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Biomedical subjects

M Antonelli

Publications and source records attributed to M Antonelli.

At least 37 records · Page 2Linked to original sources

Non-invasive pressure support ventilation in patients with acute respiratory failure after bilateral lung transplantation.

OBJECTIVE: To evaluate non-invasive ventilation (NIV) prospectively in a group of patients developing acute respiratory failure (ARF) after bilateral lung transplantation (BLT). SETTING: General intensive care unit (ICU) of Rome "La Sapienza" University. PATIENTS: Twenty-one patients (18 with cystic fibrosis) undergoing BLT. RESULTS: All consecutive patients developing ARF (according to predefined criteria) and requiring ventilatory support, received non-invasive pressure support ventilation through a face-mask (PEEP 5 cmH2O, PSV 14+/-2 cmH2O) for a mean period of 5+/-4 days. Eighteen out of 21 patients avoided intubation and were discharged from the ICU; 3 patients required intubation: 1 of them survived while 2 developed septic shock and died. CONCLUSIONS: NIV administration was well tolerated and avoided intubation in the large majority of patients (86%); in NIV responders the rate of complications was low and ICU mortality nil. NIV should be considered as an interesting alternative to conventional ventilation in patients who require ventilatory support after BLT.

Acute Disease↗

De-escalation antimicrobial chemotherapy in critically III patients: pros and cons.

In spite of advances in critical care, nosocomial infections still have a considerable impact on Intensive Care Unit (ICU) and hospital length of stay, mortality and costs. Several authors suggest that antibiotic therapy should be instituted as soon as sepsis is suspected in critically patients. Over the last two decades the rates of occurrence for pathogens have significantly changed under selective pressure from broad-spectrum antimicrobial therapy. Shifts from predominance of gram-negative to gram-positive organisms and outbreaks of resistant pathogens address the need for appropriate empirical regimens. Agents such as ceftazidime, imipenem and, more recently, meropenem and tazobactam have been used successfully as monotherapy. Two different clinical trials have reported that meropenem monotherapy is significantly more effective than ceftazidime-based therapy. Because of the outbreak of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, some investigators suggest adding a glycopeptide to beta-lactamase inhibitor and carbapenem as initial empirical therapy. Such a regimen should be administered before definitive proof of infections and until the results of microbial investigation are available (de-escalation antimicrobial chemotherapy). On the other hand, several authors do not recommend glycopeptide administration in an attempt to limit nosocomial outbreaks of vancomycin-resistant enterococci (VRE) and staphylococci (VRS) and to avoid secondary drawbacks, such as nephrotoxicity and ototoxicity. De-escalation antimicrobial chemotherapy should be tailored to critically ill patients according to their clinical status, severity of illness and suspicion of sepsis or nosocomial pneumonia.

Anti-Bacterial Agents↗

Noninvasive mechanical ventilation in acute hypoxaemic respiratory failure.

In acute hypoxaemic respiratory failure (HRF), oxygenation, reduction in the work of breathing and in dyspnoea may be achieved by delivering noninvasive mechanical ventilation (NIMV). Several uncontrolled and 13 randomized controlled studies (RCS) were reviewed. Uncontrolled studies confirmed the feasibility and the possibility to improve arterial blood oxygenation with NIMV. The 13 RCS compared NIMV versus a conventional approach in a total of 720 patients with HRF. Endotracheal intubation was required in 186 of the 358 patients (median (95% confidence interval (CI)) 51%, (40-63%)) assigned to a conventional approach and in 107 of the 362 patients (29% (20-39%)) assigned to NIMV. Eleven of the 13 RCS found a reduction in the rate of endotracheal intubation with NIMV with an absolute risk reduction of 31% (30-33%). Ten of the 13 RCS found a reduction in the mortality rate which was 30% (19-40%) in the control group and 19% (13-26%) in the NIMV group. The mean absolute risk reduction was 15% (10-20%). In conclusion, noninvasive ventilation appears to be a useful method in avoiding endotracheal intubation and probably in reducing the morbidity of patients with hypoxaemic respiratory failure.

Acute Disease↗

Lipid peroxidation, circulating cytokine and endothelin 1 levels in healthy volunteers undergoing hyperbaric oxygenation.

BACKGROUND: The aim of the present study was to evaluate the effects of hyperbaric oxygenation on lipid peroxidation, on the release of circulating cytokines (TNFa, IL6, IL1b) and endothelin-1 (ET1). METHODS EXPERIMENTAL DESIGN: single arm, prospective study. SETTING: ICU hyperbaric division of a University Hospital. PATIENTS: fifteen healthy volunteers (10 male and 5 female, mean age 32+/-7 years) studied during hyperbaric oxygenation divided at random into two groups: group A (7 subjects) and group B (8 subjects). INTERVENTIONS: Both groups were consecutively pressurized at 2 atmospheres (2 atm abs) and 2.8 atm abs, with a constant descending rate of 1 m/min; in accordance with the experimental design, group A breathed pure oxygen continuously through facial masks and group B breathed chamber air during pressurization. MEASURES: Twenty millilitres of blood were drawn from all individuals at the following times: 1) basal, before HBO; 2) after 10 min at 2 atm abs; 3) after 10 min at 2.8 atm abs; 4) 30 min after the end of HBO. In all collected samples thiobarbituric reacting substances were evaluated, using the spectrophotometric technique, IL1 TNF and IL6 serum levels by ELISA and endothelin 1 plasma levels by radioimmunoassay. RESULTS: In both groups, TBARS levels showed a twofold increase (p<0.05) in relation to the baseline, during and after hyperbaric oxygenation. Serum IL6 and IL1b values did not significantly change over the study in any of the volunteers. TNFa amounts significantly increased (p<0.05) during HBO, at 2 atm abs and 2.8 atm abs in both groups, with almost twofold increments. ET1 plasma values increased (p<0.05) in all volunteers during and after HBO: at 2 atm abs (range 7 to 24 pg/ml), 2.8 atm abs (range 7 to 19 pg/ml) and 30 min after (range 8 to 17 pg/ml) in relation to baseline (range 4 to 12 pg/ml). All the studied compounds had a similar trend in the two groups. CONCLUSIONS: Hyperbaric oxygenation in healthy volunteers can induce not only lipid peroxidation, but also liberation of compounds such as TNFa and endothelins, no matter whether pure oxygen is breathed or not. These results suggest that the phenomenon behind this release might be leukocyte activation as induced by HBO. The possible role of ET1 in determining vasoconstriction occurring during HBO is also suggested.

Adult↗

[Acute respiratory failure in organ transplantation and immunodepressed patients].

Recently, noninvasive ventilation (NIV) has been introduced as a new and alternative ventilatory method. The efficacy of NIV has been reported in immunosuppressed patients, with the decrease in drawbacks related to mechanical ventilation by endotracheal intubation. The authors propose an up-date on the use of NIV in transplanted patients.

Adult↗

Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: A randomized controlled trial.

CONTEXT: Continuous positive airway pressure (CPAP) is widely used in the belief that it may reduce the need for intubation and mechanical ventilation in patients with acute hypoxemic respiratory insufficiency. OBJECTIVE: To compare the physiologic effects and the clinical efficacy of CPAP vs standard oxygen therapy in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency. DESIGN, SETTING, AND PATIENTS: Randomized, concealed, and unblinded trial of 123 consecutive adult patients who were admitted to 6 intensive care units between September 1997 and January 1999 with a PaO(2)/FIO(2) ratio of 300 mm Hg or less due to bilateral pulmonary edema (n = 102 with acute lung injury and n = 21 with cardiac disease). INTERVENTIONS: Patients were randomly assigned to receive oxygen therapy alone (n = 61) or oxygen therapy plus CPAP (n = 62). MAIN OUTCOME MEASURES: Improvement in PaO(2)/FIO(2) ratio, rate of endotracheal intubation at any time during the study, adverse events, length of hospital stay, mortality, and duration of ventilatory assistance, compared between the CPAP and standard treatment groups. RESULTS: Among the CPAP vs standard therapy groups, respectively, causes of respiratory failure (pneumonia, 54% and 55%), presence of cardiac disease (33% and 35%), severity at admission, and hypoxemia (median [5th-95th percentile] PaO(2)/FIO(2) ratio, 140 [59-288] mm Hg vs 148 [62-283] mm Hg; P =.43) were similarly distributed. After 1 hour of treatment, subjective responses to treatment (P<.001) and median (5th-95th percentile) PaO(2)/FIO(2) ratios were greater with CPAP (203 [45-431] mm Hg vs 151 [73-482] mm Hg; P =.02). No further difference in respiratory indices was observed between the groups. Treatment with CPAP failed to reduce the endotracheal intubation rate (21 [34%] vs 24 [39%] in the standard therapy group; P =.53), hospital mortality (19 [31%] vs 18 [30%]; P =.89), or median (5th-95th percentile) intensive care unit length of stay (6.5 [1-57] days vs 6.0 [1-36] days; P =.43). A higher number of adverse events occurred with CPAP treatment (18 vs 6; P =.01). CONCLUSION: In this study, despite early physiologic improvement, CPAP neither reduced the need for intubation nor improved outcomes in patients with acute hypoxemic, nonhypercapnic respiratory insufficiency primarily due to acute lung injury. JAMA. 2000;284:2352-2360.

APACHE↗

Noninvasive positive pressure ventilation as treatment for acute respiratory failure in critically ill patients.

Our current state of knowledge on noninvasive positive pressure ventilation (NPPV) and technical aspects are discussed in the present review. In patients with chronic obstructive pulmonary disease, NPPV can be considered a valid therapeutic option to prevent endotracheal intubation. Evidence suggests that, before eventual endotracheal intubation, NPPV should be considered as first-line intervention in the early phases of acute exacerbation of chronic obstructive pulmonary disease. Small randomized and non-randomized studies on the application of NPPV in patients with acute hypoxaemic respiratory failure showed promising results, with reduction in complications such as sinusitis and ventilator-associated pneumonia, and in the duration of intensive care unit stay. The conventional use of NPPV in hypoxaemic acute respiratory failure still remains controversial, however. Large randomized studies are still needed before extensive clinical application in this condition.

Acute Disease↗

Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial.

CONTEXT: Noninvasive ventilation (NIV) has been associated with lower rates of endotracheal intubation in populations of patients with acute respiratory failure. OBJECTIVE: To compare NIV with standard treatment using supplemental oxygen administration to avoid endotracheal intubation in recipients of solid organ transplantation with acute hypoxemic respiratory failure. DESIGN AND SETTING: Prospective randomized study conducted at a 14-bed, general intensive care unit of a university hospital. PATIENTS: Of 238 patients who underwent solid organ transplantation from December 1995 to October 1997, 51 were treated for acute respiratory failure. Of these, 40 were eligible and 20 were randomized to each group. INTERVENTION: Noninvasive ventilation vs standard treatment with supplemental oxygen administration. MAIN OUTCOME MEASURES: The need for endotracheal intubation and mechanical ventilation at any time during the study, complications not present on admission, duration of ventilatory assistance, length of hospital stay, and intensive care unit mortality. RESULTS: The 2 groups were similar at study entry. Within the first hour of treatment, 14 patients (70%) in the NIV group, and 5 patients (25%) in the standard treatment group improved their ratio of the PaO2 to the fraction of inspired oxygen (FIO2). Over time, a sustained improvement in PaO2 to FIO2 was noted in 12 patients (60%) in the NIV group, and in 5 patients (25%) randomized to standard treatment (P = .03). The use of NIV was associated with a significant reduction in the rate of endotracheal intubation (20% vs 70%; P = .002), rate of fatal complications (20% vs 50%; P = .05), length of stay in the intensive care unit by survivors (mean [SD] days, 5.5 [3] vs 9 [4]; P = .03), and intensive care unit mortality (20% vs 50%; P = .05). Hospital mortality did not differ. CONCLUSIONS: These results indicate that transplantation programs should consider NIV in the treatment of selected recipients of transplantation with acute respiratory failure.

Female↗

Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score.

OBJECTIVES: To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. DESIGN: Prospective, multicenter, observational cohort analysis. SETTING: Forty ICUs in 16 countries. PATIENTS: All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. MEASUREMENTS AND RESULTS: Of the patients, 348 (24.7%) developed ARF, as diagnosed by a serum creatinine of 300 micromol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p < 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8% vs 14.0%, p < 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95%: 1.23-2.06], p < 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. CONCLUSION: In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.

Acute Kidney Injury↗

[Gas conditioning in artificial respiration].

The authors review the main systems used in the clinical setting to condition inspiratory gases during mechanical ventilation. More in details, the functional principles of hot water humidifiers and heat and moisture exchangers are described.

Conditioning, Psychological↗

[Non-invasive ventilation in intensive care. Update 2000].

NIV indications and application in critically ill patients have considerably expanded in the last few years: the aim of this paper is to shortly review NIV main indications, on the basis of data from the current scientific literature.

Critical Care↗

[Home mechanical ventilation: the extra-hospital phase].

Home mechanical ventilation is the choice option, when there are no contraindications of medical or socio-economic order, in all cases of impossible complete weaning from ventilatory support. Easy to use, reliable and size limited positive pressure ventilators lead to a spread diffusion of this technique. In the patient/ventilator interface, tracheostomy is the golden choice for patient with great reduction in spontaneous ventilatory ability. For all other patients, perfectioning of non-invasive access (nasal and oral nasal mask) represent an effective progress. Major limitations in home ventilation are still, up to present, the lack of multidisciplinary structures able to give territorial assistance. Home ventilation therapy in the experience of the Policlinico Universtitario "La Sapienza", Rome is presented.

Home Care Services, Hospital-Based↗

Application of SOFA score to trauma patients. Sequential Organ Failure Assessment.

OBJECTIVE: To assess the ability of the SOFA score (Sequential Organ Failure Assessment) to describe the evolution of organ dysfunction/failure in trauma patients over time in intensive care units (ICU). DESIGN: Retrospective analysis of a prospectively collected database. SETTING: 40 ICUs in 16 countries. PATIENTS: All trauma patients admitted to the ICU in May 1995. MAIN OUTCOME MEASURES AND RESULTS: Incidence of dysfunction/failure of different organs during the first 10 days of stay and the relation between the dysfunction, outcome, and length of stay. Included in the SOFA study were 181 trauma patients (140 males and 41 females). The non-survivors were significantly older than the survivors (51 years+/-20 vs 38+/-16 years, p < 0.05) and had a higher global SOFA score on admission (8+/-4 vs 4+/-3, p < 0.05) and throughout the 10-day stay. On admission, the non-survivors had higher scores for respiratory ( > 3 in 47% of non-survivors vs 17% of survivors), cardiovascular ( > 3 in 24% of non-survivors vs 5.7% of survivors), and neurological systems ( > 4 in 41% of non-survivors vs 16% of survivors); although the trend was maintained over the whole study period, the differences were greater during the first 4-5 days. After the first 4 days, only respiratory dysfunction was significantly related to outcome. A higher SOFA score, admission to the ICU from the same hospital, and the presence of infection on admission were the three major variables associated with a longer length of stay in the ICU (additive regression coefficients: 0.85 days for each SOFA point, 4.4 for admission from the same hospital, 7.26 for infection on admission). CONCLUSIONS: The SOFA score can reliably describe organ dysfunction/ failure in trauma patients. Regular and repeated scoring may be helpful for identifying categories of patients at major risk of prolonged ICU stay or death.

APACHE↗

The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM.

OBJECTIVE: To evaluate the performance of total maximum sequential organ failure assessment (SOFA) score and a derived measure, delta SOFA (total maximum SOFA score minus admission total SOFA) as a descriptor of multiple organ dysfunction/failure in intensive care. DESIGN: Prospective, multicentre and multinational study. SETTING: Forty intensive care units (ICUs) from Australia, Europe, North and South America. PATIENTS: Data on 1,449 patients, evaluated at admission and then consecutively every 24 h until ICU discharge (11,417 records) during May 1995. Excluded from data collection were all patients with a length of stay in the ICU less than 2 days following uncomplicated scheduled surgery. MAIN OUTCOME MEASURE: Survival status at ICU discharge. INTERVENTIONS: The collection of raw data necessary for the computation of a SOFA score on admission and then every 24 h, and basic demographic and clinical statistics. MEASUREMENTS AND MAIN RESULTS: Mean total maximum SOFA score presented a very good correlation to ICU outcome, with mortality rates ranging from 3.2% in patients without organ failure to 91.3% in patients with failure of all the six organs analysed. A maximum score was reached 1.1 +/- 0.2 days after admission for all the organ systems analysed. The total maximum SOFA score presented an area under the ROC curve of 0.847 (SE 0.012), which was significantly higher than any of its individual components. The cardiovascular score (odds ratio 1.68) was associated with the highest relative contribution to outcome. No independent contribution could be demonstrated for the hepatic score. No significant interactions were found. Principal components analysis demonstrated the existence of a two-factor structure that became clearer when analysis was limited to the presence or absence of organ failure (SOFA score > or = 3 points) during the ICU stay. The first factor comprises respiratory, cardiovascular and neurological systems and the second coagulation, hepatic and renal systems. Delta SOFA also presented a good correlation to outcome. The area under the receiver operating characteristic (ROC) curve was 0.742 (SE 0.017) for delta SOFA, lower than the total maximum SOFA score or admission total SOFA score. The impact of delta SOFA on prognosis remained significant after correction for admission total SOFA. CONCLUSIONS: The results show that total maximum SOFA score and delta SOFA can be used to quantify the degree of dysfunction/failure already present on ICU admission, the degree of dysfunction/failure that appears during the ICU stay and the cumulative insult suffered by the patient. These properties make it a good instrument to be used in the evaluation of organ dysfunction/failure.

Adolescent↗

Structural interpretation of site-directed mutagenesis and specificity of the catalytic subunit of protein kinase CK2 using comparative modelling.

The catalytic subunit of protein kinase casein kinase 2 (CK2alpha), which has specificity for both ATP and GTP, shows significant amino acid sequence similarity to the cyclin-dependent kinase 2 (CDK2). We constructed site-directed mutants of CK2alpha and used a three-dimensional model to investigate the basis for the dual specificity. Introduction of Phe and Gly at positions 50 and 51, in order to restore the pattern of the glycine-rich motif, did not seriously affect the specificity for ATP or GTP. We show that the dual specificity probably originates from the loop situated around the position His115 to Asp120 (HVNNTD). The insertion of a residue in this loop in CK2 alpha subunits, compared with CDK2 and other kinases, might orient the backbone to interact with the base A and G; this insertion is conserved in all known CK2alpha. The mutant deltaN118, the design of which was based on the modelling, showed reduced affinity for GTP as predicted from the model. Other mutants were intended to probe the integrity of the catalytic loop, alter the polarity of a buried residue and explore the importance of the carboxy terminus. Introduction of Arg to replace Asn189, which is mapped on the activation loop, results in a mutant with decreased k(cat), possibly as a result of disruption of the interaction between this residue and basic residues in the vicinity. Truncation at position 331 eliminates the last 60 residues of the alpha subunit and this mutant has a reduced catalytic efficiency compared with the wild-type. Catalytic efficiency is restored in the truncation mutant by the replacement of a potentially buried Glu at position 252 by Lys, probably owing to a higher stability resulting from the formation of a salt bridge between Lys252 and Asp208.

Amino Acid Sequence↗

Sepsis and septic shock: pro-inflammatory or anti-inflammatory state?

A considerable body of evidence indicates that together with an important pro-inflammatory reaction, a anti-inflammatory response contributes to the onset of sepsis and organ failure. At a local site of injury or infection and during the initial appearance of pro- and anti-inflammatory mediators in the circulation, the beneficial effects of these compounds counterbalance their harmful effects. Only when the balance between these two forces is lost may these substances become harmful. The sequelae of an unbalanced systemic inflammatory reaction include derangement of microcirculation, shock, transudation into organs and defects of coagulation. An unbalanced systemic compensatory anti-inflammatory response often results in anergy and immunosuppression. The pro-inflammatory and anti-inflammatory conditions may ultimately reinforce each other, creating a state of destructive immunologic dissonance. In the present report, recent literature on cytokines was reviewed together with the 89 clinical papers published between 1993 and 1997 on the role of cytokines during sepsis and other inflammatory reactions. Cytokines were analyzed in more than 5,000 patients. Sepsis and septic shock were the two groups most represented (2834 individuals and 550 respectively). Only 12% (11) of the studies showed a correlation with the presence of sepsis or septic complications. Overall 27 (39%) studies found a correlation between levels of cytokine and mortality. Fifty (62%) of the 80 studies that investigated this correlation found that the amount of cytokines did not predict death. The rest of the 30 (48%) investigations depicted an unhomogeneous picture: even though 27 studies evidenced higher levels of cytokines in non-survivors, 3 studies found the opposite.

Blood Coagulation Disorders↗

Antibody response to P. aeruginosa in patients with cystic fibrosis: evaluation of two methods.

The immunological response to Ps. aeruginosa antigens may be a sensitive and early indicator of the colonisation of the lungs with these organisms in patients with cystic fibrosis. This study used an immunoenzymatic system and immunoblotting to evaluate the antibody response of 20 patients without apparent Ps. aeruginosa lung infection. These was an agreement in the results obtained with the two methods in 87.5% of cases.

Antibodies, Bacterial↗