Prediabetes Induces More Severe Acute COVID-19 Associated With IL-6 Production Without Worsening Long-Term Symptoms.

Aims: Pre-existing conditions, such as age, hypertension, obesity, and diabetes, constitute known risk factors for severe COVID-19. However, the impact of prediabetes mellitus (PDM) on COVID-19 severity is less clear. This study aimed to evaluate the influence of PDM in the acute and long-term phases of COVID-19. Materials and methods: We compared inflammatory mediators, laboratory and clinical parameters and symptoms in COVID-19 patients with prediabetes (PDM) and without diabetes (NDM) during the acute phase of infection and at three months post-hospitalization. Results: Patients with PDM had longer hospital stays and required intensive care unit admission more frequently than NDM. Upon hospitalization, PDM patients exhibited higher serum levels of interleukin 6 (IL-6), which is related to reduced partial pressure of oxygen (PaO2) in arterial blood, oxygen saturation (SpO2) and increased COVID-19 severity. However, at three months after discharge, those with PDM did not exhibit significant alterations in laboratory parameters or residual symptoms; however, PDM was observed to influence the profile of reported symptoms. Conclusions: PDM seems to be associated with increased risk of severe COVID-19, as well as higher serum levels of IL-6, which may constitute a potential biomarker of severe COVID-19 risk in affected patients. Furthermore, while PDM correlated with more severe acute-phase COVID-19, no long-term worsening of sequelae was observed.

Prediction of hemodynamic tolerance of intermittent hemodialysis in critically ill patients: a cohort study.

The evaluation and management of fluid balance are key challenges when caring for critically ill patients requiring renal replacement therapy. The aim of this study was to assess the ability of clinical judgment and other variables to predict the occurrence of hypotension during intermittent hemodialysis (IHD) in critically ill patients. This was a prospective, observational, single-center study involving critically ill patients undergoing IHD. The clinical judgment of hypervolemia was determined by the managing nephrologists and critical care physicians in charge of the patients on the basis of the clinical data used to calculate the ultrafiltration volume and rate for each dialysis treatment. Seventy-nine (31.9%) patients presented with hypotension during IHD. Patients were perceived as being hypervolemic in 109 (43.9%) of the cases by nephrologists and in 107 (43.1%) by intensivists. The agreement between nephrologists and intensivists was weak (kappa = 0.561). Receiver operating characteristic curve analysis yielded an AUC of 0.81 (95% CI 0.75 to 0.84; P < 0.0001), and a cutoff value of 70 mm for the vascular pedicle width (VPW) had the highest accuracy for the prediction of the absence of hypotension. The clinical judgment of hypervolemia did not predict hypotension during IHD. The high predictive ability of the VPW may assist clinicians with critical thinking.

Unplanned Transfers From Intermediate Care Units to Intensive Care Units: A Cohort Study.

This study evaluated unplanned transfers from the intermediate care unit (IMCU) to the intensive care unit (ICU) among urgent admissions. This retrospective, observational study was conducted in 2 ICUs and 1 IMCU. Three patterns of urgent admission were assessed: admissions to the ICU only, admissions to the IMCU only, and admissions to the IMCU with subsequent transfer to the ICU. Of 5296 admissions analyzed, 1396 patients (26.4%) were initially admitted to the IMCU. Of these, 172 (12.3%) were transferred from the IMCU to the ICU. Mortality was higher in patients transferred from the IMCU to the ICU than in the 3900 ICU-only patients (odds ratio, 3.22; 95% CI, 1.52-6.80). Most transfers from the IMCU to the ICU (135; 78.5%) were due to deterioration of the condition for which the patient was admitted. Patient transfers from the IMCU to the ICU were common, were associated with increased hospital mortality, and were mostly due to deterioration in the condition that was the reason for admission.

LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes.

Diabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19), the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B4 (LTB4) pathway (ALOX5). We found that diabetes activates the LTB4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19-related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO2) and arterial partial pressure of oxygen/FiO2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.

Realistic simulation is associated with healthcare professionals' increased self-perception of confidence in providing acute stroke care: a before-after controlled study.

BACKGROUND: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. OBJECTIVE: To assess the impact of a stroke realistic simulation course on clinicians' self-perception of confidence in the management of acute stroke. METHODS: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees' self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. RESULTS: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. CONCLUSIONS: This stroke realistic simulation course was associated with an improvement on trainees' self-perception of confidence in providing acute stroke care.

Differential impact of on-site or telepharmacy in the intensive care unit: a controlled before-after study.

BACKGROUND: Clinical pharmacists have an important role in the intensive care unit (ICU) team but are scarce resources. Our aim was to evaluate the impact of on-site pharmacists on medical prescriptions in the ICU. METHODS: This is a retrospective, quasi-experimental, controlled before-after study in two ICUs. Interventions by pharmacists were evaluated in phase 1 (February to November 2016) and phase 2 (February to May 2017) in ICU A (intervention) and ICU B (control). In phase 1, both ICUs had a telepharmacy service in which medical prescriptions were evaluated and interventions were made remotely. In phase 2, an on-site pharmacist was implemented in ICU A, but not in ICU B. We compared the number of interventions that were accepted in phase 1 versus phase 2. RESULTS: During the study period, 8797/9603 (91.6%) prescriptions were evaluated, and 935 (10.6%) needed intervention. In phase 2, there was an increase in the proportion of interventions that were accepted by the physician in comparison to phase 1 (93.9% versus 76.8%, P < 0.001) in ICU A, but there was no change in ICU B (75.2% versus 73.9%, P = 0.845). CONCLUSION: An on-site pharmacist in the ICU was associated with an increase in the proportion of interventions that were accepted by physicians.

Realistic simulation is associated with healthcare professionals' increased self-perception of confidence in providing acute stroke care: a before-after controlled study / Simulação realística é associada a aumento na autopercepção de segurança de profissionais de saúde no atendimento a pacientes com acidente vascular cerebral agudo: um estudo antes-depois controlado

ABSTRACT Background: Simulations are becoming widely used in medical education, but there is little evidence of their effectiveness on neurocritical care. Because acute stroke is a neurological emergency demanding prompt attention, it is a promising candidate for simulation training. Objective: To assess the impact of a stroke realistic simulation course on clinicians' self-perception of confidence in the management of acute stroke. Methods: We conducted a controlled, before-after study. For our intervention, 17 healthcare professionals participated in a stroke realistic simulation course. As controls, participants were chosen from a convenience sample of attendees to the courses Emergency Neurologic Life Support (ENLS) (18 participants) and Neurosonology (20 participants). All participants responded pre- and post-test questionnaires evaluating their self-perception of confidence in acute stroke care, ranging from 10 to 50 points. We evaluated the variation between pre- and post-test results to assess the change on trainees' self-perception of confidence in the management of acute stroke. Multivariate analysis was performed to control for potential confounders. Results: Forty-six (83.63%) subjects completed both questionnaires. The post-test scores were higher than those from the pretests in the stroke realistic simulation course group [pretest median (interquartile range - IQR): 41.5 (36.7-46.5) and post-test median (IQR): 47 (44.7-48); p=0.033], but not in the neurosonology [pretest median (IQR): 46 (44-47) and post-test median (IQR): 46 (44-47); p=0.739] or the ENLS [pretest median (IQR): 46.5 (39-48.2), post-test median (IQR): 47 (40.2-49); p=0.317] groups. Results were maintained after adjustment for covariates. Conclusions: This stroke realistic simulation course was associated with an improvement on trainees' self-perception of confidence in providing acute stroke care.

RESUMO Introdução: Simulações são amplamente utilizadas na educação médica, mas há pouca evidência de sua eficácia no tratamento de pacientes neurocríticos. Como o acidente vascular cerebral agudo (AVC) é uma patologia que requer atendimento imediato, o uso de simulação pode ser uma ferramenta útil no treinamento do manejo desses pacientes. Objetivo: Avaliar o impacto do uso de simulação realística na autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo. Métodos: Estudo antes-depois controlado. No grupo da intervenção, 17 profissionais da área de saúde participaram de um curso de simulação realística de atendimento a pacientes com AVC. Como controles, os participantes foram escolhidos a partir de uma amostra de conveniência composta por 18 participantes do curso Emergency Neurologic Life Support (ENLS) e 20 participantes de um curso de Neurossonologia. Foram respondidos questionários antes e após o curso para avaliar a autopercepção de segurança no atendimento a pacientes vítimas de AVC agudo, variando de 10 a 50 pontos. Foi avaliada a variação entre os resultados pré- e pós-teste, para avaliar a mudança na autopercepção de confiança do trainee no manejo do AVC agudo. Análise multivariada foi realizada para controlar possíveis fatores de confusão. Resultados: Quarenta e seis (83,63%) participantes responderam aos questionários. A pontuação no questionário pós-curso foi maior do que a obtida no questionário pré-curso no grupo de participantes do curso de simulação realística em AVC [mediana do questionário pré-curso: 41,5 (36,7-46,5) e mediana do questionário pós-curso: 47,0 (44,7-48,0); p=0,033]. Essa diferença não foi observada no curso de Neurossonologia [mediana pré-curso (IQR): 46,0 (44,0-47,00), mediana pós-curso (IQR): 46,0 (44,0-47,0); p=0,739] nem no ENLS [mediana pré-curso (IQR): 46,5 (39,0-48,2) mediana pós-curso (IQR): 47,0 (40,2-49,0); p=0,317]. Esses resultados persistiram após ajuste das variáveis. Conclusão: O curso de simulação realística em AVC foi associado a um aumento na autopercepção de segurança dos participantes em atender pacientes vítimas de AVC agudo.

Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática / Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review

RESUMO Objetivo: Revisar sistematicamente a evidência atual da eficácia de milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea. Métodos: Triaram-se as bases de dados Pubmed®, Cochrane e Embase quanto a artigos publicados entre abril de 2001 e fevereiro de 2019. Dois revisores independentes realizaram uma triagem metodológica da qualidade e a extração dos dados dos estudos. Resultados: Encontraram-se 22 estudos considerados relevantes, sendo que apenas um deles era um ensaio randomizado controlado. Os estudos demonstraram acentuada heterogeneidade e debilidade de seus critérios metodológicos. A maioria dos pacientes apresentava vasoespasmo moderado a grave. O principal método para diagnóstico do vasoespasmo foi a angiografia. Em três estudos, realizou-se administração de milrinona por via intra-arterial; em nove estudos, a administração foi endovenosa, e, em seis estudos, utilizaram-se ambas as vias de administração. A via intratecal foi utilizada em dois estudos, em um estudo, a administração foi realizada via cisterna e, em um estudo, a via de administração foi a endovascular. Os efeitos colaterais de milrinona foram descritos em seis estudos. Vinte e um estudos indicaram a resolução do vasoespasmo. Conclusão: A evidência atual indica que o uso de milrinona teve um papel no tratamento do vasoespasmo após hemorragia subaracnóidea aneurismática. Contudo, só foi realizado um ensaio randomizado controlado, com baixo nível de qualidade. Nossos achados indicam a necessidade de futuros estudos randomizados controlados com desfechos centrados no paciente, com o fim de proporcionar recomendações definitivas.

ABSTRACT Objective: To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage. Methods: The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies. Results: Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm. Conclusion: The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review. / Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática.

OBJECTIVE: To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage. METHODS: The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies. RESULTS: Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm. CONCLUSION: The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

OBJETIVO: Revisar sistematicamente a evidência atual da eficácia de milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea. MÉTODOS: Triaram-se as bases de dados Pubmed®, Cochrane e Embase quanto a artigos publicados entre abril de 2001 e fevereiro de 2019. Dois revisores independentes realizaram uma triagem metodológica da qualidade e a extração dos dados dos estudos. RESULTADOS: Encontraram-se 22 estudos considerados relevantes, sendo que apenas um deles era um ensaio randomizado controlado. Os estudos demonstraram acentuada heterogeneidade e debilidade de seus critérios metodológicos. A maioria dos pacientes apresentava vasoespasmo moderado a grave. O principal método para diagnóstico do vasoespasmo foi a angiografia. Em três estudos, realizou-se administração de milrinona por via intra-arterial; em nove estudos, a administração foi endovenosa, e, em seis estudos, utilizaram-se ambas as vias de administração. A via intratecal foi utilizada em dois estudos, em um estudo, a administração foi realizada via cisterna e, em um estudo, a via de administração foi a endovascular. Os efeitos colaterais de milrinona foram descritos em seis estudos. Vinte e um estudos indicaram a resolução do vasoespasmo. CONCLUSÃO: A evidência atual indica que o uso de milrinona teve um papel no tratamento do vasoespasmo após hemorragia subaracnóidea aneurismática. Contudo, só foi realizado um ensaio randomizado controlado, com baixo nível de qualidade. Nossos achados indicam a necessidade de futuros estudos randomizados controlados com desfechos centrados no paciente, com o fim de proporcionar recomendações definitivas.

Intravenous administration of Milrinone, as an alternative approach to treat vasospasm in subarachnoid hemorrhage: A case report of transcranial Doppler monitoring.

This case illustrates the importance and potential of having TCD monitoring in intensive care. This easy-to-use, safe, low-cost, and bedside tool allows evaluation of the safety and feasibility of an alternative treatment of VSP in SCH and demonstrates the potential to avoid the use of angiography, a high cost, invasive procedure.

Acid base variables predict survival early in the course of treatment with continuous venovenous hemodiafiltration.

Metabolic acid-base disorders, especially metabolic acidosis, are common in critically ill patients who require renal replacement therapy. Continuous veno-venous hemodiafiltration (CVVHDF) achieves profound changes in acid-base status, but metabolic acidosis can remain unchanged or even deteriorate in some patients. The objective of this study is to understand the changes of acid-base variables in critically ill patients with septic associated acute kidney injury (SA-AKI) during CVVHDF and to determine how they relate to clinical outcome.Observational study of 200 subjects with SA-AKI treated with CVVHDF for at least 72 hours. Arterial blood gases and electrolytes and other relevant acid-base variables were analyzed using quantitative acid-base chemistry.Survivors and nonsurvivors had similar demographic characteristics and acid-base variables on day one of CVVHDF. However, during the next 48 hours, the resolution of acidosis was significantly different between the 2 groups, with an area under the ROC curve for standard base excess (SBE) and mortality of 0.62 (0.54-0.70), this was better than APACHE II score prediction power. Quantitative physicochemical analysis revealed that the majority of the change in SBE was due to changes in Cl and Na concentrations.Survivors of SA-AKI treated with CVVHDF recover hyperchloremic metabolic acidosis more rapidly than nonsurvivors. Further study is needed to determine if survival can be improved by measures to correct acidosis more rapidly.

Prognostic ability of quick-SOFA across different age groups of patients with suspected infection outside the intensive care unit: A cohort study.

OBJECTIVES: Sepsis identification in older patients is challenging. We evaluated the performance of qSOFA across different age groups of patients with suspected infection outside the intensive care unit (ICU). METHODS: Retrospective cohort in a tertiary hospital in Brazil, from January 2016 to December 2016. Outcomes were hospital mortality, ICU admission and bacteremia. Performance of qSOFA was compared over three age groups: (1) reference: ≤65 years, (2) old: 65 to 79 years and (3) very old: ≥80 years. RESULTS: There were 420 patients in the study, of which 259 (61.7%) were ≤65 years, 80 (19%) were 65 to 79 years and 81 (19.3%) were ≥80 years. Old and very old patients had higher qSOFA scores and lower SIRS scores. Overall, qSOFA ≥2 was associated to hospital mortality [OR (95% CI) = 5.8 (3.3-10.4), p < 0.001], ICU admission [OR (95% CI) = 2.7 (1.6-4.6), p < 0.001] and bacteremia [OR (95% CI) = 3.1 (1.7-5.8), p < 0.001]. Those associations were stronger in old and very old patients. qSOFA and SIRS demonstrated overall AUROCs for hospital mortality of 0.72 and 0.50, respectively. CONCLUSION: qSOFA demonstrated good overall accuracy and was more strongly associated to outcomes in old and very old patients, when compared to younger patients.