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In-hospital mortality of adult veno-venous extracorporeal membrane oxygenation (V-V ECMO) patients remains invariably high. However, little is known regarding timing and causes of in-hospital death, either on-ECMO or after weaning. The current review aims to investigate the timing and causes of death of adult patients during hospital admittance for V-V ECMO, and to define the V-V ECMO gap, which is represented by the patients that are successfully weaned of ECMO but still die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V-V ECMO patients from January 2006 to December 2020 were screened. Studies that did not report on at least on-ECMO mortality and discharge rate were excluded from analysis as they could not provide the required information regarding the proposed V-V ECMO-gap. Mortality rates on-ECMO and after weaning, as well as weaning and discharge rates, were analyzed as primary outcomes. Secondary outcomes were the causes of death and complications. Initially, 35 studies were finally included in this review. Merely 24 of these studies (comprising 975 patients) reported on prespecified V-V ECMO outcomes (on-ECMO mortality and discharge rate). Mortality on V-V ECMO support was 27.8% (95% confidence interval (CI) 22.5%-33.2%), whereas mortality after successful weaning was 12.7% (95% CI 8.8%-16.6%, defining the V-V ECMO gap). 72.2% of patients (95% CI 66.8%-77.5%) were weaned successfully from support and 56.8% (95% CI 49.9%-63.8%) of patients were discharged from hospital. The most common causes of death on ECMO were multiple organ failure, bleeding, and sepsis. Most common causes of death after weaning were multiorgan failure and sepsis. Although the majority of patients are weaned successfully from V-V ECMO support, a significant proportion of subjects still die during hospital stay, defining the V-V ECMO gap. Overall, timing and causes of death are poorly reported in current literature. Future studies on V-V ECMO should describe morbidity and mortality outcomes in more detail in relation to the timing of the events, to improve patient management, due to enhanced understanding of the clinical course., (© 2021 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

For patients with untreated hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) with multi-organ dysfunction (MOD), mortality is >80%. We conducted a pooled analysis of three studies that assessed Day 100 survival in relationship to MOD severity, with dialysis and/or ventilator dependence representing the most severe organ dysfunction. All patients in the analysis were diagnosed using Baltimore criteria/biopsy. This analysis of patients with VOD/SOS and MOD after haematopoietic cell transplantation (HCT; n = 651) demonstrated higher Day 100 survival rates amongst defibrotide-treated patients with VOD/SOS with less versus more severe forms of MOD. Even patients with severe forms of MOD post-HCT benefitted from defibrotide., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Current sepsis biomarkers may be helpful in determining organ failure and evaluating patient clinical course; however, direct molecular biomarkers to predict subsequent organ failure have not yet been discovered. Exosomes, a small population of extracellular vesicles, play an important role in the inflammatory response, coagulation process and cardiac dysfunction in sepsis. Nonetheless, the association of plasma exosome with severity and mortality of sepsis is not well known. Therefore, the overall levels of plasma exosome in sepsis patients were assessed and whether exosome levels were associated with organ failure and mortality was evaluated in the present study. Plasma level of exosomes was measured by ELISA. Among 220 patients with sepsis, 145 (66%) patients were diagnosed with septic shock. A trend of increased exosome levels in control, sepsis and septic shock groups was observed (204 µg/mL vs 525 µg/mL vs 802 µg/mL, P < 0.001). A positive linear relationship was observed between overall exosome levels and Sequential Organ Failure Assessment (SOFA) score in the study cohorts (r value = 0.47). When patients were divided into two groups according to best cut-off level, a statistical difference in 28- and 90-day mortality between patients with high and low plasma exosomes was observed. Elevated levels of plasma exosomes were associated with severity of organ failure and predictive of mortality in critically ill patients with sepsis., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: It is well known that low platelet count on admission to intensive care units (ICU) is associated with increased mortality. However, it is unknown whether prothrombin time (PT-INR) and activated partial thromboplastin time (APTT) on admission correlate with mortality and organ failure. Therefore, the aim of this study was to investigate whether PT-INR and APTT at admission can predict outcome in the critically ill patient after adjusting for severity of illness measured with Simplified Acute Physiology Score 3 (SAPS 3)., Materials and Methods: Data were retrospectively collected. APTT and PT-INR taken on admission and SAPS 3 score were independent variables in all regression analyses. Survival analysis was done with Cox regression. Organ failure was reported as days alive and free (DAF) of vasopressors and invasive ventilation, need of continuous renal replacement therapy (CRRT) and Acute Kidney Injury Network creatinine score (AKIN-crea)., Results: A total of 3585 ICU patients were included. Prolonged APTT correlated with mortality with 95% confidence interval (CI) of hazard ratio 1.001-1.010. Prolonged APTT also correlated with DAF vasopressor, CRRT and AKIN-crea with 95% CI of odds ratio (OR) 1.009-1.034, 1.016-1.037 and 1.009-1.028, respectively. Increased PT-INR correlated with DAF vasopressor and DAF ventilator with 95% CI of OR 1.112-2.014 and 1.135-1.847, respectively., Conclusions: Activated partial thromboplastin time prolongation was associated with mortality and all morbidity outcomes except the DAF ventilator. PT-INR increase at admission was associated with DAF vasopressor and DAF ventilator. APTT and PT-INR at admission correlate with morbidity, which is not accounted for in the SAPS 3 model., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The major limitation of cord blood transplantation (CBT) for adults remains the delayed hematopoietic recovery and higher incidence of graft failure, which result in a higher risk of early mortality in CBT. We evaluated early overall survival (OS), non-relapse mortality (NRM), neutrophil engraftment, acute graft-vs-host disease, and cause of early death among 9678 adult patients who received single-unit CBT in Japan between 1998 and 2017. The probability of OS at 100 days was 64.4%, 71.7%, and 78.9% for the periods 1998 to 2007, 2008 to 2012, and 2013 to 2017, respectively (P < .001). The cumulative incidences of NRM at 100 days during the same period were 28.3%, 20.8%, and 14.6%, respectively (P < .001). The cumulative incidences of neutrophil engraftment were also improved during the same period (P < .001). The most common cause of death within 100 days after CBT was bacterial infection in 1998 to 2007 and primary disease in the latter two time periods. Across the three time periods, the proportions of deaths from bacterial and fungal infection, graft failure, hemorrhage, sinusoidal obstructive syndrome, and organ failure decreased in a stepwise fashion. Landmark analysis of OS and NRM after 100 days showed that OS did not change over time in the multivariate analysis. Our registry-based data demonstrated a significant improvement of early OS after CBT for adults over the past 20 years. The landmark analysis suggested that improvement of early mortality could lead to an improvement of long-term OS after CBT., (© 2019 Wiley Periodicals, Inc.)

Left ventricular assist devices (LVADs) are used as an alternative therapy for heart transplantation in patients with advanced heart failure. However, the mortality rate of these patients remains relatively high. A large proportion of deaths after LVAD implantation occur during intensive care unit (ICU) stay. We conducted a retrospective study to identify the risk factors for all-cause ICU mortality in patients with an implanted LVAD. Between January 1, 2008 and December 31, 2016, 70 consecutive patients who had received an LVAD were analyzed. The median ICU length of stay was 14 days (IQR: 8-31) and 16 patients (22.9% [95%CI: 13.1-32.7]) died in the ICU. The 90-day mortality rate was 25.7% (95%CI: 15.5-35.9). The main causes of ICU mortality were: multiple organ failure, stroke, and hemorrhagic events. The univariate analysis identified the following perioperative risk factors for all-cause ICU mortality: hypertension, preoperative platelet count, preoperative white cell count, inotropic support before LVAD implantation, mechanical ventilation before LVAD implantation, renal replacement therapy before LVAD implantation, short-term mechanical support before LVAD implantation, INTERMACS class 1 to 2, low intraoperative platelet count, low early postoperative hemoglobin level, low early postoperative platelet count, low early postoperative pH, and massive perioperative blood transfusion. In the multivariate logistic regression analysis, only mechanical ventilation before LVAD implantation was retained as an independent risk factor for ICU mortality (OR = 11.96 [95%CI: 2.67-53.45], P < .01). These findings confirm that most deaths after LVAD implantation occur in the ICU. Patients that receive mechanical ventilation preoperatively have the highest risk of death. This confirms the need to actively treat respiratory failure and to wean patients from respiratory support before LVAD implantation. Such a strategy offers the best opportunity to initiate active rehabilitation., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Current evidence indicates that it is safe to use a lower haemoglobin (Hb) threshold for red blood cell (RBC) transfusion as compared to a higher Hb-threshold. However, the recent Transfusion Requirements in Cardiac Surgery (TRICS-3) trial reported a significant interaction between patient age and the effect of lower vs higher Hb-thresholds for RBC transfusion. The interaction between patient age and transfusion strategy appears to differ between trials., Methods: This is the protocol and statistical analysis plan for a post hoc analysis of the Transfusion Requirements in Septic Shock (TRISS) trial. We will assess the effect of a lower vs a higher Hb-threshold for RBC transfusion in patients of different ages with septic shock. The primary and secondary outcomes are 1-year mortality and 90-day mortality respectively. We will assess age divided into six age groups and as a continuous variable and present baseline characteristics and odds ratios derived from both simple and adjusted (for the Sequential Organ Failure Assessment score, haematological malignancy, age and trial site) logistic regression models and P-values for the test-of-interaction. Furthermore, we will compare outcomes according to Hb-threshold in each age group using Kaplan-Meier curves and log-rank tests., Discussion: The outlined study will make a detailed assessment of potential interaction of patient age with transfusion strategy in patients with septic shock. This may inform future trials on the benefits and harms of RBC transfusion., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Patients with multiple organ failure (MOF) often receive large amounts of resuscitation fluid, making them at high risk of fluid overload (FO). Our main objective was to investigate if the ability to achieve a negative fluid balance during the first 3 continuous renal replacement therapy (CRRT) days was associated with mortality in children with MOF., Methods: Retrospective cohort study in a tertiary multidisciplinary academic paediatric hospital. The study included 63 patients (age 0-18 years) with 3 or more failing organs receiving CRRT due to acute kidney injury and/or fluid overload., Results: The median age was 4 months, and PICU mortality was 29%. Survivors had significantly lower degree of FO at CRRT initiation, (median 15% (Interquartile range 9-22)) than non-survivors (24% (17%-37%), P = 0.002). On PICU admission, PIM-3 score was significantly higher in non-survivors (P = 0.01), but at CRRT initiation there was no difference in PELOD-2 score (P = 0.98). Mortality in patients achieving a cumulative net negative fluid balance during the first 3 days after CRRT initiation was 12%, compared to 86% in those not achieving this (P < 0.0001). In multivariate analysis, the inability to achieve a net negative fluid balance during 3 days after CRRT initiation (P < 0.0001) and FO >20% at CRRT initiation (P = 0.0019) remained associated with mortality., Conclusion: Our results suggest that early fluid removal is associated with improved patient outcome in critically ill children receiving CRRT, and that prompt measures should be taken to prevent fluid overload in critical illness. These results need to be verified in further, prospective studies., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Chronic end-organ complications result in morbidity and mortality in adults with sickle cell disease (SCD). In a retrospective-prospective cohort of 150 adults with SCD who received standard care screening for pulmonary function abnormalities, cardiac disease, and renal assessment from January 2003 to 2016, we tested the hypothesis that clustering of end-organ disease is common and multiple organ impairment predicts mortality. Any end-organ disease occurred in 59.3% of individuals, and 24.0% developed multiple organ (>1) end-organ disease. The number of end-organs affected was associated with mortality (P ≤ .001); 8.2% (5 of 61) of individuals with no affected end-organ, 9.4% (5 of 53) of those with 1 affected organ, 20.7% (6 of 29) of those with 2 affected end-organs, and 85.7% (6 of 7) with 3 affected end-organs died over a median follow up period of 8.7 (interquartile range 3.5-11.4) years. Of the 22 individuals who died, 77.3% had evidence of any SCD-related end-organ impairment, and this was the primary or secondary cause of death in 45.0%. SCD-related chronic impairment in multiple organs, and its association with mortality, highlights the need to understand the common mechanisms underlying chronic end-organ damage in SCD, and the urgent need to develop interventions to prevent irreversible end-organ complications in SCD., (© 2018 Wiley Periodicals, Inc.)

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic stem cell transplant (HSCT) conditioning and chemotherapy. Defibrotide is approved for treatment of hepatic VOD/SOS with pulmonary or renal dysfunction [i.e., multi-organ dysfunction (MOD)] after HSCT in the United States and severe VOD/SOS after HSCT in patients aged older than 1 month in the European Union. Defibrotide was available as an investigational drug by an expanded-access treatment programme (T-IND; NCT00628498). In the completed T-IND, the Kaplan-Meier estimated Day +100 survival for 1000 patients with documented defibrotide treatment after HSCT was 58·9% [95% confidence interval (CI), 55·7-61·9%]. Day +100 survival was also analysed by age and MOD status, and post hoc analyses were performed to determine Day +100 survival by transplant type, timing of VOD/SOS onset (≤21 or >21 days) and timing of defibrotide treatment initiation after VOD/SOS diagnosis. Day +100 survival in paediatric patients was 67·9% (95% CI, 63·8-71·6%) and 47·1% (95% CI, 42·3-51·8%) in adults. All patient subgroups without MOD had higher Day +100 survival than those with MOD; earlier defibrotide initiation was also associated with higher Day +100 survival. The safety profile of defibrotide in the completed T-IND study was similar to previous reports., (© 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction., (© 2017 The Association of Anaesthetists of Great Britain and Ireland.)

Background: Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replacement in patients at high surgical risk. However, there is little published literature on the exact causes of death., Methods and Results: The PubMed database was systematically searched for studies reporting causes of death within and after 30 days following TAVR. Twenty-eight studies out of 3934 results retrieved were identified. In the overall analysis, 46.4% and 51.6% of deaths were related to noncardiovascular causes within and after the first 30 days, respectively. Within 30 days of TAVR, infection/sepsis (18.5%), heart failure (14.7%), and multiorgan failure (13.2%) were the top 3 causes of death. Beyond 30 days, infection/sepsis (14.3%), heart failure (14.1%), and sudden death (10.8%) were the most common causes. All possible subgroup analyses were made. No significant differences were seen for proportions of cardiovascular deaths except the comparison between moderate (mean STS score 4 to 8) and high (mean STS score >8) -risk patients after 30 days post-TAVR (56.0% versus 33.5%, P=0.005)., Conclusions: Cardiovascular and noncardiovascular causes of death are evenly balanced both in the perioperative period and at long-term follow-up after TAVR. Infection/sepsis and heart failure were the most frequent noncardiovascular and cardiovascular causes of death. This study highlights important areas of clinical focus that could further improve outcomes after TAVR., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: In patients with a body mass index (BMI) > 35 kg/m(2) , or in extreme cases weighting > 250 kg, we are faced with special challenges in therapy and logistics. The aim was to analyze the feasibility of the extracorporeal membrane oxygenation (ECMO) in these patients., Methods: We report 12 adult patients [10 male, 2 female; mean age 56.7 (34-74) years; mean BMI 47.9 (35-88.6) kg/m(2) ] with acute lung failure treated with veno-venous ECMO from 1 January 2009 to 30 June 2013. All patients were cannulated percutaneously into the right internal jugular vein and one of the femoral veins at the bedside., Results: The mean time to ECMO after admission to the intensive care unit (ICU) was 2 days (0-10), and the mean ECMO run time was 9 days (4 h-20 days). Lung failure occurred in the contexts of wound infection (two patients), anaphylactic shock (one patient), major trauma (one patients) and pneumonia after surgery (four patients), and respiratory failure in abdominal sepsis (four patients). The mean time in the ICU was 31 days (0-89), and the mean time at the hospital was 38 days (0-101). Three patients died on the system because of multiorgan failure; nine patients were weaned from ECMO (75%); and six were patients discharged from the ICU and from the hospital (survival rate 50%)., Conclusions: ECMO in obese patients is feasible and life saving. Therefore, a percutaneous cannulation remains feasible. The goals of the ECMO therapy include early spontaneous breathing, tracheotomy, rapid reduction of sedation and adequate analgesia. Rehabilitation includes nutritional therapy, as well as psychiatric therapy and bariatric surgery, as perspectives for the future., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Echocardiography is increasingly becoming an integrated tool for circulatory evaluation in the intensive care unit and the operating room. Therefore, it is imperative to know the reproducibility of measurements obtained by echocardiography. In this study, a comparison of cardiac output (CO) measurements obtained with transesophageal echocardiography (TEE) and pulmonary artery catheter (PAC) thermodilution (TD) was carried out to test the precision, accuracy and trending ability of CO measurements obtained with TEE., Methods: Twenty-five patients completed the study. Each patient was placed in the following successive positions: supine, head-down tilt, head-up tilt, supine, supine with phenylephrine administration, pace heart rate 80 beats per minute (bpm), pace heart rate 110 bpm. TEE CO and PAC CO were measured simultaneously. The agreement was analysed by Bland-Altman plots, and to assess trending ability, a polar plot was constructed., Results: Both methods showed an acceptable precision 8% (PAC TD) and 16% (TEE). In comparison with PAC TD, the TEE was associated with a bias of -0.22 l/minute [95% confidence interval: -0.54; 0.10], wide limits of agreement (-1.73 l/minute; 1.29 l/minute), a percentage error of 38.6% and a trending ability with a radial degree of 53.6°, corresponding to a poor trending ability., Conclusion: In comparison, CO measurements obtained with TEE and PAC TD had wide limits of agreement, a larger percentage error than would be expected from the precision of the two methods, and a poor trending ability. Thus, TEE is not interchangeable with PAC TD for measuring CO., (© 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients., Method: One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality., Results: The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104-557), P = 0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100 ml/24 h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P = 0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P = 0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95% CI (1.45-18.24), P = 0.011]., Conclusion: A cumulative positive fluid balance higher than 1100 ml/24 h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Background: The short-term survival of critically ill patients with cancer has improved over time. Studies providing long-term outcome for these patients are scarce., Methods: We prospectively analyzed outcomes and rates of successful discharge of 111 consecutive critically ill cancer patients admitted to intensive care unit (ICU) in 2008 and identified factors influencing these results., Results: ICU mortality was 32% and hospital mortality was 41%. None of the characteristics of the malignancy nor age or neutropenia were significantly different between survivors and others. Two variables were independently associated with ICU mortality: high Logistic Organ Dysfunction score on day 7 and a diagnosis of viral infection and/or reactivation. The 1-year mortality rate for ICU survivors was 58% and was significantly lower in patients with a diagnosis of acute leukemia or multiple myeloma., Conclusion: Organ failure scores on day 7 can predict outcome for cancer patients in the ICU. Viral infection and reactivation appear to worsen the prognosis. One-year mortality rate is high and depends on the malignancy., (© 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.)

Aims: Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose., Results: Between 1992 and 2008, 663 patients were admitted with paracetamol-induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P= 0.025), although this overdose pattern did not independently predict death. The King's College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P= 0.009)., Conclusions: Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi-organ failure and should be considered for early transfer to specialist liver centres., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

Background: The systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores are widely used as prognostic markers in critical care settings and could improve triage of high-risk paracetamol (acetaminophen) overdose patients., Aim: To evaluate the prognostic accuracy of the SIRS and SOFA scores following single time point paracetamol overdose., Methods: Analysis of 100 single time point paracetamol overdoses admitted to a tertiary liver centre, with subsequent prospective validation of identified thresholds. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily SOFA and SIRS scores calculated., Results: A total of 74 (74%) patients developed the SIRS, which occurred significantly earlier in patients who died (n=21) compared with spontaneous survivors (n=53, P=0.05). The SIRS occurred in 70 (70%) patients by 96h post-overdose, with a 30% mortality rate; compared with 0% mortality in the 30 non-SIRS patients (P=0.001). Median SOFA scores were significantly higher in nonsurvivors at 48 (P=0.009), 72 (P<0.001), and 96h (P<0.001). A SOFA score >7 during the first 96h post-overdose predicted death/transplantation with a sensitivity of 95.0 (95% CI 78.5-99.1) and specificity of 70.5 (95% CI 66.3-71.6). A validation cohort of 38 single time point paracetamol overdoses confirmed the extremely high negative predictive value of both the SIRS and SOFA thresholds., Conclusions: The absence of either a SOFA score >7 or a SIRS response during the first 96 h following paracetamol overdose could improve triage and reduce transfers of lower risk patients to tertiary liver centres., (© 2011 Blackwell Publishing Ltd.)

Background and Aims: Zinc deficiency leads to susceptibility to infections and may affect pulmonary epithelial cell integrity. Low zinc levels have also been associated with a degree of organ failure and decreased survival in critically ill children. Accordingly, the purpose of the study was to assess serum zinc in adult patients with acute respiratory failure, its association with ventilatory support time, intensive care unit (ICU) length of stay (LOS), organ dysfunction and 30-day mortality., Methods: We included consecutive patients with acute respiratory failure during an eight-week prospective, observational multicentre study (the FINNALI-study). Acute respiratory failure was defined as a need for either non-invasive or invasive positive pressure ventilation for >6 h regardless of the underlying cause or risk factors. After informed consent, a sample for zinc measurement was drawn at 6 h after the start of treatment and analysed from 551 of these patients., Results: Low serum zinc was frequent (95.8%) at the onset acute respiratory failure. The median interquartile range [IQR] was 4.7 [3.0-6.9] μmol/l. The median [IQR] serum zinc levels in non-infectious, sepsis and septic shock patients were 5.0 [3.1-7.1], 5.1 [3.5-7.3] and 3.8 [2.6-5.9] μmol/l, respectively, P<0.01. Baseline zinc levels were not associated with ventilatory support time (P=0.98) or ICU LOS (P=0.053). The area under curve in receiver operating characteristics analysis for serum zinc regarding 30-day mortality was 0.55 (95% CI 0.49-0.60)., Conclusions: Serum zinc on initiation of ventilation had no predictive value for 30-day mortality, ventilatory support time or intensive care unit LOS.

Background: We investigated the incidence and severity of post-injury morbidity and mortality in intensive care unit (ICU)-treated trauma patients. We also identified risk factors in the early phase after injury that predicted the later development of complications., Methods: A prospective observational cohort study design was used. One hundred and sixty-four adult patients admitted to the ICU for more than 24 h were included during a 21-month period. The incidence and severity of morbidity such as multiple organ failure (MOF), acute lung injury (ALI), severe sepsis and 30-day post-injury mortality were calculated and risk factors were analyzed with uni- and multivariable logistic regression analysis., Results: The median age was 40 years, the injury severity score was 24, the new injury severity score was 29, the acute physiology and chronic health evaluation II score was 15, sequential organ failure assessment maximum was 7 and ICU length of stay was 3.1 days. The incidences of post-injury MOF were 40.2%, ALI 25.6%, severe sepsis 31.1% and 30-day mortality 10.4%. The independent risk factors differed to some extent between the outcome parameters. Age, severity of injury, significant head injury and massive transfusion were independent risk factors for several outcome parameters. Positive blood alcohol was only a predictor of MOF, whereas prolonged rescue time only predicted death. Unexpectedly, injury severity was not an independent risk factor for mortality., Conclusions: Although the incidence of morbidity was considerable, mortality was relatively low. Early post-injury risk factors that predicted later development of complications differed between morbidity and mortality.

Background: Hospital admissions for cirrhosis have been increasing in the United Kingdom, leading to increased pressure on intensive care (ICU) services. Outcome data for patients admitted to ICU are currently limited to transplant centre reports, with mortality rates exceeding 70%. These tertiary reports could fuel a negative bias when patients with cirrhosis are reviewed for ICU admission in secondary care., Aims: To determine whether disease severity and mortality rates in non-transplant general ICU are less severe than those reported by tertiary datasets., Methods: A prospective dual-centre non-transplant ICU study. Admissions were screened for cirrhosis and physiological and biochemical data were collected. Disease-specific and critical illness scoring systems were evaluated., Results: Cirrhosis was present in 137/4198 (3.3%) of ICU admissions. ICU and hospital mortality were 38% and 47%, respectively; median age 50 [43-59] years, 68% men, 72% alcoholic cirrhosis, median Child Pugh Score (CPS) 10 [8-11], Model for End-Stage Liver Disease (MELD) 18 [12-24], Acute Physiology and Chronic Health Evaluation II score (APACHE II) 16 [13-22]., Conclusions: Mortality rates and disease staging were notably lower than in the published literature, suggesting that patients have a more favourable outlook than previously considered. Transplant centre data should therefore be interpreted with caution when evaluating the merits of intensive care admission for patients in general secondary care ICUs.

Background: Left ventricular free wall rupture (LVFWR) is still one of the often fatal complications of acute myocardial infarction. Surgical repair is mandatory even with high operative mortality. The optimal surgical technique is controversial since the results depend on type of rupture. We present our mid-term surgical experience according to the status of the left ventricular tear and type of surgical repair., Methods: From January 1997 to December 2007, 19 consecutive patients with LVFWR were treated at our institution. The mean age was 72 +/- 8 ranging from 53 to 81 years; there were eight males and 11 females. According to the intraoperative findings, patients were divided into two groups: group 1 (eight patients), where no macroscopic tear of the LVFW could be detected with blood oozing from infarcted zone (Oozing type LVFWR); and group 2 (11 patients), where a macroscopic defect of the epicardium, with free communication between left ventricular cavity and pericardial space, was identified (Blow-out type LVFWR). The patch covering and glue technique was applied for group 1 patients, while closure of the ventricular tear either by direct suture or by patch repair was used for group 2 patients., Results: The interval between diagnosis of LVFWR and surgery was 2.9 +/- 1.1 hours. However, reevaluation of echocardiographic studies showed an early missed diagnosis of LVFWR in three patients of group 1 and in eight of group 2. Thus, the mean interval between initial signs of rupture and surgery was 9 +/- 8 hours and 21 +/- 15 hours, respectively, for oozing and blow-out type rupture. On arrival in the operating room, four patients were on cardiopulmonary resuscitation, while four were in cardiogenic shock. The hospital mortality was 12% (one death) in group 1 and 36% (four deaths) in group 2 mainly due to multiorgan failure. Fourteen patients were discharged with a mean follow-up of 3.8 +/- 3.5 years. During follow-up, one patient in group 1 died after 7.5 years. No recurrence of free wall rupture or aneurysm formation was demonstrated in all cases. At last follow-up, all survivors showed excellent clinical results with a preserved left ventricular function. Patients with oozing type LVFWR and patch covering technique repair showed an absence of left ventricular-restricted motion at the echocardiographic study., Conclusion: In patients with LVFWR, early diagnosis and surgical treatment are crucial for successful outcome when excellent results can be achieved with a simple glued patch covering technique.

This study compared the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II score with two organ failure scores in predicting hospital mortality of critically ill patients. A total of 1311 consecutive adult patients in a tertiary 22-bed multidisciplinary intensive care unit (ICU) in Western Australia were considered. The APACHE II score had a better calibration and discrimination than the Max Sequential Organ Failure Score (Max SOFA) (area under receiver operating characteristic (ROC) curve 0.858 vs 0.829), Admission SOFA (area under ROC 0.858 vs 0.791), and the first day or cumulative 5-day Royal Perth Hospital Intensive Care Unit (RPHICU) organ failure score (area under ROC 0.858 vs 0.822 and 0.819, respectively) in predicting hospital mortality. The APACHE II score predicted hospital mortality of critically ill patients better than the SOFA and RPHICU organ failure scores in our ICU.

To determine the incidence and outcome of critical illness amongst the total population of hospital patients with haematological malignancy (including patients treated on the ward as well as those admitted to the intensive care unit), consecutive patients with haematological malignancy were prospectively studied. One hundred and one of the 1437 haemato-oncology admissions (7%) in 2001 were complicated by critical illness (26% of all new referrals). Fifty-four (53%) of these critically ill patients survived to leave hospital and 33 (34%) were still alive after 6 months. The majority (77/101) were not admitted to the intensive care unit but were managed on the ward, often with the assistance of the intensive care team. Independent risk factors for dying in hospital included hepatic failure (odds ratio 5.3, 95% confidence intervals 1.3-21.2) and central nervous system failure (odds ratio 14.5, 95% confidence intervals 1.7-120.5). No patient with four or more organ failures or a Simplified Acute Physiology Score II >/= 65 survived to leave hospital. There was close agreement between actual and predicted mortality with increasing Simplified Acute Physiology Score II for all patients, including those not admitted to intensive care.

Drotrecogin alfa (activated) is licensed in Europe for the treatment of severe sepsis in patients with multiple organ failure. We constructed a model to assess the cost effectiveness of drotrecogin alfa (activated) from the perspective of the UK National Health Service when used in adult intensive care units. Patient outcomes from a 28-day international clinical trial (PROWESS) and a subsequent follow-up study (EVBI) were supplemented with UK data. Cost effectiveness was assessed as incremental cost per life year and per quality adjusted life year saved compared to placebo alongside best usual care. Applying the 28-day mortality outcomes of the PROWESS study, the model produced a cost per life year saved of 4608 UK pounds and cost per quality adjusted life year saved of 6679 UK pounds. Equivalent results using actual hospital outcomes were 7625 UK pounds per life year and 11,051 UK pounds per quality adjusted life year. Drotrecogin alfa (activated) appears cost effective in treating severe sepsis in UK intensive care units.

We measured the plasma level of fibrinogen in 560 patients with disseminated intravascular coagulation (DIC) and evaluated its relationship with outcome and with other hemostatic markers. Forty-seven percent of patients had >200 mg/dL of plasma fibrinogen and 24% had <100 mg/dl of plasma fibrinogen, suggesting that plasma fibrinogen level is not a sensitive marker for DIC. In our analysis of outcome and plasma fibrinogen levels, the rate of death was high in leukemia/lymphoma patients with high fibrinogen concentration, but no significant difference in outcome was observed in relation to plasma fibrinogen concentration in non-leukemia/lymphoma patients with DIC. Among patients with leukemia/lymphoma, the frequency of organ failure was markedly high in patients with high plasma levels of fibrinogen. Among patients without leukemia/lymphoma, the frequency of organ failure increased concomitantly with the increase in plasma fibrinogen levels. The international normalized ratio was significantly increased in leukemia/lymphoma patients with low fibrinogen. FDP levels were slightly increased in patients with low fibrinogen. Platelet count was significantly low in patients without leukemia/lymphoma with high fibrinogen. DIC score increased concomitantly with the reduction in plasma fibrinogen levels. Plasma levels of thrombomodulin and tissue factor were significantly high in patients with high fibrinogen levels. Plasma levels of antiplasmin and plasminogen were significantly decreased in patients with low fibrinogen. Plasma levels of plasmin plasmin-inhibitor complex and tissue type plasminogen activator/plasminogen activator inhibitor-1 complex (PAI-I) were significantly higher in patients with low fibrinogen than in those with high fibrinogen. Plasma levels of PAI-I and IL-6 were significantly higher in patients with high fibrinogen than in those with low fibrinogen. Patients with high fibrinogen levels showed less activation of secondary fibrinolysis, which might explain the occurrence of organ failure and poor outcome., (Copyright 2002 Wiley-Liss, Inc.)

Multiorgan dysfunction syndrome (MODS) is one of the most frequent conditions encountered in intensive-care medicine. MODS is defined as total or partial loss of two or more organs with vital functions. The development of acute renal failure (ARF) in MODS leads to an additional aggravation with considerably higher hospital mortality than in other ICU patients with MODS. Whereas dissolved substances involved in the regulation of regional blood flow, endothelial cell injury, microvascular permeability, oxygenation, and nutrition of cells are at the focus of interest in MODS, hardly any scientific attention is paid to their main solvent water. An impaired renal water excretion and an increased metabolic water volume requiring excretion interfere with diffusive and convective oxygen transport through the different fluid compartments. It will be shown first that the ratio of U(osm)/ P(osm) appears to be a reliable tool to assess overhydration in ARF. Secondly, the limits of urinary output in response to water intake will be considered. Furthermore, the metabolic water formation by an enhanced degradation of endogenous protein and fat will be discussed. Finally, the daily caloric intake is questioned with respect to energy expenditure and metabolic water formation.

Multiple system organ failure after cardiac surgery in children is a severe complication with unknown mid- and long-term sequelae. We therefore evaluated 11 children (aged 20-126 mo, median: 67 mo) having survived multiple system organ failure after cardiac operations for congenital cardiac defects in a cross-sectional follow-up study 12-76 mo (median: 32 mo) after surgery. Clinical and laboratory examinations included cardiac, pulmonary, renal, hepatic, neurological and psychological function tests. All patients had adequate cardiac function. Lung mechanics were abnormal in three children and glomerular renal function was abnormal in two patients. Slight elevation of gamma-glutamyl transpeptidase and coagulation factor deficiency was present in six and seven patients, respectively (five of whom had undergone the Fontan operation). Severe neurological sequelae such as diplegia (n = 1) and mental retardation (n = 1) were observed in two patients. In addition, five children presented delayed motor, graphomotor and/or speech development. Two children were found to have abnormal intelligence. We conclude that with the exception of neurological impairment, mid-term sequelae of multiple system organ failure after cardiac surgery in children are mild. However, longer follow-up using an appropriate control group is mandatory.

We have used heparin-bonded partial cardiopulmonary bypass to support distal aortic circulation during aortic cross-clamping. However, there were no cardiotomy reservoirs with fully reliable thromboresistance. To resolve this problem, a short-acting anticoagulant (nafamostat mesilate) was added into a cardiotomy reservoir. The present study was designed to evaluate the efficacy of our distal perfusion system. From May 1995 through the end of May 1996, 27 patients underwent descending thoracic and thoracoabdominal aortic aneurysm repairs with this adjunct, 4 being excluded from the experiment. Twenty patients who had undergone conventional partial cardiopulmonary bypass were defined as the control group. There were no significant differences between the 2 groups in the morbidity, mortality, gas transfer, or transfusion requirements despite the fact that more complicated surgical procedures (shown by a two-fold increase in the prevalence of reoperation) were required in the group that had received the current distal perfusion adjunct the heparin-bonded group. In conclusion, our perfusion system is very effective for descending thoracic and thoracoabdominal aortic aneurysm repairs.

Although the natural history of acute myocarditis leads to complete recovery in the majority of patients, rapid and irreversible cardiac decompensation resulting in death is known to occur. One possible therapy to improve the poor prognosis of this patient group may be the implantation of circulatory support systems that allow myocardial recovery or bridging to heart transplantation. Therapeutic protocols have been suggested, but clinical experiences in this area are few. In this paper we report on our clinical experiences in cardiogenic shock after acute fulminant myocarditis using different types of circulatory support systems. Three different systems were used: a biomedicus centrifugal pump as a ventricular assist device (VAD) or femoro-femoral bypass (FFB) including oxygenator; Abiomed BVS 5000, and Thoratec ventricular assist device. Hemodynamic criteria for implantation of support systems were cardiac index < 2.0 L/min/m2. SVR = 1000 dyne-s-cm-5, central venous pressure (CVP) or left atrial pressure (LAP) > 20 mm Hg, and urine output < 20 ml/h despite maximal pharmacological therapy. Age total of 5 patients (mean age 29 years, range 15-55 years) in cardiogenic shock after acute fulminant myocarditis were included. Two patients initially were supported for stabilization and transportation from an outside hospital by FFB. Both patients died after a support time of 24 h because of multiorgan failure or neurological disorders after longer periods of resuscitation in the referral hospital. The third patient (55 years) received the Biomedicus pump as CVAD. Myocardial function recovered after a support time of 120 h, and the patient could be weaned. Unfortunately, 2 days after weaning, he developed malignant arrhythmias and died. The 2 remaining patients (15 years and 27 years) with diagnosis of acute fulminant virus myocarditis were supported by biventricular assist device (1 x Thoratec/111 days, 1 x Abiomed/7 days). During the entire time of support, there were no signs of myocardial recovery. The patients were accepted for the heart transplantation (HTX) program. In both cases, HTXs were performed without any complication. The postoperative course was uneventful. The results of mechanical circulatory support in patients with acute fulminant myocarditis are encouraging and justify the resources.

Between January 1984 and March 1995, biventricular bypass (BVB) with oxygenation was used in 17 patients for postcardiotomy ventricular failure at the Heart Institute of Japan, Tokyo Women's Medical College. Of the 17 patients, 12 (70.6%) were weaned from the circulatory support, and 8 (47.1%) were discharged from the hospital. The time interval from the endo of cardiopulmonary bypass to the start of BVB was significantly shorter in weaned patients than in unweaned patients. The duration on support also has been shortened significantly in the last 6 years, compared with the earlier 6 years. Causes of death were severe heart failure or ventricular arrhythmia in 6 patients and multiple organ failure in 3 patients. These results suggest that early application and timely weaning from biventricular bypass with oxygenation might be the effective circulatory support of choice for treatment of postcardiotomy ventricular failure.

From October 1982 to the present, 16 patients have been supported by a pneumatic ventricular assist device (VAD). Since April 1990, we have introduced a venoarterial bypass (VAB) with percutaneous cardiopulmonary support (PCPS) system. This PCPS system was used in 12 patients. The long-term survival rate of PCPS cases (41%) was much better than that of VAD cases (19%). The main cause of death in VAD cases was multiple organ failure (MOF). Although VAB was initiated more recently than VAD, the duration on support was longer in the VAD group than in the VAB group. Because of the longer support duration and the presence of many patients with MOF, coagulopathy deteriorated more readily in the VAD group than in the VAB group. In the case of postcardiotomy cardiopulmonary bypass weaning or low-output syndrome (LOS), the VAB with PCPS system should be applied first under intraaortic balloon pumping assist because of its simplicity and low cost. Thereafter, VAD should be applied in cases refractory to VAB support.

In the last 10 years, 37 patients received assisted circulation or a ventricular assist device after open-heart operations at the Heart Institute of Japan. After cardiovascular surgery, 12 patients underwent venoarterial bypass (VAB), 13 had biventricular bypass (BVB), 8 had left ventricular bypass (LVB), and the remaining 4 received a left ventricular assist device (LVAD). Weaning and discharge rates of the patients by type of circulatory supports were 41.7 and 25.0% with VAB, 69.3 and 46.2% with BVB, 87.5 and 37.5% with LVB, 75.0 and 50.0% with LVAD, and 44.4 and 11.1% with PCPS, respectively. Concerning complications of postcardiotomy circulatory support, hemorrhage and ventricular arrhythmia postcardiotomy circulatory support, hemorrhage, and ventricular arrhythmia (immature weaning) decreased with low-heparinized isolated left ventricular supports (i.e., LVB, LVAD). However, profound biventricular failure, infection, and multiple organ failure remain as possible complications with any type of assisted circulation. These results suggest that early application of circulatory support and appropriate selection of the mode of support and devices used are important for successful circulatory support.

Intraabdominal infections are a wide range of diseases that include penetrating abdominal trauma, appendicitis, peritonitis, and abscess. Most are polymicrobic, involving aerobic and anaerobic bacteria. The primary treatment is surgery, but important issues regarding administration of antimicrobials may affect patient outcome. Evaluation of an antimicrobial regimen must include consideration of outcomes--survival, organ failure, adverse drug effects, and superinfection. Single-agent regimens have demonstrated benefit in patients with acute intraabdominal contamination and established infections. Guidelines for selecting antimicrobial agents are available from the Surgical Infection Society. Regimens are effective when active against most bacteria isolated from the focus of abdominal infection. The patient's clinical response, not culture results independent of clinical findings, is the primary guide for directing changes in therapy.

Unlabelled: According to our hypothesis ICU patients with signs of early hypercoagulation should develop more organ system failures that result in higher mortality rates and longer treatment periods. Routine coagulation tests are unreliable for measuring early hypercoagulation., Methods: Soluble fibrin (SF), reflecting hypercoagulation, was assessed at an early stage in 101 ICU patients. A spectrophotometric method using chromogenic peptide substrates was employed. The patients were divided into four groups, depending on the patient's highest level of SF within the first week after admission: Group I (21 patients), SF < 15 nmol/L (reference level); Group II (27 patients), SF 15-29 nmol/L; Group III (26 patients), SF 30-50 nmol/L and Group IV (27 patients), SF > 50 nmol/L. The number of secondary failing organ systems and the ventilator time, ICU time and mortality rates were recorded., Results: There was a significant increase in the number of secondary failing organ systems (P < 0.0001) and a significantly increased mortality for the groups with higher SF (P = 0.01). There was a mean of 0.6, 1.3, 2.4, and 3.4 failing organs and a mortality of 14%, 22%, 30%, and 46% in the respective groups. The ventilator time and the ICU time were longest in Group III, but again shorter for Group IV (with the highest mortality). The mean ventilator times were 2.7, 6.4, 8.4, and 5.9 days and the mean ICU times were 4.1, 8.6, 10.3, and 7.3 days in the respective groups. Thirteen patients with SF > 100 nmol/L had a mean of 4.2 failing organ systems and an 85% mortality., Conclusion: Soluble fibrin, a marker of hypercoagulation, seems to predict organ system failure and outcome in ICU patients.

Serum osmolality gap (OG), the difference between measured and predicted serum osmolality, has been shown to be an excellent parameter to express the amount of conventionally unmeasurable middle-molecular-weight substances. OG was determined on 29 patients with multiple organ failure (MOF) treated with or without hemopurification. OG significantly increased in proportion to the increase in the number of failed organs and correlated well with APACHE II score. Nonsurvivors showed persistently high OG. OG decreased with plasma exchange and hemoadsorption, but not with hemodialysis, indicating that pathogenic factors can be removed effectively with plasma exchange and hemoadsorption. The patients with OG greater than 20 mOsm/kg-H2O had very little possibility of survival. These results indicate that OG is an easily determinable, effective parameter to evaluate the severity of the patients' condition, efficacy of hemopurification in removing pathogenic middle-molecular-weight substances, and the prognosis of the patient in the treatment of MOF.