Evaluation of nociception in unconscious critically ill patients using a multimodal approach.

This prospective observational study included 80 adults (>18 years) patients admitted to the intensive care unit who were unconscious (Glasgow Coma Scale [GCS] score <9 with a motor response <5) and receiving mechanical ventilation. A tetanic stimulation was used to assess nociception; automated pupillometry (Algiscan, ID-MED, France) was used to compute the pupillary pain index score (PPI), with a PPI > 4 considered as nociception. Concomitantly, the number of skin conductance fluctuations (NSCF) per second, measured using a Skin Conductance Algesimeter (SCA, MEDSTORM Innovation AS, Norway; > 0.27 fluctuations/sec indicating nociception), and the instantaneous Analgesia Nociception Index (iANI, MDoloris Medical Systems, France; <50 indicating nociception) were collected. Tetanic stimulation resulted in a median pupillary dilation of 16 [6-25]% and a PPI of 5 [2-7]. According to the PPI assessment, 44 patients (55%) had nociception, whereas 23 (29%) and 18 (23%) showed nociception according to the algesimeter and iANI assessment, respectively. No significant changes in measured physiologic variables were observed after the tetanic stimulation. There were no correlations between PPI, post-stimulation iANI, and SCA-derived variables. There were no differences in PPI, iANI, and SCA variables in patients with low and normal baseline EEG power at baseline. PERSPECTIVES: Detection of nociception varies across different devices in unconscious critically ill patients. Further studies are required to understand which method to implement for analgesic administration in this patient population.

Fever management in critically ill COVID-19 patients: a retrospective analysis.

BACKGROUND: Fever has been reported as a common symptom in COVID-19 patients. The aim of the study was to describe the characteristics of COVID-19 critically ill patients with fever and to assess if fever management had an impact on some physiologic variables. METHODS: This is a retrospective monocentric cohort analysis of critically ill COVID-19 patients admitted to the Department of Intensive Care Unit (ICU) of Erasme Hospital, Brussels, Belgium, between March 2020 and May 2020. Fever was defined as body temperature ≥38 °C during the ICU stay. We assessed the independent predictors of fever during ICU stay. We reported the clinical and physiological variables before and after the first treated episode of fever during the ICU stay. RESULTS: A total of 72 critically ill COVID-19 patients were admitted to the ICU over the study period and were all eligible for the final analysis; 53 (74%) of them developed fever, after a median of 4 [0-13] hours since ICU admission. In the multivariable analysis, male gender (OR 5.41 [C.I. 95% 1.34-21.92]; P=0.02) and low PaO2/FiO2 ratio (OR 0.99 [C.I. 95% 0.99-1.00]; P=0.04) were independently associated with fever. After the treatment of the first febrile episode, heart rate and respiratory rate significantly decreased together with an increase in PaO2 and SaO2. CONCLUSIONS: In our study, male gender and severe impairment of oxygenation were independently associated with fever in critically ill COVID-19 patients. Fever treatment reduced heart rate and respiratory rate and improved systemic oxygenation.

Eosinopenia in COVID-19 Patients: A Retrospective Analysis.

Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm3. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia. Results: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic-ROC curve, 0.84 (95% CIs 0.78-0.90) and 0.84 (95% CIs 0.77-0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings. Conclusions: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available.

Interleukine-6 in critically ill COVID-19 patients: A retrospective analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) appeared in China in December 2019 and has spread around the world. High Interleukin-6 (IL-6) levels in COVID-19 patients suggest that a cytokine storm may play a major role in the pathophysiology and are considered as a relevant parameter in predicting most severe course of disease. The aim of this study was to assess repeated IL-6 levels in critically ill COVID-19 patients admitted to our Intensive Care Unit (ICU) and to evaluate their relationship with patient's severity and outcome. METHODS: We conducted a retrospective study on patients admitted to the ICU with a diagnosis of COVID-19 between March 10 (i.e. the date of the first admitted patients) and April 30, 2020. Demographic, clinical and laboratory data were collected at admission. On the day of IL-6 blood concentration measurement, we also collected results of D-Dimers, C-Reactive Protein, white blood cells and lymphocytes count, lactate dehydrogenase (LDH) and ferritin as well as microbiological samples, whenever present. RESULTS: Of a total of 65 patients with COVID-19 admitted to our ICU we included 41 patients with repeated measure of IL-6. There was a significant difference in IL-6 levels between survivors and non-survivors over time (p = 0.001); moreover, non survivors had a significantly higher IL-6 maximal value when compared to survivors (720 [349-2116] vs. 336 [195-646] pg/mL, p = 0.01). The IL-6 maximal value had a significant predictive value of ICU mortality (AUROC 0.73 [95% CI 0.57-0.89]; p = 0.01). CONCLUSIONS: Repeated measurements of IL-6 can help clinicians in identifying critically ill COVID-19 patients with the highest risk of poor prognosis.

The Prognostic Role of Lactate Concentrations after Aneurysmal Subarachnoid Hemorrhage.

Blood lactate concentrations are often used to assess global tissue perfusion in critically ill patients; however, there are scarce data on lactate concentrations after subarachnoid hemorrhage (SAH). We aimed to assess the prognostic role of serial blood lactate measurements on hospital mortality and neurological outcomes at 3 months after SAH. We reviewed all SAH patients admitted to the intensive care unit from 2007 to 2019 and recorded the highest daily arterial lactate concentration for the first 6 days. Patients with no lactate concentration were excluded. Hyperlactatemia was defined as a blood lactate concentration >2.0 mmol/L. A total of 456 patients were included: 158 (35%) patients died in hospital and 209 (46%) had an unfavorable outcome (UO) at 3 months. The median highest lactate concentration was 2.7 (1.8-3.9) mmol/L. Non-survivors and patients with UO had significantly higher lactate concentrations compared to other patients. Hyperlactatemia increased the chance of dying (OR 4.19 (95% CI 2.38-7.39)) and of having UO in 3 months (OR 4.16 (95% CI 2.52-6.88)) after adjusting for confounding factors. Therefore, initial blood lactate concentrations have prognostic implications in patients with SAH; their role in conjunction with other prognostic indicators should be evaluated in prospective studies.

The Acquisition of Multidrug-Resistant Bacteria in Patients Admitted to COVID-19 Intensive Care Units: A Monocentric Retrospective Case Control Study.

Whether the risk of multidrug-resistant bacteria (MDRB) acquisition in the intensive care unit (ICU) is modified by the COVID-19 crisis is unknown. In this single center case control study, we measured the rate of MDRB acquisition in patients admitted in COVID-19 ICU and compared it with patients admitted in the same ICU for subarachnoid hemorrhage (controls) matched 1:1 on length of ICU stay and mechanical ventilation. All patients were systematically and repeatedly screened for MDRB carriage. We compared the rate of MDRB acquisition in COVID-19 patients and in control using a competing risk analysis. Of note, although we tried to match COVID-19 patients with septic shock patients, we were unable due to the longer stay of COVID-19 patients. Among 72 patients admitted to the COVID-19 ICUs, 33% acquired 31 MDRB during ICU stay. The incidence density of MDRB acquisition was 30/1000 patient days. Antimicrobial therapy and exposure time were associated with higher rate of MDRB acquisition. Among the 72 SAH patients, 21% acquired MDRB, with an incidence density was 18/1000 patient days. The septic patients had more comorbidities and a greater number of previous hospitalizations than the COVID-19 patients. The incidence density of MDRB acquisition was 30/1000 patient days. The association between COVID-19 and MDRB acquisition (compared to control) risk did not reach statistical significance in the multivariable competing risk analysis (sHR 1.71 (CI 95% 0.93-3.21)). Thus, we conclude that, despite strong physical isolation, acquisition rate of MDRB in ICU patients was at least similar during the COVID-19 first wave compared to previous period.

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.

Polyamines as physiological regulators of 14-3-3 interaction with the plant plasma membrane H+-ATPase.

Polyamines are abundant polycationic compounds involved in many plant physiological processes such as cell division, dormancy breaking, plant morphogenesis and response to environmental stresses. In this study, we investigated the possible role of these polycations in modulating the association of 14-3-3 proteins with the H(+)-ATPase. In vivo experiments demonstrate that, among the different polyamines, spermine brings about 2-fold stimulation of the H(+)-ATPase activity and this effect is due to an increase in 14-3-3 levels associated with the enzyme. In vivo administration of polyamine synthesis inhibitors causes a small but statistically significant decrease of the H(+)-ATPase phosphohydrolytic activity, demonstrating a physiological role for the polyamines in regulating the enzyme activity. Spermine stimulates the activity of the H(+)-ATPase AHA1 expressed in yeast, in the presence of exogenous 14-3-3 proteins, with a calculated S(50) of 70 microM. Moreover, spermine enhances the in vitro interaction of 14-3-3 proteins with the H(+)-ATPase and notably induces 14-3-3 association with the unphosphorylated C-terminal domain of the proton pump. Comparison of spermine with Mg(2+), necessary for binding of 14-3-3 proteins to different target proteins, shows that the polyamine effect is stronger than and additive to that of the divalent cation.

The maize root plasma membrane H(+)-ATPase is regulated by a sugar-induced transduction pathway.

H(+)-ATPase, the key enzyme for the energization of ion and nutrient transport across the plasma membrane, is activated by phosphorylation-dependent 14-3-3 binding. Since the involvement of 14-3-3 proteins in sugar sensing-regulated processes has recently emerged, here we address the question as to whether sugar sensing plays a role in the regulation of H(+)-ATPase. The data reported here show that sugar depletion inhibits the association of 14-3-3 proteins with H(+)-ATPase by hampering phosphorylation of the 14-3-3 binding site of the enzyme. By using non-metabolizable disaccharides, we show that H(+)-ATPase regulation by 14-3-3 proteins can involve a specific sugar perception and transduction mechanism.