Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial.

OBJECTIVE: To evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia. METHODS: We conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875. RESULTS: Thirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group. CONCLUSION: Early fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.

Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial

OBJECTIVE: To evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia. METHODS: We conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875. RESULTS: Thirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group. CONCLUSION: Early fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.

Usos de antimicrobianos em uma Unidade de Terapia Intensiva Neonatal em Fortaleza / Use of antimicrobials in a Neonatal Intensive Care Unit in Fortaleza

Introdução: A utilização de antimicrobianos é o tratamento de escolha para infecções em recém-nascidos (RNs) e o respeito aos horários do aprazamento, além do tempo de uso, da posologia e da escolha adequada do medicamento, são critérios fundamentais para uma boa eficácia do tratamento. Objetivo: Descrever o uso de antimicrobianos na Unidade de Terapia Intensiva Neonatal (UTIN), identificando os esquemas mais utilizados em nosso meio, além de verificar as alterações mais comuns no aprazamento dos antimicrobianos. Material e método: Estudo transversal com 94 RNs prematuros que fizeram uso de antimicrobianos e permaneceram pelo menos 48 horas na UTIN de uma instituição pública de Fortaleza. A pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da Universidade Estadual do Ceará, conforme resolução 196/96. A coleta dos dados foi realizada através de um formulário contendo variáveis como tipo de antimicrobiano utilizado e alterações do aprazamento. O software utilizado para a análise estatística foi o SPSS-13. Resultados: A idade gestacional mais prevalente por ocasião do parto foi entre 32 e 37 semanas (57,5) e 39,4% dos RNs pesavam menos de 1.500 g. A síndrome do desconforto respiratório foi a principal causa de internação (48,9%), mas a condição que mais necessitou da utilização de antimicrobianos foi a amniorrexe prematura (34%). O principal esquema utilizado foi o esquema único de ampicilina e amicacina (36,2%). Alterações de aprazamento foram 39 (41,4%), seguidas de erro de aprazamento em 9,6% dos casos.

Aminophylline (a theophylline-ethylenediamine complex) blocks ethanol behavioral effects in mice.

Aminophylline is a complex of theophylline-ethylenediamine, where theophylline is the main component. Theophylline is a methyxanthine and besides inhibiting phosphodiesterase enzymes, it is also a nonselective adenosine antagonist. Several reports suggested the involvement of the brain adenosinergic system in the ethanol-induced motor incoordination. Thus, the objective of this work was to study the effects of the interaction of ethanol with aminophylline as assessed by behavioral tests in mice. Eight groups of male Swiss mice were used. The animals were treated with either distilled water (control) or ethanol (E; 2, 4, and 6 g/kg, orally) for 5 days, or with distilled water for 4 days, and on the fifth day with aminophylline (A; 5 and 10 mg/kg, intraperitoneally). In the association groups (association protocols), the animals were treated with ethanol (E; 6 g/kg, orally) for 4 days, and on the fifth day received aminophylline (A; 10 mg/kg, intraperitoneally), 30 min after the last ethanol administration (first protocol, E/A). In the second association protocol (A/E), ethanol was administered for 4 days, and on the fifth day the animals received aminophylline (A; 10 mg/kg, intraperitoneally), followed again by ethanol (E; 6 g/kg, orally) administration, 30 min later. E (6 g/kg) evoked a central nervous system depressor effect, by decreasing both the locomotor activity and rearing in the open field test, and A (5 and 10 mg/kg) showed opposite effects. However, the E/A or A/E associations blocked the ethanol effect. In the rota rod test, ethanol presented a muscular relaxant effect, which was decreased in both association protocols. In the tail suspension test, while the E/A association decreased immobility, A/E association increased it, as compared with controls. In conclusion, the effects of ethanol were inhibited by its association with aminophylline, suggesting that ethanol acts on the adenosine neurotransmission.

Determination of amino acid levels in the rat striatum, after administration of ethanol alone and associated with ketamine, a glutamatergic antagonist.

The main goal of this study was to determine the amino acids (glutamate, aspartate, glutamine and tyrosine) levels in the rat striatum, after ethanol administration alone and/or associated with ketamine. In protocol 1 (Et+ketamine-1), ethanol was administered to male Wistar rats until the 7th day, and at the next day the group received only ketamine (25mg/kg, i.p.) up to the 14th day. In protocol 2 (Et+ketamine-2), ethanol was also administered up to the 7th day, and was associated with ketamine from the 8th up to the 14th day. In other groups, animals were treated daily with ethanol (4 g/kg, p.o.), for 7 or 14 days or ketamine daily for 7 days. Controls were administered with distilled water for 7 days. Results showed that, in protocol 1, aspartate (ASP) levels increased after ketamine administration, as compared to the controls. This effect was inhibited in the group Et+ketamine-1. Ethanol (7 days) increased glutamate (GLU) levels, as compared to control, and this effect did not differ significantly from that observed in the ketamine group. When ketamine was administered after the ethanol withdrawal (protocol 1), no alterations in those amino acid concentrations were seen, as compared to the control and ketamine groups. A tendency for increasing GLU levels was observed, after administration of ethanol (14 days) or ketamine alone or associated (protocol 2), when compared to control values. In protocol 2, TYR levels decreased as related to controls and to the 14-day ethanol-treated group. We can assume that ketamine presents only an antagonist effect, in animals pretreated with ethanol, followed by ketamine administered from the 8th day on. This is due to the fact that NMDA receptors are already sensitized, leading to a decrease in these receptors functions and consequently to ASP and GLU releases.