Septic Participation in Cardiogenic Shock: Exposure to Bacterial Endotoxin.

OBJECTIVE: In cardiogenic shock (CS), presence of fever, leukocytosis, relatively low systemic vascular resistances, and high serum procalcitonin levels are quite frequent and recurrently involve the search for an infectious complication. We hypothesized that endotoxin exposure in CS could explain this sepsis-like syndrome. DESIGN AND SETTING: Prospective observational study of consecutive CS patients admitted to our intensive care unit (ICU). Patients were followed during the first 3 days after CS onset. All clinical, hemodynamic, and microbiological data were collected. Inflammatory biomarkers and anti-endotoxin antibodies (IgM EndoCAb) were daily measured. PATIENTS: We included 37 consecutive CS patients. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients (60%) had body temperature >38.3°C or <35°C; and 23 patients (62%) had a leucocyte count >14,000/mm or <4,000/mm. Microbiological study was performed in 30 patients (81%). No infection was diagnosed in the studied patients. All the patients had serum inflammatory biomarkers levels above normal values including procalcitonin (19 patients [51%] had serum procalcitonin above 2 ng/mL). All the patients had IgM EndoCAb below the normal median value; 22 patients (59.5%) had IgM anti-endotoxin value below 10th percentile range for healthy people. Hemodynamic and respiratory stabilization was achieved in 23 patients (62%) and the ICU mortality rate was 38%, only procalcitonin and interleuquin-6 were associated with higher mortality rate. CONCLUSION: We have detected extremely low titers of IgM EndoCAb in CS suggesting endotoxin exposure. However, only inflammatory biomarkers were related to ICU mortality.

Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis.

OBJECTIVES: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. METHODS: A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true (-) results. RESULTS: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT <0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. CONCLUSION: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.

Blood culture contamination rate in an intensive care setting: Effectiveness of an education-based intervention.

BACKGROUND: Blood culture (BC) contamination rate is an indicator of quality of care scarcely explored in intensive care units (ICUs). We analyzed the BC contamination rate in our ICU to assess the effectiveness of an education-based intervention. METHODS: We conducted an interventional study with concurrent controls. Consecutive BCs drawn during a 6-month period were included. An education-based intervention was presented to case nurses (optimal technique). The remaining nurses comprised the control group (standard technique). Two independent observers assessed clinical significance of saprophytic skin bacteria isolated in BCs. RESULTS: Six hundred fifty-six BCs were obtained: 308 (47%) via optimal technique and 348 (53%) via standard technique (47%). One hundred eighty-seven BCs were positive for saprophytic microorganisms; 127 (89%) were considered unrelated to infection. Coagulase-negative staphylococci isolation was lower in the optimal technique group (14% vs 26%; P < .001), as well as contamination due to coagulase-negative staphylococci (12% vs 21%; P = .002) or Acinetobacter baumannii (0.3% vs 2%; P = .013). BC contamination rate was 13% in the optimal technique group versus 23% in the standard group (P < .005). In the optimal technique group, BC contamination rate was higher in BCs drawn through the catheter (17% vs 7%; P = .028). CONCLUSIONS: An education-based intervention significantly reduced the BC contamination rate in our ICU. It seems necessary to design a tool to extract BCs through the catheter to minimize the risk of contamination.

Diagnosing external ventricular drain-related ventriculitis by means of local inflammatory response: soluble triggering receptor expressed on myeloid cells-1.

INTRODUCTION: External ventricular drainage (EVD)-related ventriculitis is one of the most severe complications associated with the use of EVDs. Establishing an early and certain diagnosis can be difficult in critically ill patients. We performed this prospective study to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) determination in cerebrospinal fluid (CSF) in the diagnosis of ventriculitis. METHODS: A prospective observational study was conducted of 73 consecutive patients with EVD. Samples of CSF for culture, cytobiochemical analysis and sTREM-1 determination were extracted three times a week. Ventriculitis diagnosis required a combination of microbiological, cytobiochemical and clinical criteria. RESULTS: Seventy-three consecutive patients were included. EVD-related ventriculitis was diagnosed in six patients and EVD-colonization in ten patients. Patients without clinical or microbiological findings were considered controls. The median CSF sTREM-1 was 4,320 pg/ml (interquartile range (IQR): 2,987 to 4,886) versus 266 pg/ml (118 to 689); P <0.001. There were no differences when comparing colonized-patients and controls. The best cut-off sTREM-1 value for the diagnosis of ventriculitis was 2,388.79 pg/ml (sensitivity 100%, specificity 98.5%, positive predictive value 85.71%, negative predictive value 100%). CSF proteins, glucose and the ratio CSF/serum glucose were also significantly different (P = 0.001). Serum biomarkers were not useful to diagnose EVD-related infection. These results were confirmed by a case-control study with ventriculitis patients (cases) and non-ventriculitis (control subjects) matched by age, comorbidities, severity scales and EVD duration (P = 0.004). CONCLUSIONS: CSF sTREM-1 was useful in the diagnosis of ventriculitis, in a similar measure to classical CSF parameters. Furthermore, CSF sTREM-1 could prove the diagnosis in uncertain cases and discriminate between EVD-colonization and infection.

Impact of microbial ecology on accuracy of surveillance cultures to predict multidrug resistant microorganisms causing ventilator-associated pneumonia.

OBJECTIVES: The objective of this study was to assess surveillance cultures (SC) prediction accuracy in two periods and settings of the same Department with a different microbiological epidemiology (high and low prevalence of multi-drug resistant microorganisms (MDRM)). METHODS: Prospective and observational study. SC were obtained twice a week in consecutive mechanically ventilated patients. Patients fulfilling VAP criteria were analyzed. RESULTS: 440 patients were followed up, 71 patients had VAP (50 in period I and 21 in period II). MDRM causing VAP were more prevalent in the first period (48% vs. 19%; p = 0.033). The rate of empirical appropriate treatment in period I was lower than in period II (52% vs.76%; p = 0.031). SC prediction accuracy was similar in the two periods (80% vs. 81%; p = 0.744). However, if antibiotic treatment had been guided by SC, the percentage of appropriate treatment would have increased by 28% in the first period but only by 5% in the second; p = 0.024. CONCLUSIONS: SC were able to predict VAP etiology in 80% of cases regardless the prevalence of MDRM. However, the potential benefit of SC in terms of appropriate empirical treatment could be only observed when MDRM were prevalent.

The administration of a loading dose of aspirin to patients presenting with acute myocardial infarction while receiving chronic aspirin treatment reduces thromboxane A2-dependent platelet reactivity.

Abstract The optimal dose of aspirin for patients presenting with acute myocardial infarction (AMI) while receiving chronic aspirin therapy has not been clearly established. We evaluated whether continued treatment with 100 mg of aspirin or a loading dose (200-500 mg) influences thromboxane A2 (TX) suppression or platelet reactivity. Sixty-four consecutive patients with AMI and 98 healthy subjects (82 aspirin-free and 16 receiving 100 mg daily for a week) were evaluated. Treatment was at the discretion of the attending physician. Collagen (1 µg/ml)-induced TX synthesis, (14)C-serotonin-release, platelet aggregation, and the PFA-100 assay were evaluated. The platelet TX synthesis of patients receiving a loading dose of aspirin was sixfold lower than that of patients receiving 100 mg of aspirin (p<0.005). This was associated with marked reductions in (14)C-serotonin-release and arachidonic-acid-induced aggregation and an increase in the PFA-100 closure time (p<0.01). Categorization of patients according to their TX synthesis (<95% or ≥ 95% inhibition vs. healthy aspirin-free subjects) revealed that 8% of the patients treated with loading doses had a poor response (<95% inhibition) vs. 53% of those treated with 100 mg (p<0.001). Patients with lower TX inhibition had higher serum NT-Pro-BNP (p<0.005), a marker of poor left ventricular systolic function. Administration of a loading dose of aspirin to patients with AMI during existing chronic aspirin treatment induced greater reductions in platelet TX synthesis and TX-dependent platelet reactivity than the continued treatment alone.

Survival of hematological patients after discharge from the intensive care unit: a prospective observational study.

INTRODUCTION: Although the survival rates of hematological patients admitted to the ICU are improving, little is known about the long-term outcome. Our objective was to identify factors related to long-term outcome in hematological patients after ICU discharge. METHODS: A prospective, observational study was carried out in seven centers in Spain. From an initial sample of 161 hematological patients admitted to one of the participating ICUs during the study period, 62 were discharged alive and followed for a median time of 23 (1 to 54) months. Univariate and multivariate analysis were performed to identify the factors related to long term-survival. Finally, variables that influence the continuation of the scheduled therapy for the hematological disease were studied. RESULTS: Mortality after ICU discharge was 61%, with a median survival of 18 (1 to 54) months. In the multivariate analysis, an Eastern Cooperative Oncology Group score (ECOG) >2 at ICU discharge (Hazard ratio 11.15 (4.626 to 26.872)), relapse of the hematological disease (Hazard ratio 9.738 (3.804 to 24.93)) and discontinuation of the planned treatment for the hematological disease (Hazard ratio 4.349 (1.286 to 14.705)) were independently related to mortality. Absence of stem cell transplantation, high ECOG and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores decreased the probability of receiving the planned therapy for the hematological malignancy. CONCLUSIONS: Both ICU care and post-ICU management determine the long-term outcome of hematological patients who are discharged alive from the ICU.

Ventilatory support in critically ill hematology patients with respiratory failure.

INTRODUCTION: Hematology patients admitted to the ICU frequently experience respiratory failure and require mechanical ventilation. Noninvasive mechanical ventilation (NIMV) may decrease the risk of intubation, but NIMV failure poses its own risks. METHODS: To establish the impact of ventilatory management and NIMV failure on outcome, data from a prospective, multicenter, observational study were analyzed. All hematology patients admitted to one of the 34 participating ICUs in a 17-month period were followed up. Data on demographics, diagnosis, severity, organ failure, and supportive therapies were recorded. A logistic regression analysis was done to evaluate the risk factors associated with death and NIVM failure. RESULTS: Of 450 patients, 300 required ventilatory support. A diagnosis of congestive heart failure and the initial use of NIMV significantly improved survival, whereas APACHE II score, allogeneic transplantation, and NIMV failure increased the risk of death. The risk factors associated with NIMV success were age, congestive heart failure, and bacteremia. Patients with NIMV failure experienced a more severe respiratory impairment than did those electively intubated. CONCLUSIONS: NIMV improves the outcome of hematology patients with respiratory insufficiency, but NIMV failure may have the opposite effect. A careful selection of patients with rapidly reversible causes of respiratory failure may increase NIMV success.

Implications of endotracheal tube biofilm in ventilator-associated pneumonia response: a state of concept.

INTRODUCTION: Biofilm in endotracheal tubes (ETT) of ventilated patients has been suggested to play a role in the development of ventilator-associated pneumonia (VAP). Our purpose was to analyze the formation of ETT biofilm and its implication in the response and relapse of VAP. METHODS: We performed a prospective, observational study in a medical intensive care unit. Patients mechanically ventilated for more than 24 hours were consecutively included. We obtained surveillance endotracheal aspirates (ETA) twice weekly and, at extubation, ETTs were processed for microbiological assessment and scanning electron microscopy. RESULTS: Eighty-seven percent of the patients were colonized based on ETA cultures. Biofilm was found in 95% of the ETTs. In 56% of the cases, the same microorganism grew in ETA and biofilm. In both samples the most frequent bacteria isolated were Acinetobacter baumannii and Pseudomonas aeruginosa. Nineteen percent of the patients developed VAP (N = 14), and etiology was predicted by ETA in 100% of the cases. Despite appropriate antibiotic treatment, bacteria involved in VAP were found in biofilm (50%). In this situation, microbial persistence and impaired response to treatment (treatment failure and relapse) were more frequent (100% vs 29%, P = 0.021; 57% vs 14%, P = 0.133). CONCLUSIONS: Airway bacterial colonization and biofilm formation on ETTs are early and frequent events in ventilated patients. There is microbiological continuity between airway colonization, biofilm formation and VAP development. Biofilm stands as a pathogenic mechanism for microbial persistence, and impaired response to treatment in VAP.

Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients.

BACKGROUND: There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. METHODS: A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. RESULTS: Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. CONCLUSION: Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.

Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A.

OBJECTIVES: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A (2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between the timing of antiviral administration and intensive care unit (ICU) outcomes. METHODS: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection. Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint. Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality. RESULTS: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients required mechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy and were included in the study group. All patients received oseltamivir for a median duration of 10 days (interquartile range 8-14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groups were comparable in terms of main clinical variables. ICU length of stay (22.7 ±â€Š16.7 versus 18.4 ±â€Š14.2 days; P = 0.03), hospital length of stay (34.0 ±â€Š20.3 versus 27.2 ±â€Š18.2 days; P = 0.001) and MV days (17.4 ±â€Š15.2 versus 14.0 ±â€Š12.4; P = 0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than in ET (21.5%; OR = 1.9; 95% CI 1.06-3.41). A multivariate model identified ET (OR = 0.44; 95% CI 0.21-0.87) as an independent variable associated with reduced ICU mortality. These results were confirmed by propensity score analysis (OR = 0.44; 95% CI 0.22-0.90; P < 0.001). CONCLUSIONS: Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.

Diagnostic implications of soluble triggering receptor expressed on myeloid cells-1 in patients with acute respiratory distress syndrome and abdominal diseases: a preliminary observational study.

INTRODUCTION: Patients admitted to the intensive care unit (ICU) because of acute or decompensated chronic abdominal disease and acute respiratory failure need to have the potential infection diagnosed as well as its site (pulmonary or abdominal). For this purpose, we measured soluble triggering receptor expression on myeloid cells-1 (sTREM-1) in alveolar and peritoneal fluid. METHODS: Consecutive patients (n = 21) with acute or decompensated chronic abdominal disease and acute respiratory failure were included. sTREM was measured in alveolar (A-sTREM) and peritoneal (P-sTREM) fluids. RESULTS: An infection was diagnosed in all patients. Nine patients had a lung infection (without abdominal infection), 5 had an abdominal infection (without lung infection) and seven had both infections. A-sTREM was higher in the patients with pneumonia compared to those without pneumonia (1963 ng/ml (1010-3129) vs. 862 ng/ml (333-1011); P 0.019). Patients with abdominal infection had an increase in the P-sTREM compared to patients without abdominal infection (1941 ng/ml (1088-3370) vs. 305 ng/ml (288-459); P < 0.001). A cut-off point of 900 pg/ml of A-sTREM-1 had a sensitivity of 81% and a specificity of 80% (NPV 57%; PPV 93%, AUC 0.775) for the diagnosis of pneumonia. In abdominal infections, a cut-off point for P-sTREM of 900 pg/ml had the best results (sensitivity 92%; specificity 100%; NPV 90%, PPV 100%, AUC = 0.903). CONCLUSIONS: sTREM-1 measured in alveolar and peritoneal fluids is useful in assessing pulmonary and peritoneal infection in critical-state patients-A-sTREM having the capacity to discriminate between a pulmonary and an extra-pulmonary infection in the context of acute respiratory failure.

Acute kidney injury in critical ill patients affected by influenza A (H1N1) virus infection.

INTRODUCTION: Little information exists about the impact of acute kidney injury (AKI) in critically ill patients with the pandemic 2009 influenza A (H1N1) virus infection. METHODS: We conducted a prospective, observational, multicenter study in 148 Spanish intensive care units (ICUs). Patients with chronic renal failure were excluded. AKI was defined according to Acute Kidney Injury Network (AKIN) criteria. RESULTS: A total of 661 patients were analyzed. One hundred eighteen (17.7%) patients developed AKI; of these, 37 (31.4%) of the patients with AKI were classified as AKI I, 15 (12.7%) were classified as AKI II and 66 (55.9%) were classified as AKI III, among the latter of whom 50 (75.7%) required continuous renal replacement therapy. Patients with AKI had a higher Acute Physiology and Chronic Health Evaluation II score (19.2 ± 8.3 versus 12.6 ± 5.9; P < 0.001), a higher Sequential Organ Failure Assessment score (8.7 ± 4.2 versus 4.8 ± 2.9; P < 0.001), more need for mechanical ventilation (MV) (87.3% versus 56.2%; P < 0.01, odds ratio (OR) 5.3, 95% confidence interval (CI) 3.0 to 9.4), a greater incidence of shock (75.4% versus 38.3%; P < 0.01, OR 4.9, 95% CI, 3.1 to 7.7), a greater incidence of multiorgan dysfunction syndrome (92.4% versus 54.7%; P < 0.01, OR 10.0, 95% CI, 4.9 to 20.21) and a greater incidence of coinfection (23.7% versus 14.4%; P < 0.01, OR 1.8, 95% CI, 1.1 to 3.0). In survivors, patients with AKI remained on MV longer and ICU and hospital length of stay were longer than in patients without AKI. The overall mortality was 18.8% and was significantly higher for AKI patients (44.1% versus 13.3%; P < 0.01, OR 5.1, 95% CI, 3.3 to 7.9). Logistic regression analysis was performed with AKIN criteria, and it demonstrated that among patients with AKI, only AKI III was independently associated with higher ICU mortality (P < 0.001, OR 4.81, 95% CI 2.17 to 10.62). CONCLUSIONS: In our cohort of patients with H1N1 virus infection, only those cases in the AKI III category were independently associated with mortality.

Severe pandemic (H1N1)v influenza A infection: report on the first deaths in Spain.

BACKGROUND AND OBJECTIVE: The impact of pandemic influenza A (H1N1)v infection is still unknown but it is associated with a high case-fatality rate. METHODS: This was a prospective, observational, multicentre study conducted in 144 Spanish intensive care units. Demographic and clinical data were reviewed for all cases of pandemic influenza A (H1N1)v infection reported from 23 June 2009 through 11 February 2010 and confirmed by reverse transcriptase PCR assay. RESULTS: Out of 872 cases reported by statewide surveillance, data for the first 131 deceased patients were analysed. Thirty-seven patients (28.2%) died within the first 14 days. The median age of these patients was 46 years (interquartile range 35-58) and 60.3% were male. Twenty-eight patients (21.4%) did not present with any comorbidities on admission. Forty-six per cent of patients were reported to be obese and 22 (16.8%) had COPD. The vast majority of the patients (72.5%) had viral pneumonia; 95.4% of these had bilateral patchy alveolar opacities (predominantly basal), affecting three or four quadrants. One hundred and fifteen patients (87.8%) developed multi-organ dysfunction syndrome. Ninety-seven patients (74%) required vasopressor drugs, 37 (27.2%) received renal replacement therapy, and 47 (35.1%) received intravenous corticosteroids on admission to the intensive care unit. Only 68 patients (51.9%) received empirical antiviral treatment. CONCLUSIONS: One-third of patients with pandemic influenza A (H1N1)v infection died within the first two weeks and these were young patients, with rapidly progressive viral pneumonia as the primary cause of admission. Obese patients were at high risk but one in four patients did not present with any risk factors on admission. Only half the patients received empirical antiviral therapy and this was administered late.

Bacterial translocation in heat stroke.

The scientific community is fully aware of the importance of heat-related illness and heat stroke syndrome. Numerous guidelines have been recently published and most of them agree on the key role played by the intestine. Likewise, the role of endotoxinemia in the pathophysiology is well established. However, the possibility of bacterial translocation is not mentioned. Our patient illustrates the likelihood of bacterial translocation in heat stroke and consistently the potential need of antibiotic therapy. A 45-year-old man diagnosed with paranoid schizophrenia was confined in a penitentiary center. One summer day in which a temperature of 41 degrees C was observed in the shade, the patient was found in deep coma with an axillary temperature of 42 degrees C. Multiorgan failure was detected in the hospital. Other causes of coma and/or hyperthermia were excluded, and heat stroke was diagnosed. Blood cultures were positive for Pseudomonas aeruginosa and Escherichia coli. Infection site was not identified despite of an exhaustive search. The patient fully recovered after 48 hours. On the basis of review of the literature, we think that bacterial translocation can take part in the pathophysiology of heat stroke. Therefore, antibiotic treatment must be evaluated in heat stroke patients.