A. L. Ortiz

The effect of high doses of remifentanil in brain near- infrared spectroscopy and in electroencephalographic parameters in pigs

OBJECTIVE To study the effects of a high remifentanil bolus dose on pigs electroencephalographic indices and on brain regional and global oxygenation. STUDY DESIGN Prospective experimental study. ANIMALS Twelve healthy Large-White male pigs, age 3 months and weight 26.2 ± 3.6 kg. METHODS Anaesthesia was induced with intravenous propofol 4 mg kg⁻¹, then maintained with constant rate infusions of propofol (15 mg kg⁻¹ hour⁻¹) and remifentanil (0.3 μg kg⁻¹ minute⁻¹). Following instrumentation, all pigs received a 5 μg kg⁻¹ remifentanil bolus. The responses of jugular venous oxygen saturation, cardiac output and cerebral oxygen saturation to the remifentanil bolus were studied. The Bispectral index, spectral edge frequency 95%, total power, approximate entropy and permutation entropy were also studied. Repeated measures anova and Pearson correlation were used to analyze the effect of remifentanil bolus on these variables until 5 minutes after the bolus. RESULTS Cardiac output and cerebral oxygen saturation decreased significantly after the remifentanil bolus from 4.6 ± 0.9 to 3.8 ± 1.0 L minute⁻¹ and from 65 ± 6 to 62 ± 1% (p < 0.05), respectively. No significant changes were observed in the jugular venous oxygen saturation (p > 0.05) nor in any of the electroencephalogram derived indices (p > 0.05). Correlation analysis revealed strong positive significant correlations between cerebral oxygen saturation and cardiac output (r = 0.82, p < 0.001) and between cerebral oxygen saturation and approximate entropy (r = 0.65, p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE The effect caused by the remifentanil bolus on the brain oxygenation seems to be better reflected by the cerebral oxygen saturation than the jugular venous oxygen saturation. The effect of remifentanil on the electroencephalogram may not be reflected in indices derived from the electroencephalogram, but the potential of the approximate entropy in reflecting changes caused by opioids on the electroencephalogram should be further investigated.

Effects of acute bleeding followed by hydroxyethyl starch 130/0.4 or a crystalloid on propofol concentrations, cerebral oxygenation, and electroencephalographic and haemodynamic variables in pigs.

Bleeding changes the haemodynamics, compromising organ perfusion. In this study, the effects of bleeding followed by replacement with hydroxyethyl starch 130/0.4 (HES) or lactated Ringers (LR) on cerebral oxygenation and electroencephalogram-derived parameters were investigated. Twelve young pigs under propofol-remifentanil anaesthesia were bled 30 mL/kg and, after a 20-minute waiting period, volume replacement was performed with HES (GHES; N = 6) or LR (GRL; N = 6). Bleeding caused a decrease of more than 50% in mean arterial pressure (P < 0.01) and a decrease in cerebral oximetry (P = 0.039), bispectral index, and electroencephalogram total power (P = 0.04 and P < 0.01, resp.), while propofol plasma concentrations increased (P < 0.01). Both solutions restored the haemodynamics and cerebral oxygenation similarly and were accompanied by an increase in electroencephalogram total power. No differences between groups were found. However, one hour after the end of the volume replacement, the cardiac output (P = 0.03) and the cerebral oxygenation (P = 0.008) decreased in the GLR and were significantly lower than in GHES (P = 0.02). Volume replacement with HES 130/0.4 was capable of maintaining the cardiac output and cerebral oxygenation during a longer period than LR and caused a decrease in the propofol plasma concentrations.

Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs

This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringers lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n = 11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related.

The influence of Ringer's lactate or HES 130/0.4 administration on the integrity of the small intestinal mucosa in a pig hemorrhagic shock model under general anesthesia

Objective To determine the effect of fluid resuscitation with 2 different physiological solutions, Ringers lactate (RL) and hydroxyethyl starch (HES) 130/0.4, on histological lesions of the small intestinal mucosa in anesthetized pigs subjected to severe acute bleeding. Design Prospective experimental study. Setting University teaching hospital. Animals Twenty-eight healthy Large White pigs, 3 months of age. Interventions Pigs were subjected to severe acute bleeding (30 mL/kg) under total intravenous anesthesia with propofol and remifentanil. Pigs were randomly allocated to 3 groups: Group 1 (n = 11) received RL solution (25 mL/kg) after bleeding; Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg) after bleeding; and Group 3 (n = 6) volume replacement nor induced bleeding. Pigs were euthanized and the small intestine was harvested for histopathological analysis. Measurements and Main Results The small intestine was histologically evaluated and the presence of the following lesions were characterized: edema, congestion, hyperemia, hemorrhage, inflammatory infiltration, cellular degeneration, necrosis, and epithelial detachment. Mucosal loss percentage (%ML) and crypt:interstitium ratio (C:I) were also assessed. In the duodenum, jejunum, and ileum, and the entire small intestine, the %ML was significantly higher in Group 1, than in Groups 2 and 3. Hyperemia in the small intestine was significantly higher in pigs resuscitated with HES 130/0.4 compared to pigs resuscitated with RL. Conclusions and Clinical Relevance In a setting of controlled hemorrhage, resuscitation with HES 130/0.4 was associated with a lower percentage of mucosal loss on the small intestine, compared with resuscitation with RL solution. Our study also suggests that the duodenum may be more sensitive to hypovolemia induced by severe hemorrhage.OBJECTIVE To determine the effect of fluid resuscitation with 2 different physiological solutions, Ringers lactate (RL) and hydroxyethyl starch (HES) 130/0.4, on histological lesions of the small intestinal mucosa in anesthetized pigs subjected to severe acute bleeding. DESIGN Prospective experimental study. SETTING University teaching hospital. ANIMALS Twenty-eight healthy Large White pigs, 3 months of age. INTERVENTIONS Pigs were subjected to severe acute bleeding (30 mL/kg) under total intravenous anesthesia with propofol and remifentanil. Pigs were randomly allocated to 3 groups: Group 1 (n = 11) received RL solution (25 mL/kg) after bleeding; Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg) after bleeding; and Group 3 (n = 6) volume replacement nor induced bleeding. Pigs were euthanized and the small intestine was harvested for histopathological analysis. MEASUREMENTS AND MAIN RESULTS The small intestine was histologically evaluated and the presence of the following lesions were characterized: edema, congestion, hyperemia, hemorrhage, inflammatory infiltration, cellular degeneration, necrosis, and epithelial detachment. Mucosal loss percentage (%ML) and crypt:interstitium ratio (C:I) were also assessed. In the duodenum, jejunum, and ileum, and the entire small intestine, the %ML was significantly higher in Group 1, than in Groups 2 and 3. Hyperemia in the small intestine was significantly higher in pigs resuscitated with HES 130/0.4 compared to pigs resuscitated with RL. CONCLUSIONS AND CLINICAL RELEVANCE In a setting of controlled hemorrhage, resuscitation with HES 130/0.4 was associated with a lower percentage of mucosal loss on the small intestine, compared with resuscitation with RL solution. Our study also suggests that the duodenum may be more sensitive to hypovolemia induced by severe hemorrhage.

Renal Apoptosis Signalling in a Pig Haemorrhagic Model after Volume Replacement with HES 130/0.4 or Ringer's Solution

RENAL APOPTOSIS SIGNALLING IN A PIG HAEMORRHAGIC MODEL AFTER VOLUME REPLACEMENT WITH HES 130/0.4 OR RINGER’S SOLUTION R. Cruz*,y,z, H. Vala*,y, A. Machado*,y, C. Venâncio z, J.R. Mesquita*,y, A. Silva x, A.L. Ortiz{ and D. Ferreira *ESAV, IPV, yCI&DETS, IPV, zUTAD, xREQUIMTE, Portugal, {Le on University, Spain and CICV/FMV-ULHT, Portugal Introduction: TUNEL labelling is one of the most frequently used methods to detect apoptosis in renal tissues. The aim of this study was to evaluate kidney damage after acute haemorrhage and volume replacement with a colloid or a crystalloid, in a pig model. Materials and Methods: In accord with animal welfare regulations, three groups (n 5 6) of large white pigs were enrolled in the study. All groups underwent total intravenous anaesthesia and were subjected to acute haemorrhage and volume replacement with Ringer’s lactate or HES 130/0.4, 20 min after haemorrhage. Control pigs did not undergo bleeding and volume replacement. Pigs were killed and renal samples were taken and analyzed by the TUNEL method. ANOVA was used to compare data between groups. Results: An intense positive signal in tubular epithelial cells was observed in all samples. The level of signalling per mm was significantly lower in the group receiving Ringer’s lactate (11.94) compared with the group receiving HES130/0.4 (67.94) and controls (146.34) (P !0.05). Conclusions: Signalling levels were lower in pigs subjected to fluid replacement with Ringer’s lactate when compared with the control group. Ringer’s lactate might promote better renal perfusion in the presence of severe hypoperfusion. HISTOLOGICAL EVALUATION OF THE SPLEEN AFTER ACUTE BLEEDING FOLLOWED BY VOLUME REPLACEMENT WITH TWO DIFFERENT PHYSIOLOGICAL SOLUTIONS M. Cabral*, A. Ortiz y, C. Venâncio z, J. Mesquita x, C. N obrega x, A. Silva{, H. Vala x and D. Ferreira *Agrarian Superior School, IPV Viseu, Portugal, yUniversity of Le on, Spain, zIBMC-Porto, xCEETS-IPV Viseu, {REQUIMTE, Porto and CICVULHT, Lisboa, Portugal Introduction: The spleen is important for many haemopoietic and immunological functions, particularly in haemodynamic compensation during haemorrhagic shock, with a crucial role in restoring blood volume in situations of acute haemorrhage. The administration of physiological solutions is of great importance for the correction of circulating volume, avoiding complications due to hypovolaemia. The aim of this study was to evaluate histopathological changes in the spleen associated with volume replacement using two different physiological solutions (hydroxyethyl starch [HES] 130/0.4 and Ringer’s lactate), after acute controlled bleeding, in a pig model. Materials andMethods: Thirty-one large white pigs underwent total intravenous anaesthesia with propofol and remifentanil. A total of 25ml/kg of blood was removed passively over 20 min. Intravascular volume was replaced using Ringer’s lactate at 25 ml/kg (group 1, n 5 13) or HES130/0.4 at 20 ml/kg (group 2, n 5 11). Spleen samples were processed for routine histopathological evaluation. Results: Significant differences were found in lymphoid follicular hyperplasia between the control group and group 1, and between group 1 and group 2, with increased follicular hyperplasia in group 1. Conclusions: Volume replacement with HES130/0.4 may reduce follicular lymphoid hyperplasia when compared with volume replacement with Ringer’s lactate after acute bleeding.