The effect of passive leg raising test on intracranial pressure and cerebral autoregulation in brain injured patients: a physiological observational study.

BACKGROUND: The use of the passive leg raising (PLR) is limited in acute brain injury (ABI) patients with increased intracranial pressure (ICP) since the postural change of the head may impact on ICP and cerebral autoregulation. However, the PLR use may prevent a positive daily fluid balance, which had been recently associated to worse neurological outcomes. We therefore studied early and delayed effects of PLR on the cerebral autoregulation of patients recovering from ABI. MATERIALS AND METHODS: This is a Prospective, observational, single-center study conducted in critically ill patients admitted with stable ABI and receiving invasive ICP monitoring, multimodal neuromonitoring and continuous hemodynamic monitoring. The fluid challenge consisted of 500 mL of crystalloid over 10 min; fluid responsiveness was defined as cardiac index increase ≥ 10%. Comparisons between different variables at baseline and after PLR were made by paired Wilcoxon signed-rank test. The correlation coefficients between hemodynamic and neuromonitoring variables were assessed using Spearman's rank test. RESULTS: We studied 23 patients [12 patients (52.2%) were fluid responders]. The PLR significantly increased ICP [from 13.7 (8.3-16.4) to 15.4 (12.0-19.2) mmHg; p < 0.001], cerebral perfusion pressure (CPP) [from 51.1 (47.4-55.6) to 56.4 (49.6-61.5) mmHg; p < 0.001] and the pressure reactivity index (PRx) [from 0.12 (0.01-0.24) to 0.43 (0.34-0.46) mmHg; p < 0.001]. Regarding Near Infrared Spectroscopy (NIRS)-derived parameters, PLR significantly increased the arterial component of regional cerebral oxygen saturation (O2Hbi) [from 1.8 (0.8-3.7) to 4.3 (2.5-5.6) µM cm; p < 0.001], the deoxygenated hemoglobin (HHbi) [from 1.6 (0.2-2.9) to 2.7 (1.4-4.0) µM cm; p = 0.007] and total hemoglobin (cHbi) [from 3.6 (1.9-5.3) to 7.8 (5.2-10.3): p < 0.001]. In all the patients who had altered autoregulation after PLR, these changes persisted ten minutes afterwards. After the PLR, we observed a significant correlation between MAP and CPP and PRx. CONCLUSIONS: In ABI patient with stable ICP, PLR test increased ICP, but mostly within safety values and thresholds. Despite this, cerebral autoregulation was importantly impaired, and this persisted up to 10 min after the end of the maneuvre. Our results discourage the use of PLR test in ABI even when ICP is stable.

Vancouver type B2 periprosthetic femoral fractures: clinical and radiological outcomes from a tertiary care center.

INTRODUCTION: The purpose of this study was to report mid-term clinical and radiographic results after hip arthroplasty revision in Vancouver type B2 femoral periprosthetic fractures (PPFx). Specifical focus of the paper is as follows: (1) the description of a standardized and reproducible surgical technique, (2) functional outcomes presentation and (3) type and number of complications and implants' survival rate analysis. METHODS: We retrospectively reviewed all patients treated for hip revision with non-modular tapered fluted titanium stem in patients with Vancouver type B2 femur PPFx at a single institution. At least 18 months' follow-up period was required. Harris Hip Scores and SF-12 were obtained, and radiographical follow-up was performed. Complications were reported and analyzed. RESULTS: The authors included 114 patients (114 hips) with a mean follow-up of 62.8 ± 30.6 months. All patients were treated with Wagner SL revision hip stem (Zimmer-Biomet), metal cerclage wires ± trochanteric plate. The mean HHS and SF-12 score at the last follow-up evaluation were respectively 81.3 ± 9.7 and 32.5 ± 7.6. Seventeen (14.9%) complications occurred. We observed five cases of dislocations, two of periprosthetic joint infections and six cases of new PPFx. The stem-related revision rate for any cause at the final FU was 1.7%, due to PJI. No patients underwent stem revision surgery for aseptic loosening. Fracture healed in all the included patients with a union-rate of 100%. The re-operation rate for any cause was 9.6%, with an implant survival rate for overall failure of 96.5%. CONCLUSION: The presented standard and reproducible surgical technique obtains optimal clinical and radiological results with limited complication rate at mid-term follow up. Preoperative planning as well as careful intraoperative surgical technique is of a paramount importance.

Early versus late intubation in COVID-19 patients failing helmet CPAP: A quantitative computed tomography study.

PURPOSE: To describe the effects of timing of intubation in COVID-19 patients that fail helmet continuous positive airway pressure (h-CPAP) on progression and severity of disease. METHODS: COVID-19 patients that failed h-CPAP, required intubation, and underwent chest computed tomography (CT) at two levels of positive end-expiratory pressure (PEEP, 8 and 16 cmH2O) were included in this retrospective study. Patients were divided in two groups (early versus late) based on the duration of h-CPAP before intubation. Endpoints included percentage of non-aerated lung tissue at PEEP of 8 cmH2O, respiratory system compliance and oxygenation. RESULTS: Fifty-two patients were included and classified in early (h-CPAP for ≤2 days, N = 26) and late groups (h-CPAP for >2 days, N = 26). Patients in the late compared to early intubation group presented: 1) lower respiratory system compliance (median difference, MD -7 mL/cmH2O, p = 0.044) and PaO2/FiO2 (MD -29 mmHg, p = 0.047), 2) higher percentage of non-aerated lung tissue (MD 7.2%, p = 0.023) and 3) similar lung recruitment increasing PEEP from 8 to 16 cmH2O (MD 0.1%, p = 0.964). CONCLUSIONS: In COVID-19 patients receiving h-CPAP, late intubation was associated with worse clinical presentation at ICU admission and more advanced disease. The possible detrimental effects of delaying intubation should be carefully considered in these patients.

Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.

BACKGROUND: Critically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia. METHODS: This was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue-shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support. RESULTS: Thirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median [interquartile range] 33% [24-49%] vs. 63% [44-68%], p < 0.001); and a larger extent of gas:blood volume mismatch (43% [30-49%] vs. 25% [14-28%], p = 0.001), due to higher shunt (23% [15-32%] vs. 5% [2-16%], p = 0.001) and non-aerated/non perfused regions (5% [3-10%] vs. 1% [0-2%], p = 0.001). The PaO2/FiO2 ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = - 0.633, p < 0.001). CONCLUSIONS: In critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.

Mechanical ventilation in neurocritical care setting: A clinical approach.

Neuropatients often require invasive mechanical ventilation (MV). Ideal ventilator settings and respiratory targets in neuro patients are unclear. Current knowledge suggests maintaining protective tidal volumes of 6-8 ml/kg of predicted body weight in neuropatients. This approach may reduce the rate of pulmonary complications, although it cannot be easily applied in a neuro setting due to the need for special care to minimize the risk of secondary brain damage. Additionally, the weaning process from MV is particularly challenging in these patients who cannot control the brain respiratory patterns and protect airways from aspiration. Indeed, extubation failure in neuropatients is very high, while tracheostomy is needed in one-third of the patients. The aim of this manuscript is to review and describe the current management of invasive MV, weaning, and tracheostomy for the main four subpopulations of neuro patients: traumatic brain injury, acute ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage.

Bronchoalveolar lavage fluid characteristics and outcomes of invasively mechanically ventilated patients with COVID-19 pneumonia in Genoa, Italy.

BACKGROUND: The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors. MATERIALS AND METHODS: Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed. RESULTS: Sixty-four patients were enrolled, median age of 64 years (IQR 58-69). The majority cells in the BALF were neutrophils (70%, IQR 37.5-90.5) and macrophages (27%, IQR 7-49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82-95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014-1.759, p = 0.039). CONCLUSIONS: In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

Computed tomography assessment of PEEP-induced alveolar recruitment in patients with severe COVID-19 pneumonia.

BACKGROUND: There is a paucity of data concerning the optimal ventilator management in patients with COVID-19 pneumonia; particularly, the optimal levels of positive-end expiratory pressure (PEEP) are unknown. We aimed to investigate the effects of two levels of PEEP on alveolar recruitment in critically ill patients with severe COVID-19 pneumonia. METHODS: A single-center cohort study was conducted in a 39-bed intensive care unit at a university-affiliated hospital in Genoa, Italy. Chest computed tomography (CT) was performed to quantify aeration at 8 and 16 cmH2O PEEP. The primary endpoint was the amount of alveolar recruitment, defined as the change in the non-aerated compartment at the two PEEP levels on CT scan. RESULTS: Forty-two patients were included in this analysis. Alveolar recruitment was median [interquartile range] 2.7 [0.7-4.5] % of lung weight and was not associated with excess lung weight, PaO2/FiO2 ratio, respiratory system compliance, inflammatory and thrombophilia markers. Patients in the upper quartile of recruitment (recruiters), compared to non-recruiters, had comparable clinical characteristics, lung weight and gas volume. Alveolar recruitment was not different in patients with lower versus higher respiratory system compliance. In a subgroup of 20 patients with available gas exchange data, increasing PEEP decreased respiratory system compliance (median difference, MD - 9 ml/cmH2O, 95% CI from - 12 to - 6 ml/cmH2O, p < 0.001) and the ventilatory ratio (MD - 0.1, 95% CI from - 0.3 to - 0.1, p = 0.003), increased PaO2 with FiO2 = 0.5 (MD 24 mmHg, 95% CI from 12 to 51 mmHg, p < 0.001), but did not change PaO2 with FiO2 = 1.0 (MD 7 mmHg, 95% CI from - 12 to 49 mmHg, p = 0.313). Moreover, alveolar recruitment was not correlated with improvement of oxygenation or venous admixture. CONCLUSIONS: In patients with severe COVID-19 pneumonia, higher PEEP resulted in limited alveolar recruitment. These findings suggest limiting PEEP strictly to the values necessary to maintain oxygenation, thus avoiding the use of higher PEEP levels.

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review.

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.

Six-Month Outcome of Immunocompromised Patients with Severe Acute Respiratory Distress Syndrome Rescued by Extracorporeal Membrane Oxygenation. An International Multicenter Retrospective Study.

Rationale: Because encouraging rates for hospital and long-term survival of immunocompromised patients in ICUs have been described, these patients are more likely to receive invasive therapies, like extracorporeal membrane oxygenation (ECMO).Objectives: To report outcomes of immunocompromised patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and to identify their pre-ECMO predictors of 6-month mortality and main ECMO-related complications.Methods: Retrospective multicenter study in 10 international ICUs with high volumes of ECMO cases. Immunocompromised patients, defined as having hematological malignancies, active solid tumor, solid-organ transplant, acquired immunodeficiency syndrome, or long-term or high-dose corticosteroid or immunosuppressant use, and severe ECMO-treated ARDS, from 2008 to 2015 were included.Measurements and Main Results: We collected demographics, clinical data, ECMO-related complications, and ICU- and 6 month-outcome data for 203 patients (median Acute Physiology and Chronic Health Evaluation II score, 28 [25th-75th percentile, 20-33]; age, 51 [38-59] yr; PaO2/FiO2, 60 [50-82] mm Hg before ECMO) who fulfilled our inclusion criteria. Six-month survival was only 30%, with a respective median ECMO duration and ICU stay of 8 (5-14) and 25 (16-50) days. Patients with hematological malignancies had significantly poorer outcomes than others (log-rank P = 0.02). ECMO-related major bleeding, cannula infection, and ventilator-associated pneumonia were frequent (36%, 10%, and 50%, respectively). Multivariate analyses retained fewer than 30 days between immunodeficiency diagnosis and ECMO cannulation as being associated with lower 6-month mortality (odds ratio, 0.32 [95% confidence interval, 0.16-0.66]; P = 0.002), and lower platelet count, higher Pco2, age, and driving pressure as independent pre-ECMO predictors of 6-month mortality.Conclusions: Recently diagnosed immunodeficiency is associated with a much better prognosis in ECMO-treated severe ARDS. However, low 6-month survival of our large cohort of immunocompromised patients supports restricting ECMO to patients with realistic oncological/therapeutic prognoses, acceptable functional status, and few pre-ECMO mortality-risk factors.

Comparison of the efficacy and safety of FP-1201-lyo (intravenously administered recombinant human interferon beta-1a) and placebo in the treatment of patients with moderate or severe acute respiratory distress syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) results in vascular leakage, inflammation and respiratory failure. There are currently no approved pharmacological treatments for ARDS and standard of care involves treatment of the underlying cause, and supportive care. The vascular leakage may be related to reduced concentrations of local adenosine, which is involved in maintaining endothelial barrier function. Interferon (IFN) beta-1a up-regulates the cell surface ecto-5'-nucleotidase cluster of differentiation 73 (CD73), which increases adenosine levels, and IFN beta-1 may, therefore, be a potential treatment for ARDS. In a phase I/II, open-label study in 37 patients with acute lung injury (ALI)/ARDS, recombinant human IFN beta-1a was well tolerated and mortality rates were significantly lower in treated than in control patients. METHODS/DESIGN: In this phase III, double-blind, randomized, parallel-group trial, the efficacy and safety of recombinant human IFN beta-1a (FP-1201-lyo) will be compared with placebo in adult patients with ARDS. Patients will be randomly assigned to receive 10 µg FP-1201-lyo or placebo administered intravenously once daily for 6 days and will be monitored for 28 days or until discharged from the intensive care unit. Follow-up visits will then take place at days 90, 180 and 360. The primary endpoint is a composite endpoint including any cause of death at 28 days and days free of mechanical ventilation within 28 days among survivors. Secondary endpoints include: all-cause mortality at 28, 90, 180 and 360 days; organ failure-free days; length of hospital stay; pharmacodynamic assessment including measurement of myxovirus resistance protein A concentrations; and measures of quality of life, respiratory and neurological function at 180 and 360 days. The estimated sample size to demonstrate a reduction in the primary outcome between groups from 30% to 15% is 300 patients, and the study will be conducted in 70-80 centers in nine countries across Europe. DISCUSSION: There are no effective specific treatments for patients with ARDS and mortality rates remain high. The results from this study will provide evidence regarding the efficacy of a potential new therapeutic agent, FP-1201-lyo, in improving the clinical course and outcome for patients with moderate/severe ARDS. TRIAL REGISTRATION: European Union Clinical Trials Register, no: 2014-005260-15 . Registered on 15 July 2017.

Intrinsic positive end-expiratory pressure during ventilation through small endotracheal tubes during general anesthesia: incidence, mechanism, and predictive factors.

STUDY OBJECTIVE: To assess the safety of mechanical ventilation and effectiveness of extrinsic positive end-expiratory pressure (PEEP) (PEEPe) in improving peripheral oxygen saturation (SpO2) during direct microlaryngeal laser surgery; to assess the incidence, amount, and nature (dynamic hyperinflation or airflow obstruction) of ensuing intrinsic PEEP (PEEPi); and to find a surrogate PEEPi indicator. DESIGN: Quasiexperimental. SETTING: S. Raffaele Hospital (Milano), November 2009 to December 2010. PATIENTS: Fifty-two adults scheduled for direct microlaryngeal laser surgery. Exclusion criterion is pregnancy. INTERVENTIONS: Twenty-one percent O2 mechanical ventilation through 4.5- to 5.5-mm internal diameter endotracheal tubes; in 29 patients, after measurement of PEEPi, an identical amount of PEEPe was added; and PEEPi. MEASUREMENTS: SpO2, peak (Pawpeak) and plateau (Pawplateau) airway pressure, and end-expiratory carbon dioxide were measured every 5 minutes. Respiratory compliance (Crs) was computed. PEEPi was measured (end-expiratory occlusion method). MAIN RESULTS: PEEPi ≥5 cm H2O occurred in 14 patients (27%) after intubation, in 16 (30%) at the beginning, and in 14 (27.3%) at the end of surgery. Thirty-one patients (59.4%) exhibited PEEPi ≥5 cm H2O on at least 1 time point. PEEPi at the beginning of surgery was positively correlated with Pawplateau, Crs, tidal volume, and body mass index. Body mass index was the only predictor for the occurrence of PEEPi ≥5 cm H2O. At the beginning of surgery, the Pawplateau receiver operating characteristic curve predicting PEEPi ≥5 cm H2O had area under the receiver operating characteristic curve of 0.85; best cutoff value of 15.5 cm H2O (sensitivity, 88.9%; specificity, 75%; correctly classified cases, 86.1%). When PEEPe was applied, in 23 cases (82.1%), total PEEP equaled PEEPe+ PEEPi; in 3 (10.7%), it was lower; and in 2 (7.1%), it was higher. Application of PEEPe increased SpO2 (P< .05) and Crs (P< .05). CONCLUSIONS: During ventilation through small endotracheal tubes, PEEPi (mostly due to dynamic hyperinflation) is common. Hemodynamic complications, barotrauma, and O2 desaturation (reversible with PEEPe) are rare. Pawplateau provided by ventilators is useful in suspecting and monitoring the occurrence of PEEPi and allows detection of lung overdistension as PEEPe is applied.

Effects on membrane lung gas exchange of an intermittent high gas flow recruitment maneuver: preliminary data in veno-venous ECMO patients.

Gas exchange capabilities of polymethylpentene membrane lungs (MLs) worsen over time. ML deterioration is related to protein deposit and clot formation. Condensation and trapping of water vapor inside ML hollow fibers might affect ML performances as well. Increasing sweep gas flow (GF) could remove such fluid. The purpose of this study was to evaluate the effects on ML gas exchange of a recruitment maneuver (RM) based on a brief increase in GF, during veno-venous ECMO support. Short-term (15 min) effects of 20 RMs were assessed. RM raised ML CO2 removal from 149 ± 37 to 174 ± 41 ml/min (p < 0.001). Conversely, RM did not improve ML O2 transfer (155 ± 31 and 158 ± 31 ml/min before and after RM, respectively). ML outlet pCO2 decreased after RM from 51.2 ± 5.8 to 45.8 ± 5.4 mmHg (p < 0.001), while ML outlet pO2 increased from 520 ± 61 to 555 ± 51 mmHg (p < 0.001). Both ML dead space and shunt fractions decreased from 47.8 ± 15.3 to 29.6 ± 14.7 % (p < 0.001) and from 8.8 ± 4.2 to 7.0 ± 3.8 % (p < 0.001), respectively. Furthermore, a subset of 5 RMs was evaluated on a 6-h time frame. The beneficial effects on ML performances due to the RM gradually diminished and waned over a 6-h interval after the RM. The RM improved ML CO2 removal substantially, albeit temporarily. ML oxygenation performance was marginally affected.

Respiratory pattern during neurally adjusted ventilatory assist in acute respiratory failure patients.

PURPOSE: To investigate the effect of a wide range of assistance levels during neurally adjusted ventilatory assist (NAVA) and pressure support ventilation (PSV) on respiratory pattern, breathing variability, and incidence of tidal volumes (V (T)) above 8 and 10 ml/kg in acute respiratory failure patients. METHODS: Eight increasing NAVA levels (0.5, 1, 1.5, 2, 2.5, 3, 4, and 5 cmH(2)O/µV) and four increasing pressure support (PSV) levels (4, 8, 12, and 16 cmH(2)O) were applied to obtain 10 min of stable recordings in 15 patients. RESULTS: One out of 15 patients did not sustain the NAVA levels of 3, 4, and 5 cmH(2)O/µV and was excluded. The 5 cmH(2)O/µV NAVA level was not tolerated by three patients and it was excluded. Increasing NAVA levels were associated with decreased diaphragm electrical activity (EAdi), and, at variance with PSV, with small changes in V (T), no changes in respiratory rate (RR), and increases in V (T) and EAdi variability. At high NAVA levels, an increase in V (T) variability was associated with increased incidence of V (T) above 8 and 10 ml/kg and an uncomfortable respiratory pattern in some patients. CONCLUSIONS: Increasing NAVA levels were associated with no effect on RR, small increase in V (T), and increase in V (T) and EAdi variability. Effective decrease in EAdi occurred at NAVA levels below 2-2.5 cmH(2)O/µV, while preserving respiratory variability and low risks of V (T) above 8 or 10 ml/kg.

Performance of different continuous positive airway pressure helmets equipped with safety valves during failure of fresh gas supply.

PURPOSE: We assessed the performance of different continuous positive airway pressure (CPAP) helmets equipped with a safety valve during discontinuation of fresh gas flow. METHODS: This was a physiological study of five healthy volunteers. We delivered CPAP (fresh gas flow 60 l/min, FiO(2) 60%, PEEP 5 cmH(2)O) with three different helmets in a random sequence: 4Vent (Rüsch), HelmHAR-cp (Harol) and CaStar CP210 (StarMed). For each helmet we randomly applied, for up to 4 min, three disconnections of fresh gas flow: helmet inlet (D(inlet)), flowmeter (D(flowmeter)) and gas source (D(source)). We continuously recorded from a nostril: end-tidal CO(2) (PetCO(2)), inspiratory CO(2) (PiCO(2)), fraction of inspired oxygen (FiO(2)) and respiratory rate (RR). RESULTS: During every disconnection we observed an increase in PiCO(2) and PetCO(2) with a drop in FiO(2), while RR did not change. FiO(2) decreased more quickly in the CaStar, equipped with the largest safety valve, during D(source) and D(flowmeter), while FiO(2) decreased more quickly during D(inlet) in CaStar and in 4Vent. PiCO(2) resulted in a lower increase in CaStar during D(source) and D(flowmeter) compared to 4Vent. PetCO(2) in CaStar increases more slowly compared to 4Vent during D(source) and more slowly compared to the other two helmets during D(flowmeter). During D(inlet) similar degrees of CO(2) rebreathing and PetCO(2) were recorded among all the helmets. CONCLUSIONS: To minimize CO(2) rebreathing during disconnection of the fresh gas supply while performing helmet CPAP, it is desirable to utilize large helmets with a large anti-suffocation valve. Monitoring and alarm systems should be employed for safe application of helmet CPAP.

Lung regional metabolic activity and gas volume changes induced by tidal ventilation in patients with acute lung injury.

RATIONALE: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [(18)F]fluoro-2-deoxy-D-glucose. OBJECTIVES: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. METHODS: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolic activity was measured from the [(18)F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. MEASUREMENTS AND MAIN RESULTS: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H(2)O, and with regional Vt normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. CONCLUSIONS: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional Vt normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment-derecruitment and increased metabolic activity.

Reasons for refusal of admission to intensive care and impact on mortality.

PURPOSE: To identify factors influencing triage decisions and investigate whether admission to the intensive care unit (ICU) could reduce mortality compared with treatment on the ward. METHODS: A multicentre cohort study in 11 university hospitals from seven countries, evaluating triage decisions and outcomes of patients referred for admission to ICU who were either accepted, or refused and treated on the ward. Confounding in the estimation of the effect of ICU admission on mortality was controlled by use of a propensity score approach, which adjusted for the probability of being admitted. Variability across centres was accounted for in both analyses of factors influencing ICU admission and effect of ICU admission on mortality. RESULTS: Eligible were 8,616 triages in 7,877 patients referred for ICU admission. Variables positively associated with probability of being admitted to ICU included: ventilators in ward; bed availability; Karnofsky score; absence of comorbidity; presence of haematological malignancy; emergency surgery and elective surgery (versus medical treatment); trauma, vascular involvement, liver involvement; acute physiologic score II; ICU treatment (versus ICU observation). Multiple triages during patient's hospital stay and age were negatively associated with ICU admission. The area under the receiver operating characteristic (ROC) curve of the model was 0.83 [95% confidence interval (CI): 0.81-0.84], with Hosmer-Lemeshow test P = 0.300. ICU admission was associated with a statistically significant reduction of both 28-day mortality [odds ratio (OR): 0.73; 95% CI: 0.62-0.87] and 90-day mortality (0.79; 0.66-0.93). The benefit of ICU admission increased substantially in patients with greater severity of illness. CONCLUSIONS: We suggest that intensivists take great care to avoid ICU admission of patients judged not severe enough for ICU or with low performance status, and they tend to admit surgical patients more readily than medical patients. Interestingly, they do not judge age per se as a reason for refusal of ICU admission. Admission to ICU was associated with a reduction of both 28- and 90-day mortality, particularly in patients with greater severity of illness at time of triage.

Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality.

PURPOSE: Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis. METHODS: This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F(1+2))] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90. RESULTS: Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F(1+2) concentration and with PAI-1 activity and concentration (p < 0.05 for all). CONCLUSIONS: Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.

Extracorporeal gas exchange.

PURPOSE OF REVIEW: We report on recent advances and achievements on the use of extracorporeal gas exchange for long-term application in the therapy of critically ill patients with various forms of respiratory failure. RECENT FINDINGS: The most important results regarding the use of extracorporeal gas exchange are expected from the Conventional Ventilatory Support vs. Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) study, a randomized clinical trial assessing the effectiveness of extracorporeal lung assist in acute respiratory distress syndrome patients. Although not yet formally published, the results of this study, if confirmed, represent the first positive randomized clinical trial on adult extracorporeal membrane oxygenation application in acute respiratory distress syndrome patients. Other important results come from the clinical application of interventional lung assist, a pumpless arteriovenous extracorporeal technique, in different clinical conditions (acute respiratory distress syndrome, bridge to transplantation, asthma, and trauma). Among technical progress, of particular interest is the development of microfiber, microporous polymethylpentene membrane lungs, which offer low resistance to blood flow, high gas transfer capability, and high leak-proof performance. SUMMARY: Results of recent clinical trials, widespread use of clinical applications, and technical progress are leading to reevaluation and extension of extracorporeal gas exchange in critically ill patients with respiratory failure of various forms. Further developments may come from low invasive techniques with high efficiency of CO2 removal from low blood flow.

Danger of helmet continuous positive airway pressure during failure of fresh gas source supply.

OBJECTIVE: To assess the behavior of different helmets after discontinuation of fresh gas flow by disconnection at the helmet inlet, flow generator, or gas source. DESIGN AND SETTING: Randomized physiological study in a university research laboratory. PATIENTS: Five healthy volunteers. INTERVENTION: CPAP (FIO2 50%, PEEP 5 cmH2O) delivered in random sequence with three different helmets: 4Vent (Rüsch), PN500 (Harol), CaStar (StarMed) with antisuffocation valve open or locked. For each helmet all three disconnections were randomly employed up to 4 min. MEASUREMENTS AND RESULTS: During flow disconnection we measured: respiratory rate and tidal volume by respitrace; inspiratory and expiratory CO2 concentration, and FIO2 from a nostril; SpO2 by pulse oxymetry. Independently of the site of disconnection we observed a fast increase in CO2 rebreathing and minute ventilation, associated with a decrease in inspired O2 concentration. In the absence of an operational safety valve, larger helmet size and lower resistance of the inlet hose resulted in slower increase in CO2 rebreathing. The presence of the safety valve limited the rebreathing of CO2, and the increase in minute ventilation but did not protect from a decrease in FIO2 and loss of PEEP. CONCLUSIONS: While the use of a safety valve proved effective in limiting CO2 rebreathing, it did not protect from the risk of hypoxia related to decrease in FIO2 and loss of PEEP. In addition to a safety antisuffocation valve, a dedicated monitoring and alarming systems are needed to employ helmet CPAP safely.