Higher Intensity Thromboprophylaxis Regimens and Pulmonary Embolism in Critically Ill Coronavirus Disease 2019 Patients.

OBJECTIVES: To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients. DESIGN: Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020. SETTING: ICU of an University Hospital in Belgium. PATIENTS AND INTERVENTIONS: Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin). MEASUREMENTS AND MAIN RESULTS: Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4-8 d) since ICU admission and 12 days (9-16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78-1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%-odds ratio 0.13 [0.02-0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24-3.26]; p = 0.99). CONCLUSIONS: In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.

Is slower advancement of enteral feeding superior to aggressive full feeding regimens in the early phase of critical illness.

PURPOSE OF REVIEW: An excessive caloric intake during the acute phase of critical illness is associated with adverse effects, presumably related to overfeeding, inhibition of autophagy and refeeding syndrome. The purpose of this review is to summarize recently published clinical evidence in this area. RECENT FINDINGS: Several observational studies, a few interventional trials, and systematic reviews/metaanalyses were published in 2017-2019. Most observational studies reported an association between caloric intakes below 70% of energy expenditure and a better vital outcome. In interventional trials, or systematic reviews, neither a benefit nor a harm was related to increases or decreases in caloric intake. Gastrointestinal dysfunction can be worsened by forced enteral feeding, whereas the absorption of nutrients can be impaired. SUMMARY: Owing to the risks of the delivery of an excessive caloric intake, a strategy of permissive underfeeding implying a caloric intake matching a maximum of 70% of energy expenditure provides the best risk-to-benefit ratio during the acute phase of critical illness.

Comparison of extracorporeal and conventional cardiopulmonary resuscitation: a retrospective propensity score matched study.

BACKGROUND: The potential benefit of extracorporeal cardiopulmonary resuscitation (ECPR) compared to conventional CPR (CCPR) for patients with refractory cardiac arrest (CA) remains unclear. METHODS: This study is a retrospective analysis of a prospective database of CA patients, which includes all consecutive adult patients admitted to the Department of Intensive Care after CA between January 2012 and December 2017. The decision to initiate ECPR was made by the attending physician and ECPR performed by the ECPR team, which is composed of ICU physicians. A propensity score was derived using a logistic regression model, including characteristics that varied between groups with a p <  0.10 and were potentially related to outcome. Primary outcomes were survival to ICU discharge and favorable 3-month neurologic outcome, assessed by a Cerebral Performance Category (CPC) score of 1-2. RESULTS: From a total of 635 patients with CA during the study period (ECPR, n = 112), 80 ECPR patients were matched to 80 CCPR patients. The time from arrest to termination of CPR (i.e., return of spontaneous circulation [ROSC], extracorporeal membrane oxygenation [ECMO] initiation, or death) was 54 ± 22 and 54 ± 19 min in the ECPR and CCPR groups, respectively. ROSC rates were 77/80 (96%) for ECPR and 30/80 (38%) for CCPR (p <  0.001). Survival to ICU discharge was 18/80 (23%) vs. 14/80 (18%) in the ECPR and CCPR groups, respectively (p = 0.42). At 3 months, 17/80 (21%) ECPR patients and 9/80 (11%) CCPR patients had a favorable outcome (p = 0.11). Cox regression analysis stratified by matched pairs showed a significantly higher neurologic outcome rate in the ECPR group than in the CCPR group (log-rank test p = 0.003). CONCLUSIONS: ECPR after CA may be associated with improved long-term neurological outcome.

Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients.

OBJECTIVES: Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5-15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients. DESIGN: Prospective, cluster-randomized, crossover study. SETTING: Thirty-five-bed medico-surgical department of intensive care with four separate ICUs. PATIENTS: Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy. INTERVENTIONS: A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was adjusted to keep blood glucose between 90 and 150 mg/dL using the blood glucose values displayed on the continuous glucose monitor (continuous glucose monitoring group-unblinded units) or according to intermittent blood glucose readings (intermittent glucose monitoring group-blinded units). MEASUREMENTS AND MAIN RESULTS: The quality and safety of glycemic control were assessed using the proportion of time in range, the frequency of blood glucose less than 70 mg/dL, and the time spent with blood glucose less than 70 mg/dL (TB70), using blood glucose values measured by the continuous glucose monitoring device. Seventy-seven patients were enrolled: 39 in the continuous glucose monitoring group and 38 in the intermittent glucose monitoring group. A total of 43,107 blood glucose values were recorded. The time in range was similar in the two groups. The incidence of hypoglycemia (8/39 [20.5%] vs 15/38 [39.5%]) and the TB70 (0.4% ± 0.9% vs 1.6% ± 3.4%; p < 0.05) was lower in the continuous glucose monitoring than in the intermittent glucose monitoring group. CONCLUSIONS: Use of a continuous glucose monitoring-based strategy decreased the incidence and severity of hypoglycemia, thus improving the safety of glycemic control.

Cerebral Near-Infrared Spectroscopy in Adult Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Acute cerebral complications (ACC) of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are associated with poor long-term neurologic outcome. We described the role of rSO2 monitoring in detecting ACC and desaturations and their relationship with poor outcome when employing VA-ECMO. METHODS: Retrospective analysis of patients monitored by cerebral frontal near-infrared spectroscopy (NIRS) (CAS Medical Systems Inc., Branford, CT, USA) during VA-ECMO (November 2008-December 2015). ACC was defined as the presence of stroke and/or brain death, while cerebral desaturation as cortical oxygen tissue saturation (rSO2) < 60%. RESULTS: Fifty-six of 159 VA-ECMO patients (age 55 [36-60] years) were included; 18 (32%) developed ACC and 36 died (64%). Cerebral desaturation occurred in 43 (74%) patients, who had a higher mortality than those without cerebral desaturation (74 vs. 31%). A high sequential organ failure assessment (SOFA) score on the first day of ECMO (OR 1.40 [95% CIs 1.06-1.84]) and the minimum ECMO blood flow during the first 4 days of therapy (OR 3.05 [1.01-9.17]) were independently associated with the occurrence of cerebral desaturation. Cerebral desaturation occurred more frequently in patients with ACC than others (94 vs. 68%); patients with ACC also had a lower minimal rSO2 over time (49 vs. 54%) and more frequently had high right-left rSO2 differences (33 vs. 8%), which were both independent predictors of ACC. The occurrence of cerebral desaturation (OR 7.93 [1.62-38.74]) and high lactate concentrations during the first 4 days of ECMO support (OR 1.22 [1.03-1.46]) was independently associated with hospital mortality. CONCLUSIONS: Monitoring of rSO2 could be considered as an interesting tool to monitor the brain of patients on VA-ECMO.

Serum ß-lactam concentrations in critically ill patients with cirrhosis: a matched case-control study.

BACKGROUND & AIMS: The pharmacokinetics of ß-lactam antibiotics have not been well defined in critically ill patients with cirrhosis. METHODS: We reviewed data from critically ill patients with cirrhosis and matched controls in whom routine therapeutic drug monitoring of two broad-spectrum ß-lactam antibiotics (piperacillin/tazobactam and meropenem) had been performed. Serum drug concentrations were measured twice by high-performance liquid chromatography. Antibiotic pharmacokinetics were calculated using a one-compartment model. We considered that therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration of Pseudomonas aeruginosa during optimal periods of time for each drug (≥ 50% for piperacillin/tazobactam; ≥ 40% for meropenem). RESULTS: We studied 38 patients with cirrhosis (16 for piperacillin/tazobactam and 22 for meropenem) and 38 matched controls. Drug dosing was similar in the two groups. The pharmacokinetics analysis showed a lower volume of distribution of meropenem (P = 0.05) and a lower antibiotic clearance of piperacillin/tazobactam (P = 0.009) in patients with cirrhosis than in the matched controls. Patients with cirrhosis were more likely than those without cirrhosis to have excessive serum ß-lactam concentrations (P = 0.015), in particular for piperacillin/tazobactam. CONCLUSIONS: Standard ß-lactam antibiotics regimens resulted in excessive serum concentrations in two thirds of the patients with cirrhosis. This was particularly true for piperacillin/tazobactam, probably because of reduced drug clearance.

Year in review 2013: Critical Care--metabolism.

Novel insights into the metabolic alterations of critical illness, including new findings on association between blood glucose at admission and poor outcome, were published in Critical Care in 2013. The role of diabetic status in the relation of the three domains of glycemic control (hyperglycemia, hypoglycemia, and glycemic variability) was clarified: the association between mean glucose, high glucose variability, and ICU mortality was stronger in the non-diabetic than in diabetic patients. Improvements in the understanding of pathophysiological mechanisms of stress hyperglycemia were presented. Novel developments for the management of glucose control included automated closed-loop algorithms based on subcutaneous glucose measurements and microdialysis techniques. In the field of obesity, some new hypotheses that could explain the 'obesity paradox' were released, and a role of adipose tissue in the response to stress was suggested by the time course of adipocyte fatty-acid binding protein concentrations. In the field of nutrition, beneficial immunological effects have been associated with early enteral nutrition. Early enteral nutrition was significantly associated with potential beneficial effects on the phenotype of lymphocytes. Uncertainties regarding the potential benefits of small intestine feeding compared with gastric feeding were further investigated. No significant differences were observed between the nasogastric and nasojejunal feeding groups in the incidence of mortality, tracheal aspiration, or exacerbation of pain. The major risk factors to develop diarrhea in the ICU were described. Finally, the understanding of disorders associated with trauma and potential benefits of blood acidification was improved by new experimental findings.

Early Findings after Implementation of Veno-Arteriovenous ECMO: A Multicenter European Experience.

Extracorporeal membrane oxygenation (ECMO) is increasingly used to treat cardiopulmonary failure in critically ill patients. Peripheral cannulation may be complicated by a persistent low cardiac output in case of veno-venous cannulation (VV-ECMO) or by differential hypoxia (e.g., lower PaO2 in the upper than in the lower body) in case of veno-arterial cannulation (VA-ECMO) and severe impairment of pulmonary function associated with cardiac recovery. The treatment of such complications remains challenging. We report the early effects of the use of veno-arterial-venous (V-AV) ECMO in this setting. METHODS: Retrospective analysis including patients from five different European ECMO centers (January 2013 to December 2016) who required V-AV ECMO. We collected demographic data as well as comorbidities and ECMO characteristics, hemodynamics, and arterial blood gas values before and immediately after (i.e., within 2 h) V-AV implementation. RESULTS: A total of 32 patients (age 53 (interquartiles, IQRs: 31-59) years) were identified: 16 were initially supported with VA-ECMO and 16 with VV-ECMO. The median time to V-AV conversion was 2 (1-5) days. After V-AV implantation, heart rate and norepinephrine dose significantly decreased, while PaO2 and SaO2 significantly increased compared to baseline values. Lactate levels significantly decreased from 3.9 (2.3-7.1) to 2.8 (1.4-4.4) mmol/L (p = 0.048). A significant increase in the overall ECMO blood flow (from 4.5 (3.8-5.0) to 4.9 (4.3-5.9) L/min; p < 0.01) was observed, with 3.0 (2.5-3.2) L/min for the arterial and 2.8 (2.1-3.6) L/min for the venous return flows. CONCLUSIONS: In ECMO patients with differential hypoxia or persistently low cardiac output syndrome, V-AV conversion was associated with improvement in some hemodynamic and respiratory parameters. A significant increase in the overall ECMO blood flow was also observed, with similar flow distributed into the arterial and venous return cannulas.

Nutrition evaluation and management of critically ill patients with COVID-19 during post-intensive care rehabilitation.

BACKGROUND: Among hospitalized patients with coronavirus disease 2019 (COVID-19), up to 12% may require intensive care unit (ICU) management. The aim of this prospective cohort study is to assess nutrition status and outcome in patients with COVID-19 following ICU discharge. METHODS: Patients requiring a minimum of 14 days' stay in the ICU with mechanical ventilation were included. Nutrition status was assessed at inclusion (ICU discharge) and follow-up (after 15, 30, and 60 days). All patients had standardized medical nutrition therapy with defined targets regarding energy (30 kcal/kg/d) and protein intake (1.5 g/kg/d). RESULTS: Fifteen patients were included (67% males); the median age was 60 (33-75) years old. Body mass index at ICU admission was 25.7 (IQR, 24-31) kg/m². After a median ICU stay of 33 (IQR, 26-39) days, malnutrition was present in all patients (11.3% median weight loss and/or low muscle mass based on handgrip strength measurement). Because of postintubation dysphagia in 60% of patients, enteral nutrition was administered (57% nasogastric tube; 43% percutaneous endoscopic gastrostomy). After 2 months, a significant improvement in muscle strength was observed (median handgrip strength, 64.7% [IQR, 51%-73%] of the predicted values for age vs 19% [IQR, 4.8%-28.4%] at ICU discharge [P < 0.0005]), as well as weight gain of 4.3 kg (IQR, 2.7-6.7 kg) (P < 0.0002). CONCLUSIONS: Critically ill patients with COVID-19 requiring ICU admission and mechanical ventilation have malnutrition and low muscle mass at ICU discharge. Nutrition parameters improve during rehabilitation with standardized medical nutrition therapy.

Haemoptysis treated by bronchial artery embolisation in severe acute respiratory syndrome coronavirus 2: case report.

BACKGROUND: We found no data in the literature on the embolization of the bronchial arteries in the context of hemoptysis associated with severe acute respiratory syndrome coronavirus 2. We therefore decided to share this experience. CASE PRESENTATION: A 62-year-old patient with no significant medical history was admitted with acute respiratory distress. Chest computed tomography showed diffuse bilateral ground-glass opacities with limited consolidations. Diagnostic tests confirmed severe acute respiratory syndrome coronavirus 2 infection. The severity of respiratory failure required the implantation of veno-venous extracorporeal membrane oxygenation. The patient developed severe haemoptysis, which was successfully treated by bronchial artery embolisation. CONCLUSIONS: In the case of coronavirus-19 pneumonia, our experience suggests that the treatment of severe haemoptysis by bronchial artery embolisation is feasible and effective. The survival benefit should be assessed in the future.

Glucose and Lactate Concentrations in Cerebrospinal Fluid After Traumatic Brain Injury.

BACKGROUND: Studies in which brain metabolism has been monitored using microdialysis have indicated decreases in cerebral glucose concentration and increases in lactate concentration in patients with traumatic brain injury (TBI). However, few data are available on glucose and lactate concentrations in the cerebrospinal fluid (CSF) of TBI patients. This study investigates the relationship between CSF glucose and lactate concentrations and outcomes after TBI. METHODS: Consecutive adult (>18 y) TBI patients were admitted to our 35-bed medicosurgical between 2011 and 2014 and were included in the study if they met the following inclusion criteria: presence of an external ventricular drain (EVD) for intracranial pressure monitoring, daily analysis of CSF glucose and lactate concentrations for 4 consecutive days, and concomitant measurements of blood glucose/lactate concentrations. Neurological outcome was assessed at 3 months using the extended Glasgow Outcome Scale (GOS), and unfavorable outcome defined as a GOS 1 to 4. RESULTS: Of 151 TBI patients who had an EVD, 56 met the inclusion criteria. Most EVDs were placed on the day of intensive care unit admission, and maintained for 10 (interquartile range: 6 to 14) days. On day 1, there was a weak but significant correlation between blood and CSF glucose concentrations (R=0.07, P=0.04), and a greater correlation between blood and CSF lactate (R=0.32, P<0.001). In multivariable analysis, day 1 CSF glucose/lactate ratio was independently associated with mortality (odds ratio: 0.22, 95% confidence interval: 0.08-0.61; P=0.003), and day 1 CSF lactate concentration with unfavorable outcome (odds ratio: 4.86; 95% confidence interval: 1.86-12.67; P=0.001). CONCLUSIONS: Low CSF glucose/lactate ratio is observed in nonsurvivors after severe TBI and may have prognostic value.

Effects of digoxin on muscle reflexes in normal humans.

Blockade of the skeletal muscle Na(+)-K(+)-ATPase pump by digoxin could result in a more marked hyperkaliema during a forearm exercise, which in turn could stimulate the mechano- and metaboreceptors. In a randomized, double-blinded, placebo-controlled, and cross-over-design study, we measured mean blood pressure (MBP), heart rate (HR), ventilation (V(E)), oxygen saturation (SpO(2)), muscle sympathetic nerve activity (MSNA), venous plasma potassium and lactic acid during dynamic handgrip exercises, and local circulatory arrest in 11 healthy subjects. Digoxin enhanced MBP during exercise but not during the post-handgrip ischemia and had no effect on HR, V(E), SpO(2), and MSNA. Venous plasma potassium and lactic acid were also not affected by digoxin-induced skeletal muscle Na(+)-K(+)-ATPase blockade. We conclude that digoxin increased MBP during dynamic exercise in healthy humans, independently of changes in potassium and lactic acid. A modest direct sensitization of the muscle mechanoreceptors is unlikely and other mechanisms, independent of muscle reflexes and related to the inotropic effects of digoxin, might be implicated.

Update on glucose in critical care.

The aim of this review is to summarize recent developments on the mechanisms involved in stress hyperglycemia associated with critical illness. Different aspects of the consequences of stress hyperglycemia as well as the therapeutic approaches tested so far are discussed: the physiological regulations of blood glucose, the mechanisms underlying stress hyperglycemia, the clinical associations, and the results of the prospective trials and meta-analyses to be taken into consideration when interpreting the available data. Current recommendations, challenges, and technological hopes for the future are be discussed.

Role of Nutrition Support in Inflammatory Conditions [Formula: see text].

This review intends to summarize recent development on the potential nutrition implications of acute inflammation encountered during critical illness. Different aspects of the inflammatory response and their impact on nutrition management during critical illness will be discussed: the timing of the postinjury metabolic response, the integration of regulatory mechanisms involved in the metabolic response to stress, the oxidative stress, the metabolic and clinical consequences in terms of energy expenditure, use of energy, changes in body composition, and behavior.

Role of Nutrition Support in Inflammatory Conditions.

This review intends to summarize recent development on the potential nutrition implications of acute inflammation encountered during critical illness. Different aspects of the inflammatory response and their impact on nutrition management during critical illness will be discussed: the timing of the postinjury metabolic response, the integration of regulatory mechanisms involved in the metabolic response to stress, the oxidative stress, the metabolic and clinical consequences in terms of energy expenditure, use of energy, changes in body composition, and behavior.

False-positive galactomannan assay in broncho-alveolar lavage after enteral nutrition solution inhalation: a case report.

Introduction. Diagnosis of invasive aspergillosis is challenging and the gold standard for definite diagnosis remains histopathological tissue examination. However, invasive procedures such as lung biopsy are often not feasible in critically ill patients. The detection of fungal cell wall components like Aspergillus galactomannan in broncho-alveolar lavage remains a key component of the diagnostic procedure. False-positive of the Aspergillus galactomannan assay is not frequent. Case presentation. We report a case of positive galactomannan in broncho-alveolar lavage fluid after enteral nutrition aspiration without signs of invasive aspergillosis. Galactomannan was positive in the enteral nutrition solution. Conclusion. Physicians should be aware of this previously unrecognized cause of false-positive galactomannan in broncho-alveolar fluid which can result in unnecessary treatments.