Effects of rocuronium, sugammadex and rocuronium-sugammadex complex on coagulation in rats / Efeitos do rocurônio, sugamadex e complexo rocurônio-sugamadex sobre a coagulação em ratos

Abstract Background and objectives: Sugammadex is an alternative pharmacological drug capable of reversing neuromuscular blockades without the limitations that are presented by anticholinesterase drugs. Coagulation disorders that are related to treatment with sugammadex were reported. The exact mechanism of the effects on coagulation are not fully understood. The objective of this research is to evaluate the effects of rocuronium, sugammadex and the rocuronium-sugammadex complex on coagulation in an experimental model in rats. Methods: This is an experimental randomized animal study. Wistar rats were randomly assigned into the following groups: the Control Group; the Ssal Group - 0.5 mL of intravenous saline; the Sugammadex Group - intravenous sugammadex (100 mg kg−1); and the Rocuronium-Sugammadex Group - intravenous solution with rocuronium (3.75 mg kg−1) and sugammadex (100 mg kg−1). Anesthesia was performed by using isoflurane with controlled ventilation. Coagulation factors were measured 10 minutes after the end of the preoperative preparation and 30 minutes after the administration of the drugs in accordance with the chosen groups. Results: Platelet counts, prothrombin times, and activated partial thromboplastin times were similar between the groups and between the moments within each group. There were reductions in the plasma fibrinogen levels between sample times 1 and 2 in the Rocuronium-Sugammadex group (p = 0.035). Conclusions: The rocuronium-sugammadex complex promoted reductions in plasma fibrinogen counts, although the levels were still within normal limits.

Resumo Introdução e objetivos: O sugamadex é uma substância farmacológica alternativa capaz de reverter o bloqueio neuromuscular sem as limitações apresentadas pelos anticolinesterásicos. Entretanto, há relatos de transtornos de coagulação relacionados ao tratamento com sugamadex sem que mecanismos exatos de seus efeitos sobre a coagulação sejam totalmente compreendidos. O objetivo da presente pesquisa foi avaliar os efeitos do rocurônio, sugamadex e do complexo rocurônio-sugamadex sobre a coagulação em um modelo experimental com ratos. Métodos: Este é um estudo randomizado experimental animal. Ratos Wistar foram aleatoriamente designados aos seguintes grupos: grupo controle; Grupo Ssal - 0,5 mL de solução salina intravenosa; Grupo sugamadex - sugamadex intravenoso (100 mg.kg-1); e Grupo rocurônio-sugamadex - solução intravenosa com rocurônio (3,75 mg.kg-1) e sugamadex (100 mg.kg-1). A anestesia foi realizada utilizando-se isoflurano com ventilação controlada. Os fatores de coagulação foram medidos 10 minutos após o final do preparo pré-operatório e 30 minutos após a administração de drogas de acordo com os grupos escolhidos. Resultados: Contagem de plaquetas, tempo de protrombina e tempo de tromboplastina parcial ativada foram semelhantes entre os grupos e entre os momentos dentro de cada grupo. Houve redução nos níveis de fibrinogênio plasmático entre os tempos 1 e 2 no grupo rocurônio-sugamadex (p = 0,035). Conclusões: O complexo rocurônio-sugamadex promoveu reduções na contagem de fibrinogênio plasmático, apesar de os níveis continuarem dentro dos limites normais.

[Effects of rocuronium, sugammadex and rocuronium-sugammadex complex on coagulation in rats]. / Efeitos do rocurônio, sugamadex e complexo rocurônio­sugamadex sobre a coagulação em ratos.

BACKGROUND AND OBJECTIVES: Sugammadex is an alternative pharmacological drug capable of reversing neuromuscular blockades without the limitations that are presented by anticholinesterase drugs. Coagulation disorders that are related to treatment with sugammadex were reported. The exact mechanism of the effects on coagulation are not fully understood. The objective of this research is to evaluate the effects of rocuronium, sugammadex and the rocuronium-sugammadex complex on coagulation in an experimental model in rats. METHODS: This is an experimental randomized animal study. Wistar rats were randomly assigned into the following groups: the Control Group; the Ssal Group - 0.5 mL of intravenous saline; the Sugammadex Group - intravenous sugammadex (100 mg.kg-1); and the Rocuronium-Sugammadex Group - intravenous solution with rocuronium (3.75 mg.kg-1) and sugammadex (100 mg.kg-1). Anesthesia was performed by using isoflurane with controlled ventilation. Coagulation factors were measured 10 minutes after the end of the preoperative preparation and 30 minutes after the administration of the drugs in accordance with the chosen groups. RESULTS: Platelet counts, prothrombin times and activated partial thromboplastin times were similar between the groups and between the moments within each group. There were reductions in the plasma fibrinogen levels between sample times 1 and 2 in the Rocuronium-Sugammadex group (p=0.035). CONCLUSIONS: The rocuronium-sugammadex complex promoted reductions in plasma fibrinogen counts, although the levels were still within normal limits.

Improving Intraoperative Communication in Trauma: The Educational Effect of the Joint DSTC™-DATC™ Courses.

BACKGROUND: Operative management of severe trauma requires excellent communication among team members. The surgeon and anesthesiologist need to interact efficiently, exchanging vital information. The Definitive Surgical Trauma Care (DSTC) and Definitive Anesthesia Trauma Care (DATC) courses provide an excellent opportunity for teamwork training. Our goal was to study the impact of the joint DSTC-DATC courses in candidates' self-reported assessment in communication skills and techniques in a simulated intraoperative trauma scenario. METHODS: Study population consists of 93 candidates (67 surgeons and 26 anesthesiologists) participating in four consecutive joint DSTC-DATC courses in May and June 2019 in Brazil (3) and in Portugal (1). Median age was 30 years; 53 (60%) of subjects were male (46 senior residents and 47 specialists). All participants attended joint lectures, case discussions and surgical skills session, emphasizing intraoperative communication. Post-course survey on several aspects of perioperative communication (responses on a Likert scale) was conducted with participants being asked which aspects of intraoperative communication they valued the most. RESULTS: All participants responded to the survey. Results displayed an increase in the self-assessed importance of team briefing and intraoperative communication, particularly routine periodic communication, rather than only at critical moments. Postoperative team debriefing was also valued as highly relevant. Closed-loop and direct, by-name communication were highly rated. Self-reported communication skills improved significantly during the course. CONCLUSIONS: Joint training in the DSTC-DATC courses improved candidates' perception and skills on proficient intraoperative communication. Further studies should address both the durability of these changes and the potential impact on patient care.

Predictors and their prognostic value for no ROSC and mortality after a non-cardiac surgery intraoperative cardiac arrest: a retrospective cohort study.

Data on predictors of intraoperative cardiac arrest (ICA) outcomes are scarce in the literature. This study analysed predictors of poor outcome and their prognostic value after an ICA. Clinical and laboratory data before and 24 hours (h) after ICA were analysed as predictors for no return of spontaneous circulation (ROSC) and 24 h and 1-year mortality. Receiver operating characteristic curves for each predictor and sensitivity, specificity, positive and negative likelihood ratios, and post-test probability were calculated. A total of 167,574 anaesthetic procedures were performed, including 158 cases of ICAs. Based on the predictors for no ROSC, a threshold of 13 minutes of ICA yielded the highest area under curve (AUC) (0.867[0.80-0.93]), with a sensitivity and specificity of 78.4% [69.6-86.3%] and 89.3% [80.4-96.4%], respectively. For the 1-year mortality, the GCS without the verbal component 24 h after an ICA had the highest AUC (0.616 [0.792-0.956]), with a sensitivity of 79.3% [65.5-93.1%] and specificity of 86.1 [74.4-95.4]. ICA duration and GCS 24 h after the event had the best prognostic value for no ROSC and 1-year mortality. For 24 h mortality, no predictors had prognostic value.

Ultrasound dynamics of gastric content volumes after the ingestion of coconut water or a meat sandwich. A randomized controlled crossover study in healthy volunteers / Dinâmica ultrassonográfica dos volumes do conteúdo gástrico após a ingestão de água de coco ou sanduíche de carne. Um estudo cruzado controlado e randômico com voluntários saudáveis

Abstract Background: Adequate preoperative fasting is critical in preventing pulmonary aspiration of gastric content. We proposed to study the sonographic gastric content dynamics after the ingestion of liquid or solid food in healthy volunteers and confront it with current guidelines for preoperative fasting times. Methods: We performed a prospective, crossover, evaluator-blinded study involving 17 healthy volunteers of both sexes. Each participant fasted for 10 h and was subjected to a baseline gastric ultrasound, intake of 400 mL of coconut water or a 145 g, 355 kcal meat sandwich, and sonographic gastric evaluations after 10 min and every hour until the stomach was completely empty. Results: At baseline, all subjects had an empty stomach. At 10 min, gastric content [mean + standard deviation (SD)] was 240.4 + 69.3 and 248.2 + 119.2 mL for liquid and solid foods, respectively (p > 0.05). Mean + SD gastric emptying times were 2.5 + 0.7 and 4.5 + 0.9 h for liquid and solid foods, respectively (p < 0.001). For the drink, the stomach was completely empty in 59% and 100% of the subjects after two and four hours, and for the sandwich, 65% and 100% of the subjects after four and seven hours, respectively. Conclusions: Sonographic gastric dynamics for coconut water and a meat sandwich resulted in complete gastric emptying times higher and lower, respectively, than those suggested by current guidelines for preoperative fasting.

Resumo Justificativa: O jejum pré-operatório adequado é fundamental para prevenir a aspiração pulmonar do conteúdo gástrico. Nossa proposta foi avaliar a dinâmica ultrassonográfica do conteúdo gástrico após a ingestão de alimentos líquidos ou sólidos em voluntários sadios e confrontá-la com as diretrizes atuais para os períodos de jejum no pré-operatório. Métodos: Um estudo prospectivo, cruzado e avaliador-cego foi feito com 17 voluntários saudáveis de ambos os sexos. Cada participante jejuou por 10 horas e foi submetido a uma ultrassonografia gástrica na fase basal, ingestão de 400 mL de água de coco ou 355 g de sanduíche de carne e avaliações gástricas ultrassonográficas foram feitas após 10 minutos e a cada hora até o estômago estar completamente vazio. Resultados: Na fase basal, todos os participantes estavam com o estômago vazio. Aos 10 minutos, o conteúdo gástrico [média + desvio-padrão (DP)] foi de 240,4 + 69,3 e 248,2 + 119,2 mL para alimentos líquidos e sólidos, respectivamente (p > 0,05). Os tempos médios de esvaziamento gástrico + DP foram de 2,5 + 0,7 e 4,5 + 0,9 horas para alimentos líquidos e sólidos, respectivamente (p < 0,001). Para a bebida, o estômago ficou completamente vazio em 59% e 100% dos sujeitos após duas e quatro horas; para o sanduíche, o estômago ficou completamente vazio em 65% e 100% dos sujeitos após quatro e sete horas, respectivamente. Conclusões: A dinâmica ultrassonográfica do volume gástrico para água de coco e sanduíche de carne resultou em tempos totais de esvaziamento gástrico maiores e menores, respectivamente, do que os sugeridos pelas diretrizes atuais para o jejum pré-operatório.

[Ultrasound dynamics of gastric content volumes after the ingestion of coconut water or a meat sandwich. A randomized controlled crossover study in healthy volunteers]. / Dinâmica ultrassonográfica dos volumes do conteúdo gástrico após a ingestão de água de coco ou sanduíche de carne. Um estudo cruzado controlado e randômico com voluntários saudáveis.

BACKGROUND: Adequate preoperative fasting is critical in preventing pulmonary aspiration of gastric content. We proposed to study the sonographic gastric content dynamics after the ingestion of liquid or solid food in healthy volunteers and confront it with current guidelines for preoperative fasting times. METHODS: We performed a prospective, crossover, evaluator-blinded study involving 17 healthy volunteers of both sexes. Each participant fasted for 10h and was subjected to a baseline gastric ultrasound, intake of 400mL of coconut water or a 145g, 355kcal meat sandwich, and sonographic gastric evaluations after 10min and every hour until the stomach was completely empty. RESULTS: At baseline, all subjects had an empty stomach. At 10min, gastric content [mean + standard deviation (SD)] was 240.4 + 69.3 and 248.2 + 119.2mL for liquid and solid foods, respectively (p>0.05). Mean + SD gastric emptying times were 2.5 + 0.7 and 4.5 + 0.9h for liquid and solid foods, respectively (p<0.001). For the drink, the stomach was completely empty in 59% and 100% of the subjects after two and four hours, and for the sandwich, 65% and 100% of the subjects after four and seven hours, respectively. CONCLUSIONS: Sonographic gastric dynamics for coconut water and a meat sandwich resulted in complete gastric emptying times higher and lower, respectively, than those suggested by current guidelines for preoperative fasting.

Noradrenaline and dobutamine effects on the volume expansion with normal saline in rabbits subjected to hemorrhage.

PURPOSE:: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS:: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS:: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION:: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.

Noradrenaline and dobutamine effects on the volume expansion with normal saline in rabbits subjected to hemorrhage

ABSTRACT PURPOSE: To evaluate the effects of dobutamine (DB), noradrenaline (NA), and their combination (NADB), on volume retention in rabbits submitted to hemorrhage. METHODS: Thirty six rabbits were randomly divided into 6 groups: SHAM, Control, Saline, DB, NA, DB+NA. All the animals, except for SHAM, were subjected to hemorrhage of 25% of the calculated blood volume. Control animals were replaced with their own blood. The other groups received NSS 3 times the volume withdrawn. The intravascular retention, hematocrit, diuresis, central venous pressure, mean arterial pressure, NGAL, dry-to-wet lung weight ratio (DTWR) and the lung and kidney histology were analyzed. RESULTS: Replacement with NSS and NA, DB or NA+DB did not produce differences in the intravascular retention. After hemorrhage, the animals presented a significant decrease in the MAP and CVP, which were maintained until volume replacement. Regarding NGAL, dry-to-wet-lung-weight ratio, lung and kidney histology, there were no statistical differences between the groups. CONCLUSION: The use of noradrenaline, dobutamine or their combination did not increase the intravascular retention of volume after normal saline infusion.

Evaluation of genotoxicity of general anesthesia maintained with desflurane in patients under minor surgery.

There is controversy over the genotoxic effects of volatile anesthetics. The available literature on the genotoxicity of desflurane, one of the newest volatile halogenated agents used for general anesthesia maintenance, is scarce. This study aimed to evaluate the genotoxic potential of desflurane in 15 patients without comorbidities, of both sexes, who underwent minor surgeries lasting at least 90 min. Patients enrolled in the study received desflurane anesthesia (6%); blood samples were collected before anesthesia induction (T0), 90 min after the beginning of anesthesia (T1), and on the day following surgery (T2). DNA damage was evaluated in lymphocytes using the alkaline comet assay. We found statistically significant increases in DNA damage in T2 samples compared to T0. The findings suggest that desflurane anesthesia induces DNA strand breaks/alkali-labile sites on the day after minimally invasive surgery in healthy patients.

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis.

PURPOSE: To verify the effects of different catecholamines on volemic expansion and on the autonomic nervous system in rabbits that were subjected to hemorrhage. METHODS: Twenty four rabbits subjected to hemorrhage (with a 25% loss of blood volume) and were randomly divided into four experimental groups: 1) HEMO Group underwent replacement with their own blood in an equal volume; 2) SS Group underwent replacement with saline solution (SS) in a volume that corresponded to three times the removed blood volume; 3) ISP Group underwent replacement with SS and isoprenaline; 4) FNL Group underwent replacement with SS and phenylephrine. Spectral Analysis of the heart rate and heart rate variability were performed from the recorded data. Hematocrit was measured throughout the experiment. RESULTS: Replacement with SS and an α- or ß-agonist did not produce differences in the intravascular retention compared to replacement with SS alone. An analysis of HRV showed that the FNL group maintained the LF/HF ratio better than ISP and SS. CONCLUSIONS: No difference in vascular retention when α- or ß- agonists were added to SS during post-hemorrhagic recovery. The animals in the FNL group maintained the integrity of the autonomic response within normal physiological standards during hemorrhagic stress.

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis

PURPOSE: To verify the effects of different catecholamines on volemic expansion and on the autonomic nervous system in rabbits that were subjected to hemorrhage. METHODS: Twenty four rabbits subjected to hemorrhage (with a 25% loss of blood volume) and were randomly divided into four experimental groups: 1) HEMO Group underwent replacement with their own blood in an equal volume; 2) SS Group underwent replacement with saline solution (SS) in a volume that corresponded to three times the removed blood volume; 3) ISP Group underwent replacement with SS and isoprenaline; 4) FNL Group underwent replacement with SS and phenylephrine. Spectral Analysis of the heart rate and heart rate variability were performed from the recorded data. Hematocrit was measured throughout the experiment. RESULTS: Replacement with SS and an α- or β-agonist did not produce differences in the intravascular retention compared to replacement with SS alone. An analysis of HRV showed that the FNL group maintained the LF/HF ratio better than ISP and SS. CONCLUSIONS: No difference in vascular retention when α- or β- agonists were added to SS during post-hemorrhagic recovery. The animals in the FNL group maintained the integrity of the autonomic response within normal physiological standards during hemorrhagic stress. .

Effects of propofol in lipid-based emulsion and in microemulsion on the incidence of endothelial lesion in rabbits.

PURPOSE: To compare the incidence of endothelial injury after single-dose or continuous propofol infusion in conventional lipid-based emulsion (LE) versus microemulsion (ME). METHODS: Forty-two rabbits (2.5-4.5 Kg) were randomly allocated into seven groups of six animals each: SHAM- surgical treatment alone; Bolus Control Group - 3 mL-intravenous (IV) bolus of saline; Continuous Infusion Control Group - 3 mL- IV bolus of saline followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Bolus LE Propofol Group - IV bolus of LE propofol (3 mg/kg); Bolus ME Propofol Group - IV ME propofol bolus (3 mg/kg); Continuous LE Propofol Group - IV LE propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Continuous ME Propofol Group - IV ME propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min. RESULTS: There were no statistically significant differences between the studied groups in blood pressure, in central venous pressure and in the biochemical profile. No significant differences were found in inflammatory mediators and in tissue analysis between the two emulsions. CONCLUSION: Microemulsion and lipid-based emulsion propofol had similar inflammatory, biochemical and microscopy profiles. Thus, microemulsion propofol can be used as an alternative to lipid-based emulsion propofol.

Effects of propofol in lipid-based emulsion and in microemulsion on the incidence of endothelial lesion in rabbits

PURPOSE: To compare the incidence of endothelial injury after single-dose or continuous propofol infusion in conventional lipid-based emulsion (LE) versus microemulsion (ME). METHODS: Forty-two rabbits (2.5-4.5 Kg) were randomly allocated into seven groups of six animals each: SHAM- surgical treatment alone; Bolus Control Group - 3 mL-intravenous (IV) bolus of saline; Continuous Infusion Control Group - 3 mL- IV bolus of saline followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Bolus LE Propofol Group - IV bolus of LE propofol (3 mg/kg); Bolus ME Propofol Group - IV ME propofol bolus (3 mg/kg); Continuous LE Propofol Group - IV LE propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min; Continuous ME Propofol Group - IV ME propofol bolus (3 mg/kg) followed by a continuous infusion of 0.2 ml/kg/min for 60 min. RESULTS: There were no statistically significant differences between the studied groups in blood pressure, in central venous pressure and in the biochemical profile. No significant differences were found in inflammatory mediators and in tissue analysis between the two emulsions. CONCLUSION: Microemulsion and lipid-based emulsion propofol had similar inflammatory, biochemical and microscopy profiles. Thus, microemulsion propofol can be used as an alternative to lipid-based emulsion propofol.

Effects of magnesium sulphate on the pharmacodynamics of rocuronium in patients aged 60 years and older: A randomised trial.

BACKGROUND: There is little information on the interaction between magnesium sulphate (MgSO4) and rocuronium in elderly patients. With a growing number of older patients who need surgical procedures, it is increasingly important to study this age group. OBJECTIVE: To evaluate the effects of MgSO4 administration on the pharmacodynamics of rocuronium in patients aged 60 years or older. DESIGN: A randomised controlled trial. SETTING: A tertiary care hospital. PATIENTS: Sixty-four patients, aged 60 years or older, American Society of Anesthesiologists (ASA) physical status classes I to III, scheduled for elective oncological head and neck surgery. Exclusion criteria were severe renal insufficiency (calculated creatinine clearance <30 ml min(-1)), preoperatorive serum magnesium concentration of more than 1.25 mmol l(-1) and patients receiving drugs known to affect neuromuscular function. INTERVENTIONS: Patients were randomly allocated to one of two groups: in the magnesium group, patients received MgSO4 30 mg kg(-1) intravenously, for 10 min, and then a continuous intravenous infusion at a rate of 1 g h(-1). The control group received the same volume of physiological saline. Neuromuscular function was evaluated continuously in both groups. MAIN OUTCOME MEASURES: Total recovery time was the primary outcome. Onset time, clinical duration, recovery index and recovery time were considered as secondary endpoints. Values are given as mean [SD]. RESULTS: Total recovery time from neuromuscular block (NMB) was 113 [36] min in the magnesium group and 101 [39] min in the control group. Clinical duration was 69 [23] min in the magnesium group and 59 [28] min in the control group. Recovery index was 19 [36] min in the magnesium group and 17 [6] min in the control group. Recovery time was 44 [22] min in the magnesium group and 42 [18] min in the control group. There were no statistically significant differences between the groups in any of the recovery indices. In the magnesium group, the mean onset time was 144 [58] s, significantly shorter than the onset time in the group that received physiological saline, which was 187 [90] s (P = 0.03). Group variances were compared using an F test: onset time varied significantly less in the magnesium group (P = 0.02). CONCLUSION: In oncology patients of 60 or more years of age, preadministration of MgSO4, with the doses used in this study, significantly reduced the onset time of NMB induced by rocuronium. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01804205.

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(-1) or 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.

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.

The effects of 6% hydroxyethyl starch-hypertonic saline in resuscitation of dogs with hemorrhagic shock.

BACKGROUND: Hemodynamic and global oxygen transport variables have failed to reflect splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock. Volemic expansion after fluid resuscitation is essential to improve global and regional oxygen in hemorrhagic shock. We hypothesized that, in contrast to conventional plasma expanders, the smaller volemic expansion from 7.5 NaCl/6% hydroxyethyl starch (HHES) solution administration in hemorrhagic shock may provide lesser systemic oxygen delivery and gastric perfusion. We used hemorrhaged dogs to compare intravascular volume expansion and the early systemic oxygenation and gastric perfusion effects of fixed fluid bolus administration, which are usually used in clinical situations with severe hemorrhage, of HHES, lactated Ringer (LR), and 6% hydroxyethyl starch (HES) solutions. METHODS: Thirty dogs were bled (30 mL · kg(-1)) to hold mean arterial blood pressure at 40 to 50 mm Hg over 45 minutes and were resuscitated in 3 groups: LR (n = 10) at 3:1 ratio to shed blood; HES (mean molecular weight 130 kDa, degree of substitution 0.4) (n = 10) at 1:1 to shed blood; and HHES (n = 10), 4 mL · kg(-1). Intravascular volume expansion (Evans blue and hemoglobin dilution), hemodynamic, systemic oxygenation, venous-to-arterial CO(2) gradient (Pv-aCO(2)), and gastric intramucosal-arterial PCO(2) gradient (PCO(2) gap) variables were measured at baseline, after 45 minutes of hemorrhage, and 5, 45, and 90 minutes after fluid resuscitation. RESULTS: HHES increased blood volume because of the high volume expansion efficiency, but intravascular volume expansion with this solution was the smallest of the solutions (P < 0.05). All 3 solutions induced a similar hemodynamic performance but HHES showed lower mixed venous PO(2) and higher systemic oxygenation extraction, Pv-aCO(2), and PCO(2) gap than LR and HES (P < 0.05). CONCLUSIONS: In dogs submitted to pressure-guided hemorrhagic shock and fixed-volume resuscitation, the smaller intravascular volume expansion from HHES solutions provides worse recovery of systemic oxygenation and gastric perfusion compared with LR and HES solutions despite its high volume expansion efficiency, which was limited by low infused volume.