NEUROPROTECCION. TRAUMA CRANEOENCEFÁLICO. CASO CLÍNICO TERAPÉUTICO
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DEPARTAMENTO DE FARMACOLOGIA CLÍNICA Y TERAPÉUTICA. CAMPUS BIOMÉDICO. UNIVERSIDAD DE LA SABANA.
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NEUROPROTECCION. TRAUMA CRANEOENCEFÁLICO. CASO CLÍNICO TERAPÉUTICO
- 1. CASO CLÍNICO TERAPÉUTICO NEUROPROTECCIÓN EFRAIN ESTEBAN MANCERA MEDICO RESIDENTE FARMACOLOGIA CLINICA UNIVERSIDAD DE LA SABANA
- 2. DATOS PERSONALES • Fecha de ingreso 18 noviembre 2015 - 14+46 • Edad 17 años • Masculino • Natural de gacheta - Procedente y residente en guasca • Ocupación estudiante bachiller • Soltero
- 3. MOTIVO DE CONSULTA Remitido de centro de salud de Guasca – Cundinamarca
- 4. ENFERMEDAD ACTUAL Paciente que ingresa en traslado primario de centro de salud de guasca por presentar accidente de transito de 14 horas de evolución en calidad de pasajero de motocicleta el cual ocasiona trauma craneoencefálico, con Glasgow inicial de 12/15. Durante la observación paciente presenta deterioro del estado de conciencia por lo cual realizan traslado primario.
- 5. ANTECEDENTES • Patológicos niegan • Quirúrgicos niegan • Toxico niegan • Alérgicos niegan • Farmacológicos niegan
- 6. EXAMEN FISICO TA 130/70 FC 110 FR 20 SAT 92 % Cabeza con hematoma temporal derecho de 10 x 8 cm, con herida suturada con puntos separados de aproximadamente 10 cm, escoriaciones en región malar izquierda con edema asociado.
- 7. • Extremidades con localización de dolor y movilización en las 4 extremidades, llenado capilar menor de 2 segundos • Neurológico Glasgow 7 /15, pupilas isocoricas, 8 mm, derecha reactiva, izquierda no reactiva a la luz.
- 8. DIAGNOSTICO 1. Politraumatismo – calidad pasajero motocicleta 2. Trauma craneoencefálico Severo
- 9. TRATAMIENTO INICIAL • Protección de la vía aérea bajo secuencia de intubación rápida – Midazolam 5 mg bolo iv – Fentanyl 100 mcg bolo iv – Rocuronio 50 mg bolo iv
- 10. • SSN 120 cc/h IV • Midazolam 50 mcg kilo hora iv • Fentanyl 2 mcg kilo hora. iv • Diclofenaco 75 mg iv c 12 h • Metoclopramida 10 mg c 8 h iv • Ranitidina 50 mg c 8 iv
- 11. • Paso de catéter venoso central subclavio derecho • Se solicita: tomografía cerebral simple, rx torax, tomografía cara simple, tomografía columna cervical, ecografía abdomen total • Traslado a unidad de cuidados intensivos. • Valoración servicio de cirugía maxilofacial y neurocirugía
- 12. TAC CRANEO SIMPLE • Fractura lineal, no desplazada de la región temporal derecha, asociada a neumoencéfalo • No hay colecciones intra ni extra axiales ni tampoco signos de hemorragia subaracnoidea. • La densidad del parénquima cerebral es normal con adecuada diferenciación corticosubcortical. • El espacio subaracnoideo periférico, las cisternas de la base y el tamaño ventricular no presentan alteraciones. • La línea media es central. • Las estructuras de la fosa posterior no presentan alteraciones.
- 15. TAC ORBITA • Se observa fractura no desplazada del piso de la órbita izquierda con respeto de la grasa retroconal y de los músculos orbitarios. • Se observa fractura de la pared anterior y posterior del seno maxilar izquierdo que se extienden hasta el alveolo dentario de la pieza dental 26. • Ocupación con material de tejidos blandos de los senos maxilar izquierdo y celdillas etmoidales del mismo lado , hemoseno. • Fractura del tercio medio del arco cigomático izquierdo. • fractura de la pared lateral de la órbita izquierda. • Edema y aire en los tejidos blandos de la hemicara izquierda y región frontotemporal derecha.
- 16. TOMOGRAFIA COLUMNA CERVICAL • Fracturas de los procesos transversos izquierdos en los cuerpos vertebrales c6 y c7, con compromiso en esta ultima vertebra del agujero vertebral ipsilateral. • Fractura de las apófisis espinosas de las vertebras de c7 y t1.
- 17. EVOLUCION • Servicio de cirugía maxilofacial • Sugieren continuar manejo medico instaurado, se programa para reducción abierta de fracturas faciales posterior a resolución de edema facial y estabilización en UCI
- 18. EVOLUCION Servicio de neurocirugía considera que paciente cursa con fractura lineal parietal derecha, neumoencefalo marginal y hematoma subgaleal, sin apreciar signos de sangrado, ni lesiones intra o extra axiales susceptibles de tratamiento neuroquirurgico
- 19. UCI ADULTOS 1. Ceftriaxona 2 grs día 2. Midazolam 50 mcg kg hora iv 3. Fentanyl 2 mcg kg hora. iv 4. Diclofenaco 75 mg iv c 12 h 5. Metoclopramida 10 mg c 8 h iv 6. Ranitidina 50 mg c 8 iv 7. Cloruro de sodio 0.9% 1000 cc bolo, continuar a 120 cc hora iv 8. Solucion salina hipertonica 7,5% - 125 cc c/6 h iv 9. Dexametasona 4 mgrs iv cada 8 hrs 10. Fenitoina bolo 750 mg iv, continuar 125 mg c 12 h iv
- 21. TRAUMA CRANEO ENCEFALICO • 10 millones de personas al año • Aumento incidencia global – países desarrollados • Accidentes de trafico • Disminución mortalidad – últimos 30 años (Implementación guías)
- 22. SEVERIDAD Martin Seule, Thomas Brunner, Alexander Mack, Gerhard Hildebrandt, Jean-Yves Fournier. Neurosurgical and Intensive Care Management of Traumatic Brain Injury Facial Plast Surg 2015;31:325–331.
- 23. ABORDAJE TCE
- 24. DAÑO SECUNDARIO
- 26. PRESION INTRACRANEAL • EDEMA CEREBRAL HIC MUERTE ENCEFALICA • Teoría Monro-Kellie Parénquima cerebral (80%) LCR (10%) Sangre (10%)
- 29. MONITORIZACION PIC • Glasgow 3-8 + TAC anormal • TCE – TAC NORMAL MAYORES DE 40 AÑOS Anomalías pupilares PAS menor de 90 mm Hg • Medición Catéter intraventricular
- 31. HIPERTENSION INTRACRANEANA • PPC = PAM – PIC Mayor de 20 mm Hg Objetivo: PIC <20 mmHg PPC > 60 mm Hg
- 35. MANITOL • MANITOL Gradiente osmótico entre plasma y compartimiento intracraneal • Reducción edema por arrastre de agua en espacio vascular • Administración periférica
- 36. • Aumento volumen y flujo sanguíneo cerebral NO paso barrera sangre-LCR • t ½ - 15 min – 2 horas • 10 % eliminación renal • DIURESIS OSMOTICA Alteraciones electrolíticas Depleción de volumen Insuficiencia renal (estadío final)
- 37. MANITOL • 0.25 – 1 g /kg IV durante 20 – 30 minutos • Repetir bolos c/ 6 horas • Monitorización osmolaridad sérica (evitar deshidratación sistémica) menor de 320 mosmol/Kg
- 38. SOLUCION HIPERTONICA • Concentraciones 1.7%, 3%,7.5 %, 10%, 14.6%, 23.4%, 29.2 % > 3 % Vía central • Gradiente plasma-compartimiento cerebral • NO efecto diurético • Aumento Na y Cl
- 39. • Numerosos regímenes – Pocas conclusiones de dosis y concentración a usar • Expansión de volumen sin alteración electrolítica ni daño renal vs manitol • ACIDOCIS METABOLICA • HIPERNATREMIA – HIPERCLOREMIA • Falla cardiaca
- 40. • Solución hipertónica 7.5 %: Mejoría oxigenación cerebral y hemodinámia sistémica-cerebral Bolos 75-100 cc en 20 minutos – C 6 h IV Infusión 48 – 72 horas • 3 % Bolos 150 cc • 14.6% Bolos 24 cc • 23.4 % Bolos 30 cc
- 47. PROFILAXIS - CONVULSIONES • Convulsiones de impacto (24 h) • Convulsiones tempranas (<1 semana) • Convulsiones tardías (<2 años) • Generalizadas – Tempranas • Parciales - Tardias
- 54. Dosis de carga 18 mg/kg IV Mantenimiento 100 mg 3 veces al día IV TOLERANCIA VIA ORAL 300 mg C 8 H hasta 900 mg, luego 125 mg c 8 horas ANA
- 55. CALCIOANTAGONISTAS Gene Gurkoff , Kiarash Shahlaie , Bruce Lyeth and Robert Berman.Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury. Pharmaceuticals 2013, 6, 788-812
- 56. 10 Pacientes, grupo amlodipino (5 pacientes) (2 mg/h iv) disminucion PIC, Aumento glasgow
- 59. Ratones Microglia murina BV2 Nicardipino disminuye proliferacion celular de microglia
- 60. SEDACION
- 61. SEDACION • PROPOFOL – MIDAZOLAM – FENTANIL – KETAMINA - EFECTOS SIMILARES EN HIC • Midazolam 0.01-0.05 mg/kg c 10 minutos (sedación), luego 0.02 mg/kg/h IV Asociación Fentanyl 0.5-1.5 mcg/kg/h IV Ketamina : despertar agitado Propofol - < 48 horas, no mas 4 mg/kg/h IV
- 62. BARBITURICOS
- 63. BARBITURICOS • Disminución flujo sanguíneo cerebral – disminución demanda metabólica • Efectos secundarios Inmunosupresion, infecciones, hipotensión • No diferencias tiopental vs fenobarbital • BENEFICIO: HIC RESISTENTE
- 64. CORTICOIDES
- 65. CORTICOIDES •1960 – edema cerebral •Uso controversial •Aumento MORTALIDAD •TUMORES CEREBRALES
- 68. INJURIA SECUNDARIA DAVID J. LOANE, BOGDAN A. STOICA, AND ALAN I. FADEN.Neuroprotection for traumatic brain injury. Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I
- 69. AIF: Factor inductor de apoptosis – condensación cromatina y degradación ADN Parthanatos: muerte celular dependiente de PARP1 (Modificación proteínas nucleares por ribosilacion) Necroptosis: Estimulación por TNF alpha Paraptosis: Vacuolización citoplasmática DAVID J. LOANE, BOGDAN A. STOICA, AND ALAN I. FADEN.Neuroprotection for traumatic brain injury. Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I
- 70. 1. Activación microglía 2. Reclutamiento celular pro inflamatorias 3. Producción citoquinas (IL1, TNF alpha) DAVID J. LOANE, BOGDAN A. STOICA, AND ALAN I. FADEN.Neuroprotection for traumatic brain injury. Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I
- 71. Kara N. Corps, DVM, DACVP; Theodore L. Roth, MS; Dorian B. McGavern, PhD.Inflammation and Neuroprotection in Traumatic Brain Injury. JAMA Neurol. 2015;72(3):355-362.
- 72. DAVID J. LOANE, BOGDAN A. STOICA, AND ALAN I. FADEN.Neuroprotection for traumatic brain injury. Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I
- 73. Activación fosfolipasas, endonucleasas, Proteasas (calpaina) DAVID J. LOANE, BOGDAN A. STOICA, AND ALAN I. FADEN.Neuroprotection for traumatic brain injury. Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I
- 74. FISIOPATOLOGIA DAVID J. LOANE, BOGDAN A. STOICA, AND ALAN I. FADEN.Neuroprotection for traumatic brain injury. Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I
- 75. DAVID J. LOANE, BOGDAN A. STOICA, AND ALAN I. FADEN.Neuroprotection for traumatic brain injury. Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I
- 76. Shruti V. Kabadi and Alan I. Faden.Neuroprotective Strategies for Traumatic Brain Injury:Improving Clinical Translation. Int. J. Mol. Sci. 2014, 15, 1216-1236
- 77. Shruti V. Kabadi and Alan I. Faden.Neuroprotective Strategies for Traumatic Brain Injury:Improving Clinical Translation. Int. J. Mol. Sci. 2014, 15, 1216-1236
- 78. ESTATINAS
- 79. ESTATINAS • Actividad antinflamatoria Reducción adhesión leucocitaria Disminución apoptosis cerebral • Rosuvastatina: Disminución actividad TNF alpha • Mayores estudios
- 80. PROGESTERONA • Reducción edema cerebral - inflamación • Atenuación excitotoxicidad • Disminución peroxidación lipídica
- 81. Hanna Algattas, and Jason H. Huang.Traumatic Brain Injury Pathophysiology and Treatments: Early, Intermediate, and Late Phases Post-Injury. Int. J. Mol. Sci. 2014, 15, 309-341
- 82. PROGESTERONA
- 83. CICLOSPORINA A • Disminución daño mitocondrial • Atenuación apoptosis • Estudios preclínicos: Menor lesión axonal difusa • Pobre penetración SNC – Depresión medular
- 84. Ye Xiong†, Yanlu Zhang, Asim Mahmood & Michael Chopp Investigational agents for treatment of traumatic brain injury. Expert Opin. Investig. Drugs
- 85. Ye Xiong†, Yanlu Zhang, Asim Mahmood & Michael Chopp Investigational agents for treatment of traumatic brain injury. Expert Opin. Investig. Drugs
- 87. W. David Freeman, MD, FSNS, FAAN. Management of Intracranial Pressure. Continuum (Minneap Minn) 2015;21(5):1299–1323
- 88. • Medidas no farmacologicas (cabecera 30- 45 grados, hipotermia) • SOLUCION HIPERTONICA, leve ventaja sobre manitol • Profilaxis convulsiones usar FENITOINA por siete dias (ojo niveles 9 dosis) • Sedacion usar Midazolam, Fentanyl
Hinweis der Redaktion
- Alteraciones priamrias llevan a alteraciones secundarias
- Teoria m kellie: si aumenta un comartimiento los otros dos deben disminuir Priemro se modifica el lcr que se distribuye a medula Luego se disminuye el flujo sanguineo cerebral Por ultimo se modifica el parenquima cronicamente
- Mannitol is usually administered as a slow bolus (0.2 to 1 g/kg) over 20 to 30 minutes, and its effect lasts between 90 minutes and over 8 hours. Sometimes repeated boluses are given after an interval of 6 hours each,
- Similar to mannitol, hypertonic saline can be given as a slow bolus (100mL of 7.5% within 20 min), but it may be administered as a continuous infusion over 48 to 72 hours and then slowly weaned It is used in a 3% solution (513 mmol per liter) in boluses of approximately 150 ml, in a 7.5% solution (1283 mmol per liter) in 75-ml boluses, or in a 23.4% solution (4008 mmol per liter, which is routinely available in hospital pharmacies for intravenous solution admixture and referred to as “23%”) in 30-ml boluses
- metabolic acidosis from relative bicarbonate depletion. When there is sodium excess, bicarbonate is often wasted by the kidneys. This state can be corrected by enteral free water flushes, although in patients receiving hypertonic saline, there is no true water deficit, but rather an excess of sodium chloride
- Similar to mannitol, hypertonic saline can be given as a slow bolus (100mL of 7.5% within 20 min), but it may be administered as a continuous infusion over 48 to 72 hours and then slowly weaned It is used in a 3% solution (513 mmol per liter) in boluses of approximately 150 ml, in a 7.5% solution (1283 mmol per liter) in 75-ml boluses, or in a 23.4% solution (4008 mmol per liter, which is routinely available in hospital pharmacies for intravenous solution admixture and referred to as “23%”) in 30-ml boluses
- The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4mL/kg; n = 25 patients) or HTS 7.5% (2 mL/kg; n = 22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.
- Purpose of review—discuss trends in the use of osmotic therapy. Recent findings—use of osmotic therapy has evolved from bolus administration of mannitol to routine use of hypertonic saline (HS) as a bolus as well as in continuous infusions to creating a sustained hyperosmolar state. In a survey of neurointensivists 55% favored HS over mannitol. Retrospective studies suggest better ICP control with HS. While a prospective study in adults with head injury compared alternating doses of mannitol and HS found no difference in change in ICP control or outcome, two meta-analyses, which did not include this study, favored HS for ICP control (although the absolute difference of 2 mm Hg is of little clinical values) with no difference in outcome. HS has also been administered by infusions to creating a sustained stable hyperosmolar state. Two studies, using historical controls, suggested benefit of HS infusions. In a prospective, randomized study, in children with severe head injury Lactated Ringer’s solution was compared hypertonic saline. Although ICP control was similar, the HS group required fewer other interventions. Summary—the existing data do not support favoring boluses of HS over mannitol in terms of ICP control let alone outcome. The rationale for continuous infusions to create a sustained hyperosmolar state
- Object Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI. Methods The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of &gt; 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of &gt; 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chisquare test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples. Results A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56). Conclusions HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.
- diferenciadas por intervalo de tiempo de presentación seguido del trauma: I. convulsiones de impacto, ocurren en las primeras 24 horas subsecuentes al trauma; II. Convulsiones tempranas, ocurren antes de 1 semana de instaurado el traumatismo; III. Convulsiones tardías comprenden después del día 8 hasta 2 años después del trauma, en ocasiones se pueden presentar después de los 5 años. (6) Los tipos de convulsión también varían dependiendo del periodo de tiempo de presentación posterior a la injuria, se habla que con una relativamente alta proporción en estados tempranos se presentan convulsiones generalizadas, mientras que en estados tardíos predominan la prevalencia de convulsiones parciales. También se describe ocurrencia de estatus epiléptico con mayor frecuencia en estadios tempranos, siendo reportado hasta el 20% de incidencia.
- Phenytoin increases the refractory period and reversibly inhibits action potentials [40]. In severe TBI, phenytoin has been found to reduce the incidence of early seizures from 14.2% to 3.6% [41]. Also, this drug should only be used within the first 48 h post-trauma because a randomized control trial showed a trend toward higher mortality when used at later time points [35]. In a separate study, the use of this anticonvulsant beyond 1 week was associated with idiosyncratic side effects (Table 2) [37,40]. The onset of rashes is also suggested with a RR of 1.57 from a recent meta-analysis [37]. In addition, long-term prophylaxis has not been shown to improve morbidity, mortality, or PTE develop- ment with this drug [35]. The current recommendation is early prophylaxis and acute treatment with each episode of seizure activity. 3.2. Carbamazepine Another rarely prescribed medication for prophylaxis is carbamazepine [40]. One preliminary study has demonstrated that carbamazepine reduces PTS by 61% [38]. According to a meta-analysis, early preventive treatment with carbamazepine showed a RR of 0.96 for reduction in mortality and disability [37]. This is consistent with other studies demonstrating no association between early prophylaxis and long-term prognosis. It is important to note that this medication is associated with several side effects and is administered intravenously limiting its use (Table 2) [40]. These adverse reactions must be carefully considered 3.3. Valproate Valproate inhibits GABA transaminase increasing GABA levels in the synaptic cleft [40]. Studies have demonstrated a similar efficacy as compared to phenytoin [38]. However, valproate is also associated with a higher mortality [42]. Potential adverse effects of valproate are outlined in Table 2 [40]. Despite its efficacy, this medication cannot be recommended due to increased mortality in patients with PTS [42].
- Barbiturate coma is effective in reducing the ICP by suppressing cerebral metabolism, thus reducing cerebral metabolic demands and cerebral blood volume.[44] This therapy is associated with many complications including immunosuppression, infectious complications and hypotension. There is no clinical evidence of improved patient outcomes after barbiturate coma though an infusion of thiopentone to achieve EEG burst suppression is still commonly used when trying to control severe refractory intracranial hypertension.[44] Thiopentone was found to be better ICP reducing agent in comparison to pentobarbital; however, incidence of hypotensive episodes, outcome and mortality data were similar in both groups.[45] Recent Cochrane review (7 clinical trials, 341 patients) also showed no outcome benefit using the barbiturate therapy in patients with severe head injury; however, there was more frequent episodes of hypotension (1 in every four patients), which offset the improvement in ICP by decreasing the CPP.[44]
- The Corticosteroid Administration after Severe Head Injury trial showed increased mortality at 2 weeks (21.1% vs. 17.9%) as well as at 6 month (25.7% vs. 22.3%) when compared with placebo.[32,33] In this trial, 10,008 adults patients with head injury (GCS &lt;14) within 8 h of injury were randomly allocated to either 48 h infusion of corticosteroids (methylprednisolone) or placebo. However, one RCTs on 150 patients with severe multiple trauma highlighted that low dose of steroids (hydrocortisone 200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) may prevent hospital acquired pneumonia and found to decrease in the length of ICU stay.[34] The other results of other RCT on the role of low dose of steroids (hydrocortisone and fludrocortisones vs. double placebo) patients with TBI has yet to be published and may provide some important guidelines related to steroid use in this subgroup of patients.[35]
- Comparison of brain anatomy in the meninges and superficial neocortex before and after focal mild TBI (mTBI). The dura mater contains numerous small vessels that are lined by thin, elongated meningeal macrophages. The subarachnoid space contains vessels, fibroblastlike stromal cells, and cerebrospinal fluid (CSF). The glial limitans, composed of astrocytic foot processes, lies beneath the pia mater and forms a barrier between the CSF and underlying parenchyma. Mild focal brain injury mechanically compresses the meningeal space, compromising vascular integrity and inducing rapid necrosis of meningeal macrophages and structural cells. Leakage of fluid from meningeal blood vessels results in edema, and damaged cells within the meninges release reactive oxygen species (ROS) and adenosine triphosphate (ATP), initiating a sterile immune reaction. B and C,
- Excitotoxicidad es el proceso patológico por el cual las neuronas son dañadas y destruidas por las sobreactivaciones de receptores del neurotransmisor excitatorio glutamato, como el receptor NMDA y el receptor AMPA. Las excitotoxinas como el NMDA y el ácido kaínico que se unen a estos receptores, así como altos niveles patológicos de glutamato, pueden provocar la excitotoxicidad al permitir que niveles elevados de iones de calcio1 entren en la célula. La entrada de Ca++ en las células activa una serie de enzimas, incluyendo las fosfolipasas, las endonucleasas, y proteasas tales como la calpaína. Estas enzimas continúan dañando estructuras celulares como las que componen el citoesqueleto, la membrana y el ADN.
- Statins are a well-known class of medications which act through their inhibition of 3-hydroxy-3- methylglutaryl coenzyme A reductase to decrease hepatic cholesterol synthesis which in turns lowers serum low density lipoprotein levels by hepatic LDL-receptor up regulation. However, due to the numerous secondary effects and well known safety profile, the use of these agents has been investigated as treatments in other disease processes. There is evidence that statins may have anti-inflammatory properties by way of reduced leukocyte adhesion (Weitz-Schmidt, 2002). Additionally, improvements in cerebrovascular dynamics via increased endothelial nitric oxide synthase activity, decreased neuronal apoptosis and increased production of VEGF and BDNF have also been reported (Wible and Laskowitz, 2010). rosuvastatin significantly reduced levels of TNFα at 3 days but did not significantly alter serum IL-1β, IL-6 or IL-10