High vs. Low PEEP in ARDS Patients Exhibiting Intense Inspiratory Effort During Assisted Ventilation: A Randomized Crossover Trial.

BACKGROUND: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury. RESEARCH QUESTION: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation? STUDY DESIGN AND METHODS: Sixteen patients with Pao2/Fio2 ≤ 200 mm Hg and ΔPes ≥ 10 cm H2O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H2O or PEEP = 15 cm H2O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography. RESULTS: ΔPes was not systematically different at high vs low PEEP (PSV: median, 20 cm H2O; range, 15-24 cm H2O vs median, 15 cm H2O; range, 13-23 cm H2O; P = .24; PC-IMV: median, 20; range, 18-23 vs median, 19; range, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = -0.85, P < .001; r = -0.75, P < .001; r = -0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = -0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (PSV: median, 0.49; range, 0.37-0.83 vs median, 0.96; range, 0.62-1.56; P = .003; PC-IMV: median, 0.65; range, 0.42-1.31 vs median, 1.14; range, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance. INTERPRETATION: The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04241874; URL: www. CLINICALTRIALS: gov.

Acute confusional state in HaNDL syndrome.

OBJECTIVE: To assess epidemiological, clinical and neuroimaging features of acute confusional state in the Headache and Neurological Deficits with cerebrospinal fluid Lymphocytosis (HaNDL) syndrome. BACKGROUND: HaNDL is an increasingly recognized syndrome in which migraine-like headache episodes accompanied by hemiparaesthesia and/or hemiparesis and/or dysphasia are associated to CSF lymphocytic pleocytosis. The International Classification of Headache Disorders (ICHD-3) includes HaNDL syndrome in group 7 "headache attributed to non-vascular intracranial disorder" code 7.3.5, and lists the HaNDL-associated signs/symptoms that may be found less frequently. Confusional state is not mentioned in the 7.3.5-ICHD-3 "notes" or "comments" section as part of the HaNDL neurological spectrum. Moreover, the acute confusional state pathogenesis in HaNDL syndrome remains still uncertain and debated. METHODS: Here, we report a 32-year-old male who complained episodes of migraine-like headache and left hemiparaesthesia complicated by confusional state which led to discovering CSF lymphocytosis. Since other workup to determine the cause of his symptoms was otherwise negative, he was diagnosed as having HaNDL syndrome. We also ascertained and reviewed all available reports of HaNDL to assess the significance of confusional state in this syndrome. RESULTS: The search yielded 159 HaNDL cases among single reports and small/large series. Out of 159 patients who fulfilled the inclusion criteria for HaNDL according to the current ICHD at the time of diagnosis, 41 (25.7%) presented with acute confusional state. Among 41 HaNDL patients with confusional state, 16 (66.6%) out of 24 who underwent spinal tap had increased opening pressure. CONCLUSION: We propose that a mention of acute confusional state may be included in the "comments" section of "7.3.5-syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL)," when ICHD-3 diagnostic criteria will be updated. Moreover, we speculate that intracranial hypertension may play a role in the pathogenesis of the acute confusional state associated to HaNDL syndrome. Larger case series are needed to evaluate this hypothesis.

Risk Factors Associated with Post-Operative Complications in Multidisciplinary Treatment of Descending Necrotizing Mediastinitis.

BACKGROUND: Descending necrotizing mediastinitis (DNM) is a severe, life-threatening complication of oropharyngeal infections with cervical necrotizing fasciitis. In this study, we aimed to identify any possible factors that correlate with favorable outcomes. METHODS: We retrospectively analyzed our series of 18 patients who underwent surgical treatment for DNM from a cervical abscess. Gender, age, symptoms, etiopathogenesis, comorbidities, time to surgery from diagnosis, degree of diffusion, identified microorganisms, surgical procedure, days in the intensive care unit, need for tracheostomy, complications, and surgical outcomes were reviewed. RESULTS: The main type of surgery was thoracotomy + cervicotomy in eight cases (50.0%), followed by cervicotomy +VATS in four (22.2%). Seven patients (38.9%) had two or more surgeries; a bilateral operation was necessary for four patients. Evaluating the risk factors associated with post-operative complications, age ≥ 60 years (p:0.031), cervicotomy alone as surgical approach (p = 0.040), and the bilateral approach (p = 0.048) resulted in significance in terms of the univariate analysis; age ≥ 60 years (p = 0.04) and cervical approach (p = 0.05) maintained their significance in terms of the multivariate analysis. CONCLUSIONS: The low mortality of our series emphasizes the importance of an extensive and immediate surgical drainage of both the neck and the mediastinum. Mediastinal drainage from cervicotomy seems to be a risk factor for post-operative complications. Minimally invasive surgery on the chest cavity, such as with Uniportal-VATS, could be a good approach above all in elderly patients and all those cases where bilateral access is required.

Unusual malposition of a peripherally inserted central catheter into the left pericardiophrenic vein: A case report.

We report a case of primary malposition of a PICC inserted by guidewire replacement in the emergency room. Intraprocedural tip location by intracavitary electrocardiography was not feasible because the patient had atrial fibrillation; intraprocedural tip location by ultrasound (using the so-called "bubble test") showed that the tip was not in the superior vena cava or in the right atrium. A post-procedural chest X-ray confirmed the malposition but could not precise the location of the tip. A CT scan (scheduled for other purposes) finally visualized the tip in a very unusual location, the left pericardiophrenic vein.

Gas conditioning during helmet noninvasive ventilation: effect on comfort, gas exchange, inspiratory effort, transpulmonary pressure and patient-ventilator interaction.

BACKGROUND: There is growing interest towards the use of helmet noninvasive ventilation (NIV) for the management of acute hypoxemic respiratory failure. Gas conditioning through heat and moisture exchangers (HME) or heated humidifiers (HHs) is needed during facemask NIV to provide a minimum level of humidity in the inspired gas (15 mg H2O/L). The optimal gas conditioning strategy during helmet NIV remains to be established. METHODS: Twenty patients with acute hypoxemic respiratory failure (PaO2/FiO2 < 300 mmHg) underwent consecutive 1-h periods of helmet NIV (PEEP 12 cmH2O, pressure support 12 cmH2O) with four humidification settings, applied in a random order: double-tube circuit with HHs and temperature set at 34 °C (HH34) and 37 °C (HH37); Y-piece circuit with HME; double-tube circuit with no humidification (NoH). Temperature and humidity of inhaled gas were measured through a capacitive hygrometer. Arterial blood gases, discomfort and dyspnea through visual analog scales (VAS), esophageal pressure swings (ΔPES) and simplified pressure-time product (PTPES), dynamic transpulmonary driving pressure (ΔPL) and asynchrony index were measured in each step. RESULTS: Median [IqR] absolute humidity, temperature and VAS discomfort were significantly lower during NoH vs. HME, HH34 and HH37: absolute humidity (mgH2O/L) 16 [12-19] vs. 28 [23-31] vs. 28 [24-31] vs. 33 [29-38], p < 0.001; temperature (°C) 29 [28-30] vs. 30 [29-31] vs. 31 [29-32] vs 32. [31-33], p < 0.001; VAS discomfort 4 [2-6] vs. 6 [2-7] vs. 7 [4-8] vs. 8 [4-10], p = 0.03. VAS discomfort increased with higher absolute humidity (p < 0.01) and temperature (p = 0.007). Higher VAS discomfort was associated with increased VAS dyspnea (p = 0.001). Arterial blood gases, respiratory rate, ΔPES, PTPES and ΔPL were similar in all conditions. Overall asynchrony index was similar in all steps, but autotriggering rate was lower during NoH and HME (p = 0.03). CONCLUSIONS: During 1-h sessions of helmet NIV in patients with hypoxemic respiratory failure, a double-tube circuit with no humidification allowed adequate conditioning of inspired gas, optimized comfort and improved patient-ventilator interaction. Use of HHs or HME in this setting resulted in increased discomfort due to excessive heat and humidity in the interface, which was associated with more intense dyspnea. Trail Registration Registered on clinicaltrials.gov (NCT02875379) on August 23rd, 2016.

Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study.

BACKGROUND: A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients. METHODS: Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed. RESULTS: Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72-0.88). The cut-off values of DTF for prediction of NIV failure were < 36.3% and < 37.1% for the operator 1 and 2 (p < 0.0001), respectively. The cut-off value of respiratory rate/DTF ratio for prediction of NIV failure was > 0.6 for both operators (p < 0.0001). CONCLUSION: DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF. Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.

High Failure Rate of Noninvasive Oxygenation Strategies in Critically Ill Subjects With Acute Hypoxemic Respiratory Failure Due to COVID-19.

BACKGROUND: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19. METHODS: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, [Formula: see text] and [Formula: see text] at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes. RESULTS: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score (P = .009) and serum lactate dehydrogenase at enrollment (P = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, P = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, P = .01). CONCLUSIONS: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score ≥ 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk.

Effect of the COVID-19 pandemic and the lockdown measures on the local stroke network.

INTRODUCTION: The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers. METHODS: This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020-4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year. RESULTS: A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed. DISCUSSION: Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers.

Management of Pleural Effusions in the Emergency Department.

BACKGROUND: In symptomatic patients, admitted in emergency department for acute chest pain and dyspnea, who require an urgent treatment, a rapid diagnosis and prompt management of massive pleural effusion or hemothorax can be lifesaving. AIM: The aim of this review was to summarize the current diagnostic and therapeutic approaches for the management of the main types of pleural effusions that physicians can have in an emergency department setting. METHODS: Current literature about the topic was reviewed and critically reported, adding the experience of the authors in the management of pleural effusions in emergency settings. RESULTS: The paper analyzed the main types of pleural effusions that physicians can have to treat. It illustrated the diagnostic steps by the principal radiological instruments, with a particular emphasis to the role of ultrasonography, in facilitating diagnosis and guiding invasive procedures. Then, the principal procedures, like thoracentesis and insertion of small and large bore chest drains, are indicated and illustrated according to the characteristics and the amount of the effusion and patient clinical conditions. CONCLUSION: The emergency physician must have a systematic approach that allows rapid recognition, clinical cause identification and definitive management of potential urgent pleural effusions.

Indications for Non-Invasive Ventilation in Respiratory Failure.

BACKGROUND: Non-invasive ventilation (NIV) is increasingly being used to treat episodes of acute respiratory failure not only in critical care and respiratory wards, but also in emergency departments. AIM: Aim of this review is to summarize the current indications for the management of NIV for respiratory failure. METHODS: Current literature about the topic was reviewed and critically reported to describe the rationale and physiologic advantages of NIV in various situations of respiratory failure. RESULTS: Early NIV use is commonly associated with the significant decrease in endotracheal intubation rate, the incidence of infective complications (especially ventilatory associated pneumonia), Intensive Care Units and the length of hospital stay and, in selected conditions, also in mortality rates. Severe acute exacerbation of chronic obstructive pulmonary disease (pH<7.35 and relative hypercarbia) and acute cardiogenic pulmonary oedema are the most common NIV indications; in these conditions NIV advantages are clearly documented. Not so evident are the NIV benefits in hypoxaemic respiratory failure occurring without prior chronic respiratory disease (De novo respiratory failure). One recent randomized control trial reported in hypoxaemic respiratory failure a survival benefit of high-flow nasal cannulae over standard oxygen therapy and bilevel NIV. Evidence suggests the advantages of NIV also in respiratory failure in immunocompromised patients or chest trauma patients. Use during a pandemic event has been assessed in several observational studies but remains controversial; there also is not sufficient evidence to support the use of NIV treatment in acute asthma exacerbation. CONCLUSION: NIV eliminates morbidity related to the endotracheal tube (loss of airway defense mechanism with increased risk of pneumonia) and in selected conditions (COPD exacerbation, acute cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates and hypoxia) is clearly associated with a better outcome in comparison to conventional invasive ventilation. However, NIV is associated with complications, especially minor complications related to interface. Major complications like aspiration pneumonia, barotrauma and hypotension are infrequent.

Early nasal high-flow versus Venturi mask oxygen therapy after lung resection: a randomized trial.

BACKGROUND: Data on high-flow nasal oxygen after thoracic surgery are limited and confined to the comparison with low-flow oxygen. Different from low-flow oxygen, Venturi masks provide higher gas flow at a predetermined fraction of inspired oxygen (FiO2). We conducted a randomized trial to determine whether preemptive high-flow nasal oxygen reduces the incidence of postoperative hypoxemia after lung resection, as compared to Venturi mask oxygen therapy. METHODS: In this single-center, randomized trial conducted in a teaching hospital in Italy, consecutive adult patients undergoing thoracotomic lung resection, who were not on long-term oxygen therapy, were randomly assigned to receive high-flow nasal or Venturi mask oxygen after extubation continuously for two postoperative days. The primary outcome was the incidence of postoperative hypoxemia (i.e., ratio of the partial pressure of arterial oxygen to FiO2 (PaO2/FiO2) lower than 300 mmHg) within four postoperative days. RESULTS: Between September 2015 and April 2018, 96 patients were enrolled; 95 patients were analyzed (47 in high-flow group and 48 in Venturi mask group). In both groups, 38 patients (81% in the high-flow group and 79% in the Venturi mask group) developed postoperative hypoxemia, with an unadjusted odds ratio (OR) for the high-flow group of 1.11 [95% confidence interval (CI) 0.41-3] (p = 0.84). No inter-group differences were found in the degree of dyspnea nor in the proportion of patients needing oxygen therapy after treatment discontinuation (OR 1.34 [95% CI 0.60-3]), experiencing pulmonary complications (OR 1.29 [95% CI 0.51-3.25]) or requiring ventilatory support (OR 0.67 [95% CI 0.11-4.18]). Post hoc analyses revealed that PaO2/FiO2 during the study was not different between groups (p = 0.92), but patients receiving high-flow nasal oxygen had lower arterial pressure of carbon dioxide, with a mean inter-group difference of 2 mmHg [95% CI 0.5-3.4] (p = 0.009), and were burdened by a lower risk of postoperative hypercapnia (adjusted OR 0.18 [95% CI 0.06-0.54], p = 0.002). CONCLUSIONS: When compared to Venturi mask after thoracotomic lung resection, preemptive high-flow nasal oxygen did not reduce the incidence of postoperative hypoxemia nor improved other analyzed outcomes. Further adequately powered investigations in this setting are warranted to establish whether high-flow nasal oxygen may yield clinical benefit on carbon dioxide clearance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02544477 . Registered 9 September 2015.

Necrotizing Fasciitis Following Herpes Zoster Ophthalmicus in an Immunocompromised Patient.

Necrotizing fasciitis (NF) is a rare infection that spreads rapidly along the subcutaneous soft tissue planes. NF rarely involves the periorbital region due to the excellent blood supply of this region. We report a case of periorbital necrotising fasciitis following herpes zoster (HZ) in an immunocompromised 70-year-old patient with a dramatically rapid evolution into septic shock. In our patient, the surprisingly rapid spread of the bacterial superinfection led the periorbital cellulitis to turn into frank NF within 2 hours, with an overwhelming evolution. Despite the prompt start of a systemic antibiotic therapy and the immediate surgical intervention, the patient had a septic shock; she was treated in ITU for 31 days and then discharged to a medical ward and eventually died for a mix of complications of the medical treatment and comorbidities. This case is unique because any documented cases of periorbital NF triggered by HZ had never led to a septic shock and death. Ophthalmologists should be aware that even common skin lesions caused by shingles can determine a dramatic clinical picture, in presence of predisposing factors.

CO2 driven endotracheal tube cuff control in critically ill patients: A randomized controlled study.

BACKGROUND: To determine the safety and clinical efficacy of an innovative integrated airway system (AnapnoGuard™ 100 system) that continuously monitors and controls the cuff pressure (Pcuff), while facilitating the aspiration of subglottic secretions (SS). METHODS: This was a prospective, single centre, open-label, randomized, controlled feasibility and safety trial. The primary endpoint of the study was the rate of device related adverse events (AE) and serious AE (SAE) as a result of using AnapnoGuard (AG) 100 during mechanical ventilation. Secondary endpoints were: (1) mechanical complications rate (2) ICU staff satisfaction; (3) VAP occurrence; (4) length of mechanical ventilation; (5) length of Intensive Care Unit stay and mortality; (6) volume of evacuated subglottic secretions. Sixty patients were randomized to be intubated with the AG endotracheal-tube (ETT) and connected to the AG 100 system allowing Pcuff adjustment and SS aspiration; or with an ETT combined with SS drainage and Pcuff controlled manually. RESULTS: No difference in adverse events rate was identified between the groups. The use of AG system was associated with a significantly higher incidence of Pcuff determinations in the safety range (97.3% vs. 71%; p<0.01) and a trend to a greater volume of aspirated SS secretions: (192.0[64-413] ml vs. 150[50-200], p = 0.19 (total)); (57.8[20-88.7] ml vs. 50[18.7-62] ml, p = 0.11 (daily)). No inter-group difference was detected using AG system vs. controls in terms of post-extubation throat pain level (0 [0-2] vs. 0 [0-3]; p = 0.7), hoarseness (42.9% vs. 75%; p = 0.55) and tracheal mucosa oedema (16.7% vs. 10%; p = 0.65). Patients enrolled in the AG group had a trend to reduced VAP risk of ventilator-associated pneumonia(VAP) (14.8% vs. 40%; p = 0.06), which were more frequently monomicrobial (25% vs. 70%; p = 0.03). No statistically significant difference was observed in duration of mechanical ventilation, ICU stay, and mortality. CONCLUSIONS: The use AG 100 system and AG tube in critically ill intubated patients is safe and effective in Pcuff control and SS drainage. Its protective role against VAP needs to be confirmed in a larger randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01550978. Date of registration: February 21, 2012.

Clinical impact of pulmonary sampling site in the diagnosis of ventilator-associated pneumonia: A prospective study using bronchoscopic bronchoalveolar lavage.

PURPOSE: It is unclear whether ventilator-associated pneumonia (VAP) is actually a bilateral and multifocal process. In addition, the diagnostic role of chest x-ray is under debate. Assuming a low microbiologic concordance between the left and right lungs, the reliability of a single pulmonary sampling becomes questionable. The purpose of this study was to determine whether the choice of the pulmonary sampling area is clinically relevant in the management of VAP. METHODS: In 79 patients admitted to a university general intensive care unit with clinically suspected VAP, right- and left-lung bronchoalveolar lavage (BAL) samples were taken with separate bronchoscopes and quantitatively cultured. Primary end-point variable was microbiologic concordance rate between right- and left-lung BAL cultures. Secondary outcomes included predictors of microbiologic concordance, rates of appropriate antibiotic treatment, and diagnostic accuracy of chest x-ray. RESULTS: BAL cultures were bilaterally negative in 21 (27%) of 79 patients, bilaterally positive in 36 (46%), and unilaterally positive (right in 12, left in 10) in 22 (28%). Intra-patient concordance was observed in 47 (59.5%) of 79 cases and independently associated with purulent secretions and bilateral infiltrates on chest x-ray. In simulated prescribing experiments, treatments chosen based on right or left cultures alone were as appropriate as those based on bilateral data in >90% of cases. The presence of a radiographic infiltrate in the sampling area predicted BAL culture positivity with a positive predictive value of only 61%. CONCLUSIONS: In patients with clinically suspected VAP (especially those without purulent secretions or without radiographically documented bilateral infiltrates), quantitative culture of a single BAL sample may provide an incomplete assessment of lung microbiology, without having a relevant impact on the appropriateness of antimicrobial treatment. These findings suggest that single sampling of respiratory secretions, regardless radiographic opacity, seems to be a reliable diagnostic method in the management of VAP.

Linezolid plasma and intrapulmonary concentrations in critically ill obese patients with ventilator-associated pneumonia: intermittent vs continuous administration.

PURPOSE: Clinical application of an antibiotic's pharmacokinetic/pharmacodynamic (PK/PD) properties may improve the outcome of severe infections. No data are available on the use of linezolid (LNZ) continuous infusion in critically ill obese patients affected by ventilator-associated pneumonia (VAP). METHODS: We conducted a prospective randomized controlled trial to compare LNZ concentrations in plasma and epithelial lining fluid (ELF), when administered by intermittent and continuous infusion (II, CI), in obese critically ill patients affected by VAP. RESULTS: Twenty-two critically ill obese patients were enrolled. At the steady state, in the II group, mean ± SD total and unbound maximum-minimum concentrations (C max/C max,u - C min/Cmin,u) were 10 ± 3.7/6.8 ± 2.6 mg/L and 1.7 ± 1.1/1.2 ± 0.8 mg/L, respectively. In the CI group, the mean ± SD total and unbound plasma concentrations (C ss and C ss,u) were 6.2 ± 2.3 and 4.3 ± 1.6 mg/L, respectively. Within a minimum inhibitory concentration (MIC) range of 1-4 mg/L, the median (IQR) time LNZ plasma concentration persisted above MIC (% T > MIC) was significantly higher in the CI than the II group [100 (100-100) vs 100 (89-100), p = 0.05; 100 (100-100) vs 82 (54.8-98.8), p = 0.009; 100 (74.2-100) vs 33 (30.2-78.5), p = 0.005; respectively]. Pulmonary penetration (%) was higher in the CI group, as confirmed by a Monte Carlo simulation [98.8 (IQR 93.8-104.3) vs 87.1 (IQR 78.7-95.4); p < 0.001]. CONCLUSIONS: In critically ill obese patients affected by VAP, LNZ CI may overcome the limits of standard administration but these advantages are less evident with difficult to treat pathogens (MIC = 4 mg/L). These data support the usefulness of LNZ continuous infusion, combined with therapeutic drug monitoring (TDM), in selected critically ill populations.

Racemic ketamine in adult head injury patients: use in endotracheal suctioning.

INTRODUCTION: Endotracheal suctioning (ETS) is essential for patient care in an ICU but may represent a cause of cerebral secondary injury. Ketamine has been historically contraindicated for its use in head injury patients, since an increase of intracranial pressure (ICP) was reported; nevertheless, its use was recently suggested in neurosurgical patients. In this prospective observational study we investigated the effect of ETS on ICP, cerebral perfusion pressure (CPP), jugular oxygen saturation (SjO2) and cerebral blood flow velocity (mVMCA) before and after the administration of ketamine. METHODS: In the control phase, ETS was performed on patients sedated with propofol and remifentanil in continuous infusion. If a cough was present, patients were assigned to the intervention phase, and 100 γ/kg/min of racemic ketamine for 10 minutes was added before ETS. RESULTS: In the control group ETS stimulated the cough reflex, with a median cough score of 2 (interquartile range (IQR) 1 to 2). Furthermore, it caused an increase in mean arterial pressure (MAP) (from 89.0 ± 11.6 to 96.4 ± 13.1 mmHg; P <0.001), ICP (from 11.0 ± 6.7 to 18.5 ± 8.9 mmHg; P <0.001), SjO2 (from 82.3 ± 7.5 to 89.1 ± 5.4; P = 0.01) and mVMCA (from 76.8 ± 20.4 to 90.2 ± 30.2 cm/sec; P = 0.04). CPP did not vary with ETS. In the intervention group, no significant variation of MAP, CPP, mVMCA, and SjO2 were observed in any step; after ETS, ICP increased if compared with baseline (15.1 ± 9.4 vs. 11.0 ± 6.4 mmHg; P <0.05). Cough score was significantly reduced in comparison with controls (P <0.0001). CONCLUSIONS: Ketamine did not induce any significant variation in cerebral and systemic parameters. After ETS, it maintained cerebral hemodynamics without changes in CPP, mVMCA and SjO2, and prevented cough reflex. Nevertheless, ketamine was not completely effective when used to control ICP increase after administration of 100 γ/kg/min for 10 minutes.

The role of mannose-binding lectin in severe sepsis and septic shock.

Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.

Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients.

PURPOSE: Our aim was to identify the clinical profile of intensive care unit (ICU) patients with Pseudomonas aeruginosa (PA) pneumonia and the impact on ICU mortality and duration of mechanical ventilation (MV) of multidrug resistance (MDR) in the PA isolate and inadequate initial antibiotic therapy (IIAT). METHODS: We conducted a retrospective analysis of data prospectively collected in the 18-bed general ICU of a major teaching hospital in Rome, Italy. The study cohort consisted of 110 adult patients with culture-confirmed PA pneumonia consecutively diagnosed in 2008-2010. ICU survivor and nonsurvivor groups were compared to identify factors associated with ICU mortality. RESULTS: In 42 (38 %) of the 110 cases of PA pneumonia analyzed, the PA isolate was MDR. Fifty-six (50.9 %) of the patients received IIAT, and 49 (44.5 %) died in ICU. In logistic regression analysis, IIAT, diabetes mellitus, higher Simplified Acute Physiology Score (SAPS) II scores, and older age were independently associated with ICU mortality. Among survivors, those who received IIAT or had MDR PA pneumonia had significantly longer median (interquartile ranges, IQR) periods of post-pneumonia onset MV (16.5 [14.5-20] and 15 [12-18] days, respectively) compared with those whose initial therapy was adequate (8 [6-13] days, P < 0.001) and those whose infections were caused by non-MDR PA (10.5 [6.5-13] days, P = 0.01). CONCLUSIONS: Our findings highlight the importance of IIAT as a risk factor for mortality in ICU patients with PA pneumonia. MDR in the PA isolate, like IIAT, can significantly increase the need for MV.