Christophe Cracco

Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial

BACKGROUND Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting. METHODS In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667. FINDINGS Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001). INTERPRETATION A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes. FUNDING Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.

Accuracy of pulse oximetry in the intensive care unit.

Abstract. Objective: Pulse oximetry (SpO2) is a standard monitoring device in intensive care units (ICUs), currently used to guide therapeutic interventions. Few studies have evaluated the accuracy of SpO2 in critically ill patients. Our objective was to compare pulse oximetry with arterial oxygen saturation (SaO2) in such patients, and to examine the effect of several factors on this relationship. Design: Observational prospective study. Setting: A 26-bed medical ICU in a university hospital. Patients: One hundred two consecutive patients admitted to the ICU in whom one or serial arterial blood gas analyses (ABGs) were performed and a reliable pulse oximeter signal was present. Interventions: For each ABG, we collected SaO2, SpO2, the type of pulse oximeter, the mode of ventilation and requirement for vasoactive drugs. Measurements and results: Three hundred twenty-three data points were collected. The mean difference between SpO2 and SaO2 was –0.02% and standard deviation of the differences was 2.1%. From one sample to another, the fluctuations in SpO2 to arterial saturation difference indicated that SaO2 could not be reliably predicted from SpO2 after a single ABG. Subgroup analysis showed that the accuracy of SpO2 appeared to be influenced by the type of oximeter, the presence of hypoxemia and the requirement for vasoactive drugs. Finally, high SpO2 thresholds were necessary to detect significant hypoxemia with good sensitivity. Conclusion: Large SpO2 to SaO2 differences may occur in critically ill patients with poor reproducibility of SpO2. A SpO2 above 94% appears necessary to ensure a SaO2 of 90%.

Reduced breathing variability as a predictor of unsuccessful patient separation from mechanical ventilation.

Objectives:To compare descriptors of the breath-to-breath respiratory variability during a 60-min spontaneous breathing trial in patients successfully and unsuccessfully separated from the ventilator and the endotracheal tube and to assess the usefulness of these predictors in discriminating these two categories of patients. Design:Prospective observational study. Setting:Four general intensive care units in university hospitals. Patients:A total of 51 consecutive patients mechanically ventilated for >24 hrs. Interventions:None. Measurements and Main Results:Tidal volume, respiratory period, inspiratory time, expiratory time, mean inspiratory flow (tidal volume/inspiratory time), and duty cycle (inspiratory time/respiratory period) were obtained from the flow signal. Breath-by-breath variability was expressed in terms of their coefficients of variation (CV), the number of breaths among which a significant correlation was found (lag), and the autocorrelation coefficient between one breath and the following one. Five patients were excluded because of nonstationarity of the data, leaving 46 cases for analysis. Between-group comparison was conducted with the Mann-Whitney test, and a nonparametric classification and regression tree was used to identify variables discriminating “success” (n = 32) and “failure” patients (n = 14). All coefficients of variation were significantly higher in success patients, who also exhibited significantly less respiratory autocorrelation (shorter “short memory”). The classification and regression tree analysis allocated all success patients to a group defined by a coefficient of variation of tidal volume/inspiratory time of ≥19% and a coefficient of variation of inspiratory time/respiratory period of ≥10% that did not contain any failure patient. All failure patients belonged to a group with coefficient of variation of tidal volume/inspiratory time of <19%, a lag tidal volume of ≥11, and that contained no success patient. Conclusions:In intensive care unit patients undergoing a spontaneous breathing trial, breathing variability is greater in patients successfully separated from the ventilator and the endotracheal tube. Variability indices are sufficient to separate success from failure cases.

Neurally Adjusted Ventilatory Assist Increases Respiratory Variability and Complexity in Acute Respiratory Failure

Background:Neurally adjusted ventilatory assist (NAVA) is a partial ventilatory support mode where positive pressure is provided in relation to diaphragmatic electrical activity (EAdi). Central inspiratory activity is normally not monotonous, but it demonstrates short-term variability and complexity. The authors reasoned that NAVA should produce a more “natural” or variable breathing pattern than other modes. This study compared respiratory variability and complexity during pressure support ventilation (PSV) and NAVA. Methods:Flow and EAdi were recorded during routine PSV (tidal volume ∼6–8 ml/kg) and four NAVA levels (1–4 cm H2O/&mgr;VEAdi) in 12 intubated patients. Breath-by-breath variability of flow and EAdi-related variables was quantified by the coefficient of variation (CV) and autocorrelation analysis. Complexity of flow and EAdi was described using noise titration, largest Lyapunov exponent, Kolmogorov-Sinai entropy, and three-dimensional phase portraits. Results:Switching from PSV to NAVA increased the CV and decreased the autocorrelation for most flow-related variables in a dose-dependent manner (P < 0.05, partial &eegr;2 for the CV of mean inspiratory flow 0.642). The changes were less marked for EAdi. A positive noise limit was consistently found for flow and EAdi. Largest Lyapunov exponent and Kolmogorov-Sinai entropy for flow were greater during NAVA than PSV and increased with NAVA level (P < 0.05, partial &eegr;2 0.334 and 0.312, respectively). Largest Lyapunov exponent and Kolmogorov-Sinai entropy for EAdi were not influenced by ventilator mode. Conclusions:Compared with PSV, NAVA increases the breathing pattern variability and complexity of flow, whereas the complexity of EAdi is unchanged. Whether this improves clinical outcomes remains to be determined.

Multiple organ failure complicating probable scrub typhus.

This report describes a case of life-threatening acute respiratory distress syndrome with multiple organ failure complicating probable scrub typhus. Favorable outcome was associated with fluoroquinolone therapy. Scrub typhus should be suspected in travelers returning from Southeast Asia presenting with unexplained respiratory manifestations.

Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series

BackgroundOpportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis.Case presentationWe describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and agressive symptomatic treatment.ConclusionInvasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities.

Complicated grief after death of a relative in the intensive care unit

An increased proportion of deaths occur in the intensive care unit (ICU). We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months. Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives). End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements. End-of-life care and communication in the ICU are associated with the prevalence of complicated grief http://ow.ly/DCqjB

Mise en place et surveillance de l’assistance ventilatoire à domicile

Resume Introduction Une mise en route efficace et une surveillance optimale sont les elements essentiels a la reussite de la ventilation a domicile (VAD). Etat des connaissances La mise en route est preferablement realisee dans une structure hospitaliere. Le choix du materiel est d’une importance capitale mais il n’y a pas de superiorite demontree d’un type de materiel par rapport a un autre. La surveillance de la VAD sera inevitablement marquee par de multiples problemes pouvant faire interrompre la therapeutique. Tous ces problemes auront souvent des solutions simples, recensees dans cet article. Perspectives Malheureusement, il existe encore de nombreux ecueils dans la surveillance. Le principal etant l’absence de donnees precises sur le sommeil des patients ventiles ne permettant pas une surveillance nocturne optimale. Un autre ecueil important est l’absence d’adaptation des interfaces aux patients handicapes. Enfin, le transfert des responsabilites et de la charge de travail vers les intervenants a domicile, dont la famille, avec un desengagement de l’hopital est aussi un fait marquant de la VAD. Conclusions Une mise en route et une surveillance optimale sont les gages d’efficacite de la VAD. Les pieges, les erreurs, des manques de connaissances sont souvent cause d’abandon de la therapeutique. Cet article propose des outils d’amelioration de ces deux etapes essentielles.

Identification of prolonged phrenic nerve conduction time in the ICU: magnetic versus electrical stimulation

PurposeRetrospective study of prospectively collected data to assess the reliability of cervical magnetic stimulation (CMS) to detect prolonged phrenic nerve (PN) conduction time at the bedside. Because PN injuries may cause diaphragm dysfunction, their diagnosis is relevant in intensive care units (ICU). This is achieved by studying latency and amplitude of diaphragm response to PN stimulation. Electrical stimulation (ES) is the gold standard, but it is difficult to perform in the ICU. CMS is an easy noninvasive tool to assess PN integrity, but co-activates muscles that could contaminate surface chest electromyographic recordings.MethodsIn a first set of 56 ICU patients with suspected PN injury, presence and latency of compound motor action potentials elicited by CMS and ES were compared. With ES as the reference method, CMS was evaluated as a test designed to indicate presence or absence of PN injury. In eight additional patients, intramuscular diaphragm recordings were compared with surface diaphragm recordings and with the electromyograms of possible contamination sources.ResultsThe sensitivity of CMS to diagnose abnormal PN conduction was 0.91, and specificity was 0.84, whereas positive and negative predictive values were 0.81 and 0.92, respectively. Passing–Bablok regression analysis suggested no differences between the two measures. The correlation between PN latency in response to CMS and ES was significant. The “diaphragm surface” and “needle” latencies were close, and were significantly different from those of possibly contaminating muscles. One hemidiaphragm showed likely signal contamination.ConclusionCMS provides an easy reliable tool to detect prolonged PN conduction time in the ICU.

Atteintes thoraciques au cours des lymphomes hodgkiniens

Resume Introduction Le lymphome de Hodgkin (LH) est une hemopathie lymphoide caracterisee par la presence de cellules de Reed-Sternberg ou de Hodgkin en histologie. Son evolution est marquee par une survie superieure a 80 %. Etats des connaissances L’atteinte thoracique initiale est frequente, surtout mediastinale, plus que parenchymateuse pulmonaire ou pleurale. Dans ces deux derniers cas, elle change le pronostic et un diagnostic est donc necessaire. Les complications des traitements du LH etaient representees, precocement, par les infections. Actuellement, ce sont plutot les atteintes fonctionnelles respiratoires apres radiotherapie mediastinale et chimiotherapie (incluant de la bleomycine) qui surviennent frequemment dans le suivi du LH. Par ailleurs, certaines atteintes granulomateuses precedent, accompagnent ou emaillent l’evolution du LH et le diagnostic differentiel avec des localisations specifiques est souvent difficile. Enfin, ces patients sont plus a risque de voir apparaitre des neoplasies, notamment bronchiques, a long terme. Perspectives et conclusions Les patients porteurs de LH ont maintenant une faible mortalite imputable directement a la maladie en comparaison de celle, souvent plus tardive, rapportee aux traitements. L’enjeu actuel est de developper des protocoles therapeutiques moins toxiques mais tout aussi efficaces.