle was impaired by Hydroxyethyl Starch and gelatin but not by crystalloids (p < 0.05). The strength of formatted coagulum represented by MCF parameter was impaired both in Extem and Fibtem test by HES and in Fibtem also by crystalloids (p < 0.05). Intem test was not negatively influenced by any crystalloid or colloid solution in any parameter (p > 0.05). Conclusion Extem test appears to be sensitive to coagulopathy effect of modern colloids and crystalloids. Hydroxyethyl starch has the most obvious negative effect on clot formation followed by gelatin and finally by crystalloids. Intem test seems to be insensitive to adverse effect of modern colloids and crystalloids.

Resumo Justificativa e objetivos Os cristaloides e coloides modernos são soluções balanceadas e cada vez mais utilizadas no período perioperatório. No entanto, não há estudos que avaliem seu efeito negativo na coagulação do sangue total e o intenso debate sobre a solução que cause um efeito mínimo na coagulopatia permanece. O objetivo de nosso estudo foi avaliar o efeito das soluções líquidas modernas na coagulação do sangue total com o uso da tromboelastometria rotacional. Métodos De acordo com a randomização, amostras de sangue foram colhidas de 30 pacientes durante a artroscopia de joelho, antes e após a administração de 500 mL de cristaloides, hidroxietilamido e gelatina. A tromboelastometria rotacional (testes Extem, Intem e Fibtem) foi utilizada para avaliar o efeito negativo das soluções líquidas na coagulação do sangue total. Resultados No teste Extem, a fase de iniciação da formação de coágulos de fibrina representada pelo parâmetro CT não foi influenciada por qualquer solução líquida (p > 0,05). A velocidade da formação de coágulos representada pelo CFT e pelo ângulo α foi prejudicada pelo hidroxietilamido e pela gelatina, mas não pelos cristaloides (p < 0,05). A força do coágulo formatado representado pelo parâmetro MCF foi prejudicada tanto no teste Extem quanto no teste Fibtem pelo HES e no teste Fibtem também pelos cristaloides (p < 0,05). O teste Intem não foi influenciado negativamente por nenhuma solução cristaloide ou coloide em nenhum parâmetro (p > 0,05). Conclusão O teste Extem parece ser sensível ao efeito de coagulopatia dos coloides e cristaloides modernos. O hidroxietilamido apresentou o efeito negativo mais óbvio na formação do coágulo, seguido pela gelatina e finalmente pelos cristaloides. O teste Intem parece ser insensível ao efeito adverso dos coloides e cristaloides modernos.

Impacts of albumin synergized with hydroxyethyl starch on early microvascular albumin leakage after major abdominal surgery in rabbits

Abstract Purpose: To investigate the impacts of albumin synergized with hydroxyethyl starch (HES) on early microvascular albumin leakage after major abdominal surgery in rabbits. Methods: Forty male Japanese rabbits were randomly divided into four groups: the control group, the saline group, the albumin group, and the Syn group (hydroxyethyl starch+albumin). The latter three groups were performed gastrectomy plus resection of pancreatic body and tail and splenectomy. The serum albumin concentration was detected before and 48h after surgery, and the conditions of mesenteric microvascular leakage in these 4 groups were observed under microscope 48 h after surgery to calculate the leakage rate. Results: Compared with the saline group, the albumin group and the Syn group exhibited significantly increased serum albumin concentrations 48h after surgery (P<0.05). The albumin leakage rate was the most obvious in the albumin group, followed by the saline group, while that in the Syn group was the minimal, and there existed significant differences among these groups (P<0.05) . Conclusion: Simple administration of albumin in the early stage after major abdominal surgery could increase the albumin leakage, while the synergization of albumin and hydroxyethyl starch could reduce the albumin leakage.

Conservative treatment of Angle Class III malocclusion with anterior crossbite

Angle Class III malocclusion is characterized by anteroposterior dental discrepancy which might be associated or not with skeletal changes. Class III molar relationship is associated with vertical or lingually tipped mandibular incisors and a usually concave profile. These characteristics seriously affect facial esthetics and most frequently are the reason why patients seek orthodontic treatment. This case was presented to the committee of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO) as part of the requisites to become a BBO Diplomate.

A má oclusão de Classe III de Angle é caracterizada por uma discrepância dentária anteroposterior, que pode ou não estar acompanhada por alterações esqueléticas. Observa-se uma relação molar de Classe III associada ao posicionamento vertical ou retroinclinado dos incisivos inferiores e, geralmente, perfil facial côncavo. Esse aspecto gera grande comprometimento estético na face, sendo justamente esse o fator que, na maioria das vezes, motiva o paciente a procurar pelo tratamento ortodôntico. O presente caso clínico foi apresentado à Diretoria do Board Brasileiro de Ortodontia e Ortopedia Facial (BBO) como parte dos requisitos para a obtenção do título de Diplomado pelo BBO.

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. .

Dehydration, hemodynamics and fluid volume optimization after induction of general anesthesia

OBJECTIVES: Fluid volume optimization guided by stroke volume measurements reduces complications of colorectal and high-risk surgeries. We studied whether dehydration or a strong hemodynamic response to general anesthesia increases the probability of fluid responsiveness before surgery begins. METHODS: Cardiac output, stroke volume, central venous pressure and arterial pressures were measured in 111 patients before general anesthesia (baseline), after induction and stepwise after three bolus infusions of 3 ml/kg of 6% hydroxyethyl starch 130/0.4 (n = 86) or Ringer's lactate (n = 25). A subgroup of 30 patients who received starch were preloaded with 500 ml of Ringer's lactate. Blood volume changes were estimated from the hemoglobin concentration and dehydration was estimated from evidence of renal water conservation in urine samples. RESULTS: Induction of anesthesia decreased the stroke volume to 62% of baseline (mean); administration of fluids restored this value to 84% (starch) and 68% (Ringer's). The optimized stroke volume index was clustered around 35-40 ml/m2/beat. Additional fluid boluses increased the stroke volume by ≥10% (a sign of fluid responsiveness) in patients with dehydration, as suggested by a low cardiac index and central venous pressure at baseline and by high urinary osmolality, creatinine concentration and ...

Effect of intraoperative HES 6% 130/0.4 on the need for blood transfusion after major oncologic surgery: a propensity-matched analysis

OBJECTIVES: To evaluate the effect of the intraoperative use of hydroxyethyl starch on the need for blood products in the perioperative period of oncologic surgery. The secondary end-points included the need for other blood products, the clotting profile, the intensive care unit mortality and length of stay. METHODS: Retrospective observational analysis in a tertiary oncologic ICU in Brazil including 894 patients submitted to oncologic surgery for a two-year period from September 2007. Patients were grouped according to whether hydroxyethyl starch was used during surgery (hydroxyethyl starch and No-hydroxyethyl starch groups) and compared using a propensity score analysis. A total of 385 propensity-matched patients remained in the analysis (97 in the No-hydroxyethyl starch group and 288 in the hydroxyethyl starch group). RESULTS: A higher percentage of patients in the hydroxyethyl starch group required red blood cell transfusion during surgery (26% vs. 14%; p = 0.016) and in the first 24 hours after surgery (5% vs. 0%; p = 0.015) but not in the 24- to 48-hour period after the procedure. There was no difference regarding the transfusion of other blood products, intensive care unit mortality or length of stay. CONCLUSION: Hydroxyethyl starch use in the intraoperative period of major oncologic surgery is associated with an increase in red blood cell transfusions. There are no differences in the need for other blood products, intensive care unit length of stay or mortality. .

Terapia de reposição volêmica durante artroplastia de quadril usando hidroxietilamido (130/0, 4) comparado com Ringer lactato diminui transfusão de sangue alogênico e infecção pós-operatória / Volume replacement therapy during hip arthroplasty using hydroxyethyl starch (130/0. 4) compared to lactated Ringer decreases allogeneic blood transfusion and postoperative infection / Terapia de reposición volémica durante la artroplastia de cadera usando hidroxietilalmidón (130/0, 4): comparado con lactato de Ringer reduce la transfusión de sangre alogénica y la infección posoperatoria

JUSTIFICATIVA E OBJETIVOS: O hidroxietilamido 130/0,4 (HES 130/0,4) é considerado um expansor plasmático efetivo quando comparado com cristaloides. Há controvérsia sobre sua superioridade em relação à otimização hemodinâmica e sobre possíveis efeitos prejudiciais na coagulação. O objetivo deste estudo foi comparar os efeitos do HES 130/0,4 com os da solução de Ringer lactato durante artroplastia de quadril em pacientes adultos sob raquianestesia e levou em consideração sangramento intraoperatório, parâmetros hemodinâmicos, coagulograma, necessidade de transfusão e desfechos clínicos. MÉTODOS: Neste estudo randômico e controlado, 48 pacientes agendados para artroplastia de quadril com raquianestesia foram alocados em dois grupos: 24 receberam uma pré-carga de HES 130/0,4 (15 mL.kg-1) e 24 receberam uma pré-carga de solução de Ringer lactato (30 mL. kg-1) antes da cirurgia. Mensurações hemodinâmicas, concentração de hemoglobina, parâmetros bioquímicos e testes de coagulação foram avaliados em três períodos durante o procedimento cirúrgico. Os pacientes receberam acompanhamento médico durante a internação e até 30 dias no período pós-operatório. O principal fator foi a necessidade de transfusão de hemácias entre os grupos durante a internação. Os fatores secundários foram parâmetros hemodinâmicos, tempo de internação, mortalidade e ocorrência de complicações clínicas. no período pós-operatório. O principal fator foi a necessidade de transfusão de hemácias entre os grupos durante a internação. Os fatores secundários foram parâmetros hemodinâmicos, tempo de internação, mortalidade e ocorrência de complicações clínicas. RESULTADOS: A transfusão de hemácias foi necessária em 17% dos pacientes do grupo HES e em 46% dos pacientes do grupo Ringer lactato (p = 0,029). Infecções pós-operatórias foram observadas com mais frequência no grupo de Ringer lactato (17%) em comparação com o grupo HES (0), p = 0,037. Não houve diferenças significativas entre os grupos em relação à mortalidade, ao tempo de internação e às complicações clínicas, exceto infecção. CONCLUSÕES: Durante a artroplastia de quadril, os pacientes tratados com hemodiluição hipervolêmica normal com hidroxietilamido 130/0,4 precisaram de menos transfusão e apresentaram índice menor de infecção em comparação com os pacientes que receberam Ringer lactato.

BACKGROUND AND OBJECTIVES: Hydroxyethyl starch (HES) 130/0.4 is considered an effective plasma expander when compared to crystalloids. There is controversy around its superiority regarding hemodynamic optimization and about possible detrimental effects on coagulation. The aim of this study was to compare the effects of HES 130/0.4 to lactated Ringer solution during hip arthroplasty in adult patients under spinal anesthesia regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. METHODS: In this randomized, controlled trial, 48 patients scheduled for hip arthroplasty with spinal anesthesia were randomized into two groups: 24 patients were allocated to receive a preload of 15 mL.kg-1 of HES 130/0.4 and 24 patients received a preload of 30 mL.kg-1 lactated Ringer solution before surgery. Hemodynamic measurements, hemoglobin concentrations, biochemical parameters and coagulation tests were evaluated in three periods during surgical procedure. Patients received medical follow-up during their hospital stay and up to postoperative 30 days. Primary outcome was the requirement of red blood cell transfusion between groups during hospital stay. Secondary outcome were hemodynamic parameters, length of hospital stay, mortality and occurrence of clinical postoperative complications. RESULTS: Red blood cell transfusion was required in 17% of patients in the HES group and in 46% in the Ringer group (p = .029). Postoperative infections were more frequently observed in the Ringer group (17%) compared to the HES group (0), p = .037. There were no significant differences between groups in mortality, hospital length of stay and clinical complications other than infection. Conclusions: During hip arthroplasty, patients treated with hypervolemic hemodilution with hydroxyethyl starch 130/0.4 required less transfusion and presented lower infection rate compared to patients who received lactated Ringer.

JUSTIFICATIVA Y OBJETIVOS: El hidroxietilalmidón 130/0,4 (HES 130/0,4) está considerado como un expansivo plasmático efectivo cuando se le compara con los cristaloides. Existen controversias sobre su superioridad con relación a la optimización hemodinámica y sobre posibles efectos perjudiciales en la coagulación. El objetivo de este estudio, fue comparar los efectos del HES 130/0,4 con los de la solución de lactato de Ringer durante la artroplastia de cadera en pacientes adultos bajo raquianestesia, considerando el sangramiento intraoperatorio, los parámetros hemodinámicos, el coagulograma, la necesidad de transfusión y los resultados clínicos. MÉTODOS: En este estudio aleatorio y controlado, 48 pacientes citados para la artroplastia de cadera con raquianestesia fueron aleatoriamente divididos en dos grupos: 24 pacientes fueron ubicados para recibir una pre-carga de HES 130/0,4 (15 mL.kg-1) y 24 pacientes recibieron una pre-carga de solución de lactato de Ringer (30 mL.kg-1) antes de la cirugía. Las medidas hemodinámicas, concentración de hemoglobina, parámetros bioquímicos y los test de coagulación fueron evaluados en tres períodos durante el procedimiento quirúrgico. Los pacientes recibieron un acompañamiento médico durante el ingreso y de 30 días en el período del postoperatorio. El principal factor fue la necesidad de transfusión de hematíes entre los grupos durante el ingreso. Los factores secundarios fueron los parámetros hemodinámicos, tiempo de ingreso, mortalidad y aparecimiento de complicaciones clínicas. RESULTADOS: La transfusión de hematíes fue necesaria en un 17% de los pacientes del grupo HES y en un 46% de los pacientes del grupo lactato de Ringer (p = 0,029). Las infecciones postoperatorias fueron observadas con más frecuencia en el grupo lactato de Ringer (17%) en comparación con el grupo HES (0), p = 0,037. No hubo diferencias significativas entre los grupos con relación a la mortalidad, tiempo de ingreso y complicaciones clínicas, excepto en la infección. Conclusiones: Durante la artroplastia de cadera, los pacientes tratados con hemodilución hipervolémica normal con hidroxietilalmidón 130/0.4 necesitaron menos transfusión y presentaron un índice menor de infección en comparación con los pacientes que recibieron lactato de Ringer.

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

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

Comparison of 7.2% hypertonic saline - 6% hydroxyethyl starch solution and 6% hydroxyethyl starch solution after the induction of anesthesia in patients undergoing elective neurosurgical procedures

OBJECTIVE: The ideal solution for fluid management during neurosurgical procedures remains controversial. The aim of this study was to compare the effects of a 7.2% hypertonic saline - 6% hydroxyethyl starch (HS-HES) solution and a 6% hydroxyethyl starch (HES) solution on clinical, hemodynamic and laboratory variables during elective neurosurgical procedures. METHODS: Forty patients scheduled for elective neurosurgical procedures were randomly assigned to the HS-HES group orthe HES group. Afterthe induction of anesthesia, patients in the HS-HES group received 250 mL of HS-HES (500 mL/h), whereas the patients in the HES group received 1,000 mL of HES (1000 mL/h). The monitored variables included clinical, hemodynamic and laboratory parameters. Chictr.org: ChiCTR-TRC-12002357 RESULTS: The patients who received the HS-HES solution had a significant decrease in the intraoperative total fluid input (p<0.01), the volume of Ringer's solution required (p<0.05), the fluid balance (p<0.01) and their dural tension scores (p<0.05). The total urine output, blood loss, bleeding severity scores, operation duration and hemodynamic variables were similar in both groups (p>0.05). Moreover, compared with the HES group, the HS-HES group had significantly higher plasma concentrations of sodium and chloride, increasing the osmolality (p<0.01). CONCLUSION: Our results suggest that HS-HES reduced the volume of intraoperative fluid required to maintain the patients undergoing surgery and led to a decrease in the intraoperative fluid balance. Moreover, HS-HES improved the dural tension scores and provided satisfactory brain relaxation. Our results indicate that HS-HES may represent a new avenue for volume therapy during elective neurosurgical procedures.

Intraoperative fluid management in open gastrointestinal surgery: goal-directed versus restrictive

OBJECTIVE: The optimal strategy for fluid management during gastrointestinal surgery remains unclear. Minimizing the variation in arterial pulse pressure, which is induced by mechanical ventilation, is a potential strategy to improve postoperative outcomes. We tested this hypothesis in a prospective, randomized study with lactated Ringer's solution and 6% hydroxyethyl starch solution. METHOD: A total of 60 patients who were undergoing gastrointestinal surgery were randomized into a restrictive lactated Ringer's group (n = 20), a goal-directed lactated Ringer's group (n = 20) and a goal-directed hydroxyethyl starch group (n = 20). The goal-directed fluid treatment was guided by pulse pressure variation, which was recorded during surgery using a simple manual method with a Datex Ohmeda S/5 Monitor and minimized to 11% or less by volume loading with either lactated Ringer's solution or 6% hydroxyethyl starch solution (130/0.4). The postoperative flatus time, the length of hospital stay and the incidence of complications were recorded as endpoints. RESULTS: The goal-directed lactated Ringer's group received the greatest amount of total operative fluid compared with the two other groups. The flatus time and the length of hospital stay in the goal-directed hydroxyethyl starch group were shorter than those in the goal-directed lactated Ringer's group and the restrictive lactated Ringer's group. No significant differences were found in the postoperative complications among the three groups. CONCLUSION: Monitoring and minimizing pulse pressure variation by 6% hydroxyethyl starch solution (130/0.4) loading during gastrointestinal surgery improves postoperative outcomes and decreases the discharge time of patients who are graded American Society of Anesthesiologists physical status I/II.

Evaluation of hemostatic changes using n thromboelastography after crystalloid or colloid fluid administration during major orthopedic surgery

The effects of Ringer lactate, 6% hydroxyethyl starch (HES) (130/0.4) or 4% succinylated gelatin solutions on perioperative coagulability were measured by thromboelastography (TEG). Seventy-five patients (ASA I-III) who were to undergo major orthopedic procedures performed under epidural anesthesia were included in the study. Patients were randomly divided into three groups of 25 each for the administration of maintenance fluids: group RL (Ringer lactate), group HES (6% HES 130/0.4), and group JEL (4% gelofusine solution). Blood samples were obtained during the perioperative period before epidural anesthesia (t1, baseline), at the end of the surgery (t2), and 24 h after the operation (t3). TEG data, reaction time (R), coagulation time (K), angle value (α), and maximum amplitude (MA) were recorded. TEG parameters changed from normal values in all patients. In group RL, R and K times decreased compared to perioperative values while the α angle and MA increased (P < 0.05). In group HES, R and K times increased, however, the α angle and MA decreased (P < 0.05). In group JEL, R time increased (P < 0.05), but K time, α angle and MA did not change significantly. In the present study, RL, 6% HES (130/0.4) and 4% JEL solutions caused changes in the coagulation system of all patients as measured by TEG, but these changes remained within normal limits.

Protective perioperative strategy using a third generation hydroxyethyl starch during surgery in a murine model of liver reperfusion injury / Estratégia protetora perioperatória usando um hidroxietilamido de terceira geração para expansão volêmica durante a cirurgia em modelo murino de lesão de reperfusão hepática

PURPOSE: To investigate whether a third generation colloid, hydroxyethyl starch (HES 130/0.4), used for perioperative fluid therapy, protects the rat liver against the late-phase response of ischemia/reperfusion injury (IRI) and if inhibition of neutrophil hepatic infiltration plays a part in this mechanism. METHODS: Wistar rats were used (8 in each group). Three groups had IRI induced by lobar vascular occlusion (60 minutes) and reperfusion (24 hours) and received HES (13 mL/kg iv), 7.5 percent saline (HS) (13 mL/kg iv) or no fluid. Three other groups were sham-operated and received the same fluid as the test groups. After 24 hours of reperfusion, blood was drawn for alanine aminotransferase (ALT) quantification and ischemic liver samples were taken for histological study (hematoxylin and eosin and chloroacetate staining of neutrophils). RESULTS: HES treatment attenuated the elevation in serum ALT (P=0.001) and reduced the extent of hepatocellular necrosis (P<0.01) compared with the IRI controls. HES-mediated cytoprotection was associated with a decrease of infiltration of neutrophils in the necrotic areas (P<0.05) compared with the untreated IRI rats, but not with the volume control IRI rats (P>0.05). CONCLUSION: Hydroxyethyl starch suppresses inflammatory response and ameliorates the late-phase response of hepatic ischemia/reperfusion injury.

OBJETIVO: Investigar se um colóide de terceira geração (HES 130/0.4), utilizado para fluidoterapia perioperatória, protege o fígado de rato contra a resposta da fase tardia de isquemia/reperfusão e se a inibição da infiltração hepática de neutrófilos desempenha um papel neste mecanismo. MÉTODOS: Foram utilizados ratos Wistar (8 em cada grupo). Três grupos tiveram lesão de isquemia/reperfusão (IRI) induzida por oclusão vascular lobar (60 minutos) e reperfusão (24 horas) e receberam HES (13 ml / kg iv), soro fisiológico a 7,5 por cento (HS) (13 ml / kg iv) ou nenhum fluido. Três outros grupos foram sham-operados e receberam o mesmo tipo de fluido dos grupos de teste. Após 24 horas de reperfusão, o sangue foi retirado para quantificação da alanina aminotransferase (ALT) e amostras de fígado isquêmico foram retiradas para estudo histológico (hematoxilina e eosina e coloração cloroacetato para neutrófilos). RESULTADOS: O tratamento com HES atenuou a elevação da ALT sérica (P = 0,001) e reduziu a extensão da necrose hepatocelular (P<0,01) em comparação com os controles da IRI. A citoproteção mediada por HES foi associada a uma diminuição da infiltração de neutrófilos nas áreas de necrose (P<0,05) em comparação com os ratos não tratados IRI, mas não com os ratos controlo IRI (P> 0,05). CONCLUSÃO: HES suprime a resposta inflamatória e melhora a resposta na fase tardia da isquemia/reperfusão hepática.

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.

Efeitos cardiovascular e metabólico da reposição volêmica com hidroxietilamido 130/0, 4 em felinos domésticos com hipovolemia induzida / Cardiovascular and metabolic effects of volemic expansion with hydroxyethyl starch 130/0, 4 in domestic cats with induced hypovolemia

O objetivo deste estudo foi comparar os efeitos da expansão volêmica produzida pelo hidroxietilamido 130/0,4 (HES 130/0,4) ou pelo sangue em gatas com hipovolemia induzida. Foram utilizadas 12 gatas adultas, sem raça definida (SRD), com peso médio de 2,85±0,28kg e hígidas. Os animais foram induzidos à anestesia geral com isofluorano a 5V por cento, intubados e conectados a um sistema sem reinalação de gases. Após a instrumentação, os animais foram mantidos sob anestesia com isoflurano em 1,3V por cento e mantidos em ventilação mecânica, ciclada a pressão. Em seguida, foi induzida a hipovolemia por meio da retirada de 30ml kg-1 de sangue da artéria femoral. Após 60 minutos da estabilização do paciente, os tratamentos foram iniciados. No grupo hidroxietilamido (GH, n=06), os animais receberam, como reposição volêmica, o hidroxietilamido 130/0,4 no mesmo volume de sangue retirado e, no grupo sangue (GS, n=06), os animais receberam o próprio sangue retirado, sendo considerado grupo controle. A pressão arterial sistólica, a diastólica e a média e a pressão venosa central aumentaram após a reposição volêmica em ambos os grupos. Observou-se, para o GH, aumento da PaCO2 no T15, no T30 e no T60. Houve redução do pH no T30 e no T45 e de íons Na+ no T90 para GH. A restauração das pressões arteriais com a administração de HES 130/0,4 foi similar ao grupo controle. A reposição volêmica com HES 130/0,4 produz aumento acentuado da PVC; e o uso do HES 130/0,4 em gatas submetidas à hipovolemia não produziu alterações clinicamente significativas no equilíbrio ácido-básico.

The aim of this study was to compare the volemic expansion effects produced by hydroxyethyl starch 130/0.4 (HES 130/0.4) or blood, in female cats with induced hypovolemia. Twelve healthy adult female cats, crossbreed and weighing an average of 2.85±0.28kg were used. They were induced into general anesthesia with isofluorane at 5V percent, intubated and connected to a non-rebreathing system. After instrumentation, the animals were maintained under anesthesia with isofluorane at 1.3V percent and maintained on pressure cycled mechanic ventilation. Afterwards, hypovolemia was induced by withdrawal of 30ml kg-1 of blood from the femoral artery. After 60 minutes of stabilization of the patient, the treatments were initiated. In the hydroxyethyl starch group (GH, n=06) the animals received hydroxyethyl starch 130/0.4 as volemic expansion at the same volume of blood withdrawed, in the blood group (GS, n=06) the animals received their own withdrawed blood, being considered the control group. The systolic, diastolic and mean arterial pressures and central venous pressure increased after volemic expansion in both groups. An increase of PaCO2 at T15, T30 and T60 in GH was observed. In addition, there was reduction of pH at T30 and T45 and Na+ ions at T90 in GH. The arterial pressure restoration with the use of HES 130/0.4 was similar to the control group; the volemic expansion with HES 130/0,4 produces accentuated increase of CVP; the use of HES 130/0,4 in female cats submitted to hypovolemia did not produce clinically significant alterations in acid-base equilibrium.

Estudo prospectivo randomizado comparando duas técnicas de expansão volêmica em cirurgia de artroplastia total de quadril: hidroxietilamido (130/0.4) e Ringer lactato / Comparison between two techniques of volemic expansion during surgery to total hip arthroplasty: hydroxyethyl starch (130/0,4) and lactateds Ringer solutions: study prospective, randomized

Introdução: Os hidroxietilamidos (HES) são considerados expansores plasmáticos efetivos em pacientes submetidos a procedimentos cirúrgicos de grande porte. Entretanto, seu uso clínico é limitado principalmente por sua interferência na hemostasia, representada por alterações da função plaquetária e na coagulação. A extensão dessas alterações está relacionada ao seu peso molecular ou à sua substituição molar. Este estudo clínico, foi realizado durante cirurgia de artroplastia de quadril em pacientes adultos para comparar os efeitos do HES (130/0,4) e a solução de Ringer lactato em relação ao sangramento intra-operatório, parâmetros hemodinâmicos, alterações na coagulação, necessidade de transfusões e resultados clínicos. Métodos: Quarenta e oito pacientes candidatos à cirurgia de artroplastia total de quadril sob anestesia subaracnoidea foram distribuídos aleatoriamente em dois grupos 24 pacientes foram selecionados para receber HES (30 ml/kg após anestesia) e 24 pacientes para receber solução de Ringer lactato (30ml/kg). O período de observação teve início após a indução da anestesia e terminou 5 horas após o termino do procedimento cirúrgico. Durante esse período o critério para a infusão de doses adicionais de fluido (10ml/kg de Solução de Ringer lactato para ambos os grupos) foi pressão arterial sistólica inferior a 90 mmHg e/ou um decréscimo de 20% da pressão arterial inicial, frequência cardíaca acima de 100 bpm, e/ou débito urinário menor de 0,4ml/kg/h. Vasopressor foi utilizado nos casos em que a hipotensão persistiu, após a reposição de volume. Transfusão de concentrado de hemácias foi administrada nos pacientes que se mantiveram instáveis hemodinamicamente após bolus adicionais de Ringer lactato ou vasopressor, Parâmetros hemodinâmicos foram mensurados em três períodos da cirurgia; dados bioquímicos foram coletados e testes da coagulação realizados e comparados. Os pacientes foram acompanhados durante sua internação hospitalar...

Introduction: Hydroxyethyl starches (HES) are considered effective plasma expanders in patients undergoing major surgeries. However, the clinical use of HES is limited mainly by their affection of hemostasis, detectable by impaired platelet function and altered coagulation. The extent of such alteration has classically been related to the molecular weight or molar substitution of the used HES solution. This prospective, randomized study was performed during hip arthroplasty in adult patients under spinal anesthesia to compare the effects of HES 130/0.4 with lactateds Ringer solution regarding intraoperative bleeding, hemodynamic parameters, coagulation profile, transfusion requirements and clinical outcomes. Methods: Forty eight patients scheduled to hip arthroplasty after spinal anesthesia were randomized in two groups 24 patients were allocated to receive HES 130/0.4 (30 ml/Kg just after anesthesia) and 24 patients were signaled to receive lactateds Ringer solution (30 ml/Kg). The observational period started after the induction of anesthesia and finished 5 hours after the end of the surgery. During this period, the triggers for infusion of additional boluses of fluids (10 ml/Kg of lactateds Ringer for both groups) were a systolic blood pressure lower than 90 mmHg and/or a decrease of 20% from baseline, a heart rate higher than 100 bpm, and/or a urine output lower than 0.4 ml.Kg-1.h-1. Vasopressors were used if there was persistent hypotension despite of fluid reposition. Red blood cell transfusion was administered if patient remained unstable despite of additional boluses of Ringer or vasopressors, according to the preestablished triggers. Hemodynamic measurements were done in three periods of the surgery, biochemical parameters were analyzed and coagulation tests were performed and compared between groups. After surgery, patients were followed during the hospital stay. Results: The groups were well matched regarding demographic data, type of surgery...

Aislamiento de células mononucleares de sangre periférica para trasplante de células madre: método simplificado / Isolation of mononuclear cells of peripheral blood for stem cell transplant: simplified method

En los últimos años el tema de las células madre ha despertado creciente interés por su potencial terapéutico en enfermedades que hasta el momento no tienen un tratamiento efectivo. Se realizó un estudio prospectivo y exploratorio en pacientes con arteriosclerosis obliterante de miembros inferiores, en el que se evaluó la seguridad y efectividad de un método manual de recolección y procesamiento de células mononucleares y de células CD34+ a partir de sangre periférica movilizada. La sangre se procesó en sistemas cerrados de recolección, utilizando el hidroxietilalmidón como potenciador de la sedimentación eritrocitaria. Los pacientes fueron tratados con factor estimulador de colonias granulocítico en dosis total de 40ìcg/kg de peso durante 2 días, y después si el conteo de leucocitos era superior a 20 x 109/L se procedió a la autodonación. Para valorar la eficacia del método se analizaron las cantidades de células nucleadas, de células mononucleares y de células CD 34+ en el concentrado celular; se determinó la viabilidad celular y además se hizo el estudio microbiológico del material obtenido. Se demostró que el método es eficaz y seguro, ya que logra niveles celulares adecuados, con elevada viabilidad y ausencia de contaminación bacteriana. Por otra parte, es sencillo y de bajo costo, lo que permite su extensión a otros centros de salud, en particular a los de menos recursos. Esto facilita que un mayor número de pacientes se puedan beneficiar con el tratamiento a base de células madre.

In the last years, the topic of stem cells has arisen an increasing interest for its therapeutic potential in diseases that have not an effective treatment so far. A prospsective and exploratory study was conducted in patients with obliterant atherosclerosis of the lower limbs to evaluate the safety and effectiveness of a manual method of collection and processing of mononuclear cells and of CD34+ cells, starting from mobilized peripheral blood. The blood was processed in closed collection systems, using hydroxyethyl starch as a potentiator of erythrocyte sedimentation. The patients were treated with granulocyte colony stimulating factor at total doses of 40µcg/kg of weight during 2 days. Self-donation was performed when the leukocyte count was higher than 20 x 109/L. To assess the efficacy of the method, the amounts of nucleated cells, of mononuclear cells and of CD 34+ cells in the cellular concentrate were analyzed. Cellular viability was determined and a microbiological study of the material obtained was conducted. It was proved that the method is efficient and safe, since adequate cellular levels with a high viability and absence of bacterial contamination are attained. On the other hand, it is simple and cheap, which allows its application in other health centres, particularly in those with less resources. This makes possible that more patients benefit from the stem cell treatment.