Body-weight support gait training in neurological intensive care: safety, feasibility, and delays before walking with or without suspension.

BACKGROUND: Early Mobilization in Intensive Care Units (ICUs) enhances patients' evolution, but has been rarely studied in neurological ICUs. The aim of this study was to assess gait training with body-weight support (BWS) in neuroICU, and to report on its safety, feasibility and on delays before walking with and without BWS. METHODS: This study was an observational one-year single-center study. Inclusion criteria were adults with a neurological injury requiring mechanical ventilation. Exclusion criteria were early death or ICU transfer. After weaning from ventilation, patients were screened for indications of BWS walking using predefined criteria. RESULTS: Patients' conditions were mostly brain injuries: 32% subarachnoid hemorrhages, 42% focal strokes, and 12% traumatic brain injuries. Out of 272 admissions, 136 patients were excluded, 78 were eligible, and 33 performed BWS walking. Among non-eligible patients, 36 walked unsuspended upon ventilation weaning, 17 presented too severe impairments. Among the 45 eligible patients who did not receive BWS training, main reasons were workload and weekends (31%), medical barriers (29%), and early ICU discharge (22%). 78 BWS sessions were performed on the 33 beneficiaries (median sessions per patient 2, max 10). Pre-session, most patients had inadequate response to pain, orders, or simple orientation questions. Sitting without support was impossible for 74%. Most pre-post changes in hemodynamic, respiratory, and pain parameters were small, and recovered spontaneously after the session. Eight sessions were interrupted; reasons were pain, fatigue or major imbalance (4), syncope (1), occurrence of stool (2), and battery failure (1). None of these adverse events required medical intervention, patients recovered upon session interruption. Median session duration was 31 min, patients walked on median 17 m. First BWS session occurred on median 3 days after ventilation weaning, and 11 days before patients were able to walk unsuspended. CONCLUSIONS: Verticalization and walking using a suspension device in patients in neuroICU allows early gait training, despite challenging neurological impairments. It is safe and generally well tolerated. TRIAL REGISTRATION: ClinicalTrials database (ID: NCT04300491).

Anxiety and depression symptoms in relatives of moderate-to-severe traumatic brain injury survivors - A multicentre cohort.

INTRODUCTION: The prevalence and risk factors of anxiety and depression symptoms in relatives of moderate to severe traumatic brain injury (TBI) survivors have not been thoroughly investigated. METHODS: Ancillary study of a multicentric prospective randomized-controlled trial in nine university hospitals in 370 moderate-to-severe TBI patients. TBI survivor-relative dyads were included in the 6th month of follow-up. Relatives responded to the Hospital Anxiety and Depression Scale (HADS). The primary endpoints were the prevalence of severe symptoms of anxiety (HADS-Anxiety ≥ 11) and depression (HADS-Depression ≥ 11) in relatives. We explored the risk factors of severe anxiety and depression symptoms. RESULTS: Relatives were predominantly women (80.7%), spouse-husband (47.7%), or parents (39%). Out of the 171 dyads included, 83 (50.6%) and 59 (34.9%) relatives displayed severe symptoms of anxiety and depression, respectively. Severe anxiety symptoms in relatives were independently associated with the patient's discharge at home (OR 2.57, 95%CI [1.04-6.37]) and the patient's higher SF-36 Mental Health domain scores (OR 1.03 95%CI [1.01-1.05]). Severe depression symptoms were independently associated with a lower SF-36 Mental Health domain score (OR = 0.98 95%CI [0.96-1.00]). No ICU organization characteristics were associated with psychological symptoms in relatives. DISCUSSION: There is a high prevalence of anxiety and depression symptoms among relatives of moderate-to-severe TBI survivors at 6 months. Anxiety and depression were inversely correlated with the patient's mental health status at 6 months. CONCLUSIONS: Long-term follow-up must provide psychological care to relatives after TBI.

Impact of continuous hypertonic (NaCl 20%) saline solution on renal outcomes after traumatic brain injury (TBI): a post hoc analysis of the COBI trial.

BACKGROUND: To evaluate if the increase in chloride intake during a continuous infusion of 20% hypertonic saline solution (HSS) is associated with an increase in the incidence of acute kidney injury (AKI) compared to standard of care in traumatic brain injury patients. METHODS: In this post hoc analysis of the COBI trial, 370 patients admitted for a moderate-to-severe TBI in the 9 participating ICUs were enrolled. The intervention consisted in a continuous infusion of HSS to maintain a blood sodium level between 150 and 155 mmol/L for at least 48 h. Patients enrolled in the control arm were treated as recommended by the latest Brain Trauma foundation guidelines. The primary outcome of this study was the occurrence of AKI within 28 days after enrollment. AKI was defined by stages 2 or 3 according to KDIGO criteria. RESULTS: After exclusion of missing data, 322 patients were included in this post hoc analysis. The patients randomized in the intervention arm received a significantly higher amount of chloride during the first 4 days (intervention group: 97.3 ± 31.6 g vs. control group: 61.3 ± 38.1 g; p < 0.001) and had higher blood chloride levels at day 4 (117.9 ± 10.7 mmol/L vs. 111.6 ± 9 mmol/L, respectively, p < 0.001). The incidence of AKI was not statistically different between the intervention and the control group (24.5% vs. 28.9%, respectively; p = 0.45). CONCLUSIONS: Despite a significant increase in chloride intake, a continuous infusion of HSS was not associated with AKI in moderate-to-severe TBI patients. Our study does not confirm the potentially detrimental effect of chloride load on kidney function in ICU patients. TRIAL REGISTRATION: The COBI trial was registered on clinicaltrial.gov (Trial registration number: NCT03143751, date of registration: 8 May 2017).

Transcranial sonographic assessment of the third ventricle in neuro-ICU patients to detect hydrocephalus: a diagnostic reliability pilot study.

BACKGROUND: Transcranial sonography is a point-of-care tool recommended in intensive care units (ICU) to monitor brain injured patients. Objectives of the study was to assess feasibility and reliability of the third ventricle (V3) diameter measurement using transcranial sonography (TCS) compared to brain computed-tomography (CT), the gold standard measurement, and to measure the TCS learning curve. DESIGN: prospective study, in a 16-bed neurological ICU in an academic hospital. Every consecutive brain injured adult patient, who required a brain CT and TCS monitoring were included. The V3 diameter was blindly measured by TCS and CT. Intraclass correlation coefficient (ICC) and Bland-Altman plot were used to assess the reliability and agreement between TCS and CT V3 measurements. Diagnosis performance of the V3 diameter using TCS to detect hydrocephalus was measured. Absolute difference between V3 measurement by residents and experts was measured consecutively to assess the learning curve. RESULTS: Among the 100 patients included in the study, V3 diameter could be assessed in 87 patients (87%) from at least one side of the skull. Both temporal windows were available in 70 patients (70%). The ICC between V3 diameter measured by TCS and CT was 0.90 [95% CI 0.84-0.93] on the right side, and 0.92 [0.88-0.95] on the left side. In Bland-Altman analysis, mean difference, standard deviation, 95% limits of agreement were 0.36, 1.52, - 2.7 to 3.3 mm, respectively, on the right side; 0.25, 1.47, - 2.7 to 3.1 mm, respectively, on the left side. Among the 35 patients with hydrocephalus, V3 diameters could be measured by TCS in 31 patients (89%) from at least one side. Hydrocephalus was, respectively, excluded, confirmed, or inconclusive using TCS in 35 (40%), 25 (29%) and 27 (31%) of the 87 assessable patients. After 5 measurements, every resident reached a satisfactory measurement compared to the expert operator. CONCLUSION: TCS allows rapid, simple and reliable V3 diameter measurement compared with the gold standard in neuro-ICU patients. Aside from sparing irradiating procedures and transfers to the radiology department, it may especially increase close patient monitoring to detect clinically occult hydrocephalus earlier. Further studies are needed to measure the potential clinical benefit of this method. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02830269.

Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial.

Importance: Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. Objective: To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. Design, Setting, and Participants: Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. Interventions: Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. Main Outcomes and Measures: The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. Results: Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47; P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, -2.6% [95% CI, -12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, -4.9% [95% CI, -12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). Conclusions and Relevance: Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03143751.

Interstitial Lung Disease Worsens Short- and Long-Term Outcomes of Systemic Rheumatic Disease Patients Admitted to the ICU: A Multicenter Study.

Critically ill patients with systemic rheumatic diseases (SRDs) have a fair prognosis, while those with interstitial lung disease (ILD) have a poorer outcome. However, the prognosis of SRD patients with ILD admitted to the intensive care unit (ICU) remains unclear. We conducted a case-control study to investigate the outcomes of critically ill SRD-ILD patients. Consecutive SRD-ILD patients admitted to five ICUs from January 2007 to December 2017 were compared to SRD patients without ILD. Mortality rates were compared between groups, and prognostic factors were then identified. One hundred and forty critically ill SRD patients were included in the study. Among the 70 patients with SRD-ILD, the SRDs were connective tissue diseases (56%), vasculitis (29%), sarcoidosis (13%), and spondylarthritis (3%). Patients were mainly admitted for acute exacerbation of SRD-ILD (36%) or infection (34%). ICU, in-hospital, and one-year mortality rates in SRD-ILD patients were higher than in SRD patients without ILD (n = 70): 40% vs. 16% (p < 0.01), 49% vs. 19% (p < 0.01), and 66% vs. 40% (p < 0.01), respectively. Hypoxemia, high sequential organ failure assessment (SOFA) score, and admission for ILD acute exacerbation were associated with ICU mortality. In conclusion, ILD worsened the outcomes of SRD patients admitted to the ICU. Admissions related to SRD-ILD acute exacerbation and the severity of the acute respiratory failure were associated with ICU mortality.

Long-term outcome in patients with aneurysmal subarachnoid hemorrhage requiring mechanical ventilation.

BACKGROUND: Patients affected with aneurysmal subarachnoid hemorrhage (aSAH) often require intensive care, and then present distinctive outcome from less severe patients. We aimed to specify their long-term outcome and to identify factors associated with poor outcome. METHODS: We conducted a retrospective study in a French university hospital intensive care unit. Patients with aSAH requiring mechanical ventilation hospitalized between 2010 and 2015 were included. At least one year after initial bleeding, survival and degree of disability were assessed using the modified Rankin Scale (mRS) via telephone interviews. A multivariable logistic regression analysis was performed to determine independent factors associated with poor outcome defined as mRS≥3. RESULTS: Two-hundred thirty-six patients were included. Among them, 7 were lost to follow-up, and 229 were analyzed: 73 patients (32%) had a good outcome (mRS<3), and 156 (68%) had a poor outcome (mRS≥3). The estimated 1-year survival rate was 63%. One-hundred sixty-three patients patients (71%) suffered from early brain injuries (EBI), 33 (14%) from rebleeding, 80 (35%) from vasospasm and 63 (27%) from delayed cerebral ischemia (DCI). Multivariable logistic regression identified independent factors associated with poor outcome including delay between aSAH diagnosis and mRS assessment (OR, 0.96; 95% CI, 0.95-0.98; p<.0001), age (OR per 10 points, 1.57; 95% CI, 1.12-2.19; p = 0.008), WFNS V versus WFNS III (OR, 5.71; 95% CI 1.51-21.61; p = 0.004), subarachnoid rebleeding (OR, 6.47; 95% CI 1.16-36.06; p = 0.033), EBI (OR, 4.52; 95% CI 1.81-11.29; p = 0.001) and DCI (OR, 4.73; 95% CI, 1.66-13.49; p = 0.004). CONCLUSION: Among aSAH patients requiring assisted ventilation, two-third of them survived at one year, and one-third showed good long-term outcome. As it appears as an independant factor associated with poor outcome, DCI shoud retain particular attention in future studies beyond angiographic vasospasm.

Optimal intracranial pressure in patients with aneurysmal subarachnoid hemorrhage treated with coiling and requiring external ventricular drainage.

Optimal management of intracranial pressure (ICP) among aneurysmal subarachnoid hemorrhage (aSAH) patients requiring external ventricular drainage (EVD) is controversial. To analyze predictors of delayed cerebral ischemia (DCI)-related cerebral infarction after aSAH and the influence of ICP values on DCI, we prospectively collected consecutive patients with aSAH receiving coiling and requiring EVD. Predictors of DCI-related cerebral infarction (new CT hypodensities developed within the first 3 weeks not related to other causes) were studied. Vasospasm and brain hypoperfusion were studied with CT angiography and CT perfusion (RAPID-software). Among 50 aSAH patients requiring EVD, 21 (42%) developed DCI-related cerebral infarction, while 27 (54%) presented vasospasm. Mean ICP ranged between 2 and 19 mmHg. On the multivariate analysis, the mean ICP (OR = 2, 95%CI = 1.01-3.9, p = 0.042) and the mean hypoperfusion volume on Tmax delay > 6 (OR = 1.2, 95%CI = 1.01-1.3, p = 0.025) were independent predictors of DCI. To predict DCI-related cerebral infarction, Tmax delay > 6 s presented the highest AUC (0.956, SE = 0.025), with a cutoff value of 18 ml showing sensitivity, specificity, PPV, NPV, and accuracy of 90.5% (95%CI = 69-98.8%), 86.2% (95%CI = 68.4-96%), 82.6% (95%CI = 65.4-92%), 92.5% (95%CI = 77-98%), and 88% (95%CI = 75-95%), respectively. The AUC of the mean ICP was 0.825 (SE = 0.057), and the best cutoff value was 6.7 mmHg providing sensitivity, specificity, PPV, NPV, and accuracy of 71.4% (95%CI = 48-89%), 62% (95%CI = 42-79%), 58% (95%CI = 44-70%), 75% (95%CI = 59-86%), and 66% (95%CI = 51-79%) for the prediction of DCI-related cerebral infarction, respectively. Among aSAH patients receiving coiling and EVD, lower ICP (< 6.7 mmHg in our study) could potentially be beneficial in decreasing DCI-related cerebral infarction. Brain hypoperfusion with a volume > 18 ml at Tmax delay > 6 s presents a high sensibility and specificity in prediction of DCI-related cerebral infarction.

One-Year Outcome of Critically Ill Patients With Systemic Rheumatic Disease: A Multicenter Cohort Study.

BACKGROUND: Critically ill patients with systemic rheumatic disease (SRD) have benefited from better provision of rheumatic and critical care in recent years. Recent comprehensive data regarding in-hospital mortality rates and, most importantly, long-term outcomes are scarce. RESEARCH QUESTION: The aim of this study was to assess short and long-term outcome of patients with SRD who were admitted to the ICU. STUDY DESIGN AND METHODS: All records of patients with SRD who were admitted to ICU between 2006 and 2016 were reviewed. In-hospital and one-year mortality rates were assessed, and predictive factors of death were identified. RESULTS: A total of 525 patients with SRD were included. Causes of admission were most frequently shock (40.8%) and acute respiratory failure (31.8%). Main diagnoses were infection (39%) and SRD flare-up (35%). In-hospital and one-year mortality rates were 30.5% and 37.7%, respectively. Predictive factors that were associated with in-hospital and one-year mortalities were, respectively, age, prior corticosteroid therapy, simplified acute physiology score II ≥50, need for invasive mechanical ventilation, or need for renal replacement therapy. Knaus scale C or D and prior conventional disease modifying antirheumatic drug therapy was associated independently with death one-year after ICU admission. INTERPRETATION: Critically ill patients with SRD had a fair outcome after an ICU stay. Increased age, prior corticosteroid therapy, and severity of critical illness were associated significantly with short- and long-term mortality rates. The one-year mortality rate was also associated with prior health status and conventional disease modifying antirheumatic drug therapy.

Assessing pain in critically ill brain-injured patients: a psychometric comparison of 3 pain scales and videopupillometry.

Three clinical scales (the Nociception Coma Scale adapted for Intubated patients [NCS-I], its Revised version [NCS-R-I], and the Behavioral Pain Scale [BPS]) and videopupillometry were compared for measuring pain in intubated, noncommunicating, critically ill, brain-injured patients. Pain assessment was performed before, during, just after, and 5 minutes after 3 procedures: the reference non-nociceptive procedure (assessment of the Richmond Agitation Sedation Scale) and 2 nociceptive procedures (turning and tracheal suctioning). The primary endpoint was construct validity (discriminant and criterion validation), determined by comparing pain measurements between different times/procedures. Secondary endpoints were internal consistency, inter-rater reliability, and feasibility. Fifty patients (54% women, median age 63 years [56-68]) were included 13 [7-24] days after brain injury (76% hemorrhagic or ischemic strokes). All tools increased significantly more (P < 0.001) during the nociceptive procedures vs the non-nociceptive procedure. The BPS was the only pain tool that did not increase significantly during the non-nociceptive procedure (P = 0.41), suggesting that it was the most discriminant tool. The BPS, NCS-I, and NCS-R-I were good predictors of nociception with areas under the curves ≥0.96, contrary to videopupillometry (area under the curve = 0.67). The BPS, NCS-I, and NCS-I-R had high inter-rater reliabilities (weighted kappa = 0.86, 0.82 and 0.84, respectively). Internal consistency was moderate (>0.60) for all pain scales. Factor analysis represented a majority of information on a first dimension, with motor domains represented on a second dimension. Scale feasibility was better for the NCS-I and NCS-R-I than for the BPS. In conclusion, the BPS, NCS-I, and NCS-R-I are valid, reliable, and acceptable pain scales for use in intubated critically ill, brain-injured patients, unlike videopupillometry. Future research requires tool design centered on domains of observation adapted to this very specific population.

Success of tardive electroconvulsive therapy sessions after loxapine-induced malignant syndrome in the context of very poor metabolisation.

We report the success of tardive electroconvulsive therapy in a case of loxapine malignant syndrome with catatonia. Loxapine and its metabolites were measured in biological samples by liquid chromatography coupled to tandem mass spectrometry. Genes were studied by sequencing and quantitative polymerase chain reaction (PCR). Plasmatic drug concentrations showed a supratherapeutic concentration of loxapine with a very low 8-hydroxyloxapine/loxapine ratio (range from 0.32 to 0.66, normal value>2 for 100mg) and a very long elimination half-life of loxapine (half-life>140h, normal value from 1 to 4hours). We tried to explain this kinetics by exploring the main pharmacogenes implicated in the metabolism of loxapine. No genetic abnormality for CYP1A2 was observed. The study of associated treatments showed the potential contribution of valproate. Pharmacokinetics and pharmacogenetics investigations revealed a blockade of the CYP1A2 metabolic pathway without genetic abnormalities, probably due to valproate co-medication. Toxicological monitoring of loxapine and its metabolites helped to explain the persistence of symptoms and to adapt the therapeutic management.