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3.  Prevention of Central Line–Associated Bloodstream Infections Through Quality Improvement Interventions: A Systematic Review and Meta-analysis 
Central venous catheters are associated with preventable bloodstream infections, leading to increased morbidity, length of stay, and costs. Quality improvement interventions aim to improve professional adherence to prevention measures. This meta-analysis provides evidence that quality improvement interventions decrease infection rates.
This systematic review and meta-analysis examines the impact of quality improvement interventions on central line–associated bloodstream infections in adult intensive care units. Studies were identified through Medline and manual searches (1995–June 2012). Random-effects meta-analysis obtained pooled odds ratios (ORs) and 95% confidence intervals (CIs). Meta-regression assessed the impact of bundle/checklist interventions and high baseline rates on intervention effect. Forty-one before–after studies identified an infection rate decrease (OR, 0.39 [95% CI, .33–.46]; P < .001). This effect was more pronounced for trials implementing a bundle or checklist approach (P = .03). Furthermore, meta-analysis of 6 interrupted time series studies revealed an infection rate reduction 3 months postintervention (OR, 0.30 [95% CI, .10–.88]; P = .03). There was no difference in infection rates between studies with low or high baseline rates (P = .18). These results suggest that quality improvement interventions contribute to the prevention of central line–associated bloodstream infections. Implementation of care bundles and checklists appears to yield stronger risk reductions.
PMCID: PMC4305144  PMID: 24723276
central line–associated bloodstream infection; catheter-related bloodstream infection; quality improvement intervention; meta-analysis
4.  Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes 
Critical Care  2015;19(1):7.
Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting.
An observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation.
A total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis.
IA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.
PMCID: PMC4344741  PMID: 25928694
5.  How to avoid microaspiration? A key element for the prevention of ventilator-associated pneumonia in intubated ICU patients 
BMC Infectious Diseases  2014;14:119.
Microaspiration of subglottic secretions through channels formed by folds in high volume-low pressure poly-vinyl chloride cuffs of endotracheal tubes is considered a significant pathogenic mechanism of ventilator-associated pneumonia (VAP). Therefore a series of prevention measures target the avoidance of microaspiration. However, although some of these can minimize microaspiration, benefits in terms of VAP prevention are not always obvious. Polyurethane-cuffed endotracheal tubes successfully reduce microaspiration but high quality data demonstrating VAP rate reduction are lacking. An analogous conclusion can be made regarding taper-shaped cuffs compared with classic barrel-shaped cuffs. More clinical data regarding these endotracheal tube designs are needed to demonstrate clinical value in addition to in vitro-based evidence. The clinical usefulness of endotracheal tubes developed for subglottic secretions drainage is established in multiple studies and confirmed by meta-analysis. Any change in cuff design will fail to prevent microaspiration if the cuff is insufficiently inflated. At least one well-designed trial demonstrated that continuous cuff pressure monitoring and control decrease the risk of VAP. Gel lubrication of the cuff prior to intubation temporarily hampers microaspiration through sludging the channels formed by folds in high volume-low pressure cuffs. As the beneficial effect of gel lubrication is temporarily, its potential to reduce VAP risk is probably nonsignificant. A minimum positive end-expiratory pressure of at least 5 cmH2O can be recommended as it reduces the risk of microaspiration in vitro and in vivo. One randomized controlled study demonstrated a reduced risk of VAP in patients ventilated with PEEP (5–8 cmH2O). Regarding head-of-bed elevation, it can be recommended to avoid supine positioning. Whether a 45° head-of-bed elevation is to be preferred above 25-30° head-of-bed elevation remains unproven. Finally, the routine monitoring of gastric residual volumes in mechanically ventilated patients receiving enteral nutrition cannot be recommended.
PMCID: PMC4289393  PMID: 25430629
Ventilator-associated pneumonia; Pneumonia; Micro-aspiration; Prevention; Infection
6.  Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study 
Critical Care  2014;18(3):R99.
The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response.
The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L).
Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5).
This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in critically ill patients is needed to more rapidly and consistently achieve sufficient vancomycin exposure.
PMCID: PMC4075416  PMID: 24887569
7.  Toothbrushing for preventing ventilator-associated pneumonia 
Critical Care  2013;17(2):417.
PMCID: PMC3672493  PMID: 23462424
8.  Prevention of ventilator-associated pneumonia in intensive care units: an international online survey 
On average 7% of patients admitted to intensive-care units (ICUs) suffer from a potentially preventable ventilator-associated pneumonia (VAP). Our objective was to survey attitudes and practices of ICUs doctors in the field of VAP prevention.
A questionnaire was made available online in 6 languages from April, 1st to September 1st, 2012 and disseminated through international and national ICU societies. We investigated reported practices as regards (1) established clinical guidelines for VAP prevention, and (2) measurement of process and outcomes, under the assumption “if you cannot measure it, you cannot improve it”; as well as attitudes towards the implementation of a measurement system. Weighted estimations for Europe were computed based on countries for which at least 10 completed replies were available, using total country population as a weight. Data from other countries were pooled together. Detailed country-specific results are presented in an online additional file.
A total of 1730 replies were received from 77 countries; 1281 from 16 countries were used to compute weighted European estimates, as follows: care for intubated patients, combined with a measure of compliance to this guideline at least once a year, was reported by 57% of the respondents (95% CI: 54–60) for hand hygiene, 28% (95% CI: 24–33) for systematic daily interruption of sedation and weaning protocol, and 27% (95%: 23–30) for oral care with chlorhexidine. Only 20% (95% CI: 17–22) were able to provide an estimation of outcome data (VAP rate) in their ICU, still 93% (95% CI: 91–94) agreed that “Monitoring of VAP-related measures stimulates quality improvement”. Results for 449 respondents from 61 countries not included in the European estimates are broadly comparable.
This study shows a low compliance with VAP prevention practices, as reported by ICU doctors in Europe and elsewhere, and identifies priorities for improvement.
PMCID: PMC3623895  PMID: 23531169
Healthcare associated infection; Ventilator-associated pneumonia; Patient safety; Preventive measures; Quality of care
9.  Essentials for Selecting Antimicrobial Therapy for Intra-Abdominal Infections 
Drugs  2012;72(6):e17-e32.
Intra-abdominal infection (IAI) is a complex disease entity in which different aspects must be balanced in order to select the proper antimicrobial regimen and determine duration of therapy. A current classification indicates different faces of peritonitis. Primary peritonitis implies an intact gastrointestinal tract without overt barrier disruption. Secondary peritonitis refers to localized or diffuse peritoneal inflammation and abscess formation due to disruption of the anatomical barrier. Tertiary peritonitis includes cases that cannot be solved by a single or even sequential surgical intervention, often in combination with sequential courses of antimicrobial therapy. The most frequently used classification distinguishes ‘uncomplicated’ and ‘complicated’ IAI. In uncomplicated IAI, the infectious process is contained within a single organ, without anatomical disruption. In complicated IAI, disease is extended, with either localized or generalized peritonitis. However, there exists more than a single dimension of complexity in IAI, including severity of disease expression through systemic inflammation. As the currently used classifications of IAI often incite confusion by mixing elements of anatomical barrier disruption, severity of disease expression and (the likelihood of) resistance involvement, we propose an alternative for the current widely accepted classification. We suggest abandoning the terms ‘uncomplicated’ and ‘complicated’ IAI, as they merely confuse the issue. Furthermore, the term ‘tertiary peritonitis’ should likewise be discarded, as this simply refers to treatment failure of secondary peritonitis resulting in a state of persistent infection and/or inflammation. Hence, anatomical disruption and disease severity should be separated into different phenotypes for the same disease in combination with either presence or absence of risk factors for involvement of pathogens that are not routinely covered in first-line antimicrobial regimens (Pseudomonas aeruginosa, enterococci, Candida species and resistant pathogens). Generally, these risk factors can be brought back to recent exposure to antimicrobial agents and substantial length of stay in healthcare settings (5–7 days). As such, we developed a grid based on the different components of the classification: (i) anatomical disruption; (ii) severity of disease expression; and (iii) either community-acquired/early-onset healthcare-associated origin or healthcare-associated origin and/or recent antimicrobial exposure. The grid allows physicians to define the index case of IAI in a more unequivocal way and to select the most convenient empirical antimicrobial regimens. The grid advises on the necessity of covering nosocomial Gram-negative bacteria (including P. aeruginosa), enterococci and yeasts. The basis of antimicrobial therapy for IAI is that both Gram-negative and anaerobic bacteria should always be covered.
In recent years, some newer agents such as doripenem, moxifloxacin and tigecycline have been added to the antimicrobial armamentarium for IAI. For patients in whom the source can be adequately controlled, antimicrobial therapy should be restricted to a short course (e.g. 3–7 days in peritonitis).
PMCID: PMC3585770  PMID: 22480338
10.  Impact estimates of nosocomial bloodstream infection: looking from a different angle 
Critical Care  2011;15(3):169.
Mortality associated with nosocomial bloodstream infection is multifactorial. Source of infection, etiology, age, underlying disease, acute illness, and appropriateness of antimicrobial therapy all contribute to the final outcome. As such, estimates of mortality attributable to bloodstream infection may differ largely according to the presence or absence of risk factors in distinct patient populations. The adverse effect of nosocomial bloodstream infection for the individual patient is substantial, with about a doubling of the risk of death. Yet, in settings with a high standard of care in terms of infection prevention and control, the occurrence rate of bloodstream infection is relatively low and therefore its impact on overall ICU mortality rather limited. As a consequence, untargeted interventional studies focused on infection prevention should use occurrence rate of infection rather than mortality as outcome variable.
PMCID: PMC3219020  PMID: 21745423
11.  The rising problem of antimicrobial resistance in the intensive care unit 
Mainly due to its extremely vulnerable population of critically ill patients, and the high use of (invasive) procedures, the intensive care unit (ICU) is the epicenter of infections. These infections are associated with an important rise in morbidity, mortality, and healthcare costs. The additional problem of multidrug-resistant pathogens boosts the adverse impact of infections in ICUs. Several factors influence the rapid spread of multidrug-resistant pathogens in the ICU, e.g., new mutations, selection of resistant strains, and suboptimal infection control. Among gram-positive organisms, the most important resistant microorganisms in the ICU are currently methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In gram-negative bacteria, the resistance is mainly due to the rapid increase of extended-spectrum Beta-lactamases (ESBLs) in Klebsiella pneumonia, Escherichia coli, and Proteus species and high level third-generation cephalosporin Beta-lactamase resistance among Enterobacter spp. and Citrobacter spp., and multidrug resistance in Pseudomonas aeruginosa and Acinetobacter species. To conclude, additional efforts are needed in the future to slow down the emergence of antimicrobial resistance. Constant evaluation of current practice on basis of trends in MDR and antibiotic consumption patterns is essential to make progress in this problematic matter.
PMCID: PMC3231873  PMID: 22112929
13.  Severe burn injury in europe: a systematic review of the incidence, etiology, morbidity, and mortality 
Critical Care  2010;14(5):R188.
Burn injury is a serious pathology, potentially leading to severe morbidity and significant mortality, but it also has a considerable health-economic impact. The aim of this study was to describe the European hospitalized population with severe burn injury, including the incidence, etiology, risk factors, mortality, and causes of death.
The systematic literature search (1985 to 2009) involved PubMed, the Web of Science, and the search engine Google. The reference lists and the Science Citation Index were used for hand searching (snowballing). Only studies dealing with epidemiologic issues (for example, incidence and outcome) as their major topic, on hospitalized populations with severe burn injury (in secondary and tertiary care) in Europe were included. Language restrictions were set on English, French, and Dutch.
The search led to 76 eligible studies, including more than 186,500 patients in total. The annual incidence of severe burns was 0.2 to 2.9/10,000 inhabitants with a decreasing trend in time. Almost 50% of patients were younger than 16 years, and ~60% were male patients. Flames, scalds, and contact burns were the most prevalent causes in the total population, but in children, scalds clearly dominated. Mortality was usually between 1.4% and 18% and is decreasing in time. Major risk factors for death were older age and a higher total percentage of burned surface area, as well as chronic diseases. (Multi) organ failure and sepsis were the most frequently reported causes of death. The main causes of early death (<48 hours) were burn shock and inhalation injury.
Despite the lack of a large-scale European registration of burn injury, more epidemiologic information is available about the hospitalized population with severe burn injury than is generally presumed. National and international registration systems nevertheless remain necessary to allow better targeting of prevention campaigns and further improvement of cost-effectiveness in total burn care.
PMCID: PMC3219295  PMID: 20958968
14.  Implementation of an evidence-based sepsis program in the intensive care unit: evident or not? 
Critical Care  2009;13(5):193.
Severe sepsis and septic shock are among the most serious health conditions and are associated with unwelcome clinical, social, and economic outcomes. With the introduction of the Surviving Sepsis Campaign guidelines, the campaign leaders aimed to reduce mortality from severe sepsis by at least one quarter by 2009 by means of a six-point action plan, namely, building awareness among health care professionals, improving early and accurate disease recognition and diagnosis, increasing the use of appropriate treatments and interventions, education, getting better post-intensive care unit access, and developing standard processes of care. However, adherence to these recommendations is a first but crucial step in obtaining these goals. A comprehensive evaluation of both, adherence to a sepsis program and whether this results in better outcomes for patients, is therefore essential to guide informed decision-making regarding the implementation of such an evidence-based protocol.
PMCID: PMC2784379  PMID: 19833007
15.  Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections 
BMC Infectious Diseases  2010;10:262.
The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission.
Baseline HIV-1 pol sequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients' demographics, laboratory and clinical data, were retrieved anonymously. Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics.
Multivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection with Chlamydia (p = 0.01) and infection with Hepatitis C virus (p = 0.017). More and larger transmission-clusters were identified among the subtype B infections (p < 0.001). Overall, in multivariate analysis, clustering was significantly associated with Caucasian origin, infection through homosexual contact and younger age (all p < 0.001). Bivariate analysis additionally showed a correlation between clustering and syphilis (p < 0.001), higher CD4 counts (p = 0.002), Chlamydia infection (p = 0.013) and primary HIV (p = 0.017).
Combination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions. This finding elucidates observed epidemiological trends through molecular analysis, and justifies sustained focus in prevention on this high risk group.
PMCID: PMC2940905  PMID: 20822507
16.  Determinants and impact of multidrug antibiotic resistance in pathogens causing ventilator-associated-pneumonia 
Critical Care  2008;12(6):R142.
The idea that multidrug resistance (MDR) to antibiotics in pathogens causing ventilator-associated pneumonia (VAP) is an independent risk factor for adverse outcome is still debated. We aimed to identify the determinants of MDR versus non-MDR microbial aetiology in VAP and assessed whether MDR versus non-MDR VAP was independently associated with increased 30-day mortality.
We performed a retrospective analysis of a prospectively registered cohort of adult patients with microbiologically confirmed VAP, diagnosed at a university hospital intensive care unit during a three-year period. Determinants of MDR as compared with non-MDR microbial aetiology and impact of MDR versus non-MDR aetiology on mortality were investigated using multivariate logistic and competing risk regression analysis.
MDR pathogens were involved in 52 of 192 episodes of VAP (27%): methicillin-resistant Staphylococcus aureus in 12 (6%), extended-spectrum β-lactamase producing Enterobacteriaceae in 28 (15%), MDR Pseudomonas aeruginosa and other non-fermenting pathogens in 12 (6%). Multivariable logistic regression identified the Charlson index of comorbidity (odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08 to 1.75, p = 0.01) and previous exposure to more than two different antibiotic classes (OR = 5.11, 95% CI = 1.38 to 18.89, p = 0.01) as predictors of MDR aetiology. Thirty-day mortality after VAP diagnosis caused by MDR versus non-MDR was 37% and 20% (p = 0.02), respectively. A multivariate competing risk regression analysis showed that renal replacement therapy before VAP (standardised hazard ratio (SHR) = 2.69, 95% CI = 1.47 to 4.94, p = 0.01), the Charlson index of comorbidity (SHR = 1.21, 95% CI = 1.03 to 1.41, p = 0.03) and septic shock on admission to the intensive care unit (SHR = 1.86, 95% CI = 1.03 to 3.35, p = 0.03), but not MDR aetiology of VAP, were independent predictors of mortality.
The risk of MDR pathogens causing VAP was mainly determined by comorbidity and prior exposure to more than two antibiotics. The increased mortality of VAP caused by MDR as compared with non-MDR pathogens was explained by more severe comorbidity and organ failure before VAP.
PMCID: PMC2646301  PMID: 19014695
17.  Discriminating invasive fungal infection from colonization 
Critical Care  2008;12(2):412.
PMCID: PMC2447572  PMID: 18439323
18.  Dynamics of C-reactive protein and white blood cell count in critically ill patients with nosocomial Gram positive vs. Gram negative bacteremia: a historical cohort study 
Nosocomial bacteremia is associated with a poor prognosis. Early adequate therapy has been shown to improve outcome. Consequently, rapid detection of a beginning sepsis is therefore of the utmost importance. This historical cohort study was designed to evaluate if different patterns can be observed in either C-reactive protein (CRP) and white blood cell count (WCC) between Gram positive bacteremia (GPB) vs. Gram negative bacteremia (GNB), and to assess the potential benefit of serial measurements of both biomarkers in terms of early antimicrobial therapy initiation.
A historical study (2003–2004) was conducted, including all adult intensive care unit patients with a nosocomial bacteremia. CRP and WCC count measurements were recorded daily from two days prior (d-2) until one day after onset of bacteremia (d+1). Delta (Δ) CRP and Δ WCC levels from the level at d-2 onward were calculated.
CRP levels and WCC counts were substantially higher in patients with GNB. Logistic regression analysis demonstrated that GNB and Acute Physiology and Chronic Health Evaluation (APACHE) II score were independently associated with a CRP increase of 5 mg/dL from d-2 to d+1, and both were also independently associated with an increase of WCC levels from d-2 to d+1 of 5,000 × 103 cells/mm3.
Increased levels of CRP and WCC are suggestive for GNB, while almost unchanged CRP and WCC levels are observed in patients with GPB. However, despite the different patterns observed, antimicrobial treatment as such cannot be guided based on both biomarkers.
PMCID: PMC2040151  PMID: 17868441
19.  To the editor: 
Journal of Korean Medical Science  2007;22(4):770-771.
PMCID: PMC2693838  PMID: 17728528
20.  Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients 
Critical Care  2006;10(1):R31.
The diagnosis of invasive pulmonary aspergillosis, according to the criteria as defined by the European Organisation for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG), is difficult to establish in critically ill patients. The aim of this study is to address the clinical significance of isolation of Aspergillus spp. from lower respiratory tract samples in critically ill patients on the basis of medical and radiological files using an adapted diagnostic algorithm to discriminate proven and probable invasive pulmonary aspergillosis from Aspergillus colonisation.
Using a historical cohort (January 1997 to December 2003), all critically ill patients with respiratory tract samples positive for Aspergillus were studied. In comparison to the EORTC/MSG criteria, a different appreciation was given to radiological features and microbiological data, including semiquantitative cultures and direct microscopic examination of broncho-alveolar lavage samples.
Over a 7 year period, 172 patients were identified with a positive culture. Of these, 83 patients were classified as invasive aspergillosis. In 50 of these patients (60%), no high risk predisposing conditions (neutropenia, hematologic cancer and stem cell or bone marrow transplantation) were found. Typical radiological imaging (halo and air-crescent sign) occurred in only 5% of patients. In 26 patients, histological examination either by ante-mortem lung biopsy (n = 10) or necropsy (n = 16) was performed, allowing a rough estimation of the predictive value of the diagnostic algorithm. In all patients with histology, all cases of clinical probable pulmonary aspergillosis were confirmed (n = 17). Conversely, all cases classified as colonisation had negative histology (n = 9).
A respiratory tract sample positive for Aspergillus spp. in the critically ill should always prompt further diagnostic assessment, even in the absence of the typical hematological and immunological host risk factors. In a minority of patients, the value of the clinical diagnostic algorithm was confirmed by histological findings, supporting its predictive value. The proposed diagnostic algorithm needs prospective validation.
PMCID: PMC1550813  PMID: 16507158
21.  Intra-abdominal hypertension in patients with severe acute pancreatitis 
Critical Care  2005;9(4):R452-R457.
Abdominal compartment syndrome has been described in patients with severe acute pancreatitis, but its clinical impact remains unclear. We therefore studied patient factors associated with the development of intra-abdominal hypertension (IAH), the incidence of organ failure associated with IAH, and the effect on outcome in patients with severe acute pancreatitis (SAP).
We studied all patients admitted to the intensive care unit (ICU) because of SAP in a 4 year period. The incidence of IAH (defined as intra-abdominal pressure ≥ 15 mmHg) was recorded. The occurrence of organ dysfunction during ICU stay was recorded, as was the length of stay in the ICU and outcome.
The analysis included 44 patients, and IAP measurements were obtained from 27 patients. IAH was found in 21 patients (78%). The maximum IAP in these patients averaged 27 mmHg. APACHE II and Ranson scores on admission were higher in patients who developed IAH. The incidence of organ dysfunction was high in patients with IAH: respiratory failure 95%, cardiovascular failure 91%, and renal failure 86%. Mortality in the patients with IAH was not significantly higher compared to patients without IAH (38% versus 16%, p = 0.63), but patients with IAH stayed significantly longer in the ICU and in the hospital. Four patients underwent abdominal decompression because of abdominal compartment syndrome, three of whom died in the early postoperative course.
IAH is a frequent finding in patients admitted to the ICU because of SAP, and is associated with a high occurrence rate of organ dysfunction. Mortality is high in patients with IAH, and because the direct causal relationship between IAH and organ dysfunction is not proven in patients with SAP, surgical decompression should not routinely be performed.
PMCID: PMC1269467  PMID: 16137360
22.  Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy 
Bacterial vaginosis (BV) is the single most common vaginal infection in women of childbearing age and associated with a sizeable infectious disease burden among both non-pregnant and pregnant women, including a significantly elevated risk of adverse pregnancy outcome. Overall, little progress has been made in identifying causal factors involved in BV acquisition and persistence. We sought to evaluate maternal iron status in early pregnancy as a putative risk factor for BV, considering that micronutrients, and iron deficiency in particular, affect the host response against bacterial colonization, even in the setting of mild micronutrient deficiencies.
In a nested case-control study, we compared maternal iron status at entry to prenatal care (mean gestational age 9.2 ± 2.6 weeks) between eighty women with healthy vaginal microflora and eighteen women with vaginosis-like microflora. Vaginal microflora status was assessed by assigning a modified Nugent score to a Gram-stained vaginal smear. Maternal iron status was assayed by an array of conventional erythrocyte and serum indicators for iron status assessment, but also by more sensitive and more specific indicators of iron deficiency, including soluble transferrin receptors (sTfR) as an accurate measure of cellular and tissue iron deficiency and the iron deficiency log10[sTfR/ferritin] index as the presently most accurate measure of body storage iron available.
We found no statistically significant correlation between vaginal microflora status and routinely assessed iron parameters. In contrast, a highly significant difference between the healthy and vaginosis-like microflora groups of women was shown in mean values of sTfR concentrations (1.15 ± 0.30 mg/L versus 1.37 ± 0.38 mg/L, p = 0.008) and in mean iron deficiency log10[sTfR/ferritin] index values (1.57 ± 0.30 versus 1.08 ± 0.56, p = 0.003), indicating a strong association between iron deficiency and vaginosis-like microflora. An sTfR concentration >1.45 mg/L was associated with a 3-fold increased risk (95%CI: 1.4–6.7) of vaginosis-like microflora and after controlling for maternal age, gestational length, body mass, parity, and smoking habits with an adjusted odds ratio of 4.5 (95%CI: 1.4–14.2).
We conclude that subclinical iron deficiency, presumably resulting from inadequate preconceptional iron supplies, is strongly and independently associated with vaginosis-like microflora during early pregnancy.
PMCID: PMC1199597  PMID: 16000177
23.  Perioperative factors determine outcome after surgery for severe acute pancreatitis 
Critical Care  2004;8(6):R504-R511.
There is evidence that postponing surgery in critically ill patients with severe acute pancreatitis (SAP) leads to improved survival, but previous reports included patients with both sterile and infected pancreatic necrosis who were operated on for various indications and with different degrees of organ dysfunction at the moment of surgery, which might be an important bias. The objective of this study is to analyze the impact of timing of surgery and perioperative factors (severity of organ dysfunction and microbiological status of the necrosis) on mortality in intensive care unit (ICU) patients undergoing surgery for SAP.
We retrospectively (January 1994 to March 2003) analyzed patients admitted to the ICU with SAP. Of 124 patients, 56 were treated surgically; these are the subject of this analysis. We recorded demographic characteristics and predictors of mortality at admission, timing of and indications for surgery, and outcome. We also studied the microbiological status of the necrosis and organ dysfunction at the moment of surgery.
Patients' characteristics were comparable in patients undergoing early and late surgery, and there was a trend toward a higher mortality in patients who underwent early surgery (55% versus 29%, P = 0.06). In univariate analysis, patients who died were older, had higher organ dysfunction scores at the day of surgery, and had sterile necrosis more often; there was a trend toward earlier surgery in these patients. Logistic regression analysis showed that only age, organ dysfunction at the moment of surgery, and the presence of sterile necrosis were independent predictors of mortality.
In this cohort of critically ill patients operated on for SAP, there was a trend toward higher mortality in patients operated on early in the course of the disease, but in multivariate analysis, only greater age, severity of organ dysfunction at the moment of surgery, and the presence of sterile necrosis, but not the timing of the surgical intervention, were independently associated with an increased risk for mortality.
PMCID: PMC1065077  PMID: 15566598
acute necrotizing pancreatitis; infected pancreatic necrosis; multiple organ failure; severe acute pancreatitis

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