-
European Journal of Intensive Care Medicine 05/2013; · 5.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acute lung injury is a life-threating condition characterized by surfactant dysfunction and raised secretory phospholipase A2 (sPLA2) activity. Varespladib is a sPLA2 inhibitor shown to be effective in animal models of acute lung injury. We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity. Alveolar macrophages were cultured and stimulated with lipopolysaccharide and then treated with either varespladib, surfactant, varespladib followed by surfactant or nothing. sPLA2 activity, free fatty acids, tumour necrosis factor-(TNF- ) and protein concentrations were measured in culture supernatants. Treatment with varespladib (p=0.019) and varespladib + surfactant (p=0.013), reduced the enzyme activity by approximately 15% from the basal level measured in the untreated cultures. Surfactant, varespladib and varespladib + surfactant, respectively decreased free fatty acids by -45% (p=0.045), -62% (p=0.009) and -48% (p=0.015), from the baseline concentration of the untreated cultures. Varespladib and poractant- co-administration reduces sPLA2 activity and free fatty acids release in cultured rat alveolar macrophages, although a clear drug synergy was not evident. Since co-administration may be useful to reduce inflammation and surfactant inactivation in acute lung injury, further in vivo studies are warranted to verify its clinical usefulness.
Current pharmaceutical biotechnology 04/2013; · 3.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: s u m m a r y Chronic obstructive pulmonary disease (COPD) is a cluster of heterogenic disorders, characterized by expiratory flow limitation that is not completely reversible and in most cases progressive. COPD exac-erbation represents one of the leading causes of ICU admission; while in the past patients with COPD exacerbation were treated with conventional pharmacological treatment plus O 2 , followed by invasive ventilation in case of treatment failure, an integrated approach combining noninvasive ventilation (NIV) as first-line treatment with conventional ventilation only in those patients who fail NIV or present contraindications seem able to offer optimal clinical results. The aim of this review is to discuss an updated approach for the optimal treatment of patients with COPD exacerbation, starting from a pathophysiological basis. Chronic obstructive pulmonary disease (COPD) is a cluster of heterogenic disorders, characterized by expiratory flow limita-tion that is not completely reversible and in most case pro-gressive. 1 Chronic obstructive pulmonary disease is a multi-factorial disorder caused by chronic environmental insults e most commonly cigarette smoking e in individuals with predispositions due to variations in one or multiple genes. 2 The combination of environment and genes lead to distinct aberrant pathophysiolog-ical processes/pathways, the combination of which causes COPD. The airflow limitation is caused by chronic inflammation of the airways and lung parenchyma and the primary physiological ab-normality is an accelerated decline in the forced expiratory volume in one second (FEV1) followed by a pulmonary hyperinflation. It is manifested primarily by an increase in the functional residual ca-pacity, which places the respiratory muscles at a mechanical disadvantage, thereby increasing the work of breathing and reducing exercise tolerance. 3 COPD is a disease of inflammation where tissue destruction, fibrotic tissue accumulation, or repair likely depends on a complex balance of factors. 4 According to the World Health Organization, COPD is the fourth leading cause of death in the world and it is predicted to be a major cause of death worldwide during the next two decades. 5 Exacerbations are a significant cause of morbidity and mortality in COPD and are associated with more rapid disease progression and poor quality of life. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which it occurs appears to reflect an independent susceptibility phenotype. 6 1. Pathophysiology Acute respiratory failure in patients with COPD is usually multifactorial. At baseline, patients with COPD frequently have impaired oxygenation because of loss of alveolar volume and impaired ventilation from increased dead space and poor respira-tory mechanics. 7 Because of these baseline abnormalities, tolerance of acute pulmonary insults is poor. Small entity pneumonia causes new hypoxaemia or worsening of hypoxaemia. The patient re-sponds by increasing minute ventilation but an emphysema-induced increase in residual volume (RV) limits tidal ventilation. Increasing respiratory rates decreases expiratory time and pro-duces or worsens air trapping which further limits ventilation. Other factors such as chest wall mechanics, nutritional deficiencies, pulmonary hypertension, and chronic CO 2 retention can make the situation worse. Eventually, the respiratory efficiency declines, the work of breathing becomes unsustainable, the patient tires, and respiratory failure ensues. 5 In other words, we can say that the pathophysiology of acute respiratory failure in COPD is the load-capacity imbalance of the respiratory muscles unable to generate an adequate pressure to an increased mechanical load. Equations of motion applied to the respiratory system have fully explained the relationship between the respiratory muscles and inspiratory load (Fig. 1).
trends on anestesia and critical care. 04/2013;
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND:: Positive end expiratory pressure (PEEP) improves oxygenation by optimizing alveolar recruitment and reducing intrapulmonary shunt. Unfortunately, PEEP can interfere with intracranial pressure (ICP) by increasing intrathoracic pressure. We hypothesized that the use of different PEEP levels could have an effect on intracranial and cerebral perfusion pressure (CPP), gas exchange, respiratory system mechanics, and hemodynamics in pediatric patients undergoing major neurosurgical procedures. METHOD:: Twenty-one consecutive pediatric patients undergoing surgical procedure for intracranial tumors were enrolled in this study, conducted between April 2008 and August 2009. Invasive radial pressure, central venous pressure (CVP), arterial oxygen saturation, ICP, and CPP were monitored. The middle cerebral artery mean velocity (Vmed) was determined by transcranial Doppler. At 0 cm H2O (ZEEP), the following parameters were recorded: systolic, mean, and diastolic arterial pressure, CVP, ICP, CPP, Vmed, and arterial blood gases. After assessment at 0 PEEP (ZEEP), PEEP 4 and PEEP 8 were applied: all parameters were recorded at each level. RESULTS:: The application of PEEP (from ZEEP to PEEP 8) significantly increased compliance of the respiratory system indexed to the weight of the patients (CrsI) (P=0.0001) without ICP modifications. No significant variations were observed in values of arterial pressure (MAP), CPP, Vmed, total resistance of the respiratory system indexed to the weight of the patients (RRSmaxI), and ohmic resistance of the respiratory system indexed to the weight of the patients (RRSminI). CVP significantly increased between ZEEP and PEEP 8 (P=0.02), and between PEEP 4 and PEEP 8 (P<0.05). Partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), partial arterial pressure of oxygen/inspiratory fraction of oxygen (PaO2/FiO2), and pH were not significantly modified. CONCLUSION:: We describe cerebral hemodynamic responses to PEEP application in pediatrics. PEEP values up to 8 cm H2O seem to be safe in pediatric patients with intracranial neoplasm, and, in our opinion, PEEP should be applied immediately after surgery to restore lung recruitment.
Journal of neurosurgical anesthesiology 03/2013; · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PurposeThe aim of this study was to compare helmet-NIV (non invasive ventilation), in terms of patientventilator interaction and performance, using two different circuits for connection: a double tube circuit (with one inspiratory and one expiratory line) and a standard circuit (an Y piece connected only to one side of the helmet, closing the other side).MethodsA mannequin, connected to a test lung, set at two different respiratory rates (20 and 30 breaths/min), was ventilated in Pressure Support Ventilation (PSV) mode with two different settings, randomly applied: Pressurization time/Expiratory trigger (Time(press)/Tr(exp)) 50%/25%, Default setting and Time(press)/Tr(exp) 80%/60%, Fast setting, through a helmet. The helmet was connected to the ventilator randomly with the double and the standard circuit.Patient-ventilator interaction was evaluated measuring: Inspiratory trigger delay (Delay(trinsp)), Expiratory trigger delay (Delay(trexp)), Pressurization Time (Time(press)), Time of synchrony (Time(syn)). The performance was analyzed measuring: Trigger pressure drop, Inspiratory Pressure-Time Product (PTPt), Pressure Time Product at 300 ms and 500 ms (PTP 300 and PTP 500 respectively) and Pressure Time Product 500 ms expressed as percentage of an ideal PTP500 (PTP500 index).ResultsAt both respiratory rates and ventilator settings helmet-NIV with the double tube circuit showed better interaction, with shorter Delay(trinsp), Delay(trexp) and Time(press) and longer Time(syn) (p<0.01) compared to the standard circuit (p<0.01). Moreover, the helmet performance was significantly improved by the double tube circuit as shown by higher PTP 300, PTP500 and PTP 500 index (p<0.01).Conclusions
Compared to the standard circuit, helmet-NIV with the double tube circuit showed a significantly better patient-ventilator interaction associated with a significantly better performance and a lower rate of wasted effort at30 breaths/min .
Respiratory care 02/2013; · 2.01 Impact Factor
-
Massimo Antonelli,
Marc Bonten,
Maurizio Cecconi,
Jean Chastre,
Giuseppe Citerio, Giorgio Conti,
J R Curtis,
Goran Hedenstierna,
Michael Joannidis,
Duncan Macrae,
Salvatore M Maggiore,
Jordi Mancebo,
Alexandre Mebazaa,
Jean-Charles Preiser,
Patricia Rocco,
Jean-François Timsit,
Jan Wernerman,
Haibo Zhang
European Journal of Intensive Care Medicine 01/2013; · 5.17 Impact Factor
-
Massimo Antonelli,
Marc Bonten,
Maurizio Cecconi,
Jean Chastre,
Giuseppe Citerio, Giorgio Conti,
J Randall Curtis,
Goran Hedenstierna,
Michael Joannidis,
Duncan Macrae,
Salvatore M Maggiore,
Jordi Mancebo,
Alexandre Mebazaa,
Jean-Charles Preiser,
Patricia Rocco,
Jean-François Timsit,
Jan Wernerman,
Haibo Zhang
European Journal of Intensive Care Medicine 01/2013; · 5.17 Impact Factor
-
Massimo Antonelli,
Marc Bonten,
Maurizio Cecconi,
Jean Chastre,
Giuseppe Citerio, Giorgio Conti,
J Randall Curtis,
Goran Hedenstierna,
Michael Joannidis,
Duncan Macrae,
Salvatore M Maggiore,
Jordi Mancebo,
Alexandre Mebazaa,
Jean-Charles Preiser,
Patricia Rocco,
Jean-François Timsit,
Jan Wernerman,
Haibo Zhang
European Journal of Intensive Care Medicine 12/2012; · 5.17 Impact Factor
-
Pediatric Pulmonology 11/2012; · 2.53 Impact Factor
-
European Journal of Pediatric Surgery 07/2012; · 0.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypothermia may reduce the CO(2) production by decreasing the metabolism of the cooled tissue. We describe the first clinical use of hypothermia to lower hypercarbia in a case of bronchiolitis related respiratory failure unresponsive to maximal respiratory support. In this case, hypothermia allowed sparing the use of extracorporeal life support. Conclusion Hypothermia might be useful for severe acute respiratory failure unresponsive to aggressive respiratory support.
European Journal of Pediatrics 06/2012; · 1.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Brain injury is the leading cause of death in pediatric ICU. Current evidence supports the use of therapeutic hypothermia (TH) in unconscious patients after out-of-hospital cardiac arrest when the initial heart rhythm was ventricular fibrillation. TH has been proved to be also beneficial in term neonates after hypoxic-ischemic encephalopathy (HIE) and in children with traumatic brain injury (TBI). Recent reports have also investigated TH for the treatment of superrefractory status epilepticus. The clinical application of TH is based on the possibility to inhibit or lessen a myriad of destructive processes (including excitotoxicty, neuroinflammation, apoptosis, free radical production, seizure activity, blood- brain barrier disruption, blood vessel leakage) that take place in the injured tissue following ischemia-reperfusion. TH may also represent a useful tool when conventional therapy fails to achieve an effective control of elevated intracranial pressure. This review is aimed to provide an update of the available literature concerning this intriguing topic.
Current Drug Targets 05/2012; 13(7):925-935. · 3.55 Impact Factor
-
Current drug targets 04/2012; 13(7):877. · 3.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threating conditions still lacking a definite therapy and carrying a high mortality and morbidity, especially in children and infants. Albeit respiratory assistance and supportive therapies are crucial for ALI/ARDS, many drugs have been proposed to treat such syndromes through various mechanisms of action. On the whole the pharmacological therapy might play an important role in such a complex clinical situation but few evidence based data are available in pediatric and neonatal critical care. This review will focus on drugs directly available on the bedside, that is, medicines already administered in the practice or investigated in at least one clinical study. We will value the differences due to patient's age and the various causes of the syndrome, that may affect the response to the pharmacological therapy. A special attention will be given to the drugs directly deliverable into the lungs, as this strategy allows a total availability to the lung tissue. The experimental background behind each drug will be discussed and then clinical data in neonates and infants will be presented, if available. Data coming from adult critical care and thought to be somehow pertinent for the pediatric setting will otherwise be reviewed. Quality and evidence for or against each therapy will be evaluated according to the Scottish Intercollegiate Guidelines Network statement and practical reminders for clinicians will accordingly be provided.
Current drug targets 04/2012; 13(7):906-16. · 3.93 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a selected patient population, we evaluated the glycemic response to different infusional policies in the management of
posterior cranial fossa tumor (PFT) removal. We analyzed the perioperative course, prospectically collected, of 137 children
undergoing 150 surgical procedures. Patients were divided in two groups according to different intraoperative fluids (group
A, 2.5% glucose; group B, crystalloids). In group B glycemia remained below 125mgdl−1, while group A showed persistently supranormal glycemic plasma values, reaching statistical significance at the end of surgery
(P<0.018). As no perioperative mortality occurred and no differences were found between groups regarding PICU respiratory
or infectious complications, PICU length of stay (LOS) was assumed as the main outcome indicator. LOS was not influenced by
group A or B inclusion, while a new indicator, namely the Glycemic Stress Index (GSI), representing both glycemic intraoperative
change and procedure length, showed significantly different results in the study groups (P=0.004). Our clinical experience suggests that both intraoperative glucose-free solutions are safe, and GSI can be a useful
tool to identify prolonged PICU stay patients.
Journal of Neuro-Oncology 04/2012; 93(3):361-368. · 3.21 Impact Factor
-
European Journal of Intensive Care Medicine 03/2012; 38(6):1082-3. · 5.17 Impact Factor
-
The Lancet 03/2012; 379(9819):976. · 38.28 Impact Factor
-
Massimo Antonelli,
Marc Bonten,
Jean Chastre,
Giuseppe Citerio, Giorgio Conti,
J Randall Curtis,
Daniel De Backer,
Goran Hedenstierna,
Michael Joannidis,
Duncan Macrae,
Jordi Mancebo,
Salvatore M Maggiore,
Alexandre Mebazaa,
Jean-Charles Preiser,
Patricia Rocco,
Jean-François Timsit,
Jan Wernerman,
Haibo Zhang
European Journal of Intensive Care Medicine 03/2012; 38(3):345-58. · 5.17 Impact Factor
-
Massimo Antonelli,
Marc Bonten,
Jean Chastre,
Giuseppe Citerio, Giorgio Conti,
J Randall Curtis,
Daniel De Backer,
Goran Hedenstierna,
Michael Joannidis,
Duncan Macrae,
Jordi Mancebo,
Salvatore M Maggiore,
Alexandre Mebazaa,
Jean-Charles Preiser,
Patricia Rocco,
Jean-François Timsit,
Jan Wernerman,
Haibo Zhang
European Journal of Intensive Care Medicine 02/2012; 38(4):542-56. · 5.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Non-invasive high frequency oscillatory ventilation through nasal prongs (nHFOV) has been proposed to combine the advantages of oscillatory pressure waveform and non-invasive interface. We studied the effect of oscillation amplitude and inspiratory time on the pressure transmission and tidal volume delivery through different nasal prongs.
In vitro mechanical study on a previously described bench model of nHFOV. The model was built connecting SM3100A tubings to a neonatal lung model, via two differently sized binasal prongs. A circuit with no nasal prongs was used as control. Tidal volume (T(v) ), oscillatory pressure ratio (ΔP(dist) /ΔP(prox) ), and ventilation (DCO(2) ) were measured across a range of amplitudes and inspiratory times (I(T) ). Measurements were performed with a low-dead space hot wire anemometer coupled with a pressure transducer.
Using both nasal prongs, T(v) , ΔP(dist) /ΔP(prox) , and DCO(2) were 83%, 40%, and 71%, respectively, of those provided with the control circuit. No differences were noticed between small and large prongs. T(v) and ΔP(prox) were linked by a quadratic relationship. T(v) plateaus for amplitude values >65 cmH(2) O. ΔP(dist) /ΔP(prox) shows same tendency. Same results were obtained with both types of prongs and with increasing I(T) . On the whole, mean T(v) was higher with I(T) at 50% than at 33% (2.4 ml vs. 1.4 ml; P < 0.001).
Changing oscillation amplitude and I(T) has a significant effect on ventilation. Varying these two parameters provides a theoretical T(v) within the ideal values for HFOV also using the smallest nasal prongs. Pediatr Pulmonol. 2012. 47:1012-1018. © 2012 Wiley Periodicals, Inc.
Pediatric Pulmonology 02/2012; 47(10):1012-8. · 2.53 Impact Factor
