N-acetylcysteine (NAC) protects against acute kidney injury (AKI) following prolonged pneumoperitoneum in the rat.

BACKGROUND: Acute kidney injury (AKI) following prolonged laparoscopy is a documented phenomenon. Carbon dioxide pneumoperitoneum induces oxidative stress. Previous experimental studies have shown that the antioxidant, N-acetylcysteine, protects the rat from AKI following ischemia-reperfusion. The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on rat renal function after prolonged pneumoperitoneum. METHODS: Normal rats treated or not with NAC were submitted to abdominal CO(2) insufflation of 10 mmHg, at short and long periods of time of 1 and 3 h, respectively, and evaluated at 24, 72 h, and 1 wk after deinsufflation. Glomerular filtration rate (GFR) was measured by inulin clearance and oxidative stress was evaluated by serum thiobarbituric acid reactive substances (TBARS) RESULTS: No significant alterations in GFR were observed in normal animals submitted to the pneumoperitoneum of 1 h and evaluated after 24 h desufflation. With 3 h of pneumoperitoneum, a significant and progressive decrease in GFR occurred 24 and 72 h after desufflation with an increase in serum TBARS. GFR returned to normal levels a week later. In the NAC-treated rats, a complete protection against GFR drops was observed 24 and 72 h following 3 h of pneumoperitoneum associated with a decrease in TBARS. CONCLUSION: These results suggest that NAC protects against acute kidney injury following prolonged pneumoperitoneum. These findings have significant clinical implications.

Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial.

INTRODUCTION: Patients undergoing mechanical ventilation (MV) are frequently administered prolonged and/or high doses of opioids which when removed can cause a withdrawal syndrome and difficulty in weaning from MV. We tested the hypothesis that the introduction of enteral methadone during weaning from sedation and analgesia in critically ill adult patients on MV would decrease the weaning time from MV. METHODS: A double-blind randomized controlled trial was conducted in the adult intensive care units (ICUs) of four general hospitals in Brazil. The 75 patients, who met the criteria for weaning from MV and had been using fentanyl for more than five consecutive days, were randomized to the methadone (MG) or control group (CG). Within the first 24 hours after study enrollment, both groups received 80% of the original dose of fentanyl, the MG received enteral methadone and the CG received an enteral placebo. After the first 24 hours, the MG received an intravenous (IV) saline solution (placebo), while the CG received IV fentanyl. For both groups, the IV solution was reduced by 20% every 24 hours. The groups were compared by evaluating the MV weaning time and the duration of MV, as well as the ICU stay and the hospital stay. RESULTS: Of the 75 patients randomized, seven were excluded and 68 were analyzed: 37 from the MG and 31 from the CG. There was a higher probability of early extubation in the MG, but the difference was not significant (hazard ratio: 1.52 (95% confidence interval (CI) 0.87 to 2.64; P = 0.11). The probability of successful weaning by the fifth day was significantly higher in the MG (hazard ratio: 2.64 (95% CI: 1.22 to 5.69; P < 0.02). Among the 54 patients who were successfully weaned (29 from the MG and 25 from the CG), the MV weaning time was significantly lower in the MG (hazard ratio: 2.06; 95% CI 1.17 to 3.63; P < 0.004). CONCLUSIONS: The introduction of enteral methadone during weaning from sedation and analgesia in mechanically ventilated patients resulted in a decrease in the weaning time from MV.

The effects of low and high tidal volume and pentoxifylline on intestinal blood flow and leukocyte-endothelial interactions in mechanically ventilated rats.

BACKGROUND: The combination of high PEEP and low tidal volume (V(T)) decreases some risks of mechanical ventilation, including pulmonary overdistention, damage due to cyclic opening and closing of the alveoli, and inflammatory responses that can lead to multiple-organ dysfunction. We hypothesized that high V(T) and high PEEP induce mesenteric microcirculatory disturbances and that those disturbances would be attenuated by pentoxifylline, which is anti-inflammatory. METHODS: We anesthetized (isoflurane 1.5%), tracheostomized, and mechanically ventilated 57 male Wistar rats with PEEP of 10 cm H(2)O and F(IO(2)) of 0.21 for 2 hours. One group received low V(T) (7 mL/kg), another group received high V(T) (10 mL/kg), and a third group received high V(T) plus pentoxifylline (25 mg/kg). We measured mean arterial pressure, respiratory mechanics, mesenteric blood flow, and leukocyte-endothelial interactions. RESULTS: The mean arterial pressure was similar among the groups at baseline (108 mm Hg [IQR 94-118 mm Hg]) and after 2 hours of mechanical ventilation (104 mm Hg [IQR 90-114 mm Hg]). Mesenteric blood flow was also similar between the groups: low V(T) 15.1 mL/min (IQR 12.4-17.7 mL/min), high V(T) 11.3 mL/min (IQR 8.6-13.8 mL/min), high-V(T)/pentoxifylline 12.4 mL/min (10.8-13.7 mL/min). Peak airway pressure after 2 hours was lower (P = .03) in the low-V(T) group (10.4 cm H(2)O [IQR 10.2-10.4 cm H(2)O]) than in the high-V(T) group (12.6 cm H(2)O [10.2-14.9 cm H(2)O]) or the high-V(T)/pentoxifylline group (12.8 cm H(2)O [10.7-16.0 cm H(2)O]). There were fewer adherent leukocytes (P = .005) and fewer migrated leukocytes (P = .002) in the low-V(T) group (5 cells/100 µm length [IQR 4-7 cells/100 µm length] and 1 cell/5,000 µm(2) [IQR 1-2 cells/5,000 µm(2)], respectively) and the high-V(T)/pentoxifylline group (5 cells/100 µm length [IQR 3-10 cells/100 µm length] and 1 cell/5,000 µm(2) [IQR 1-3 cells/5,000 µm(2)], respectively) than in the high-V(T) group (14 cells/100 µm length [IQR 11-16 cells/100 µm length] and 9 cells/5,000 µm(2) [IQR 8-12 cells/5,000 µm(2)], respectively). CONCLUSIONS: Low V(T) with high PEEP was lung-protective, and early pentoxifylline reduced the inflammatory response to high V(T) with high PEEP (and presumed lung overdistention) during mechanical ventilation.

Endoscopy Ultra- Sonography -guided biliary drainage in the surgical -endoscopy era.

BACKGROUND: US-guided hepatico - gastrostomy, choledocho-duodenostomy and choledocho-antrostomy are advanced procedures on biliary and pancreatic endoscopy and together make up the echo-guided biliary drainage. Hepatico - gastrostomy is indicated in cases of hiliar obstruction, while the procedure of choice is choledocho - duodenostomy in distal lesions. Both procedures must be done only after unsuccessful ERCP. AIMS: To clarify to the readers about indication of these procedures, they must be made under a multidisciplinary view while sharing information with the patient or legal guardian. METHODS: All series cases report and selected cohort studies were selected according to the DDTS system in which key words were EUS biliary drainage, choledocho-duodenostomy, hepatico-gastrostomy, EUS, palliation and pancreatic biliary advanced cancer. RESULTS: Separately it was stated definition on the EUS biliary drainage procedures and it includes the techniques details and critical analysis. CONCLUSION: Hepatico- gastrostomy and Choledocho- duodenostomy are feasible when performed by endoscopists with expertise in bilio pancreatic endoscopy and advanced echo-endoscopy and should be performed currently under rigorous protocol in educational institutions.

Fluid resuscitation with isotonic or hypertonic saline solution avoids intraneural calcium influx after traumatic brain injury associated with hemorrhagic shock.

BACKGROUND: Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. METHODS: Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion ("clinical penumbra") and from the corresponding contralateral side ("lesion's mirror") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. RESULTS: Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. CONCLUSION: Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Fluid replacement with hypertonic or isotonic solutions guided by mixed venous oxygen saturation in experimental hypodynamic sepsis.

BACKGROUND: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoncotic solution would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. METHODS: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. RESULTS: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. CONCLUSIONS: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

In vivo observation of mesenteric leukocyte-endothelial interactions after cecal ligation/puncture and surgical sepsis source control.

PURPOSE: Cecal ligation and puncture (CLP) has been used as a useful model for the induction of polymicrobial sepsis. Necrotic tissue resection and peritoneal lavage (REL) are the surgical procedures for controlling perforated appendicitis. The aim of this study was to evaluate leukocyte-endothelial interactions in the rat mesentery in vivo after CLP and REL. METHODS: Thirty-seven male Wistar rats (250-300 g) underwent laparotomy and were randomly assigned to the following groups: 1) SHAM; 2) CLP: animals submitted to CLP, 3) CLP+REL: animals submitted to CLP and REL. Mesenteric leukocyte-endothelial interactions were studied by intravital microscopy assessed once in each animal (3-5 postcapillary venules, 15-25 microm diameter) 24 hours after intervention. Follow-up was performed in all animals; this included analysis of glycemia, lactate, hematocrit, white blood cell count as well as a functional score that was the sum of scoring on the following parameters: alertness, mobility, piloerection, diarrhea, encrusted eyes, and dirty nose and tail. RESULTS: None of the animals showed significant changes in body weight (265 +/- 20 g) or in hematocrit levels (46% +/- 2%) during the experimental protocol. Compared to SHAM animals, CLP animals showed an increased number of rolling (2x), adherent, and migrating leukocytes (7x) in the mesenteric microcirculation, an increase in blood glucose (136 +/- 8 mg/dL), lactate (3.58 +/- 0.94 mmol/L), white cell count (23,570 +/- 4,991 cells/mm(3)) and functional alterations (score 11 +/- 1), characterized by impaired alertness and mobility, and presence of piloerection, diarrhea, encrusted eyes, and dirty nose and tail. The REL procedure normalized the number of rolling, adherent, and migrated leukocytes in the mesentery; glycemia; lactate; and white blood cell count. The REL procedure also improved the functional score (7 +/- 1). CONCLUSION: Local and systemic inflammation was induced by CLP, while REL completely overcame the inflammatory process.

Variation in amplitude of central venous pressure curve induced by respiration is a useful tool to reveal fluid responsiveness in postcardiac surgery patients.

We tested the hypothesis that the dynamic evaluation of central venous pressure (CVP) amplitude could be a reliable predictor of fluid responsiveness in patients under mechanical ventilation, similar to the variation of arterial pulse pressure (DeltaPp). Thirty postcardiac surgery patients, under mechanical ventilation, were evaluated. The percentual difference between inspiratory (Ppins) and expiratory pulse pressure (Ppins) was so calculated: DeltaPp (%) = 100 x (Ppins - Ppexp)/[(Ppins + Ppexp)/2]. The respiratory variation of CVP curves amplitude were calculated by determining the percentual difference between inspiratory (CVPpins) and expiratory (CVPpexp) variation using vena cava "pressure" collapsibility index according the following formula: Cvci (%) = [(CVPpexp - CVPpins)/CVPpexp] x 100. There was a correlation between DeltaPp and Cvci (Pearson correlation coefficient, r = 0.45). Receiver operating characteristic curves showed that the Cvci value more than or equal to 5% predicted DeltaPp more than or equal to 13% with 91% specificity, 89% sensitivity, and AUC of 0.90. Therefore, Cvci presented a good agreement with DeltaPp (kappa = 0.76) to identify potential fluid responders (patients with DeltaPp > or =13%). In 9 potential fluid responders, both DeltaPp and Cvci significantly decreased from 18% +/- 8% to 8% +/- 6% (P < 0.004) and 23% +/- 15% to 7% +/- 6% (P < 0.004), respectively, after fluid replacement. Our findings suggest that vena cava "pressure" collapsibility index can be used as a marker of fluid responsiveness in postcardiac surgery patients under mechanical ventilation, such as arterial pulse pressure respiratory variation.

Measurement of S-100B for risk classification of victims sustaining minor head injury--first pilot study in Brazil.

BACKGROUND: Release of the neuronal protein S-100B into the circulation has been suggested as a specific indication of neuronal damage. The hypothesis that S-100B is a useful and cost-effective screening tool for the management of minor head injuries was tested. METHODS: Fifty consecutive patients sustaining isolated minor head injury were prospectively evaluated in the emergency room of a Brazilian hospital by routine cranial computed tomography scan. Venous blood samples (processed to serum) were assayed for S-100B using a newly developed immunoassay test kit. Twenty-one normal healthy individuals served as negative controls. Data are presented as median and 25 to 75 percentiles. RESULTS: Patients reached the emergency room an average of 45 minutes (range: 30-62 minutes) after minor head injury. Six of 50 patients (12%) showed relevant posttraumatic lesions in the initial cranial computed tomography scan and were counted as positive. The median systemic concentration of S-100B in those patients was 0.75 microg/L (range: 0.66-6.5 microg/L), which was significantly different (U-test, P < .05) from the median concentration of 0.26 microg/L (range: 0.12-0.65 microg/L), of patients without posttraumatic lesions as counted by the cranial computed tomography. A sensitivity of 100%, a specificity of 20%, a positive predictive value of 15%, and a negative predictive value of 100% was calculated for the detection of patients suffering from intracranial lesions. CONCLUSIONS: Protein S-100B had a very high sensitivity and negative predictive value and could have an important role in ruling out the need for cranial computed tomography scan after minor head injury. This appears to be of substantial clinical relevance, particularly in countries where trauma incidence is high and medical resources are limited, such as in Brazil.

[Initial evaluation of systemic and regional pCO2 gradients as markers of mesenteric hypoperfusion]. / Avaliação inicial dos gradientes sistêmicos e regionais da pCO2 como marcadores de hipoperfusão mesentérica.

BACKGROUND: Mesenteric ischemia is a life-threatening emergency with a mortality rates still ranging between 60% and 100%. AIM: To evaluate the systemic and regional pCO2 gradients changes induced by mesenteric ischemia-reperfusion injury. In addition, we sought to determine if other systemic marker of splanchnic hypoperfusion could detect the initial changes in intestinal mucosal microcirculation after superior mesenteric artery occlusion. METHODS: Seven pentobarbital anesthetized mongrel dogs (20.6 +/- 1.1 kg) were subjected to superior mesenteric artery occlusion for 45 minutes, and followed for an additional 120 minutes. Systemic hemodynamic was evaluated through a Swan-Ganz and arterial catheters, while gastrointestinal tract perfusion by superior mesenteric vein and jejunal serosal blood flows (ultrasonic flowprobe). Intestinal oxygen delivery, extraction and consumption (DO2intest, ERO2intest and VO2intest, respectively), intramucosal pH (gas tonometry), and mesenteric-arterial and mucosal arterial pCO2 gradients (D(vm-a)pCO2 and D(t-a)pCO2, respectively) were calculated. RESULTS: Superior mesenteric artery occlusion was not associated with significant changes on systemic hemodynamics parameters. A significant increase of D(vm-a)pCO2 (1.7 +/- 0.5 to 5.7 +/- 1.8 mm Hg) and D(t-a)pCO2 (8.2 +/- 4.8 to 48.7 +/- 4.6 mm Hg) were detected. During the reperfusion period a significant decrease on DO2intest (67.7 +/- 9.9 to 38.8 +/- 5.3 mL/min) and a compensatory increase on ERO2intest from 5.0 +/- 1.1% to 12.4 +/- 2.7% was observed. CONCLUSION: We conclude that gas tonometry can detect the mesenteric blood flow disturbances sooner than other analyzed parameters. Additionally, we demonstrated that changes on systemic or regional pCO2 gradients are not able to detect the magnitude of intestinal mucosal blood flow reduction after mesenteric ischemia-reperfusion injury.

Small volume hypertonic resuscitation of circulatory shock.

Small volume hypertonic resuscitation is a relatively new conceptual approach to shock therapy. It was originally based on the idea that a relatively large blood volume expansion could be obtained by administering a relatively small volume of fluid, taking advantage of osmosis. It was soon realized that the physiological vasodilator property of hypertonicity was a useful byproduct of small volume resuscitation in that it induced reperfusion of previously ischemic territories, even though such an effect encroached upon the malefic effects of the ischemia-reperfusion process. Subsequent research disclosed a number of previously unsuspected properties of hypertonic resuscitation, amongst them the correction of endothelial and red cell edema with significant consequences in terms of capillary blood flow. A whole set of actions of hypertonicity upon the immune system are being gradually uncovered, but the full implication of these observations with regard to the clinical scenario are still under study. Small volume resuscitation for shock is in current clinical use in some parts of the world, in spite of objections raised concerning its safety under conditions of uncontrolled bleeding. These objections stem mainly from experimental studies, but there are few signs that they may be of real clinical significance. This review attempts to cover the earlier and the more recent developments in this field.

Minimally invasive single-vessel coronary artery bypass with the internal thoracic artery and early postoperative angiography: midterm results of a prospective study in 120 consecutive patients.

BACKGROUND: This prospective study was undertaken to determine the role of the minimally invasive direct coronary artery bypass with early postoperative angiography and midterm follow-up in 120 consecutive patients with single-vessel coronary artery disease. METHODS: Minimal access (6 to 10 cm), without complete sternotomy and no cardiopulmonary bypass, was used. The lesions were located at the proximal left anterior descending coronary artery in 95% of the patients. Routine coronary angiography was performed before discharge. RESULTS: Postoperative angiography was performed in 104 (90.4%) of those 115 patients who had coronary revascularization concluded by the mini-access method. The internal thoracic artery patency rate was 98.1% (95.2% grade A). Two (1.7%) patients presented with perioperative myocardial infarction, which led to the single in-hospital death (0.8%). Of the remaining 119 patients, 113 (95.0%) were asymptomatic. The event-free probability was 94.9% and the actuarial survival was 98.3% with 42 months of follow-up. CONCLUSIONS: For selected patients with single-vessel coronary artery disease and no major myocardial dysfunction, minimally invasive direct coronary artery bypass is a safe operation and a less invasive alternative to conventional coronary artery bypass grafting.

Intraportal versus Systemic Pentoxifylline Infusion after Normothermic Liver Ischemia: Effects on Regional Blood Flow Redistribution and Hepatic Ischemia-Reperfusion Injury.

Pentoxifylline (PTX) has been shown to have beneficial effects on microcirculatory blood flow. In this study we evaluate the potential hemodynamic and metabolic benefits of PTX during hepatic ischemia. We also test the hypothesis that portal PTX infusion can minimize the I/R injury when compared to systemic infusion. Methods. Twenty-four dogs (18.1 ± 0.7 kg) were subjected to portal triad occlusion (PTO) for 45 min. The animals were assigned to 3 groups: CT (control, PTO, n = 8), PTX-syst (PTO + 25 mg/Kg of PTX IV, n = 8), and PTX-pv (PTO + 25 mg/Kg of PTX in the portal vein, n = 8). Animals were followed for 120 min. Systemic hemodynamics, gastrointestinal tract perfusion, oxygen-derived variables, and liver enzymes were evaluated throughout the experiment. Results. Animals treated with PTX presented significantly higher CO in the first hour after reperfusion, when compared to the CT (~3.7 vs. 2.1 L/min, P < 0.05). Alanine aminotransferase (ALT) was similar in the PTX groups two hours after reperfusion but significantly higher in the CT (227 vs. ~64 U/L, P < 0.05). Conclusion. PTX infusion was associated with hemodynamic benefits and was able to minimize liver injury during normothermic hepatic I/R. However, local PTX infusion was not associated with any significant advantage over systemic route.

Pulse oximetry wave variation as a noninvasive tool to assess volume status in cardiac surgery.

OBJECTIVE: To compare variations of plethysmographic wave amplitude (DeltaPpleth) and to determine the percent difference between inspiratory and expiratory pulse pressure (DeltaPp) cutoff values for volume responsiveness in a homogenous population of postoperative cardiac surgery patients. INTRODUCTION: Intra-thoracic pressure variations interfere with stroke volume variation. Pulse pressure variations through arterial lines during mechanical ventilation have been recommended for the estimation of fluid responsiveness. Pulse oximetry may offer a non-invasive plethysmographic method to evaluate pulse pressure; this may be useful for guiding fluid replacement. METHODS: Controlled, prospective study in cardiac surgery patients under controlled ventilation. Simultaneous digital recordings of arterial pressure and plethysmographic waves were performed. DeltaPp, systolic pressure (DeltaPs), DPpleth, and systolic component (DeltaSpleth) were calculated. A DPp > or = 13% identified fluid-responsive patients. Volume expansion was performed in responsive subjects. Systolic and amplitude components of pressure and plethysmographic waves were compared. RESULTS: In 50 measurements from 43 patients, DeltaPp was correlated with (Ppleth (r=0.90, p<0.001), (Ps (r=0.90, p<0.001), and (Spleth (r=0.73, p<0.001). An aArea under ROC curve (AUC) identified the fluid responsiveness thresholds: (Ppleth of 11% (AUC = 0.95+/-0.04), (Ps of 8% (AUC=0.93+/-0.05), and (Spleth of 32% (AUC=0.82+/-0.07). A (Ppleth value > or = 11% predicted (Pp > or = 13% with 100% specificity and 91% sensitivity. Volume expansion, performed in 20 patients, changed (Pp, (Ppleth, (Ps and (Spleth significantly (p<0.008). CONCLUSIONS: DeltaPpleth is well correlated with DPp and constitutes a simple and non-invasive method for assessing fluid responsiveness in patients following cardiac surgery.

Experimental models of sepsis and their clinical relevance.

Sepsis remains a major cause of morbidity and mortality mainly because of sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have failed to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the potentials and limitations of various animal models of sepsis are discussed to clarify to which extent these findings are relevant to human sepsis. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models using different animal species including rats, mice, rabbits, dogs, pigs, sheep, and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be replaced by other methods. New therapeutic agents should be studied in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

Volume replacement with lactated Ringer's or 3% hypertonic saline solution during combined experimental hemorrhagic shock and traumatic brain injury.

BACKGROUND: The devastating effects of hypotension on head-trauma-related mortality are well known. This study evaluates the systemic and cerebral hemodynamic responses to volume replacement with 3% hypertonic saline (HSS) or lactated Ringer's solution (LR), during the acute phase of hemorrhagic shock (HS) associated with traumatic brain injury (TBI). METHODS: Fifteen dogs were assigned to one of three groups (n = 5, each) according to the volume replacement protocol, infused after TBI (brain fluid percussion, 4 atm) and epidural balloon to an intracranial pressure (ICP) higher than 20 mm Hg and HS, induced by blood removal to a mean arterial pressure (MAP) of 40 mm Hg in 5 minutes: Group HS+TBI+HSS (8 mL/kg of 3% HSS), HS+TBI+LR (16 mL/kg LR), and Group HS+TBI (controls, no fluids). We simulated treatment during prehospital and early hospital admission. Groups HS+ TBI and HS+TBI+LR received shed blood infusion to a target hematocrit of 30%. Measurements included shed blood volume, fluid volume infused to restore MAP, MAP, cardiac output, cerebral perfusion pressure, cerebral and systemic lactate, and oxygen extraction ratios. RESULTS: Fluid replacement with HSS 3% or LR promoted major hemodynamic benefits over control animals without luids. Cerebral perfusion pressure was higher than controls and similar between treated groups; however, HSS 3% infusion was associated with lower ICP during the "early hospital phase" and a higher serum sodium and osmolarity. CONCLUSION: In the event of severe head trauma and hemorrhagic shock, the use of HSS 3% and larger volumes of LR promote similar systemic and cerebral hemodynamic benefits. However, a lower ICP was observed after HSS 3% than after LR.

Oxygen consumption, pCO2 gradients and regional blood flow distribution in an alternative model of intestinal autotransplantation.

BACKGROUND: Postoperative complications after intestinal transplantation can be attributed to hypothermic storage and reperfusion injury. Our objective was to evaluate, in an alternative model of intestinal autotransplantation, the initial effects of isolated intestinal hypothermic perfusion (at 4 degrees C, IHP) on mucosal and serosal blood flow distribution and correlate these findings with other systemic and regional markers of mesenteric ischemia. In addition, we sought to obtain evidence that intestinal pCO2 measurement can be a useful method for monitoring graft perfusion and early histological changes after small bowel transplantation. MATERIALS AND METHODS: Eight dogs (23.3+/-1.1 kg) were submitted to a in situ IHP for 30 min, followed by a 180-min reperfusion period. Cardiac output, mesenteric vein, and intestinal serosal blood flows (SMVBF and SBF, ultrasonic flowprobe); intestinal mucosal-arterial pCO2 gradient (Dt-apCO2, tonometry); and O2-derived variables were evaluated. RESULTS: IHP induced a reduction in SMVBF (579+/-53 to 321+/-10 mL/min) and SBF, (44.7+/-3.2 to 29.1+/-5.3 mL/min), and an increase in Dt-apCO2 (2+/-2.8 to 20.5+/-4.5 mm Hg). No alterations on systemic metabolic or O2-derived variables were observed. The increase of the Dt-apCO2 correlated with the grade of mucosal injury. CONCLUSION: IHP induces a proportional reduction on blood flow in all layers of the intestine, and none of the systemic markers of splanchnic ischemia predict the intestinal blood flow disturbances during the early phase of intestinal transplantation. In addition, intestinal pCO2 measurement seems to be a useful way for monitoring graft perfusion and histological changes after hypothermic ischemia and reperfusion.

Pulse oximetry wave variation as a noninvasive tool to assess volume status in cardiac surgery

OBJECTIVE: To compare variations of plethysmographic wave amplitude (ÃPpleth) and to determine the percent difference between inspiratory and expiratory pulse pressure (ÃPp) cutoff values for volume responsiveness in a homogenous population of postoperative cardiac surgery patients. INTRODUCTION: Intra-thoracic pressure variations interfere with stroke volume variation. Pulse pressure variations through arterial lines during mechanical ventilation have been recommended for the estimation of fluid responsiveness. Pulse oximetry may offer a non-invasive plethysmographic method to evaluate pulse pressure; this may be useful for guiding fluid replacement. METHODS: Controlled, prospective study in cardiac surgery patients under controlled ventilation. Simultaneous digital recordings of arterial pressure and plethysmographic waves were performed. ÃPp, systolic pressure (ÃPs), DPpleth, and systolic component (ÃSpleth) were calculated. A DPp > 13 percent identified fluid-responsive patients. Volume expansion was performed in responsive subjects. Systolic and amplitude components of pressure and plethysmographic waves were compared. RESULTS: In 50 measurements from 43 patients, ÃPp was correlated with (Ppleth (r=0.90, p<0.001), (Ps (r=0.90, p<0.001), and (Spleth (r=0.73, p<0.001). An aArea under ROC curve (AUC) identified the fluid responsiveness thresholds: (Ppleth of 11 percent (AUC = 0.95±0.04), (Ps of 8 percent (AUC=0.93±0.05), and (Spleth of 32 percent (AUC=0.82±0.07). A (Ppleth value > 11 percent predicted (Pp > 13 percent with 100 percent specificity and 91 percent sensitivity. Volume expansion, performed in 20 patients, changed (Pp, (Ppleth, (Ps and (Spleth significantly (p<0.008). CONCLUSIONS: ÃPpleth is well correlated with DPp and constitutes a simple and non-invasive method for assessing fluid responsiveness in patients following cardiac surgery.

Emergency room retrograde transbrachial arteriography for the management of axillosubclavian vascular injuries.

BACKGROUND: Our purpose was to determine the accuracy of single-injection, retrograde transbrachial arteriography (RTBA), performed in the emergency room, for suspected axillosubclavian injuries. METHODS: Thirty-three patients were prospectively assigned for RTBA. Clinical indications for RTBA included high-risk mechanism of injury, decreased (n = 19) or absent (n = 5) brachial pulse, neurologic deficits (n = 11), external or intrathoracic bleeding (n = 4), and bruit (n = 2). Brachial artery was cannulated with an 18-gauge catheter. A sphygmomanometer cuff was placed at the forearm and inflated to 250 mm Hg. Twenty milliliters of nonionic contrast media was injected countercurrent and a single anteroposterior chest radiograph was obtained. Small intimal flaps were followed by serial ultrasound. Surgical findings were used to establish RTBA accuracy. RESULTS: RTBA was successfully performed in all cases. Arterial lesions were detected in 28 (84.8%) patients, including thrombosis (n = 8), arteriovenous fistula (n = 8), and false aneurysm (n = 7) as the most frequent lesions. A sensitivity of 96.5%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 80% were observed with RTBA. CONCLUSION: We conclude that RTBA is a safe and accurate technique to be used in the emergency room for the rapid detection of axillosubclavian arterial injuries.

Blood loss after fluid resuscitation with isotonic or hypertonic saline for the initial treatment of uncontrolled hemorrhage induced by spleen rupture.

BACKGROUND: It has been suggested that fluid resuscitation for the prehospital management of hypotensive trauma victims increases bleeding. In a model of uncontrolled hemorrhage induced by complete splenic laceration with a hilar vascular injury, we hypothesized that small-volume hypertonic saline or large-volume lactated Ringer's solution may provide sustained hemodynamic benefits despite promoting increases in intra-abdominal bleeding. METHODS: Forty anesthetized, spontaneously breathing dogs (18 +/- 1 kg) underwent laparotomy. A suture line was placed around the spleen to produce a splenic rupture with hilar vascular injury by pulling the exteriorized lines after incision closure. Intra-abdominal blood loss was measured directly, immediately after the animal was killed. Dogs were randomly assigned to four groups (n = 10 per group): Untreated controls were killed 20 (CT20) or 40 (CT40) minutes after splenic rupture to measure blood loss directly. Treatment groups received (20 minutes after spleen rupture) lactated Ringer's (LR), 33 mL/kg over 15 minutes, or 7.5% NaCl/6% dextran 70 (HSD), 4 mL/kg over 4 minutes. Blood loss was measured 40 minutes after spleen rupture. RESULTS: Mean arterial pressure dropped from an average value of 103 +/- 3 mm Hg to 67 +/- 5 mm Hg during the first 20 minutes and was partially restored afterward in all groups, with no significant differences between them. No resuscitation was associated with low cardiac output, whereas HSD restored and LR overshot baseline cardiac output. Intra-abdominal blood loss was 30 +/- 4, 38 +/- 4, 43 +/- 5, and 42 +/- 5 mL/kg for groups CT20, CT40, HSD, and LR, respectively, with no statistical significance between groups. CONCLUSION: No-fluid resuscitation in uncontrolled hemorrhage from splenic rupture resulted in a low-flow state, whereas resuscitation with small volumes of HSD or large volumes of LR produced hemodynamic benefits without significant increases in bleeding.