RESUMEN
The above article was published online with incorrect abbreviations in Figures 2 and 3 last sentence of the legend. HDA should be corrected to HADS.
RESUMEN
OBJECTIVE: To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury. METHODS: The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure. RESULTS: In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pWei-Lachin < 0.1, MWcombined = 0.63, 95% CI 0.48-0.77, derived standardized mean difference (SMD) 0.45, 95% CI -0.07 to 1.04, derived OR 2.1, 95% CI 0.89-5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (pWei-Lachin = 0.0240, MWcombined = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for "large" superiority. Safety aspects were comparable to placebo. CONCLUSION: Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.
Asunto(s)
Aminoácidos/farmacología , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Evaluación de Resultado en la Atención de Salud , Enfermedad Aguda , Adulto , Aminoácidos/administración & dosificación , Aminoácidos/efectos adversos , Asia Sudoriental , Lesiones Traumáticas del Encéfalo/complicaciones , Disfunción Cognitiva/etiología , Método Doble Ciego , Asia Oriental , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/efectos adversos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Indocyanine green angiography (ICGA) is slowly replacing conventional methods of evaluating perfusion during flap surgery. Microcirculatory changes during flap elevation create a marked state of hypoperfusion intraoperatively leading to ICGA underestimation of tissue viability and consequent resection of viable tissue. We propose a novel method of flap warming to induce maximum vasodilation before performing ICGA to increase accuracy in assessing perfusion. METHODS: Submental flaps harvested on a single perforator were created in 8 pigs. ICG angiography was performed in the intraoperative phase (ICGA-C), after inducing maximum vasodilatation by warming the flap at 42⯰C (ICGA-W) and at 24H postoperative (ICGA-24). By setting a fluorescence threshold of 33% as indicative of necrosis, the flap surface deemed viable by ICGA was measured for ICGAC, ICGAW and ICGA24. The results were then compared to the actual flap survival observed clinically at 7 days. RESULTS: The mean of ICG-C predicted flap survival (FS-Câ¯=â¯49.17%) is 12.97% lower than the mean of actual flap survival on postoperative day 7 (FS = 62.14%). The mean difference between ICG-W and ICG-24 predicted flap survival (FS-W and FS-24) and actual flap survival in the postoperative day 7 (FS) is lower, 3.13% and 2.15%, respectively. Average perfusion recovery over 24â¯h was 10.83% (FS-24-FS-C). CONCLUSIONS: Conventional intraoperative ICGA underestimated perfusion in all cases. Warming the flap intraoperatively and achieving maximum vasodilation mitigates the effects of vasoconstriction and mimics the microcirculatory environment encountered at 24â¯h. Performing angiography after induced vasodilation improves ICGA assessment of flap perfusion.