Abstract Background Although epinephrine is essential for successful return of spontaneous circulation (ROSC), the influence of this drug on recovery during the post–cardiac arrest phase is ...debatable. Objectives This study sought to investigate the relationship between pre-hospital use of epinephrine and functional survival among patients with out-of-hospital cardiac arrest (OHCA) who achieved successful ROSC. Methods We included all patients with OHCA who achieved successful ROSC admitted to a cardiac arrest center from January 2000 to August 2012. Use of epinephrine was coded as yes/no and by dose (none, 1 mg, 2 to 5 mg, >5 mg). A favorable discharge outcome was coded using a Cerebral Performance Category 1 or 2. Analyses incorporated multivariable logistic regression, propensity scoring, and matching methods. Results Of the 1,556 eligible patients, 1,134 (73%) received epinephrine; 194 (17%) of these patients had a good outcome versus 255 of 422 patients (63%) in the nontreated group (p < 0.001). This adverse association of epinephrine was observed regardless of length of resuscitation or in-hospital interventions performed. Compared with patients who did not receive epinephrine, the adjusted odds ratio of intact survival was 0.48 (95% confidence interval CI: 0.27 to 0.84) for 1 mg of epinephrine, 0.30 (95% CI: 0.20 to 0.47) for 2 to 5 mg of epinephrine, and 0.23 (95% CI: 0.14 to 0.37) for >5 mg of epinephrine. Delayed administration of epinephrine was associated with worse outcome. Conclusions In this large cohort of patients who achieved ROSC, pre-hospital use of epinephrine was consistently associated with a lower chance of survival, an association that showed a dose effect and persisted despite post-resuscitation interventions. These findings suggest that additional studies to determine if and how epinephrine may provide long-term functional survival benefit are needed.
Purpose
Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including
Pseudomonas aeruginosa
(PA) remains uncertain. We ...aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).
Methods
We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.
Results
The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (
n
= 186), the percentage of patients who reached the composite endpoint was 25.5% (
N
= 25/98) in the 15-day group versus 35.2% (
N
= 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) −1.9%–21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.
Conclusions
Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.
The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator‑associated pneumonia (PA-VAP) remain debated. The ...aim of this study was to evaluate whether a combination antibiotic therapy is superior to a monotherapy in patients with PA-VAP in terms of reduction in recurrence and death, based on the 186 patients included in the iDIAPASON trial, a multicenter, randomized controlled trial comparing 8 versus 15 days of antibiotic therapy for PA-VAP.
Patients with PA-VAP randomized in the iDIAPASON trial (short-duration-8 days vs. long-duration-15 days) and who received appropriate antibiotic therapy were eligible in the present study. The main objective is to compare mortality at day 90 according to the antibiotic therapy received by the patient: monotherapy versus combination therapy. The primary outcome was the mortality rate at day 90. The primary outcome was compared between groups using a Chi-square test. Time from appropriate antibiotic therapy to death in ICU or to censure at day 90 was represented using Kaplan-Meier survival curves and compared between groups using a Log-rank test.
A total of 169 patients were included in the analysis. The median duration of appropriate antibiotic therapy was 14 days. At day 90, among 37 patients (21.9%) who died, 17 received monotherapy and 20 received a combination therapy (P = 0.180). Monotherapy and combination antibiotic therapy were similar for the recurrence rate of VAP, the number of extra pulmonary infections, or the acquisition of multidrug-resistant (MDR) bacteria during the ICU stay. Patients in combination therapy were exposed to mechanical ventilation for 28 ± 12 days, as compared with 23 ± 11 days for those receiving monotherapy (P = 0.0243). Results remain similar after adjustment for randomization arm of iDIAPASON trial and SOFA score at ICU admission.
Except longer durations of antibiotic therapy and mechanical ventilation, potentially related to increased difficulty in achieving clinical cure, the patients in the combination therapy group had similar outcomes to those in the monotherapy group.
NCT02634411 , Registered 15 December 2015.
Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this ...study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes.
This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up.
A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80-6.59; p < 0.001), age, McCabe score, haematological cancers, SAPS II, and renal replacement therapy were independently associated with 1-year mortality. This difference was driven by mortality during the first 90 days (28 vs. 16%, p = 0.010) but not between 90 days and 1 year (7 vs. 6%, p = 0.591), at which point only the McCabe score was independently associated with mortality. Morphological phenotypes had no impact on patient-reported outcomes.
Lung morphologies reflect the acute phase of ARDS and its short-term impact but not long-term outcomes, which seem only influenced by comorbidities.
NCT02149589; May 29, 2014.
IntroductionVentilator-associated pneumonia (VAP) remains the leading cause of infections treated in the intensive care units (ICU). In a personalised care approach, we hypothesise that the duration ...of treatment of VAP can be reduced in function of the response to treatment.Methods and analysisThe Antimicrobial Stewardship for Ventilator-Associated Pneumonia in Intensive Care (ASPIC) trial is a pragmatic national multicentre, phase III, non-inferiority, comparative randomised (1:1) single-blinded clinical trial. Five hundred and ninety adult patients hospitalised in 24 French ICU with a microbiologically confirmed first episode of VAP that received appropriate empirical antibiotic therapy will be included. They will be randomly allocated to standard management with duration of appropriate antibiotic fixed for 7 days according to international guidelines or antimicrobial stewardship based on daily clinical assessment of clinical cure. The assessment of clinical cure will be repeated daily until at least three criteria of clinical cure are met, allowing the discontinuation of antibiotic therapy in experimental group. The primary endpoint is a composite endpoint combining of all-cause mortality measured at day 28, treatment failure or new episode of microbiologically confirmed VAP until day 28.The aim of the study is to demonstrate that a strategy to reduce the duration of antibiotic therapy for VAP based on clinical assessment is safe could lead to changes in practice as part of a personalised therapeutic approach, by reducing exposure to antibiotics and their side effects.Ethics and disseminationThe ASPIC trial has been approved by the French regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM; EUDRACT number 2021-002197-78, 19 August 2021) and an independent ethics committee the Comité de Protection des Personnes Ile-de-France III (CNRIPH : 21.03.25.60729, 10 October 2021) for the study protocol (version ASPIC−1.3; 03 September 2021) for all study centres. Participant recruitment is scheduled to begin in 2022. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT05124977.
IntroductionIncidence of delirium after cardiac surgery remains high and delirium has a significant burden on short-term and long-term outcomes. Multiple causes can trigger delirium occurence, and it ...has been hypothesised that sleep disturbances can be one of them. Preserving the circadian rhythm with overnight infusion of low-dose dexmedetomidine has been shown to lower the occurrence of delirium in older patients after non-cardiac surgery. However, these results remain controversial. The aim of this study was to demonstrate the usefulness of sleep induction by overnight infusion of dexmedetomidine to prevent delirium after cardiac surgery.Methods and analysisDexmedetomidine after Cardiac Surgery for Prevention of Delirium is an investigator-initiated, randomised, placebo-controlled, parallel, multicentre, double-blinded trial. Nine centres in France will participate in the study. Patients aged 65 years or older and undergoing cardiac surgery will be enrolled in the study. The intervention starts on day 0 (the day of surgery) until intensive care unit (ICU) discharge; the treatment is administered from 20:00 to 08:00 on the next day. Infusion rate is modified by the treating nurse or the clinician with an objective of Richmond Agitation and Sedation Scale score from −1 to +1. The primary outcome is delirium occurrence evaluated with confusion assessment method for the ICU two times per day during 7 days following surgery. Secondary outcomes include incidence of agitation related events, self-evaluated quality of sleep, cognitive evaluation 3 months after surgery and quality of life 3 months after surgery. The sample size is 348.Ethics and disseminationThe study was approved for all participating centers by the French Central Ethics Committee (Comité de Protection des Personnes Ile de France VI, registration number 2018-000850-22). The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03477344.
Marquet et al discuss the case study of a 65-year-old patient with a history of arterial hypertension, morbid obesity, atrial fibrillation with no systemic embolic event, and peripheral artery ...disease was admitted into the ICU after an emergency coronary bypass surgery following ST-segment elevation myocardial infarction. Failure to wean from cardiopulmonary bypass led to mechanical support by veno-arterio-venous extracorporeal membrane oxygenation (ECMO) for 10 days and veno-venous ECMO for 10 more days. In the postoperative period, he developed acute kidney infection, requiring renal replacement therapy, and ventilator-associated-pneumonia with septic shock.
Background
Sensitized patients, i.e. recipients with preformed donor-specific HLA antibodies (pfDSA), are at high-risk of developing antibody-mediated rejections (AMR) and dying after heart ...transplantation (HTx). Perioperative desensitization procedures are associated with better outcomes but can cause sensitization, which may influence their efficacy.
Methods
In sensitized patients (pfDSA>1000 mean immunofluorescence (MFI) units), we assessed the effect of perioperative desensitization by comparing treated patients to a historical control cohort. Multivariable survival analyses were performed on the time to main outcome, a composite of death and biopsy-proven AMR with 5-year follow-up.
Results
The study included 68 patients: 31 control and 37 treated patients. There was no difference in preoperative variables between the two groups, including cumulative pfDSA 4026 (1788;8725)
vs
4560 (3162;13392) MFI units,
p
=0.28. The cause of sensitization was pregnancy in 24/68, 35.3%, transfusion in 61/68, 89.7%, and previous HTx in 4/68, 5.9% patients. Multivariable analysis yielded significant protective association between desensitization and events (adjusted (adj.) hazard ratio (HR)=0.44 (95% confidence interval (95CI)=0.25-0.79),
p
=0.006) and deleterious association between cumulative pfDSA and events per 1000-MFI increase, adj.HR=1.028 (1.002-1.053), p=0.031. There was a sex-difference in the efficacy of desensitization: in men (n=35), the benefit was significant unadj.HR=0.33 (95CI=0.14-0.78); p=0.01, but not in women (n=33) unadj.HR=0.52 (0.23-1.17), p=0.11. In terms of the number of patients treated, in men, 2.1 of patients that were treated prevented 1 event, while in women, 3.1 required treatment to prevent 1 event.
Conclusion
Perioperative desensitization was associated with fewer AMR and deaths after HTx, and efficacy was more pronounced in men than women.
Aerosolised antibiotics in critical care Rello, Jordi; Bouglé, Adrien; Rouby, Jean-Jacques
Intensive care medicine,
07/2023, Letnik:
49, Številka:
7
Journal Article
Recenzirano
Aerosol therapy in mechanically ventilated patients delivers drug particles driven by inspiratory gases. Bronchodilators, steroids, mucolytics, polymyxins and aminoglycosides are the main ...prescriptions 1. Lack of knowledge among practitioners is common regarding diferences between nebulisation, technique and strategies of implementation in patients with ventilator-associated pneumonia (VAP) 1. Te part of the respiratory system to which aerosolised particles are intended influences aerosol effectiveness.
Purpose
Postoperative pain after cardiac surgery, exacerbated by cough and sternal mobilization, limits clearance of bronchopulmonary secretions and may predispose to postoperative pneumonia. In this ...study, we tested the ability of local anesthetic continuous wound infusion to prevent pneumonia after cardiac surgery with sternotomy and cardiopulmonary bypass (CPB) owing to better analgesia and bronchopulmonary drainage.
Methods
In this randomized, double-blind, placebo-controlled trial conducted in five academic centers, patients undergoing cardiac surgery with sternotomy and CPB were enrolled from February 2012 until November 2014, and were followed over 30 days. Patients were assigned to a 48-h infusion (10 ml h
−1
) of
l
-bupivacaine (12.5 mg h
−1
) or placebo (saline) via a pre-sternal multiperforated catheter. Anesthesia and analgesia protocols were standardized. The primary end point was the incidence of pneumonia during the study period, i.e., until hospital discharge or 30 days. We hypothesized a 30% reduction in the incidence of pneumonia.
Results
Among 1493 randomized patients, 1439 completed the trial. Pneumonia occurred in 36/746 patients (4.9%) in the
l
-bupivacaine group and in 42/739 patients (5.7%) in the placebo group (absolute risk difference taking into account center and baseline risk of postoperative pneumonia, − 1.3% 95% CI − 3.4; 0.8
P
= 0.22). In the predefined subgroup of patients at high risk,
l
-bupivacaine decreased the incidence of pneumonia (absolute risk difference, − 5.6% 95% CI − 10.0; − 1.1,
P
= 0.01).
Conclusions
After cardiac surgery with sternotomy, continuous wound infusion of
l
-bupivacaine failed to decrease the incidence of pneumonia. These findings do not support the use of local anesthetic continuous wound infusion in this indication. Further study should investigate its effect in high-risk patients.
Trial registration
EudraCT Number: 2011-003292-10; Clinicaltrials.gov Identifier: NCT01648777.
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