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1.
N Engl J Med ; 381(19): 1831-1842, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31693806

RESUMO

BACKGROUND: Patients who are treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm are at increased risk for ventilator-associated pneumonia. The benefit of preventive short-term antibiotic therapy has not been shown. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin-clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting less than 6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia. RESULTS: A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31 to 0.92; P = 0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups. CONCLUSIONS: A 2-day course of antibiotic therapy with amoxicillin-clavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo. No significant between-group differences were observed for other key clinical variables, such as ventilator-free days and mortality at day 28. (Funded by the French Ministry of Health; ANTHARTIC ClinicalTrials.gov number, NCT02186951.).


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Parada Cardíaca Extra-Hospitalar/complicações , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Adulto , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/efeitos adversos , Antibacterianos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/mortalidade , Pneumonia Associada à Ventilação Mecânica/etiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Resultado do Tratamento , Desmame do Respirador
2.
N Engl J Med ; 381(24): 2327-2337, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31577396

RESUMO

BACKGROUND: Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated. METHODS: We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed. RESULTS: From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, -1.9 percentage points; 95% CI, -8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups. CONCLUSIONS: Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION ClinicalTrials.gov number, NCT01994772.).


Assuntos
Reanimação Cardiopulmonar , Coma/complicações , Parada Cardíaca/terapia , Hipotermia Induzida , Idoso , Temperatura Corporal , Encefalopatias/etiologia , Feminino , Seguimentos , Parada Cardíaca/complicações , Parada Cardíaca/mortalidade , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/terapia , Método Simples-Cego
3.
Ann Intensive Care ; 9(1): 106, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31549274

RESUMO

BACKGROUND: Nephrotoxic drug prescription may contribute to acute kidney injury (AKI) occurrence and worsening among critically ill patients and thus to associated morbidity and mortality. The objectives of this study were to describe nephrotoxic drug prescription in a large intensive-care unit cohort and, through a case-control study nested in the prospective cohort, to evaluate the link of nephrotoxic prescription burden with AKI. RESULTS: Six hundred and seventeen patients (62%) received at least one nephrotoxic drug, among which 303 (30%) received two or more. AKI was observed in 609 patients (61%). A total of 351 patients were considered as cases developing or worsening AKI a given index day during the first week in the intensive-care unit. Three hundred and twenty-seven pairs of cases and controls (patients not developing or worsening AKI during the first week in the intensive-care unit, alive the case index day) matched on age, chronic kidney disease, and simplified acute physiology score 2 were analyzed. The nephrotoxic burden prior to the index day was measured in drug.days: each drug and each day of therapy increasing the burden by 1 drug.day. This represents a semi-quantitative evaluation of drug exposure, potentially easy to implement by clinicians. Nephrotoxic burden was significantly higher among cases than controls: odds ratio 1.20 and 95% confidence interval 1.04-1.38. Sensitivity analysis showed that this association between nephrotoxic drug prescription in the intensive-care unit and AKI was predominant among the patients with lower severity of disease (simplified acute physiology score 2 below 48). CONCLUSIONS: The frequently observed prescription of nephrotoxic drugs to critically ill patients may be evaluated semi-quantitatively through computing drug.day nephrotoxic burden, an index significantly associated with subsequent AKI occurrence, and worsening among patients with lower severity of disease.

4.
Ann Intensive Care ; 9(1): 54, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073873

RESUMO

BACKGROUND: It is unknown whether the recommended mean arterial pressure (MAP) target of 65 mmHg during initial resuscitation of septic shock is sufficient to maintain cerebral perfusion. Thus, we tested the hypothesis that a higher MAP target in patients with septic shock may improve level of arousal. METHODS: We performed a post hoc exploratory analysis of the SEPSISPAM trial, which assessed the effect of a "high-target" level of MAP (80-85 mmHg) versus the recommended "low-target" MAP (65-70 mm Hg) on mortality in patients with septic shock. Among the 776 patients originally recruited in SEPSISPAM trial, we selected those who were mechanically ventilated and sedated and with available evaluation of arousal level assessed by the Richmond Agitation and Sedation Scale (RASS). RESULTS: We restricted our analysis to the period in which patients were treated with vasoactive drugs. Cumulative sedative drugs were assessed daily. A total of 532 patients were included in this study: 253 (47.6%) in the low-target group and 279 (52.4%) in the high-target group. Daily cumulative sedative drugs were similar in both groups. Compared to the low-target group, minimal and maximal RASS were significantly higher in the high-target group at day 2, 4 and 5. Furthermore, in order to consider the fact that multiple measures were done for each patient and to consider the global effect of time on these measures, we used a mixed linear regression and multivariate models: we confirmed that maximal RASS values were significantly higher in the high-target group. CONCLUSION: In patients with septic shock who were mechanically ventilated and sedated, resuscitation with MAP target between 80 and 85 mmHg was associated with higher arousal level as compared to a MAP target between 65 and 70 mmHg.

5.
Lancet Infect Dis ; 19(6): 620-630, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31056427

RESUMO

BACKGROUND: Severe community-acquired pneumonia caused by Streptococcus pneumoniae is associated with high morbidity and mortality rates. CAL02, a novel antitoxin agent with an unprecedented mode of action, consists of liposomes that capture bacterial toxins known to dysregulate inflammation, cause organ damage, and impede immune defence. We aimed to assess the safety of CAL02 as an add-on therapy to antibiotics. METHODS: This randomised, double-blind, multicentre, placebo-controlled trial was done in ten intensive care units (ICUs) in France and Belgium (but only six units enrolled patients), in patients with severe community-acquired pneumococcal pneumonia who required ICU admission and had been identified as being infected with S pneumoniae. We randomly assigned participants in two stages-the first stage randomly assigned six patients (1:1) to either low-dose CAL02 or placebo, and the second stage randomly assigned 18 patients (14:4) to either high-dose CAL02 or placebo, and stratified in four blocks (4:1, 4:1, 3:1, and 3:1), in addition to standard of care. Block randomisation was done with a computer-generated random number list. Participants, investigators, other site study personnel, the sponsor, and the sponsor's designees involved in study management and monitoring were masked to the randomisation list and treatment assignment. Patients were treated with low-dose (4 mg/kg) or high-dose (16 mg/kg) CAL02 or placebo (saline), in addition to standard antibiotic therapy. Two intravenous doses of study treatment were infused, with a 24 h interval, at a concentration of 10 mg/mL, stepwise, over a maximum of 2 h on days 1 and 2. The primary objective of the study was to assess the safety and tolerability of low-dose and high-dose CAL02 in patients with severe community-acquired pneumonia treated with standard antibiotic therapy, and the primary analysis was done on the safety population (all patients who received at least one dose of the study treatment). Efficacy was a secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT02583373. FINDINGS: Between March 21, 2016, and Jan 13, 2018, we screened 280 patients with community-acquired pneumonia. 19 patients were enrolled and randomly assigned, resulting in 13 patients in the CAL02 groups (three assigned to low-dose CAL02 and ten assigned to high-dose CAL02) and six in the placebo group. One patient randomly assigned to placebo was allocated to the wrong treatment group and received high-dose CAL02 instead of placebo. Thus, 14 patients received CAL02 (three received low-dose CAL02 and 11 received high-dose CAL02) and five patients received placebo, constituting the safety population. At baseline, the mean APACHE II score for the total study population was 21·5 (SD 4·9; 95% CI 19·3-23·7) and 11 (58%) of 19 patients had septic shock. Adverse events occurred in 12 (86%) of 14 patients in the CAL02 treatment groups combined and all five (100%) patients in the placebo group. Serious adverse events occurred in four (29%) of 14 patients in the CAL02 treatment groups combined and two (40%) of five patients in the placebo group. One non-serious adverse event (mild increase in triglycerides) in a patient in the high-dose CAL02 group was reported as related to study drug. However, analysis of the changes in triglyceride levels in the CAL02 groups compared with the placebo group revealed no correlation with administration of CAL02. No adverse events were linked to local tolerability events. All patients, apart from one who died in the low CAL02 group (death not related to the study drug) achieved clinical cure at the test of cure visit between days 15 and 22. The sequential organ failure assessment score decreased by mean 65·0% (95% CI 50·7-79·4) in the combined CAL02 groups compared with 29·2% (12·8-45·5) in the placebo group between baseline and day 8. INTERPRETATION: The nature of adverse events was consistent with the profile of the study population and CAL02 showed a promising safety profile and tolerability. However, the difference between high-dose and low-dose CAL02 could not be assessed in this study. Efficacy was in line with the expected benefits of neutralising toxins. The results of this study support further clinical development of CAL02 and provide a solid basis for a larger clinical study. FUNDING: Combioxin.

6.
Pulm Pharmacol Ther ; 57: 101807, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31102741

RESUMO

BACKGROUND: Nebulization during mechanical ventilation is impeded by large extra-pulmonary drug deposition and long administration durations which currently limit implementation of inhaled antibiotic therapy. Direct intra-tracheal delivery using a sprayer represents an appealing alternative investigated in small animal models, but large animal data are lacking. METHODS: Amikacin was administered through intravenous infusion (20 mg/kg), nebulization (60 mg/kg) and direct intra-tracheal spray (30 mg/kg) to 10 intubated piglets, in a randomized cross-over design. Amikacin concentrations were measured in the serum and pulmonary parenchyma. Anatomic deposition was investigated using immuno-histochemistry. RESULTS: Spray delivery resulted in higher amikacin outputs than nebulization and infusion. Pulmonary inhaled delivery techniques yielded much higher lung concentrations and much lower serum concentrations than intravenous infusion. However, unlike nebulization and infusion, intra-tracheal spray delivery was associated with more than 100- and 1000-fold variability in lung concentrations between and within animals. Amikacin specific immuno-histochemistry showed consistent bronchial and alveolar drug deposition with all modalities. CONCLUSION: Nebulization remains the most reliable and simple technique to deliver inhaled amikacin uniformly to the lung during mechanical ventilation. Further development of tracheal sprays is required to take advantage of potential benefits related to high drug output and low extra-pulmonary deposition in large animals.

7.
Crit Care Med ; 47(4): e340-e348, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30707125

RESUMO

OBJECTIVES: Severe hypoxemia is the most common serious adverse event during endotracheal intubation. Preoxygenation is performed routinely as a preventive measure. The relative efficacy of the various available preoxygenation devices is unclear. Here, our objective was to assess associations between preoxygenation devices and pulse oximetry values during endotracheal intubation. DESIGN: Post hoc analysis of data from a multicenter randomized controlled superiority trial (McGrath Mac Videolaryngoscope Versus Macintosh Laryngoscope [MACMAN]) comparing videolaryngoscopy to Macintosh laryngoscopy for endotracheal intubation in critical care. SETTING: Seven French ICUs. PATIENTS: Three-hundred nineteen of the 371 critically ill adults requiring endotracheal intubation who were included in the MACMAN trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Minimal pulse oximetry value during endotracheal intubation was the primary endpoint. We also sought risk factors for pulse oximetry below 90%. Of 319 patients, 157 (49%) had bag-valve-mask, 71 (22%) noninvasive ventilation, 71 (22%) non-rebreathing mask, and 20 (7%) high-flow nasal oxygen for preoxygenation. Factors independently associated with minimal pulse oximetry value were the Simplified Acute Physiology Score II severity score (p = 0.03), baseline pulse oximetry (p < 0.001), baseline PaO2/FIO2 ratio (p = 0.02), and number of laryngoscopies (p = 0.001). The only independent predictors of pulse oximetry less than 90% were baseline pulse oximetry (odds ratio, 0.71; 95% CI, 0.64-0.79; p < 0.001) and preoxygenation device: with bag-valve-mask as the reference, odds ratios were 1.10 (95% CI, 0.25-4.92) with non-rebreathing mask, 0.10 (95% CI, 0.01-0.80) with noninvasive ventilation, and 5.75 (95% CI, 1.15-28.75) with high-flow nasal oxygen. CONCLUSIONS: Our data suggest that the main determinants of hypoxemia during endotracheal intubation may be related to critical illness severity and to preexisting hypoxemia. The differences across preoxygenation methods suggest that noninvasive ventilation may deserve preference in patients with marked hypoxemia before endotracheal intubation. Ongoing studies will provide further clarification about the optimal preoxygenation method for endotracheal intubation in critically ill patients.


Assuntos
Estado Terminal/terapia , Intubação Intratraqueal/métodos , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Insuficiência Respiratória/terapia , Adulto , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
8.
Eur J Emerg Med ; 26(1): 41-46, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28799985

RESUMO

BACKGROUND: In case of acute bacterial meningitis, a decision on the need for intensive care admission should be made within the first hour. The aim of this study was to assess the ability of a point-of-care glucometer to determine abnormal cerebrospinal fluid (CSF) glucose concentration at the bedside that contributes toward bacterial meningitis diagnosis. METHODS: We carried out a prospective study and simultaneously measured the glucose concentrations in CSF and blood using a central laboratory and a point-of-care glucometer. We compared CSF/blood glucose ratios obtained at the bedside with a glucometer versus those obtained by the central laboratory. We determined the performance characteristics of the CSF/blood glucose ratio provided by a glucometer to detect bacterial infection in the CSF immediately after CSF sampling. RESULTS: We screened 201 CSF collection procedures during the study period and included 172 samples for analysis. Acute bacterial meningitis was diagnosed in 17/172 (9.9%) of CSF samples. The median turnaround time for a point-of-care glucometer analysis was 5 (interquartile range 2-10) min versus 112 (interquartile range 86-154) min for the central laboratory (P<0.0001). The optimal cut-off of the CSF/blood glucose ratio calculated from a bedside glucometer was 0.46, with a sensitivity of 94.1% (95% confidence interval: 71.3-99.9%), a specificity of 91% (95% confidence interval: 85.3-95%), and a positive likelihood ratio of 10. CONCLUSION: A glucometer accurately detects an abnormal CSF/blood glucose ratio immediately after the lumbar puncture. This cheap point-of-care method has the potential to speed up the diagnostic process of patients with bacterial meningitis.


Assuntos
Meningites Bacterianas/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Doença Aguda , Adulto , Idoso , Glicemia , Feminino , Glucose/líquido cefalorraquidiano , Humanos , Laboratórios Hospitalares , Masculino , Meningites Bacterianas/sangue , Meningites Bacterianas/líquido cefalorraquidiano , Pessoa de Meia-Idade , Estudos Prospectivos , Punção Espinal
9.
J Aerosol Med Pulm Drug Deliv ; 32(3): 149-155, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30589607

RESUMO

Background: Although nebulizing beta 2-agonists during noninvasive ventilation (NIV) could prove helpful, this administration route has to date never been studied in unstable chronic obstructive pulmonary disease (COPD) patients. We sought to demonstrate that salbutamol could be nebulized through an NIV circuit in COPD exacerbation and improve forced expiratory volume in 1 second (FEV1) as compared with placebo. Patient and Methods: This is a bench study to determine the optimal pattern of nebulization followed by a randomized double-blind parallel-group trial comparing salbutamol and placebo aerosols delivered during NIV to 43 intensive care unit patients. Aerosols were generated by a vibrating mesh nebulizer positioned just after the Y-piece. Spirometry was performed immediately before and at several predetermined time points after nebulization. Clinical and biological safety parameters were recorded. Results: We failed to demonstrate a difference between salbutamol and placebo when changes in FEV1 were assessed immediately after nebulization (-20 vs. -35 mL, p = 0.66). However, FEV1 increased significantly from baseline to 40 minutes after the end of salbutamol nebulization, as compared with placebo (+30 vs. -50 mL, p = 0.04). Nebulization was well tolerated. Conclusion: When assessing FEV1 changes 40 minutes after the end of 5 mg salbutamol nebulization in patients undergoing NIV, we observed a slight improvement that was statistically significant compared with the changes observed with an equivalent saline volume.

10.
Ann Intensive Care ; 8(1): 128, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30570679

RESUMO

BACKGROUND: There is an absence of controlled clinical data showing bronchodilation effectiveness after nebulization via nasal high-flow therapy circuits. RESULTS: Twenty-five patients with reversible airflow obstruction received, in a randomized order: (1) 2.5 mg albuterol delivered via a jet nebulizer with a facial mask; (2) 2.5 mg albuterol delivered via a vibrating mesh nebulizer placed downstream of a nasal high-flow humidification chamber (30 L/min and 37 °C); and (3) nasal high-flow therapy without nebulization. All three conditions induced significant individual increases in forced expiratory volume in one second (FEV1) compared to baseline. The median change was similar after facial mask nebulization [+ 350 mL (+ 180; + 550); + 18% (+ 8; + 30)] and nasal high flow with nebulization [+ 330 mL (+ 140; + 390); + 16% (+ 5; + 24)], p = 0.11. However, it was significantly lower after nasal high-flow therapy without nebulization [+ 50 mL (- 10; + 220); + 3% (- 1; + 8)], p = 0.0009. FEV1 increases after facial mask and nasal high-flow nebulization as well as residual volume decreases were well correlated (p < 0.0001 and p = 0.01). Both techniques showed good agreement in terms of airflow obstruction reversibility (kappa 0.60). CONCLUSION: Albuterol vibrating mesh nebulization within a nasal high-flow circuit induces similar bronchodilation to standard facial mask jet nebulization. Beyond pharmacological bronchodilation, nasal high flow by itself may induce small but significant bronchodilation.

11.
Ann Intensive Care ; 8(1): 84, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30112650

RESUMO

BACKGROUND: The consequences of the ageing population concerning ICU hospitalisation need to be adequately described. We believe that this discussion should be disease specific. A focus on respiratory infections is of particular interest, because it is strongly associated with old age. Our objective was to assess trends in demographics over a decade among elderly patients admitted to the ICU for acute respiratory infections. METHODS: A cross-sectional study was performed between 2006 and 2015 based on hospital discharge databases in one French region (2.5 million inhabitants). Patients with acute respiratory infection were selected according to the specific ICD-10 diagnosis codes recorded, including acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and community-acquired pneumonia (CAP). We also identified comorbid conditions based on any significant ICD-10 secondary diagnoses adapted from the Charlson and Elixhauser indexes. RESULTS: A total of 98,381 hospital stays for acute respiratory infection were identified among the 3,856,785 stays over the 10-year period. The number of patients 75 y/o and younger increased 1.6-fold from 2006 to 2015, whereas the numbers of patients aged 85-89 and ≥ 90 y/o increased by 2.5- and 2.1-fold, respectively. Both CAP and AECOPD hospitalisations significantly increased for all age groups over the decade. ICU hospitalisations for respiratory infection increased 2.7-fold from 2006 to 2015 (p = 0.0002). The greatest increases in the use of ICU resources were for the 85-89 and ≥ 90 y/o groups, which corresponded to increases of 3.3- and 5.8-fold. Indeed, the proportion of patients hospitalized for respiratory infection in ICU that were elderly clearly grew during the decade: 11.3% were ≥ 85 y/o in 2006 versus 16.4% in 2015 (p < 0.0001). This increase in ICU hospitalisation rate of ageing patients was not associated with significant changes in the level of care or ICU mortality except for patients ≥ 90 y/o (for whom ICU mortality dropped from 40.9 to 22.3%, p = 0.03). CONCLUSION: We observed a substantial increase in acute respiratory infection diagnoses associated with hospitalisation between 2006 and 2015, with a growing demand for critical care services. Both the absolute number and the percentage of elderly patient ICU admissions increased over the last decade, with the greatest increases being observed for patients 85 years and older.

12.
Ann Intensive Care ; 7(1): 39, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28382598

RESUMO

PURPOSE: Data for ANCA-associated vasculitis (AAV) patients requiring intensive care are scarce. METHODS: We included 97 consecutive patients with acute AAV manifestations (new onset or relapsing disease), admitted to 18 intensive care units (ICUs) over a 10-year period (2002-2012). A group of 95 consecutive AAV patients with new onset or relapsing disease, admitted to two nephrology departments with acute vasculitis manifestations, constituted the control group. RESULTS: In the ICU group, patients predominantly showed granulomatosis with polyangiitis and proteinase-3 ANCAs. Compared with the non-ICU group, the ICU group showed comparable Birmingham vasculitis activity score and a higher frequency of heart, central nervous system and lungs involvements. Respiratory assistance, renal replacement therapy and vasopressors were required in 68.0, 56.7 and 26.8% of ICU patients, respectively. All but one patient (99%) received glucocorticoids, 85.6% received cyclophosphamide, and 49.5% had plasma exchanges as remission induction regimens. Fifteen (15.5%) patients died during the ICU stay. The following were significantly associated with ICU mortality in the univariate analysis: the need for respiratory assistance, the use of vasopressors, the occurrence of at least one infection event in ICU, cyclophosphamide treatment, sequential organ failure assessment at admission and simplified acute physiology score II. After adjustment on sequential organ failure assessment or infection, cyclophosphamide was no longer a risk factor for mortality. Despite a higher initial mortality rate of ICU patients within the first hospital stay (p < 0.0001), the long-term mortality of hospital survivors did not differ between ICU and non-ICU groups (18.6 and 20.4%, respectively, p = 0.36). Moreover, we observed no renal survival difference between groups after a 1-year follow-up (82.1 and 80.5%, p = 0.94). CONCLUSION: This study supports the idea that experiencing an ICU challenge does not impact the long-term prognosis of AAV patients.

13.
Front Immunol ; 8: 123, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28243234

RESUMO

Recent in silico studies suggested that the transcription cofactor LIM-only protein FHL2 is a major transcriptional regulator of mouse natural killer (NK) cells. However, the expression and role of FHL2 in NK cell biology are unknown. Here, we confirm that FHL2 is expressed in both mouse and human NK cells. Using FHL2-/- mice, we found that FHL2 controls NK cell development in the bone marrow and maturation in peripheral organs. To evaluate the importance of FHL2 in NK cell activation, FHL2-/- mice were infected with Streptococcus pneumoniae. FHL2-/- mice are highly susceptible to this infection. The activation of lung NK cells is altered in FHL2-/- mice, leading to decreased IFNγ production and a loss of control of bacterial burden. Collectively, our data reveal that FHL2 is a new transcription cofactor implicated in NK cell development and activation during pulmonary bacterial infection.

14.
JAMA ; 317(5): 483-493, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28118659

RESUMO

Importance: In the intensive care unit (ICU), orotracheal intubation can be associated with increased risk of complications because the patient may be acutely unstable, requiring prompt intervention, often by a practitioner with nonexpert skills. Video laryngoscopy may decrease this risk by improving glottis visualization. Objective: To determine whether video laryngoscopy increases the frequency of successful first-pass orotracheal intubation compared with direct laryngoscopy in ICU patients. Design, Setting, and Participants: Randomized clinical trial of 371 adults requiring intubation while being treated at 7 ICUs in France between May 2015 and January 2016; there was 28 days of follow-up. Interventions: Intubation using a video laryngoscope (n = 186) or direct laryngoscopy (n = 185). All patients received general anesthesia. Main Outcomes and Measures: The primary outcome was the proportion of patients with successful first-pass intubation. The secondary outcomes included time to successful intubation and mild to moderate and severe life-threatening complications. Results: Among 371 randomized patients (mean [SD] age, 62.8 [15.8] years; 136 [36.7%] women), 371 completed the trial. The proportion of patients with successful first-pass intubation did not differ significantly between the video laryngoscopy and direct laryngoscopy groups (67.7% vs 70.3%; absolute difference, -2.5% [95% CI, -11.9% to 6.9%]; P = .60). The proportion of first-attempt intubations performed by nonexperts (primarily residents, n = 290) did not differ between the groups (84.4% with video laryngoscopy vs 83.2% with direct laryngoscopy; absolute difference 1.2% [95% CI, -6.3% to 8.6%]; P = .76). The median time to successful intubation was 3 minutes (range, 2 to 4 minutes) for both video laryngoscopy and direct laryngoscopy (absolute difference, 0 [95% CI, 0 to 0]; P = .95). Video laryngoscopy was not associated with life-threatening complications (24/180 [13.3%] vs 17/179 [9.5%] for direct laryngoscopy; absolute difference, 3.8% [95% CI, -2.7% to 10.4%]; P = .25). In post hoc analysis, video laryngoscopy was associated with severe life-threatening complications (17/179 [9.5%] vs 5/179 [2.8%] for direct laryngoscopy; absolute difference, 6.7% [95% CI, 1.8% to 11.6%]; P = .01) but not with mild to moderate life-threatening complications (10/181 [5.4%] vs 14/181 [7.7%]; absolute difference, -2.3% [95% CI, -7.4% to 2.8%]; P = .37). Conclusions and Relevance: Among patients in the ICU requiring intubation, video laryngoscopy compared with direct laryngoscopy did not improve first-pass orotracheal intubation rates and was associated with higher rates of severe life-threatening complications. Further studies are needed to assess the comparative effectiveness of these 2 strategies in different clinical settings and among operators with diverse skill levels. Trial Registration: clinicaltrials.gov Identifier: NCT02413723.


Assuntos
Unidades de Terapia Intensiva , Intubação Intratraqueal/métodos , Laringoscópios , Laringoscopia/métodos , Adulto , Protocolos Clínicos , Feminino , Humanos , Análise de Intenção de Tratamento , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/estatística & dados numéricos , Laringoscopia/instrumentação , Laringoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Tamanho da Amostra , Falha de Tratamento
16.
J Am Coll Cardiol ; 68(1): 40-9, 2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27364049

RESUMO

BACKGROUND: Preliminary data suggested a clinical benefit in treating out-of-hospital cardiac arrest (OHCA) patients with a high dose of erythropoietin (Epo) analogs. OBJECTIVES: The authors aimed to evaluate the efficacy of epoetin alfa treatment on the outcome of OHCA patients in a phase 3 trial. METHODS: The authors performed a multicenter, single-blind, randomized controlled trial. Patients still comatose after a witnessed OHCA of presumed cardiac origin were eligible. In the intervention group, patients received 5 intravenous injections spaced 12 h apart during the first 48 h (40,000 units each, resulting in a maximal dose of 200,000 total units), started as soon as possible after resuscitation. In the control group, patients received standard care without Epo. The main endpoint was the proportion of patients in each group reaching level 1 on the Cerebral Performance Category (CPC) scale (survival with no or minor neurological sequelae) at day 60. Secondary endpoints included all-cause mortality rate, distribution of patients in CPC levels at different time points, and side effects. RESULTS: In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p = 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p = 0.01). CONCLUSIONS: In patients resuscitated from an OHCA of presumed cardiac cause, early administration of erythropoietin plus standard therapy did not confer a benefit, and was associated with a higher complication rate. (High Dose of Erythropoietin Analogue After Cardiac Arrest [Epo-ACR-02]; NCT00999583).


Assuntos
Epoetina alfa/administração & dosagem , Hematínicos/administração & dosagem , Parada Cardíaca Extra-Hospitalar/tratamento farmacológico , Idoso , Intervenção Médica Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego
17.
Ann Intensive Care ; 6(1): 57, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27342259

RESUMO

BACKGROUND: Point-of-care testing (POCT) systems enable a wide range of tests to be rapidly performed at the bedside and have attracted increasing interest in the intensive care unit (ICU). However, previous studies comparing the concordance of POCT with central laboratory testing have reported divergent findings. Most reported studies on POCT reliability have focused on analyzer performance rather than the preanalytical phase. The aim of this study was to assess the reliability of results provided by point-of-care analyzers according to the organization of the care units and the preanalytical process. METHODS: In three adult critical care units, 491 paired blood samples were analyzed for hemoglobin, potassium, and sodium concentrations by blood gas analyzers (identical reference) and the central laboratory. The clinical significance of agreement was assessed using Bland-Altman plots. A quality improvement program was then implemented to improve the preanalytical POCT process for one ICU where there was poor agreement. A second comparison was performed on 278 paired blood samples in this unit. RESULTS: Biases were clinically nonsignificant for potassium and sodium concentrations for all tested critical care units, relative to the reference method. However, biases [limits of agreements] for hemoglobin analyses were clearly affected by the preanalytical process: -3 [-6; 1] g/L in the operating room, -5 [-28; 17] g/L in a 10-bed ICU, and -19 [-64; 27] g/L in a 37-bed ICU. The quality approach was implemented in the 37-bed ICU and led to corrective actions that: (1) reduced the time for the POCT preanalytical phase; (2) implemented a checklist to validate the preanalytical conditions; (3) used technical innovations. The improvement of the preanalytical process resulted in a substantial decrease of the bias for hemoglobin concentration measurements: -3 [-10; 5] g/L in the 37-bed ICU. CONCLUSION: We clearly demonstrate that an identical analyzer can provide results of varying quality depending on the local constraints of the ICUs. We demonstrate that quality management focused on the preanalytical process and performed by the partners involved in the POCT can overcome these issues.

18.
Scand J Trauma Resusc Emerg Med ; 23: 26, 2015 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-25882712

RESUMO

BACKGROUND: Meta-analyses of nonrandomized studies have provided conflicting data on therapeutic hypothermia, or targeted temperature management (TTM), at 33°C in patients successfully resuscitated after nonshockable cardiac arrest. Nevertheless, the latest recommendations issued by the International Liaison Committee on Resuscitation and by the European Resuscitation Council recommend therapeutic hypothermia. New data are available on the adverse effects of therapeutic hypothermia, notably infectious complications. The risk/benefit ratio of therapeutic hypothermia after nonshockable cardiac arrest is unclear. METHODS: HYPERION is a multicenter (22 French ICUs) trial with blinded outcome assessment in which 584 patients with successfully resuscitated nonshockable cardiac arrest are allocated at random to either TTM between 32.5 and 33.5°C (therapeutic hypothermia) or TTM between 36.5 and 37.5°C (therapeutic normothermia) for 24 hours. Both groups are managed with therapeutic normothermia for the next 24 hours. TTM is achieved using locally available equipment. The primary outcome is day-90 neurological status assessed by the Cerebral Performance Categories (CPC) Scale with dichotomization of the results (1 + 2 versus 3 + 4 + 5). The primary outcome is assessed by a blinded psychologist during a semi-structured telephone interview of the patient or next of kin. Secondary outcomes are day-90 mortality, hospital mortality, severe adverse events, infections, and neurocognitive performance. The planned sample size of 584 patients will enable us to detect a 9% absolute difference in day-90 neurological status with 80% power, assuming a 14% event rate in the control group and a two-sided Type 1 error rate of 4.9%. Two interim analyses will be performed, after inclusion of 200 and 400 patients, respectively. DISCUSSION: The HYPERION trial is a multicenter, randomized, controlled, assessor-blinded, superiority trial that may provide an answer to an issue of everyday relevance, namely, whether TTM is beneficial in comatose patients resuscitated after nonshockable cardiac arrest. Furthermore, it will provide new data on the tolerance and adverse events (especially infectious complications) of TTM at 32.5-33.5°C. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01994772 .


Assuntos
Reanimação Cardiopulmonar/métodos , Hipotermia Induzida/métodos , Doenças do Sistema Nervoso/prevenção & controle , Parada Cardíaca Extra-Hospitalar/terapia , França , Escala de Coma de Glasgow , Humanos , Projetos de Pesquisa , Resultado do Tratamento
19.
Crit Care ; 19: 153, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25888011

RESUMO

INTRODUCTION: In a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity. METHODS: We looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10(-5) digit with no replacement). RESULTS: A total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality. CONCLUSION: In a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01002482 . Registered 26 October 2009.


Assuntos
Mortalidade Hospitalar , Hipoglicemia/mortalidade , Unidades de Terapia Intensiva , Índice de Gravidade de Doença , Glicemia/análise , Quimioterapia Assistida por Computador , Feminino , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estresse Fisiológico/fisiologia
20.
Intensive Care Med ; 41(2): 248-56, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25447804

RESUMO

PURPOSE: To describe the current practices of volume expansion in French intensive care units (ICU). METHODS: In 19 ICUs, we prospectively observed the prescription and monitoring practices of volume expansion in consecutive adult patients with shock [sustained hypotension and/or need of vasopressor therapy, associated with at least tachycardia and/or sign (s) of hypoperfusion]. Patients were included at the time of prescription of the first fluid bolus (FB). Thereafter, all the FBs administered during the 96 h following shock onset were surveyed. An FB was defined as an intravenous bolus of at least 100 ml of a blood volume expander intended to rapidly improve the patient's circulatory condition. RESULTS: We included 777 patients [age: 63 ± 15 years; female gender: 274 (35 %); simplified acute physiology score II: 55.9 ± 20.6; ICU length of stay: 6 days (interquartile range (IQR) 3-13); ICU mortality: 32.8 %] and surveyed 2,694 FBs. At enrolment mean arterial pressure was 63 mmHg (IQR 55-71). The most frequent triggers of FB were hypotension, low urine output, tachycardia, skin mottling and hyperlactataemia. Amount of fluid given at each FB was highly variable between centres. Crystalloids were used in 91 % (2,394/2,635) and synthetic colloids in 3.3 % (87/2,635) of FBs. Overall, clinicians used any kind of haemodynamic assessment (central venous pressure measurement, predictive indices of fluid responsiveness, echocardiography, cardiac output monitoring or a combination of these) in 23.6 % (635/2,694) of all FBs surveyed, with an important between-centre heterogeneity. CONCLUSIONS: High between-centre variability characterised all the aspects of FB prescription and monitoring, but overall haemodynamic exploration to help guide and monitor FB was infrequent.


Assuntos
Substitutos do Plasma/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Choque/tratamento farmacológico , Adulto , Idoso , Feminino , França , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Substitutos do Plasma/administração & dosagem , Estudos Prospectivos
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