Early antibiotic therapy is associated with a lower probability of successful liberation from mechanical ventilation in patients with severe acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: While antibiotic therapy is advocated to improve outcomes in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) whenever mechanical ventilation is required, the evidence relies on small studies carried out before the era of widespread antibiotic resistance. Furthermore, the impact of systematic antibiotic therapy on successful weaning from mechanical ventilation was never investigated accounting for the competitive risk of death. The aim of the study was to assess whether early antibiotic therapy (eABT) increases successful mechanical ventilation weaning probability as compared to no eABT, in patients with AECOPD without pneumoniae, using multivariate competitive risk regression. METHODS: Retrospective analysis of patients admitted in 2 intensive care units (ICU) from 2012 to 2020 for AECOPD without pneumonia and requiring mechanical ventilation. eABT was defined as any anti-bacterial chemotherapy introduced during the first 24 h after ICU admission. The primary outcomes were the adjusted subdistribution hazard ratio (SHR) of the probability of being successfully weaned from mechanical ventilation (i.e. non-invasive and invasive ventilation) according to eABT status and accounting for the competitive risk of death. RESULTS: Three hundred and ninety-one patients were included, of whom 66% received eABT. eABT was associated with a lower probability of successful liberation from mechanical ventilation when accounting for the competing risk of death in multivariate analyses (SHR 0.71 [95% confidence interval, 0.57-0.89], p < 0.01), after adjustment with covariates of disease severity. This association was present in all subgroups except in patients under invasive mechanical ventilation on ICU day-1, in patients with ICU day-1 worst PaCO2 > 74 torr (median value) and in patients with a documented bacterial bronchitis at ICU admission. Ventilator-free days at day 28, ICU-free days at day 28 and invasive mechanical ventilation-free days at day 28, were significantly lower in the eABT group, while there was no significant difference in mortality at day 28 between patients who received eABT and those who did not. CONCLUSIONS: eABT was independently associated with a lower probability of being successfully weaned from mechanical ventilation, suggesting that the clinician decision to overrule systematic administration of eABT was not associated with a detectable harm in AECOPD ICU patients without pneumonia.

Comparison of pleural and esophageal pressure in supine and prone positions in a porcine model of acute respiratory distress syndrome.

Patients with moderate to severe acute respiratory distress syndrome (ARDS) benefit from prone positioning. Although the accuracy of esophageal pressure (Pes) to estimate regional pleural pressure (Ppl) has previously been assessed in the supine position, such data are not available in the prone position in ARDS. In six anesthetized, paralyzed, and mechanically ventilated female pigs, we measured Pes and Ppl into dorsal and ventral parts of the right pleural cavity. Airway pressure (Paw) and flow were measured at the airway opening. Severe ARDS [arterial partial pressure of oxygen ([Formula: see text])/fraction of inspired oxygen ([Formula: see text]) < 100 mmHg at positive end-expiratory pressure (PEEP) of 5 cmH2O] was induced by surfactant depletion. In supine and prone positions assigned in a random order, PEEP was set to 20, 15, 10, and 5 cmH2O and static end-expiratory chest wall pressures were measured from Pes (PEEPtot,es) and dorsal (PEEPtot,PplD) and ventral (PEEPtot,PplV) Ppl. The magnitude of the difference between PEEPtot,es and PEEPtot,PplD was similar in each position [-3.6 cmH2O in supine vs. -3.8 cmH2O in prone at PEEP 20 cmH2O (PEEP 20)]. The difference between PEEPtot,es and PEEPtot,PplV became narrower in the prone position (-8.3 cmH2O supine vs. -3.0 cmH2O prone at PEEP 20). PEEPtot,PplV was overestimated by Pes in the prone position at higher pressures. The median (1st-3rd quartiles) dorsal-to-ventral Ppl gradient was 4.4 (2.4-6.8) cmH2O in the supine position and -1.5 (-3.5 to +1.1) cmH2O in the prone position (P < 0.0001) and marginally influenced by PEEP (P = 0.058). Prone position narrowed end-expiratory dorsal-to-ventral Ppl vertical gradient, likely because of a more even distribution of mechanical forces over the chest wall.NEW & NOTEWORTHY In a porcine model of acute respiratory distress syndrome, we found that static end-expiratory esophageal pressure did not change significantly in prone position compared with supine position at any positive end-expiratory pressure (PEEP) tested between 5 and 20 cmH2O. Prone position was associated with an increased ventral pleural pressure and reduced end-expiratory dorsal-to-ventral pleural pressure (Ppl) vertical gradient, likely due to a more even distribution of mechanical forces over the chest wall.

Management of severe imported malaria in adults.

Severe malaria accounts for approximately 10% of all cases of imported malaria in France; cases are mainly due to Plasmodium falciparum, while other Plasmodium species are possible but uncommon (P. vivax, P. knowlesi, P. malariae, and P. ovale). On the basis of WHO criteria for endemic areas, the French criteria defining severe imported malaria in adults have been progressively adapted to the European healthcare level. Management of severe imported malaria is a diagnostic and treatment emergency and must be initially conducted in the intensive care unit. Anti-infective treatment is now based on intravenous artesunate, which must be available in every hospital of the country likely to receive severe imported malaria patients. Intravenous quinine is thus used as a second-line treatment and is restricted to limited indications. Critical care management of organ failure is essential, particularly in patients presenting with very severe malaria. To date, no adjunctive therapy (including exchange transfusion) has demonstrated clear beneficial effects.

Reliability of gastric suctioning compared with ultrasound assessment of residual gastric volume: a prospective multicentre cohort study.

We aimed to compare the reliability of aspiration via a nasogastric tube with ultrasound for assessment of residual gastric volume. Sixty-one adult patients who were mechanically ventilated and received continuous enteral feeding through a nasogastric tube for > 48 h were included. A first qualitative and quantitative ultrasound examination of the gastric antrum was followed by gastric suctioning, performed by an operator blinded to the result of the ultrasound examination. A second ultrasound examination was performed thereafter, followed by re-injection of the aspirated gastric contents (≤ 250 ml) into the stomach. A third ultrasound assessment was then immediately performed. If the suctioned volume was ≥ 250 ml, 250 mg erythromycin was infused over 30 min. A fourth ultrasound was performed 90 min after the third. Sixty (98%) patients had a qualitatively assessed full stomach at first ultrasound examination vs. 52 (85%) after gastric suctioning (p = 0.016). The calculated gastric volume significantly decreased after gastric suctioning, without a significant decrease in the number of patients with volume ≥ 250 ml. Four of the nine patients with calculated gastric volume ≥ 250 ml had vomiting within the last 24 h (p = 0.013). The antral cross-sectional area significantly decreased between the third and the fourth ultrasound examination (p = 0.015). Erythromycin infusion did not make a significant difference to gastric volume (n = 10). Our results demonstrate that gastric suctioning is not a reliable tool for monitoring residual gastric volume. Gastric ultrasound is a feasible and promising tool for gastric volume monitoring in clinical practice.

Functional outcomes in adult patients with herpes simplex encephalitis admitted to the ICU: a multicenter cohort study.

PURPOSE: We aimed to study the association of body temperature and other admission factors with outcomes of herpes simplex encephalitis (HSE) adult patients requiring ICU admission. METHODS: We conducted a retrospective multicenter study on patients diagnosed with HSE in 47 ICUs in France, between 2007 and 2017. Fever was defined as a body temperature higher or equal to 38.3 °C. Multivariate logistic regression analysis was used to identify factors associated with poor outcome at 90 days, defined by a score of 3-6 (indicating moderate-to-severe disability or death) on the modified Rankin scale. RESULTS: Overall, 259 patients with a score on the Glasgow coma scale of 9 (6-12) and a body temperature of 38.7 (38.1-39.2) °C at admission were studied. At 90 days, 185 (71%) patients had a poor outcome, including 44 (17%) deaths. After adjusting for age, fever (OR = 2.21; 95% CI 1.18-4.16), mechanical ventilation (OR = 2.21; 95% CI 1.21-4.03), and MRI brain lesions > 3 lobes (OR = 3.04; 95% CI 1.35-6.81) were independently associated with poor outcome. By contrast, a direct ICU admission, as compared to initial admission to the hospital wards (i.e., indirect ICU admission), was protective (OR = 0.52; 95% CI 0.28-0.95). Sensitivity analyses performed after adjustment for functional status before admission and reason for ICU admission yielded similar results. CONCLUSIONS: In HSE adult patients requiring ICU admission, several admission factors are associated with an increased risk of poor functional outcome. The identification of potentially modifiable factors, namely, elevated admission body temperature and indirect ICU admission, provides an opportunity for testing further intervention strategies.

Correction to: Functional outcomes in adult patients with herpes simplex encephalitis admitted to the ICU: a multicenter cohort study.

The original article unfortunately contained a mistake. Due to technical problems the study group was not tagged correctly. Please find the correct tagging down below. We apologize for the mistake.

ICU survival and need of renal replacement therapy with respect to AKI duration in critically ill patients.

BACKGROUND: Transient and persistent acute kidney injury (AKI) could share similar physiopathological mechanisms. The objective of our study was to assess prognostic impact of AKI duration on ICU mortality. DESIGN: Retrospective analysis of a prospective database via cause-specific model, with 28-day ICU mortality as primary end point, considering discharge alive as a competing event and taking into account time-dependent nature of renal recovery. Renal recovery was defined as a decrease of at least one KDIGO class compared to the previous day. SETTING: 23 French ICUs. PATIENTS: Patients of a French multicentric observational cohort were included if they suffered from AKI at ICU admission between 1996 and 2015. INTERVENTION: None. RESULTS: A total of 5242 patients were included. Initial severity according to KDIGO creatinine definition was AKI stage 1 for 2458 patients (46.89%), AKI stage 2 for 1181 (22.53%) and AKI stage 3 for 1603 (30.58%). Crude 28-day ICU mortality according to AKI severity was 22.74% (n = 559), 27.69% (n = 327) and 26.26% (n = 421), respectively. Renal recovery was experienced by 3085 patients (58.85%), and its rate was significantly different between AKI severity stages (P < 0.01). Twenty-eight-day ICU mortality was independently lower in patients experiencing renal recovery [CSHR 0.54 (95% CI 0.46-0.63), P < 0.01]. Lastly, RRT requirement was strongly associated with persistent AKI whichever threshold was chosen between day 2 and 7 to delineate transient from persistent AKI. CONCLUSIONS: Short-term renal recovery, according to several definitions, was independently associated with higher mortality and RRT requirement. Moreover, distinction between transient and persistent AKI is consequently a clinically relevant surrogate outcome variable for diagnostic testing in critically ill patients.

Severe atypical pneumonia in critically ill patients: a retrospective multicenter study.

BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients could require intensive care unit (ICU) admission for acute respiratory failure. METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven atypical pneumonia were retrospectively described. Patients with MP were compared to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A total of 104 patients were included, 71 men and 33 women, with a median age of 56 [44-67] years. MP was the causative agent for 76 (73%) patients and CP for 28 (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%] patients). Median number of involved quadrants on chest X-ray was 2 [1-4], with alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra-pulmonary manifestations were present in 34 (33%) patients. Mechanical ventilation was required for 75 (72%) patients and vasopressors for 41 (39%) patients. ICU length of stay was 16.5 [9.5-30.5] days, and 11 (11%) patients died in the ICU. Compared with SP patients, MP patients had more extensive interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6 (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at admission could discriminate MP and SP. MP was more often associated with hemolytic anemia, abdominal manifestations, and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial pneumonia requiring ICU admission, mortality was 11%. The comparison with SP pneumonia identified clinical, laboratory, and radiographic features that may suggest MP or CP pneumonia.

A systematic review of interventions and performance measures for antifungal stewardship programmes.

Objectives: Antifungal resistance is a significant and emerging threat. Stewardship programmes (SPs) have been proposed as an opportunity to optimize antifungal use. While examples of antifungal SP implementation have been recently described, there is yet to be an overview of interventions and their impacts on performance measures. Methods: We systematically reviewed published articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses check-list 2009. MEDLINE was searched using the term 'antifungal stewardship' on 15 February 2017. Eligible studies were those that described an antifungal SP and included an intervention and an evaluation of performance measures. Results: A total of 97 studies were identified and 14 were included. Only five studies reported an antifungal stewardship team composed of all the recommended members. The main intervention was the formulation of recommendations to change treatment (12 of 14). The main performance measure collected was antifungal consumption (10 of 14), followed by antifungal expenditure (7 of 14), adherence to therapeutic advice (4 of 14) and impact on mortality (4 of 14). Antifungal consumption was reduced by 11.8% to 71% and antifungal expenditure by as much as 50%. Adherence to therapeutic advice ranged from 40% to 88%, whereas antifungal SPs had no impact on mortality. Conclusions: All antifungal SPs had an impact, in particular on antifungal consumption and antifungal expenditure. Active intervention including a review of prescriptions seems to have more impact than implementation of treatment guidelines only. According to available published studies, antifungal consumption appears to be the most achievable performance measure to evaluate the impact of an antifungal SP.

An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital.

PURPOSE: The Berlin definition for acute respiratory distress syndrome (ARDS) is a new proposal for changing the American-European consensus definition but has not been assessed prospectively as yet. In the present study, we aimed to determine (1) the prevalence and incidence of ARDS with both definitions, and (2) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition. METHODS: We performed a 6-month prospective observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon, France, from March to September 2012. Patients under invasive or noninvasive mechanical ventilation, with PaO2/FiO2 <300 mmHg regardless of the positive end-expiratory pressure (PEEP) level, and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge. Patients with cardiogenic pulmonary edema were excluded. Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria. The complete data set was measured at the time of inclusion. Patient outcome was measured at day 28 after inclusion. RESULTS: During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria. Among them, 18 (6.5 %) did not comply with the Berlin criterion PEEP ≥ 5 cmH2O and 20 (7.2 %) had PaO2/FiO2 ratio ≤200 while on noninvasive ventilation. By using the Berlin definition in the remaining 240 patients (n = 42 mild, n = 123 moderate, n = 75 severe), the overall prevalence was 6.85 % and it was 1.20, 3.51, and 2.14 % for mild, moderate, and severe ARDS, respectively (P > 0.05 between the three groups). The incidence of ARDS amounted to 32 per 100,000 population per year, with values for mild, moderate, and severe ARDS of 5.6, 16.3, and 10 per 100,000 population per year, respectively (P < 0.05 between the three groups). The 28-day mortality was 35.0 %. It amounted to 30.9 % in mild, 27.9 % in moderate, and 49.3 % in severe categories (P < 0.01 between mild or moderate and severe, P = 0.70 between mild and moderate). In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28. CONCLUSIONS: The present study did not validate the Berlin definition of ARDS. Neither the stratification by severity nor the PaO2/FiO2 at study entry was independently associated with mortality.

Benefits of smart pumps for automated changeovers of vasoactive drug infusion pumps: a quasi-experimental study.

BACKGROUND: Manual changeover of vasoactive drug infusion pumps (CVIP) frequently lead to haemodynamic instability. Some of the newest smart pumps allow automated CVIP. The aim of this study was to compare automated CVIP with manual 'Quick Change' relays. METHODS: We performed a prospective, quasi-experimental study, in a university-affiliated intensive care unit (ICU). All adult patients receiving continuous i.v. infusion of vasoactive drugs were included. CVIP were successively performed manually (Phase 1) and automatically (Phase 2) during two 6-month periods. The primary endpoint was the frequency of haemodynamic incidents related to the relays, which were defined as variations of mean arterial pressure >15 mm Hg or heart rate >15 bpm. The secondary endpoints were the nursing time dedicated to relays and the number of interruptions in care because of CVIP. A multivariate mixed effects logistic regression was fitted for analytic analysis. RESULTS: We studied 1329 relays (Phase 1: 681, Phase 2: 648) from 133 patients (Phase 1: 63, Phase 2: 70). Incidents related to CVIP decreased from 137 (20%) in Phase 1 to 73 (11%) in Phase 2 (P<0.001). Automated relays were independently associated with a 49% risk reduction of CVIP-induced incidents (adjusted OR=0.51, 95% confidence interval 0.34-0.77, P=0.001). Time dedicated to the relays and the number of interruptions in care to manage CVIP were also significantly reduced with automated relays vs manual relays (P=0.001). CONCLUSIONS: These results demonstrate the benefits of automated CVIP using smart pumps in limiting the frequency of haemodynamic incidents related to relays and in reducing the nursing workload.

[Evaluation of the management of COPD exacerbations: an audit in French emergency services]. / Prise en charge des exacerbations de BPCO : audit de pratique aux urgences.

INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (COPD) patients are major events in the history of this chronic respiratory disease. Their management in French emergency services is unknown, although national guidelines exist. METHODS: This is a descriptive audit study, over a 10 weeks period (12/01-22/03/2009), of the management of COPD exacerbations in the RESUVal (Réseau des Urgences de la Vallée du Rhône, France) network emergency departments. RESULTS: The enrollement of 16 emergency units allowed the analysis of 221 exacerbations of COPD. Measurement of respiratory rate and description of the sputum were mentioned in only 99 (45%) medical records. The rest of the initial assessment was generally satisfactory. Regarding the therapeutic management, 215 (97%) patients received oxygen, beta-2-agonist aerosols were administrated for 209 (95%) patients and anticholinergic aerosols were used for 176 (80%) patients. A systemic corticosteroid and antibiotics were respectively prescribed for 116 (52%) and 123 (56%) patients. Non-invasive ventilation (NIV) was used in only 59% of patients presenting a pH<7.35. CONCLUSIONS: These findings demonstrate that management of exacerbations of COPD could be improved through systematic patients' respiratory rate and sputum characteristics recording or NIV utilization reinforcement.

[Description of patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit and identification of severity risk factors]. / Description des cas confirmés de grippe A(H1N1)pdm09 admis en réanimation et identification des facteurs de gravité

OBJECTIVE: The authors had for objective to describe patients with confirmed influenza A(H1N1)pdm09 admitted to an intensive care unit (ICU) in a university hospital and to identify risk factors correlated with the severity of the disease. DESIGN: A prospective study was conducted in an university hospital during the A(H1N1)pdm09 influenza pandemic. Severe laboratory confirmed cases (admitted to an ICU) were described and compared with non-severe confirmed cases (not admitted to an ICU). RESULTS: Sixty-nine patients were included; 36 (52%) were 15 to 44 years of age. Sixteen (23%) cases were defined as severe, ten of these (63%) concerned patients 45 to 64 years of age. The independent factors associated with severity were: a history of heart disease, obesity, and tobacco abuse. CONCLUSIONS: This work reinforces the need to identify and protect groups at risk of severe outcomes.

Necrotizing gastritis due to Bacillus cereus in an immunocompromised patient.

Bacillus cereus is increasingly being acknowledged as a serious bacterial pathogen in immunocompromised patients. We present a case of acute necrotizing gastritis caused by B. cereus in a 37-year-old woman with acute myeloblastic leukemia, who recovered following total parenteral nutrition and treatment with imipenem and vancomycin. B. cereus was isolated from gastric mucosa and blood cultures. Up to now, no case of acute necrotizing gastritis due to this organism has been reported.

Loading dose of vancomycin in critically ill patients: 15 mg/kg is a better choice than 500 mg.

Delays in antimicrobial therapy in high-risk patients with infection may have deleterious effects on clinical outcomes. Therefore, appropriate treatment must be initiated promptly. The objective of this prospective study was to determine the better loading dose of vancomycin in critically ill patients with suspected Gram-positive infections. Two groups of patients were studied successively: Group A, loading dose of 500 mg; and Group B, loading dose of 15 mg/kg. The mean post-loading dose serum vancomycin concentration was significantly higher in Group B than in Group A (19.1 +/- 7.4 mg/L versus 10.4 +/- 2.7 mg/L; P < 0.001), without producing toxic peak levels. Clinical cure rates were significantly different for infected patients in Group B compared with Group A: 93% (14 of 15 patients) versus 56% (10 of 18 patients), respectively. However, the proportion of patients surviving to Intensive Care Unit discharge was similar. Because vancomycin is believed to achieve maximum killing at concentrations in serum of four to five times the minimum inhibitory concentration for the infecting organism, our results suggest that the 15 mg/kg loading dose should be preferred.

Fas-independent mitochondrial damage triggers cardiomyocyte death after ischemia-reperfusion.

The Fas/Fas ligand and mitochondria pathways have been involved in cell death in several cell types. We combined the genetic inactivation of the Fas receptor (lpr mice), on the one hand, to the pharmacological inhibition of the mitochondrial permeability transition pore (mPTP), on the other hand, to investigate which of these pathways is predominantly activated during prolonged ischemia-reperfusion. Anesthetized C57BL/6JICO (control) and C57BL/6-lpr mice were pretreated with either saline or cyclosporin A (CsA; 40 mg/kg, 3 times a day), an inhibitor of the mPTP, and underwent 25 min of ischemia and 24 h of reperfusion. After 24 h of reperfusion, hearts were harvested: infarct size was assessed by 2,3,5-triphenyltetrazolium chloride staining, myocardial apoptosis by caspase 3 activity, and mitochondrial permeability transition by Ca2+-induced mPTP opening using a potentiometric approach. Infarct size was comparable in untreated control and lpr mice, ranging from 77 +/- 5% to 83 +/- 3% of the area at risk. CsA significantly reduced infarct size in control and lpr hearts. Control and lpr hearts exhibited comparable increase in caspase 3 activity that averaged 57 +/- 18 and 49 +/- 5 pmol x min(-1) x mg(-1), respectively. CsA treatment significantly reduced caspase 3 activity in control and lpr hearts. The Ca2+ overload required to open the mPTP was decreased to a similar extent in lpr and controls. CsA significantly attenuated Ca2+-induced mPTP opening in both groups. Our results suggest that the Fas pathway likely plays a minor role, whereas mitochondria are preferentially involved in mice cardiomyocyte death after a lethal ischemia-reperfusion injury.