Removal of Bilirubin with a New Adsorbent System: In Vitro Kinetics.

BACKGROUND/AIMS: Many potentially toxic molecules accumulate in the blood during hepatic dysfunction. In clinical practice, it is very difficult to remove bilirubin, the most widely studied toxin, and particularly the unconjugated form, strongly albumin-bound. The aim of this in vitro study was to assess irreversible bilirubin adsorption as a protein-bound compound marker, using Cytosorb® (Cytosorbents Corp.), a new hemoadsorption device designed to remove cytokines. METHODS: We performed 4 in vitro experiments, dynamic and static, with different albumin-bilirubin solutions. RESULTS: All experiments showed the resin's ability to break the albumin-bilirubin complex (Experiment 1, 2), leading to efficient bilirubin removal for 24 h (Removal Rate: 90% Experiment 3) with minimal albumin loss. No sign of bilirubin release from the charged resin was detected (Experiment 4). CONCLUSION: Cytosorb® seems a promising artificial liver support, thanks to its ability to adsorb bilirubin and its proven ability to modulate the cytokines involved in hepatic dysfunction.

Early infections in the intensive care unit after liver transplantation-etiology and risk factors: A single-center experience.

BACKGROUND: Infectious complications represent one of the main causes of perioperative morbidity and mortality of liver transplant recipients. The primary objective of this retrospective observational study was to evaluate incidence and etiology of early (within 1 month from surgery and occurring in the intensive care unit [ICU]) postoperative infections as well as donor- and recipient-related risk factors. METHODS: The data of 280 patients undergoing 299 consecutive liver transplant procedures from January 2012 to December 2015 were extracted from the Italian ICU registry database and hospital registries. Perioperative risk factors, etiology of infections, and antibiotic susceptibility of isolated microorganisms were taken into consideration. RESULTS: Global incidence of postoperative infections was 21%. Pneumonia was the most frequent infection and, globally, gram-negative bacteria were the most common agents. Septic shock was present in 22% of infection cases and hospital mortality was higher in patients with postoperative infection. Preoperative chronic obstructive pulmonary disease, malnutrition, preoperative ascites, encephalopathy, and early re-transplantation were significantly associated to post orthotopic LT infections. CONCLUSION: Infections represent a major cause of early postoperative morbidity and mortality. The impact of single risk factors and the results of their preoperative management should be further investigated in order to reduce the incidence and evolution of postoperative infections.

Post-reperfusion syndrome during orthotopic liver transplantation, which definition best predicts postoperative graft failure and recipient mortality?

Post-reperfusion syndrome during orthotopic liver transplantation, which definition best predicts postoperative graft failure and recipient mortality? PURPOSE: Post-reperfusion syndrome (PRS) is a serious complication of liver transplantation, at present two main definitions are in use, and they differ both clinically and temporally. The primary objective of this study was to evaluate these two definitions as risk factors for post-transplantation mortality and primary graft non-function. MATERIALS AND METHODS: We conducted a retrospective observational study on 794 patients undergoing orthotopic liver transplantation at our university hospital. The presence of PRS was evaluated according to both definitions and correlated with the end points: three months mortality, primary graft non-function (PGNF) and the combined outcome of the two. RESULTS: Both definitions proved to be independent risk factors for three months mortality and the combined outcome. The definition according to Aggarwal et al. was also an independent risk factor for PGNF when adjusted for the propensity score. The Hilmi definition, despite being more comprehensive, did not improve the predictivity of the Aggarwal definition for the evaluated outcomes. CONCLUSIONS: PRS proved to be an independent risk factor for post-transplantation mortality and occurrence of PGNF. The pathophysiological mechanisms of this entity are still not fully understood and preventive strategies could help in reducing patients and graft losses.

Role of epidural anesthesia in a fast track liver resection protocol for cirrhotic patients - results after three years of practice.

AIM: To evaluate the potential benefits and risks of the use of epidural anaesthesia within an enhanced recovery protocol in this specific subpopulation. METHODS: A retrospective review was conducted, including all cirrhotic patients who underwent open liver resection between January 2013 and December 2015 at Bologna University Hospital. Patients with an abnormal coagulation profile contraindicating the placement of an epidural catheter were excluded from the analysis. The control group was composed by patients refusing epidural anaesthesia. RESULTS: Of the 183 cirrhotic patients undergoing open liver resections, 57 had contraindications to the placement of an epidural catheter; of the remaining 126, 86 patients received general anaesthesia and 40 combined anaesthesia. The two groups presented homogeneous characteristics. Intraoperatively the metabolic data did not differ between the two groups, whilst the epidural group had a lower mean arterial pressure (P = 0.041) and received more colloid infusions (P = 0.007). Postoperative liver and kidney function did not differ significantly. Length of mechanical ventilation (P = 0.003) and hospital stay (P = 0.032) were significantly lower in the epidural group. No complications related to the epidural catheter placement or removal was recorded. CONCLUSION: The use of Epidural Anaesthesia within a fast track protocol for cirrhotic patients undergoing liver resections had a positive impact on the patient's outcomes and comfort as demonstrated by a significantly lower length of mechanical ventilation and hospital stay in the epidural group. The technique appears to be safely manageable in this fragile population even though these results need confirmation in larger studies.

Ventilator associated pneumonia following liver transplantation: Etiology, risk factors and outcome.

AIM: To determine the incidence, etiology, risk factors and outcome of ventilator-associated pneumonia (VAP) in patients undergoing orthotopic liver transplantation (OLT). METHODS: This retrospective study considered 242 patients undergoing deceased donor OLT. VAP was diagnosed according to clinical and microbiological criteria. RESULTS: VAP occurred in 18 (7.4%) patients, with an incidence of 10 per 1000 d of mechanical ventilation (MV). Isolated bacterial etiologic agents were mainly Enterobacteriaceae (79%). Univariate logistic analysis showed that model for end-stage liver disease (MELD) score, pre-operative hospitalization, treatment with terlipressin, Child-Turcotte-Pugh score, days of MV and red cell transfusion were risk factors for VAP. Multivariate analysis, considering significant risk factors in univariate analysis, demonstrated that pneumonia was strongly associated with terlipressin usage, pre-operative hospitalization, days of MV and red cell transfusion. Mortality rate was 22% in the VAP group vs 4% in the group without VAP. CONCLUSION: Our data suggest that VAP is an important cause of nosocomial infection during postoperative period in OLT patients. MELD score was a significant risk factor in univariate analysis. Multiple transfusions, treatment with terlipressin, preoperative hospitalization rather than called to the hospital while at home and days of MV constitute important risk factors for VAP development.

Post reperfusion syndrome during liver transplantation: From pathophysiology to therapy and preventive strategies.

This review aims at evaluating the existing evidence regarding post reperfusion syndrome, providing a description of the pathophysiologic mechanisms involved and possible management and preventive strategies. A PubMed search was conducted using the MeSH database, "Reperfusion" AND "liver transplantation" were the combined MeSH headings; EMBASE and the Cochrane library were also searched using the same terms. 52 relevant studies and one ongoing trial were found. The concept of post reperfusion syndrome has evolved through years to a multisystemic disorder. The implications of the main organ, recipient and procedure related factors in the genesis of this complex syndrome are discussed in the text as the novel pharmacologic and technical approaches to reduce its incidence. However the available evidence about risk factors, physiopathology and preventive measures is still confusing, the presence of two main definitions and the numerosity of possible confounding factors greatly complicates the interpretation of the studies.

Thoracic epidural anesthesia: Effects on splanchnic circulation and implications in Anesthesia and Intensive care.

AIM: To evaluate the currently available evidence on thoracic epidural anesthesia effects on splanchnic macro and microcirculation, in physiologic and pathologic conditions. METHODS: A PubMed search was conducted using the MeSH database. Anesthesia, Epidural was always the first MeSH heading and was combined by boolean operator AND with the following headings: Circulation, Splanchnic; Intestines; Pancreas and Pancreatitis; Liver Function Tests. EMBASE, Cochrane library, ClinicalTrials.gov and clinicaltrialsregister.eu were also searched using the same terms. RESULTS: Twenty-seven relevant studies and four ongoing trials were found. The data regarding the effects of epidural anesthesia on splanchnic perfusion are conflicting. The studies focusing on regional macro-hemodynamics in healthy animals and humans undergoing elective surgery, demonstrated no influence or worsening of regional perfusion in patients receiving thoracic epidural anesthesia (TEA). On the other hand most of the studies focusing on micro-hemodynamics, especially in pathologic low flow conditions, suggested that TEA could foster microcirculation. CONCLUSION: The available studies in this field are heterogeneous and the results conflicting, thus it is difficult to draw decisive conclusions. However there is increasing evidence deriving from animal studies, that thoracic epidural blockade could have an important role in modifying tissue microperfusion and protecting microcirculatory weak units from ischemic damage, regardless of the effects on macro-hemodynamics.

High-dose weekly liposomal amphotericin b antifungal prophylaxis in patients undergoing liver transplantation: a prospective phase II trial.

BACKGROUND: To assess the safety and tolerability of high-dose weekly (10 mg/kg) liposomal amphotericin B (LamB) for antifungal prophylaxis in liver transplantation (LT) recipients with predefined risk factors for invasive fungal infection (IFI), a prospective phase II noncomparative trial was performed at our center over a 4-year period. METHODS: In the selected LT recipients, LamB was administered weekly until hospital discharge after LT for minimum 2 weeks. Criteria for early discontinuing prophylaxis were: (i) any adverse event (AE); (ii) suspicion of IFI. Safety and tolerability were assessed according to the incidence of grades 3 to 4 AEs based on Common Toxicity Criteria (CTC) classification. Post-LT follow-up was of 180 days. RESULTS: Overall, 76 patients were included. Liposomal amphotericin B was started within a median of 1 (interquartile range, 1-4) day after LT. Overall, 66 of 76 (86.8%) patients completed the prophylaxis, 10 discontinued the study protocol: 6 for infusion-related AE, 4 for suspected IFI. Adverse events consisted of five cases of lumbar pain and one case of thoracic pain which occurred after a median of 1.5 (interquartile range, 1-2) LamB infusions. None of the patients reported CTC grades 3 to 4 hypokalemia, three reported CTC grade 3 acute renal injury, none of which were deemed directly attributable to LamB. No drug-drug interactions with immunosuppressive drugs were reported, and no episode of rejection occurred during the prophylaxis. In only two of the four patients with suspected IFI was the diagnosis of invasive candidiasis confirmed. CONCLUSION: Our results suggest high-dose weekly LamB may be a safe prophylactic strategy for high-risk LT recipients.

Laparoscopic versus Open Liver Resection: Differences in Intraoperative and Early Postoperative Outcome among Cirrhotic Patients with Hepatocellular Carcinoma-A Retrospective Observational Study.

Introduction. Laparoscopic liver resection is considered risky in cirrhotic patients, even if minor surgical trauma of laparoscopy could be useful to prevent deterioration of a compromised liver function. This study aimed to identify the differences in terms of perioperative complications and early outcome in cirrhotic patients undergoing minor hepatic resection for hepatocellular carcinoma with open or laparoscopic technique. Methods. In this retrospective study, 156 cirrhotic patients undergoing liver resection for hepatocellular carcinoma were divided into two groups according to type of surgical approach: laparoscopy (LS group: 23 patients) or laparotomy (LT group: 133 patients). Perioperative data, mortality, and length of hospital stay were recorded. Results. Groups were matched for type of resection, median number of nodules, and median diameter of largest lesions. Groups were also homogeneous for preoperative liver and renal function tests. Intraoperative haemoglobin decrease and transfusions of red blood cells and fresh frozen plasma were significantly lower in LS group. MELD score lasted stable after laparoscopic resection, while it increased in laparotomic group. Postoperative liver and renal failure and mortality were all lower in LS group. Conclusions. Lower morbidity and mortality, maintenance of liver function, and shorter hospital stay suggest the safety and benefit of laparoscopic approach.

Albumin replacement in patients with severe sepsis or septic shock.

BACKGROUND: Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS: In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS: During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS: In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

Influence of the admission pattern on the outcome of patients admitted to a respiratory intensive care unit: does a step-down admission differ from a step-up one?

BACKGROUND: The outcomes of patients admitted to a respiratory ICU (RICU) have been evaluated in the past, but no study has considered the influence of location prior to RICU admission. METHODS: We analyzed prospectively collected data from 326 consecutive patients admitted to a 7-bed RICU. The primary end points were survival and severity of morbidity-related complications, evaluated according to the patient's location prior to RICU admission. Three admission pathways were considered: step-down for patients transferred from the ICUs of our hospital; step-up for patients coming from our respiratory wards or other medical wards; and directly for patients coming from the emergency department. The secondary end point was the potential influence of several risk factors for morbidity and mortality. RESULTS: Of the 326 subjects, 92 (28%) died. Overall, subjects admitted in a step-up process had a significantly higher mortality (P < .001) than subjects in the other groups. The mortality rate was 64% for subjects admitted from respiratory ward, 43% for those from medical wards, and 18% for subjects from both ICU and emergency department (respiratory ward vs medical ward P = .04, respiratory ward vs emergency department P < .001, respiratory ward vs ICU P < .001, medical ward vs emergency department P < .001, and medical ward vs ICU P < .001). Subjects admitted from a respiratory ward had a lower albumin level, and Simplified Acute Physiology Score II was significantly higher in subjects following a step-up admission. About 30% of the subjects admitted from a respiratory ward received noninvasive ventilation as a "ceiling treatment." The highest odds ratios related to survival were subject location prior to RICU admission and female sex. Lack of use of noninvasive ventilation, younger age, female sex, higher albumin level, lower Simplified Acute Physiology Score II, higher Barthel score, and absence of chronic heart failure were also statistically associated with a lower risk of death. CONCLUSIONS: The pathway of admission to a RICU is a determinant of outcome. Patients following a step-up pattern are more likely to die. Other major determinants of survival are age, nutritional status and female sex.

Post-reperfusion syndrome during isolated intestinal transplantation: outcome and predictors.

BACKGROUND: Post-reperfusion syndrome (PRS) during isolated intestinal transplantation (ITx) is characterized by decreased systemic blood pressure, systemic vascular resistance, and cardiac output and by a moderate increased pulmonary arterial pressure. We hypothesize that the more severe PRS causes a poorer long-term outcome. The primary aim of this study was to determine the independent clinical predictors of intra-operative PRS, as well as to investigate the link between the severity of PRS and the intra-operative profiles and to examine the post-operative complications and their relationship with transplant outcome. METHODS: This observational study was conducted on 27 patients undergoing isolated ITx in a single adult liver and multivisceral transplantation center. PRS was considered when the mean arterial blood pressure was 30% lower than the pre-unclamping value and lasted for at least one min within 10 min after unclamping. RESULTS AND CONCLUSIONS: The main results of this study can be summarized in two findings: in patients undergoing ITx, the duration of cold ischemia and the pre-operative glomerular filtration rate were independent predictors of PRS and the occurrence of intra-operative PRS was associated with significantly more frequent post-operative renal failure and early post-operative death.

Opioid-induced hyperalgesia and rapid opioid detoxification after tacrolimus administration.

Opioids can induce central sensitization and hyperalgesia, referred to as "opioid-induced hyperalgesia." Our report describes a patient who underwent intestinal transplant followed by immunosuppressant-related neuropathic pain. Her pain was treated with limited success over the course of 3 yr with different therapies, including i.v. morphine. She developed opioid-induced hyperalgesia, which was successfully treated with rapid detoxification under general anesthesia. Detoxification improved her quality of life, including the ability to resume physiotherapy. Six months after treatment, she remained opioid free. Our experience suggests that rapid detoxification under general anesthesia may be an effective treatment for opioid-induced hyperalgesia and merits comparison to traditional detoxification methods.

Metabolic, coagulative, and hemodynamic changes during intestinal transplant: good predictors of postoperative damage?

BACKGROUND: Analysis of intraoperative changes of metabolic, hemodynamic, and coagulative parameters is useful to detect early ischemia-reperfusion damage after intestinal transplant. METHODS: The objective of our study is to correlate the histological damage at the end of transplant in relation to the intraoperative changes after reperfusion. The histological aspect was graded according to Park's classification at the end of the surgical procedure with biopsies of the graft. Patients were divided into two groups according to the presence or absence of histological damage of the small bowel wall: group A (normal mucosa/minimal damage: Park's grades 0-1) and group B (mucosal damage: Park's grades 2-8). RESULTS: Significant hemodynamic, metabolic, and coagulative disorders were observed in group B. Consequently, these disorders are thought to be early indicators of graft damage. CONCLUSIONS: Actual monitoring procedures used for postoperative graft surveillance remain paramount in detecting postoperative intestinal dysfunction, but the indicators described in this paper could represent a further help in intraoperative and postoperative management.

Modification of acid-base balance in cirrhotic patients undergoing liver resection for hepatocellular carcinoma.

OBJECTIVE: To examine modifications of acid-base balance of cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Acid-base disorders are frequently observed in cirrhotics; however, modifications during hepatectomy and their impact on prognosis have never been investigated. METHODS: Two hundred and two hepatectomies for HCC on cirrhosis were reviewed. Arterial blood samples were collected immediately before and at the end of resection. Preresection and postresection acid-base parameters were compared and related to patient characteristics and postoperative course. The accuracy of acid-base parameters in predicting postoperative liver failure, defined as an impairment of liver function after surgery that led to patient death or required transplantation, was assessed using receiver operating characteristic analysis (ROC). RESULTS: All patients showed a significant reduction in pH, bicarbonate, and base excess at the end of hepatectomy (P < 0.001 in all cases), worsened by intraoperative blood loss (P < 0.010) and preoperative Model for end-stage liver disease score > or =11 (P < 0.010). ROC curve analysis identifies patients with postresection bicarbonate <19.4 mmol/L at high risk for liver failure (50.0%) whereas levels >22.1 mmol/L did not lead to the event (0%; P < 0.001). Postoperative prolongation of prothrombin time and increases in bilirubin, creatinine, and morbidity were also more frequent in patients with lower postresection bicarbonate, resulting in a longer in-hospital stay. CONCLUSION: In cirrhotic patients, a trend toward a relative acidosis can be expected during surgery and is worsened by the severity of the underlying liver disease and intraoperative blood loss. Postresection bicarbonate level lower than 19.4 mmol/L is an adverse prognostic factor.

Laboratory test variability and model for end-stage liver disease score calculation: effect on liver allocation and proposal for adjustment.

BACKGROUND: The use of the Model for End-Stage Liver Disease (MELD) score to prioritize patients on liver waiting lists must take the bias of different laboratories into account. METHODS: We evaluated the outcome of 418 patients listed during 1 year whose MELD score was computed by two laboratories (lab 1 and lab 2). The two labs had different normality ranges for bilirubin (maximal normal value [Vmax]: 1.1 for lab 1 and 1.2 for lab 2) and creatinine (Vmax: 1.2 for lab 1 and 1.4 for lab 2). The outcome during the waiting time was evaluated by considering the liver transplantations and the dropouts, which included deaths on the list, tumor progression, and patients who were too sick. RESULTS: Although the clinical features of patients were similar between the two laboratories, 36 (13.1%) out of 275 were dropped from the list in lab 1, compared to 5 (3.5%) out of 143 in lab 2 (P<0.01). The differences were mainly due to the deaths on the list (8% lab 1 vs. 2.1% lab 2, P<0.05). The competing risk analysis confirmed the different risk of dropout between the two labs independently of the MELD score, blood group, and preoperative diagnosis. The bias on MELD calculation was considered and bilirubin and creatinine values were "normalized" to Vmax of lab 1 (corrected value=measured value x Vmax lab 1/Vmax lab 2). By comparing receiver operating characteristic curves, the ability of MELD to predict the 6-month dropouts significantly increased from an area under the curve of 0.703 to 0.716 after "normalization" (P<0.05). CONCLUSIONS: Normalization of MELD is a correct and good compromise to avoid systematic bias due to different laboratory methods.

Liver support systems.

Liver insufficiency is a dramatic syndrome with multiple organ involvement. A multiplicity of toxic substances (hydrophilic like ammonia and lipophilic like bilirubin or bile acids or mercaptans) are released into the systemic circulation, thus altering many enzymatic cellular processes. Patients frequently die while on the transplantation waiting list because of organ scarcity. Systems supporting liver function may be useful to avoid further complications due to the typical toxic state, 'bridging' the patients to the transplantation, or, in the event of an acute decompensation of a chronic liver disease, sustain liver function long enough to permit the organ's regeneration and functional recovery. An ideal liver support system should substitute the main functions of the liver (detoxification, synthesis and regulation). Extracorporeal systems now available may be totally artificial or bioartificial. While the first are only able to perform detoxification, the second may add the functions of synthesis (plasma proteins, coagulation factors) and regulation (neurotransmitters). Bioartificial liver working with isolated hepatocytes and a synthetic membrane in an extracorporeal system are however still far from being ready for clinical use. At present, liver insufficiency may be treated with an extracorporeal support technology aimed either at detoxification alone or at a real purification. Charcoal hemoperfusion or exchange/absorption resins may be used for blood detoxification. Blood or plasma exchange, from a theoretical point of view, could be suitable for a polyvalent intoxication, such as liver failure; however, the multicompartmental distribution of some solutes largely endangers the efficacy of these procedures. Selective plasmapheresis techniques are now available for some solutes (e.g. styrene for bilirubin) and may progressively reduce the plasma levels and presumably the deposits of the solute. Novel treatments introduced to improve detoxification, mainly of the protein-bound substances, are the molecular adsorbent recirculation system (MARS) and Prometheus systems. MARS performs an albumin dialysis, where albumin is the exogenous carrier for the toxic substances, and different experiences have proved its efficacy mainly in the treatment of hepatic encephalopathy, while data on survival are still limited to small case series. With Prometheus, the most recent system developed for a wide Liver Support Systems 397 detoxification, albumin-bound toxins are directly removed in two separate cartridges with different solute affinity, without the need for exogenous albumin; plasmadsorption is then coupled with a real dialysis process. After promising initial results, the efficacy of Prometheus in the patients' hard endpoints will be evaluated in a large international trial. On the whole, liver support systems may offer, in many cases, a survival benefit. Stem cells are however, even in this filed, the real great hope for the future of patients with end-stage liver disease.

Hemodynamic indices versus gastric tonometric measurements for prognosis of hemorrhagic shock: a porcine model.

The aim of the study reported here was to assess the prognostic value of gastric tonometry and its implications in the initial phases of hemorrhagic shock. Hemorrhagic shock was induced by use of femoral arterial bleeding in 12 hybrid swine under general anesthesia. Approximately 30% of the circulating blood volume was removed, until mean arterial pressure of 45 mmHg was reached. The shock conditions were observed over a limited period (90 min) by comparing traditional hemodynamic parameters with gastric tonometric measurements and tissue oxygenation. After a shock period of 90 min without pharmacologic treatment, blood was collected in acid-citrate dextrose-treated bags and was reinfused via the right femoral vein. At the end of the experiment, seven animals had good hemodynamic recovery on reinfusion (group A), whereas values in five animals deceased in the same phase (group B). Hemodynamic and gastric tonometric results were compared between survivors and nonsurvivors. Intravascular volume restoration and reduction of systemic vascular resistance (SVR) enabled the animals of group A to maintain standard ventricular kinetics and recover in terms of splanchnic regional flow. In addition, increase in intramucosal gastric pH (pHi), decrease in the pH-gap (pHa-Hi), and progressive restoration in gastric wall tissue oxygenation (PtO2) also were observed. These results suggest that useful diagnostic and therapeutic indications can be obtained by acquisition of simple hemodynamic measurements at the beginning of the shock period. On the basis of results of statistical analysis, only mean arterial pressure and SVR were good indicators of shock development, whereas pHi was not a significant factor in this experimental model.