naloxone and Brain-Injuries

The efficiency of naloxone for the management of secondary brain injury after severe traumatic brain injury (sTBI) remains undefined. The aim of this study is to evaluate the current evidence regarding the clinical efficiency and safety of naloxone as a treatment for sTBI in mainland China.. A systematic search of the China Biology Medicine disc (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Internet (CNKI), and Wan Fang Database was performed to identify randomized controlled trials (RCTs) of naloxone treatment for patients with sTBI in mainland China. The quality of the included trials was assessed, and the RevMan 5.1 software was employed to conduct this meta-analysis. Nineteen RCTs including 2332 patients were included in this study. The odds ratio (OR) showed statistically significant differences between the naloxone group and the control group (placebo) in terms of mortality at 18 months after treatment (OR, 0.51, 95%CI: 0.38-0.67; p<0.00001), prevalence of abnormal heart rates (OR, 0.30, 95%CI: 0.21-0.43; p<0.00001), abnormal breathing rate (OR, 0.25, 95%CI: 0.17-0.36; p<0.00001) at discharge, the level of intracranial pressure at discharge (OR, 2.00, 95%CI: 1.41-2.83; p = 0.0001), verbal or physical dysfunction rate (OR, 0.65, 95%CI: 0.43-0.98; p = 0.04), and severe disability rate (OR, 0.47, 95%CI: 0.30-0.73; p = 0.0001) at 18 months after the treatment. The mean difference (MD) showed statistically significant differences in awakening time at discharge (MD, -4.81, 95%CI: -5.49 to -4.12; p<0.00001), and GCS at 3 days (MD, 1.00, 95%CI: 0.70-1.30; p<0.00001) and 10 days (MD, 1.76, 95%CI: 1.55-1.97; p<0.00001) after treatment comparing naloxone with placebo group.. This study indicated that applying naloxone in the early stage for sTBI patients might effectively reduce mortality, control intracranial pressure (ICP), and significantly improve the prognosis.

Topics: Brain Injuries; Case-Control Studies; Clinical Trials as Topic; Humans; Naloxone; Narcotic Antagonists

Clinicians in the emergency department are often confronted with coma patients due to poisoning. A systematic general approach involving early consultation with a neurologist is of paramount importance. A high index of suspicion, a systematic first assessment already in the prehospital phase and early stabilisation of vital functions are the essential first steps. Specific antidotes like hypertonic glucose and thiamine are part of a "coma cocktail". The opiate antagonist naloxone should be used only when clinically indicated and in a titrated way. Flumazenil should only be used with caution and in restricted cases. Clinical neurological evaluation and technical investigations like CT-scan and laboratory tests should make part of a careful diagnostic plan. Toxicological tests deserve their place in the diagnostic work up of a coma patient with suspected poisoning. Knowledge of the possibilities of the toxicology lab and optimal communication with the clinical toxicologist is important for optimal patient care.

Topics: Accidental Falls; Alcohol-Induced Disorders, Nervous System; Alcoholic Intoxication; Antidotes; Brain Injuries; Coma; Diabetic Coma; Diagnosis, Differential; Diagnostic Tests, Routine; Drug Overdose; Emergencies; Ethanol; First Aid; Flumazenil; Glucagon; Glucose; Humans; Hypoglycemia; Hypoxia, Brain; Monitoring, Physiologic; Naloxone; Neurologic Examination; Stroke; Thiamine

Effective management of brain-injured patients requires that nurses have a specialized body of knowledge relating to the pathophysiology and treatment of traumatic brain injury (TBI). Current research in this area has focused on the cascade of secondary injury which leads to the irreversible tissue damage following TBI. Such processes involve excitatory amino acids, neurotransmitters, ion changes, lipid peroxidation, oxygen free radicals, opioids, lactic acidosis and magnesium to name but a few. Given that no accepted treatment paradigm exists to attenuate these secondary processes, nurses may have to autonomously devise individual care plans based on their current understanding of brain injury pathophysiology.

Topics: Brain Injuries; Excitatory Amino Acids; Free Radicals; Humans; Ion Channels; Lactic Acid; Lipid Peroxidation; Naloxone; Narcotics; Neurotransmitter Agents; Nurses; Oxygen

Topics: Acute Disease; Brain Injuries; Clinical Trials as Topic; Drug Administration Schedule; Humans; Methylprednisolone; Methylprednisolone Hemisuccinate; Naloxone; Spinal Cord Injuries; Time Factors

To evaluate the efficacy and safety of moderate dosage naloxone in acute moderate and severe traumatic brain injury.. A randomized double-blind prospective clinical trial was done to compare the differences of naloxone and saline in acute moderate and severe traumatic brain injury. Naloxone or saline placebo was intravenously given for 10 days. We followed up for at least 1 month. The indexes of assessment of prognosis were Glasgow outcome scale, verbal function and motor function.. Forty cases were enrolled in the clinical trial, evenly divided into the naloxone group, and the saline group. On the 10th day after the treatment, Glasgow coma scale, improvement of abnormity of blood pressure, rhythm of the heart and breath in the naloxone group were significantly higher than those in the saline group. The mortalities of the naloxone group and the saline group were 0 and 5% respectively. After the one-month follow-up, Glasgow outcome scale and verbal function in the naloxone group were significantly higher than those in the saline group. In addition, a patient was found with mania possibly caused by naloxone.. Early application of moderate dosage naloxone in acute traumatic brain injury may significantly reduce the mortality rate and improve the recovery of nerve function.

Topics: Adolescent; Adult; Aged; Brain Injuries; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Prognosis; Prospective Studies; Trauma Severity Indices

Topics: Acute Disease; Brain Injuries; Clinical Trials as Topic; Drug Administration Schedule; Humans; Methylprednisolone; Methylprednisolone Hemisuccinate; Naloxone; Spinal Cord Injuries; Time Factors

Cardiopulmonary arrest is a serious disease that claims many lives every day; 30% of the patients suffer irreversible central nervous system injury after restoration of systemic circulation (ROSC).. Naloxone combined with epinephrine was tested in a cardiac arrest rat model in which asphyxia was induced to determine if this drug combination could increase the resuscitation rate (survival) and decrease the cerebral damage.. Twenty-four male Wistar rats were randomly assigned to one of three groups: the group treated with 1 mL saline (SA group; n = 8), the group treated with only epinephrine 5 microg/100 g (EP group; n = 8), or the group treated with epinephrine 5 microg/100 g combined with naloxone 1 mg/kg (NA group; n = 8). Eight minutes after arrest, cardiopulmonary resuscitation was initiated and the different drugs were administered to the rats in their respective groups at the same time. Mean arterial pressure (MAP), heart rate (HR), and neurodeficit score (NDS) were measured.. The HR in the NA group (414 +/- 45 beats/min) was faster than in the EP group (343 +/- 29 beats/min) at the 5-min time point (P < 0.01). The HR in the NA group was 392 +/- 44 beats/min and 416 +/- 19 beats/min at the 60-min and 180-min time points, respectively. There were no statistically significant differences in MAP before or after ROSC. The rates of ROSC were 2 of 8, 6 of 8, and 7 of 8 animals in the SA group, EP group, and NA group, respectively. Three days later, the rates decreased to 1, 3, and 5 in the SA group, EP group, and NA group, respectively. The average resuscitation time in the NA group was significantly shorter than in the other two groups. The NDS in the NA group was 57 +/- 13, higher than in the EP group (45 +/- 13) and SA group (38).. Naloxone combined with epinephrine significantly increased the resuscitation rate in a rat model. Furthermore, the combination of naloxone and epinephrine increased the NDS after cardiopulmonary resuscitation.

Topics: Animals; Asphyxia; Brain Injuries; Cardiopulmonary Resuscitation; Chi-Square Distribution; Epinephrine; Heart Rate; Male; Naloxone; Random Allocation; Rats; Rats, Wistar

To investigate the capacity of blood draining from the central nervous system of patients with acute brain injury to induce cell death, and to determine whether this phenomenon could be a way to induce the production of autoantibodies.. The induction of cell death of several human leukemia cell lines cultured in vitro in the presence of serum collected from the brain or the systemic circulation of patients with acute brain injury was analyzed by flow cytometry after staining with annexin V and propidium iodide. The percentages of apoptotic lymphocytes derived directly from the patients were also quantified. To investigate the mechanisms responsible for the induction of cell death, the expression of apoptosis-related molecules, as well as the effect of addition of several molecules known to interfere with apoptosis, was evaluated in the cell cultures. The presence of serum autoantibodies at the time of injury and 6 months later was studied.. Systemic serum and, especially, serum draining from the brain lesions induced the in vitro death of the leukemia cell lines used. Moreover, there were higher percentages of ex vivo dead lymphocytes in regional blood than in systemic blood 48 hours after injury. These effects seemed to be induced by an exogenous and/or endogenous opioid, since they were blocked by the opioid antagonist, naloxone. Furthermore, such effects were mediated by an increased expression of Bax. Importantly, apoptotic Jurkat cells were bound to autoantibodies, and patients with acute brain injury produced serum autoantibodies some months after the injury. However, they did not develop a full autoimmune disease at that time.. Serum factors from acute brain injuries induce cell death, both in vivo and in vitro. Apoptotic cells and, even more so, necrotic cells in acute brain injury are potential sources for autoantigen presentation that may stimulate autoimmune responses.

Topics: Acute Disease; Adult; Aged; Autoantibodies; bcl-2-Associated X Protein; Blood Physiological Phenomena; Brain Injuries; Cell Death; Cells, Cultured; Female; Humans; Jurkat Cells; Male; Middle Aged; Naloxone; Narcotic Antagonists; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2

Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1-3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p < 0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p < 0.01). Naloxone antagonized the anti-oedema effects and anti-nociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 possibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.

Topics: Animals; Arginine Vasopressin; Benzeneacetamides; Blood-Brain Barrier; Brain Chemistry; Brain Edema; Brain Injuries; Cold Temperature; Diuretics; Evans Blue; Male; Naloxone; Potassium; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa; Sodium; Spectrophotometry, Atomic

The present study was designed to characterize the relationship between cerebral opioid concentration, cerebral hemodynamics, and cerebral oxygenation following percussion brain injury in neonatal pigs. Previous research found that opioids represent a significant vasoactive component in the regulation of the neonatal piglet cerebral circulation. Anesthetized newborn (1-5 days old) pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm.) was produced by allowing the pendulum to strike a piston on the cylinder. Fluid percussion brain injury decreased pial arteriolar diameter (132 +/- 5 to 110 +/- 5 microns within 10 min). Cerebral blood flow also fell within 10 min of injury and continued to fall progressively for 3 h, resulting in a 46 +/- 4% decrease. Within 30 s of brain injury, there was a transient increase in cerebral hemoglobin-O2 saturation that was reversed to a progressive profound decrease in cerebral hemoglobin-O2 saturation for the next 3 h, as measured by near infrared spectroscopy. CSF opioid concentrations were increased 10 min after brain injury; dynorphin showed the largest proportional increase (5.8 +/- 0.9 fold). The CSF concentration for other opioids continued to increase over 180 min while the dynorphin concentration progressively decreased with time. In naloxone (1 mg/kg i.v.) pretreated piglets, the brain injury induced decrease in arteriolar diameter was attenuated (129 +/- 5 to 121 +/- 5 microns within 10 min). Similarly, the decrease in regional cerebral blood flow and cerebral hemoglobin-O2 saturation observed following brain injury were also blunted by naloxone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Animals, Newborn; Arterioles; Brain Injuries; Cerebrovascular Circulation; Endorphins; Female; Hemodynamics; Infusions, Intravenous; Male; Naloxone; Norepinephrine; Pia Mater; Swine; Wounds, Nonpenetrating

Neurobehavioral dysfunction following traumatic brain injury results, in part, from delayed biochemical changes initiated by the traumatic insult. Endogenous opioid peptides have been implicated as one type of neurochemical factor involved in the delayed pathological sequelae of central nervous system (CNS) injury, including brain trauma. Both opiate antagonists and thyrotropin-releasing hormone (TRH) and its analogs, which antagonize the physiologic effects of endogenous opioids, have been shown to improve cardiovascular, cerebrovascular, metabolic, and neurologic status following both traumatic and ischemic CNS injury. The present study evaluated the ability of the opiate antagonist naloxone hydrochloride to improve posttraumatic neurologic motor function following experimental fluid-percussion brain injury in the rat, and compared the therapeutic effectiveness of naloxone to the long-acting, centrally active TRH analog YM-14673. Thirty minutes following fluid-percussion brain injury of moderate severity, animals received an intravenous bolus of either naloxone (2.0 mg/kg with constant infusion of 1.7 mg/kg/h, n = 8), YM-14673 (1.0 mg/kg, n = 8), or saline (n = 8). Although naloxone caused a modest and nonsignificant increase in mean arterial blood pressure (MAP); YM-14673 significantly increased MAP within 5 min of administration (p < 0.05), an effect that continued up to 4 h postinjury. Postinjury administration of both naloxone and YM-14673 caused a significant improvement in neurobehavioral outcome which persisted up to 4 weeks postinjury. These results suggest that endogenous opioid peptides may be involved in the pathologic response to traumatic CNS injury and that pharmacotherapies directed at antagonizing opioid peptides may enhance neurobehavioral recovery after brain injury.

Topics: Animals; Azetidines; Behavior, Animal; Blood Gas Analysis; Blood Pressure; Brain Injuries; Dipeptides; Hemodynamics; Hydrogen-Ion Concentration; Male; Motor Skills; Naloxone; Rats; Rats, Sprague-Dawley

Experiments in rats showed i. p. injections of a dose of 0.1 mg/kg of highly mu-selective agonist DAGO, relatively selective delta-receptor agonist DSLET and Tyr-D-Ala-Gly-MePhe-Leu-Arg-NH-Et to attenuate markedly the development of cerebral edema 24 hours after brain injury. The same effect was found with administration of DSLET 4 days after trauma. Naloxone (1 mg/kg, i. p.) had no effect on this process, but completely blocked protective effect of peptides. These data demonstrate that both mu and delta opioid receptors are involved in the pathogenesis of traumatic cerebral edema.

Topics: Animals; Brain Edema; Brain Injuries; Dose-Response Relationship, Drug; Enkephalins; Female; Male; Naloxone; Rats; Receptors, Opioid; Time Factors

Naloxone (0.1, 1.0, or 20.0 mg/kg), morphine (1.0 or 10.0 mg/kg), or saline was administered systemically intraperitoneally to rats 15 minutes prior to moderate fluid-percussion brain injury. The effects of the drugs were measured on systemic physiological, neurological, and body-weight responses to injury. The animals were trained prior to injury and were assessed for 10 days after injury on body-weight responses and neurological endpoints. Low doses of naloxone (0.1 or 1.0 mg/kg) significantly exacerbated neurological deficits associated with injury. Morphine (10.0 mg/kg) significantly reduced neurological deficits associated with injury. The drugs had no effect on neurological measures or body weight in sham-injured animals. Drug treatments did not significantly alter systemic physiological responses to injury. Data from these experiments suggest the involvement of endogenous opioids in at least some components of neurological deficits following traumatic brain injury and suggest the possibility that at least some classes of endogenous opioids may protect against long-term neurological deficits produced by fluid-percussion injury to the rat.

Topics: Animals; Blood Pressure; Brain Injuries; Dizziness; Dose-Response Relationship, Drug; Male; Morphine; Motor Skills; Naloxone; Rats; Rats, Inbred Strains; Unconsciousness

Forty-five cats were randomly divided into four groups: (1) the control group (n = 11); (2) the head injury group (n = 17); (3) the naloxone group (n = 8); (4) the saline group (n = 9). Naloxone (10mg/kg) was directly injected into cisterna cerebello-medullaris 2 hours after injury. The results showed that naloxone had some effects in maintaining MABP, CPP, lowering of ICP and edema of brain).

Topics: Animals; Brain Injuries; Cats; Intracranial Pressure; Male; Naloxone

Topics: Animals; Brain Injuries; Cats; Cerebrovascular Disorders; Humans; Naloxone; Rats; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Topics: Brain Death; Brain Injuries; Endorphins; Humans; Naloxone