Initial Low Oxygen Extraction Ratio Is Related to Severe Organ Dysfunction and High In-Hospital Mortality in Severe Sepsis and Septic Shock Patients.

BACKGROUND: In severe sepsis and septic shock, global tissue hypoxia is a key development preceding multi-organ failure and death. OBJECTIVE: Our aim was to find whether the initial low oxygen extraction ratio (OER) is related to the severity of organ dysfunction and to predict the in-hospital mortality in severe sepsis or septic shock patients. METHODS: This was a secondary analysis of 169 patients with severe sepsis or septic shock in an emergency department. We calculated OER with 1- central venous oxygen saturation (ScvO2)/arterial oxygen saturation and compared the data according to the level of OER (high > 0.3, 0.2 ≤ normal ≤ 0.3, lower < 0.2). RESULTS: A total 133 patients were selected for analysis. OER was inversely proportional to ScvO2 (r(2) = 0.878; p < 0.001). The sepsis-related organ failure assessment score and in-hospital mortality of each group were 6.2 ± 3.7 and 37.0% for high OER, 5.7 ± 3.0 and 11.8% for normal OER, and 7.7 ± 3.9 and 41.7% for low OER, respectively (p = 0.034; p = 0.003). In patients with initial ScvO2 of >70%, in-hospital mortality of patients with low OER was significantly higher than patients with normal OER. CONCLUSIONS: Initial low OER was associated with severe organ dysfunction that resulted in high mortality with severe sepsis and septic shock. When patients had initial ScvO2 of > 70% but abnormally low OER, their in-hospital mortality was higher than in normal OER patients. Therefore, the OER should be considered when attempting to predict the outcome of septic patients using ScvO2 at an early stage of management for sepsis.

An optimal transition time to extracorporeal cardiopulmonary resuscitation for predicting good neurological outcome in patients with out-of-hospital cardiac arrest: a propensity-matched study.

INTRODUCTION: Prolonged conventional cardiopulmonary resuscitation (CCPR) is associated with a poor prognosis in out-of-hospital cardiac arrest (OHCA) patients. Alternative methods can be needed to improve the outcome in patients with prolonged CCPR and extracorporeal cardiopulmonary resuscitation (ECPR) can be considered as an alternative method. The objectives of this study were to estimate the optimal duration of CPR to consider ECPR as an alternative resuscitation method in patients with CCPR, and to find the indications for predicting good neurologic outcome in OHCA patients who received ECPR. METHODS: This study is a retrospective analysis based on a prospective cohort. We included patients ≥ 18 years of age without suspected or confirmed trauma and who experienced an OHCA from May 2006 to December 2013. First, we determined the appropriate cut-off duration for CPR based on the discrimination of good and poor neurological outcomes in the patients who received only CCPR, and then we compared the outcome between the CCPR group and ECPR group by using propensity score matching. Second, we compared CPR related data according to the neurologic outcome in matched ECPR group. RESULTS: Of 499 patients suitable for inclusion, 444 and 55 patients were enrolled in the CCPR and ECPR group, respectively. The predicted duration for a favorable neurologic outcome (CPC1, 2) is < 21 minutes of CPR in only CCPR patients. The matched ECPR group with ≥ 21 minutes of CPR duration had a more favorable neurological outcome than the matched CCPR group at 3 months post-arrest. In matched ECPR group, younger age, witnessed arrest without initial asystole rhythm, early achievement of mean arterial pressure ≥ 60 mmHg, low rate of ECPR-related complications, and therapeutic hypothermia were significant factors for expecting good neurologic outcome. CONCLUSIONS: ECPR should be considered as an alternative method for attaining good neurological outcomes in OHCA patients who required prolonged CPR, especially of ≥ 21 minutes. Younger or witnessed arrest patients without initial asystole were good candidates for ECPR. After implantation of ECPR, early hemodynamic stabilization, prevention of ECPR-related complications, and application of therapeutic hypothermia may improve the neurological outcome.

Comparative analysis of acute toxic poisoning in 2003 and 2011: analysis of 3 academic hospitals.

Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the characteristics of patients with acute toxic poisoning is important for treating such patients. Therefore, this study investigated the characteristics of patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and 2011 were included in this study. Data on all patients who were admitted to the emergency departments with acute toxic poisoning were retrospectively obtained from medical records. Total 939 patients were analyzed. The average age of patients was 40.0 ± 20 yr, and 335 (36.9%) patients were men. Among the elements that did not change over time were the facts that suicide was the most common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and that there were more women than men. Furthermore, acetaminophen and doxylamine remained the most common poisoning agents. In conclusion, the average patient age and psychotic drug poisoning has increased over time, and the use of lavage treatment has decreased.

Effect of hypertonic saline on apoptosis of polymorphonuclear cells.

BACKGROUND: The function of polymorphonuclear (PMN) cells can be influenced by the choice of resuscitation fluids in hemorrhagic shock. Widespread interest in the use of hypertonic solutions for resuscitation has led to extensive investigation of their immune-modulating properties. Hypertonic saline (HTS) is known to modulate immune reactions, preventing the multiorgan failure mediated by immune reactions in trauma and hemorrhagic shock. PMN cells play a key role in such immune-mediated inflammatory processes, and HTS is believed to affect these PMN cells. However, how these events influence the actual event of apoptosis has not yet been described. Thus, in the present study, we aimed to investigate the differences in the apoptosis of PMN cells when exposed to isotonic and hypertonic environments and the temporal relations between the interval of administration of HTS after the stimulation of PMN cells. METHODS: Whole blood was sampled from healthy volunteers, and the PMN cells were isolated. The isolated layer of PMN cells was washed twice with phosphate-buffered saline to yield the PMN cells. The number of cells was kept uniform, and an overall survival rate greater than 95% was maintained. After stimulation of the isolated PMN cells with N-formyl-methionyl-leucyl-phenylalanine, the PMN cells were allocated into 3 study groups (i.e., 1 isotonic group and 2 hypertonic groups with an osmolarity of 160 mM and 180 mM each). The extent of apoptosis was investigated in each group after culturing the PMN cells for 0, 1, 3, 6, 12, 15, 18, and 24 h. Depending on whether the PMN cells were stimulated with N-formyl-methionyl-leucyl-phenylalanine, they were also divided into stimulated and nonstimulated groups. In the stimulated group, the hypertonic environment was fostered immediately (HTS 0 h) and 6 h (HTS 6 h) after stimulation, which was accomplished after allocating the cells into an isotonic group (140 mM) and a hypertonic group (180 mM), according to the concentration of the culture medium. The PMN cells were then cultured at 37°C for 15 h with 5% carbon dioxide incubation. Each PMN suspension was labeled with Annexin V-fluorescein isothiocyanate and propidium iodide. Each sample underwent immediate flow cytometric analysis. PMN cells with high propidium iodide uptake were considered nonviable (necrotic). Among the viable PMN cells, those with no Annexin V uptake were considered normal and those with Annexin V uptake were considered apoptotic. RESULTS: Decreased apoptosis was observed in the PMN cells stimulated with N-formyl-methionyl-leucyl-phenylalanine. Increased apoptosis was observed in the stimulated PMN cells incubated in hypertonic condition compared with the cells incubated in isotonic condition. Early HTS administration demonstrated increased apoptosis compared with late administration. CONCLUSIONS: HTS treatment resulted in increased PMN apoptosis and an anti-inflammatory effect. Decreased apoptosis (prolonged lifespan) has been implicated in neutrophil-mediated tissue damage. HTS, by increasing the apoptosis of PMN cells, attenuates the postinjury inflammatory response. Also, early treatment with HTS was more efficient than delayed treatment.

Radiological misinterpretations by emergency physicians in discharged minor trauma patients.

INTRODUCTION: Unerring radiological interpretation is essential in discharged minor trauma patients without follow-up visits based on the rapid decision of emergency physicians (EPs). Misinterpretation may raise issues concerning patient care, reimbursement and lawsuits. The authors investigated the discrepancies and associated factors in radiological interpretation for discharged trauma patients between EPs and radiologists. METHODS: The authors included trauma patients who visited the emergency department, from 1 August 2009 to 31 July 2010, and searched for cases showing discrepancy using the 'modified quality assurance model for radiological interpretation'. The overall/clinically significant discrepancy (CSD)/clinically insignificant discrepancy (CinSD) rates were calculated. The authors also looked at the relationship between discrepancies and several factors including age and time of visit. RESULTS: 10,243 cases were related to minor trauma, in which the radiological images were interpreted as normal by EPs. The overall discrepancy, the CSD and CinSD rates were 0.77% (n=79), 0.47% (n=48) and 0.3% (n=31), respectively. No discrepancy was shown to be related to the day or time of visit. The discrepancy rate turned out to be relatively higher with increasing age, and for injuries of the extremities. No associated factors were found between the CSD and CinSD groups. CONCLUSIONS: Despite a relatively low CSD rate, careful interpretation is recommended considering age and body areas imaged. A modified model would be needed as a supportive tool for training and improving the quality of care. A further development of the modified system for efficient use of resources will be needed to focus on quality improvement and education in each hospital.

Acute traumatic coagulopathy decreased actual survival rate when compared with predicted survival rate in severe trauma.

OBJECTIVE: To determine whether acute traumatic coagulopathy (ATC) should be combined with the trauma and injury severity score (TRISS) to predict outcome in severe trauma patients and investigate effects of the change in coagulation state during early resuscitation on the actual survival rate. METHODS: This was a retrospective study. Significant variables that affected 28-day mortality were analysed using multivariate logistic regression. Study patients were classified into three groups: no coagulopathy, mild coagulopathy or severe coagulopathy. Concordance between actual and predicted survival rates were compared for each group. The predicted survival rate was calculated using the TRISS method. The study also determined whether changes in the coagulation state during inhospital resuscitation affected the relationship between actual and predicted survival in patients who had rechecked coagulation profile within 12 h after presentation. RESULTS: Data from a total of 336 patients were analysed. At presentation, 20.8% of the study patients had mild coagulopathy, whereas 7.7% had severe coagulopathy. Age, injury severity score, revised trauma score and presence of ATC at presentation were independently associated with 28-day mortality. Actual survival was significantly lower than predicted survival in the mild and severe coagulopathy groups. Aggravation of coagulation state from normal or mild to severe coagulopathy or persistent severe coagulopathy during inhospital resuscitation mainly contributed to the discrepancy between actual and predicted survival. CONCLUSIONS: ATC decreased actual survival more than expected. ATC should be combined with TRISS to predict trauma outcome in severely injured patients. Improvement in coagulopathy during resuscitation may reduce the incidence of preventable death after trauma.

Concentration of arginine and optimal time of hypertonic saline in restoration of T-cell dysfunction.

BACKGROUND: Hypertonic saline (HS) restores prostaglandin E(2) (PGE(2))-induced T-cell suppression in the presence of 1100 microM arginine. However, under arginine-free culture conditions, HS dose not restore T-cell proliferation. Therefore, we wanted to determine if HS can restore PGE(2)-induced T-cell suppression in the presence of 80 microM of arginine, the physiologically relevant arginine concentration. We also wanted to determine the concentration of arginine that induces HS restoration of PGE(2)-suppressed T-cell proliferation and whether HS restoration of T-cell dysfunction is dependent on the injection time of HS. MATERIALS AND METHODS: Jurkat cells were cultured in media containing 0, 40, 80, 400, 800, or 1100 microM arginine. In both the PGE(2)-stimulated and HS-treated group, we measured cell proliferation using MTT assay and arginase activity. We also measured cell proliferation relative to HS injection time. RESULTS: In 80 microM arginine, HS did not restore Jurkat cell proliferation that had been suppressed by PGE(2). Increased concentrations of arginine in the media increased MTT cell proliferation. In 800 microM arginine media, HS restored PGE(2)-suppressed Jurkat cell proliferation to normal. HS restored PGE(2)-suppressed Jurkat cell proliferation when it was added at 2 h, similar to at same time and 1 h after PGE(2) stimulation. CONCLUSIONS: In order to restore PGE(2)-suppressed Jurkat cell proliferation, HS requires at least 800 microM arginine. HS restored PGE(2)-suppressed Jurkat cell proliferation even though HS was added at 2 h after PGE(2) stimulation.

The additional use of end-tidal alveolar dead space fraction following D-dimer test to improve diagnostic accuracy for pulmonary embolism in the emergency department.

PURPOSE: To determine the diagnostic performance of bedside assessment of end-tidal alveolar dead space fraction (ADSF) for pulmonary embolism (PE) and whether the use of additional ADSF assessment following D-dimer assay can improve the diagnostic accuracy in suspected PE patients in the emergency department. METHODS: A prospective observational study of 112 consecutive adult patients suspected of PE of whom 102 were eligible for analysis. ADSF was calculated using arterial carbon dioxide and end-tidal carbon dioxide. An ADSF less than 0.2 was considered normal. RESULTS: PE was confirmed in 11 (10.8%) of 102 patients. D-dimer assay alone as a reference standard test for PE had a sensitivity of 100%, specificity of 38.5% and false negativity of 0%. Area under the receiver-operator characteristic curve for the diagnosis of PE using ADSF values alone was 0.894, Sensitivity, specificity and false negativity for the combined results of a positive D-dimer test and abnormal ADSF were 100%, 78.0% and 0% for the presence of PE, respectively. Of 65 patients with a low or intermediate clinical probability and a positive D-dimer assay, 36 (55.4%) patients displayed normal ADSF and had no PE. CONCLUSIONS: By itself ADSF assessment performed well in diagnosis of PE. The combined result of a positive D-dimer and abnormal ADSF increased the specificity for diagnosing PE compared with the D-dimer test alone. The use of additional bedside ADSF assessment following a positive D-dimer test may reduce the need for further imaging studies to detect PE in patients with a low or intermediate clinical probability.

Concordance of end-tidal carbon dioxide and arterial carbon dioxide in severe traumatic brain injury.

OBJECTIVE: It is important for preventing hyperventilation so as to improve the outcomes of patients with severe traumatic brain injuries. End-tidal CO2 (Petco2) reflects arterial CO2 (Paco2), noninvasively and continuously. The aim of this study is to examine the concordance between Paco2 and Petco2 among adults presenting to the emergency department with severe traumatic brain injury and to elucidate the patient groups who had discordance. METHODS: From July 1, 2006 to December 31, 2007, 77 patients who presented in the emergency department of the hospital after severe brain injury were enrolled. Glasgow Coma Scale, blood pressure, heart rate, respiration rate, body temperature, arterial blood gas variables, and serum lactate levels were measured under the mechanical ventilation support. Finally, Injury Severity Score and Abbreviated Injury Scale of head and chest were recorded. The concordance between Petco2 and Paco2 was analyzed using Bland-Altman plot. We defined that normal gap of Paco2 and Petco2 [P(a-et)co2] is -5 mm Hg to 5 mm Hg, and compared the normal and high P(a-et)co2 groups to find the factors affecting the P(a-et)co2. RESULTS: Sixty-six patients after exception of 11 patients with nontraumatic brain injury were analyzed. Ten patients (15.2%) were below 30 mm Hg of Paco2. Pearson's correlation coefficient between Paco2 and Petco2 was 0.666 (p < 0.001) and the concordance between Paco2 and Petco2 was 77.3%. The patients with high P(a-et)co2 showed significantly higher Injury Severity Score, lower systolic blood pressure, lower arterial pH, lower base deficit, and higher serum lactate levels than patients with normal P(a-et)co2. Patients with severe chest trauma, hypotension, and metabolic acidosis increased the risk of the discordance between Paco2 and Petco2. Twenty-eight patients who had no hypotension, no metabolic acidosis, and no severe chest trauma showed concordance rate of 100.0% between Paco2 and Petco2. CONCLUSIONS: Severe chest trauma and hemodynamic and tissue perfusion state should be considered when attempting to monitor the hyperventilation in severe brain injury patients using Petco2.

Successful extracorporeal life support in cardiac arrest with recurrent ventricular fibrillation unresponsive to standard cardiopulmonary resuscitation.

Extracorporeal life support has been used as an extension of conventional cardiopulmonary resuscitation (CPR). However, the appropriate indications for extracorporeal CPR (ECPR) including the duration of CPR are unknown. We present a case of a male, 37-year-old out-of-hospital cardiac arrest patient who received prolonged CPR followed by ECPR. Despite advanced cardiac life support, he did not regain a sustained spontaneous circulation and had recurrent ventricular fibrillation (VF) during the prolonged CPR. VF was unresponsive to CPR, defibrillation, adrenaline (epinephrine), and antiarrhythmics. The CPR time before ECPR was approximately 2h. During extracorporeal life support, the VF did not recur and percutaneous coronary angioplasty was achieved. Ultimately, the patient was discharged without neurological complications. Although cardiac arrest occurred out-of-hospital and CPR was performed for a long time, a patient might be a candidate for ECPR if perfusing rhythms are restored transiently but not successfully maintained due to recurrent VF. ECPR may be used for VF unresponsive to standard CPR techniques.

Arterial minus end-tidal CO2 as a prognostic factor of hospital survival in patients resuscitated from cardiac arrest.

AIMS: The purpose of this study was to determine the clinical value of arterial minus end-tidal CO(2) [P(a-et)CO(2)] and alveolar dead space ventilation ratio (V(dA)/V(t)) as indicators of hospital mortality in patients that have been resuscitated from cardiac arrest at emergency department. MATERIALS AND METHODS: Forty-four patients with a return of spontaneous circulation (ROSC) after cardiac arrest were studied in the emergency department of a university teaching hospital from March 2004 to February 2006. Mean arterial pressure (MAP), serum lactate, arterial blood gas studies, end-tidal CO(2) (EtCO(2)), P(a-et)CO(2), and V(dA)/V(t) were evaluated at 1 h after ROSC. We compared these variables between hospital survivors and non-survivors. RESULTS: The rates of ventricular fibrillation and pulseless ventricular tachycardia in hospital survivors were higher than those of non-survivors (53.0 and 9.7%, respectively, p=0.002). Hospital survivors had significantly higher MAP, lower serum lactate, lower P(a-et)CO(2), and lower V(dA)/V(t) value than non-survivors. Receiver operator characteristic (ROC) curves of serum lactate, P(a-et)CO(2), and V(dA)/V(t) showed significant sensitivity and specificity for hospital mortality. Specifically, lactate > or = 10.0 mmol/L, P(a-et)CO(2) > or = 12.5 mmHg, and V(dA)/V(t) > or = 0.348 were all associated with high hospital mortality (p=0.000, 0.001 and 0.000, respectively). CONCLUSIONS: This study showed that high serum lactate, high P(a-et)CO(2) and high V(dA)/V(t) during early ROSC in cardiac arrest patients suggest high hospital mortality. If future studies validate this model, the P(a-et)CO(2) and V(dA)/V(t) may provide useful guidelines for the early post-resuscitation care of cardiac arrest patients in emergency departments.

Successful extracorporeal life support after potentially fatal pulmonary oedema caused by inhalation of nitric and hydrofluoric acid fumes.

Two patients presented with potentially fatal pulmonary oedema after accidental exposure to nitric and hydrofluoric acid fumes during electroplating. Despite aggressive respiratory support, one succumbed to respiratory failure 3.5h after inhalation. The other patient also rapidly progressed to respiratory failure. Extracorporeal life support (ECLS) was started 5h after exposure at the ED. During ECLS, hypoxia improved, but pulmonary oedema shown by chest radiography became aggravated. N-Acetyl cysteine and calcium gluconate were given i.v. on the first day of admission and nebulised for 48 h after exposure. Pulmonary secretions were significantly reduced 24 h after the nebulising therapy began. Ultimately, the patient was discharged without serious pulmonary or neurological complications after 28 days of hospitalisation. In this case, early ECLS, nebulised antioxidant and antidote were available to treat potentially fatal pulmonary oedema after exposure to nitric and hydrofluoric acid fumes.

Can spontaneous pneumothorax patients be treated by ambulatory care management?

OBJECTIVE: In the Emergency Department, it would be worthwhile to treat pneumothorax patients on an outpatient basis by utilizing a small-calibre catheter and Heimlich valve insertion. We evaluated this treatment and compared it with the closed thoracostomy. METHODS: In this comparative study, the success rate, complications and recurrence rate of treating spontaneous pneumothorax patients by using a small-calibre catheter and Heimlch valve were compared with those of a similar-sized group treated by closed thoracostomy. RESULTS: Pneumothorax was successfully treated on an ambulatory basis by using the small-calibre catheter and Heimlch valve in 20 patients (47%); this was less than the 42 patients (89%) who were successfully treated by closed thoracostomy. While no complications were encountered in the group treated using the small-calibre catheter and Heimlich valve, 11 patients in the group treated by closed thoracostomy developed complications. The medical expenses for the treatment involving the small-calibre catheter and Heimlich valve were less than those for closed thoracostomy. CONCLUSION: Prior to the treatment, the patients should be fully informed of the success rate of this treatment and the possibility of requiring closed thoracostomy in the event of treatment failure.

Effects of atmospheric temperature and humidity on outbreak of diseases.

OBJECTIVE: The present study aimed to determine the plausibility of forecasting the outbreak of diseases based on the weather by analysing the impact of atmospheric temperature and humidity on the occurrence of different diseases. METHODS: The subjects of the present study were the 30,434 patients who visited the ED in 1 year from 1 February 2005 to 3 February 2006. The present study analysed the correlation between the daily number of patients who suffered from 22 types of traumatic and non-traumatic diseases and the data on atmospheric temperature and humidity provided by the Korea Meteorological Administration. RESULTS: With traumatic disease, the occurrence tended to increase in proportion to the rise in temperature and humidity; whereas with non-traumatic disease, the occurrence tended to increase according to the rise in temperature, irrespective of humidity changes. The research on the impact of atmospheric temperature and humidity on different diseases revealed a high level of distribution of most diseases in an environment with high temperature and humidity. However, in the case of pulmonary diseases and trauma to multiple body regions, the occurrence increased in environments with low temperature and high humidity for pulmonary diseases, and with low temperature and low humidity for trauma to multiple body regions. CONCLUSION: Most diseases tend to increase in proportion to the rise in atmospheric temperature whereas being less affected by humidity. However, an increase in humidity in an optimum range of atmospheric temperature (12 degrees C or higher) triggers an increase in the occurrence of diseases.

A system-wide approach from the community to the hospital for improving neurologic outcomes in out-of-hospital cardiac arrest patients.

OBJECTIVE: In the present study, we aimed to determine the effects of a system-wide approach from the community to the hospital in improving the neurologic outcomes in out-of-hospital cardiac arrest (OHCA) patients within Sungbuk in Korea. METHODS: This study used a before-after design. In 2011, compression-only cardiopulmonary resuscitation (CPR) for citizens, a state-wide standard dispatcher assisted-CPR protocol, medical control for regional emergency medical service (EMS), provision of high-quality advanced cardiac life support (ACLS) with capnography and extracorporeal CPR, and the standard postcardiac arrest care protocol were implemented in the system-wide CPR program. CPR provision and outcomes were compared between the 2009-2010 and the 2012-2013 periods. A multivariate logistic regression model for good outcome of OHCA was used to identify interventions with a significant impact. RESULTS: In total, 581 adult nontraumatic OHCA patients who received resuscitation attempts from 2009 to 2013 were selected for the analysis of CPR provision and outcomes. CPR provision improved significantly, as indicated by the following results from 2009-2010 to 2012-2013: from 15.9 to 50.4% for bystander CPR (P<0.001), 6.0 to 0% for the proportion of no documented arrest rhythm by EMS (P=0.004), 41.4 to 62.2% for ACLS with capnography (P=0.008), 1.4 to 10.5% for extracorporeal CPR (P=0.052), 3.7 to 34.4% for successful therapeutic hypothermia in coma patients (P<0.001), and 61.5 to 87.1% for immediate coronary angiography for presumed cardiac etiology (P=0.005). Moreover, the proportion of OHCA patients who received early EMS activation, bystander CPR, appropriate attempt of defibrillation at the prehospital level, high-quality ACLS, and standard postcardiac arrest care increased from 0.5% in 2009-2010 to 8.5% in 2012-2013 (P<0.001). The rates of discharge with a good neurologic outcome improved from 3.3% in 2009-2010 to 8.5% in 2012-2013 (P<0.001). CONCLUSION: The system-wide CPR program was associated with enhancements in CPR performance at both the prehospital and the hospital level, and yielded improved neurologic outcomes in OHCA patients in a small region.

The effect of cyclosporine A in hemorrhagic shock model of rats.

BACKGROUND: The inhibition of mitochondrial permeability transition pore opening during ischemia-reperfusion can ameliorate injuries. This study aimed to investigate the effects of cyclosporine A (CsA) in rats after hemorrhagic shock. METHODS: Male Sprague-Dawley rats were subjected to pressure-controlled hemorrhagic shock (mean arterial pressure, 38 ± 1 mm Hg) for 90 minutes. After the hemorrhagic shock period, rats were randomly allocated to one of three groups as follows: a control group, a CsA10 group, or a CsA50 group. CsA for the treatment groups (10 mg/kg for the CsA10 group and 50 mg/kg for the CsA50 group) or normal saline for the control group was administered via tail vein for 10 minutes, and shed blood was transfused for 15 minutes. For the survival study, animals were observed for up to 9 hours, and their survival time was recorded until death. Separate experiments were performed to examine the effect of CsA on inflammatory responses and liver injury. Rats were sacrificed at 210 minutes after the shock period, and blood and liver tissues were harvested. RESULTS: Survival times were shown to be significantly longer in the CsA-treated groups (i.e., the CsA10 and CsA50 groups) than in the control group. Plasma interleukin-6 and thiobarbituric acid-reactive substances were significantly lower in the CsA50 group than in the control group and phosphorylation of Akt, GSK-3ß, and Bad were significantly increased in the CsA-treated groups compared with the control group. Expressions of Bcl-2, cleaved caspase 3, and cytoplasmic cytochrome C were significantly decreased in the CsA-treated groups compared with the control group. Although histologic liver injury was not significantly different among the groups, ultrastructural changes of mitochondria were more prominent in the control group than in the CsA-treated groups. CONCLUSION: CsA increased survival time, decreased proinflammatory cytokine and lipid peroxidation, and augmented Akt survival pathways in rats subjected to pressure-controlled hemorrhagic shock.

Randomized comparison of piperacillin/tazobactam versus imipenem/cilastatin in the treatment of patients with intra-abdominal infection.

OBJECTIVES: Treatment of intra-abdominal infections remains a challenge because of their polymicrobial nature and associated mortality risk. Broad-spectrum empiric coverage is usually required. This randomized study compared the efficacy and safety of intravenous piperacillin/tazobactam with those of intravenous imipenem/cilastatin in the treatment of 293 hospitalized patients with intra-abdominal infection. METHODS: A total of 149 patients received piperacillin/tazobactam 4 g/500 mg every 8 hours, and 144 patients received imipenem/cilastatin 500 mg/500 mg every 6 hours. Efficacy was evaluated by clinical and bacteriological response. Safety was evaluated by analysis of adverse events and physical and laboratory examinations. RESULTS: Clinical and bacteriological responses in both evaluable treatment groups were equivalent. The clinical success was 97% (108/111) for piperacillin/tazobactam and 97% (100/103) for imipenem/cilastatin. Bacteriological success was 97% (67/69) for piperacillin/tazobactam and 95% (61/64) for imipenem/cilastatin. The most common pathogens were Escherichia coli, Klebsiella pneumoniae, Enterobacter species and Pseudomonas aeruginosa. The frequencies of treatment-related adverse events were similar (16 with piperacillin/tazobactam and 19 with imipenem/cilastatin). CONCLUSIONS: These results suggest that the safety and efficacy of piperacillin/tazobactam administered every 8 hours are equivalent to those of imipenem/cilastatin administered every 6 hours for the treatment of intra-abdominal infections.