Background

Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers.

Methods

In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti–factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti–factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication.

Results

The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti–factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti–factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up.

Conclusions

On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti–factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%.

Background

The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear.

Methods

From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to “upper good recovery” [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively.

Results

The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03).

Conclusions

At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups.

Background

Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage.

Methods

We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm³) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments.

Results

Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002).

Conclusions

The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg.

Meilleure guérison avec administration d’ATB en continu ?

http://icmjournal.esicm.org/journals/abstract.html?v=42&j=134&i=10&a=4188_10.1007_s00134-015-4188-0&doi=

Abdul-Aziz et al., ICM, 2016

Purpose

This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/pharmacodynamic (PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis.

Methods

This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation.

Results

A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p < 0.043) than IB participants. PK/PD target attainment rates were higher in the CI arm at 100 % fT_>MIC than the IB arm on day 1 (97 versus 70 %, p < 0.001) and day 3 (97 versus 68 %, p < 0.001) post-randomisation. There was no difference in 14-day or 30-day survival between the treatment arms.

Conclusions

In critically ill patients with severe sepsis not receiving RRT, CI demonstrated higher clinical cure rates and had better PK/PD target attainment compared to IB dosing of beta-lactam antibiotics. Continuous beta-lactam infusion may be mostly advantageous for critically ill patients with high levels of illness severity and not receiving RRT.

Epuration extra-corporelle de CO2 en cas d’échec de la VNI pour éviter la ventilation mécanique

http://icmjournal.esicm.org/journals/abstract.html?v=42&j=134&i=9&a=4452_10.1007_s00134-016-4452-y&doi=

Braune et al., ICM, 2016

Introduction

The aim of the study was to evaluate the feasibility and safety of avoiding invasive mechanical ventilation (IMV) by using extracorporeal CO₂ removal (ECCO₂R) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure refractory to noninvasive ventilation (NIV).

Methods

Case–control study. Patients with acute hypercapnic respiratory failure refractory to NIV being treated with a pump-driven veno-venous ECCO₂R system (iLA-Activve^®; Novalung, Heilbronn, Germany) were prospectively observed in five European intensive care units (ICU). Inclusion criteria were respiratory acidosis (pH ≤ 7.35, PaCO₂ > 45 mmHg) with predefined criteria for endotracheal intubation (ClinicalTrials.gov NCT01784367). The historical controls were patients with acute hypercapnic respiratory failure refractory to NIV who were treated with IMV. The matching criteria were main diagnosis, age, SAPS-II score and pH.

Results

Twenty-five cases (48.0 % male, mean age 67.3 years) were matched with 25 controls. Intubation was avoided in 14 patients (56.0 %) in the ECCO₂R group with a mean extracorporeal blood flow of 1.3 L/min. Seven patients were intubated because of progressive hypoxaemia and four owing to ventilatory failure despite ECCO₂R and NIV. Relevant ECCO₂R-associated adverse events were observed in 11 patients (44.0 %), of whom 9 (36.0 %) suffered major bleeding complications. The mean time on IMV, ICU stay and hospital stay in the case and control groups were 8.3 vs. 13.7, 28.9 vs. 24.0 and 36.9 vs. 37.0 days, respectively, and the 90-day mortality rates were 28.0 vs. 28.0 %.

Conclusions

The use of veno-venous ECCO₂R to avoid invasive mechanical ventilation was successful in just over half of the cases. However, relevant ECCO₂R-associated complications occurred in over one-third of cases. Despite the shorter period of IMV in the ECCO₂R group there were no significant differences in length of stay or in 28- and 90-day mortality rates between the two groups. Larger, randomised studies are warranted for further assessment of the effectiveness of ECCO₂R.

Déclin physique chez les survivants d’un SDRA à 5 ans

http://icmjournal.esicm.org/journals/abstract.html?v=42&j=134&i=10&a=4530_10.1007_s00134-016-4530-1&doi=

Pfoh et al., ICM, 2016

Purpose

Survivors of acute respiratory distress syndrome (ARDS) are at high risk for new or ongoing physical declines after hospital discharge. The objective of our study was to evaluate the epidemiology of physical declines over 5-year follow-up and identify patients at risk for decline.

Methods

This multi-site prospective cohort study evaluated ARDS survivors who completed a physical status assessment at 3 or 6 months post-discharge. Three measures were evaluated: muscle strength (Medical Resource Council sumscore); exercise capacity [6-min walk test (6MWT)]; physical functioning [36-Item Short Form Health Survey (SF-36 survey)]. Patients were defined as “declined” if a comparison of their current and prior score showed a decrease that was greater than the Reliable Change Index—or if the patient died. Risk factors [pre-ARDS baseline status, intensive care unit (ICU) illness severity, and other intensive care variables] were evaluated using longitudinal, generalized linear regression models for each measure.

Results

During the follow-up of 193 ARDS survivors (55 % male; median age 49 years), 166 (86 %) experienced decline in ≥1 physical measure (including death) and 133 (69 %) experienced a physical decline (excluding death). For all measures, age was a significant risk factor [odds ratios (OR) 1.34–1.69 per decade; p < 0.001]. Pre-ARDS comorbidity (Charlson Index) was independently associated with declines in strength and exercise capacity (OR 1.10 and 1.18, respectively; p < 0.02), and organ failure [maximum daily Sequential Organ Failure Assessment (SOFA) score in ICU] was associated with declines in strength (OR 1.06 per 1 point of SOFA score; p = 0.02).

Conclusions

Over the follow-up period, the majority of ARDS survivors experienced a physical decline, with older age and pre-ICU comorbidity being important risk factors for this decline.

Facteurs hôte-parasite de sévérité des crises palustres

http://icmjournal.esicm.org/journals/abstract.html?v=42&j=134&i=10&a=4356_10.1007_s00134-016-4356-x&doi=

Bruneel et al., ICM, 2016

Purpose

Prospective data on potential factors associated with severity of imported Plasmodium falciparum malaria are lacking. We evaluated whether several host- and parasite-related biomarkers may improve early severity evaluation.

Methods

Prospective multicenter observational study comparing uncomplicated and severe imported falciparum malaria in adults conducted in France in 52 units, from 2007 to 2010. Association of several host- and parasite-related biomarkers with severity of malaria was tested using univariate and multivariate analyses.

Results

Of 295 patients, 140 had uncomplicated malaria and 155 severe malaria (including very severe and less severe cases according to predefined criteria). Curative intravenous quinine treatment was used in 154/155 patients with severe malaria and atovaquone/proguanil in 74 % of patients with uncomplicated malaria. Hospital mortality was 5.2 % (8 patients), all in the severe malaria group. Among host-related biomarkers, CRP, procalcitonin, and sTREM-1 were significantly higher and albumin was significantly lower in severe versus uncomplicated malaria; only the last three biomarkers also differed significantly between the very and less severe malaria groups. Among parasite-related biomarkers, only plasma PfHRP2 was significantly higher in severe versus uncomplicated malaria and in very severe versus less severe malaria; parasitemia did not differ between very and less severe malaria. By multivariate analysis, only lower plasma albumin and higher sTREM-1 were associated with greater severity, with intermediate accuracies.

Conclusions

During imported malaria, the most useful biomarkers associated with severity seem to be plasma albumin and sTREM-1; and among parasite-related parameters, PfHRP2 was more strongly associated with severity than parasitemia was.

Méta-analyse et analyse séquentielle sur le Milrinone sur la dysfonction cardiaque en réanimation

Etude sur les techniques de sauvetage après échec de laryngoscopie : Vive la vidéo-laryngoscopie ?

http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2542535

Aziz et al., Anesthesiology, 2016

Background

Multiple attempts at tracheal intubation are associated with mortality, and successful rescue requires a structured plan. However, there remains a paucity of data to guide the choice of intubation rescue technique after failed initial direct laryngoscopy. The authors studied a large perioperative database to determine success rates for commonly used intubation rescue techniques.

Methods

Using a retrospective, observational, comparative design, the authors analyzed records from seven academic centers within the Multicenter Perioperative Outcomes Group between 2004 and 2013. The primary outcome was the comparative success rate for five commonly used techniques to achieve successful tracheal intubation after failed direct laryngoscopy: (1) video laryngoscopy, (2) flexible fiberoptic intubation, (3) supraglottic airway as part of an exchange technique, (4) optical stylet, and (5) lighted stylet.

Results

A total of 346,861 cases were identified that involved attempted tracheal intubation. A total of 1,009 anesthesia providers managed 1,427 cases of failed direct laryngoscopy followed by subsequent intubation attempts (n = 1,619) that employed one of the five studied intubation rescue techniques. The use of video laryngoscopy resulted in a significantly higher success rate (92%; 95% CI, 90 to 93) than other techniques: supraglottic airway conduit (78%; 95% CI, 68 to 86), flexible bronchoscopic intubation (78%; 95% CI, 71 to 83), lighted stylet (77%; 95% CI, 69 to 83), and optical stylet (67%; 95% CI, 35 to 88). Providers most frequently choose video laryngoscopy (predominantly GlideScope^® [Verathon, USA]) to rescue failed direct laryngoscopy (1,122/1,619; 69%), and its use has increased during the study period.

Conclusions

Video laryngoscopy is associated with a high rescue intubation success rate and is more commonly used than other rescue techniques.

Le Doppler Trans-crânien : Outil prédictif ?

http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2526163

Bouzat et al., Anesthesiology, 2016

Background

To assess the performance of transcranial Doppler (TCD) in predicting neurologic worsening after mild to moderate traumatic brain injury.

Methods

The authors conducted a prospective observational study across 17 sites. TCD was performed upon admission in 356 patients (Glasgow Coma Score [GCS], 9 to 15) with mild lesions on cerebral computed tomography scan. Normal TCD was defined as a pulsatility index of less than 1.25 and diastolic blood flow velocity higher than 25 cm/s in the two middle cerebral arteries. The primary endpoint was secondary neurologic deterioration on day 7.

Results

Twenty patients (6%) developed secondary neurologic deterioration within the first posttraumatic week. TCD thresholds had 80% sensitivity (95% CI, 56 to 94%) and 79% specificity (95% CI, 74 to 83%) to predict neurologic worsening. The negative predictive values and positive predictive values of TCD were 98% (95% CI, 96 to 100%) and 18% (95% CI, 11to 28%), respectively. In patients with minor traumatic brain injury (GCS, 14 to 15), the sensitivity and specificity of TCD were 91% (95% CI, 59 to 100%) and 80% (95% CI, 75 to 85%), respectively. The area under the receiver operating characteristic curve of a multivariate predictive model including age and GCS was significantly improved with the adjunction of TCD. Patients with abnormal TCD on admission (n = 86 patients) showed a more altered score for the disability rating scale on day 28 compared to those with normal TCD (n = 257 patients).

Conclusions

TCD measurements upon admission may provide additional information about neurologic outcome after mild to moderate traumatic brain injury. This technique could be useful for in-hospital triage in this context.

Pas de différence entre Anesthésie volatile vs IV en Chirurgie Thoracique ?

http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2526162

Beck-Schimmer et al., Anesthesiology, 2016

Background

One-lung ventilation during thoracic surgery is associated with hypoxia–reoxygenation injury in the deflated and subsequently reventilated lung. Numerous studies have reported volatile anesthesia–induced attenuation of inflammatory responses in such scenarios. If the effect also extends to clinical outcome is yet undetermined. We hypothesized that volatile anesthesia is superior to intravenous anesthesia regarding postoperative complications.

Methods

Five centers in Switzerland participated in the randomized controlled trial. Patients scheduled for lung surgery with one-lung ventilation were randomly assigned to one of two parallel arms to receive either propofol or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to occurrence of the first major complication according to the Clavien-Dindo score was defined as primary (during hospitalization) or secondary (6-month follow-up) endpoint. Cox regression models were used with adjustment for prestratification variables and age.

Results

Of 767 screened patients, 460 were randomized and analyzed (n = 230 for each arm). Demographics, disease and intraoperative characteristics were comparable in both groups. Incidence of major complications during hospitalization was 16.5% in the propofol and 13.0% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71).

Conclusions

This is the first multicenter randomized controlled trial addressing the effect of volatile versus intravenous anesthetics on major complications after lung surgery. No difference between the two anesthesia regimens was evident.

Les HEA pour une meilleure perfusion hépatique ?

http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2528135

Itakura et al., Anesthesiology, 2016

Background

Rapid fluid infusion resulting in increased hepatic blood flow may decrease the propofol plasma concentration (Cp) because propofol is a high hepatic extraction drug. The authors investigated the effects of rapid colloid and crystalloid infusions on the propofol Cp during target-controlled infusion.

Methods

Thirty-six patients were randomly assigned to 1 of 3 interventions (12 patients per group). At least 30 min after the start of propofol infusion, patients received either a 6% hydroxyethyl starch (HES) solution at 24 ml·kg⁻¹·h⁻¹ or acetated Ringer’s solution at 24 or 2 ml·kg⁻¹·h⁻¹ during the first 20 min. In all groups, acetated Ringer’s solution was infused at 2 ml·kg⁻¹·h⁻¹ during the next 20 min. The propofol Cp was measured every 2.5 min as the primary outcome. Cardiac output, blood volume, and indocyanine green disappearance rate were determined using a pulse dye densitogram analyzer before and after the start of fluid administration. Effective hepatic blood flow was calculated as the blood volume multiplied by the indocyanine green disappearance rate.

Results

The rapid HES infusion significantly decreased the propofol Cp by 22 to 37%, compared to the Cp at 0 min, whereas the rapid or maintenance infusion of acetate Ringer’s solution did not decrease the propofol Cp. Rapid HES infusion, but not acetate Ringer’s solution infusion, increased the effective hepatic blood flow.

Conclusions

Rapid HES infusion increased the effective hepatic blood flow, resulting in a decreased propofol Cp during target-controlled infusion. Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia.

Le bain de Chlorhexidine diminue le taux d’infections nosocomiales en Réanimation ?

http://journals.lww.com/ccmjournal/Abstract/2016/10000/Effect_of_Chlorhexidine_Bathing_Every_Other_Day_on.4.aspx

Swan et al., CCM, 2016

Le mythe de l’ulcère de stress ?

http://journals.lww.com/ccmjournal/Abstract/2016/10000/Pantoprazole_or_Placebo_for_Stress_Ulcer.6.aspx

Selvanderan et al., CCM, 2016

Congestion des lits en Réa : Impact médico-économique

http://journals.lww.com/ccmjournal/Abstract/2016/10000/Association_Among_ICU_Congestion,_ICU_Admission.3.aspx

Kim et al., CCM, 2016

Méta-analyse sur le syndrome dépressif post-Réanimation

http://journals.lww.com/ccmjournal/Fulltext/2016/09000/Depressive_Symptoms_After_Critical_Illness___A.14.aspx

Rabiee et al., CCM, 2016

Estimation des GDS artériels à partir de sang veineux

http://bja.oxfordjournals.org/content/117/3/341.abstract

Boulain et al., BJA, 2016

Background

The estimation of arterial blood gas and lactate from central venous blood analysis and pulse oximetry (SpO2) readings has not yet been extensively validated.

Revue sur la néphropathie liée aux produits de contraste

http://bja.oxfordjournals.org/content/117/suppl_2/ii63.full

Wong et al., BJA, 2016