Oddeke van Ruler

Variables associated with positive findings at relaparotomy in patients with secondary peritonitis.

Objective:The decision whether and when to perform a relaparotomy in secondary peritonitis is largely subjective and based on professional experience. No existing scoring system aids in this decisional process. Our aim was to search for variables that could predict positive findings at relaparotomy. Design:Retrospective, clinical study. Setting:Tertiary university hospital. Patients:Two hundred and nineteen patients of a consecutive series who underwent an emergency laparotomy for secondary peritonitis. Interventions:None. Sequential prediction models were constructed by accumulation of clinical information in chronological order using logistic regression to determine the strength of association between predictive variables and positive findings at relaparotomy outcome. Positive findings were defined as persistent peritonitis or a new infectious focus at relaparotomy. Measurements and Main Results:Relaparotomy (planned or on demand) for secondary peritonitis was performed in 117 of 219 patients (53%), yielding either positive (n = 62) or negative (n = 55) findings. Discriminatory power for positive findings at relaparotomy improved in the successive (multivariate) models: general patient characteristics (area under the curve, 0.60; 95% confidence interval, 0.52–0.68), adding peritonitis-related variables (area under the curve, 0.73; 95% confidence interval, 0.66–0.80), adding operation-related variables (area under the curve, 0.74; 95% confidence interval, 0.67–0.81), and adding postoperative variables (area under the curve, 0.87; 95% confidence interval, 0.82–0.92). Bootstrap resampling reduced the areas under the curve of the subsequent models only slightly. Sensitivity and specificity of the final model were 82% and 76%, respectively, at a total error rate of 16%. One preoperative predictor and five postoperative predictors significantly increased the need for relaparotomy: younger age, decreased hemoglobin levels, temperature >39°C, lower Pao2/Fio2 ratio, increased heart rate, and increased sodium levels. Conclusions:These data suggest that the causes of secondary peritonitis and findings at emergency laparotomy for peritonitis are poor indicators for whether patients will need a relaparotomy. Factors indicative of progressive or persistent organ failure during early postoperative follow-up are the best indicators for ongoing infection and associated positive findings at relaparotomy.

Clinical Predictors of Ongoing Infection in Secondary Peritonitis: Systematic Review

IntroductionThe decision to perform a relaparotomy in patients with secondary peritonitis is based on “clinical judgment” with inherent variability among surgeons. Our objective was to review the literature on prognostic variables for ongoing abdominal infection. Predictive variables for positive findings at relaparotomy can generate more objective criteria to support the decision whether to perform a relaparotomy in patients with secondary peritonitis.MethodsMultiple databases were searched for studies assessing the prognostic value of clinical variables predicting outcome of relaparotomy or general outcome in patients with secondary peritonitis. Data on the methodologic quality of the study as well as statistical strength of predictors and validity of individual variables were extracted and scored. A cumulative score was calculated from these three scores, and the variables were ranked.ResultsA total of 37 of 197 retrieved articles were included for final assessment. The median score for methodologic quality of individual articles was 36 (range 19–54). After calculation of the combined scores, 76 individual variables (patient, peritonitis, surgery, clinical, and laboratory variables) were identified from which the top 10 were eventually selected. These variables were age, concomitant disease, upper gastrointestinal source of peritonitis, generalized peritonitis, elimination of the focus, bilirubin, creatinine, lactate, PaO2/FiO2 ratio, and albumin. This set of variables proved to be moderately predictive for positive findings during relaparotomy in a retrospective cohort of 219 patients operated on for secondary peritonitis (receiver operator curve 0.75, with 95% confidence interval 0.68–0.82).ConclusionsThis review generated a hierarchy (weighted ranking) of published variables that could play a role in the decision to perform a relaparotomy in patients with secondary peritonitis. The top sixtile of ranked variables (10 variables) showed promising results in the discrimination between patients having a positive and negative relaparotomy when tested on a peritonitis patient database. This ranking of variables provides evidence for potential inclusion of variables in future predictive scores, although improvement in overall predictive strength of a set of variables in such a score is needed.

Failure of available scoring systems to predict ongoing infection in patients with abdominal sepsis after their initial emergency laparotomy

BackgroundTo examine commonly used scoring systems, designed to predict overall outcome in critically ill patients, for their ability to select patients with an abdominal sepsis that have ongoing infection needing relaparotomy.MethodsData from a RCT comparing two surgical strategies was used. The study population consisted of 221 patients at risk for ongoing abdominal infection. The following scoring systems were evaluated with logistic regression analysis for their ability to select patients requiring a relaparotomy: APACHE-II score, SAPS-II, Mannheim Peritonitis Index (MPI), MODS, SOFA score, and the acute part of the APACHE-II score (APS).ResultsThe proportion of patients requiring a relaparotomy was 32% (71/221). Only 2 scores had a discriminatory ability in identifying patients with ongoing infection needing relaparotomy above chance: the APS on day 1 (AUC 0.61; 95%CI 0.52-0.69) and the SOFA score on day 2 (AUC 0.60; 95%CI 0.52-0.69). However, to correctly identify 90% of all patients needing a relaparotomy would require such a low cut-off value that around 80% of all patients identified by these scoring systems would have negative findings at relaparotomy.ConclusionsNone of the widely-used scoring systems to predict overall outcome in critically ill patients are of clinical value for the identification of patients with ongoing infection needing relaparotomy. There is a need to develop more specific tools to assist physicians in their daily monitoring and selection of these patients after the initial emergency laparotomy.Trial registration numberISRCTN: ISRCTN 51729393

The innate immune response to secondary peritonitis.

ABSTRACT Secondary peritonitis continues to cause high morbidity and mortality despite improvements in medical and surgical therapy. This review combines data from published literature, focusing on molecular patterns of inflammation in pathophysiology and prognosis during peritonitis. Orchestration of the innate immune response is essential. To clear the microbial infection, activation and attraction of leukocytes are essential and beneficial, just like the expression of inflammatory cytokines. Exaggeration of these inflammatory systems leads to tissue damage and organ failure. Nonsurvivors have increased proinflammation, complement activation, coagulation, and chemotaxis. In these patients, anti-inflammatory systems are decreased in blood and lungs, whereas the abdominal compartment shows decreased neutrophil activation and decreased or stationary chemokine and cytokine levels. A later down-regulation of proinflammatory mediators with concomitant overexpression of anti-inflammatory mediators leads to immunoparalysis and failure to clear residual bacterial load, resulting in the occurrence of superimposed infections. Thus, in patients with adverse outcome, the inflammatory reaction is no longer contained within the abdomen, and the inflammatory response has shifted to other compartments. For the understanding of the host response to secondary peritonitis, it is essential to realize that the defense systems presumably are expressed differently and, in part, autonomously in different compartments.

Costs of relaparotomy on-demand versus planned relaparotomy in patients with severe peritonitis: an economic evaluation within a randomized controlled trial

IntroductionResults 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.MethodsAn 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.ResultsCosts 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.ConclusionsThe 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 RegistrationISRCTN51729393

sTREM-1 is a potential useful biomarker for exclusion of ongoing infection in patients with secondary peritonitis.

Identification of patients with ongoing abdominal infection after emergency surgery for abdominal sepsis is difficult. The purpose of this study was to evaluate whether plasma and abdominal fluid sTREM-1 levels can adequately select patients with ongoing abdominal infection. In a single center retrospective observational study, plasma and abdominal fluid samples were collected every 24 h for 4 days in patients who underwent an emergency laparotomy for severe secondary peritonitis. Patients after elective esophagus surgery served as controls. sTREM-1 levels were measured with an ELISA. Plasma sTREM-1 levels were not elevated compared to controls. Abdominal fluid sTREM-1 levels were initially high (median (246 [IQR 121-455] pg/ml), and declined 24 h after surgery (P=0.01). On day 2 and 3, patients with ongoing infection had significantly higher abdominal fluid sTREM-1 levels (319 [180-671] and 245 [173-541] pg/ml, respectively) compared to patients without infection (85 [49-306] and 121 [20-196] pg/ml, respectively). sTREM-1 levels were moderately predictive for persistent infection but had a high negative predictive value (0.86 (95% CI 0.69-0.94) below a cut-off level of 160 pg/ml. In clinical practice, abdominal fluid sTREM-1 levels may be useful for exclusion but not detection of ongoing abdominal infection after surgery for secondary peritonitis.

Has Mortality from Sepsis Improved and What to Expect from New Treatment Modalities: Review of Current Insights

BACKGROUND The incidence of sepsis is increasing continuously, making mortality rate reduction through improved intensive care unit (ICU) care and new treatment modalities a pressing issue. This study aimed to provide insight into the effects of modern ICU care on mortality trends from severe sepsis and to provide a quantitative review of the relative effectiveness of new treatment modalities in reducing deaths. METHODS Mortality data from severe sepsis were extracted from the control arms of several large randomized trials of sepsis treatment published within the last two decades. The effectiveness of recent treatment strategies was expressed as the number of patients it is necessary to treat by that method to save one life (number needed to treat: NNT). RESULTS Death from severe sepsis showed a decline from 44% to 35% between 1990 and 2000. The two most effective strategies in critically ill patients are early appropriate antibiotics (NNT 3; 95% confidence interval [CI] 2, 4) and early goal-directed therapy (NNT 6; 95% CI 4, 24). Infusion of recombinant human activated protein C is the most effective anticoagulant therapy (NNT 15; 95% CI 10, 27). Intensive insulin therapy is only moderately effective (NNT 27; 95% CI 15, 124). CONCLUSIONS The mortality rate from severe sepsis has decreased significantly with modernization of ICU care. New therapeutic strategies may reduce further the mortality rate. However, focused implementation of these new strategies in accordance with their relative effectiveness is needed before we can expect to see their true effect on mortality rates.

Single-drug therapy or selective decontamination of the digestive tract as antifungal prophylaxis in critically ill patients: a systematic review

IntroductionThe objective of this study was to determine and compare the effectiveness of different prophylactic antifungal therapies in critically ill patients on the incidence of yeast colonisation, infection, candidemia, and hospital mortality.MethodsA systematic review was conducted of prospective trials including adult non-neutropenic patients, comparing single-drug antifungal prophylaxis (SAP) or selective decontamination of the digestive tract (SDD) with controls and with each other.ResultsThirty-three studies were included (11 SAP and 22 SDD; 5,529 patients). Compared with control groups, both SAP and SDD reduced the incidence of yeast colonisation (SAP: odds ratio [OR] 0.38, 95% confidence interval [CI] 0.20 to 0.70; SDD: OR 0.12, 95% CI 0.05 to 0.29) and infection (SAP: OR 0.54, 95% CI 0.39 to 0.75; SDD: OR 0.29, 95% CI 0.18 to 0.45). Treatment effects were significantly larger in SDD trials than in SAP trials. The incidence of candidemia was reduced by SAP (OR 0.32, 95% CI 0.12 to 0.82) but not by SDD (OR 0.59, 95% CI 0.25 to 1.40). In-hospital mortality was reduced predominantly by SDD (OR 0.73, 95% CI 0.59 to 0.93, numbers needed to treat 15; SAP: OR 0.80, 95% CI 0.64 to 1.00). Effectiveness of prophylaxis reduced with an increased proportion of included surgical patients.ConclusionAntifungal prophylaxis (SAP or SDD) is effective in reducing yeast colonisation and infections across a range of critically ill patients. Indirect comparisons suggest that SDD is more effective in reducing yeast-related outcomes, except for candidemia.

A decision rule to aid selection of patients with abdominal sepsis requiring a relaparotomy.

BackgroundAccurate 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.MethodsData 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.ResultsOne 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.ConclusionsTo 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.

Health related quality of life six months following surgical treatment for secondary peritonitis – using the EQ-5D questionnaire

BackgroundTo compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL.DesignA prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQ-VAS 6-months following initial laparotomy.SettingMulticenter study in two academic and seven regional teaching hospitals.Patients130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires.ResultsHR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p < 0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS.ConclusionSix months following initial surgery, patients with secondary peritonitis report more problems in HR-QoL than a healthy reference population. Unfavorable disease characteristics at initial presentation were not predictive for poorer HR-QoL, but a more complicated course of the disease was most predictive of HR-QoL at 6 months.