Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study.

BACKGROUND: The presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP. METHODS: This was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients. RESULTS: Among 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone. CONCLUSION: Bacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors.

Host-pathogen interactions and prognosis of critically ill immunocompetent patients with pneumococcal pneumonia: the nationwide prospective observational STREPTOGENE study.

PURPOSE: To assess the relative importance of host and bacterial factors associated with hospital mortality in patients admitted to the intensive care unit (ICU) for pneumococcal community-acquired pneumonia (PCAP). METHODS: Immunocompetent Caucasian ICU patients with PCAP documented by cultures and/or pneumococcal urinary antigen (UAg Sp) test were included in this multicenter prospective study between 2008 and 2012. All pneumococcal strains were serotyped. Logistic regression analyses were performed to identify risk factors for hospital mortality. RESULTS: Of the 614 patients, 278 (45%) had septic shock, 270 (44%) had bacteremia, 307 (50%) required mechanical ventilation at admission, and 161 (26%) had a diagnosis based only on the UAg Sp test. No strains were penicillin-resistant, but 23% had decreased susceptibility. Of the 36 serotypes identified, 7 accounted for 72% of the isolates, with different distributions according to age. Although antibiotics were consistently appropriate and were started within 6 h after admission in 454 (74%) patients, 116 (18.9%) patients died. Independent predictors of hospital mortality in the adjusted analysis were platelets ≤ 100 × 109/L (OR, 7.7; 95% CI, 2.8-21.1), McCabe score ≥ 2 (4.58; 1.61-13), age > 65 years (2.92; 1.49-5.74), lactates > 4 mmol/L (2.41; 1.27-4.56), male gender and septic shock (2.23; 1.30-3.83 for each), invasive mechanical ventilation (1.78; 1-3.19), and bilateral pneumonia (1.59; 1.02-2.47). Women with platelets ≤ 100 × 109/L had the highest mortality risk (adjusted OR, 7.7; 2.8-21). CONCLUSIONS: In critically ill patients with PCAP, age, gender, and organ failures at ICU admission were more strongly associated with hospital mortality than were comorbidities. Neither pneumococcal serotype nor antibiotic regimen was associated with hospital mortality.

The rendu-osler-weber disease revealed by a refractory hypoxemia and severe cerebral fat embolism.

The Rendu-Osler-Weber disease is a genetic disease which may lead to severe hemorrhage and less frequently to severe organ dysfunction. We report the case of a 22-year-old patient with no personal medical history who was involved in a motorcycle accident and exhibited severe complications related to large arteriovenous pulmonary shunts during his ICU stay. The patient developed an unexplained severe hypoxemia which was attributed to several arteriovenous shunts of the pulmonary vasculature by a contrast study during a transesophageal echocardiographic examination. The course was subsequently complicated by a prolonged coma associated with hemiplegia which was attributed to a massive paradoxical fat embolism in the setting of an untreated femoral fracture. In addition to hemorrhagic complications which may lead to intractable shock, arteriovenous malformations associated with the Rendu-Osler-Weber disease may involve the pulmonary vasculature and result in unexpected complications, such as hypoxemia or severe cerebral fat embolism in high-risk patients.

Localized cardiac tamponade after open-heart surgery.

PURPOSE: To describe the clinical presentation and echocardiographic findings associated with localized tamponade after open-heart surgery. METHODS: Retrospective analysis of a case series with a surgically proven diagnosis. RESULTS: Among 23 patients with surgically proven localized cardiac tamponade after elective open-heart surgery, 5 patients (22%) died in the ICU from multiorgan failure. At the time of diagnosis (median delay: 2 days; range: 0-8 days), shock was present in 19 patients, 8 of them being hypotensive. Transthoracic echocardiography (TTE) depicted the localized cardiac tamponade in 3 of 4 examined patients, whereas transesophageal echocardiography (TEE) was always conclusive. The right atrium was primarily involved, solely (n = 11) or with the right ventricle (n = 5), whereas the left cardiac cavities were less frequently compressed (left atrium: n = 6, left ventricle: n = 1). The free wall curvature of the involved cardiac chamber was consistently inverted, and blood flow turbulences were depicted in 12 patients. Surgical removal of the compressive hematoma improved the clinical status of 18 patients (78%) who were discharged from the hospital. CONCLUSION: Since localized tamponade complicating open-heart surgery has various, non-specific clinical presentations and TTE is not diagnostic, indications of TEE must be liberal in this setting to prompt diagnosis and surgical reoperation.

Safety and pharmacokinetics of an anti-PcrV PEGylated monoclonal antibody fragment in mechanically ventilated patients colonized with Pseudomonas aeruginosa: a randomized,double-blind, placebo-controlled trial.

OBJECTIVE: The type III secretion system is an important Pseudomonas aeruginosa-virulence determinant in animal models of infection and in humans. Antibody-mediated inhibition of the PcrV protein, an essential component of this system, might abrogate the Pseudomonas aeruginosa ability to damage epithelial cells, neutrophils, and macrophages, thereby limiting its pathogenicity. The objective of the trial was to determine the safety, pharmacokinetics, and ability to prevent Pseudomonas aeruginosa ventilator-associated pneumonia of KB001, a recombinant, PEGylated, engineered, human Fab' fragment that specifically binds to a Pseudomonas aeruginosa PcrV epitope and blocks its function. DESIGN: Multicenter, randomized, placebo-controlled, double-blind, phase-2a trial. SETTING: Ten intensive care units across France. PATIENTS: Thirty-nine Pseudomonas aeruginosa-colonized, but not infected, mechanically ventilated patients. INTERVENTIONS: Patients were randomized 1:1:1 to receive a single intravenous infusion of KB001, 3 mg/kg (n=13) or 10 mg/kg (n=14), or placebo (n=12). MEASUREMENTS AND MAIN RESULTS: The primary end points were KB001 safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Secondary end points included serum and lung KB001 pharmacokinetics, and Pseudomonas aeruginosa pneumonia rate within 28 days of its infusion. KB001 was well tolerated and not immunogenic. The 3- and 10-mg/kg groups had respective maximum serum concentrations of 52,811-88,660 and 121,857-285,454 ng/mL, with mean elimination half-lives of 8.1 and 9.3 days. KB001 was detected in endotracheal aspirates from all patients receiving it, as early as day 1 and up to 28 days. Respective mean endotracheal aspirate/serum concentration ratios were 0.092 and 0.085 for the 3- and 10-mg/kg groups, who developed Pseudomonas aeruginosa pneumonia less frequently (33% and 31%, respectively) than placebo recipients (60%). CONCLUSIONS: KB001 was safe and well tolerated in this study, with a favorable pharmacokinetic profile and promising potential for reducing Pseudomonas aeruginosa pneumonia incidence in intensive care unit mechanically ventilated patients colonized with this bacterium.

Assessment of left ventricular ejection fraction using an ultrasonic stethoscope in critically ill patients.

INTRODUCTION: Assessment of cardiac function is key in the management of intensive care unit (ICU) patients and frequently relies on the use of standard transthoracic echocardiography (TTE). A commercially available new generation ultrasound system with two-dimensional imaging capability, which has roughly the size of a mobile phone, is adequately suited to extend the physical examination. The primary endpoint of this study was to evaluate the additional value of this new miniaturized device used as an ultrasonic stethoscope (US) for the determination of left ventricular (LV) systolic function, when compared to conventional clinical assessment by experienced intensivists. The secondary endpoint was to validate the US against TTE for the semi-quantitative assessment of left ventricular ejection fraction (LVEF) in ICU patients. METHODS: In this single-center prospective descriptive study, LVEF was independently assessed clinically by the attending physician and echocardiographically by two experienced intensivists trained in critical care echocardiography who used the US (size: 135×73×28 mm; weight: 390 g) and TTE. LVEF was visually estimated semi-quantitatively and classified in one of the following categories: increased (LVEF>75%), normal (LVEF: 50 to 75%), moderately reduced (LVEF: 30 to 49%), or severely reduced (LVEF<30%). Biplane LVEF measured using the Simpson's rule on TTE loops by an independent investigator was used as reference. RESULTS: A total of 94 consecutive patients were studied (age: 60±17 years; simplified acute physiologic score 2: 41±15), 63 being mechanically ventilated and 36 receiving vasopressors and/or inotropes. Diagnostic concordance between the clinically estimated LVEF and biplane LVEF was poor (Kappa: 0.33; 95% CI: 0.16 to 0.49) and only slightly improved by the knowledge of a previously determined LVEF value (Kappa: 0.44; 95% CI: 0.22 to 0.66). In contrast, the diagnostic agreement was good between visually assessed LVEF using the US and TTE (Kappa: 0.75; CI 95%: 0.63 to 0.87) and between LVEF assessed on-line and biplane LVEF, regardless of the system used (Kappa: 0.75; CI 95%: 0.64 to 0.87 and Kappa: 0.70; CI 95%: 0.59 to 0.82, respectively). CONCLUSIONS: In ICU patients, the extension of physical examination using an US improves the ability of trained intensivists to determine LVEF at bedside. With trained operators, the semi-quantitative assessment of LVEF using the US is accurate when compared to standard TTE.

Early bacterial genome detection in body fluids from patients with severe sepsis: a pilot study.

PURPOSE: The purpose of this study is to evaluate the feasibility and interest of real-time polymerase chain reaction (RT-PCR) testing for bacterial genomes in body fluids other than blood in patients with acute severe sepsis. METHODS: Twenty-six consecutive patients admitted for severe sepsis or septic shock were prospectively studied. Body fluids were sampled as clinically indicated and tested using standard microbiological methods and modified RT-PCR methods (universal PCR and specific PCRs). Results of standard microbiological tests were compared with those of PCR tests. RESULTS: Direct RT-PCR testing was successfully performed on all nonblood body fluids. Of 29 body fluids collected, 23 were positive for at least 1 microorganism with conventional tests. Of 18 microbiological tests positive for a single microorganism, 15 fully agreed with RT-PCR assays, and the remaining 3 samples were infected with bacteria not screened by PCR testing. Among the 5 polymicrobial results obtained with conventional tests, RT-PCR agreed in 4 patients. The RT-PCR tests allowed additional clinically relevant bacterial identification in 3 of 6 samples with negative microbiological culture. CONCLUSIONS: Our results indicate that direct PCR testing may improve the detection of bacteria in body fluids other than blood in patients with acute severe sepsis.

Extracorporeal albumin dialysis in three cases of acute calcium channel blocker poisoning with life-threatening refractory cardiogenic shock.

We describe 3 patients admitted to the medical-surgical ICU in a university hospital with life-threatening cardiogenic shock after the ingestion of high doses of calcium channel blockers (8.4 g sustained-release diltiazem, 4.2 g sustained-release diltiazem, and 14.4 g slow-release verapamil). Cardiovascular failure and cardiac conduction disturbances were unresponsive to the usual therapy (eg, intravenous injection of high doses of calcium, glucagon, hyperinsulinemia-euglycemia therapy, fluid resuscitation) and to increasing doses of simultaneous infusions of adrenergic agonists. Albumin dialysis with Molecular Adsorbents Recirculating System (MARS) therapy was performed because of its unique ability to selectively remove from circulation protein-bound toxins (and potentially drugs) that are not cleared by conventional hemodialysis. A single procedure was successfully performed in each patient, which was followed by rapid weaning of adrenergic agonist agents and full recovery of the life-threatening cardiovascular failure. At 2-year follow-up, patients were asymptomatic. Albumin dialysis with MARS therapy may be effective when used as a rescue procedure in patients presenting with sustained, life-threatening cardiogenic shock as a result of massive calcium channel blocker poisoning.

Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia.

OBJECTIVES: Nosocomial Pseudomonas aeruginosa pneumonia remains a major concern in critically ill patients. We explored the potential impact of microorganism-targeted adjunctive immunotherapy in such patients. PATIENTS AND METHODS: This multicentre, open pilot Phase 2a clinical trial (NCT00851435) prospectively evaluated the safety, pharmacokinetics and potential efficacy of three doses of 1.2 mg/kg panobacumab, a fully human monoclonal anti-lipopolysaccharide IgM, given every 72 h in 18 patients developing nosocomial P. aeruginosa (serotype O11) pneumonia. RESULTS: Seventeen out of 18 patients were included in the pharmacokinetic analysis. In 13 patients receiving three doses, the maximal concentration after the third infusion was 33.9 ±â€Š8.0 µg/mL, total area under the serum concentration-time curve was 5397 ±â€Š1993 µg h/mL and elimination half-life was 102.3 ±â€Š47.8 h. Panobacumab was well tolerated, induced no immunogenicity and was detected in respiratory samples. In contrast to Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction, all 13 patients receiving three doses survived, with a mean clinical resolution in 9.0 ±â€Š2.7 days. Two patients suffered a recurrence at days 17 and 20. CONCLUSIONS: These data suggest that panobacumab is safe, with a pharmacokinetic profile similar to that in healthy volunteers. It was associated with high clinical cure and survival rates in patients developing nosocomial P. aeruginosa O11 pneumonia. We concluded that these promising results warrant further trials.

Basic critical care echocardiography: validation of a curriculum dedicated to noncardiologist residents.

OBJECTIVE: To assess the efficacy of a limited, tailored training program for noncardiologist residents without experience in ultrasound to reach competence in basic critical care echocardiography. DESIGN: Prospective descriptive clinical study. SETTING: Medical-surgical intensive care unit of a teaching hospital. PATIENTS: 201 patients (125 men; age: 61 ± 16 yrs; Simplified Acute Physiologic Score II: 37 ± 17; 145 ventilated patients) who required a transthoracic echocardiography were studied. INTERVENTION AND MEASUREMENTS: The curriculum consisted of a 12-hr learning program blending didactics, interactive clinical cases, and tutored hands-on sessions. After completion of this tailored training program, all eligible patients subsequently underwent a transthoracic echocardiography performed in random order by a recently trained resident and an experienced intensivist with expertise in critical care echocardiography who was used as a reference. The agreement between responses to clinical questions provided by the two investigators who independently interpreted the transthoracic echocardiography study at bedside was used as an indicator of effectiveness of the tested curriculum. MAIN RESULTS: Residents performed a mean of 33 transthoracic echocardiograms during the study period (range: 29-38). Experienced intensivists had significantly fewer unaddressed clinical questions than did residents (57 [5.7%] vs. 111 [11.0%] of 1,005 clinical questions: p < .0001). When compared to residents, the experienced intensivists performed shorter transthoracic echocardiography examinations (3.0 ± 1.0 min vs. 7.0 ± 2.5 min: p < .0001) with more acoustic windows (888 vs. 828 of 1,005 potential windows: p < .0001). Residents adequately assess global left ventricle systolic function (κ: 0.84; 95% confidence interval: 0.76-0.92). They accurately identified dilated left ventricle (κ: 0.90; 95% confidence interval: 0.80-1.0), dilated right ventricle (κ: 0.76; 95% confidence interval: 0.64-0.89), dilated inferior vena cava (κ: 0.79; 95% confidence interval: 0.63-0.94), and pericardial effusion (κ: 0.79; 95% confidence interval: 0.58-0.99) and diagnosed two cases of tamponade. CONCLUSIONS: A 12-hr training program blending didactics, interactive clinical cases, and tutored hands-on sessions dedicated to noncardiologist residents without experience in ultrasound appears well suited for reaching competence in basic critical care echocardiography.

Leptospirosis: An Unusual Cause of ARDS.

Severe leptospirosis usually associates shock, jaundice, renal failure, and thrombocytopenia. Massive hemoptysis due to diffuse alveolar haemorrhage may rarely occur leading to an acute respiratory failure and multiple organ failure. We present the case of an acute respiratory distress syndrome caused by a severe leptospirosis. The severity of the respiratory failure contrasted with the absence of significant liver or renal dysfunction. Bedside open lung biopsy was only consistent with a postinfectious BOOP. The diagnosis was retrospective when the niece of the patient presented with similar inaugural symptoms ten days later after being scratched by a wild rat which was considered by our patient as a pet.

Focused training for goal-oriented hand-held echocardiography performed by noncardiologist residents in the intensive care unit.

OBJECTIVE: We sought to evaluate the efficacy of a limited training dedicated to residents without knowledge in ultrasound for performing goal-oriented echocardiography in ICU patients. DESIGN: Prospective pilot observational study. SETTING: Medical-surgical ICU of a teaching hospital. PATIENTS: 61 consecutive adult ICU patients (SAPS II score: 38 +/- 17; 46 ventilated patients) requiring a transthoracic echocardiography were studied. INTERVENTIONS: After a curriculum including a 3-h training course and 5 h of hands-on training, one of four noncardiologist residents and an intensivist experienced in ultrasound subsequently performed hand-held echocardiography (HHE), independently and in random order. Assessable "rule in, rule out" clinical questions were purposely limited to easily identifiable conditions by the sole use of two-dimensional imaging. MEASUREMENTS AND RESULTS: When compared with residents, the experienced intensivist performed shorter examinations (4 +/- 1 vs. 11 +/- 4 min: p < 0.0001) and had significantly less unsolved clinical questions [3 (0.8%) vs. 27 (7.4%) of 366 clinical questions: p < 0.0001]. When addressed, clinical questions were adequately appraised by residents: left ventricular systolic dysfunction [Kappa: 0.76 +/- 0.09 (95% CI: 0.59-0.93)], left ventricular dilatation [Kappa: 0.66 +/- 0.12 (95% CI: 0.43-0.90)], right ventricular dilatation [Kappa: 0.71 +/- 0.12 (95% CI: 0.46-0.95)], pericardial effusion [Kappa: 0.68 +/- 0.18 (95 CI: 0.33-1.03)], and pleural effusion [Kappa: 0.71 +/- 0.09 (95% CI: 0.53-0.88)]. The only case of tamponade was accurately diagnosed by the resident. CONCLUSIONS: Limited training of noncardiologist ICU residents without previous knowledge in ultrasound appears feasible and efficient to address simple clinical questions using point-of-care echography. Influence of the learning curve on diagnostic accuracy and potential therapeutic impact remain to be determined.

Efficacy of and tolerance to mild induced hypothermia after out-of-hospital cardiac arrest using an endovascular cooling system.

INTRODUCTION: We evaluated the efficacy of and tolerance to mild therapeutic hypothermia achieved using an endovascular cooling system, and its ability to reach and maintain a target temperature of 33 degrees C after cardiac arrest. METHODS: This study was conducted in the medical-surgical intensive care unit of an urban university hospital. Forty patients admitted to the intensive care unit following out-of-hospital cardiac arrest underwent mild induced hypothermia (MIH). Core temperature was monitored continuously for five days using a Foley catheter equipped with a temperature sensor. Any equipment malfunction was noted and all adverse events attributable to MIH were recorded. Neurological status was evaluated daily using the Pittsburgh Cerebral Performance Category (CPC). We also recorded the mechanism of cardiac arrest, the Simplified Acute Physiologic Score II on admission, standard biological variables, and the estimated time of anoxia. Nosocomial infections during and after MIH until day 28 were recorded. RESULTS: Six patients (15%) died during hypothermia. Among the 34 patients who completed the period of MIH, hypothermia was steadily maintained in 31 patients (91%). Post-rewarming 'rebound hyperthermia', defined as a temperature of 38.5 degrees C or greater, was observed in 25 patients (74%) during the first 24 hours after cessation of MIH. Infectious complications were observed in 18 patients (45%), but no patient developed severe sepsis or septic shock. The biological changes that occurred during MIH manifested principally as hypokalaemia (< 3.5 mmol/l; in 75% of patients). CONCLUSION: The intravascular cooling system is effective, safe and allows a target temperature to be reached fairly rapidly and steadily over a period of 36 hours.