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World Neurosurg ; 132: e21-e27, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521754


BACKGROUND: To investigate role of Low-dose, Early Fresh frozen plasma Transfusion (LEFT) therapy in preventing perioperative coagulopathy and improving long-term outcome after severe traumatic brain injury (TBI). METHODS: A prospective, single-center, parallel-group, randomized trial was designed. Patients with severe TBI were eligible. We used a computer-generated randomization list and closed opaque envelops to randomly allocate patients to treatment with fresh frozen plasma (5 mL/kg body weight; LEFT group) or normal saline (5 mL/kg body weight; NO LEFT group) after admission in the operating room. RESULTS: Between January 1, 2018, and November 31, 2018, 63 patients were included and randomly allocated to LEFT (n = 28) and NO LEFT (n = 35) groups. The final interim analysis included 20 patients in the LEFT group and 32 patients in the NO LEFT group. The study was terminated early for futility and safety reasons because a high proportion of patients (7 of 20; 35.0%) in the LEFT group developed new delayed traumatic intracranial hematoma after surgery compared with the NO LEFT group (3 of 32; 9.4%) (relative risk, 5.205; 95% confidence interval, 1.159-23.384; P = 0.023). Demographic characteristics and indexes of severity of brain injury were similar at baseline. CONCLUSIONS: LEFT therapy was associated with a higher incidence of delayed traumatic intracranial hematoma than normal fresh frozen plasma transfusion in patients with severe TBI. A restricted fresh frozen plasma transfusion protocol, in the right clinical setting, may be more appropriate in patients with TBIs.

Transfusão de Sangue/métodos , Lesões Encefálicas Traumáticas/terapia , Plasma , Idoso , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/cirurgia , Craniotomia , Método Duplo-Cego , Feminino , Hematoma Subdural Agudo/cirurgia , Hematoma Subdural Agudo/terapia , Humanos , Hemorragia Intracraniana Traumática/complicações , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prevenção Secundária , Resultado do Tratamento
Free Radic Biol Med ; 141: 299-309, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31265876


OBJECTIVE: Carbon monoxide (CO) releasing molecule (CORM)-3, a water-soluble CORM, has protective effects against inflammatory and ischemia/reperfusion injury. We determined the effect of CORM-3 against neuronal pyroptosis in a model of hemorrhagic shock and resuscitation (HSR) in rats via mitochondrial regulation. METHODS: Rats were treated with CORM-3 (4 mg/kg) in vitro after HSR. We measured cortical CO content 3-24 h after HSR; assessed neuronal pyroptosis, mitochondrial morphology, ROS production, and mitochondrial membrane potential at 12 h after HSR; and evaluated brain magnetic resonance imaging at 24 h after HSR and learning ability 30 days after HSR. We also measured soluble guanylate-cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway activity using a blocker of sGC, NS2028, and 125I-cGMP assay. RESULTS: Among rats that underwent HSR, CORM-3-treated rats had more CO in the cortical tissue than sham- and iCORM-3-treated rats. CORM-3-treated rats had significantly less neuronal pyroptosis in the cortical tissue; higher sGC activity and cGMP content; lower ROS production; better mitochondrial morphology, function, and membrane potential; and enhanced learning/memory ability than HSR-treated rats. However, these neuroprotective effects of CORM-3 were partially inhibited by NS2028. CONCLUSION: CORM-3 may alleviate neuronal pyroptosis and improve neurological recovery in HSR through mitochondrial regulation mediated by the sGC-cGMP pathway. Thus, CO administration could be a promising therapeutic strategy for hemorrhagic shock.