DOI： 10.1053/j.jvca.2017.11.006

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

A 32-year-old woman, pregnant with twins, presented with a chief complaint of general fatigue. Her general condition had rapidly deteriorated since her last visit to the primary obstetrician; the patient was then referred to our hospital because of suspected fetal death. She underwent emergency cesarean section because fetal death had indeed occurred, and she was then admitted to the intensive care unit (ICU). On ICI: admission, she was found to he in shock. Laboratory analysis revealed extreme hemoconcentration and a low albumin level, and initially, septic shock with obstetric complications was suspected. However, because she did not respond to conventional therapy but instead, rapidly developed severe generalized edema, systemic capillary leak syndrome (SCLS) was diagnosed. The patient remained in shock for several days until undergoing plasma exchange (PE), despite some earlier empirical treatments. She eventually recovered from profound shock status and was discharged from the ICU without sequelae. Among potentially effective treatments, PE seemed to be the most reasonable choice for the treatment of her SCLS.

DOI： 10.18926/AMO/54814

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

Postoperative cognitive dysfunction (POCD) occurs in nearly one-third of patients after non-cardiac surgery. Many animal behavior studies have investigated the effect of general anesthesia on cognitive function. However, there have been no studies examining the effects on working memory specifically, with a focus on the retention of working memory. We demonstrate here that isoflurane anesthesia induces deficits in the retention of spatial working memory in rats, as revealed by an increase in isoflurane-induced across-phase errors in the delayed spatial win-shift (SWSh) task with a 30-min delay in an 8-arm radial arm maze on post-anesthesia days (PADs) 1,2,4, and 10. A post-hoc analysis revealed a significant increase in across-phase errors on PAD 1 and recovery on PAD 10 in the isoflurane group. In contrast, within-phase errors independent of the retention of working memory were unaffected by isoflurane. These results demonstrate that isoflurane anesthesia transiently impairs the retention of spatial working memory in rats.

DOI： 10.18926/AMO/54808

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

Objective: Mortality and morbidity of acute kidney injury (AKI) after cardiac surgery still remain high. The authors undertook the present study to evaluate the utility of early postoperative urinary albumin (uAlb) as a diagnostic marker for predicting occurrence of AKI and its severity in pediatric patients undergoing cardiac surgery.
Design: A prospective observational study.
Setting: A single-institution university hospital.
Participants: All patients <18 years of age who underwent repair of congenital heart disease with cardiopulmonary bypass between July 2010 and July 2012 were included in the study. Neonates age <1 month were excluded from the study population.
Interventions: The association between uAlb and occurrence of AKI within 3 days after admission to the intensive care unit was investigated. Criteria from pediatric modified Risk Injury Failure Loss and End-stage kidney disease (pRIFLE) were used to determine the occurrence of AKI. The value of uAlb was measured at intensive care unit admission immediately after cardiac surgery in all participants from whom a 5-mL urine sample was obtained.
Measurements and Main Results: Of 376 patients, AKI assessed by pRIFLE was identified in 243 (64.6%): 172 for risk (R; 45.7%), 44 for injury (I; 11.7%), and 27 for failure (F; 7.2%). One hundred thirty-three patients (35.4%) were classified as being without AKI (normal [N]) by pRIFLE. The concentration of uAlb was significantly higher in AKI patients than in non-AKI patients (median [interquartile range]): uAlb (mu g/mL): 13.5 (6.4-39.6) v 6.0 (3.4-16), p < 0.001; uAlb/Cr (mg/gCr): 325 (138-760) v 121 (53-269), p < 0.001.
Conclusions: The utility of uAlb for prompt diagnosis of AKI was shown. Obtaining uAlb measurements early after pediatric cardiac surgery may be useful for predicting the occurrence and severity of AKI. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1053/j.jvca.2015.05.194

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

Objective: Mortality and morbidity of acute kidney injury (AKI) after cardiac surgery still remain high. The authors undertook the present study to evaluate the utility of early postoperative urinary albumin (uAlb) as a diagnostic marker for predicting occurrence of AKI and its severity in pediatric patients undergoing cardiac surgery.
Design: A prospective observational study.
Setting: A single-institution university hospital.
Participants: All patients <18 years of age who underwent repair of congenital heart disease with cardiopulmonary bypass between July 2010 and July 2012 were included in the study. Neonates age <1 month were excluded from the study population.
Interventions: The association between uAlb and occurrence of AKI within 3 days after admission to the intensive care unit was investigated. Criteria from pediatric modified Risk Injury Failure Loss and End-stage kidney disease (pRIFLE) were used to determine the occurrence of AKI. The value of uAlb was measured at intensive care unit admission immediately after cardiac surgery in all participants from whom a 5-mL urine sample was obtained.
Measurements and Main Results: Of 376 patients, AKI assessed by pRIFLE was identified in 243 (64.6%): 172 for risk (R; 45.7%), 44 for injury (I; 11.7%), and 27 for failure (F; 7.2%). One hundred thirty-three patients (35.4%) were classified as being without AKI (normal [N]) by pRIFLE. The concentration of uAlb was significantly higher in AKI patients than in non-AKI patients (median [interquartile range]): uAlb (mu g/mL): 13.5 (6.4-39.6) v 6.0 (3.4-16), p < 0.001; uAlb/Cr (mg/gCr): 325 (138-760) v 121 (53-269), p < 0.001.
Conclusions: The utility of uAlb for prompt diagnosis of AKI was shown. Obtaining uAlb measurements early after pediatric cardiac surgery may be useful for predicting the occurrence and severity of AKI. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1053/j.jvca.2015.05.194

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Language：English   Publisher：JAPAN NEUROSURGICAL SOC  

Perioperative management is critical for positive neurosurgical outcomes. In order to maintain safe and authentic perioperative management, a perioperative management center (PERIO) was introduced to patients of our Neurosurgery Department beginning in June 2014. PERIO involves a multidisciplinary team consisting of anesthesiologists, dentists/dental hygienists/technicians, nurses, physical therapists, pharmacists, and nutritionists. After neurosurgeons decide on the course of surgery, a preoperative evaluation consisting of blood sampling, electrocardiogram, chest X-ray, and lung function test was performed. The patients then visited the PERIO clinic 7-14 days before surgery. One or two days before surgery, the patients without particular issues enter the hospital and receive a mouth cleaning one day before surgery. After surgery, postoperative support involving eating/swallowing evaluation, rehabilitation, and pain control is provided. The differences in duration from admission to surgery, cancellation of surgery, and postoperative complications between PERIO and non-PERIO groups were examined. Eighty-five patients were enrolled in the PERIO group and 131 patients in the non-PERIO group. The duration from admission to surgery was significantly decreased in the PERIO group (3.6 +/- 0.3 days), compared to that in the non-PERIO group (4.7 +/- 0.2 days). There was one cancelled surgery in the PERIO group and six in the non-PERIO group. Postoperative complications and the overall hospital stay did not differ between the two groups. The PERIO system decreased the duration from admission to surgery, and it is useful in providing high-quality medical service, although the system should be improved so as not to increase the burden on medical staff.

DOI： 10.2176/nmc.oa.2016-0085

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objectives: To evaluate the cerebral blood flow thresholds for membrane depolarization and repolarization and the effect of brain hypothermia on the cerebral blood flow threshold for membrane repolarization.
Design: Prospective animal study.
Setting: Experimental laboratory in a university hospital.
Subjects: Male Sprague-Dawley rats (n = 40).
Interventions: Cerebral blood flow and membrane depolarization and repolarization in the cerebral cortex were simultaneously monitored by laser Doppler and extracellular potential, respectively. Following bilateral occlusion of the common carotid arteries, cerebral blood flow was decreased by draining blood at a rate of 2.5% of the control level/min until membrane depolarization was initiated. At 5 and 10 minutes (Normothermia 5 and Normothermia 10 groups, respectively) after depolarization onset, cerebral blood flow was restored at the same rate until membrane repolarization was observed. In some animals, intraischemic brain hypothermia targeting 31 degrees C was initiated immediately after the onset of depolarization (Hypothermia 5 and Hypothermia 10 groups).
Measurements and Main Results: The cerebral blood flow threshold for repolarization (46.5% +/- 12%) was significantly higher than that for depolarization (18.9% +/- 4.8%; p < 0.01) in the Normothermia 5 group and was further increased to 61.5% +/- 14% (p < 0.01) in the Normothermia 10 group. With initiation of hypothermia, the cerebral blood flow threshold for membrane repolarization was suppressed to 33.8% +/- 10% in the Hypothermia 5 group (p < 0.01 vs Normothermia 5 group) and was unaltered by prolongation of ischemia (Hypothermia 10 group; 36.6% +/- 6%).
Conclusions: Cerebral blood flow thresholds were significantly higher for repolarization than for depolarization and were further increased by prolonged ischemia. Intraischemic brain hypothermia decreased the repolarization threshold and abrogated the increase in the repolarization threshold caused by prolonged ischemia.

DOI： 10.1097/CCM.0000000000001095

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Language：English   Publisher：BIOMED CENTRAL LTD  

Background: A change of serum lactate concentrations appeared to be useful for predicting outcomes in various acute ill settings. However, there is little information on intraoperative change of lactate level in pediatric cardiac surgery patients.
Methods: We conducted a retrospective observational study of 459 children who received pediatric cardiac surgery to determine the association between change of lactate level after cardiopulmonary bypass (CPB) and patient prognosis (length of ICU stay and incidence of postoperative serious adverse events (SAEs)). We defined change of lactate level after CPB (LAC.) as (final lactate level measurement in the operating room) - (lactate level measured at the end of CPB). To study the independent association of LAC. with length of ICU stay, we used linear regression model.
Results: There were 1145 lactate measurements after CPB in this study cohort. After weaning from CPB, the serum lactate levels significantly increased from 2.1 mmol/L to 2.5 mmol/L (p < 0.001). Patients with higher LAC. had significantly longer stay in ICU (p = 0.017) and higher incidence of SAEs (p = 0.002). In multivariate linear regression analysis, higher LAC. showed a significant independent association with longer length of ICU stay.
Conclusions: Increased lactate level after CPB was associated with the longer duration of ICU stay and increased risk of postoperative SAEs in pediatric cardiac surgery patients. Future studies should be conducted to determine the clinical utility of intraoperative trend of lactate levels.

DOI： 10.1186/s12871-015-0007-y

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Language：English   Publisher：AUSTRALASIAN MED PUBL CO LTD  

Objective: Delirium is a common complication in postoperative, critically ill patients. The mechanism of postoperative delirium is not well understood but many studies have shown significant associations between benzodiazepine use, alcohol withdrawal and cirrhosis, and an increased risk of delirium. We aimed to investigate a possible link with alterations of gamma-aminobutyric acid (GABA) activity.
Design, setting and participants: A prospective observational investigation of 40 patients >20 years old who had undergone elective surgery with general anaesthesia and were expected to need postoperative intensive care for more than 48 hours. We assessed postoperative delirium using the confusion assessment method in the intensive care unit at 1 hour after the operation and on postoperative Day (POD) 1 and POD 2. We collected blood samples for measurement of plasma GABA concentrations before the operation and on POD 1 and 2.
Main outcome measures: Postoperative delirium and perioperative plasma GABA concentrations in patients with and without delirium. Results: Postoperative delirium occurred in 13 of the patients. Patients with delirium had significantly higher Acute Physiology and Chronic Health Evaluation IF scores than patients without delirium. The mean plasma GABA concentration on POD 2 was significantly lower in patients with delirium than in those without delirium. After adjustment of relevant variables, plasma GABA concentration on POD 2 was independently associated with postoperative delirium.
Conclusions: Plasma GABA level on POD 2 has a significant independent association with postoperative delirium.

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

We encountered a 74-year-old male patient with tongue laceration after convulsive seizures under intensive care. The tongue showed severe swelling, and the right ventral surface had been lacerated by his isolated and pointed right lower canine. Our university hospital has established a perioperative management center, and is promoting interprofessional collaboration, including dentists, in perioperative management. Dentists collaborating in the perioperative management center took dental impressions, with the support of anesthesiologists who opened the patient's jaw under propofol sedation, to produce a mouth protector. By raising the patient's bite, the completed mouth protector prevented the isolated tooth from contacting the tongue and protected the lacerated wound. Use of the mouth protector prevented the lacerated tongue from coming into contact with the pointed tooth, and the tongue healed gradually. These findings underscore that interprofessional collaboration including dentists can improve the quality of medical care.

DOI： 10.18926/AMO/53027

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Language：English   Publisher：OKAYAMA UNIV MED SCHOOL  

The main purpose of this study was to determine the relationships between Japanese individuals' interest in living wills and their preferred end-of-life care and death locations. Questionnaires were mailed to 1,000 individuals aged >= 50 to measure these 2 factors. We examined the associations between the respondents' characteristics and their preferred care and death locations by using multinomial logistic regression models. The response rate was 74%. Home was the most frequently preferred place for end-of-life care (64%), and a palliative care unit (PCU) was the most commonly preferred place to die (51%). Living will interest was associated with a preference for care (odds ratio [OR] 4.74, 95% confidence interval [CI] 1.95-12.1) and death (OR 2.75, 95% CI 1.70-4.47) in a PCU rather than a hospital, but it was not associated with the choice between receiving care or dying at home instead of a hospital. We must consider why Japanese people think home death is impracticable. The Japanese palliative care system should be expanded to meet patients' end-of-life needs, and this includes not only facilitating home care but also increasing access to PCU care.

DOI： 10.18926/AMO/53023

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DOI： 10.2199/jjsca.34.169

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DOI： 10.11321/jjspc.13-0033

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Language：English   Publisher：DOVE MEDICAL PRESS LTD  

Metastatic bone cancer causes severe pain, but current treatments often provide insufficient pain relief. One of the reasons is that mechanisms underlying bone cancer pain are not solved completely. Our previous studies have shown that brain-derived neurotrophic factor (BDNF), known as a member of the neurotrophic family, is an important molecule in the pathological pain state in some pain models. We hypothesized that expression changes of BDNF may be one of the factors related to bone cancer pain; in this study, we investigated changes of BDNF expression in dorsal root ganglia in a rat bone cancer pain model. As we expected, BDNF mRNA (messenger ribonucleic acid) and protein were significantly increased in L3 dorsal root ganglia after intra-tibial inoculation of MRMT-1 rat breast cancer cells. Among the eleven splice-variants of BDNF mRNA, exon 1-9 variant increased predominantly. Interestingly, the up-regulation of BDNF is localized in small neurons (mostly nociceptive neurons) but not in medium or large neurons (non-nociceptive neurons). Further, expression of nerve growth factor (NGF), which is known as a specific promoter of BDNF exon 1-9 variant, was significantly increased in tibial bone marrow. Our findings suggest that BDNF is a key molecule in bone cancer pain, and NGF-BDNF cascade possibly develops bone cancer pain.

DOI： 10.2147/JPR.S63527

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

Purpose: Delirium is a common complication in postoperative critically ill patients. Although abnormal melatonin metabolism is thought to be one of the mechanisms of delirium, there have been few studies in which the association between alteration of perioperative plasma melatonin concentration and postoperative delirium was assessed.
Materials: We conducted a prospective observational study to assess the association of perioperative alteration of plasma melatonin concentration with delirium in 40 postoperative patients who required intensive care for more than 48 hours. We diagnosed postoperative delirium using Confusion Assessment Method for the intensive care unit and measured melatonin concentration 4 times (before the operation as the preoperative value, 1 hour after the operation, postoperative day 1, and postoperative day 2).
Results: Postoperative delirium occurred in 13 (33%) of the patients. Although there was no significant difference in preoperative melatonin concentration, Delta melatonin concentration at 1 hour after the operation was significantly lower in patients with delirium than in those without delirium (-1.1 vs 0 pg/mL, P = .036). After adjustment of relevant confounders, Delta melatonin concentration was independently associated with risk of delirium (odds ratio, 0.50; P = .047).
Conclusions: Delta melatonin concentration at 1 hour after the operation has a significant independent association with risk of postoperative delirium. (c) 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jcrc.2012.11.004

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Language：English   Publisher：PUBLIC LIBRARY SCIENCE  

Hemorrhagic shock and resuscitation induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent cytoprotective, anti-inflammatory, and anti-oxidant effects. This study aimed to examine the effects of intravenous biliverdin administration on lung injury induced by hemorrhagic shock and resuscitation in rats. Biliverdin or vehicle was administered to the rats 1 h before sham or hemorrhagic shock-inducing surgery. The sham-operated rats underwent all surgical procedures except bleeding. To induce hemorrhagic shock, rats were bled to achieve a mean arterial pressure of 30 mmHg that was maintained for 60 min, followed by resuscitation with shed blood. Histopathological changes in the lungs were evaluated by histopathological scoring analysis. Inflammatory gene expression was determined by Northern blot analysis, and oxidative DNA damage was assessed by measuring 8-hydroxy-2' deoxyguanosine levels in the lungs. Hemorrhagic shock and resuscitation resulted in prominent histopathological damage, including congestion, edema, cellular infiltration, and hemorrhage. Biliverdin administration prior to hemorrhagic shock and resuscitation significantly ameliorated these lung injuries as judged by histopathological improvement. After hemorrhagic shock and resuscitation, inflammatory gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase were increased by 18- and 8-fold, respectively. Inflammatory gene expression significantly decreased when biliverdin was administered prior to hemorrhagic shock and resuscitation. Moreover, after hemorrhagic shock and resuscitation, lung 8-hydroxy-2' deoxyguanosine levels in mitochondrial DNA expressed in the pulmonary interstitium increased by 1.5-fold. Biliverdin administration prior to hemorrhagic shock and resuscitation decreased mitochondrial 8-hydroxy-2' deoxyguanosine levels to almost the same level as that in the control animals. We also confirmed that biliverdin administration after hemorrhagic shock and resuscitation had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against hemorrhagic shock and resuscitation-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

DOI： 10.1371/journal.pone.0063606

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Language：English   Publisher：SPANDIDOS PUBL LTD  

Even after successful resuscitation, hemorrhagic shock frequently causes pulmonary inflammation that induces acute lung injury (ALI). We previously demonstrated that when CO is inhaled at a low concentration both prior to and following hemorrhagic shock and resuscitation (HSR) it ameliorates HSR-induced ALI in rats due to its anti-inflammatory effects. In the present study, we administered CO to the same model of ALI only after resuscitation and examined whether it exerted a therapeutic effect without adverse events on HSR-induced ALI, since treatment of animals with CO prior to HSR did not prevent lung injury. HSR were induced by bleeding animals to achieve a mean arterial pressure of 30 mmHg for I h followed by resuscitation with the removed blood. HSR resulted in the upregulation of inflammatory gene expression and increased the rate of apoptotic cell death in the lungs. This was determined from an observed increase in the number of cells positive for transferase-mediated dUTP-fluorescein isothiocyanate (FITC), nick-end labeling staining and activated caspase-3. HSR also resulted in prominent histopathological damage, including congestion, edema, cellular infiltration and hemorrhage. By contrast, CO inhalation for 3 h following resuscitation significantly ameliorated these inflammatory events, demonstrated by reduced histological damage, inflammatory mediators and apoptotic cell death. The protective effects of CO against lung injury were notably associated with an increase in the protein expression level of peroxisome proliferator-activated receptor (PPAR)-gamma, an anti-inflammatory transcriptional regulator in the lung. Moreover, CO inhalation did not affect the hemodynamic status or tissue oxygenation during HSR. These findings suggest that inhalation of CO at a low concentration exerts a potent therapeutic effect against HSR-induced ALI and attenuates the inflammatory cascade by increasing PPAR-gamma protein expression.

DOI： 10.3892/mmr.2012.1173

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Language：English   Publisher：SPANDIDOS PUBL LTD  

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IX alpha. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-I gene expression by polymerase chain reaction and HO-I localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-I gene expression levels significantly increased after I/R. In addition, HO-I levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-I gene expression levels. These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO-1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-I gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage.

DOI： 10.3892/ijmm.2011.821

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Language：English   Publisher：SPANDIDOS PUBL LTD  

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IX alpha. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-I gene expression by polymerase chain reaction and HO-I localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-I gene expression levels significantly increased after I/R. In addition, HO-I levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-I gene expression levels. These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO-1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-I gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage.

DOI： 10.3892/ijmm.2011.821

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Language：English   Publisher：HINDAWI PUBLISHING CORPORATION  

Little is known on the clinical effects of chloride on critically ill patients. We conducted this retrospective, observational study in 488 critically ill patients to investigate the incidence of chloride abnormalities, effects of hypochloremia in acid-base disorders, and association between chloride and clinical outcome. The study involved retrieval of arterial blood gas analyses, biochemical and demographical data from electrical records as well as quantitative acid-base analyses. For statistical analysis, the patients were stratified into three groups according to their chloride level (normal range: 98-106 mEq/L). The distribution of chloride levels was hyperchloremia 16.6%, normochloremia 74.6%, and hypochloremia 8.8%. The hypochloremic group was significantly alkalemic (P < 0.0001) and has significantly higher apparent strong ion difference (SIDa) (P < 0.0001) compared to the two other groups. The hypochloremic group had significantly longer stays in the ICU and hospital (P < 0.0001) with higher mortality (P < 0.0001). However, multiple regression analysis showed that chloride was not an independent factor of poorer outcome. In conclusion, the acid-base characteristics of the hypochloremic patients were alkalemia coexisting with higher SIDa. And although it was not an independent prognostic factor, hypochloremia was related to poorer outcome in critically ill settings.

DOI： 10.1100/2012/474185

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Language：English   Publisher：SPRINGER TOKYO  

Purpose The benefit of tranexamic acid (TXA) in pediatric cardiac surgery on postoperative bleeding has varied among studies. It is also unclear whether the effects of TXA differ between cyanotic patients and acyanotic patients. The aim of this study was to test the benefit of TXA in pediatric cardiac surgery in a well-balanced study population of cyanotic and acyanotic patients.
Methods A total of 160 pediatric patients undergoing cardiac surgery with cardiopulmonary bypass (81 cyanotic, 79 acyanotic) were included in this single-blinded, randomized trial at a tertiary care university-affiliated teaching hospital. Eighty-one children (41 cyanotic, 40 acyanotic) were randomly assigned to a TXA group, in which they received 50 mg/kg of TXA as a bolus followed by 15 mg/kg/h infusion and another 50 mg/kg into the bypass circuit. The other 79 patients were randomly assigned to a placebo group. The primary end point was the amount of 24-h blood loss.
Results The amount of 24-h blood loss was significantly less in the TXA group than in the placebo group [mean (95% confidence interval): 18.6 (15.8-21.4) vs. 23.5 (19.4-27.5) ml/kg, respectively; mean difference -4.9 (-9.7 to -0.01) ml/kg; p = 0.049]. This effect of TXA was already significant at 6 h [9.5 (7.5-11.5) vs. 13.2 (10.6-15.9) ml/kg, respectively; mean difference -3.47 (-7.0 to -0.4) ml/kg; p = 0.027]. However, there was no significant difference in the amount of blood transfusion between the groups. There was also no statistical difference in the effect of TXA in each cyanotic and acyanotic subgroup.
Conclusion TXA can reduce blood loss in pediatric cardiac surgery but not the transfusion requirement (http://ClinicalTrials.gov number NCT00994994).

DOI： 10.1007/s00540-011-1235-z

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/CCM.0b013e31820a4f61

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Language：English   Publisher：OXFORD UNIV PRESS  

Some patients with cirrhosis experience rupture of venous varices before operation, and liver transplantation is a therapy of last resort for these patients. However, we have experienced two cases of intraoperative rupture in whom no abnormalities of the venous varices were seen on endoscopy before operation. One patient with ruptured gastrointestinal varices was treated by direct surgical ligation and the other with ruptured oesophageal gastric varices, spontaneously recovered with a Sengstaken-Blakemore tube. These cases suggest that acute variceal haemorrhage should always be considered as a possibility during living-donor liver transplantation in patients with a history of upper gastrointestinal bleeding. Careful observation of the nasogastic tube is important during clamping of the hepatic portal vein.

DOI： 10.1093/bja/aer008

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Language：English   Publisher：SPRINGER TOKYO  

Pituitary apoplexy occurring after surgery is a rare but life-threatening acute clinical condition that follows extensive hemorrhagenous necrosis within a pituitary adenoma. Pituitary apoplexy has been reported to occur spontaneously in the majority of cases or in association with various inducing factors. Reported is a case of pituitary apoplexy complicated by diabetes insipidus following living donor liver transplantation (LDLT). To the best of our knowledge, this has not been previously reported. A 56-year-old woman with nonalcoholic steatohepatitis underwent LDLT from her daughter. The patient also required dopamine support and transfusions because of massive intraoperative bleeding. Postoperatively, her coagulopathy continued, and she underwent a second laparotomy because of unknown bleeding on postoperative day 7, when she needed transfusions and dopamine support to maintain her vital signs. She complained of severe headache, excessive thirst, frequent urination, and diplopia from postoperative day 10. She also had polyuria greater than 300 ml/h and was diagnosed with pituitary apoplexy precipitating diabetes insipidus on postoperative day 13. She was treated conservatively without surgery because of the hormonally inactive status and slight mass effect of her tumor. It is important for anesthesiologists and critical care personnel in LDLT settings to take into consideration this complication as a differential diagnosis.

DOI： 10.1007/s00540-010-1070-7

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DOI： 10.3918/jsicm.18.215

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Language：English   Publisher：IOP PUBLISHING LTD  

Despite recent progress in Critical Care Medicine, sepsis is still a major medical problem with a high rate of mortality and morbidity especially in intensive care units. Oxidative stress induced by inflammation associated with sepsis causes degradation of heme protein, increases microsomal free heme content, promotes further oxidative stress and results in cellular and organ damage. Heme-oxygenase-1 (HO-1) is a rate-limiting enzyme for heme breakdown. HO-1 breaks down heme to yield CO, iron and biliverdin. Measurement of CO in exhaled air may potentially be useful in monitoring changes in HO enzyme activity in vivo, which might reflect the degree of inflammation or oxidative stress in patients with systemic inflammation. The increased exhaled CO concentrations were observed after anesthesia/surgery, in critically ill patients and also in systemic inflammation/sepsis. Some reports also showed that exhaled CO concentration is related to mortality. Further studies are needed to elucidate whether increased endogenous CO production may predict a patient's morbidity and mortality. Techniques for monitoring CO are continuously being refined and this technique may find its way into the office of clinicians.

DOI： 10.1088/1752-7155/4/4/047103

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Language：English   Publisher：SPANDIDOS PUBL LTD  

The progression and interrelationship of mediators that are released, activated or suppressed after major surgery appear to play an important role in responses to surgical stress. Heat shock protein 70 (HSP70) is stress-induced and acts like a cytokine to modulate pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS), by stimulating toll-like receptor 4 (TLR4) signaling. We hypothesized that this effect would occur after major surgery, such as esophagectomy. We therefore measured the expression of HSP70, TLR4, TNF-alpha and iNOS mRNA in peripheral blood mononuclear cells (PBMCs) from 11 patients who underwent esophagectomy with thoracoabdominal procedures at postoperative day (POD) 1 and POD3 using real-time polymerase chain reaction, and compared the results to expression levels in 6 healthy adult volunteers (controls). We also measured plasma cortisol as a well-known stress hormone. The expression of HSP70 mRNA in PBMCs was 2.1-fold higher on POD1 compared to the controls (P=0.041) and was positively correlated with TLR4 mRNA (r(2)=0.45, P=0.0007). The expression of TNF-alpha mRNA tended to be lower on POD1 (P=0.055) and was significantly decreased on POD3 (P=0.016), and iNOS mRNA were significantly lower on POD1 (P=0.0015) and POD3 (P=0.0003) compared to the controls. Moreover, there was a positive correlation between the expression of TLR4 mRNA and plasma cortisol levels (r(2)=0.24, P=0.021). The expression of HSP70 mRNA in PBMCs in the early postoperative period was significantly higher and positively correlated with TLR4 mRNA. This suggests that HSP70-TLR4 signaling has an important role in postoperative inflammatory responses. However, the expression of pro-inflammatory mediators, including TNF-alpha and iNOS mRNA, was significantly decreased postoperatively. This may be caused by the anti-inflammatory mechanism of cortisol. Our findings indicate that responses to surgical stress reflect simultaneous pro-inflammatory and anti-inflammatory responses, and are complex.

DOI： 10.3892/mmr.2010.335

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Language：English   Publisher：SPRINGER TOKYO  

Thrombotic microangiopathy (TMA) is a rare but potentially lethal complication encountered in solid organ and bone marrow transplant recipients that requires rapid recognition, diagnosis, and initiation of therapy. Several causes have been identified, including viral infections and various medications. We report a case of TMA after living-donor liver transplantation (LDLT). A 60-year-old man underwent LDLT for end-stage liver disease secondary to hepatitis C virus. After 6 months, he required re-transplantation because graft failure was caused by a small-for-size graft. The immunosuppressive regimen for the second transplantation consisted of tacrolimus and prednisolone; cyclosporine (CsA), mycophenolate mofetil, and prednisolone had been used for the first transplantation. Despite multiple transfusions of packed red blood cells and concentrated platelets, his hemoglobin and platelets decreased and lactate dehydrogenase increased following re-transplantation. Hematological evaluation revealed findings consistent with TMA. As soon as TMA was diagnosed, the calcineurin inhibitor (CNI) was changed from tacrolimus to CsA, and fresh frozen plasma (FFP) was given. The patient's platelets gradually increased after the CNI was changed, and no transfusions were needed. Therefore, tacrolimus was suspected as the cause of the patient's TMA. Early diagnosis, switching CNIs, and FFP supplementation allowed the TMA to resolve without the need for plasma exchange.

DOI： 10.1007/s00540-010-0953-y

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Background: Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Carbon monoxide (CO), a by-product of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. The aim of this study was to examine the effects of CO inhalation at low concentration on lung injury induced by HSR in rats.
Methods: Rats were subjected to HSR by bleeding to achieve mean arterial pressure of 30 mm Hg for 60 minutes followed by resuscitation with shed blood and saline as needed to restore blood pressure. HSR animals were either maintained in room air or were exposed to CO at 250 ppm for 1 hour before and 3 hours after HSR.
Results: HSR caused an increase in the DNA binding activity of nuclear factor-kappa B and activator protein-1 in the lung followed by the up-regulation of pulmonary gene expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and interleukin (IL)-10. HSR also resulted in an increase in myeloperoxidase activity and wet weight to dry weight ratio in the lung, and more prominent histopathologic changes including congestion, edema, cellular infiltration, and hemorrhage. In contrast, CO inhalation significantly ameliorated these inflammatory events as judged by fewer histologic changes, less up-regulation of inflammatory mediators, and less activation of nuclear factor-kappa B and activator protein-1. Interestingly, the protective effects against lung injury afforded by CO were associated with further increases in mRNA expression of IL-10 in the lung.
Conclusions: These findings suggest that inhaled CO at a low concentration ameliorated HSR-induced lung injury and attenuated inflammatory cascades by up-regulation of anti-inflammatory IL-10.

DOI： 10.1097/TA.0b013e3181bbd516

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Language：English   Publisher：SPRINGER  

Sepsis is the most common trigger for acute kidney injury (AKI) in critically ill patients. We sought to determine whether there are unique patterns to plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in septic compared with non-septic AKI.
Prospective observational study.
Two adult ICUs in Melbourne, Australia.
Critically ill patients with septic and non-septic AKI.
None.
Blood and urine specimens collected at enrollment, 12, 24 and 48 h to measure plasma and urine NGAL. Eighty-three patients were enrolled (septic n = 43). Septic AKI patients had more co-morbid disease (p = 0.005), emergency surgical admissions (p < 0.001), higher illness severity (p = 0.008), more organ dysfunction (p = 0.008) and higher white blood cell counts (p = 0.01). There were no differences at enrollment between groups in AKI severity. Septic AKI was associated with significantly higher plasma (293 vs. 166 ng/ml) and urine (204 vs. 39 ng/mg creatinine) NGAL at enrollment compared with non-septic AKI (p < 0.001). Urine NGAL remained higher in septic compared with non-septic AKI at 12 h (p < 0.001) and 24 h (p < 0.001). Plasma NGAL showed fair discrimination for AKI progression (area under receiver-operator characteristic curve 0.71) and renal replacement therapy (AuROC 0.78). Although urine NGAL performed less well (AuROC 0.70, 0.70), peak urine NGAL predicted AKI progression better in non-septic AKI (AuROC 0.82).
Septic AKI patients have higher detectable plasma and urine NGAL compared with non-septic AKI patients. These differences in NGAL values in septic AKI may have diagnostic and clinical relevance as well as pathogenetic implications.

DOI： 10.1007/s00134-009-1724-9

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DOI： 10.3892/ijmm-00000430

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DOI： 10.3918/jsicm.17.353

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes. However, there is lack of information on how and under what conditions continuous renal replacement therapy is discontinued.
Design: Post hoc analysis of a prospective observational study.
Setting. Fifty-four intensive care units in 23 countries.
Patients: Five hundred twenty-nine patients (52.6%) who survived initial therapy among 1006 patients treated with continuous renal replacement therapy.
Interventions: None.
Measurements and Main Results., Three hundred thirteen patients were removed successfully from continuous renal replacement therapy and did not require any renal replacement therapy for at least 7 days and were classified as the "success" group and the rest (216 patients) were classified as the "repeat-RRT" (renal replacement therapy) group. Patients in the "success" group had lower hospital mortality (28.5% vs. 42.7%, p < .0001) compared with patients in the "repeat-RRT" group. They also had lower creatinine and urea concentrations and a higher urine output at the time of stopping continuous renal replacement therapy. Multivariate logistic regression analysis for successful discontinuation of continuous renal replacement therapy identified urine output (during the 24 hrs before stopping continuous renal replacement therapy: odds ratio, 1.078 per 100 mL/day increase) and creatinine (odds ratio, 0.996 per mu mol/L increase) as significant predictors of successful cessation. The area under the receiver operating characteristic curve to predict successful discontinuation of continuous renal replacement therapy was 0.808 for urine output and 0.635 for creatinine. The predictive ability of urine output was negatively affected by the use of diuretics (area under the receiver operating characteristic curve, 0.671 with diuretics and 0.845 without diuretics).
Conclusions. We report on the current practice of discontinuing continuous renal replacement therapy in a multinational setting. Urine output at the time of initial cessation (if continuous renal replacement therapy was the most important predictor of successful discontinuation, especially if occurring without the administration of diuretics. (Crit Care Med 2009; 37:2576-2582)

DOI： 10.1097/CCM.0b013e3181a38241

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Language：English   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Validation of a scoring algorithm for non-overt disseminated intravascular coagulation (DIC) proposed by the International Society on Thrombosis and Haemostasis (ISTH) is still incomplete. It was the objective of this study to assess the impact of including AT to non-overt DIC scoring on the predictability for intensive care unit (ICU) death and the later development of overt-DIC defined by the Japanese Ministry of Health and Welfare (JMHW) or the ISTH. We performed a retrospective observational study conducted in 364 patients in critical care. Coagulation parameters obtained daily for DIC screening were utilised for scoring. There were 194 and 196 patients scored as positive non-overt DIC with and without AT, respectively; diagnostic agreement between the two was 78%. As compared with patients without non-overt DIC, these non-overt DIC patients had significantly higher mortality. In 37 ICU non-survivors, positive non-overt DIC scoring with AT preceded ICU death by a median of 6.8 days, which was significantly earlier as compared with a median of 5.4 days for non-overt DIC without AT (p=0.022). In patients who developed overt-DIC after admission, the time period from positive non-overt DIC to positive overt-DIC was significantly longer when AT was utilised (overt-DIC ISTH; 1.3 days vs. 0.1 days, p=0.004, overt-DIC JMHW; 2.5 days vs. 2.0 days, p=0.04, with AT vs. without AT, respectively). Non-overt DIC scoring predicted a high risk of death in critically ill patients. When information on AT levels was included, non-overt DIC scoring was found to predict development of overt-DIC significantly earlier than non-overt DIC scoring without AT.

DOI： 10.1160/TH08-07-0448

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

Purpose: The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes.
Methods: This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients.
Results: Timing of RRT was stratified into "early" and "late" by median urea and creatinine at the time RRT was started. Timing was also categorized temporally from ICU admission into early (<2 days), delayed (2-5 days), and late (>5 days). Renal replacement therapy timing by serum urea showed no significant difference in crude (63.4% for urea <= 24.2 mmol/L vs 61.4% for urea >24.2 mmol/L; odds ratio [OR], 0.92; 95% confidence interval [CI], 0.73-1.15; P = .48) or covariate-adjusted mortality (OR, 1.25; 95% CI, 0.91-1.70; P = .16). When stratified by creatinine, late RRT was associated with lower crude (53.4% for creatinine >309 mu mol/L vs 71.4% for creatinine <= 309 mu mol/L; OR, 0.46; 95% CI, 0.36-0.58; P < .0001) and covariate-adjusted mortality (OR, 0.51; 95% CI, 0.37-0.69; P < .001).However, for timing relative to ICU admission, late RRT was associated with greater crude (72.8% vs 62.3% vs 59%, P < .001) and covariate-adjusted mortality (OR, 1.95; 95% CI, 1.30-2.92; P = .001). Overall, late RRT was associated with a longer duration of RRT and stay in hospital and greater dialysis dependence.
Conclusion: Timing of RRT, a potentially modifiable factor, might exert an important influence on patient survival. However, this largely depended on its definition. Late RRT (days from admission) was associated with a longer duration of RRT, longer hospital stay, and higher dialysis dependence. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jcrc.2007.12.017

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Language：English   Publishing type：Book review, literature introduction, etc.   Publisher：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.

DOI： 10.3164/jcbn.08-210-HO

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Language：English   Publishing type：Book review, literature introduction, etc.  

Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.

DOI： 10.3164/jcbn.08-210-HO

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Hemorrhagic shock (HS) is an oxidative stress that causes intestinal tissue injury. Heme oxygenase 1 (HO-1) is induced by oxidative stress and is thought to play an important role in the protection of tissues from oxidative injury. We previously reported the ileum to be the most susceptible to HS-induced tissue injury site in the intestine because HO-1 induction is the lowest at this site. We also previously demonstrated that glutamine (GLN) significantly induced HO-1 in the lower intestinal tract. In the present study, we investigated whether GLN pretreatment improves HS-induced intestinal tissue injury in the ileum by HO-1 induction. Treatment of rats with GLN (0.75 g/kg, i.v.) markedly induced functional HO-1 protein in mucosal epithelial cells in the ileum. Glutamine treatment before HS (MAP of 30 mmHg for 60 min) significantly ameliorated HS-induced mucosal inflammation and apoptotic cell death in the ileum, as judged by significant decreases in gene expression of TNF-alpha, iNOS, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1, myeloperoxidase activity, the number of infiltrated neutrophils, DNA fragmentation by in situ oligo ligation assay, and activated caspase-3 expression, and by increases in gene expression of IL-10 and Bcl-2. In contrast, treatment with tin mesoporphyrin, a specific inhibitor of HO activity, abolished the beneficial effect of GLN pretreatment. These findings indicate that GLN pretreatment significantly ameliorated tissue injury in the ileum after HS by inducing HO-1. Glutamine treatment may thus protect mucosal cells from HS-induced oxidative damage via the anti-inflammatory and antiapoptotic properties of HO-1.

DOI： 10.1097/SHK.0b013e318177823a

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Language：English   Publishing type：Book review, literature introduction, etc.  

Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.

DOI： 10.3164/jcbn.08-210-HO

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Language：English   Publisher：IOS PRESS  

Impaired deformability might contribute to the accumulation of activated leukocytes within pulmonary microcapillaries, leading to acute lung injury. The purpose of our study was to investigate changes in leukocyte deformability during periods of inflammation after esophagectomy. The study group comprised 20 patients who underwent esophagectomy. Changes in leukocyte deformability were investigated by examining filtration through a silicon microchannel, which simulated human pulmonary microcapillaries. Changes in the neutrophil cytoskeleton were investigated by measuring neutrophil F-actin assembly. The severity of patient clinical outcome was evaluated by the lung injury score. Leukocyte filtration through the microchannel was significantly weaker in esophagectomy patients than in healthy subjects (p < 0.01). After esophagectomy, filtration was further impaired compared with preoperative values (p < 0.05). The neutrophil F-actin content was higher in patients than in controls (p < 0.01), and increased after esophagectomy compared with preoperative values (p < 0.01). We concluded that circulating leukocytes showed reduced deformability and appeared to be sequestered within microcapillaries after esophagectomy. Changes in neutrophil cytoskeleton were considered to be responsible for the reduced deformability. Leukocyte accumulation within pulmonary microcapillaries might be related to the pathogenesis of lung injury after esophagectomy.

DOI： 10.3233/CH-2009-1164

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Language：English   Publisher：BENTHAM SCIENCE PUBL LTD  

Treatment of rats with monocrotaline (MCT), a pyrrolizidine alkaloid plant toxin, is known to cause pulmonary hypertension (PH), and it has been used as a useful experimental model of PH. Recent findings suggested that pulmonary inflammation may play a significant role in the pathogenesis of MCT-induced PH. We also demonstrated that, following MCT administration to rats, there was a significant and sustained increase in the pulmonary expression of heme oxygenase-1 (HO-1), which is known to be induced by various oxidative stresses, including inflammation and free heme, and is thought to be essential in the protection against oxidative tissue injuries. In this study, we administered hemin (ferriprotoporphyrin chloride, 30 mol/kg b.w., subcutaneously), a potent inducer of HO-1, every 3 days to rats following subcutaneous administration of MCT (60 mg/kg) and examined its effect on MCT-induced PH and pulmonary inflammation. MCT administration caused pulmonary arterial wall thickening with marked elevation of right ventricular pressure, in association with prominent pulmonary inflammation as revealed by the increase in gene expression of tumor necrosis factor-alpha and the number of infiltrated neutrophils in the lung. In contrast, hemin treatment of MCT-administered animals, which led to a further increase in pulmonary HO-1 mRNA expression, significantly ameliorated MCT-induced PH as well as tissue inflammation. These findings suggest that hemin treatment ameliorates MCT-induced PH possibly mediated through induction of pulmonary HO-1 which leads to the attenuation of pulmonary inflammation.

DOI： 10.2174/157340608786241972

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Language：English   Publisher：SPRINGER  

DOI： 10.1007/s00134-008-1166-9

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Heme oxygenase (HO) 1 is inducible by a variety of oxidative stress and is thought to play an important role in the protection of tissues from oxidative injuries. Because hemorrhagic shock (HS) is an oxidative stress that results in tissue injury, we examined in this study the role of HO-1 induction in intestinal tissue injuries in a rat model of HS. The levels of HO-1 were significantly increased after HS both at transcriptional and protein levels in mucosal epithelia[ cells in the duodenum, jejunum, and colon, whereas their expression in the ileum was hardly detectable and not increased at all by the treatment. In contrast, HS-induced mucosal inflammation and apoptotic cell death in the duodenum, jejunum, and colon were far less than those observed in ileum as judged by the levels of expression of TNF-alpha, NOS, activated caspase 3, and BcI-2. Of note, inhibition of HO activity by tin-mesoporphyrin resulted in an aggravation of HS-induced tissue inflammation and apoptotic cell death. These findings indicate that HO-1 expression in the intestine is regulated in a highly site-specific manner after HS, and that HO-1 induction plays a fundamental role in protecting mucosal cells of the intestine from oxidative damages induced by HS.

DOI： 10.1097/shk.0b013e3180cab913

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Heme oxygenase (HO) 1 is inducible by a variety of oxidative stress and is thought to play an important role in the protection of tissues from oxidative injuries. Because hemorrhagic shock (HS) is an oxidative stress that results in tissue injury, we examined in this study the role of HO-1 induction in intestinal tissue injuries in a rat model of HS. The levels of HO-1 were significantly increased after HS both at transcriptional and protein levels in mucosal epithelia[ cells in the duodenum, jejunum, and colon, whereas their expression in the ileum was hardly detectable and not increased at all by the treatment. In contrast, HS-induced mucosal inflammation and apoptotic cell death in the duodenum, jejunum, and colon were far less than those observed in ileum as judged by the levels of expression of TNF-alpha, NOS, activated caspase 3, and BcI-2. Of note, inhibition of HO activity by tin-mesoporphyrin resulted in an aggravation of HS-induced tissue inflammation and apoptotic cell death. These findings indicate that HO-1 expression in the intestine is regulated in a highly site-specific manner after HS, and that HO-1 induction plays a fundamental role in protecting mucosal cells of the intestine from oxidative damages induced by HS.

DOI： 10.1097/shk.0b013e3180cab913

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DOI： 10.11321/jjspc.07-0019

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/01.CCM.0000284489.62413.90

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Language：English   Publisher：AMERICAN SOCIETY NEPHROLOGY  

Sepsis is the most common cause of acute kidney injury (AKI) in critical illness, but there is limited information on septic AKI. A prospective, observational study of critically ill patients with septic and nonseptic AKI was performed from September 2000 to December 2001 at 54 hospitals in 23 countries. A total of 1753 patients were enrolled. Sepsis was considered the cause in 833 (47.5%); the predominant sources of sepsis were chest and abdominal (54.3%). Septic AKI was associated with greater aberrations in hemodynamics and laboratory parameters, greater severity of illness, and higher need for mechanical ventilation and vasoactive therapy. There was no difference in enrollment kidney function or in the proportion who received renal replacement therapy (RRT; 72 versus 71%; P=0.83). Oliguria was more common in septic AKI (67 versus 57%; P<0.001). Septic AKI had a higher in-hospital case-fatality rate compared with nonseptic AKI (70.2 versus 51.8%; P<0.001). After adjustment for covariates, septic AKI remained associated with higher odds for death (1.48; 95% confidence interval 1.17 to 1.89; P=0.001). Median (IQR) duration of hospital stay for survivors (37 [19 to 59] versus 21 [12 to 42] d; P<0.0001) was longer for septic AKI. There was a trend to lower serum creatinine (106 [73 to 158] versus 121 [88 to 184] mu mol/L; P=0.01) and RRT dependence (9 versus 14%; P=0.052) at hospital discharge for septic AKI. Patients with septic AKI were sicker and had a higher burden of illness and greater abnormalities in acute physiology. Patients with septic AKI had an increased risk for death and longer duration of hospitalization yet showed trends toward greater renal recovery and independence from RRT.

DOI： 10.2215/CJN.03681106

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Language：English   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background. During perioperative management of patients with gastrointestinal cancer complicated by diabetes mellitus, adequate alimentation is required, but we often face difficulties associated with hyperglycemia and other accompanying complications. Recently, we investigated the effects of a novel palatinose based enteral formula (MHN-01) in suppressing post-prandial hyperglycemia and improving lipid metabolism in experimental animals and perioperative management of patients with esophageal cancer complicated by diabetes mellitus.
Materials and methods. We gave normal rats and rats with type 2 diabetes mellitus a single oral dose of fluid diet, and analyzed comparatively the time course of blood glucose level in each group until 3 h after the dose. In both the normal rat group and the type 2 diabetes group, peak blood glucose level after the MHN-01 dose was significantly lower than after a dose of ordinary fluid diet and was comparable to the peak level after a dose of a fluid diet rich in MUFA (monounsaturated fatty acid). We allowed normal mice free access to fluid diet for 43 days, and measured their body fat levels. Fat accumulation was significantly lower in mice given MHN-01 than in mice given ordinary fluid diet. We also analyzed the respiratory quotient and resting energy expenditure of normal Sprague-Dawley rats fed by MHN-01 or an ordinary fluid diet. The respiratory quotient of the MHN-01 group was significantly lower than the ordinary fluid group, although the resting energy expenditure of both groups was almost the same level. The effect of MHN-01 was estimated to be based on improvement of lipid metabolism.
Results. Between 2003 and 2005, among 164 patients who underwent radical thoracic esophagectomy and/or reconstruction for esophageal carcinoma at Okayama University Hospital, nine patients (5.5%) were diagnosed with diabetes mellitus in preoperative screening and were treated with MHN-01. Clinical courses of two cases with severe status of diabetes mellitus were presented as successful case reports of MHN-01.
Conclusion. MHN-01 was very useful in perioperative management of patients complicated by diabetes mellitus, unable to ingest food p.o. such as esophageal cancer or other diseases. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2006.06.025

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: We tested the hypothesis that the difference between indirect and direct sodium assays would be related to the plasma albumin concentration. Further, we proposed that differences between indirect and direct chloride assays might be explained by interference from other plasma constituents, particularly bicarbonate, and possibly albumin.
METHODS: We studied 300 critically ill patients at the time of admission to the intensive care unit (ICU) and compared each patient's plasma sodium and chloride measurements from a central laboratory assay (indirect electrode) and an ICU blood gas machine assay (direct electrode).
RESULTS: The central laboratory sodium measurement was, on average, 2.1 mmol/L more than the ICU assay, limits of agreement 1.8-2.4 mmol/L greater, P < 0.001. The central laboratory chloride measurement was, on average, I mmol/L less than the ICU assay (limits of agreement 1.3-0.7 mmol/L less, P < 0.001). All correlations between the assay differences and plasma constituents were weak except for a moderately strong correlation between differences in sodium measurements and albumin. The difference in plasma sodium concentration between the assays (central laboratory ICU) increased as the plasma concentration albumin decreased (difference 6.2-0.16 albumin (g/L); P < 0.001, r = -0.46, r(2) = 0.22).
CONCLUSIONS: The central laboratory and ICUs assays are analytic-ally, statistically, and clinically different for both sodium and chloride. Unless taken into account, the differences could be large enough in hypoalbuminemic populations (such as critically ill patients) to affect clinical diagnosis and decision making.

DOI： 10.1213/01.ane.0000258015.87381.61

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DOI： 10.2199/jjsca.27.28

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DOI： 10.2174/138955707781024517

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DOI： 10.2174/138955707781024517

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DOI： 10.1007/s00134-007-0754-4

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DOI： 10.3918/jsicm.14.611

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DOI： 10.1254/fpj.130.252

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DOI： 10.1254/fpj.130.252

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: To test whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in acid-base status and serum electrolytes.
Design: Nested cohort study.
Setting. Three general intensive care units.
Patients: Six hundred and ninety-one critically ill patients.
Interventions: Randomization of patients to receive blinded solutions of either 4% human albumin or normal saline for fluid resuscitation.
Measurements and Main Results. Albumin was given to 339 patients and saline to 352. At baseline, both groups had a similar serum bicarbonate, albumin, and base excess levels. After randomization, bicarbonate and base excess increased significantly and similarly over time (p <.0001). On multivariate analysis, fluid resuscitation with albumin predicted a smaller increase in pH (p =.0051), bicarbonate (p =.034), and base excess (p =.015). The amount of fluid was an independent predictor of pH (p <.0001), serum chloride (p <.0001), calcium (p =.0001), bicarbonate (p =.0002), and base excess (p <.0001) on the first day of treatment. In patients who received >3 L of fluids in the first 24 hrs, albumin administration was associated with a significantly greater increase in serum chloride (p =.0026). Acute Physiology and Chronic Health Evaluation II score and the presence of sepsis also independently predicted changes in several electrolytes and acid-base variables.
Conclusions. When comparing albumin and saline, the choice and amount of resuscitation fluid are independent predictors of acid-base status and serum electrolytes. When large volumes are given, albumin administration leads to a higher chloride concentration. However, overall differences between the types of fluid are minor, whereas the volume of fluid administered is a much stronger predictor of such changes, which are also influenced by illness severity and the passage of time.

DOI： 10.1097/01.CCM.0000242159.32764.86

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Decreases in plasma bicarbonate are associated with hyperchloremic acidosis and lactic acidosis. According to the Stewart approach to acid-base physiology, the strong-ion difference regulates plasma bicarbonate, with chloride and lactate being the only strong anions routinely measured in clinical chemistry. We hypothesized that the plasma strong-ion difference, both with and without lactate, would have a stronger association with plasma bicarbonate than plasma chloride alone would have with bicarbonate. We used plasma acid-base data from 300 critically ill patients. The correlation with bicarbonate became progressively weaker (P < 0.001): all measured strong ions, r = 0.60; measured strong ions without lactate, r = 0.42; chloride alone, r = -0.27. In a subgroup of 26 patients with traditional hyperchloremic acidosis (base excess < -2mmol/L and anion gap < 17 mmol/L), the measured strong-ion difference (without lactate) had a stronger correlation (P < 0.001) with bicarbonate than chloride had: r = 0.85 versus r = -0.60. We conclude that hyperchloremic acidosis and lactic acidosis are strong-ion acidoses. Hyperchloremia should be viewed relative to the plasma strong cations. A practical conclusion is that both managing and preventing acid-base disorders with IV fluid therapy involves manipulating each of the plasma strong ions, particularly sodium and chloride.

DOI： 10.1213/01.ane.0000221449.67354.52

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Language：English  

A 13-year-old boy with epidermolysis bullosa underwent a repair of pseudosyndactyly. He had a long history of bullae formation in the oral cavity and on the pharynx and body surface, and some were active at the time of surgery. We chose inhalational general anesthesia with tracheal intubation using sevoflurane and nitrous oxide. The trachea was successfully extubated after the surgery, and no major bulla formation was observed. General anesthesia with tracheal intubation may be chosen as anesthesia for patients with epidermolysis bullosa. © JSA 2006.

DOI： 10.1007/s00540-006-0388-7

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Language：English  

Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. We previously demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1, ameliorated HSR-induced lung injury and inflammation. Cellular redox state is known to modulate the DNA biding activity of the transcription factors
nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). In the present study, we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its effect on the DNA binding activity of NF-κB and AP-1 at 1.5 h after HSR. HSR significantly increased the DNA binding activity of NF-κB as well as AP-1, while HA pretreatment markedly attenuated the activities of these transcription factors. In contrast, administration of tin mesoporphyrin, a specific competitive inhibitor of HO activity, to HA-pretreated animals abolished the suppressive effect of HA on the activities of NF-κB and AP-1, and increased these activities to almost the same level as those in HSR animals. Our findings indicate that HA pretreatment can significantly suppress the increased activity of NF-κB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR-induced lung injury at least in part mediated through the suppression of the activities of these transcription factors. © 2006 Bentham Science Publishers Ltd.

DOI： 10.1263/jbb.101.271

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Language：English   Publisher：AMER PHYSIOLOGICAL SOC  

It has been reported that exhaled carbon monoxide (CO) concentrations and arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in critically ill patients. However, there was no study that examined correlation among amount of CO in exhaled air, CO-Hb concentrations in erythrocytes, and bilirubin IX alpha (BR) in serum, i.e., the three major indexes of heme catabolism, within the same subject. Here, we examined CO concentrations in exhaled air, CO-Hb concentrations in arterial blood, and BR levels in serum in 29 critically ill patients. Measurements of exhaled CO, arterial CO-Hb, and serum total BR have been done in the intensive care unit. As control, exhaled CO concentration was also measured in eight healthy volunteers. A median exhaled CO concentration was significantly higher in critically ill patients compared with control. There was significant correlation between CO and CO-Hb and CO and total BR level. We also found CO concentrations correlated with indirect BR but not direct BR. Multivariate linear regression analysis for amount of exhaled CO concentrations also showed significant correlation with CO-Hb and total BR, despite the fact that respiratory variables of study subjects were markedly heterogeneous. We found no correlation among exhaled CO, patients' severity, and degree of inflammation, but we found a strong trend of a higher exhaled CO concentration in survivors than in nonsurvivors. These findings suggest there is an increased heme breakdown in critically ill patients and that exhaled CO concentration, arterial CO-Hb, and serum total BR concentrations may be useful markers in critically ill conditions.

DOI： 10.1152/ajplung.00031.2005

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Language：English   Publisher：BIOMED CENTRAL LTD  

Introduction The choice of invasive systemic haemodynamic monitoring in critically ill patients remains controversial as no multicentre comparative clinical data exist. Accordingly, we sought to study and compare the features and outcomes of patients who receive haemodynamic monitoring with either the pulmonary artery catheter (PAC) or pulse contour cardiac output (PiCCO) technology.
Methods We conducted a prospective multicentre, multinational epidemiological study in a cohort of 331 critically ill patients who received haemodynamic monitoring by PAC or PiCCO according to physician preference in intensive care units (ICUs) of eight hospitals in four countries. We collected data on haemodynamics, demographic features, daily fluid balance, mechanical ventilation days, ICU days, hospital days, and hospital mortality. We statistically compared the two techniques.
Results Three hundred and forty-two catheters ( PiCCO 192 and PAC 150) were inserted in 331 patients. On direct comparison, patients with PAC were older ( 68 versus 64 years of age; p = 0.0037), were given inotropic drugs more frequently 37.3% versus 13%; p < 0.0001), and had a lower cardiac index (2.6 versus 3.2 litres/ minute per square meter; p < 0.0001). Mean daily fluid balance was significantly greater during PiCCO monitoring (+ 659 versus + 350 ml/day; p = 0.017) and mechanical ventilation-free days were fewer ( 12 for PiCCO versus 21 for PAC; p = 0.045). However, after multiple regression analysis, we found no significant effect of monitoring technique on mean daily fluid balance, mechanical ventilation-free days, ICU-free days, or hospital mortality. A secondary multiple logistic regression analysis for hospital mortality which included mean daily fluid balance showed that positive fluid balance was a significant predictor of hospital mortality ( odds ratio = 1.0002 for each ml/day; p = 0.0073).
Conclusion On direct comparison, the use of PiCCO was associated with a greater positive fluid balance and fewer ventilator-free days. After correction for confounding factors, the choice of monitoring did not influence major outcomes, whereas a positive fluid balance was a significant independent predictor of outcome. Future studies may best be targeted at understanding the effect of pursuing different fluid balance regimens rather than monitoring techniques per se.

DOI： 10.1186/cc5126

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

We investigated whether perioperative extensive epidural block (C3-L) affects postoperative immune response in patients undergoing radical esophagectomy. Patients undergoing radical esophagectomy were randomly assigned to either general anesthesia with continuous epidural infusion via 2 epidural catheters that was continued for postoperative analgesia (group E, n = 15) or intraoperative general anesthesia and postoperative IV morphine analgesia (group G, n = 15). Plasma levels of stress hormones, cytokines, C-reactive protein (CRP), leukocyte counts, and distribution of lymphocyte subsets were assessed before and after surgery and on postoperative days (PODs) 1 and 3. In comparison with group E, significant increases in plasma epinephrine level at the end of surgery (P < 0.05) and norepinephrine level at the end of surgery (P < 0.01) and on POD1 (P < 0.01) and POD3 (P < 0.01) and significant decrease in cluster of differentiation (CD4/CD8 ratio) at the end of surgery (P < 0.05) were observed in group G. However, there were no significant differences in other variables between groups. In both groups, plasma cortisol, adrenocorticotropic hormone, interleukin (IL)-1 beta, IL-6, IL-10, and CRP levels were increased after surgery (each group P < 0.01) and IL-1 beta, IL-6, IL-10, and CRP were still increased on POD1 and POD3 (each change, each group P < 0.01). Leukocyte counts were increased on PODI (each group P < 0.05) and POD3 (each group P < 0.01). The proportion of lymphocytes decreased from the end of surgery to POD3 (each group P < 0.01). The proportion of B cells was increased on POD1 (each group P < 0.01); that of natural killer cells was decreased at PODI and POD3 (each group P < 0.01). We conclude that tissue damage and inflammation apparently overcome the effects of extensive epidural block on stress response and immune function in radical esophagectomy.

DOI： 10.1213/01.ANE.0000184287.15086.1E

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective. Several different severity scoring systems specific to acute renal failure have been proposed. However, most validation studies of these scoring systems were conducted in a single center or in a small number of centers, often the same ones used for their development. Therefore, it is not known whether such severity scoring systems may be widely applied.
Design: Prospective clinical investigation.
Setting: Intensive care units.
Patients: One thousand seven hundred and forty-two intensive care unit patients with acute renal failure who were either treated with renal replacement therapy or fulfilled predefined criteria.
Interventions: Demographic and clinical information and outcomes were measured.
Measurements and Main Results. Scores for four acute renal failure-specific scoring systems and two general scoring systems (Simplified Acute Physiology Score II and Sequential Organ Failure Assessment) were calculated, and their discrimination and calibration were tested with receiver operating characteristic curves and Hosmer-Lemeshow goodness-of fit-tests. For the receiver operating characteristic curves, blood lactate levels were also used as a reference. All scores had an area under the receiver operating characteristic curve < 0.7 (Mehta 0.670, Liano 0.698, Chertow 0.610, Paganini 0.643, Simplified Acute Physiology Score II 0.645, Sequential Organ Failure Assessment 0.675, lactate 0.639). For scores that can calculate predicted mortality, the Hosmer-Lemeshow goodness-of-fit test showed poor calibration.
Conclusions: None of the scoring systems tested had a high level of discrimination or calibration to predict mortality for patients with acute renal failure when tested in a broad cohort of patients from multiple countries. A large, multiple-center database might be needed to improve the discrimination and calibration of acute renal failure scoring system.

DOI： 10.1097/01.CCM.0000172279.66229.07

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DOI： 10.1213/01.ANE.0000146646.02457.55

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DOI： 10.1001/jama.294.7.813

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

A young woman with primary pulmonary hypertension developed severe interstitial pneumonia (IP) 5 days after induction of epoprostenol infusion. Although the pathogen involved was not identified, her IP was initially responsive to steroids, and discontinuation of steroid therapy caused the redevelopment of IP. After intensive treatment, including steroid therapy and inhaled nitric oxide, epoprostenol was successfully switched to prostaglandin E-1 infusion and she recovered. Epoprostenol infusion can cause a rapid severe IP, even soon after the induction of therapy. Clinicians should keep this syndrome in mind, especially when treating a severe case of IP.

DOI： 10.1213/01.ANE.0000130615.28893.52

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: According to recent research, diuretics may increase mortality in acute renal failure patients. The administration of diuretics in such patients has been discouraged. Our objective was to determine the impact of diuretics on the mortality rate of critically ill patients with acute renal failure.
Design: Prospective, multiple-center, multinational epidemiologic study.
Setting, Intensive care units from 54 centers and 23 countries.
Patients, Patients were 1,743 consecutive patients who either were treated with renal replacement therapy or fulfilled predefined criteria for acute renal failure.
Interventions: Three distinct multivariate models were developed to assess the relationship between diuretic use and subsequent mortality: a) a propensity score adjusted multivariate model containing terms previously identified to be important predictors of outcome; b) a new propensity score adjusted multivariate model; and c) a multivariate model developed using standard methods, compensating for collinearity.
Measurements and Main Results: Approximately 70% of patients were treated with diuretics at study inclusion. Mean age was 68 and mean Simplified Acute Physiology Score II was 47. Severe sepsis/septic shock (43.8%), major surgery (39.1), low cardiac output (29.7), and hypovolemia (28.2%) were the most common conditions associated with the development of acute renal failure. Furosemide was the most common diuretic used (98.3%). Combination therapy was used in 98 patients only. In all three models, diuretic use was not associated with a significantly increased risk of mortality.
Conclusions: Diuretics are commonly prescribed in critically ill patients with acute renal failure, and their use is not associated with higher mortality. There is full equipoise for a randomized controlled trial of diuretics in critically ill patients with renal dysfunction.

DOI： 10.1097/01.CCM.0000132892.51063.2F

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Language：English   Publisher：ELSEVIER SCI IRELAND LTD  

Background: The timing and use of norepinephrine (noradrenaline) (NE) in septic shock remain a matter of controversy. Aim: To study the outcome of septic patients treated with early and exclusive NE. Setting: Tertiary Intensive Care Unit. Patients: 142 patients with septic shock. Intervention: Exclusive NE infusion within 24 hours of admission to ICU. Methods and main results: Retrospective analysis of data from a unit database identified 142 patients. Their median admission simplified acute physiology score (SAPS II) score was 46 [38, 56] with 98 (69%) receiving mechanical ventilation. Mean arterial pressure (MAP) at the start of NE infusion was 60 [58, 68] mmHg. NE infusion was started at a median of 1.3 [0.3, 5.0] h after ICU admission. Restoration and maintenance of target MAP was achieved initially in all patients and, in 61.3%, within 30 min. The median peak dose of NE was 0.28 [0.14, 0.61] mug/(kg min) and the duration of infusion was 88 [42, 175] h. SAPS II predicted mortality was 40.8%, however, only 34.5% (P = 0.27) died. Among the most severely ill patients (SAPS II score > 56) actual mortality was 50.0% versus 74.7% predicted (P = 0.07). Conclusions: Early and exclusive use of NE in hyperdynamic septic shock achieved a stable MAP > 75 mmHg in all patients. Survival compared favorably with that predicted by illness severity scores. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.resuscitation.2004.03.016

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

We conducted a prospective observational study to assess the efficacy of continuous venovenous hemofiltration (CVVH) with no anticoagulation. A standard anticoagulation protocol for CVVH, which prescribed no anticoagulation for patients at risk of bleeding, was applied to 48 critically ill patients treated with CVVH. Circuit life was prospectively observed, and the following data were obtained for each circuit: heparin use and dose, protamine use, daily prothrombin time-international normalized ratio, activated partial thromboplastin time, and platelet count. Out of 300 consecutive circuits 143 (47.6%) received no anticoagulation, 31 (10.3%) received regional anti coagulation, and 126 received low dose heparin. No patients experienced bleeding complications secondary to CVVH. Platelet count was significantly lower in the no anticoagulation group (73 X 10(3)/mul) compared with the low dose heparin group (19 X 10(3)/mul) and the protamine group (104 X 10(3)/mul) (p < 0.01 for both comparisons). There was no significant difference in mean circuit life among the three groups (heparin, 20.9 hours; no anti coagulation, 19.3 hours; protamine, 21.2 hours; not significant). In conclusion, for a group of patients deemed to be at risk of bleeding, CVVH without anticoagulation achieved an acceptable circuit life, which was similar to that obtained in other patients with low dose heparin atiticoagulation or regional anticoagulation with heparin/protamine.

DOI： 10.1097/01.MAT.0000104822.30759.A7

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Language：English   Publisher：OXFORD UNIV PRESS  

Background. The Fencl-Stewart approach to acid-base disorders uses five equations of varying complexity to estimate the base excess effects of the important components: the strong ion difference (sodium and chloride), the total weak acid concentration (albumin) and unmeasured ions. Although this approach is straightforward, most people would need a calculator to use the equations. We proposed four simpler equations that require only mental arithmetic and tested the hypothesis that these simpler equations would have good agreement with more complex Fencl-Stewart equations.
Methods. We reduced two complex equations for the sodium-chloride effect on base excess to one simple equation: sodium-chloride effect (meq litre(-1))=[Na+]-[Cl-]-38. We simplified the equation of the albumin effect on base excess to an equation with two constants: albumin effect (meq litre(-1))=0.25x(42-[albumin]g litre(-1)). Using 300 blood samples from critically ill patients, we examined the agreement between the more complex Fencl-Stewart equations and our simplified versions with Bland-Altman analyses.
Results. The estimates of the sodium-chloride effect on base excess agreed well, with no bias and limits of agreement of -0.5 to 0.5 meq litre(-1). The albumin effect estimates required log transformation. The simplified estimate was, on average, 90% of the Fencl-Stewart estimate. The limits of agreement for this percentage were 82-98%.
Conclusions. The simplified equations agree well with the previous, more complex equations. Our findings suggest a useful, simple way to use the Fencl-Stewart approach to analyse acid-base disorders in clinical practice.

DOI： 10.1093/bja/aeh018

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DOI： 10.1378/chest.125.6.2260

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