Excess ICU mortality attributable to ventilator-associated pneumonia: The role of early vs late onset

Objective To determine the impact of ventilator-associated pneumonia (VAP) on ICU mortality, and whether it is related to time of onset of pneumonia. Design Prospective cohort study. Setting 16-bed medical-surgical ICU at a university-affiliated hospital. Patients and measurements From 2002 to 2003, we recorded patients receiving mechanical ventilation for > 72 h. Patients developing an infection other than VAP were excluded. Patients definitively diagnosed with VAP (n = 40) were cases and patients free of any infection acquired during ICU stay (n = 61) were controls. The VAP-attributed mortality was defined as the difference between observed mortality and predicted mortality (SAPS II) on admission. Results Mechanical ventilation was longer in VAP patients (25 ± 20 vs 11 ± 9 days; p < 0.001), as was ICU stay (33 ± 23 vs 14 ± 12 days; p < 0.001). In the non-VAP group, no difference was found between observed and predicted mortality (27.9 vs 27.4%; p > 0.2). In the VAP group, observed mortality was 45% and predicted mortality 26.5% (p < 0.001), with attributable mortality 18.5%, and relative risk (RR) 1.7 (95% CI 1.12–23.17). No difference was observed between observed and predicted mortality in early-onset VAP (27.3 vs 25.8%; p > 0.20); in late-onset VAP, observed mortality was higher (51.7 vs 26.7%; p < 0.01) with attributable mortality of 25% and an RR 1.9 (95% CI 1.26–2.63). Empiric antibiotic treatment was appropriate in 77.5% of episodes. No differences in mortality were related to treatment appropriateness. Conclusions In mechanically ventilated patients, VAP is associated with excess mortality, mostly restricted to late-onset VAP and despite appropriate antibiotic treatment.     

Effects of vertical positioning on gas exchange and lung volumes in acute respiratory distress syndrome

Objective Supine position may contribute to the loss of aerated lung volume in patients with acute respiratory distress syndrome (ARDS). We hypothesized that verticalization increases lung volume and improves gas exchange by reducing the pressure surrounding lung bases.Design and setting Prospective observational physiological study in a medical ICU.Subjects and intervention In 16 patients with ARDS we measured arterial blood gases, pressure-volume curves of the respiratory system recorded from positive-end expiratory pressure (PEEP), and changes in lung volume in supine and vertical positions (trunk elevated at 45° and legs down at 45°).Measurements and results Vertical positioning increased PaO₂ significantly from 94 ± 33 to 142 ± 49 mmHg, with an increase higher than 40% in 11 responders. The volume at 20 cmH₂O measured on the PV curve from PEEP increased using the vertical position only in responders (233 ± 146 vs. –8 ± 91 ml in nonresponders); this change was correlated to oxygenation change (ρ = 0.55). End-expiratory lung volume variation from supine to vertical and 1 h later back to supine, measured in 12 patients showed a significant increase during the 1-h upright period in responders (n = 7) but not in nonresponders (n = 5; 215 ± 220 vs. 10 ± 22 ml), suggesting a time-dependent recruitment.Conclusions Vertical positioning is a simple technique that may improve oxygenation and lung recruitment in ARDS patients.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Outcome in bacteremia associated with nosocomial pneumonia and the impact of pathogen prediction by tracheal surveillance cultures

Objective To assess whether pathogen prediction in bacteremia associated with nosocomial pneumonia (NP) by tracheal surveillance cultures improves adequacy of early antibiotic therapy and impacts mortality.Design and setting A retrospective observational study of a prospectively gathered cohort. This cohort included all adult patients admitted to the ICU of a tertiary care hospital from 1992 through 2001 and who developed bacteremia associated with NP. Measurements and main results 128 episodes of bacteremia associated with NP were identified. In 110 episodes a tracheal surveillance culture 48–96 h prior to bacteremia was available: this culture predicted the pathogen in 67 episodes (61%). Overall rates of appropriate empiric antibiotic therapy within 24 and 48 h were 62 and 87%, respectively. Pathogen prediction was associated with a significantly higher rate of appropriate antibiotic therapy within 24 h (71 vs 45%; p = 0.01), but not within 48 h (91 vs 82%; p = 0.15). Crude in-hospital mortality was 50%. Pathogen prediction was associated with increased survival in univariate (OR 0.43; CI 0.19–0.93; p = 0.04) and multivariate analysis (OR 0.32; CI 0.12–0.82; p = 0.02). Multivariate analysis further identified age (OR 1.04; CI 1.01–1.07; p = 0.02), increasing APACHE II score (OR 1.08; CI 1.02–1.15; p = 0.01), and methicillin-resistant Staphylococcus aureus (OR 5.90; CI 1.36–25.36; p = 0.01) and Pseudomonas aeruginosa (OR 3.30; CI 1.04–10.4; p = 0.04) as independent risk factors for mortality.Conclusion Pathogen prediction in bacteremia associated with NP by tracheal surveillance cultures is associated with a higher rate of adequate empiric antibiotic therapy within 24 h and with increased survival.     

Cytokeratin 19 fragments in patients with acute lung injury: a preliminary observation

Objective Cytokeratin 19 (CK19) is a specific cytoskeletal structure for alveolar epithelium. We hypothesized that the levels of CK19 fragments in bronchoalveolar lavage (BAL) fluid could serve as an index of epithelial injury and as a prognosis marker in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The aims of our study were, in patients with ALI/ARDS: (1) to measure CK19 fragments concentrations in BAL fluid, (2) to assess its prognostic value, and (3) to identify the cellular source of CK19 in the alveolar space.Design Prospective preliminary study.Setting University hospital surgical ICU.Patients Twenty-two mechanically ventilated patients with ALI/ARDS and 10 non-ventilated control patients. Plasma samples were obtained for 11 ALI/ARDS patients.Measurements and results The concentration of BAL CK19 fragments was higher in patients (median 4916 pg/ml, 25th–75th percentile 2717–10533) than in controls (2208 pg/ml. 767–3923; p = 0.05), and higher in 10 non-survivors (7051 pg/ml, 4372–13371) than in 12 survivors (2888 pg/ml, 1315–5639; p = 0.03 among ALI/ARDS patients). BAL CK19 fragment concentration did not correlate with simplified acute physiologic score, lung injury score or PaO₂/FIO₂ ratio, but correlated positively with BAL albumin concentration (p = 0.002) and with number of BAL macrophages (p = 0.0001). Plasma CK19 fragment concentrations were 10 times lower than those in BAL. Immunohistochemical staining for CK19 showed a strong labelling of injured detached epithelial cells and hyperplastic epithelium in ALI/ARDS lung samples.Conclusion CK19 fragment concentrations were found to be elevated in BAL fluid in ALI/ARDS patients compared with control subjects. High BAL CK19 fragment levels were associated with a poor prognosis.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.     

Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature

Objectives To compare the design and results of randomized trials investigating prolonged glucocorticoid treatment (≥ 7 days) in patients with acute lung injury–acute respiratory distress syndrome (ALI–ARDS), and review factors affecting response to therapy, including the role of secondary prevention. Design Trials were retrieved from the Cochrane Central Register of Controlled Trials (CENTRAL). Two investigators collected data on study characteristics, treatment intervention, and outcomes. The methodological quality of trials was determined and data were analyzed with Review Manager 4.2.3. Measurements and results Five selected trials (n = 518) consistently reported significant improvement in gas exchange, reduction in markers of inflammation, and decreased duration of mechanical ventilation and intensive care unit stay (all p < 0.05). Two early small clinical trials showed marked reductions in the relative risk (RR) of death with glucocorticoid therapy (RR = 0.14, 95% CI 0.04–0.53; p = 0.004, I² = 0%). Three subsequent larger trials, when combined, although nominally beneficial, did not reproduce the marked reductions observed in the earlier trials (RR = 0.84; 95% CI 0.68–1.03; p = 0.09, I² = 9.1%), but achieved a distinct reduction in the RR of death in the larger subgroup of patients (n = 400) treated before day 14 of ARDS [82/214 (38%) vs. 98/186 (52.5%), RR = 0.78; 95% CI 0.64–0.96; p = 0.02, I² = 0%]. Conclusions Prolonged glucocorticoid treatment substantially and significantly improves meaningful patient-centered outcome variables, and has a distinct survival benefit when initiated before day 14 of ARDS.     

Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study

Objective To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO₂) and prevents intramucosal acidosis in septic shock. Design Prospective, controlled experimental study. Setting University-based research laboratory. Subjects Nineteen anesthetized, mechanically ventilated sheep. Interventions Endotoxin-treated sheep were randomly assigned to three groups: control (n = 7), dobutamine (10 μg/kg/min, n = 6) and levosimendan (100 μg/kg over 10 min followed by 100 μg/kg/h, n = 6) and treated for 120 min. Measurements and main results After endotoxin administration, systemic and intestinal DO₂ decreased (24.6 ± 5.2 vs 15.3 ± 3.4 ml/kg/min and 105.0 ± 28.1 vs 55.8 ± 25.9 ml/kg/min, respectively; p < 0.05 for both). Arterial lactate and the intramucosal–arterial PCO₂ difference (ΔPCO₂) increased (1.4 ± 0.3 vs 3.1 ± 1.5 mmHg and 9 ± 6 vs 23 ± 6 mmHg mmol/l, respectively; p < 0.05). Systemic DO₂ was preserved in the dobutamine-treated group (22.3 ± 4.7 vs 26.8 ± 7.0 ml/min/kg, p = NS) but intestinal DO₂ decreased (98.9 ± 0.2 vs 68.0 ± 22.9 ml/min/kg, p < 0.05) and ΔPCO₂ increased (12 ± 5 vs 25 ± 11 mmHg, p < 0.05). The administration of levosimendan prevented declines in systemic and intestinal DO₂ (25.1 ± 3.0 vs 24.0 ± 6.3 ml/min/kg and 111.1 ± 18.0 vs 98.2 ± 23.1 ml/min/kg, p = NS for both) or increases in ΔPCO₂ (7 ± 7 vs 10 ± 8, p = NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6 ± 0.3 vs 2.5 ± 0.7 and 1.4 ± 0.4 vs. 2.9 ± 1.1 mmol/l, p = NS between groups). Conclusions Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This study was solely funded by the Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata. None of the authors have any financial interests to disclose. This article is discussed in the editorial available at: .     

De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate

Objective To assess outcomes with de-escalation therapy in ventilator-associated pneumonia (VAP). Design Prospective observational study. Setting Multidisciplinary intensive care unit. Patients and participants VAP was diagnosed by positive quantitative cultures of both tracheal aspirate and bronchoalveolar lavage (BAL) and treated appropriately for all significant isolates of tracheal aspirate and BAL in 143 patients who were assigned to de-escalation therapy by BAL or tracheal aspirate. Interventions None. Measurements and results Antibiotic therapy was de-escalated in 58 patients (40.5%), who had decreased mortality at day 15 (5.1% vs. 31.7%) and day 28 (12% vs. 43.5%) and shorter intensive care unit (17.2 ± 1.2 vs. 22.7 ± 6.3 days) and hospital (23.7 ± 2.8 vs. 29.8 ± 11.1 days) stay (p < 0.05). Of the 81 patients assigned to tracheal aspirate, the 17 (21%) who achieved de-escalation of therapy had reduced 15-day mortality (5.8% vs. 34.3%), reduced 28-day mortality (11.6% vs. 45.3%), and shorter intensive care unit (17.2 ± 1.6 vs. 22.4 ± 6.4 days) and hospital (23.1 ± 4.4 vs. 29.9 ± 11.1 days) stay (p < 0.05). Of the 62 patients assigned to BAL, the 41 (66.1%) who achieved de-escalation of therapy had decreased 15-day mortality (4.8% vs. 23.8%), decreased 28-day mortality (12.1% vs. 38%), and shorter intensive care unit (17.2 ± 1.1 vs. 23.2 ± 6 days) and hospital (23.8 ± 2.4 vs. 29.8 ± 11.4 days) stay (p < 0.05). Conclusions For patients with VAP who have had appropriate treatment and shown a favorable clinical response, mortality and duration of stay can be further improved by de-escalation therapy.     

Point of care management of heparin administration after heart surgery

Objectives Determination of activated partial thromboplastin time (aPTT) is used in coagulation management after heart surgery. Results from the central laboratory take long to be obtained. We sought to shorten the time to obtain coagulation results and the desired coagulation state and to reduce blood loss and transfusions using point of care (POC) aPTT determination.Design Randomized, controlled trial.Setting University-affiliated 20-bed surgical ICU.Patients and participants Forty-two patients planned for valve surgery (Valves) and 84 for coronary artery bypass grafting (CABG) with cardiopulmonary bypass.Interventions Valves and CABG were randomized to postoperative coagulation management monitored either by central laboratory aPTT (Lab group) or by POC aPTT (POC group). Heparin was administered according to guidelines.Measurements and results POC aPTT results were available earlier than Lab aPTT after venipuncture in Valves (3 ± 2 vs. 125 ± 68 min) and in CABG (3 ± 4 vs. 114 ± 62 min). Heparin was introduced earlier in the POC group in Valves (7 ± 23 vs. 13 ± 78 h, p = 0.01). Valves of the POC group bled significantly less than Valves in the Lab group (647 ± 362 ml vs. 992 ± 647ml, p < 0.04), especially during the first 8 h after ICU admission. There was no difference in bleeding in CABG (1074 ± 869 ml vs. 1102 ± 620, p = NS). In Valves, fewer patients in the POC group than in the Lab group needed blood transfusions (1/21 vs. 8/21; p = 0.03). No difference was detected in CABG.Conclusions In Valves in the POC group the time to the desired coagulation state was reduced, as was the thoracic blood loss, reducing the number of patients transfused. This improvement was not observed in CABG. Side effects were similar in the two groups.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.Presented in part at the annual congress of the European Society of Intensive Care Medicine (ESICM) in Amsterdam, 6–8 October 2003.     

Urinary biomarker of oxidative stress correlating with outcome in critically septic patients

Objective To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Design and setting Clinical outcome study in an adult medical ICU. Patients Eighty-five consecutive septic patients: 59 men and 26 women. Measurements and results Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality in these 85 septic patients was 25.9% (n = 22) and hospital mortality 38.8% (n = 33). APACHE II scores of survivors on day 1, on day 3, and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. Conclusions This is a preliminary study. The excretion of the urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, as the APACHE II score, were correlated with the outcome of critically septic patients in medical ICU. An erratum to this article can be found at     

Adult congenital heart disease: intensive care management and outcome prediction

Objective Improved patient survival and increasingly complex surgery have expanded the requirement for specialist care for patients with adult congenital heart disease (ACHD). Despite the recent publications of management guidelines for ACHD, data concerning optimal patterns of care in the peri-operative/critical care period of this challenging population are sparse. The aims of the current study were to therefore to determine the pattern of intensive care unit (ICU) management, resource utilisation and predictors of mortality in critically ill ACHD patients. Design, setting and patients Data were collected prospectively for patients with ACHD stratified for complexity of disease admitted to the ICU of a tertiary cardiothoracic centre (1997–2002). Multivariate analysis of pre-operative indices as predictors of mortality was performed. Of 342 ACHD admissions (total mortality 4.4%, simple 0%, moderate/complex 10.6%), the requirement for specialist investigations and interventions was high, reflected in ICU admission costs per patient (simple $5391 ± 130, moderate $13218 ± 261, complex $30074 ± 689). Standard severity of illness scoring systems did not accurately predict mortality; however, abnormal pre-operative thyroid function (p = 0.0048), creatinine (p = 0.0032) and bilirubin (p = 0.0021) were highly predictive of mortality. Conclusions Peri-operative mortality in patients with ACHD is low overall but varies with disease complexity. Such patients have a high requirement for specialist ICU investigation/intervention. Although standard severity of illness scoring is unhelpful, simple pre-operative parameters may predict peri-operative mortality. These findings reflect the requirement for specialist care, and have implications for planning service provision, training and operative consent in ACHD patients.     

Validation of the SAPS 3 admission prognostic model in patients with cancer in need of intensive care

Objectives To validate the SAPS 3 admission prognostic model in patients with cancer admitted to the intensive care unit (ICU).Design Cohort study.Setting Ten-bed medical–surgical oncologic ICU.Patients and participants Nine hundred and fifty-two consecutive patients admitted over a 3-year period.Interventions None.Measurements and results Data were prospectively collected at admission of ICU. SAPS II and SAPS 3 scores with respective estimated mortality rates were calculated. Discrimination was assessed by area under receiver operating characteristic (AUROC) curves and calibration by Hosmer–Lemeshow goodness-of-fit test. The mean age was 58.3 ± 23.1 years; there were 471 (49%) scheduled surgical, 348 (37%) medical and 133 (14%) emergency surgical patients. ICU and hospital mortality rates were 24.6% and 33.5%, respectively. The mean SAPS 3 and SAPS II scores were 52.3 ± 18.5 points and 35.3 ± 20.7 points, respectively. All prognostic models showed excellent discrimination (AUROC ≥ 0.8). The calibration of SAPS II was poor (p < 0.001). However, the calibration of standard SAPS 3 and its customized equation for Central and South American (CSA) countries were appropriate (p > 0.05). SAPS II and standard SAPS 3 prognostic models tended somewhat to underestimate the observed mortality (SMR > 1). However, when the customized equation was used, the estimated mortality was closer to the observed mortality [SMR = 0.95 (95% CI = 0.84–1.07)]. Similar results were observed when scheduled surgical patients were excluded.Conclusions The SAPS 3 admission prognostic model at ICU admission, in particular its customized equation for CSA, was accurate in our cohort of critically ill patients with cancer.This work was performed at the Intensive Care Unit, Instituto Nacional de Cancer, Rio de Janeiro, Brazil. Financial support: institutional departmental funds. Conflicts of interest: none.     

Mean glucose level is not an independent risk factor for mortality in mixed ICU patients

Objective To find out if there is an association between hyperglycaemia and mortality in mixed ICU patients. Design and setting Retrospective cohort study over a 2-year period at the medical ICU of a university hospital. Measurements Admission glucose, maximum and mean glucose, length of stay, mortality, insulin therapy and Apache-II score. Results In 1085 consecutive patients, ICU- and hospital mortality were 20 and 25%, respectively. The total number of blood glucose measurements was 10.012. Admission glucose was 7.9 ± 4.5 mmol/l (mean ± SD), mean glucose 7.5 ± 2.9 and maximum glucose 10.0 ± 5.4 mmol/l. Median ICU length of stay (LOS) was 3.0 days (range 2.0–6.0 days, IQR), and hospital LOS was 16 days (range 7–32 days). In 28% of patients insulin treatment was started. Median Apache-II score was 13. 68% of patients were mechanically ventilated. Univariate analysis showed an association with ICU mortality for mean glucose (non-survivors 8.6 ± 4.3 vs 7.2 ± 2.4 survivors), maximum glucose (11.7 ± 5.9 vs 9.6 ± 5.2, non-survivors vs survivors, respectively), use of insulin (mortality 29 vs 17% in patients not using insulin) and age (61 vs 55.7 years). Gender and a history of diabetes mellitus were not associated with mortality. In a multivariate model, the Apache-II score was the only variable associated with mortality independent of other variables, including mean blood glucose. Conclusion In this retrospective study mean glucose level was not an independent risk factor for mortality in mixed ICU patients.     

Replacement of 24-h creatinine clearance by 2-h creatinine clearance in intensive care unit patients: a single-center study

Objective To estimate the usefulness of 2-h creatinine clearance (CrCl) in the ICU and define variables that may reduce agreement. Design Prospective study. Setting Polyvalent ICU of a university hospital. Patients 359 patients. Interventions We compared 24-h CrCl (CrCl-24h), as the standard measure, with 2-h CrCl (CrCl-2h) (at the start of the period) and the Cockroft–Gault equation (Ck-G). Measurements and results The 2-h sample was lost in two patients (0.6%) and the 24-h sample was lost in 50 patients (13.9%). The mean Ck-G was 87.4 ± 3.05, with CrCl-2h 109.2 ± 4.46 and CrCl-24h 100.9 ± 4.21 ml/min/1.73 m² (r ² of 0.88 for CrCl-2h and 0.84 for Ck-G). The differences from ClCr-24h were 21.8 ± 3.3 ( p < 0.001) for the Ck-G and 8.3 ± 2.6 ( p < 0.05) for CrCl-2h ( p < 0.05). In the subgroup of patients with CrCl-24h < 100 ml/min/1.73 m², the CrCl-24h value was 52.9 ± 2.71 vs. 51.6 ± 2.14 for CrCl-2h ( p = ns) and 57.6 ± 2.56 ( p < 0.001) for the Ck-G. Patients with CrCl < 100 ml/min only showed variability in hyperglycemia during the 24-h period. Conclusions In intensive care patients, 24-h CrCl results in a large proportion of non-valid determinations, even under conditions of close monitoring. Two-hour CrCl is an adequate substitute, even in patients who are unstable or who have irregular diuresis where a 24-h collection is impossible. The Cockroft–Gault equation seems less useful in this setting. All the authors participated actively in the present study. This is an original paper that has not been submitted for publication elsewhere, though partial results of the study were presented at the Annual Congress of the ESICM in Amsterdam (September 2005), and the final results were presented at the Annual Congress of the SEMICYUC (Pamplona, 2006). The authors received no external financing for conduct of the study, and there are no conflicts of interest for any of them. This article is discussed in the editorial available at: .     

Is there a safe plateau pressure in ARDS? The right heart only knows

Objective Airway pressure limitation is now a largely accepted strategy in adult respiratory distress syndrome (ARDS) patients; however, some debate persists about the exact level of plateau pressure which can be safely used. The objective of the present study was to examine if the echocardiographic evaluation of right ventricular function performed in ARDS may help to answer to this question. Design and patients For more than 20 years, we have regularly monitored right ventricular function by echocardiography in ARDS patients, during two different periods, a first (1980–1992) where airway pressure was not limited, and a second (1993–2006) where airway pressure was limited. By pooling our data, we can observe the effect of a large range of plateau pressure upon mortality rate and incidence of acute cor pulmonale. Results In this whole group of 352 ARDS patients, mortality rate and incidence of cor pulmonale were 80 and 56%, respectively, when plateau pressure was > 35 cmH₂O; 42 and 32%, respectively, when plateau pressure was between 27 and 35 cmH₂O; and 30 and 13%, respectively, when plateau pressure was < 27 cmH₂O. Moreover, a clear interaction between plateau pressure and cor pulmonale was evidenced: whereas the odd ratio of dying for an increase in plateau pressure from 18–26 to 27–35 cm H₂O in patients without cor pulmonale was 1.05 (p = 0.635), it was 3.32 in patients with cor pulmonale (p < 0.034). Conclusion We hypothesize that monitoring of right ventricular function by echocardiography at bedside might help to control the safety of plateau pressure used in ARDS.     

Angiotensin-converting enzyme insertion/deletion polymorphism is not associated with susceptibility and outcome in sepsis and acute respiratory distress syndrome

Objective The insertion/deletion (I/D) of a 289 base pair Alu repeat sequence polymorphism in the angiotensin-converting enzyme gene (ACE) has been shown to predict susceptibility and outcome in the acute respiratory distress syndrome (ARDS). We hypothesized that the I/D polymorphism also confers susceptibility to sepsis and is a predisposing factor for morbidity and mortality of patients with severe sepsis. Design and setting Case-control study including 212 consecutive patients fulfilling criteria for severe sepsis admitted to a Spanish network of postsurgical and critical care units, and 364 population-based controls. Susceptibility to severe sepsis was evaluated as primary outcome; mortality in severe sepsis, susceptibility to sepsis-induced ARDS, and mortality in sepsis-induced ARDS were examined as secondary outcomes. An additive model of inheritance in which patients were classified into three genotype groups (II, ID, and DD) was used for association testing. Measurements and results Genotype and allele frequencies of I/D were distributed similarly in all septic, ARDS, and non-ARDS patients and in population-based controls. ACE I/D polymorphism was not associated with severe sepsis susceptibility or mortality. The ACE I/D polymorphism was associated neither with sepsis-induced ARDS susceptibility (p = 0.895) or mortality (p = 0.950). These results remained nonsignificant when adjusted for other covariates using multiple logistic regression analysis or Kaplan–Meier estimates of 28-day survival. Conclusions Our data do not support an association of the ACE gene I/D polymorphism with susceptibility or mortality in severe sepsis or with sepsis-induced ARDS in Spanish patients. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This research was supported by grants from FUNCIS (53/04) and the Ministerio de Educación y Ciencia, Spain (SAF2004-06833). J.V. is the principal investigator in both grants. The authors named above wrote this article on behalf of the GRECIA and GEN-SEP groups. The members of the GRECIA and GEN-SEP groups are listed under Acknowledgements at the end of the article. J. Villar, C. Flores, and L. Pérez-Méndez contributed equally to this work.     

Internal jugular venous catheter-related bacteremia according to central and posterior accesses

Background Although there are many studies about central venous catheter-related infection, we have not found any analysis of the incidence of internal jugular venous catheter-related bacteremia associated with different accesses. Objective The objective of this study was to test whether the position of the internal jugular venous catheter, central or posterior, influences the incidence of bacteremia. Design A cohort study. Setting A 12-bed polyvalent medical–surgical intensive care unit (ICU). Patients Patients admitted to ICU between 1 May 2000 and 30 April 2004 who received one or more internal jugular venous catheters. Measurements and results A total of 1,483 patients were admitted to the polyvalent ICU, of whom 1,311 underwent central venous catheterization. A total of 547 patients received 684 internal jugular venous catheters, 169 by posterior and 515 by central access. There were no significant differences between central and posterior access patients in sex, age, APACHE II (14.1 ± 5.0 vs. 13.9 ± 5.2, p = 0.40), diagnosis, order of catheter insertion, use of mechanical ventilation, use of antimicrobials, use of total parenteral nutrition or use of pulmonary artery catheter. We found a higher incidence of internal jugular venous catheter-related bacteremia with central (4.8 per 1000 catheter-day) than with posterior (1.2 per 1000 catheter-day) access (odds ratio 3.9; 95% confidence interval 1.1–infinite; p = 0.03). Conclusion Posterior access has a lower incidence of internal jugular venous catheter-related bacteremia than central access in non-severely ill patients (according to the low APACHE II score values of the study patients). Competing interests: none declared     

Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury

Objective In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI. Design and setting Prospective, controlled study in an imaging facility. Participants Pigs tracheotomized and mechanically ventilated. Intervention Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid. Measurements and results Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO₂ under F_IO₂ 1 was significantly lower in the APC group before lung injury (473 ± 129 vs. 578 ± 54 mmHg) and 110 min (342 ± 138 vs. 446 ± 103 mmHg) and 290 min (303 ± 171 vs. 547 ± 54 mmHg) thereafter (p < 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0 ± 1.5 vs. 11.0 ± 2.5 ml/kg) (p > 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p < 0.05). Conclusions In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation–perfusion mismatch, with more perfusion to dependent nonaerated areas. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Incidence, risk factors, and outcome of aspiration pneumonitis in ICU overdose patients

Objective To assess the incidence and outcome of clinically significant aspiration pneumonitis in intensive care unit (ICU) overdose patients and to identify its predisposing factors.Design Retrospective cohort study.Setting Medical ICU of an academic tertiary care hospital.Patients A total of 273 consecutive overdose admissions.Measurements and results Clinically significant aspiration pneumonitis was defined as the occurrence of respiratory dysfunction in a patient with a localised infiltrate on chest X-ray within 72 h of admission. In our cohort we identified 47 patients (17%) with aspiration pneumonitis. Importantly, aspiration pneumonitis was associated with a higher incidence of cardiac arrest (6.4 vs 0.9%; p = 0.037) and an increased duration of both ICU stay and overall hospital stay [respectively: median 1 (interquartile range 1–3) vs 1 (1–2), p = 0.025; and median 2 (1–7) vs 1 (1–3), p < 0.001]. In multivariate logistic regression analysis, Glasgow Coma Scale (GCS) score [odds ratio (OR) for each point of GCS 0.8; 95% confidence interval (CI) 0.7–0.9; p = 0.001], ingestion of opiates (OR 4.5; 95% CI 1.7–11.6; p = 0.002), and white blood cell count (WBC) (OR for each increase in WBC of 10⁹/l 1.05; 95% CI 1.0–1.19; p = 0.049) were identified as independent risk factors.Conclusions Clinically relevant aspiration pneumonitis is a frequent complication in overdose patients admitted to the ICU. Moreover, aspiration pneumonitis is associated with a higher incidence of cardiac arrest and increased ICU and total in-hospital stay.     

Insulin glargine supplementation during early management phase of diabetic ketoacidosis in children

Objective To study the effect of subcutaneous administration of insulin glargine on the rate of resolution of acidosis and intravenous insulin infusion requirement in children with moderate and severe diabetic ketoacidosis (DKA). Study design Retrospective cohort study. Setting Pediatric intensive care unit of a university-based children's hospital. Patients Children with moderate to severe DKA admitted between March 2001 and February 2003. Results The outcomes of children who received 0.3 units/kg of subcutaneous insulin glargine in the first 6 h of management in addition to the standard treatment (n = 12) were compared with those of children who received standard treatment alone (n = 59). Measured outcomes included dose of intravenous insulin required, duration of insulin infusion and acidosis correction time. The two groups were similar in demographics and severity of illness. The mean time for acidosis correction (venous pH ≥ 7.3) in the insulin glargine group was shorter than the standard therapy group (12.4 ± 2.9 h and 17.1 ± 6.2 h respectively, p < 0.001). The insulin infusion time was shorter in the insulin glargine group (14.8 ± 6.0 h vs 24.4 ± 9.0 h, p < 0.001). There was a trend towards shorter total hospital stay in the glargine group (3.2 ± 1.0 days vs 3.72 ± 1.06 days). Conclusions In our small series of children with moderate and severe DKA, supplementing with subcutaneous insulin glargine led to a faster resolution of acidosis without any adverse effects. This could potentially lead to a shorter need for insulin infusion and a shorter ICU length of stay.     

Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration

Objective Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration. Design Animal study. Setting University-affiliated research laboratory. Subjects White farm pigs. Interventions Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls. Measurements and results After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 ± 6% (p = 0.02), ILO: 85 ± 13% (p = 0.05), TEZO-ILO: 89 ± 6% (p = 0.02), control: 70 ± 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 ± 6 torr vs.49 ± 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 ± 13 mmHg to 62 ± 12 mmHg vs.85 ± 14 mmHg to 80  ± 11 mmHg (p = 0.01). Conclusions Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.