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Papers by luciana mascia

Research paper thumbnail of Neuropsychological Outcome of Critically Ill Patients with Severe Infection

Biomedicines, 2022

Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associate... more Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associated neurological consequences have a great impact on patients, both in the acute phase and in the long term. Sepsis-associated encephalopathy (SAE) is a severe brain dysfunction that may contribute to long-term cognitive impairment. Its pathophysiology recognizes the following two main mechanisms: neuroinflammation and hemodynamic impairment. Clinical manifestations include different forms of altered mental status, from agitation and restlessness to delirium and deep coma. A definite diagnosis is difficult because of the absence of specific radiological and biological criteria; clinical management is restricted to the treatment of sepsis, focusing on early detection of the infection source, maintenance of hemodynamic homeostasis, and avoidance of metabolic disturbances or neurotoxic drugs.

Research paper thumbnail of Management of Acute Ischemic Stroke

Practical Trends in Anesthesia and Intensive Care 2019, 2020

Research paper thumbnail of Cerebral Blood Flow in Acute Brain Injury

Yearbook of Intensive Care and Emergency Medicine, 1997

Research paper thumbnail of Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study

Biomedicines, 2021

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static complianc... more The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ra...

Research paper thumbnail of Epidemiology and outcome of sepsis syndromes in Italian ICUs: a regional multicenter observational cohort

Research paper thumbnail of Acute Tubular Injury is Associated With Severe Traumatic Brain Injury: in Vitro Study on Human Tubular Epithelial Cells

Scientific Reports, 2019

Acute kidney injury following traumatic brain injury is associated with poor outcome. We investig... more Acute kidney injury following traumatic brain injury is associated with poor outcome. We investigated in vitro the effects of plasma of brain injured patients with acute tubular kidney injury on kidney tubular epithelial cell function. we performed a prospective observational clinical study in ICU in a trauma centre of the University hospital in Italy including twenty-three ICU patients with traumatic brain injury consecutively enrolled. Demographic data were recorded on admission: age 39 ± 19, Glasgow Coma Score 5 (3–8). Neutrophil Gelatinase-Associated Lipocalin and inflammatory mediators were measured in plasma on admission and after 24, 48 and 72 hours; urine were collected for immunoelectrophoresis having healthy volunteers as controls. Human renal proximal tubular epithelial cells were stimulated with patients or controls plasma. Adhesion of freshly isolated human neutrophils and trans-epithelial electrical resistance were assessed; cell viability (XTT assay), apoptosis (TUNEL...

Research paper thumbnail of Reversed differential cyanosis during veno-arterial extracorporeal membrane oxygenation in infants: the reevaluation of an old phenomenon

European journal of heart failure, May 1, 2017

Research paper thumbnail of Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study

Journal of Neuroinflammation, 2016

Background: Neuroinflammation has been proposed as a possible mechanism of brain damage after tra... more Background: Neuroinflammation has been proposed as a possible mechanism of brain damage after traumatic brain injury (TBI), but no consensus has been reached on the most relevant molecules. Furthermore, secondary insults occurring after TBI contribute to worsen neurological outcome in addition to the primary injury. We hypothesized that after TBI, a specific pattern of cytokines is related to secondary insults and outcome. Methods: A prospective observational clinical study was performed. Secondary insults by computerized multimodality monitoring system and systemic value of different cytokines were collected and analysed in the first week after intensive care unit admission. Neurological outcome was assessed at 6 months (GOSe). Multivariate projection technique was applied to analyse major sources of variation and collinearity within the cytokines dataset without a priori selecting potential relevant molecules. Results: Twenty-nine severe traumatic brain injury patients undergoing intracranial pressure monitoring were studied. In this pilot study, we demonstrated that after TBI, patients who suffered of prolonged and severe secondary brain damage are characterised by a specific pattern of cytokines. Patients evolving to brain death exhibited higher levels of inflammatory mediators compared to both patients with favorable and unfavorable neurological outcome at 6 months. Raised ICP and low cerebral perfusion pressure occurred in 21 % of good monitoring time. Furthermore, the principal components selected by multivariate projection technique were powerful predictors of neurological outcome. Conclusions: The multivariate projection method represents a valuable methodology to study neuroinflammation pattern occurring after secondary brain damage in severe TBI patients, overcoming multiple putative interactions between mediators and avoiding any subjective selection of relevant molecules.

Research paper thumbnail of Effects of dexmedetomidine and propofol on patient-ventilator interaction in difficult-to-wean, mechanically ventilated patients: a prospective, open-label, randomised, multicentre study

Critical care (London, England), Jan 2, 2016

Dexmedetomidine can be used for sedation of mechanically ventilated patients and has minor respir... more Dexmedetomidine can be used for sedation of mechanically ventilated patients and has minor respiratory effects. The aim of this study was to compare the incidence of patient-ventilator dyssynchronies during sedation with dexmedetomidine or propofol. We conducted a multicentre, prospective, open-label, randomised clinical trial, comparing dexmedetomidine with standard propofol sedation at three intensive care units of university hospitals in Italy. Twenty difficult-to-wean patients for whom the first weaning trial had failed and who were on pressure support ventilation were randomised to receive sedation with either dexmedetomidine or propofol at a similar level of sedation (Richmond Agitation-Sedation Scale [RASS] score +1 to -2). The asynchrony index (AI) was calculated using tracings of airflow, airway pressure and electrical activity of the diaphragm sampled at 0, 0.5, 1, 2, 6, 12, 18 and 24 h. The mean AI was lower with dexmedetomidine than with propofol from 2 h onwards, althou...

Research paper thumbnail of Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study

Intensive Care Medicine, 2016

Purpose: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated... more Purpose: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). Methods: After at least 24 hours of hemodynamic optimization, 45 septic shock patients, with a HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80-94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis and norepinephrine requirements, were obtained at baseline and at 4 hours after commencing esmolol. Results: The HR target was achieved in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg•l-1), arterial dP/dt max (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg•ms-1) and a parallel increase in stroke volume (48 ± 14 vs. 59 ± 18 ml), all p<0.05. Cardiac output and ejection fraction remained unchanged whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg•kg-1 •min-1 , p<0.05). Conclusions: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

Research paper thumbnail of A year in review in Minerva Anestesiologica 2009. I critical care. Experimental and clinical studies

Minerva anestesiologica, 2010

Research paper thumbnail of Extracorporeal Co2 Removal in Hypercapnic Patients At Risk of Noninvasive Ventilation Failure

Critical Care Medicine, 2015

Objectives: To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co 2 rem... more Objectives: To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co 2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. Design: Matched cohort study with historical control. Setting: Two academic Italian ICUs. Patients: Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). Interventions: Extracorporeal Co 2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ≤ 7.30 with arterial Pco 2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/ paradoxical abdominal movements). The noninvasive ventilationonly group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. Measurements and Main Results: Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal Co 2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilationplus-extracorporeal Co 2 removal (hazard ratio, 0.27; 95% CI, 0.07-0.98; p = 0.047). Intubation rate in noninvasive ventilationplus-extracorporeal Co 2 removal was 12% (95% CI, 2.5-31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6-57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal Co 2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. Conclusions: These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal Co 2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation. (Crit Care Med 2015; 43:120-127)

Research paper thumbnail of F1000Trials Review

Background-In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improve... more Background-In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improved neurobehavioral outcome. In a pilot clinical trial, albumin doses as high as 2 g per kg were safely tolerated. Trial Design and Methods-This was a randomised, parallel-group, double-blind trial to test the superiority of 25% albumin (dose 2 g [8 ml] per kg; maximum, 750 ml) over an equivalent volume of isotonic saline in improving the outcome of acute ischaemic stroke. Eligibility criteria were an ischaemic (i.e., non-haemorrhagic) stroke with baseline National Institutes of Health Stroke Scale (NIHSS) score of 6 or above, ability to treat within 5 hours of onset, age 18 through 83 years, and written informed consent. The major exclusion criteria were cardiovascular. The objective was to test the hypothesis that the primary outcome (defined as either a modified Rankin

Research paper thumbnail of F1000Trials Review

Research paper thumbnail of Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

PLOS ONE, 2015

Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarach... more Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ET A and ET B receptors. Methods Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ET A and ET B receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. Results Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ET A receptors and new expression of ET B receptors was apparent;

Research paper thumbnail of Management of Neuroendocrine Instability During Maintenance of Potential Organ Donors

Research paper thumbnail of Diagnosis and management of vasospasm

F1000 Medicine Reports, 2009

An overview of the main features of cerebral vasospasm is provided in this report, highlighting t... more An overview of the main features of cerebral vasospasm is provided in this report, highlighting the possible future direction of development in the diagnosis and management of this severe complication of aneurysmal subarachnoid hemorrhage.

Research paper thumbnail of Acute Lung Injury in Patients with Severe Brain Injury: A Double Hit Model

Neurocritical Care, 2009

The presence of pulmonary dysfunction after brain injury is well recognized. Acute lung injury (A... more The presence of pulmonary dysfunction after brain injury is well recognized. Acute lung injury (ALI) occurs in 20% of patients with isolated brain injury and is associated with a poor outcome. The ''blast injury'' theory, which proposes combined ''hydrostatic'' and ''high permeability'' mechanisms for the formation of neurogenic pulmonary edema, has been challenged recently by the observation that a systemic inflammatory response may play an integral role in the development of pulmonary dysfunction associated with brain injury. As a result of the primary cerebral injury, a systemic inflammatory reaction occurs, which induces an alteration in blood-brain barrier permeability and infiltration of activated neutrophils into the lung. This preclinical injury makes the lungs more susceptible to the mechanical stress of an injurious ventilatory strategy. Tight CO 2 control is a therapeutic priority in patients with acute brain injury, but the use of high tidal volume ventilation may contribute to the development of ALI. Establishment of a therapeutic regimen that allows the combination of protective ventilation with the prevention of hypercapnia is, therefore, required. Moreover, in patients with brain injury, hypoxemia represents a secondary insult associated with a poor outcome. Optimal oxygenation may be achieved by using an adequate FiO 2 and by application of positive end-expiratory pressure (PEEP). PEEP may, however, affect the cerebral circulation by hemodynamic and CO 2-mediated mechanisms and the effects of PEEP on cerebral hemodynamics should be monitored in these patients and used to titrate its application.

Research paper thumbnail of Cerebro-pulmonary interactions during the application of low levels of positive end-expiratory pressure

Intensive Care Medicine, 2005

Research paper thumbnail of Ventilatory setting in severe brain injured patients: does it really matter?

Intensive Care Medicine, 2006

Research paper thumbnail of Neuropsychological Outcome of Critically Ill Patients with Severe Infection

Biomedicines, 2022

Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associate... more Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associated neurological consequences have a great impact on patients, both in the acute phase and in the long term. Sepsis-associated encephalopathy (SAE) is a severe brain dysfunction that may contribute to long-term cognitive impairment. Its pathophysiology recognizes the following two main mechanisms: neuroinflammation and hemodynamic impairment. Clinical manifestations include different forms of altered mental status, from agitation and restlessness to delirium and deep coma. A definite diagnosis is difficult because of the absence of specific radiological and biological criteria; clinical management is restricted to the treatment of sepsis, focusing on early detection of the infection source, maintenance of hemodynamic homeostasis, and avoidance of metabolic disturbances or neurotoxic drugs.

Research paper thumbnail of Management of Acute Ischemic Stroke

Practical Trends in Anesthesia and Intensive Care 2019, 2020

Research paper thumbnail of Cerebral Blood Flow in Acute Brain Injury

Yearbook of Intensive Care and Emergency Medicine, 1997

Research paper thumbnail of Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study

Biomedicines, 2021

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static complianc... more The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ra...

Research paper thumbnail of Epidemiology and outcome of sepsis syndromes in Italian ICUs: a regional multicenter observational cohort

Research paper thumbnail of Acute Tubular Injury is Associated With Severe Traumatic Brain Injury: in Vitro Study on Human Tubular Epithelial Cells

Scientific Reports, 2019

Acute kidney injury following traumatic brain injury is associated with poor outcome. We investig... more Acute kidney injury following traumatic brain injury is associated with poor outcome. We investigated in vitro the effects of plasma of brain injured patients with acute tubular kidney injury on kidney tubular epithelial cell function. we performed a prospective observational clinical study in ICU in a trauma centre of the University hospital in Italy including twenty-three ICU patients with traumatic brain injury consecutively enrolled. Demographic data were recorded on admission: age 39 ± 19, Glasgow Coma Score 5 (3–8). Neutrophil Gelatinase-Associated Lipocalin and inflammatory mediators were measured in plasma on admission and after 24, 48 and 72 hours; urine were collected for immunoelectrophoresis having healthy volunteers as controls. Human renal proximal tubular epithelial cells were stimulated with patients or controls plasma. Adhesion of freshly isolated human neutrophils and trans-epithelial electrical resistance were assessed; cell viability (XTT assay), apoptosis (TUNEL...

Research paper thumbnail of Reversed differential cyanosis during veno-arterial extracorporeal membrane oxygenation in infants: the reevaluation of an old phenomenon

European journal of heart failure, May 1, 2017

Research paper thumbnail of Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study

Journal of Neuroinflammation, 2016

Background: Neuroinflammation has been proposed as a possible mechanism of brain damage after tra... more Background: Neuroinflammation has been proposed as a possible mechanism of brain damage after traumatic brain injury (TBI), but no consensus has been reached on the most relevant molecules. Furthermore, secondary insults occurring after TBI contribute to worsen neurological outcome in addition to the primary injury. We hypothesized that after TBI, a specific pattern of cytokines is related to secondary insults and outcome. Methods: A prospective observational clinical study was performed. Secondary insults by computerized multimodality monitoring system and systemic value of different cytokines were collected and analysed in the first week after intensive care unit admission. Neurological outcome was assessed at 6 months (GOSe). Multivariate projection technique was applied to analyse major sources of variation and collinearity within the cytokines dataset without a priori selecting potential relevant molecules. Results: Twenty-nine severe traumatic brain injury patients undergoing intracranial pressure monitoring were studied. In this pilot study, we demonstrated that after TBI, patients who suffered of prolonged and severe secondary brain damage are characterised by a specific pattern of cytokines. Patients evolving to brain death exhibited higher levels of inflammatory mediators compared to both patients with favorable and unfavorable neurological outcome at 6 months. Raised ICP and low cerebral perfusion pressure occurred in 21 % of good monitoring time. Furthermore, the principal components selected by multivariate projection technique were powerful predictors of neurological outcome. Conclusions: The multivariate projection method represents a valuable methodology to study neuroinflammation pattern occurring after secondary brain damage in severe TBI patients, overcoming multiple putative interactions between mediators and avoiding any subjective selection of relevant molecules.

Research paper thumbnail of Effects of dexmedetomidine and propofol on patient-ventilator interaction in difficult-to-wean, mechanically ventilated patients: a prospective, open-label, randomised, multicentre study

Critical care (London, England), Jan 2, 2016

Dexmedetomidine can be used for sedation of mechanically ventilated patients and has minor respir... more Dexmedetomidine can be used for sedation of mechanically ventilated patients and has minor respiratory effects. The aim of this study was to compare the incidence of patient-ventilator dyssynchronies during sedation with dexmedetomidine or propofol. We conducted a multicentre, prospective, open-label, randomised clinical trial, comparing dexmedetomidine with standard propofol sedation at three intensive care units of university hospitals in Italy. Twenty difficult-to-wean patients for whom the first weaning trial had failed and who were on pressure support ventilation were randomised to receive sedation with either dexmedetomidine or propofol at a similar level of sedation (Richmond Agitation-Sedation Scale [RASS] score +1 to -2). The asynchrony index (AI) was calculated using tracings of airflow, airway pressure and electrical activity of the diaphragm sampled at 0, 0.5, 1, 2, 6, 12, 18 and 24 h. The mean AI was lower with dexmedetomidine than with propofol from 2 h onwards, althou...

Research paper thumbnail of Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study

Intensive Care Medicine, 2016

Purpose: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated... more Purpose: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). Methods: After at least 24 hours of hemodynamic optimization, 45 septic shock patients, with a HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80-94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis and norepinephrine requirements, were obtained at baseline and at 4 hours after commencing esmolol. Results: The HR target was achieved in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg•l-1), arterial dP/dt max (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg•ms-1) and a parallel increase in stroke volume (48 ± 14 vs. 59 ± 18 ml), all p<0.05. Cardiac output and ejection fraction remained unchanged whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg•kg-1 •min-1 , p<0.05). Conclusions: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

Research paper thumbnail of A year in review in Minerva Anestesiologica 2009. I critical care. Experimental and clinical studies

Minerva anestesiologica, 2010

Research paper thumbnail of Extracorporeal Co2 Removal in Hypercapnic Patients At Risk of Noninvasive Ventilation Failure

Critical Care Medicine, 2015

Objectives: To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co 2 rem... more Objectives: To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co 2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. Design: Matched cohort study with historical control. Setting: Two academic Italian ICUs. Patients: Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). Interventions: Extracorporeal Co 2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ≤ 7.30 with arterial Pco 2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/ paradoxical abdominal movements). The noninvasive ventilationonly group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. Measurements and Main Results: Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal Co 2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilationplus-extracorporeal Co 2 removal (hazard ratio, 0.27; 95% CI, 0.07-0.98; p = 0.047). Intubation rate in noninvasive ventilationplus-extracorporeal Co 2 removal was 12% (95% CI, 2.5-31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6-57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal Co 2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. Conclusions: These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal Co 2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation. (Crit Care Med 2015; 43:120-127)

Research paper thumbnail of F1000Trials Review

Background-In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improve... more Background-In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improved neurobehavioral outcome. In a pilot clinical trial, albumin doses as high as 2 g per kg were safely tolerated. Trial Design and Methods-This was a randomised, parallel-group, double-blind trial to test the superiority of 25% albumin (dose 2 g [8 ml] per kg; maximum, 750 ml) over an equivalent volume of isotonic saline in improving the outcome of acute ischaemic stroke. Eligibility criteria were an ischaemic (i.e., non-haemorrhagic) stroke with baseline National Institutes of Health Stroke Scale (NIHSS) score of 6 or above, ability to treat within 5 hours of onset, age 18 through 83 years, and written informed consent. The major exclusion criteria were cardiovascular. The objective was to test the hypothesis that the primary outcome (defined as either a modified Rankin

Research paper thumbnail of F1000Trials Review

Research paper thumbnail of Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

PLOS ONE, 2015

Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarach... more Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ET A and ET B receptors. Methods Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ET A and ET B receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. Results Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ET A receptors and new expression of ET B receptors was apparent;

Research paper thumbnail of Management of Neuroendocrine Instability During Maintenance of Potential Organ Donors

Research paper thumbnail of Diagnosis and management of vasospasm

F1000 Medicine Reports, 2009

An overview of the main features of cerebral vasospasm is provided in this report, highlighting t... more An overview of the main features of cerebral vasospasm is provided in this report, highlighting the possible future direction of development in the diagnosis and management of this severe complication of aneurysmal subarachnoid hemorrhage.

Research paper thumbnail of Acute Lung Injury in Patients with Severe Brain Injury: A Double Hit Model

Neurocritical Care, 2009

The presence of pulmonary dysfunction after brain injury is well recognized. Acute lung injury (A... more The presence of pulmonary dysfunction after brain injury is well recognized. Acute lung injury (ALI) occurs in 20% of patients with isolated brain injury and is associated with a poor outcome. The ''blast injury'' theory, which proposes combined ''hydrostatic'' and ''high permeability'' mechanisms for the formation of neurogenic pulmonary edema, has been challenged recently by the observation that a systemic inflammatory response may play an integral role in the development of pulmonary dysfunction associated with brain injury. As a result of the primary cerebral injury, a systemic inflammatory reaction occurs, which induces an alteration in blood-brain barrier permeability and infiltration of activated neutrophils into the lung. This preclinical injury makes the lungs more susceptible to the mechanical stress of an injurious ventilatory strategy. Tight CO 2 control is a therapeutic priority in patients with acute brain injury, but the use of high tidal volume ventilation may contribute to the development of ALI. Establishment of a therapeutic regimen that allows the combination of protective ventilation with the prevention of hypercapnia is, therefore, required. Moreover, in patients with brain injury, hypoxemia represents a secondary insult associated with a poor outcome. Optimal oxygenation may be achieved by using an adequate FiO 2 and by application of positive end-expiratory pressure (PEEP). PEEP may, however, affect the cerebral circulation by hemodynamic and CO 2-mediated mechanisms and the effects of PEEP on cerebral hemodynamics should be monitored in these patients and used to titrate its application.

Research paper thumbnail of Cerebro-pulmonary interactions during the application of low levels of positive end-expiratory pressure

Intensive Care Medicine, 2005

Research paper thumbnail of Ventilatory setting in severe brain injured patients: does it really matter?

Intensive Care Medicine, 2006