What procalcitonin brings to management of sepsis in the ICU

In inflammatory states, particularly in response to infectious stimuli, local procalcitonin (PCT) production rises, and because these tissues cannot further process PCT into calcitonin, serum levels increase. In the critical care setting, PCT should be considered a useful tool to help physicians in some specific, although frequent, situations. Serial measurements of PCT levels may indicate the effectiveness of medical decisions such as the appropriateness of antibiotic therapy, the detection of new infections, and the exclusion of a diagnosis of sepsis. PCT-guided algorithms may also help to decrease the duration of antimicrobial therapy. However, the role of PCT as a prognostic marker in critically ill patients is controversial. In a study by Karlsson and colleagues, PCT concentrations did not differ between hospital survivors and nonsurvivors, but the outcome was better in patients whose PCT concentrations decreased more than 50%. The study of PCT kinetics thus could offer an individual risk assessment in patients with severe sepsis

Management of neurological complications of infective endocarditis in ICU patients

Patients with infective endocarditis (IE) are generally referred to the intensive care unit (ICU) for one or more organ dysfunctions caused by complications of IE. Neurologic events are frequent causes of ICU admission in patients with IE. They can arise through various mechanisms consisting of stroke or transient ischemic attack, cerebral hemorrhage, mycotic aneurysm, meningitis, cerebral abscess, or encephalopathy. Most complications occur early during the course of IE and are a hallmark of left-sided abnormalities of native or prosthetic valves. Occlusion of cerebral arteries, with stroke or transient ischemic attack, accounts for 40% to 50% of the central nervous system complications of IE. CT scan is the most easily feasible neuroimaging in critically unstable patients. However, magnetic resonance imaging is more sensitive and when performed should follow a standardized protocol. In patients with ischemic stroke who are already receiving oral anticoagulant therapy, this treatment should be replaced by unfractionated heparin for at least 2 weeks with a close monitoring of coagulation tests. Mounting evidence shows that, for both complicated left-sided native valve endocarditis and Staphylococcus aureus prosthetic valve endocarditis, valve replacement combined with medical therapy is associated with a better outcome than medical treatment alone. In a recent series, approximately 50% of patients underwent valve replacement during the acute phase of IE before completion of antibiotic treatment. After a neurological event, most patients have at least one indication for cardiac surgery. Recent data from literature suggest that after a stroke, surgery indicated for heart failure, uncontrolled infection, abscess, or persisting high emboli risk should not be delayed, provided that the patient is not comatose or has no severe deficit. Neurologic complications of IE contribute to a severe prognosis in ICU patients. However, patients with only silent or transient stroke had a better prognosis than patients with symptomatic events. In addition, more than neurologic event per se, a better predictor of mortality is neurologic dysfunction, which is associated with location and extension of brain damage. Patients with severe neurological impairment and those with brain hemorrhage have the worse outcome

Management of HIV-infected patients in the intensive care unit

The widespread use of combination antiretroviral therapies (cART) has converted the prognosis of HIV infection from a rapidly progressive and ultimately fatal disease to a chronic condition with limited impact on life expectancy. Yet, HIV-infected patients remain at high risk for critical illness due to the occurrence of severe opportunistic infections in those with advanced immunosuppression (i.e., inaugural admissions or limited access to cART), a pronounced susceptibility to bacterial sepsis and tuberculosis at every stage of HIV infection, and a rising prevalence of underlying comorbidities such as chronic obstructive pulmonary diseases, atherosclerosis or non-AIDS-defining neoplasms in cART-treated patients aging with controlled viral replication. Several patterns of intensive care have markedly evolved in this patient population over the late cART era, including a steady decline in AIDS-related admissions, an opposite trend in admissions for exacerbated comorbidities, the emergence of additional drivers of immunosuppression (e.g., anti-neoplastic chemotherapy or solid organ transplantation), the management of cART in the acute phase of critical illness, and a dramatic progress in short-term survival that mainly results from general advances in intensive care practices. Besides, there is a lack of data regarding other features of ICU and post-ICU care in these patients, especially on the impact of sociological factors on clinical presentation and prognosis, the optimal timing of cART introduction in AIDS-related admissions, determinants of end-of-life decisions, long-term survival, and functional outcomes. In this narrative review, we sought to depict the current evidence regarding the management of HIV-infected patients admitted to the intensive care unit

Initial antimicrobial management of sepsis.

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to de-escalation and antimicrobial stewardship. Biomarkers such a procalcitonin can provide decision support for antibiotic use, and may identify patients with a low likelihood of infection, and in some settings, can guide duration of antibiotic therapy. Sepsis can involve drug-resistant pathogens, and this often necessitates consideration of newer antimicrobial agents

Alveolar fluid in acute respiratory distress syndrome promotes fibroblast migration: role of platelet-derived growth factor pathway

OBJECTIVES: Fibroblast migration is an initiating step in fibroproliferation; its involvement during acute lung injury and acute respiratory distress syndrome remains poorly understood. The aims of this study were: 1) to determine whether bronchoalveolar lavage fluids from patients with acute lung injury/acute respiratory distress syndrome modulate lung fibroblast migration; 2) to assess lung fibroblast migration\u27s clinical relevance; and 3) to evaluate the role of the platelet-derived growth factor pathway in this effect. DESIGN: Prospective cohort study. SETTING: Three intensive care units of a large tertiary referral center. PATIENTS: Ninety-three ventilated patients requiring bronchoalveolar lavage fluids were enrolled (48 with acute respiratory distress syndrome, 33 with acute lung injury, and 12 ventilated patients without acute lung injury/acute respiratory distress syndrome). INTERVENTIONS: After bronchoalveolar lavage fluids collection during standard care, the patients were followed up for 28 days and clinical outcomes were recorded. Migration assays were performed by using a Transwell model; bronchoalveolar lavage fluids platelet-derived growth factor and soluble platelet-derived growth factor receptor-alpha were characterized by Western blot and measured by ELISA. MEASUREMENTS AND MAIN RESULTS: Most of the bronchoalveolar lavage fluids inhibited basal fibroblast migration. Bronchoalveolar lavage fluids chemotactic index increased with severity of lung injury (28% in patients without acute lung injury/acute respiratory distress syndrome and with acute lung injury vs. 91% in acute respiratory distress syndrome patients; p = .016). In acute lung injury/acute respiratory distress syndrome patients, inhibition of basal fibroblast migration by bronchoalveolar lavage fluids below 52% was independently associated with a lower 28-day mortality (odds ratio [95% confidence interval] 0.313 [0.10-0.98], p = .046). Platelet-derived growth factor-related peptides and soluble platelet-derived growth factor-Ralpha were detected in all bronchoalveolar lavage fluids from acute lung injury/acute respiratory distress syndrome patients. The effect of bronchoalveolar lavage fluids stimulating migration was inhibited by a specific platelet-derived growth factor receptor inhibitor (AG1296). Bronchoalveolar lavage fluids inhibiting migration reversed the effect of rh-platelet-derived growth factor-BB and reduced by 40% the binding of 125I-platelet-derived growth factor-BB to fibroblast cell surface in favor of a role for platelet-derived growth factor-sRalpha. CONCLUSIONS: : Together, our results suggest that during acute lung injury, fibroblast migration is modulated by bronchoalveolar lavage fluids through a platelet-derived growth factor/platelet-derived growth factor-sRalpha balance. Migration is associated with clinical severity and patient 28-day mortality

Systematic overdosing of oxa- and cloxacillin in severe infections treated in ICU: risk factors and side effects

Additional file 1: Figure S1. Flowchart of patients included between 2012 and 2014

Temperature control in sepsis

Fever can be viewed as an adaptive response to infection. Temperature control in sepsis is aimed at preventing potential harms associated with high temperature (tachycardia, vasodilation, electrolyte and water loss) and therapeutic hypothermia may be aimed at slowing metabolic activities and protecting organs from inflammation. Although high fever (>39.5°C) control is usually performed in critically ill patients, available cohorts and randomized controlled trials do not support its use to improve sepsis prognosis. Finally, both spontaneous and therapeutic hypothermia are associated with poor outcomes in sepsis

Pulmonary infections complicating ARDS.

Pulmonary infection is one of the main complications occurring in patients suffering from acute respiratory distress syndrome (ARDS). Besides traditional risk factors, dysregulation of lung immune defenses and microbiota may play an important role in ARDS patients. Prone positioning does not seem to be associated with a higher risk of pulmonary infection. Although bacteria associated with ventilator-associated pneumonia (VAP) in ARDS patients are similar to those in patients without ARDS, atypical pathogens (Aspergillus, herpes simplex virus and cytomegalovirus) may also be responsible for infection in ARDS patients. Diagnosing pulmonary infection in ARDS patients is challenging, and requires a combination of clinical, biological and microbiological criteria. The role of modern tools (e.g., molecular methods, metagenomic sequencing, etc.) remains to be evaluated in this setting. One of the challenges of antimicrobial treatment is antibiotics diffusion into the lungs. Although targeted delivery of antibiotics using nebulization may be interesting, their place in ARDS patients remains to be explored. The use of extracorporeal membrane oxygenation in the most severe patients is associated with a high rate of infection and raises several challenges, diagnostic issues and pharmacokinetics/pharmacodynamics changes being at the top. Prevention of pulmonary infection is a key issue in ARDS patients, but there is no specific measure for these high-risk patients. Reinforcing preventive measures using bundles seems to be the best option