Potential benefits of therapeutic drug monitoring for beta-lactam antibiotics in augmented renal clearance patients: a case report.

Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case report displays the value of therapeutic drug monitoring (TDM) of piperacillin/tazobactam (PTZ) in this population. We identified two patients with ARC and intermittent administration of PTZ who took part in a prospective, descriptive study conducted at Hôpital du Sacré-Cœur de Montréal. Both had plasma samples drawn at peak, middle, and end of their dosing intervals of PTZ. Minimal inhibitory concentrations (MICs) of 4 and 8 mg/L were chosen to evaluate therapeutic target attainment at middle and end of dosing interval. The first patient was a 52-year-old male with a renal clearance rate estimated at 147 mL/min who received 3.375 g PTZ every 6 h. The second patient, a 49-year-old male, had an estimated renal clearance rate of 163 mL/min and received the same regimen. Both patients had piperacillin concentrations above the target MICs at middle of the dosing interval, but they failed to reach a trough concentration above 8 mg/L. The present case report showcases two patients with subtherapeutic PTZ concentrations despite strict following of local administration protocols. This suboptimal administration could not only lead to treatment failure, but also to the selection and growth of resistant pathogens. Implementing TDM would offer the possibility to adjust drug regimens in real-time and prevent situations like these from occurring.

Exposure levels and target attainment of piperacillin/tazobactam in adult patients admitted to the intensive care unit: a prospective observational study.

PURPOSE: The objective of this study was to evaluate the exposure and the pharmacodynamic target attainment of piperacillin/tazobactam (PTZ) in adult critically ill patients. METHODS: We conducted a prospective observational study in the intensive care unit (ICU) of the Hôpital du Sacré-Cœur de Montréal (a Level I trauma centre in Montreal, QC, Canada) between January 2021 and June 2022. We included patients aged 18 yr or older admitted to the ICU who received PTZ by intravenous administration. Demographic and clinical characteristics were collected, and clinical scores were calculated. On study day 1 of antimicrobial therapy, three blood samples were collected at the following timepoints: one hour after PTZ dose administration and at the middle and at the end of the dosing interval. The sampling schedule was repeated on days 4 and 7 of therapy if possible. Samples were analyzed by ultra-high performance liquid chromatography with diode array detector to determine the total piperacillin concentration. Middle- and end-of-interval concentrations were used for target attainment analyses, and were defined as a concentration above the minimal inhibitory concentration of 16 mg·L-1, corresponding to the breakpoint of Enterobacteriaceae and Pseudomonas aeruginosa. RESULTS: Forty-three patients were recruited and 202 blood samples were analyzed. The most prevalent dose was 3/0.375 g every six hours (n = 50/73 doses administered, 68%) with a 30-min infusion. We observed marked variability over the three sampling timepoints, and the median [interquartile range] piperacillin concentrations at peak, middle of interval, and end of interval were 109.4 [74.0-152.3], 59.3 [21.1-74.4], and 25.3 [6.8-44.6] mg·L-1, respectively. When assessing target attainment, 37% of patients did not reach the efficacy target of a trough concentration of 16 mg·L-1. The majority of patients who were underexposed were patients with normal to augmented renal clearance. CONCLUSION: In this prospective observational study of adult ICU patients receiving intravenous PTZ, a large proportion had subtherapeutic concentrations of piperacillin. This was most notable in patients with normal to augmented renal clearance. More aggressive dosage regimens may be required for this subpopulation to ensure attainment of efficacy targets.

RéSUMé: OBJECTIF: L'objectif de cette étude était d'évaluer l'exposition et l'atteinte des cibles pharmacodynamiques de la pipéracilline/tazobactam (PTZ) chez la patientèle adulte aux soins intensifs. MéTHODES: Nous avons réalisé une étude observationnelle prospective dans l'unité de soins intensifs (USI) de l'Hôpital du Sacré-Cœur de Montréal (un centre de traumatologie de niveau 1 à Montréal, QC, Canada) entre janvier 2021 et juin 2022. Nous avons inclus les patient·es adultes âgé·es de 18 ans ou plus admis·es à l'USI ayant reçu de la PTZ par administration intraveineuse. Les caractéristiques démographiques et cliniques ont été recueillies, et les scores cliniques ont été calculés. Au jour 1 de la thérapie antimicrobienne, trois échantillons sanguins ont été prélevés aux moments suivants : 1 h après l'administration de la dose de PTZ, au milieu et à la fin de l'intervalle d'administration. Le calendrier d'échantillonnage a été répété aux jours 4 et 7 de la thérapie si possible. Les échantillons ont été analysés par chromatographie liquide à ultra-haute performance avec détecteur à diodes pour déterminer la concentration totale de pipéracilline. Les concentrations du milieu et de fin d'intervalle ont été utilisées pour les analyses d'atteinte de cible, définie comme une concentration supérieure à la concentration minimale inhibitrice de 16 mg·L-1, associée aux Enterobacteriaceae et au Pseudomonas aeruginosa. RéSULTATS: Quarante-trois patient·es ont été recruté·es et 202 échantillons sanguins ont été analysés. La dose la plus prévalente était une dose de 3/0,375 g aux 6 h (n = 50/73 doses administrées, 68 %) avec une perfusion sur 30 min. Nous avons observé une variabilité marquée aux trois temps de prélèvement, et les concentrations médianes [intervalle interquartile] de pipéracilline au pic, au milieu et à la fin de l'intervalle étaient respectivement de 109,4 [74,0-152,3], 59,3 [21,1-74,4] et 25,3 [6,8-44,6] mg·L−1. Lors de l'évaluation de l'atteinte de la cible, 37 % des patient·es n'ont pas atteint la cible d'efficacité d'une concentration de 16 mg·L−1 à la fin de l'intervalle posologique. La majorité des patient·es sous-exposé·es étaient des personnes dont la clairance rénale était normale ou augmentée. CONCLUSION: Dans cette étude observationnelle prospective de patient·es adultes aux soins intensifs recevant de la PTZ par voie intraveineuse, une grande proportion de patient·es présentait des concentrations sous-thérapeutiques de pipéracilline. Ceci était plus marqué chez les patient·es ayant une clairance rénale normale ou augmentée. Des schémas posologiques plus agressifs pourraient être nécessaires pour cette sous-population afin de favoriser l'atteinte des cibles d'efficacité.

Physicians' beliefs and perceived importance of traumatic brain injury-associated agitation in critically ill patients: a survey of Canadian intensivists.

PURPOSE: Agitation is a common behavioural problem following traumatic brain injury (TBI). Intensive care unit (ICU) physicians' perspectives regarding TBI-associated agitation are unknown. Our objective was to describe physicians' beliefs and perceived importance of TBI-associated agitation in critically ill patients. METHODS: Following current standard guidance, we built an electronic, self-administrated, 42-item survey, pretested it for reliability and validity, and distributed it to 219 physicians working in 18 ICU level-1 trauma centres in Canada. We report the results using descriptive statistics. RESULTS: The overall response rate was 93/219 (42%), and 76/93 (82%) respondents completed the full survey. Most respondents were men with ten or more years of experience. Respondents believed that pre-existing dementia (90%) and regular recreational drug use (86%) are risk factors for agitation. Concerning management, 91% believed that the use of physical restraints could worsen agitation, 90% believed that having family at the bedside reduces agitation, and 72% believed that alpha-2 adrenergic agonists are efficacious for managing TBI agitation. Variability was observed in beliefs on epidemiology, sex, gender, age, socioeconomic status, and other pharmacologic options. Respondents considered TBI agitation frequent enough to justify the implementation of management protocols (87%), perceived the current level of clinical evidence on TBI agitation management to be insufficient (84%), and expressed concerns about acute and long-term detrimental outcomes and burden to patients, health care professionals, and relatives (85%). CONCLUSION: Traumatic brain injury-associated agitation in critically ill patients was perceived as an important issue for most ICU physicians. Physicians agreed on multiple approaches to manage TBI-associated agitation although agreement on epidemiology and risk factors was variable.

RéSUMé: OBJECTIF: L'agitation est un problème de comportement courant à la suite d'un traumatisme crânien (TC). Le point de vue des médecins des unités de soins intensifs (USI) sur l'agitation associée aux traumatismes crâniens est inconnu. Notre objectif était de décrire les croyances et l'importance perçue par les médecins de l'agitation associée aux traumatismes crâniens chez les patient·es gravement malades. MéTHODE: Conformément aux lignes directrices standard actuelles, nous avons élaboré un sondage électronique auto-administré de 42 questions, l'avons testé au préalable pour en vérifier la fiabilité et la validité, et l'avons distribué à 219 médecins travaillant dans les USI de 18 centres de traumatologie de niveau 1 au Canada. Les résultats sont présentés à l'aide de statistiques descriptives. RéSULTATS: Le taux de réponse global a été de 93 sur 219 (42 %) et 76 sur 93 (82 %) personnes interrogées ont répondu à l'ensemble du sondage. La plupart des répondant·es étaient des hommes comptant dix ans ou plus d'expérience. Les répondant·es sont d'avis que la démence préexistante (90 %) et la consommation régulière de drogues à des fins récréatives (86 %) sont des facteurs de risque d'agitation. En ce qui concerne la prise en charge, 91 % des répondant·es estiment que l'utilisation de contentions physiques peut aggraver l'agitation, 90 % croient que le fait d'avoir de la famille au chevet du patient ou de la patiente réduit l'agitation et 72 % pensent que les agonistes alpha-2 adrénergiques sont efficaces pour gérer l'agitation causée par les traumatismes crâniens. Une variabilité a été observée dans les croyances concernant l'épidémiologie, le sexe, le genre, l'âge, le statut socio-économique et d'autres options pharmacologiques. Les répondant·es considéraient que l'agitation liée aux traumatismes crâniens était suffisamment fréquente pour justifier la mise en œuvre de protocoles de prise en charge (87 %), estimaient que le niveau actuel de données probantes cliniques sur la prise en charge de l'agitation causée par un traumatisme crânien était insuffisant (84 %), et se sont dit·es préoccupé·es par les conséquences préjudiciables aiguës et à long terme et par le fardeau pour les patient·es, les professionnel·les de la santé et les proches (85 %). CONCLUSION: L'agitation associée à un traumatisme crânien chez les patient·es gravement malades était perçue comme un problème important pour la plupart des médecins des soins intensifs. Les médecins s'entendaient sur plusieurs approches pour gérer l'agitation associée aux traumatismes crâniens, bien que l'accord sur l'épidémiologie et les facteurs de risque était variable.

Subtyping at-risk adolescents for predicting response toward insomnia prevention program.

BACKGROUND: Previous study has shown that a brief cognitive-behavioral prevention insomnia program could reduce 71% risk of developing insomnia among at-risk adolescents. This study aimed to evaluate the differential response to insomnia prevention in subgroups of at-risk adolescents. METHODS: Adolescents with a family history of insomnia and subthreshold insomnia symptoms were randomly assigned to a 4-week insomnia prevention program or nonactive control group. Assessments were conducted at baseline, 1 week, and 6- and 12-month after the intervention. Baseline sleep, daytime, and mood profiles were used to determine different subgroups by using latent class analysis (LCA). Analyses were conducted based on the intention-to-treat approach. RESULTS: LCA identified three subgroups: (a) insomnia symptoms only, (b) insomnia symptoms with daytime sleepiness and mild anxiety, and (c) insomnia symptoms with daytime sleepiness, mild anxiety, and depression. The incidence rate of insomnia disorder over the 12-month follow-up was significantly reduced for adolescents receiving intervention in subgroup 3 compared with the controls (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.13-0.99; p = .049) and marginally for subgroup 2 (HR = 0.14; 95% CI: 0.02-1.08; p = .059). In addition, adolescents who received intervention in subgroups 2 and 3 had a reduced risk of excessive daytime sleepiness (subgroup 2: adjusted OR [AdjOR] = 0.45, 95% CI: 0.23-0.87; subgroup 3: AdjOR = 0.32, 95% CI: 0.13-0.76) and possible anxiety (subgroup 2: AdjOR = 0.47, 95% CI: 0.27-0.82; subgroup 3: AdjOR = 0.33, 95% CI: 0.14-0.78) compared with the controls over the 12-month follow-up. CONCLUSIONS: Adolescents at risk for insomnia can be classified into different subgroups according to their psychological profiles, which were associated with differential responses to the insomnia prevention program. These findings indicate the need for further phenotyping and subgrouping at-risk adolescents to develop personalized insomnia prevention.

Association of Initial Pulseless Electrical Activity Heart Rate and Clinical Outcomes following Adult Non-Traumatic Out-of-Hospital Cardiac Arrest.

OBJECTIVE: Studies evaluating the prognostic value of the pulseless electrical activity (PEA) heart rate in out-of-hospital cardiac arrest (OHCA) patients have reported conflicting results. The objective of this study was to evaluate the association between the initial PEA heart rate and favorable clinical outcomes for OHCA patients. METHODS: The present post-hoc cohort study used the Resuscitation Outcomes Consortium Cardiac Epidemiologic Registry Version 3, which included OHCA patients in seven US and three Canadian sites from April 2011 to June 2015. The primary outcome was survival to hospital discharge and the secondary outcome was survival with a good functional outcome. For the primary analysis, the patients were separated into eight groups according to their first rhythms and PEA heart rates: (1) initial PEA heart rate of 1-20 beats per minute (bpm); (2) 21-40 bpm; (3) 41-60 bpm; (4) 61-80 bpm; (5) 81-100 bpm; (6) 101-120 bpm; (7) over 120 bpm; (8) initial shockable rhythm (reference category). Multivariable logistic regression models were used to assess the associations of interest. RESULTS: We identified 17,675 patients (PEA: 7,089 [40.1%]; initial shockable rhythm: 10,797 [59.9%]). Patients with initial PEA electrical frequencies ≤100 bpm were less likely to survive to hospital discharge than patients with initial shockable rhythms (1-20 bpm: adjusted odds ratio [AOR] = 0.15 [95%CI 0.11-0.21]; 21-40 bpm: AOR = 0.21 [0.18-0.25]; 41-60 bpm: AOR = 0.30 [0.25-0.36]; 61-80 bpm: AOR = 0.37 [0.28-0.49]; 81-100 bpm: AOR = 0.55 [0.41-0.65]). However, there were no statistical outcome differences between PEA patients with initial electrical frequencies of >100 bpm and patients with initial shockable rhythms (101-120 bpm: AOR = 0.65 [95%CI 0.42-1.01]; >120 bpm: AOR = 0.72 [95%CI 0.37-1.39]). Similar results were observed for survival with good functional outcomes (101-120 bpm: AOR = 0.60 [95%CI 0.31-1.15]; >120 bpm: AOR = 1.08 [95%CI 0.50-2.28]). CONCLUSIONS: We observed a good association between higher initial PEA electrical frequency and favorable clinical outcomes for OHCA patients. As there is no significant difference in outcomes between patients with initial PEA heart rates of more than 100 bpm and those with initial shockable rhythms, we can hypothesize that these patients could be considered in the same prognostic category.

Accuracy of the Initial Rhythm to Predict a Short No-Flow Time in Out-of-Hospital Cardiac Arrest.

OBJECTIVES: The no-flow time (NFT) can help establish prognosis in out-of-hospital cardiac arrest (OHCA) patients. It is often used as a selection criterion for extracorporeal resuscitation. In patients with an unwitnessed OHCA for whom the NFT is unknown, the initial rhythm has been proposed to identify those more likely to have had a short NFT. Our objective was to determine the predictive accuracy of an initial shockable rhythm for an NFT of 5 minutes or less (NFT ≤ 5). DESIGN: Retrospective analysis of prospectively collected data. SETTING: Prehospital OHCA in eight U.S. and three Canadian sites. PATIENTS: A total of 28,139 adult patients with a witnessed nontraumatic OHCA were included, of whom 11,228 (39.9%) experienced an emergency medical service-witnessed OHCA (NFT = 0), 695 (2.7%) had a bystander-witnessed OHCA, and an NFT less than or equal to 5, and 16,216 (57.6%) with a bystander-witnessed OHCA and an NFT greater than 5. INTERVENTIONS: Sensitivity, specificity, and likelihood ratios of an initial shockable rhythm to identify patients with an NFT less than or equal to 5 minutes. MEASUREMENTS AND MAIN RESULTS: The sensitivity of an initial shockable rhythm to identify patients with an NFT less than or equal to 5 was poor (25% [95% CI, 25-26]), but specificity was moderate (70% [95% CI, 69-71]). The positive and likelihood ratios were inverted (negative accuracy) (positive likelihood ratio, 0.76 [95% CI, 0.74-0.79]; negative likelihood ratio, 1.12 [95% CI, 1.10-1.12]). Including only patients with a bystander-witnessed OHCA improved the sensitivity to 48% (95% CI, 45-52), the positive likelihood ratio to 1.45 (95% CI, 1.33-1.58), and the negative likelihood ratio to 0.77 (95% CI, 0.72-0.83), while slightly lowering the specificity to 67% (95% CI, 66-67). CONCLUSIONS: Our analysis demonstrated that the presence of a shockable rhythm at the time of initial assessment was poorly sensitive and only moderately specific for OHCA patients with a short NFT. The initial rhythm, therefore, should not be used as a surrogate for NFT in clinical decision-making.

The Suitability of Potential Organ Donors Using Real Case-Scenarios; Do we Need to Create a "Donor Board" Process for Donors Perceived as Unlikely Suitable?

Introduction: Despite availability of selection criteria, different interpretations can lead to variability in the appreciation of donor eligibility with possible viable organs missed. Our primary objective was to test the perception of feasibility of potential organ donors through the survey of a small sample of external evaluators. Methods: Clinical scenarios summarizing 66 potential donors managed in the first year of our Organ Recovery Center were sent to four critical care physicians to evaluate the feasibility of the potential donors and the probability of organ procurement. Results: Potential donors procuring at least one organ were identified in 55 of the 66 cases (83%). Unanimity was reached in 38 cases, encompassing 35 out of the 55 converted and 3 of the non-converted donors. The overall agreement was moderate (kappa = 0.60, 95% CI: 0.37-0.82). For the organs finally procured for transplantation, organ donation was predicted for the majority of the cases, but high discrepancy was present with the final outcome of organs not procured (particularly liver and kidney). Conclusion: The assessment of a potential donor is a complex dynamic process. In order to increase organ availability, standardized electronically clinical data, as well a "donor board" structure of decision might inform future systems.

Parameters associated with successful weaning of veno-arterial extracorporeal membrane oxygenation: a systematic review.

PURPOSE: Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) can be used to restore organ perfusion in patients with cardiogenic shock until native heart recovery occurs. It may be challenging, however, to determine when patients can be weaned successfully from ECMO-surviving without requiring further mechanical support or heart transplant. We aimed to systematically review the medical literature to determine the biomarkers, hemodynamic and echocardiographic parameters associated with successful weaning of VA-ECMO in adults with cardiogenic shock and to present an evidence-based weaning algorithm incorporating key findings. METHOD: We systematically searched PubMed, Embase, ProQuest, Google Scholars, Web of Science and the Grey literature for pertinent original research reports. We excluded studies limited to extracorporeal cardiopulmonary resuscitation (ECPR) as the neurological prognosis may significantly alter the decision-making process surrounding the device removal in this patient population. Studies with a mixed population of VA-ECMO for cardiogenic shock or cardiac arrest were included. We excluded studies limited to patients in which ECMO was only used as a bridge to VAD or heart transplant, as such patients are, by definition, never "successfully weaned." We used the Risk of Bias Assessment tool for Non-Randomized Studies. The study was registered on the International prospective register of systematic reviews (PROSPERO CRD42020178641). RESULTS: We screened 14,578 records and included 47 that met our pre-specified criteria. Signs of lower initial severity of shock and myocardial injury, early recovery of systemic perfusion, left and right ventricular recovery, hemodynamic and echocardiographic stability during flow reduction trial and/or pump-controlled retrograde trial off predicted successful weaning. The most widely used parameter was the left ventricular outflow tract velocity time integral, an indicator of stroke volume. Most studies had a moderate or high risk of bias. Heterogeneity in methods, timing, and conditions of measurements precluded any meta-analysis. CONCLUSIONS: In adult patients on VA-ECMO for cardiogenic shock, multiple biomarkers, hemodynamic and echocardiographic parameters may be used to track resolution of systemic hypoperfusion and myocardial recovery in order to identify patients that can be successfully weaned.

Intermediate phenotypes of childhood obstructive sleep apnea.

An intermediate phenotype of a disease is a trait in the path of pathogenesis from genetic predisposition to disease manifestation. Identifying intermediate phenotypes with high heritability is helpful in delineating the genetics of a disorder. In this study, we aimed to examine various traits with regards to obesity, cardiovascular risk and upper airway structure to identify potential intermediate phenotypes of childhood obstructive sleep apnea (OSA). Children aged between 6 and 18 years and their parents and siblings were recruited. All subjects underwent anthropometric measurements, cardiovascular risk assessment, sonographic measurement of lateral parapharyngeal wall (LPW) thickness, X-ray cephalometry and overnight polysomnography. A total of 34 phenotypes were examined. One hundred and one families consisting of 127 children (46 overweight) and 198 adults (84 overweight) were recruited. Heritability of obstructive apnea-hypopnea index (OAHI) was significant in overweight (h2  = 0.54) but not normal-weight individuals (h2  = 0.12). LPW thickness (h2  = 0.68) and resting blood pressure (h2  = 0.36 and 0.43 for systolic blood pressure [SBP] and diastolic blood pressure [DBP], respectively) were significantly heritable and associated with OAHI. Moreover, these traits were found to have shared genetic variance with OAHI in the overweight subgroup. Hyoid bone position also had significant heritability (h2  = 0.55) and association with OAHI but genetic correlation with OSA severity was not demonstrated. These findings suggest that LPW thickness and resting blood pressure are possible intermediate phenotypes of OSA independent of body mass index, especially in overweight patients. Identifying genes relevant to these phenotypes may help to elucidate the genetic susceptibility of OSA.

Prenatal methylmercury exposure is associated with decrease heart rate variability in children.

BACKGROUND: Although several epidemiological studies have suggested mercury (Hg) might be associated with cardiotoxicity, the impact of Hg exposure on cardiac autonomic activity and blood pressure in children has not been investigated at Hg exposure levels equivalent to the Environmental Protection Agency (EPA) reference dose. OBJECTIVE: To investigate the association between low dose prenatal and recent methylmercury (MeHg) exposures and cardiac autonomic function and blood pressure with adjustment for factors such as fish consumption among children from a high fish consumption coastal city. METHODS: Children aged 7-8 years were recruited from the birth cohort of our previous study. Heart rate variability (HRV), resting heart rate (RHR) and blood pressure were measured as surrogate markers of cardiac autonomic function. Cord blood and current whole blood Hg concentration were used as biomarkers of prenatal and recent MeHg exposure, respectively. Recent fish consumption information was estimated with a food frequency questionnaire. RESULTS: Among 604 children, median cord blood and whole blood Hg concentrations were 45.9 nmol/L (IQR: 32.8-65.03 nmol/L) and 13.57 nmol/L (IQR: 9.29-19.72 nmol/L), respectively. Our results demonstrated that prenatal MeHg exposure was associated with decreased HRV (i.e. low CVRR, SDRR, and RMSSD), reflecting reduced parasympathetic activity (i.e. low CCVHF and HF), and a sympathovagal balance shift toward sympathetic predominance (i.e. high %LF and LF/HF ratio). Adjustment of recent fish consumption further increased the significance and magnitude of the adverse associations of MeHg. CONCLUSION: The results of this study suggest that prenatal MeHg exposure is associated with decreased parasympathetic modulation of cardiac autonomic function in children.

Cardiovascular risks of children with primary snoring: A 5-year follow-up study.

BACKGROUND AND OBJECTIVE: This study aimed to investigate if childhood primary snoring (PS) was associated with adverse cardiovascular outcomes at 5-year follow-up. METHODS: This was a prospective matched cohort study. Subjects were recruited from a hospital-based cohort established from years 2006 to 2012 and they were aged 6-18 years at baseline. Each subject with PS was gender, age and BMI z-score matched with a control who had normal sleep study (obstructive apnoea-hypopnoea index [OAHI] < 1/h) and without habitual snoring (<3 nights/week) at baseline. All subjects underwent measurements of flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT) and sleep study at baseline and follow-up visits. Twenty-four hour ambulatory blood pressure (ABP) was also recorded at follow-up. RESULTS: Fifty-five case-control pairs were recruited and the length of follow-up was 5.1 ± 1.3 years. At follow-up visit, subjects with PS at baseline had significantly lower FMD (-0.34% [-0.59 to -0.10]), greater cIMT (+0.01 mm [+0.001 to +0.013]), higher wake systolic blood pressure (SBP) (+2.6 mm Hg [+0.02 to +5.1]), sleep SBP (+3.0 mm Hg [+0.3 to +5.6]), sleep diastolic blood pressure (+2.2 mm Hg [+0.04 to +4.4]) and sleep mean arterial pressure (+2.2 mm Hg [+0.1 to +4.2]) compared to matched controls in the fully adjusted model for variables including change in OAHI and parental history of cardiovascular diseases. CONCLUSION: Childhood PS is associated with poorer endothelial function, greater cIMT and higher ABP at 5-year follow-up irrespective of change in obstructive sleep apnoea severity.

Continuous Renal Replacement Therapy with oXiris® Membrane in Severe Ebstein-Barr Virus-Mediated Hemophagocytic Lymphohistiocytosis: A Case Report.

Hemophagocytic lymphohistiocytosis (HLH), a life-threatening disease with uncontrolled immune activation and inflammatory reaction, often leads to a deadly cytokine storm. In severe Ebstein-Barr virus-triggered HLH receiving standard immunosuppression, continuous renal replacement therapy (CRRT) with oXiris® blood purification membrane resulted in a timely reduction of inflammatory markers and discontinuation of vasopressors. To our knowledge, this is the first report of successful use of the oXiris® membrane in HLH.

Early experience with critically ill patients with COVID-19 in Montreal.

PURPOSE: Montreal has been the epicentre of the coronavirus disease (COVID-19) pandemic in Canada. Given the regional disparities in incidence and mortality in the general population, we aimed to describe local characteristics, treatments, and outcomes of critically ill COVID-19 patients in Montreal. METHODS: A single-centre retrospective cohort of consecutive adult patients admitted to the intensive care unit (ICU) of Hôpital du Sacré-Coeur de Montréal with confirmed COVID-19 were included. RESULTS: Between 20 March and 13 May 2020, 75 patients were admitted, with a median [interquartile range (IQR)] age of 62 [53-72] yr and high rates of obesity (47%), hypertension (67%), and diabetes (37%). Healthcare-related infections were responsible for 35% of cases. The median [IQR] day 1 sequential organ failure assessment score was 6 [3-7]. Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5-22] days. Patients receiving IMV were characterized by a moderately decreased median [IQR] partial pressure of oxygen:fraction of inspired oxygen (day 1 PaO2:FiO2 = 177 [138-276]; day 10 = 173 [147-227]) and compliance (day 1 = 48 [38-58] mL/cmH2O; day 10 = 34 [28-42] mL/cmH2O) and very elevated estimated dead space fraction (day 1 = 0.60 [0.53-0.67]; day 10 = 0.72 [0.69-0.79]). Overall hospital mortality was 25%, and 21% in the IMV patients. Mortality was 82% in patients ≥ 80 yr old. CONCLUSIONS: Characteristics and outcomes of critically ill patients with COVID-19 in Montreal were similar to those reported in the existing literature. We found an increased physiologic dead space, supporting the hypothesis that pulmonary vascular injury may be central to COVID-19-induced lung damage.

RéSUMé: OBJECTIF: Montréal a été l'épicentre de la pandémie du coronavirus (COVID-19) au Canada. Étant donné les disparités régionales dans l'incidence et la mortalité dans la population générale, nous avons tenté de décrire les caractéristiques locales, les traitements et le devenir des patients atteints de la COVID-19 en état critique à Montréal. MéTHODE: Notre étude de cohorte rétrospective monocentrique a inclus tous les patients adultes admis consécutivement à l'unité de soins intensifs de l'Hôpital du Sacré-Cœur de Montréal avec un diagnostic confirmé de COVID-19. RéSULTATS: Soixante-quinze patients ont été admis entre le 20 mars et le 13 mai 2020. Ceux-ci avaient un âge médian [écart interquartile (ÉIQ)] de 62 [53­72] ans et présentaient une incidence élevée d'obésité (47 %), d'hypertension (67 %) et de diabète (37 %). Les transmissions associées aux soins de santé étaient responsables de 35 % des cas. Au jour 1, le score SOFA (Sequential Organ Failure Assessment ­ évaluation séquentielle de défaillance des organes) médian [ÉIQ] était de 6 [3­7]. La ventilation mécanique invasive (VMI) a été utilisée chez 57 % des patients, pour une durée médiane [ÉIQ] de 11 [5­22] jours. Les patients ayant reçu une VMI étaient caractérisés par une médiane [ÉIQ] modérément réduite de la pression partielle de la fraction d'oxygène inspiré (jour 1 PaO2:FiO2 = 177 [138­276]; jour 10 = 173 [147­227]), de la compliance (jour 1 = 48 [38­58] mL/cmH2O; jour 10 = 34 [28­42] mL/cmH2O), ainsi que par une fraction d'espace mort estimé très élevée (jour 1 = 0,60 [0,53-0,67]; jour 10 = 0,72 [0,69-0,79]). La mortalité hospitalière était de 25 % globalement, et de 21 % chez les patients avec VMI. La mortalité a atteint 82 % chez les patients agés de ≥ 80 ans. CONCLUSION: Les caractéristiques et le devenir des patients en état critique atteints de la COVID-19 à Montréal étaient semblables à ceux rapportés dans la littérature existante. Nous avons observé un espace mort physiologique augmenté, ce qui appuie l'hypothèse que des lésions vasculaires pulmonaires seraient primordiales dans les lésions pulmonaires induites par la COVID-19.

Safety of dexmedetomidine for the control of agitation in critically ill traumatic brain injury patients: a descriptive study.

BACKGROUND: Behavioural disturbances such as agitation are common following traumatic brain injury and can interfere with treatments, cause self-harm and delay rehabilitation. As there is a lack of evidence on the optimal approach to manage agitation in recovering TBI patients, various pharmacological agents are used including antipsychotics, anticonvulsants and sedative agents. Among sedatives, the safety and efficacy of dexmedetomidine to control agitation in traumatic brain injury patients is not well documented. OBJECTIVE: To describe the safety, use and efficacy of dexmedetomidine for the management of agitation following traumatic brain injury in the intensive care unit. METHODS: Medical records of all patients admitted to the intensive care unit of the Hôpital Sacré-Coeur de Montréal for a traumatic brain injury who received dexmedetomidine for agitation between 1 January 2017 and 31 December 2017 were reviewed. Patients who received dexmedetomidine for indications other than agitation were excluded. Data on dexmedetomidine prescription practices and safety were extracted. Frequency of agitation and concomitant psychoactive medication use was explored over a period starting two days prior to the initiation of dexmedetomidine to six days after or discontinuation, whichever came first. RESULTS: We identified 41 patients in whom dexmedetomidine was initiated. Dexmedetomidine was started on median ICU day 3 (25th -75th percentiles: 2-7) and had a median treatment duration of 3 days (25th -75th percentiles: 3-6) and a mean average rate of 0.62 mcg/kg/h (SD 0.25). Although hypotension (76%) and bradycardia (54%) were common, only one patient required intervention. The proportion of patients with at least one episode of agitation decreased from 100% on day 0, to 88%, 69% and 63% on days 1, 2 and 3 of dexmedetomidine, respectively. The decrease was statistically significant difference between days 0 and 2 as well as between days 0 and 3. Concomitant use of propofol and benzodiazepines also decreased over the course of dexmedetomidine treatment. CONCLUSION: Dexmedetomidine use was safe and associated with a reduction in agitation in traumatic brain injury patients in the 96 hours following its initiation.

Childhood OSA is an independent determinant of blood pressure in adulthood: longitudinal follow-up study.

BACKGROUND: Current literature supports cross-sectional association between childhood obstructive sleep apnoea (OSA) and elevated blood pressure (BP). However, long-term cardiovascular outcomes in children with OSA remain unexplored. OBJECTIVE: To evaluate the associations of childhood OSA with BP parameters in a prospective 10 year follow-up study. METHODS: Participants were recruited from a cohort established for our previous OSA epidemiological study. They were invited to undergo clinical examination, overnight polysomnography and 24-hour ambulatory BP monitoring. Multivariate linear regression was used to assess the associations of baseline childhood OSA with BP outcomes at follow-up. Multivariable log-binomial regression was used with inverse probability weighting to assess the adjusted associations of childhood OSA with hypertension and non-dipping of nocturnal BP in adulthood. RESULTS: 243 participants (59% male) attended the follow-up visit. The mean age was 9.8 (SD ±1.8) and 20.2 (SD ±1.9) years at baseline and follow-up respectively, with a mean follow-up duration of 10.4 (SD ±1.1) years. Childhood moderate-to-severe OSA was associated with higher nocturnal systolic blood pressure (SBP) (difference from normal controls: 6.5 mm Hg, 95% CI 2.9 to 10.1) and reduced nocturnal dipping of SBP (-4.1%, 95% CI -6.3% to 1.8%) at follow-up, adjusted for age, sex, Body Mass Index and height at baseline, regardless of the presence of OSA at follow-up. Childhood moderate-to-severe OSA was also associated with higher risk of hypertension (relative risk (RR) 2.5, 95% CI 1.2 to 5.3) and non-dipping of nocturnal SBP (RR 1.3, 95% CI 1.0 to 1.7) at follow-up. CONCLUSION: Childhood OSA was found to be an independent risk factor for adverse BP outcomes in adulthood.

Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.

OBJECTIVES: To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN: A multicenter randomized sham-controlled clinical trial. SETTING: Twelve ICUs in Canada. PATIENTS: We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS: Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS: The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS: Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.

Estimating glomerular filtration rate in patients with acute kidney injury: a prospective multicenter study of diagnostic accuracy.

BACKGROUND: Estimating glomerular filtration rate (GFR) in acute kidney injury (AKI) is challenging, with limited data comparing estimated and gold standard methods to assess GFR. The objective of our study was to assess the performance of the kinetic estimated GFR (KeGFR) and Jelliffe equations to estimate GFR in AKI, using a radioisotopic method (technetium-diethylenetriaminepentaacetic acid) as a reference measure. METHODS: We conducted a prospective multicenter observational study in hospitalized patients with AKI. We computed the Jelliffe and KeGFR equations to estimate GFR and compared these estimations to measured GFR (mGFR) by a radioisotopic method. The performances were assessed by correlation, Bland-Altman plots and smoothed and linear regressions. We conducted stratified analyses by age and chronic kidney disease (CKD). RESULTS: The study included 119 patients with AKI, mostly from the intensive care unit (63%) and with Stage 1 AKI (71%). The eGFR obtained from the Jelliffe and KeGFR equations showed a good correlation with mGFR (r = 0.73 and 0.68, respectively). The median eGFR by the Jelliffe and KeGFR equations was less than the median mGFR, indicating that these equations underestimated the mGFR. On Bland-Altman plots, the Jelliffe and KeGFR equations displayed a considerable lack of agreement with mGFR, with limits of agreement >40 mL/min/1.73 m2. Both equations performed better in CKD and the KeGFR performed better in older patients. Results were similar across AKI stages. CONCLUSIONS: In our study, the Jelliffe and KeGFR equations had good correlations with mGFR; however, they had wide limits of agreement. Further studies are needed to optimize the prediction of mGFR with estimatation equations.

Effects of insomnia symptoms and objective short sleep duration on memory performance in youths.

Sleep quantity and quality are both important for optimal development and functioning during youth. Yet few studies have examined the effects of insomnia symptoms and objective short sleep duration on memory performance among adolescents and young adults. One-hundred and ninety participants (female: 61.6%) aged from 12 to 24 years completed this study. All participants underwent a clinical interview, a 7-day actigraphic assessment, a battery of self-report questionnaires and cognitive tests to assess working memory and episodic memory. Insomnia symptoms were defined as a score ≥ 9 on the Insomnia Severity Index, and objective short sleep duration was defined as average total sleep time less than 7 hr for those aged 12-17 years, and 6 hr for those aged 18 years and above as assessed by actigraphy. Insomnia symptoms were significantly associated with worse self-perceived memory (p < .05) and poorer performance on the digit span task (p < .01), but not the dual N-back task and verbal learning task. There was no significant difference in any of the memory measures between participants with objective short sleep duration and their counterparts. No interaction effect was found between insomnia and short sleep duration on any of the objective memory outcomes. Insomnia symptoms, but not objective short sleep duration, were associated with poorer subjective memory and objective working memory performance in youths. Further studies are needed to investigate the underlying mechanisms linking insomnia and memory impairments, and to delineate the long-term impacts of insomnia on other aspects of neurocognitive functioning in youth.

Association between genetic variations in GSH-related and MT genes and low-dose methylmercury exposure in children and women of childbearing age: a pilot study.

BACKGROUND: Genetic variations in glutathione (GSH)-related and metallothionein (MT) genes, which are involved in producing enzymes in the methylmercury (MeHg) metabolism pathway, have been proposed as one of the reasons for the individual variability in MeHg toxicokinetics. OBJECTIVE: To investigate the impact of genetic variations in MT and GSH-related genes on the association of fish consumption with body burden of MeHg, as measured by hair Hg concentrations among young children and women of childbearing age. METHODS: A total of 179 unrelated children and 165 mothers with either high or low fish consumption were recruited from the community. Their hair total Hg (tHg) and MeHg levels and genotypes for SNPs located on the GCLC, GCLM, GPX1, GSTA1, GSTP1, MT1A, MT2A, and MT4 genes were determined. Based on their 14-day food records, the amounts of fish consumed and their MeHg intakes were estimated. The impact of genetic variations on hair Hg concentrations was examined by using Mann-Whitney tests and multivariable linear regression analyses. RESULTS: The presence of minor alleles of GCLC-129 (rs17883901), GPX1-198 (rs1050450) and MT1M (rs9936741) were associated with significantly lower hair tHg levels in mothers whereas mothers with minor alleles of GSTP1-105(rs1695) and MT1M (rs2270836) have significantly higher hair tHg levels. After adjustment for fish consumption and other confounding factors, apart from MT1M (rs2270836), all of the above SNPs remain significant in the multivariable linear regression models. CONCLUSIONS: Our results in a group of children and women show that genetic variants of GSH-related and MT genes are associated with hair Hg concentrations. These genetic variations are likely to significantly affect MeHg metabolism and thus influence the accumulation of Hg in the human body.

Organ donor management and delayed graft function in kidney transplant recipients: A multicenter retrospective cohort study.

Meeting donor management goals (DMGs) has been reported to decrease the incidence of delayed graft function (DGF) after kidney transplant, but whether this relationship is independent of cold machine perfusion is unclear. We aimed to determine whether meeting DMGs is associated with a reduced incidence of DGF, independent of the use of machine perfusion. We collected data on consecutive brain-dead donors and their KT recipients (KTRs) between June 2013 and December 2016 in 5 adult transplant centers. We evaluated whether DMGs were met at donor neurologic death (DND) and later time points. We defined a priori meeting optimal DMG as achieving ≥7 DMGs. Generalized estimating equations were used to predict DGF. Among 122 donors, 34% were extended-criteria donors (ECDs). The number of DMGs met increased over time (5.6 ± 1.4 at DND and 6.1 ± 1.3 at organ procurement [P < .001]). DGF occurred in 23% of 214 KTRs, and 55% received organs placed on machine perfusion. In multivariate analysis, ECD (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.13-4.45), use of machine perfusion (OR 0.45, 95% CI 0.22-0.94), and optimal DMG at DND (OR 0.39, 95% CI 0.16-0.99) were associated with DGF. Early achievement of DMGs was associated with a reduced risk of the development of DGF, independent of the use of machine perfusion.