Giuseppe Bello

A multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome

Objective: In randomized studies of heterogeneous patients with hypoxemic acute respiratory failure, noninvasive positive pressure ventilation (NPPV) was associated with a significant reduction in endotracheal intubation. The role of NPPV in patients with acute respiratory distress syndrome (ARDS) is still unclear. The objective was to investigate the application of NPPV as a first‐line intervention in patients with early ARDS, describing what happens in everyday clinical practice in centers having expertise with NPPV. Design: Prospective, multiple‐center cohort study. Setting: Three European intensive care units having expertise with NPPV. Patients: Between March 2002 and April 2004, 479 patients with ARDS were admitted to the intensive care units. Three hundred and thirty‐two ARDS patients were already intubated, so 147 were eligible for the study. Interventions: Application of NPPV. Measurements and Main Results: NPPV improved gas exchange and avoided intubation in 79 patients (54%). Avoidance of intubation was associated with less ventilator‐associated pneumonia (2% vs. 20%; p < .001) and a lower intensive care unit mortality rate (6% vs. 53%; p < .001). Intubation was more likely in patients who were older (p = .02), had a higher Simplified Acute Physiology Score (SAPS) II (p < .001), or needed a higher level of positive end‐expiratory pressure (p = .03) and pressure support ventilation (p = .02). Only SAPS II >34 and a Pao2/Fio2 ≤175 after 1 hr of NPPV were independently associated with NPPV failure and need for endotracheal intubation. Conclusions: In expert centers, NPPV applied as first‐line intervention in ARDS avoided intubation in 54% of treated patients. A SAPS II >34 and the inability to improve Pao2/Fio2 after 1 hr of NPPV were predictors of failure.

Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index

IntroductionThe culture-independent serum (1→3)-β-D-glucan (BG) detection test may allow early diagnosis of invasive fungal disease, but its clinical usefulness needs to be firmly established. A prospective single-center observational study was conducted to compare the diagnostic value of BG assay, Candida score (CS), and colonization index in intensive care unit (ICU) patients at risk for Candida sepsis.MethodsOf 377 patients, consecutively admitted to ICU for sepsis, 95 patients having an ICU stay of more than five days were studied. Blood specimens for fungal culture and BG measurement were obtained at the onset of clinical sepsis. For CS and colonization index calculations, surveillance cultures for Candida growth, and/or clinical data were recorded.ResultsSixteen (16.8%) patients were diagnosed with proven invasive fungal infection, 14 with candidiasis (13 candidemia and 1 mediastinitis) and 2 with pulmonary aspergillosis or fusariosis. Of 14 invasive Candida-infection patients, 13 had a serum sample positive for BG, 10 had a CS value ≥3, and 7 a colonization index ≥0.5. In the 12 candidemic patients, a positive BG result was obtained 24 to 72 hrs before a culture-documented diagnosis of invasive candidiasis. The positive and negative predictive values for the BG assay were higher than those of CS and colonization index (72.2% versus 57.1% and 27.3%; and 98.7% versus 97.2% and 91.7%, respectively).ConclusionsA single-point BG assay based on a blood sample drawn at the sepsis onset, alone or in combination withCS, may guide the decision to start antifungal therapy early in patients at risk for Candida infection.

Diagnosis of Invasive Aspergillosis by a Commercial Real-Time PCR Assay for Aspergillus DNA in Bronchoalveolar Lavage Fluid Samples from High-Risk Patients Compared to a Galactomannan Enzyme Immunoassay

ABSTRACT Culture-independent molecular techniques such as real-time PCRs offer the potential for early diagnosis of invasive aspergillosis (IA), thereby reducing the disease-associated mortality rate. PCR-based testing is presently excluded from disease-defining consensus criteria due to lack of standardization and clinical validation. A single-center prospective study was conducted to investigate the performance of the commercially available MycAssay Aspergillus test for detecting Aspergillus DNA in patients with suspicion of IA. To this end, a total of 158 bronchoalveolar lavage (BAL) fluid specimens that were consecutively collected from hematology (n = 68) and intensive care unit (n = 90) patients were examined. Sixteen of 17 (94.1%) specimens from patients with proven/probable IA were MycAssay positive, and 15 of these 16 patients were also positive by an “in-house” PCR assay. A total of 139 of 141 (98.6%) specimens from patients without proven/probable IA were MycAssay negative. Fifteen of 16 (94.1%) MycAssay-positive patients were also positive for BAL fluid galactomannan (GM) at an index cutoff of ≥1.0 (index range, 1.1 to 8.3), as were 3 patients without IA but with pulmonary fusariosis. Interestingly, in seven of the PCR-positive BAL specimens that tested culture positive for Aspergillus species, cycle threshold values were earlier than those of specimens with a culture-negative result. In conclusion, the MycAssay Aspergillus PCR appears to be a sensitive and specific molecular test for the diagnosis of IA, and its performance is comparable to that of the GM assay. However, more large studies are necessary to firmly establish its clinical utility in high-risk settings.

Effect of Aerosolized Colistin as Adjunctive Treatment on the Outcomes of Microbiologically Documented Ventilator-Associated Pneumonia Caused by Colistin-Only Susceptible Gram-Negative Bacteria

BACKGROUND The increasing frequency of ventilator-associated pneumonia (VAP) caused by colistin-only susceptible (COS) gram-negative bacteria (GNB) is of great concern. Adjunctive aerosolized (AS) colistin can reportedly increase alveolar levels of the drug without increasing systemic toxicity. Good clinical results have been obtained in patients with cystic fibrosis, but conflicting data have been reported in patients with VAP. METHODS We conducted a retrospective, 1:1 matched case-control study to evaluate the efficacy and safety of AS plus IV colistin vs IV colistin alone in 208 patients in the ICU with VAP caused by COS Acinetobacter baumannii, Pseudomonas aeruginosa, or Klebsiella pneumoniae. RESULTS Compared with the IV colistin cohort, the AS-IV colistin cohort had a higher clinical cure rate (69.2% vs 54.8%, P = .03) and required fewer days of mechanical ventilation after VAP onset (8 days vs 12 days, P = .001). In the 166 patients with posttreatment cultures, eradication of the causative organism was also more common in the AS-IV colistin group (63.4% vs 50%, P = .08). No between-cohort differences were observed in all-cause ICU mortality, length of ICU stay after VAP onset, or rates of acute kidney injury (AKI) during colistin therapy. Independent predictors of clinical cure were trauma-related ICU admission (P = .01) and combined AS-IV colistin therapy (P = .009). Higher mean Simplified Acute Physiology Score II (P = .002) and Sequential Organ Failure Assessment (P = .05) scores, septic shock (P < .001), and AKI onset during colistin treatment (P = .04) were independently associated with clinical failure. CONCLUSIONS Our results suggest that AS colistin might be a beneficial adjunct to IV colistin in the management of VAP caused by COS GNB.

Nonthyroidal Illness Syndrome and Prolonged Mechanical Ventilation in Patients Admitted to the ICU

BACKGROUND The effect of the nonthyroidal illness syndrome (NTIS) on the duration of mechanical ventilation (MV) has not been extensively investigated. This study aims to determine whether the NTIS is associated with the duration of MV in patients admitted to the ICU. METHODS We evaluated all patients admitted over a 6-year period to our ICU who underwent invasive MV and had measurement of serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) performed in the first 4 days after ICU admission and, subsequently, at least every 8 days during the time they received MV. The primary outcome measure was prolonged MV (PMV), which was defined as dependence on MV for > 13 days. RESULTS Two hundred sixty-four patients were included. Fifty-six patients (normal-hormone group) had normal thyroid function test results, whereas 208 patients (low-fT3 group) had, at least in one hormone dosage, low levels of fT3 with normal (n = 145)/low (n = 63) levels of fT4 and normal (n = 189)/low (n = 19) levels of TSH. Patients in the low-fT3 group showed significantly higher mortality and simplified acute physiology score II, and significantly longer duration of MV and ICU length of stay compared with the normal-hormone group. Two of the variables studied were associated with PMV, as follows: the NTIS (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.18 to 4.29; p = 0.01); and the presence of pneumonia (OR, 1.17; 95% CI, 1.06 to 3.01; p = 0.03). CONCLUSION The NTIS represents a risk factor for PMV in mechanically ventilated, critically ill patients.

Noninvasive ventilation for the immunocompromised patient: always appropriate?

Purpose of reviewOver the last few decades, the survival rate in critically ill immunocompromised patients has substantially improved, mainly because of advances in oncohematological treatments and management of organ dysfunctions in the ICU. As a result, the number of patients admitted to the ICU has rapidly grown. Immunocompromised patients in whom acute respiratory failure (ARF) develops often require mechanical ventilatory support. In these patients, noninvasive ventilation (NIV) has the potential of avoiding endotracheal intubation and its complications. This review will discuss the recent findings on the role of NIV in immunocompromised patients with ARF. Recent findingsIn recent studies, NIV success was associated with shorter periods of ventilatory assistance and ICU stays, less infectious complications, and lower ICU and hospital mortality, compared with invasive mechanical ventilation. Failure of NIV occurred in half of the hematological patients with ARF. Major risk factors for NIV failure in these patients were illness severity at baseline and the presence of acute respiratory distress syndrome on admission. SummaryUse of NIV may not be appropriate for all immunocompromised patients. However, current evidence supports the use of NIV as the first-line approach for managing mild/moderate ARF in selected patients with immunosuppression of various origin.

Severe pneumonia in intensive care: cause, diagnosis, treatment and management: a review of the literature

PURPOSE OF REVIEW Severe pneumonia is a common disease that intensive care physicians have to face. The review highlights recent findings about microbiology, diagnosis and treatment, including the management of critically ill patients with severe respiratory failure. RECENT FINDINGS Epidemiological and clinical risk factors strongly influence microbiological cause in patients with severe pneumonia. In addition to typical respiratory pathogens, less common microrganisms and multidrug-resistant (MDR) germs may cause severe lung infections. New molecular diagnostic techniques appear promising for early detection of microbes involved in severe pneumonia. Antimicrobials remain the mainstay of causative severe pneumonia treatment and the optimization of antibiotic therapy may be obtained by applying their pharmacodynamic/pharmacokinetic properties. Several new strategies have been implemented for the management of acute respiratory failure (ARF) due to severe pneumonia; however, their extensive clinical application is limited by the need for well trained physicians and adequate hospital centers. SUMMARY Despite advancements in antibiotic and life-supportive treatments, severe pneumonia remains a leading cause of intensive care unit (ICU) admission and death. Prompt and appropriate antimicrobial therapy is essential. The use of new nonconventional strategies for ARF management might be effective in more severe patients.

Treating nonthyroidal illness syndrome in the critically ill patient: still a matter of controversy.

The nonthyroidal illness syndrome (NTIS) is a clinical condition of abnormal thyroid function tests observed in patients with acute or chronic systemic illnesses. The laboratory parameters of NTIS usually include low serum levels of triiodothyronine, with normal or low levels of thyroxine and normal or low levels of thyroid-stimulating hormone. It is still a matter of controversy whether the NTIS represents a protective adaptation of the organism to a stressful event or a maladaptive response to illness that needs correction. Multiple studies have investigated the effect of thyroid hormone replacement therapy in certain clinical situations, such as caloric restriction, cardiac disease, acute renal failure, brain-dead potential donors, and burn patients. Treating patients with NTIS seems not to be harmful, but there is no persuasive evidence that it is beneficial. The administration of hypothalamic releasing factors in patients with NTIS appears to be safe and effective in improving metabolism and restoring the anterior pituitary pulsatile secretion in the chronic phase of critical illness. However, also this promising strategy needs to be explored further. Anyhow, an extremely prudent approach is needed if treatment is given. Much of the data appearing in the literature on the treatment of NTIS encourage further randomized controlled trials on large number of patients. At present, however, we believe that there is no indication for treating thyroid hormone abnormalities in critically ill patients until convincing proof of efficacy and safety is provided.

Noninvasive ventilation: practical advice.

Purpose of reviewThis critical review discusses the key points that would be of practical help for the clinician who applies noninvasive ventilation (NIV) for treatment of patients with acute respiratory failure (ARF). Recent findingsIn recent years, the growing role of NIV in the acute care setting has led to the development of technical innovations to overcome the problems related to gas leakage and dead space. A considerable amount of research has been conducted to improve the quality of the devices as well as optimize ventilation modes used to administer NIV. As a result, also mechanical ventilators have been implemented with modalities aimed at delivering NIV. SummaryThe success of NIV in patients with ARF depends on several factors, including the skills of the clinician, selection of patient, choice of interface, selection of ventilation mode and ventilator setting, monitoring, and the motivation of the patient. Recent advances in the understanding of the physiological aspects of using NIV through different interfaces and ventilator settings have led to improve patient–machine interaction, enhancing favorable NIV outcome.

Noninvasive mechanical ventilation during the weaning process: facilitative, curative, or preventive?

To avoid the complications associated with endotracheal intubation, noninvasive positive-pressure ventilation (NPPV) has been proposed in the management of ventilator weaning in patients with acute respiratory failure (ARF) of various etiologies. Several studies have been performed to assess the benefit of NPPV in various weaning strategies, including permitting early extubation in patients who fail to meet standard extubation criteria (facilitation use), avoiding reintubation in patients who fail extubation (curative use), and preventing extubation failure in nonselected and selected patients (preventive use). NPPV has been successfully used in facilitating early extubation, particularly in patients with chronic obstructive pulmonary disease. In contrast, applying curative NPPV to treat postextubation ARF in nonselected populations may not be effective and could even be deleterious. Early use of NPPV was successful in preventing ARF after extubation, and decreased the need for reintubation in selected patients at risk of developing postextubation ARF. It is important that caregivers clearly differentiate among these application modalities of NPPV. The skills and expertise of both medical and nonmedical personnel are crucial predictive factors for the success of NPPV in the ventilator weaning process.