Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in Belgium and the Netherlands.

BACKGROUND: Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2·0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1·3 g/kg per day). METHODS: The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m2, kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1·3 kcal/mL and 0·06 g of protein/mL (ie, standard protein) or 1·3 kcal/mL and 0·10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants. FINDINGS: Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35·8%) of 935 patients were female and 600 (64·2%) were male. 465 (49·7%) of 935 were assigned to the standard protein group and 470 (50·3%) were assigned to the high protein group. 430 (92·5%) of 465 patients in the standard protein group and 419 (89·1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0·05 (95% CI -0·10 to -0·01; p=0·031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0·38 (SE 0·02) in the standard protein group and 0·42 (0·02) in the high protein group (hazard ratio 1·14, 95% CI 0·92 to 1·40; p=0·22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1·76, 95% CI 1·06 to 2·92; p=0·030). Incidence of other adverse events did not differ between groups. INTERPRETATION: High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission. FUNDING: Netherlands Organisation for Healthcare Research and Development and Belgian Health Care Knowledge Centre.

EEG signature of near-death-like experiences during syncope-induced periods of unresponsiveness.

During fainting, disconnected consciousness may emerge in the form of dream-like experiences. Characterized by extra-ordinary and mystical features, these subjective experiences have been associated to near-death-like experiences (NDEs-like). We here aim to assess brain activity during syncope-induced disconnected consciousness by means of high-density EEG monitoring. Transient loss of consciousness and unresponsiveness were induced in 27 healthy volunteers through hyperventilation, orthostasis, and Valsalva maneuvers. Upon awakening, subjects were asked to report memories, if any. The Greyson NDE scale was used to evaluate the potential phenomenological content experienced during the syncope-induced periods of unresponsiveness. EEG source reconstruction assessed cortical activations during fainting, which were regressed out with subjective reports collected upon recovery of normal consciousness. We also conducted functional connectivity, graph-theoretic and complexity analyses. High quality high-density EEG data were obtained in 22 volunteers during syncope and unresponsiveness (lasting 22±8 s). NDE-like features (Greyson NDE scale total score ≥7/32) were apparent for eight volunteers and characterized by higher activity in delta, theta and beta2 bands in temporal and frontal regions. The richness of the NDE-like content was associated with delta, theta and beta2 bands cortical current densities, in temporal, parietal and frontal lobes, including insula, right temporoparietal junction, and cingulate cortex. Our analyses also revealed a higher complexity and that networks related to delta, theta, and beta2 bands were characterized by a higher overall connectivity paralleled by a higher segregation (i.e., local efficiency) and a higher integration (i.e., global efficiency) for the NDE-like group compared to the non-NDE-like group. Fainting-induced NDE-like episodes seem to be sustained by surges of neural activity representing promising markers of disconnected consciousness.

What is the nutritional status of patients with prolonged disorders of consciousness? A retrospective cross-sectional study.

BACKGROUND: Nutritional status of patients with disorders of consciousness (DoC) is poorly studied. OBJECTIVES: To evaluate the relationship between nutritional status (body mass index, daily calories intake) and clinical variables (level of consciousness, time since injury, diagnosis, etiology and spastic muscle overactivity; SMO,) in patients with prolonged DoCor emerging. Our main hypotheses are i) patients with lower level of consciousness (UWS) have worse nutritional status compared to patients in minimally conscious state (MCS) and ii) SMO could influence nutritional status. METHODS AND RESULTS: Among the 80 patients included in the study (19 UWS, 47 MCS, 14 emerging MCS; 43 ± 15 yo; 3 ± 4 years post-injury, 35 traumatic etiology, 34 females), 9% were at risk to be undernourished, with no differences between UWS and MCS. Patients without SMO had a higher BMI compared to patients with severe SMO. Compared to the recommended daily calories intake, patients with the highest BMI received less calories and patients with the lowest BMI received more calories. We observed a negative correlation between SMO (in lower limbs) and BMI. CONCLUSION: Our study shows that most patients are well nourished, independently from the level of consciousness. SMO may require additional calories in patients' daily needs; however, longitudinal studies are needed to explore the causal relationship between these variables.

Successful heart transplantation from donation after euthanasia with distant procurement using normothermic regional perfusion and cold storage.

While euthanasia has been legalized in a growing number of countries, organ donation after euthanasia is only performed in Belgium, the Netherlands, Spain, and Canada. Moreover, the clinical practice of heart donation after euthanasia has never been reported before. We describe the first case of a heart donated after euthanasia, reconditioned with thoraco-abdominal normothermic regional perfusion, preserved using cold storage while being transported to a neighboring transplant center, and then successfully transplanted following a procurement warm ischemic time of 17 min. Heart donation after euthanasia using thoraco-abdominal normothermic regional perfusion is feasible, it could expand the heart donor pool and reduce waiting lists in countries where organ donation after euthanasia can be performed.

The role of transesophageal echocardiography in guiding heart donation after circulatory death.

Heart donation after circulatory death (DCD) can significantly expand the heart donor pool, helping to overcome the problem of organ shortage and the increase in waiting list mortality and morbidity. To improve the outcome of DCD heart transplantation, thoraco-abdominal normothermic regional perfusion (TA-NRP) can be performed by selectively restoring circulation followed by in vivo functional heart assessment. Here, we report on the use of periprocedural transoesophageal echocardiography (TOE) as a minimally invasive cardiac assessment tool during different stages of a DCD heart procurement procedure using TA-NRP. We conclude that TOE is a valuable method to assess the donor heart for transplantation eligibility before and after withdrawal of life-sustaining therapy and during subsequent TA-NRP.

Virtual reality and hypnosis for anxiety and pain management in intensive care units: A prospective randomised trial among cardiac surgery patients.

BACKGROUND: Virtual reality and hypnosis are little studied in complex contexts, such as intensive care, where patients need significant physical and psychological assistance. OBJECTIVES: To compare and combine hypnosis and virtual reality benefits on anxiety and pain on patients before and after cardiac surgery. DESIGN: Prospective randomised controlled clinical trial. SETTING: The study was conducted in the University Hospital of Liege (Belgium) from October 2018 to January 2020. PATIENTS: One hundred patients (66 ±â€Š11.5 years; 24 women, 76 men) were included. Participants were adults undergoing cardiac surgery. Exclusion criteria: psychiatric diseases, claustrophobia, acrophobia, hearing loss, visual impairment, extreme fatigue, confusion surgery cancelled. INTERVENTIONS: Patients were randomly assigned to four arms (control; hypnosis; virtual reality; virtual reality hypnosis) and had 20 min of one of the techniques the day before and the day after surgery. MAIN OUTCOMES MEASURES: Anxiety, pain, fatigue, relaxation, physiological parameters, and opioid use were evaluated before and after each session. RESULTS: The main results did not show any significant differences between the groups. In all groups, anxiety decreased and pain increased from baseline to the postoperative day. Relaxation increased in all groups in the pre-operative (P < 0.0001) and postoperative period (P = 0.03). There were no significant differences for fatigue, physiological measures, or opioid use. CONCLUSION: As there were no significant differences between groups for the measured variables, we cannot affirm that one technique is better than another. Additional studies are required to compare and evaluate the cost-effectiveness of these techniques for critical care patients and caregivers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03820700. https://clinicaltrials.gov/ct2/show/NCT03820700. Retrospectively registered on 29 January 2019.

Changes in End-of-Life Practices in European Intensive Care Units From 1999 to 2016.

IMPORTANCE: End-of-life decisions occur daily in intensive care units (ICUs) around the world, and these practices could change over time. OBJECTIVE: To determine the changes in end-of-life practices in European ICUs after 16 years. DESIGN, SETTING, AND PARTICIPANTS: Ethicus-2 was a prospective observational study of 22 European ICUs previously included in the Ethicus-1 study (1999-2000). During a self-selected continuous 6-month period at each ICU, consecutive patients who died or had any limitation of life-sustaining therapy from September 2015 until October 2016 were included. Patients were followed up until death or until 2 months after the first treatment limitation decision. EXPOSURES: Comparison between the 1999-2000 cohort vs 2015-2016 cohort. MAIN OUTCOMES AND MEASURES: End-of-life outcomes were classified into 5 mutually exclusive categories (withholding of life-prolonging therapy, withdrawing of life-prolonging therapy, active shortening of the dying process, failed cardiopulmonary resuscitation [CPR], brain death). The primary outcome was whether patients received any treatment limitations (withholding or withdrawing of life-prolonging therapy or shortening of the dying process). Outcomes were determined by senior intensivists. RESULTS: Of 13 625 patients admitted to participating ICUs during the 2015-2016 study period, 1785 (13.1%) died or had limitations of life-prolonging therapies and were included in the study. Compared with the patients included in the 1999-2000 cohort (n = 2807), the patients in 2015-2016 cohort were significantly older (median age, 70 years [interquartile range {IQR}, 59-79] vs 67 years [IQR, 54-75]; P < .001) and the proportion of female patients was similar (39.6% vs 38.7%; P = .58). Significantly more treatment limitations occurred in the 2015-2016 cohort compared with the 1999-2000 cohort (1601 [89.7%] vs 1918 [68.3%]; difference, 21.4% [95% CI, 19.2% to 23.6%]; P < .001), with more withholding of life-prolonging therapy (892 [50.0%] vs 1143 [40.7%]; difference, 9.3% [95% CI, 6.4% to 12.3%]; P < .001), more withdrawing of life-prolonging therapy (692 [38.8%] vs 695 [24.8%]; difference, 14.0% [95% CI, 11.2% to 16.8%]; P < .001), less failed CPR (110 [6.2%] vs 628 [22.4%]; difference, -16.2% [95% CI, -18.1% to -14.3%]; P < .001), less brain death (74 [4.1%] vs 261 [9.3%]; difference, -5.2% [95% CI, -6.6% to -3.8%]; P < .001) and less active shortening of the dying process (17 [1.0%] vs 80 [2.9%]; difference, -1.9% [95% CI, -2.7% to -1.1%]; P < .001). CONCLUSIONS AND RELEVANCE: Among patients who had treatment limitations or died in 22 European ICUs in 2015-2016, compared with data reported from the same ICUs in 1999-2000, limitations in life-prolonging therapies occurred significantly more frequently and death without limitations in life-prolonging therapies occurred significantly less frequently. These findings suggest a shift in end-of-life practices in European ICUs, but the study is limited in that it excluded patients who survived ICU hospitalization without treatment limitations.

Prevention of ventilator-associated pneumonia and ventilator-associated conditions: a randomized controlled trial with subglottic secretion suctioning.

OBJECTIVES: Ventilator-associated pneumonia diagnosis remains a debatable topic. New definitions of ventilator-associated conditions involving worsening oxygenation have been recently proposed to make surveillance of events possibly linked to ventilator-associated pneumonia as objective as possible. The objective of the study was to confirm the effect of subglottic secretion suctioning on ventilator-associated pneumonia prevalence and to assess its concomitant impact on ventilator-associated conditions and antibiotic use. DESIGN: Randomized controlled clinical trial conducted in five ICUs of the same hospital. PATIENTS: Three hundred fifty-two adult patients intubated with a tracheal tube allowing subglottic secretion suctioning were randomly assigned to undergo suctioning (n = 170, group 1) or not (n = 182, group 2). MAIN RESULTS: During ventilation, microbiologically confirmed ventilator-associated pneumonia occurred in 15 patients (8.8%) of group 1 and 32 patients (17.6%) of group 2 (p = 0.018). In terms of ventilatory days, ventilator-associated pneumonia rates were 9.6 of 1,000 ventilatory days and 19.8 of 1,000 ventilatory days, respectively (p = 0.0076). Ventilator-associated condition prevalence was 21.8% in group 1 and 22.5% in group 2 (p = 0.84). Among the 47 patients with ventilator-associated pneumonia, 25 (58.2%) experienced a ventilator-associated condition. Neither length of ICU stay nor mortality differed between groups; only ventilator-associated condition was associated with increased mortality. The total number of antibiotic days was 1,696 in group 1, representing 61.6% of the 2,754 ICU days, and 1,965 in group 2, representing 68.5% of the 2,868 ICU days (p < 0.0001). CONCLUSIONS: Subglottic secretion suctioning resulted in a significant reduction of ventilator-associated pneumonia prevalence associated with a significant decrease in antibiotic use. By contrast, ventilator-associated condition occurrence did not differ between groups and appeared more related to other medical features than ventilator-associated pneumonia.

Prevalence, characteristics and risk factors of chronic postsurgical pain after laparoscopic colorectal surgery: Retrospective analysis.

BACKGROUND: The prevalence of chronic postsurgical pain (CPSP) is a critical medical problem with economic implications. Its prevalence after gastrointestinal surgery is not well documented, particularly when a laparoscopic approach is used. OBJECTIVE: The aim of the study was to determine the prevalence, the characteristics and the risk factors for CPSP after laparoscopic colorectal surgery. DESIGN: A retrospective analysis using a postal questionnaire. SETTING: The study was conducted at a university teaching hospital. PATIENTS: Patients who underwent laparoscopic colorectal surgery from April 2008 until December 2011 (n = 260). No epidural analgesia was used. MAIN OUTCOME MEASURES: Postoperative pain intensity, incidence and characteristics of CPSP, and impact on quality of life and sleep. RESULTS: Of 199 responses, 33 patients (17%) reported chronic pain at a median [interquartile range, IQR] of 38 [27 to 55] months after laparoscopic surgery with a median intensity of 4 [3 to 5]. CPSP had a negative impact on the quality of life in 84% of patients and on sleep in 43%. CPSP required regular analgesic(s) intake in 54% patients. Using a backward stepwise multivariate logistic regression model, the following variables were determined as independent risk factors for CPSP: redo surgery for anastomotic leakage (P = 0.01), inflammatory bowel disease (IBD) as the indication for surgery (P = 0.01) and preoperative pain (P = 0.05). CONCLUSION: The incidence of CPSP after laparoscopic colorectal surgery (17%) is similar to those reported in the literature after laparotomy. Risk factors are redo surgery for postoperative peritonitis, IBD and preoperative pain. TRIAL REGISTRATION: EudraCT 2012-005712-25.

Does comfort therapy during controlled donation after circulatory death shorten the life of potential donors?

INTRODUCTION: Controlled donation after circulatory death (DCD) remains ethically controversial. The authors developed a controlled DCD protocol in which comfort therapy is regularly used. The aim of this study was to determine whether this policy shortens the DCD donors' life. METHODS: The authors retrospectively analyzed prospectively collected data on patients proposed for DCD at the University Hospital of Liege, Belgium, over a 56-month period. The survival duration of these patients, defined as duration between the time of proposal for DCD and the time of circulatory arrest, was compared between patients who actually donated organs and those who did not. RESULTS: About 128 patients were considered for controlled DCD and 54 (43%) became donors. Among the 74 non-donor patients, 34 (46%) objected to organ donation, 38 patients (51%) were denied by the transplant team for various medical reasons, and two potential DCD donors did not undergo procurement due to logistical and organizational reasons. The survival durations were similar in the DCD donor and non-donor groups. No non-donor patient survived. CONCLUSIONS: Survival of DCD donors is not shortened when compared with non-donor patients. These data support the ethical and respectful approach to potential DCD donors in the authors' center, including regular comfort therapy.

The impact of high versus standard enteral protein provision on functional recovery following intensive care admission: Protocol for a pre-planned secondary Bayesian analysis of the PRECISe trial.

BACKGROUND: The PRECISe trial is a pragmatic, multicenter randomized controlled trial that evaluates the effect of high versus standard enteral protein provision on functional recovery in adult, mechanically ventilated critically ill patients. The current protocol presents the rationale and analysis plan for an evaluation of the primary and secondary outcomes under the Bayesian framework, with an emphasis on clinically important effect sizes. METHODS: This protocol was drafted in agreement with the ROBUST-statement, and is submitted for publication before database lock and primary data analysis. The primary outcome is health-related quality of life as measured by the EQ-5D-5L health utility score and is longitudinally assessed. Secondary outcomes comprise the 6-min walking test and handgrip strength over the entire follow-up period (longitudinal analyses), and 60-day mortality, duration of mechanical ventilation, and EQ-5D-5L health utility scores at 30, 90 and 180 days (cross-sectional). All analyses will primarily be performed under weakly informative priors. When available, informative priors elicited from contemporary literature will also be incorporated under alternative scenarios. In all other cases, objectively formulated skeptical and enthusiastic priors will be defined to assess the robustness of our results. Relevant identified subgroups were: patients with acute kidney injury, severe multi-organ failure and patients with or without sepsis. Results will be presented as absolute risk differences, mean differences, and odds ratios, with accompanying 95% credible intervals. Posterior probabilities will be estimated for clinically important benefit and harm. DISCUSSION: The proposed secondary, pre-planned Bayesian analysis of the PRECISe trial will provide additional information on the effects of high protein on functional and clinical outcomes in critically ill patients, such as probabilistic interpretation, probabilities of clinically important effect sizes, and the integration of prior evidence. As such, it will complement the interpretation of the primary outcome as well as several secondary and subgroup analyses.

Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness.

The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics.

What is the potential increase in the heart graft pool by cardiac donation after circulatory death?

Heart transplantation remains the only definite treatment option for end-stage heart diseases. The use of hearts procured after donation after circulatory death (DCD) could help decrease the heart graft shortage. The aim of this study was to evaluate the potential increase in heart graft pool by developing DCD heart transplantation. We retrospectively reviewed our local donor database from 2006 to 2011, and screened the complete controlled DCD donor population for potential heart donors, using the same criteria as for donation after brain death (DBD) heart transplantation. Acceptable donation warm ischemic time (DWIT) was limited to 30 min. During this period 177 DBD and 70 DCD were performed. From the 177 DBD, a total of 70 (39.5%) hearts were procured and transplanted. Of the 70 DCD, eight (11%) donors fulfilled the criteria for heart procurement with a DWIT of under 30 min. Within the same period, 82 patients were newly listed for heart transplantation, of which 53 were transplanted, 20 died or were unlisted, and 9 were waiting. It could be estimated that 11% of the DCD might be heart donors, representing a 15% increase in heart transplant activity, as well as potential reduction in the deaths on the waiting list by 40%.

Transcutaneous vagal nerve stimulation to treat disorders of consciousness: Protocol for a double-blind randomized controlled trial.

Background: Patients with disorders of consciousness (DoC) are a challenging population prone to misdiagnosis with limited effective treatment options. Among neuromodulation techniques, transcutaneous auricular vagal nerve stimulation (taVNS) may act through a bottom-up manner to modulate thalamo-cortical connectivity and promote patients' recovery. In this clinical trial, we aim to (1) assess the therapeutic clinical effects of taVNS in patients with DoC; (2) investigate the neural mechanisms underlying the effects of its action; (3) assess the feasibility and safety of the procedure in this challenging population; (4) define the phenotype of clinical responders; and (5) assess the long-term efficacy of taVNS in terms of functional outcomes. Methods: We will conduct a prospective parallel randomized controlled double-blind clinical trial investigating the effects of taVNS as a treatment in DoC patients. Forty-four patients in the early period post-injury (7 to 90 days following the injury) will randomly receive 5 days of either active bilateral vagal stimulation (45 min duration with 30s alternative episodes of active/rest periods; 3mA; 200-300µs current width, 25Hz.) or sham stimulation. Behavioural (i.e., Coma Recovery Scale-Revised, CRS-R) and neurophysiological (i.e., high-density electroencephalography, hd-EEG) measures will be collected at baseline and at the end of the 5-day treatment. Analyses will seek for changes in the CRS-R and the EEG metrics (e.g., alpha band power spectrum, functional connectivity) at the group and individual (i.e., responders) levels. Discussion: These results will allow us to investigate the vagal afferent network and will contribute towards a definition of the role of taVNS for the treatment of patients with DoC. We aim to identify the neural correlates of its action and pave the way to novel targeted therapeutic strategies. Clinical trial registration: Clinicaltrials.gov n° NCT04065386.

Needs and Quality of Life of Caregivers of Patients with Prolonged Disorders of Consciousness.

Background. Many patients with severe brain damage may survive and remain in a prolonged disorder of consciousness (PDoC), impacting the quality of life (QoL) and needs of their family caregivers. However, the current literature on the factors influencing these needs is contradictory. We aim to describe the needs, QoL, and emotional distress of caregivers of patients with PDoC. Methods. Questionnaires investigating the importance and satisfaction of six categories of needs (i.e., health information, emotional, instrumental, and professional supports, community support network, and involvement in care), QoL, and emotional distress were completed by the main caregivers of PDoC patients. Results. We analyzed 177 questionnaires. Seventy-nine percent of the needs were considered as important or very important, and 44% were partially met or unmet. The needs for health information and professional support were the most important, while the needs for involvement in care and for health information were the most satisfied. Mean QoL was low and emotional distress high. Variables such as care setting and time since brain injury affected the level of QoL and distress. Conclusion. The needs for health information and professional support should receive particular attention. Given their low QoL and high distress, adequate support structures should be provided to caregivers of PDoC patients.

The impact of high versus standard enteral protein provision on functional recovery following intensive care admission (PRECISE trial): study protocol for a randomized controlled, quadruple blinded, multicenter, parallel group trial in mechanically ventilated patients.

BACKGROUND: Critically ill patients are subject to severe skeletal muscle wasting during intensive care unit (ICU) stay, resulting in impaired short- and long-term functional outcomes and health-related quality of life. Increased protein provision may improve functional outcomes in ICU patients by attenuating skeletal muscle breakdown. Supporting evidence is limited however and results in great variety in recommended protein targets. METHODS: The PRECISe trial is an investigator-initiated, bi-national, multi-center, quadruple-blinded randomized controlled trial with a parallel group design. In 935 patients, we will compare provision of isocaloric enteral nutrition with either a standard or high protein content, providing 1.3 or 2.0 g of protein/kg/day, respectively, when fed on target. All unplanned ICU admissions with initiation of invasive mechanical ventilation within 24 h of admission and an expected stay on ventilator support of at least 3 days are eligible. The study is designed to assess the effect of the intervention on functional recovery at 1, 3, and 6 months following ICU admission, including health-related quality of life, measures of muscle strength, physical function, and mental health. The primary endpoint of the trial is health-related quality of life as measured by the Euro-QoL-5D-5-level questionnaire Health Utility Score. Overall between-group differences will be assessed over the three time points using linear mixed-effects models. DISCUSSION: The PRECISe trial will evaluate the effect of protein on functional recovery including both patient-centered and muscle-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04633421 . Registered on November 18, 2020. First patient in (FPI) on November 19, 2020. Expected last patient last visit (LPLV) in October 2023.

Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients.

OBJECTIVES: To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients. DESIGN: Single-center, prospective, randomized controlled study. SETTING: Five intensive care units from a tertiary teaching hospital. PATIENTS: All consecutive adult patients hospitalized for >48 hrs in the intensive care unit during a 9-month period. INTERVENTIONS: Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groups: one using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points included: a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist. MEASUREMENTS AND MAIN RESULTS: There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6±34.4% and 57.7±34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p=.11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value>1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels<0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve=0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician. CONCLUSIONS: Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.

Clinical sedation and bispectral index in burn children receiving gamma-hydroxybutyrate.

BACKGROUND: Gamma-hydroxybutyrate (GHB) may be an interesting hypnotic agent in burn patients because of its good respiratory or hemodynamic tolerance. However, its clinical and electroencephalographic (EEG) sedative effects are not yet described in children. The aim of this prospective and randomized study was to assess clinical and EEG effects of increasing intravenous (IV) doses of GHB in burn children requiring sedation for burn wound cares. METHODS: Thirty six children hospitalized in a burn care unit were included and randomly assigned into three groups (G) according to the single IV dose of GHB they received before burn wound care: 10 mg · kg(-1) in G10, 25 mg · kg(-1) in G25, or 50 mg · kg(-1) in G50. All patients received oral premedication (morphine and hydroxyzine) 30 min before GHB injection. Respiratory rate, heart rate, pulse oximetry, and bispectral index (BIS) were continuously monitored. Depth of sedation was clinically assessed using Observer's Assessment of Alertness and Sedation (OAAS) Score, every 2 min until recovery (i.e., OAAS = 4). RESULTS: Median age was 17.5 [12-34] months. Whatever the dose, BIS decreased after IV GHB. Nadir value of BIS was significantly lower in G25 and G50 than in G10, as was for OAAS score. Nadir values were reached after same delays in G25 and G50. Duration of sedation was dose-dependent. CONCLUSION: Bispectral index decreased after GHB injection and was correlated with OAAS score. Deep sedation can be safely achieved with IV doses of 25 or 50 mg · kg(-1), but the last dose was associated with prolonged duration of clinical sedation.

Multicentre observational status-epilepticus registry: protocol for ICTAL.

INTRODUCTION: Status epilepticus (SE) is a common life-threatening neurological emergency that can cause long-term impairments. Overall outcomes remain poor. Major efforts are required to clarify the epidemiology of SE and the determinants of outcomes, thereby identifying targets for improved management. METHODS AND ANALYSIS: ICTAL Registry is a multicentre open cohort of critically ill patients with convulsive, non-convulsive or psychogenic non-epileptic SE. Observational methods are applied to collect uniform data. The goal of the ICTAL Registry is to collect high-quality information on a large number of patients, thereby allowing elucidation of the pathophysiological mechanisms involved in mortality and morbidity. The registry structure is modular, with a large core data set and the opportunity for research teams to create satellite data sets for observational or interventional studies (eg, cohort multiple randomised controlled trials, cross-sectional studies and short-term and long-term longitudinal outcome studies). The availability of core data will hasten patient recruitment to studies, while also decreasing costs. Importantly, the vast amount of data from a large number of patients will allow valid subgroup analyses, which are expected to identify patient populations requiring specific treatment strategies. The results of the studies will have a broad spectrum of application, particularly given the multidisciplinary approach used by the IctalGroup research network. ETHICS AND DISSEMINATION: The ICTAL Registry protocol was approved by the ethics committee of the French Intensive Care Society (#CE_SRLF 19-68 and 19-68a). Patients or their relatives/proxies received written information to the use of the retrospectively collected and pseudonymised data, in compliance with French law. Prospectively included patients receive written consent form as soon as they recover decision-making competency; if they refuse consent, they are excluded from the registry. Data from the registry will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03457831.

Assessment of consciousness with electrophysiological and neurological imaging techniques.

PURPOSE OF REVIEW: Brain MRI (diffusion tensor imaging and spectroscopy) and functional neuroimaging (PET, functional MRI, EEG and evoked potential studies) are changing our understanding of patients with disorders of consciousness encountered after coma such as the 'vegetative' or minimally conscious states. RECENT FINDINGS: Increasing evidence from functional neuroimaging and electrophysiology demonstrates some residual cognitive processing in a subgroup of patients who clinically fail to show any response to commands, leading to the recent proposal of 'unresponsive wakefulness syndrome' as an alternative name for patients previously coined 'vegetative' or 'apallic'. SUMMARY: Consciousness can be viewed as the emergent property of the collective behavior of widespread thalamocortical frontoparietal network connectivity. Data from physiological, pharmacological and pathological alterations of consciousness provide evidence in favor of this hypothesis. Increasing our understanding of the neural correlates of consciousness is helping clinicians to do a better job in terms of diagnosis, prognosis and finally treatment and drug development for these severely brain-damaged patients. The current challenge remains to continue translating this research from the bench to the bedside. Only well controlled large multicentric neuroimaging and electrophysiology studies will enable to identify which paraclinical diagnostic or prognostic test is necessary for our routine evidence-based assessment of individuals with disorders of consciousness.