Outcome Prognostication of Acute Brain Injury using the Neurological Pupil Index (ORANGE) study: protocol for a prospective, observational, multicentre, international cohort study.

The pupillary examination is an important part of the neurological assessment, especially in the setting of acutely brain-injured patients, and pupillary abnormalities are associated with poor outcomes. Currently, the pupillary examination is based on a visual, subjective and frequently inaccurate estimation. The use of automated infrared pupillometry to measure the pupillary light reflex can precisely quantify subtle changes in pupillary functions. The study aimed to evaluate the association between abnormal pupillary function, assessed by the Neurological Pupil Index (NPi), and long-term outcomes in patients with acute brain injury (ABI). The Outcome Prognostication of Acute Brain Injury using the Neurological Pupil Index study is a prospective, observational study including adult patients with ABI requiring admission at the intensive care unit. We aimed to recruit at least 420 patients including those suffering from traumatic brain injury or haemorrhagic strokes, over 12 months. The primary aim was to assess the relationship between NPi and 6-month mortality or poor neurological outcome, measured by the Extended Glasgow Outcome Score (GOS-E, poor outcome=GOS-E 1-4). Supervised and unsupervised methods and latent class mixed models will be used to identify patterns of NPi trajectories and Cox and logistic model to evaluate their association with outcome. The study has been approved by the institutional review board (Comitato Etico Brianza) on 16 July 2020. Approved protocol V.4.0 dated 10 March 2020. The results of this study will be published in peer-reviewed journals and presented at conferences. NCT04490005

The Association Between Peri-Hemorrhagic Metabolites and Cerebral Hemodynamics in Comatose Patients With Spontaneous Intracerebral Hemorrhage: An International Multicenter Pilot Study Analysis.

Background and Objective: Cerebral microdialysis (CMD) enables monitoring brain tissue metabolism and risk factors for secondary brain injury such as an imbalance of consumption, altered utilization, and delivery of oxygen and glucose, frequently present following spontaneous intracerebral hemorrhage (SICH). The aim of this study was to evaluate the relationship between lactate/pyruvate ratio (LPR) with hemodynamic variables [mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebrovascular pressure reactivity (PRx)] and metabolic variables (glutamate, glucose, and glycerol), within the cerebral peri-hemorrhagic region, with the hypothesis that there may be an association between these variables, leading to a worsening of outcome in comatose SICH patients. Methods: This is an international multicenter cohort study regarding a retrospective dataset analysis of non-consecutive comatose patients with supratentorial SICH undergoing invasive multimodality neuromonitoring admitted to neurocritical care units pertaining to three different centers. Patients with SICH were included if they had an indication for invasive ICP and CMD monitoring, were >18 years of age, and had a Glasgow Coma Scale (GCS) score of ≤8. Results: Twenty-two patients were included in the analysis. A total monitoring time of 1,558 h was analyzed, with a mean (SD) monitoring time of 70.72 h (66.25) per patient. Moreover, 21 out of the 22 patients (95%) had disturbed cerebrovascular autoregulation during the observation period. When considering a dichotomized LPR for a threshold level of 25 or 40, there was a statistically significant difference in all the measured variables (PRx, glucose, glutamate), but not glycerol. When dichotomized PRx was considered as the dependent variable, only LPR was related to autoregulation. A lower PRx was associated with a higher survival [27.9% (23.1%) vs. 56.0% (31.3%), p = 0.03]. Conclusions: According to our results, disturbed autoregulation in comatose SICH patients is common. It is correlated to deranged metabolites within the peri-hemorrhagic region of the clot and is also associated with poor outcome

Echocardiography and pulse contour analysis to assess cardiac output in trauma patients.

Echocardiography is a valuable technique to assess cardiac output (CO) in trauma patients, but it does not allow a continuous bedside monitoring. Beat-to-beat CO assessment can be obtained by other techniques, including the pulse contour method MostCare. The aim of our study was to compare CO obtained with MostCare (MC-CO) with CO estimated by transthoracic echocardiography (TTE-CO) in trauma patients. METHODS: Forty-nine patients with blunt trauma admitted to an intensive care unit and requiring hemodynamic optimization within 24 hours from admission were studied. TTE-CO and MC-CO were estimated simultaneously at baseline, after a fluid challenge and after the start of vasoactive drug therapy. RESULTS: One hundred sixteen paired CO values were obtained. TTE-CO values ranged from 2.9 to 7.6 L·min-1, and MC-CO ranged from 2.8 to 8.2 L·min-1. The correlation between the two methods was 0.94 (95% confidence interval [CI] = 0.89 to 0.97; p<0.001). The mean bias was -0.06 L·min-1 with limits of agreements (LoA) of -0.94 to 0.82 L·min-1 (lower 95% CI, -1.16 to -0.72; upper 95% CI, 0.60 to 1.04) and a percentage error of 18%. Changes in CO showed a correlation of 0.91 (95% CI = 0.87 to 0.95; p<0.001), a mean bias of - 0.01 L·min-1 with LoA of -0.67 to 0.65 L·min-1 (lower 95% CI, -0.83 to -0.51; upper 95% CI, 0.48 to 0.81). CONCLUSION: CO measured by MostCare showed good agreement with CO obtained by transthoracic echocardiography. Pulse contour analysis can complement echocardiography in evaluating hemodynamics in trauma patients

Multimodal approach to predict neurological outcome after cardiac arrest: A single-center experience

Introduction: The aims of this study were to assess the concordance of different tools and to describe the accuracy of a multimodal approach to predict unfavorable neurological outcome (UO) in cardiac arrest patients. Methods: Retrospective study of adult (&gt;18 years) cardiac arrest patients who underwent multimodal monitoring; UO was defined as cerebral performance category 3-5 at 3 months. Predictors of UO were neurological pupillary index (NPi) 64 2 at 24 h; highly malignant patterns on EEG (HMp) within 48 h; bilateral absence of N20 waves on somato-sensory evoked potentials; and neuron-specific enolase (NSE) &gt; 75 \u3bcg/L. Time-dependent decisional tree (i.e., NPi on day 1; HMp on day 1-2; absent N20 on day 2-3; highest NSE) and classification and regression tree (CART) analysis were used to assess the prediction of UO. Results: Of 137 patients, 104 (73%) had UO. Abnormal NPi, HMp on day 1 or 2, the bilateral absence of N20 or NSE &gt;75 mcg/L had a specificity of 100% to predict UO. The presence of abnormal NPi was highly concordant with HMp and high NSE, and absence of N20 or high NSE with HMp. However, HMp had weak to moderate concordance with other predictors. The time-dependent decisional tree approach identified 73/103 patients (70%) with UO, showing a sensitivity of 71% and a specificity of 100%. Using the CART approach, HMp on EEG was the only variable significantly associated with UO. Conclusions: This study suggests that patients with UO had often at least two predictors of UO, except for HMp. A multimodal time-dependent approach may be helpful in the prediction of UO after CA. EEG should be included in all multimodal prognostic models

Chronic treatment with statins increases the availability of selenium in the antioxidant defence systems of hemodialysis patients.

Project. Oxidative stress (OS) is enhanced in hemodialysis (HD) patients. Lipid peroxidation and oxidative damage to glycids, proteins and nucleic acids are main consequences of OS and are associated to increased cardiovascular risk. Vitamin E and Glutathione Peroxidase (GSH-Px) represent main antioxidant systems in human cells. Selenium (Se), bound to the active sites of GSH-Px, plays a critical role in this antioxidant defense system. Statins are widely used and extensively investigated in the prevention of cardiovascular disease, notably in high-risk subjects. Several studies suggest that statins show antioxidant effects, protecting low-density lipoproteins from oxidation. Aim of our study was to compare serum Se concentration in ESRD patients on maintenance HD and in homogeneous healthy subjects and to investigate whether chronic assumption of statins may interfere with serum Se concentration in HD patients. Procedure. A total of 103 HD patients and 69 healthy subjects were enrolled; HD patients were then divided into patients who were not treated with statins (group A) and patients who assumed statins since six months at least (group B). Serum Se was determined by atomic absorption spectrometry. Results. Serum Se was significantly lower in HD patients of group A compared to healthy subjects (81.65±19.66mcg/L Vs. 96.47±15.62mcg/L, p<0.0040). However, in HD patients who assumed statins serum Se was significantly higher than in HD patients who did not. (111.83±18.82mcg/L Vs. 81.65±19.66mcg/L, p<0.0001). Conclusions. our results suggest that in HD patients chronic assumption of statins is related to a higher availability of active antioxidant agents and to reduced oxidative stress

Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs)

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.Peer reviewe

The acute phase management of spinal cord injury affecting polytrauma patients: the ASAP study

Background: Few data on the management of acute phase of traumatic spinal cord injury (tSCI) in patients suffering polytrauma are available. As the therapeutic choices in the first hours may have a deep impact on outcome of tSCI patients, we conducted an international survey investigating this topic. Methods: The survey was composed of 29 items. The main endpoints of the survey were to examine: (1) the hemodynamic and respiratory management, (2) the coagulation management, (3) the timing of magnetic resonance imaging (MRI) and spinal surgery, (4) the use of corticosteroid therapy, (5) the role of intraspinal pressure (ISP)/spinal cord perfusion pressure (SCPP) monitoring and (6) the utilization of therapeutic hypothermia. Results: There were 171 respondents from 139 centers worldwide. A target mean arterial pressure (MAP) target of 80–90&nbsp;mmHg was chosen in almost half of the cases [n = 84 (49.1%)]. A temporary reduction in the target MAP, for the time strictly necessary to achieve bleeding control in polytrauma, was accepted by most respondents [n = 100 (58.5%)]. Sixty-one respondents (35.7%) considered acceptable a hemoglobin (Hb) level of 7&nbsp;g/dl in tSCI polytraumatized patients. An arterial partial pressure of oxygen (PaO2) of 80–100&nbsp;mmHg [n = 94 (55%)] and an arterial partial pressure of carbon dioxide (PaCO2) of 35–40&nbsp;mmHg [n = 130 (76%)] were chosen in most cases. A little more than half of respondents considered safe a platelet (PLT) count &gt; 100.000/mm3 [n = 99 (57.9%)] and prothrombin time (PT)/activated partial thromboplastin time (aPTT) &lt; 1.5 times the normal control [n = 85 (49.7%)] in patients needing spinal surgery. MRI [n = 160 (93.6%)] and spinal surgery [n = 158 (92.4%)] should be performed after intracranial, hemodynamic, and respiratory stabilization by most respondents. Corticosteroids [n = 103 (60.2%)], ISP/SCPP monitoring [n = 148 (86.5%)], and therapeutic hypothermia [n = 137 (80%)] were not utilized by most respondents. Conclusions: Our survey has shown a great worldwide variability in clinical practices for acute phase management of tSCI patients with polytrauma. These findings can be helpful to define future research in order to optimize the care of patients suffering tSCI

Drivers and impact of antifungal therapy in critically ill patients with Aspergillus-positive respiratory tract cultures

Invasive pulmonary aspergillosis (IPA) is an increasingly recognised problem in critically ill patients. Little is known about how intensivists react to an Aspergillus-positive respiratory sample or the efficacy of antifungal therapy (AFT). This study aimed to identify drivers of AFT prescription and diagnostic workup in patients with Aspergillus isolation in respiratory specimens as well as the impact of AFT in these patients. ICU patients with an Aspergillus-positive respiratory sample from the database of a previous observational, multicentre study were analysed. Cases were classified as proven/putative IPA or Aspergillus colonisation. Demographic, microbiological, diagnostic and therapeutic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. Patients with putative/proven IPA were more likely to receive AFT than colonised patients (78.7% vs. 25.5%; P 7) (68.4% vs. 36.9%) (both P < 0.001). Once adjusted for disease severity, initiation of AFT did not alter the odds of survival (HR = 1.40, 95% CI 0.89–2.21). Likewise, treatment within 48 h following diagnosis did not change the clinical outcome (75.7% vs. 61.4%; P = 0.63). Treatment decisions appear to be based on diagnostic criteria and underlying disease severity at the time of Aspergillus isolation. IPA in this population has a dire prognosis and AFT is not associated with reduced mortality. This may be explained by delayed diagnosis and an often inevitable death due to advanced multiorgan failure

Influenza and associated co-infections in critically ill immunosuppressed patients

Background: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P &lt; 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P &lt; 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients