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1.  A decision rule to aid selection of patients with abdominal sepsis requiring a relaparotomy 
BMC Surgery  2013;13:28.
Accurate and timely identification of patients in need of a relaparotomy is challenging since there are no readily available strongholds. The aim of this study is to develop a prediction model to aid the decision-making process in whom to perform a relaparotomy.
Data from a randomized trial comparing surgical strategies for relaparotomy were used. Variables were selected based on previous reports and common clinical sense and screened in a univariable regression analysis to identify those associated with the need for relaparotomy. Variables with the strongest association were considered for the prediction model which was constructed after backward elimination in a multivariable regression analysis. The discriminatory capacity of the model was expressed with the area under the curve (AUC). A cut-off analysis was performed to illustrate the consequences in clinical practice.
One hundred and eighty-two patients were included; 46 were considered cases requiring a relaparotomy. A prediction model was build containing 6 variables. This final model had an AUC of 0.80 indicating good discriminatory capacity. However, acceptable sensitivity would require a low threshold for relaparotomy leading to an unacceptable rate of negative relaparotomies (63%). Therefore, the prediction model was incorporated in a decision rule were the interval until re-assessment and the use of Computed Tomography are related to the outcome of the model.
To construct a prediction model that will provide a definite answer whether or not to perform a relaparotomy seems a utopia. However, our prediction model can be used to stratify patients on their underlying risk and could guide further monitoring of patients with abdominal sepsis in order to identify patients with suspected ongoing peritonitis in a timely fashion.
PMCID: PMC3750491  PMID: 23870702
Secondary peritonitis; Abdominal sepsis; Relaparotomy; On-demand; Prediction model; Decision rule
2.  Initial microbial spectrum in severe secondary peritonitis and relevance for treatment 
This study aims to determine whether abdominal microbial profiles in early severe secondary peritonitis are associated with ongoing infection or death. The study is performed within a randomized study comparing two surgical treatment strategies in patients with severe secondary peritonitis (n = 229). The microbial profiles of cultures retrieved from initial emergency laparotomy were tested with logistic regression analysis for association with ‘ongoing infection needing relaparotomy’ and in-hospital death. No microbial profile or the presence of yeast or Pseudomonas spp. was related to the risk of ongoing infection needing relaparotomy. Resistance to empiric therapy for gram positive cocci and coliforms was moderately associated with ongoing abdominal infection (OR 3.43 95%CI 0.95–12.38 and OR 7.61, 95%CI 0.75–76.94). Presence of only gram positive cocci, predominantly Enterococcus spp, was borderline independently associated with in-hospital death (OR 3.69, 95%CI 0.99–13.80). In secondary peritonitis microbial profiles do not predict ongoing abdominal infection after initial emergency laparotomy. However, the moderate association of ongoing infection with resistance to the empiric therapy compels to more attention for resistance when selecting empiric antibiotic coverage.
PMCID: PMC3319890  PMID: 21800218
3.  Diffuse postoperative peritonitis -value of diagnostic parameters and impact of early indication for relaparotomy 
Current criteria for performing relaparotomy for suspected peritonitis are non explicit and based on non-quantitative, subjective arguments or hospital practice. The aim of this study was to determine the value of routinely used clinical and diagnostic parameters in early detection of postoperative, diffuse peritonitis (PP). Furthermore, the prognosis and outcome after early indication for relaparotomy in patients with PP compared to community-aquired peritonitis (CAP) was evaluated.
Between 1999 and 2008, a total of 251 patients with diffuse secondary peritonitis either postoperative (PP) or community acquired (CAP) were analyzed retrospectively. PP (n = 114) and CAP (n = 137) were compared regarding physical examination, MPI-Score, APACHE II-Score, evidence of organ failure, laboratory parameters, diagnostic instruments and clinical course. The treatment regimen comprised surgical source control (with/without programmed lavage), abdominal closure and relaparotomy on demand, broad spectrum antibiotic therapy and intensive care support.
The APACHE II-Score (20 CAP vs. 22 PP, p = 0.012), MPI-Score (27 CAP vs. 30 PP, p = 0.001) and the number of lavages differed significantly. Positive phyiscal testing and signs of sepsis [abdominal pain (81.6% PP vs. CAP 97.1%, p = 0.03), rebound tenderness (21.9% vs. 35.8%, p = 0.02), fever (35.1% vs. 51.8%, p = 0.03)] occurred significantly less often in the PP patients than in the CAP group. Conventional radiography (66.2%) and ultrasonography (44.3%) had a lower diagnostic sensitivity than did abdominal CT-scan (97.2%). Mortality was higher in the PP group but did not differ significantly between the two groups (47.4% PP vs. 35.8% CAP, p = 0.06).
The value of physical tests and laboratory parameters in diagnosing abdominal sepsis is limited. CT-scanning revealed the highest diagnostic accuracy. A treatment regimen of early relaprotomy appears to be the most reasonable strategy for as early discovery of postoperative peritonitis as possible.
PMCID: PMC3352290  PMID: 19948445
peritonitis; abdominal sepsis; relaparotomy; diagnosis; treatment
4.  Costs of relaparotomy on-demand versus planned relaparotomy in patients with severe peritonitis: an economic evaluation within a randomized controlled trial 
Critical Care  2010;14(3):R97.
Results of the first randomized trial comparing on-demand versus planned-relaparotomy strategy in patients with severe peritonitis (RELAP trial) indicated no clear differences in primary outcomes. We now report the full economic evaluation for this trial, including detailed methods, nonmedical costs, further differentiated cost calculations, and robustness of different assumptions in sensitivity analyses.
An economic evaluation was conducted from a societal perspective alongside a randomized controlled trial in 229 patients with severe secondary peritonitis and an acute physiology and chronic health evaluation (APACHE)-II score ≥11 from two academic and five regional teaching hospitals in the Netherlands. After the index laparotomy, patients were randomly allocated to an on-demand or a planned-relaparotomy strategy. Primary resource-utilization data were used to estimate mean total costs per patient during the index admission and after discharge until 1 year after the index operation. Overall differences in costs between the on-demand relaparotomy strategy and the planned strategy, as well as relative differences across several clinical subgroups, were evaluated.
Costs were substantially lower in the on-demand group (mean, €65,768 versus €83,450 per patient in the planned group; mean absolute difference, €17,682; 95% CI, €5,062 to €29,004). Relative differences in mean total costs per patient (approximately 21%) were robust to various alternative assumptions. Planned relaparotomy consistently generated more costs across the whole range of different courses of disease (quick recovery and few resources used on one end of the spectrum; slow recovery and many resources used on the other end). This difference in costs between the two surgical strategies also did not vary significantly across several clinical subgroups.
The reduction in societal costs renders the on-demand strategy a more-efficient relaparotomy strategy in patients with severe peritonitis. These differences were found across the full range of healthcare resources as well as across patients with different courses of disease.
Trial Registration
PMCID: PMC2911734  PMID: 20507557
5.  Performance Assessment of the SOFA, APACHE II Scoring System, and SAPS II in Intensive Care Unit Organophosphate Poisoned Patients 
Journal of Korean Medical Science  2013;28(12):1822-1826.
This study assessed the ability of the Sequential Organ Failure Assessment (SOFA) and Acute Physiology, Chronic Health Evaluation (APACHE) II scoring systems, as well as the Simplified Acute Physiology Score (SAPS) II method to predict group mortality in intensive care unit (ICU) patients who were poisoned with organophosphate. The medical records of 149 organophosphate poisoned patients admitted to the ICU from September 2006 to December 2012 were retrospectively examined. The SOFA, APACHE II, and SAPS II were calculated based on initial laboratory data in the Emergency Department, and during the first 24 hr of ICU admission. The probability of death was calculated for each patient based on the SOFA score, APACHE II score, and SAPS II equations. The ability to predict group mortality by the SOFA score, APACHE II score, and SAPS II method was assessed using two by two decision matrices and receiver operating characteristic (ROC) curve analysis. A total of 131 patients (mean age, 61 yr) were enrolled. The sensitivities, specificities, and accuracies were 86.2%, 82.4%, and 83.2% for the SOFA score, respectively; 65.5%, 68.6%, and 67.9% for the APACHE II scoring system, respectively; and 86.2%, 77.5%, and 79.4% for the SAPS II, respectively. The areas under the curve in the ROC curve analysis for the SOFA score, APACHE II scoring system, and SAPS II were 0.896, 0.716, and 0.852, respectively. In conclusion, the SOFA, APACHE II, and SAPS II have different capability to discriminate and estimate early in-hospital mortality of organophosphate poisoned patients. The SOFA score is more useful in predicting mortality, and easier and simpler than the APACHE II and SAPS II.
PMCID: PMC3857381  PMID: 24339715
6.  Topical negative pressure in managing severe peritonitis: A positive contribution? 
AIM: To assess the use of topical negative pressure (TNP) in the management of severe peritonitis.
METHODS: This is a four-year prospective analysis from January 2005 to December 2008 of 20 patients requiring TNP following laparotomy for severe peritonitis.
RESULTS: There were 11 males with an average age of (59.3 ± 3.95) years. Nine had a perforated viscus, five had anastomotic leaks, three had iatrogenic bowel injury, and a further three had severe pelvic inflammatory disease. TNP and the VAC® Abdominal Dressing System were initially used. These were changed every two to three days. Abdominal closure was achieved in 15/20 patients within 4.53 ± 1.64 d. One patient required relaparotomy due to residual sepsis. Two patients with severe faecal peritonitis due to perforated diverticular disease received primary anastomosis at second look laparotomy, as sepsis and their general condition improved. In the remaining 5/20 cases, the abdomen was left open due to bowel oedema and or abdominal wall oedema. Dressing was switched to TNP and VAC® GranuFoam®. Three of the five patients returned a few months later for abdominal wall reconstruction and restoration of intestinal continuity. Two patients developed intestinal fistulae. All 20 patients survived.
CONCLUSION: The use of TNP is safe. Further studies are needed to assess its value in managing these difficult cases.
PMCID: PMC2712900  PMID: 19610140
Severe peritonitis; Open abdomen; Topical negative pressure; VAC® Abdominal Dressing System; VAC® GranuFoam®
7.  Should C-reactive protein concentration at ICU discharge be used as a prognostic marker? 
BMC Anesthesiology  2010;10:17.
About one third of hospital mortality in critically ill patients occurs after Intensive Care Unit (ICU) discharge. Some authors have recently hypothesized that unresolved or latent inflammation and sepsis may be an important factor that contributes to death following successful discharge from the ICU.
The aim of our study was to determine the ability of the clinical and inflammatory markers at ICU discharge to predict post-ICU mortality.
A prospective observational cohort study was conducted during a 14-month period in an 8 bed polyvalent ICU. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, Therapeutic Intervention Scoring System-28 (TISS-28), C-reactive protein (CRP), white cell count (WCC) and body temperature of the day of ICU discharge were collected from patients who survived their first ICU admission.
During this period 156 patients were discharged alive from the ICU. A total of 29 patients (18.6%) died after ICU discharge. There were no differences in clinical and demographic characteristics between survivors and nonsurvivors. C-reactive protein levels at ICU discharge were not significantly different between survivors and nonsurvivors. The area under receiver operating characteristics curves of APACHE II, SAPS II, SOFA, TISS-28, CRP, WCC and body temperature at ICU discharge as prognostic markers of hospital death were 0.76 (95% confidence interval (CI) 0.67-0.86); 0.75 (95% CI 0.66-0.85); 0.72 (95% CI 0.62-0.83); 0.64 (95% CI 0.52-0.77); 0.55 (95% CI 0.43-0.67); 0.55 (95% CI 0.42-0.66) and 0.54 (95% CI 0.44-0.67) respectively. The hospital mortality rate of the patients with CRP <5, 5-10, >10 mg/dL was 15.1%, 16.1% and 33.3% respectively (p = NS).
At ICU discharge serum CRP concentration was a poor marker of post-ICU prognosis. Post-ICU death appears to be unrelated to the persistent inflammatory response.
PMCID: PMC2954920  PMID: 20875120
8.  Comparison of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS 
Critical Care  1999;3(1):45-50.
The relation of procalcitonin (PCT) plasma concentrations compared with C-reactive protein (CRP) was analyzed in patients with different severity of multiple organ dysfunction syndrome (MODS) and systemic inflammation.
Patients and methods:
PCT, CRP, the sepsis-related organ failure assessment (SOFA) score, the Acute Physiology, Age, Chronic Health Evaluation (APACHE) II score and survival were evaluated in 40 patients with systemic inflammation and consecutive MODS over a period of 15 days.
Higher SOFA score levels were associated with significantly higher PCT plasma concentrations (SOFA 7-12: PCT 2.62 ng/ml, SOFA 19-24: PCT 15.22 ng/ml) (median), whereas CRP was elevated irrespective of the scores observed (SOFT 7-12: CRP 131 mg/l, SOFT 19-24: CRP 135 mg/l). PCT of non-surviving patients was initially not different from that of survivors but significantly increased after the fourth day following onset of the disease, whereas CRP was not different between both groups throughout the whole observation period.
Measurement of PCT concentrations during multiple organ dysfunction syndrome provides more information about the severity and the course of the disease than that of CRP. Regarding the strong association of PCT and the respective score systems in future studies we recommend evaluation also of the severity of inflammation and MODS when PCT concentrations were compared between different types of disease.
PMCID: PMC29013  PMID: 11056723
CRP; MODS; PCT; procalcitonin; sepsis; SOFA
9.  Complement Depletion Deteriorates Clinical Outcomes of Severe Abdominal Sepsis: A Conspirator of Infection and Coagulopathy in Crime? 
PLoS ONE  2012;7(10):e47095.
The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction.
This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored.
Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups.
Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845–0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications.
Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care.
Trial Registration NCT01568853
PMCID: PMC3473032  PMID: 23091606
10.  Positive effect of septimeb™ on mortality rate in severe sepsis: a novel non antibiotic strategy 
Septimeb is a new herbal-derived remedy, recently approved for its potential immunomodulatory effects. Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients; we evaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis.
In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II) score of more than 20 to receive standard treatment of severe sepsis (control group) or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-α, total antioxidant power, platelet growth factor and matrix metalloproteinase 2.
A total of 29 patients underwent randomization (13 in control group and 16 in Septimeb group). There was significant difference between the Septimeb and control group in the 14 days mortality rate (18.8% vs. 53.85 respectively, P=0.048). Compared to control group, Septimeb was significantly effective in improving SAPS (P= 0.029), SOFA (P=0.003) and APACHE II (P=0.008) scores. Inflammatory biomarkers didn’t change significantly between the two groups (P>0.05).
Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis.
PMCID: PMC3555989  PMID: 23351964
Severe sepsis; Immunomodulation; Septimeb; ICU
11.  Abdominal negative-pressure therapy: a new method in countering abdominal compartment and peritonitis - prospective study and critical review of literature 
Annals of Intensive Care  2012;2(Suppl 1):S23.
Application of abdominal negative-pressure therapy (NPT) is lifesaving when conservative measures fail to reduce sustained increase of the intra-abdominal pressure and it is impossible to achieve source control in a single operation due to severe peritonitis. The aim of this study is to share the initial experience with abdominal NPT in Latvia and provide a review of the relevant literature.
In total, 22 patients were included. All patients were treated with KCI® ABThera™ NPT systems. Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission, daily sequential organ failure assessment score and Mannheim peritonitis index (MPI) were calculated for severity definition. The frequency of NPT system changes, daily amount of aspirated fluid effluent and the time of abdominal closure were assessed. The overall hospital and ICU stay, as well as the outcomes and the complication rate, were analysed.
A complicated intra-abdominal infection was treated in 18 patients. Abdominal compartment syndrome due to severe acute pancreatitis (SAP), secondary ileus and damage control in polytrauma were indications for NPT in four patients. The median age of the patients was 59 years (range, 28 to 81), median APACHE II score was 15 points (range, 9 to 32) and median MPI was 28 points (range, 21 to 40), indicating a prognostic mortality risk of 60%. Sepsis developed in all patients, and in 20 of them, it was severe. NPT systems were changed on a median of every 4 days, and abdominal closure was feasible on the seventh postoperative day without needing a repeated laparotomy. Two NPT systems were removed due to bleeding from the retroperitoneal space in patients with SAP. Intestinal fistulae developed in three patients that were successfully treated conservatively. Incisional hernia occurred in three patients. The overall ICU and hospital stay were 14 (range, 5 to 56) and 25 days (range, 10 to 87), respectively. Only one patient died, contributing to the overall mortality of 4.5%.
Application of abdominal NPT could be a very promising technique for the control of sustained intra-abdominal hypertension and management of severe sepsis due to purulent peritonitis. Further trials are justified for a detailed evaluation of abdominal NPT indications.
PMCID: PMC3527158  PMID: 23281649
12.  Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score 
BMC Infectious Diseases  2012;12:184.
The aim of our study was to evaluate the prognostic value of MR-proADM and PCT levels in febrile patients in the ED in comparison with a disease severity index score, the APACHE II score. We also evaluated the ability of MR-proADM and PCT to predict hospitalization.
This was an observational, multicentric study. We enrolled 128 patients referred to the ED with high fever and a suspicion of severe infection such as sepsis, lower respiratory tract infections, urinary tract infections, gastrointestinal infections, soft tissue infections, central nervous system infections, or osteomyelitis. The APACHE II score was calculated for each patient.
MR-proADM median values in controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001), while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P < 0.0001). In all patients there was a statistically significant stepwise increase in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT levels were significantly increased in accordance with the Apache II quartiles (P < 0.0001 and P = 0.0012 respectively).
In the respiratory infections, urinary infections, and sepsis-septic shock groups we found a correlation between the Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We evaluated the ability of MR-proADM and PCT to predict hospitalization in patients admitted to our emergency departments complaining of fever. MR-proADM alone had an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and MR-proADM instead showed an AUC of 0.79.
The present study highlights the way in which MR-proADM and PCT may be helpful to the febrile patient’s care in the ED. Our data support the prognostic role of MR-proADM and PCT in that setting, as demonstrated by the correlation with the APACHE II score. The combined use of the two biomarkers can predict a subsequent hospitalization of febrile patients. The rational use of these two molecules could lead to several advantages, such as faster diagnosis, more accurate risk stratification, and optimization of the treatment, with consequent benefit to the patient and considerably reduced costs.
PMCID: PMC3447640  PMID: 22874067
Procalcitonin; Mid regional pro-Adrenomedullin; Fever; APACHE II score
13.  Comparison of severity of illness scoring systems for patients with nosocomial bloodstream infection due to Pseudomonas aeruginosa 
Several acute illness severity scores have been proposed for evaluating patients on admission to intensive care units but these have not been compared for patients with nosocomial bloodstream infection (nBSI). We compared three severity of illness scoring systems for predicting mortality in patients with nBSI due to Pseudomonas aeruginosa.
We performed a historical cohort study on 63 adults in intensive care units with P. aeruginosa monomicrobial nBSI.
The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiologic Score (SAPS II), were calculated daily from 2 days prior through 2 days after the first positive blood culture. Calculation of the area under the receiver operating characteristic (ROC) curve confirmed that APACHE II and SAPS II at day -1 and SOFA at day +1 were better predictors of outcome than days -2, 0 and day 2 of BSI. By stepwise logistic regression analysis of these three scoring systems, SAPS II (OR: 13.03, CI95% 2.51–70.49) and APACHE II (OR: 12.51, CI95% 3.12–50.09) on day -1 were the best predictors for mortality.
SAPS II and APACHE II are more accurate than the SOFA score for predicting mortality in this group of patients at day -1 of BSI.
PMCID: PMC1563469  PMID: 16916466
14.  Commonly Used Severity Scores Are Not Good Predictors of Mortality in Sepsis from Severe Leptospirosis: A Series of Ten Patients 
Introduction. Severe leptospirosis, also known as Weil's disease, can cause multiorgan failure with high mortality. Scoring systems for disease severity have not been validated for leptospirosis, and there is no documented method to predict mortality. Methods. This is a case series on 10 patients admitted to ICU for multiorgan failure from severe leptospirosis. Data were collected retrospectively, with approval from the Institution Ethics Committee. Results. Ten patients with severe leptospirosis were admitted in the Patras University Hospital ICU in a four-year period. Although, based on SOFA scores, predicted mortality was over 80%, seven of 10 patients survived and were discharged from the hospital in good condition. There was no association between SAPS II or SOFA scores and mortality, but survivors had significantly lower APACHE II scores compared to nonsurvivors. Conclusion. Commonly used severity scores do not seem to be useful in predicting mortality in severe leptospirosis. Early ICU admission and resuscitation based on a goal-directed therapy protocol are recommended and may reduce mortality. However, this study is limited by retrospective data collection and small sample size. Data from large prospective studies are needed to validate our findings.
PMCID: PMC3363413  PMID: 22675620
15.  Early recognition of abdominal compartment syndrome in patients with acute pancreatitis 
AIM: To assess the value of widely used clinical scores in the early identification of acute pancreatitis (AP) patients who are likely to suffer from intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS).
METHODS: Patients (n = 44) with AP recruited in this study were divided into two groups (ACS and non-ACS) according to intra-abdominal pressure (IAP) determined by indirect measurement using the transvesical route via Foley bladder catheter. On admission and at regular intervals, the severity of the AP and presence of organ dysfunction were assessed utilizing different multifactorial prognostic systems: Glasgow-Imrie score, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, and Multiorgan Dysfunction Score (MODS). The diagnostic performance of scores predicting ACS development, cut-off values and specificity and sensitivity were established using receiver operating characteristic (ROC) curve analysis.
RESULTS: The incidence of ACS in our study population was 19.35%. IAP at admission in the ACS group was 22.0 (18.5-25.0) mmHg and 9.25 (3.0-12.4) mmHg in the non-ACS group (P < 0.01). Univariate statistical analysis revealed that patients in the ACS group had significantly higher multifactorial clinical scores (APACHE II, Glasgow-Imrie and MODS) on admission and higher maximal scores during hospitalization (P < 0.01). ROC curve analysis revealed that APACHE II, Glasgow-Imrie, and MODS are valuable tools for early prediction of ACS with high sensitivity and specificity, and that cut-off values are similar to those used for stratification of patients with severe acute pancreatitis (SAP).
CONCLUSION: IAH and ACS are rare findings in patients with mild AP. Based on the results of our study we recommend measuring the IAP in cases when patients present with SAP (APACHE II > 7; MODS > 2 or Glasgow-Imrie score > 3).
PMCID: PMC2653440  PMID: 19222096
Acute pancreatitis; Abdominal compartment syndrome; Intra-abdominal pressure; Intra-abdominal hypertension; Organ dysfunction
16.  Reoperative Inflammatory Bowel Disease Surgery 
With the advent of restorative proctocolectomy or ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC), not only has there been potential for cure of UC but also patients have enjoyed marked improvements in bowel function, continence, and quality of life. However, IPAA can be complicated by postoperative small bowel obstruction, disease recurrence, and pouch failure secondary to pelvic sepsis, pouch dysfunction, mucosal inflammation, and neoplastic transformation. These may necessitate emergent or expeditious elective reoperation to salvage the pouch and preserve adequate function. Local, transanal, and transabdominal approaches to IPAA salvage are described, and their indications, outcomes, and the clinical parameters that affect the need for salvage are discussed. Pouch excision for failed salvage reoperation is reviewed as well. Relaparotomy is also frequently required for recurrent Crohn's disease (CD), especially given the nature of this as yet incurable illness. Risk factors for CD recurrence are examined, and the various surgical options and margins of resection are evaluated with a focus on bowel-sparing policy. Stricturoplasty, its outcomes, and its importance in recurrent disease are discussed, and segmental resection is compared with more extensive procedures such as total colectomy with ileorectal anastomosis. Lastly, laparoscopy is addressed with respect to its long-term outcomes, effect on surgical recurrence, and its application in the management of recurrent CD.
PMCID: PMC2780117  PMID: 20011321
Restorative proctocolectomy; pouch failure; salvage/reoperation; ulcerative colitis; recurrent Crohn's disease
17.  Intra-abdominal pressure in severe acute pancreatitis 
Hospital mortality in patients with severe acute pancreatitis (SAP) remains high. Some of these patients develop increased intra-abdominal pressure (IAP) which may contribute to organ dysfunction. The aims of this study were to evaluate the frequency of increased IAP in patients with SAP and to assess the development of organ dysfunction and factors associated with high IAP.
During 2001–2003 a total of 59 patients with severe acute pancreatitis were treated in the intensive care unit (ICU) of Helsinki University Hospital. IAP was measured by the intravesical route in 37 patients with SAP. Data from these patients were retrospectively reviewed.
Maximal IAP, APACHE II score, maximal SOFA score, maximal creatinine, age and maximal lactate were significantly higher in nonsurvivors. There was a significant correlation of the maximal IAP with the maximal SOFA, APACHE II, maximal creatinine, maximal lactate, base deficit and ICU length of stay. Patients were divided into quartiles according to the maximal IAP. Maximal IAP was 7–14, 15–18, 19–24 and 25–33 mmHg and the hospital mortality rate 10%, 12.5%, 22.2% and 50% in groups 1–4, respectively. A statistically significant difference was seen in the maximal SOFA, ICU length of stay, maximal creatinine and lactate values. The mean ICU-free days in groups 1–4 were 45.7, 38.8, 32.0 and 27.5 days, respectively. The difference between groups 1 and 4 was statistically significant.
In patients with SAP, increased IAP is associated with development of early organ failure reflected in increased mortality and fewer ICU-free days. Frequent measurement of IAP during intensive care is important in optimizing abdominal perfusion pressure and recognizing patients potentially benefitting from decompressive laparotomy.
PMCID: PMC1800837  PMID: 17227591
18.  A comparative study of four intensive care outcome prediction models in cardiac surgery patients 
Outcome prediction scoring systems are increasingly used in intensive care medicine, but most were not developed for use in cardiac surgery patients. We compared the performance of four intensive care outcome prediction scoring systems (Acute Physiology and Chronic Health Evaluation II [APACHE II], Simplified Acute Physiology Score II [SAPS II], Sequential Organ Failure Assessment [SOFA], and Cardiac Surgery Score [CASUS]) in patients after open heart surgery.
We prospectively included all consecutive adult patients who underwent open heart surgery and were admitted to the intensive care unit (ICU) between January 1st 2007 and December 31st 2008. Scores were calculated daily from ICU admission until discharge. The outcome measure was ICU mortality. The performance of the four scores was assessed by calibration and discrimination statistics. Derived variables (Mean- and Max- scores) were also evaluated.
During the study period, 2801 patients (29.6% female) were included. Mean age was 66.9 ± 10.7 years and the ICU mortality rate was 5.2%. Calibration tests for SOFA and CASUS were reliable throughout (p-value not < 0.05), but there were significant differences between predicted and observed outcome for SAPS II (days 1, 2, 3 and 5) and APACHE II (days 2 and 3). CASUS, and its mean- and maximum-derivatives, discriminated better between survivors and non-survivors than the other scores throughout the study (area under curve ≥ 0.90). In order of best discrimination, CASUS was followed by SOFA, then SAPS II, and finally APACHE II. SAPS II and APACHE II derivatives had discrimination results that were superior to those of the SOFA derivatives.
CASUS and SOFA are reliable ICU mortality risk stratification models for cardiac surgery patients. SAPS II and APACHE II did not perform well in terms of calibration and discrimination statistics.
PMCID: PMC3058022  PMID: 21362175
19.  The predictive value of resting heart rate following osmotherapy in brain injury: back to basics 
The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia.
To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS).
By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed.
After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07).
Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury.
PMCID: PMC3556066  PMID: 23351393
Heart rate; APACHE II score; SOFA score; GCS score; Head injury
20.  Sluggish decline in a post-transplant model for end-stage liver disease score is a predictor of mortality in living donor liver transplantation 
Korean Journal of Anesthesiology  2010;59(3):160-166.
The pre-transplant model for end-stage liver disease (pre-MELD) score is controversial regarding its ability to predict patient mortality after liver transplantation (LT). Prominent changes in physical conditions through the surgery may require a post-transplant indicator for better mortality prediction. We aimed to investigate whether the post-transplant MELD (post-MELD) score can be a predictor of 1-year mortality.
Perioperative variables of 269 patients with living donor LT were retrospectively investigated on their association with 1-year mortality. Post-MELD scores until the 30th day and their respective declines from the 1st day post-MELD score were included along with pre-MELD, acute physiology and chronic health evaluation (APACHE) II, and sequential organ failure assessment (SOFA) scores on the 1st post-transplant day. The predictive model of mortality was established by multivariate Cox's proportional hazards regression.
The 1-year mortality rate was 17% (n = 44), and the leading cause of death was graft failure. Among prognostic indicators, only post-MELD scores after the 5th day and declines in post-MELD scores until the 5th and 30th day were associated with mortality in univariate analyses (P < 0.05). After multivariate analyses, declines in post-MELD scores until the 5th day of less than 5 points (hazard ratio 2.35, P = 0.007) and prolonged mechanical ventilation ≥24 hours were the earliest independent predictors of 1-year mortality.
A sluggish decline in post-MELD scores during the early post-transplant period may be a meaningful prognostic indicator of 1-year mortality after LT.
PMCID: PMC2946032  PMID: 20877699
Liver transplantation; Living donor; Mortality; Prediction
21.  Identification of enhanced cytokine generation following sepsis. Dream of magic bullet for mortality prediction and therapeutic evaluation 
Background and the purpose of the study
sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU). Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management.
This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-α), Interleukin (IL)-1β and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR) status. Cytokines (TNF-α, IL-1β and IL-6) were assayed in the first, third and seventh days in blood of patients.
Results and major conclusion
Among three measured cytokines, sequential levels of TNF-α and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC) curve indicated that APACHE II (0.858, 0.848, 0.861) and IL-6 (0.797, 0.799, 0.899) had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-α in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients.
PMCID: PMC3304360  PMID: 22615611
TNF-α; IL-1β; IL-6; APACHE; SOFA; Severe sepsis
22.  The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation* 
Critical care medicine  2009;37(5):1649-1654.
Organ failure worsens outcome in sepsis. The Sequential Organ Failure Assessment (SOFA) score numerically quantifies the number and severity of failed organs. We examined the utility of the SOFA score for assessing outcome of patients with severe sepsis with evidence of hypoperfusion at the time of emergency department (ED) presentation.
Prospective observational study.
Urban, tertiary ED with an annual census of >110,000.
ED patients with severe sepsis with evidence of hypoperfusion. Inclusion criteria: suspected infection, two or more criteria of systemic inflammation, and either systolic blood pressure <90 mm Hg after a fluid bolus or lactate >4 mmol/L. Exclusion criteria age <18 years or need for immediate surgery.
SOFA scores were calculated at ED recognition (T0) and 72 hours after intensive care unit admission (T72). The primary outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate the predictive ability of SOFA scores at each time point. The relationship between Δ SOFA (change in SOFA from T0 to T72) was examined for linearity.
A total of 248 subjects aged 57 ± 16 years, 48% men, were enrolled over 2 years. All patients were treated with a standardized quantitative resuscitation protocol; the in-hospital mortality rate was 21%. The mean SOFA score at T0 was 7.1 ± 3.6 points and at T72 was 7.4 ± 4.9 points. The area under the receiver operating characteristic curve of SOFA for predicting in-hospital mortality at T0 was 0.75 (95% confidence interval 0.68 - 0.83) and at T72 was 0.84 (95% confidence interval 0.77-0.90). The Δ SOFA was found to have a positive relationship with in-hospital mortality.
The SOFA score provides potentially valuable prognostic information on in-hospital survival when applied to patients with severe sepsis with evidence of hypoperfusion at the time of ED presentation.
PMCID: PMC2703722  PMID: 19325482
sepsis; severe sepsis; scoring system; Sequential Organ Failure Assessment; mortality
23.  Continuous regional arterial infusion and laparotomic decompression for severe acute pancreatitis with abdominal compartment syndrome 
AIM: To evaluate the therapeutic effects of abdominal decompression plus continuous regional arterial infusion (CRAI) via a drug delivery system (DDS) in severe acute pancreatitis (SAP) patients with abdominal compartment syndrome (ACS).
METHODS: We presented our recent experience in 8 patients with SAP. The patients developed clinical ACS, which required abdominal decompression. During the operation, a DDS was inserted into the peripancreatic artery (the catheter was inserted from the right gastroepiploic artery until it reached the junction between the pancreaticoduodenal and gastroduodenal artery). Through this DDS, a protease inhibitor, antibiotics and octreotide were infused continuously. The duration of the regional artery infusion ranged from 8 to 41 d. The outcomes and the changes in the APACHE II score, computed tomography (CT) severity index and intra-abdominal pressure (IAP) of the patients were retrospectively evaluated.
RESULTS: Eight patients with an initial APACHE IIscore of 18.9 (range, 13-27) and a Balthazar CT severity index of 9.1 (range, 7-10) developed severe local and systemic complications. These patients underwent subsequent surgical decompression and CRAI therapy because of intra-abdominal hypertension (IAH). After a mean interval of 131.9 ± 72.3 d hospitalization, 7 patients recovered with decreased APACHE II scores, CT severity indexes and IAP. The mean APACHE II score was 5.4 (range, 4-8), the CT severity index was 2.3 (range, 1-3), and IAP decreased to 7.7 mmHg (range, 6-11 mmHg) 60 d after operation. One patient died of multiple organ failure 1 wk after surgery.
CONCLUSION: CRAI and laparotomic decompression might be a therapeutic option for SAP patients with ACS.
PMCID: PMC3235635  PMID: 22171133
Severe acute pancreatitis; Arterial infusion; Laparotomy; Abdominal compartment syndrome
24.  APACHE IV Is Superior to MELD Scoring System in Predicting Prognosis in Patients after Orthotopic Liver Transplantation 
This study aims to compare the efficiency of APACHE IV with that of MELD scoring system for prediction of the risk of mortality risk after orthotopic liver transplantation (OLT). A retrospective cohort study was performed based on a total of 195 patients admitted to the ICU after orthotopic liver transplantation (OLT) between February 2006 and July 2009 in Guangzhou, China. APACHE IV and MELD scoring systems were used to predict the postoperative mortality after OLT. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow C statistic were used to assess the discrimination and calibration of APACHE IV and MELD, respectively. Twenty-seven patients died during hospitalization with a mortality rate of 13.8%. The mean scores of APACHE IV and MELD were 42.32 ± 21.95 and 18.09 ± 10.55, respectively, and APACHE IV showed better discrimination than MELD; the areas under the receiver operating characteristic curve for APACHE IV and MELD were 0.937 and 0.694 (P < 0.05 for both models), which indicated that the prognostic value of APACHE IV was relatively high. Both models were well-calibrated (The Hosmer-Lemeshow C statistics were 1.568 and 6.818 for APACHE IV and MELD, resp.; P > 0.05 for both). The respective Youden indexes of APACHE IV, MELD, and combination of APACHE IV with MELD were 0.763, 0.430, and 0.545. The prognostic value of APACHE IV is high but still underestimates the overall hospital mortality, while the prognostic value of MELD is poor. The function of the APACHE IV is, thus, better than that of the MELD.
PMCID: PMC3855953  PMID: 24348682
25.  Intra-Abdominal Pressure in the Early Phase of Severe Acute Pancreatitis: Canary in a Coal Mine? Results from a Rigorous Validation Protocol 
Gut and Liver  2013;7(6):731-738.
Intra-abdominal hypertension (IAH) is being increasingly reported in patients with severe acute pancreatitis (SAP) with worsened outcomes. The present study was undertaken to evaluate intra-abdominal pressure (IAP) as a marker of severity in the entire spectrum of acute pancreatitis and to ascertain the relationship between IAP and development of complications in patients with SAP.
IAP was measured via the transvesical route by measurements performed at admission, once after controlling pain and then every 4 hours. Data were collected on the length of the hospital stay, the development of systemic inflammatory response syndrome (SIRS), multiorgan failure, the extent of necrosis, the presence of infection, pleural effusion, and mortality.
In total, 40 patients were enrolled and followed up for 30 days. The development of IAH was exclusively associated with SAP with an APACHE II score ≥8 and/or persistent SIRS, identifying all patients who were going to develop abdominal compartment syndrome (ACS). The presence of ACS was associated with a significantly increased extent of pancreatic necrosis, multiple organ failure, and mortality. The mean admission IAP value did not differ significantly from the value obtained after pain control or the maximum IAP measured in the first 5 days.
IAH is reliable marker of severe disease, and patients who manifest organ failure, persistent SIRS, or an Acute Physiology and Chronic health Evaluation II score ≥8 should be offered IAP surveillance. Severe pancreatitis is not a homogenous entity.
PMCID: PMC3848541  PMID: 24312716
Intra-abdominal hypertension; Pancreatitis

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