RESUMO
BACKGROUND: The ILCOR Basic Life Support Task Force and the international drowning research community considered it timely to undertake a scoping review of the literature to identify evidence relating to the initial resuscitation, hospital-based interventions and criteria for safe discharge related to drowning. METHODS: Medline, PreMedline, Embase, Cochrane Reviews and Cochrane CENTRAL were searched from 2000 to June 2020 to identify relevant literature. Titles and abstracts and if necessary full text were reviewed in duplicate. Studies were eligible for inclusion if they reported on the population (adults and children who are submerged in water), interventions (resuscitation in water/boats, airway management, oxygen administration, AED use, bystander CPR, ventilation strategies, ECMO, protocols for hospital discharge (I), comparator (standard care) and outcomes (O) survival, survival with a favourable neurological outcome, CPR quality, physiological end-points). RESULTS: The database search yielded 3242 references (Medline 1104, Pre-Medline 202, Embase 1722, Cochrane reviews 12, Cochrane CENTRAL 202). After removal of duplicates 2377 papers were left for screening titles and abstracts. In total 65 unique papers were included. The evidence identified was from predominantly high-income countries and lacked consistency in the populations, interventions and outcomes reported. Clinical studies were exclusively observational in nature. CONCLUSION: This scoping review found that there is very limited evidence from observational studies to inform evidence based clinical practice guidelines for drowning. The review highlights an urgent need for high quality research in drowning.
Assuntos
Reanimação Cardiopulmonar , Afogamento , Serviços Médicos de Emergência , Adulto , Criança , Humanos , RessuscitaçãoRESUMO
The L-cysteine derived N2S2 ligand precursor H2L and its nickel(ii) complex L2Ni2 were investigated with respect to their behaviour in contact with electrophilic and nucleophilic methylation reagents (H2L = (N,N'-dimethyl-(2R,5R)-bis-(sulfanylmethyl)-piperazine). Treatment of deprotonated L(2-) with MeI led to the selective methylation of the thiolate groups thus generating a novel potential ligand, Me2L, which is neutral and contains two thioether donors. The coordinating properties of Me2L were demonstrated by the synthesis of a first nickel(ii) complex: reaction with NiBr2 led to a mononuclear complex 2 where all donor atoms coordinate to the nickel ion, which completes its octahedral coordination sphere by the two bromide ligands. If, however, the complex [LNi]2 (1) is treated with MeI only one thiolate function per ligand moiety is methylated, while the other one remains a thiolate. This leads to [MeLNi](+) complex metal fragments, which trimerize including a µ3-bridging iodide ion to give the compound 3 that was tested with regards to ACS reactivity. While it behaved inert towards CO, attempts to replace the bridging iodide ligand by methyl units in reactions with nucleophilic methylation reagents led to a product, which could not be identified but reacted with CO. Work-up showed that this protocol had converted the thiolate function of MeL(-) into a thioester function, which corresponds to an ACS-like reactivity.
Assuntos
Coenzima A Ligases/metabolismo , Complexos de Coordenação/química , Cisteína/química , Níquel/química , Domínio Catalítico , Coenzima A Ligases/química , Complexos de Coordenação/síntese química , Metilação , Conformação Molecular , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
OBJECTIVE: Neurosurgery often requires skull immobilization with a Mayfield clamp, which often causes brief intense nociceptive stimulation, hypertension and tachycardia. Blunting this response may help prevent increased intracranial pressure, cerebral aneurysm or vascular malformation rupture, and/or myocardial stress. While various interventions have been described to blunt this response, no reports have compared administration of a propofol versus a remifentanil bolus. METHODS: We retrospectively analyzed the hemodynamic response to Mayfield placement in over 800 patients who received a prior propofol or remifentanil bolus from 2004 to 2010. RESULTS: Patients who received remifentanil experienced a 55% smaller increase in heart rate (p < 0.0001) and a 40% smaller increase in systolic blood pressure (p < 0.0001) after Mayfield placement than patients who received propofol. These data were retrospectively obtained from patients who were not randomized to receive remifentanil versus propofol, and hence these data could be subject to possible confounding. Nonetheless, these differences remained significant after multivariate analysis for possible confounding variables. CONCLUSIONS: Thus, a remifentanil bolus is more effective than a propofol bolus in blunting hemodynamic responses to Mayfield placement, and possibly for other short, intense nociceptive stimuli.
Assuntos
Anestésicos Intravenosos/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Procedimentos Neurocirúrgicos , Piperidinas/administração & dosagem , Restrição Física/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Aneurisma Intracraniano/prevenção & controle , Pressão Intracraniana/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Dor Nociceptiva/tratamento farmacológico , Piperidinas/efeitos adversos , Propofol/administração & dosagem , Remifentanil , Estudos Retrospectivos , CrânioRESUMO
Ischaemic/hypoxic insults to the brain during surgery and anaesthesia can result in long-term disability or death. Advances in resuscitation science encourage progress in clinical management of these problems. However, current practice remains largely founded on extrapolation from animal studies and limited clinical investigation. A major step was made with demonstration that rapid induction of mild sustained hypothermia in comatose survivors of out-of-hospital ventricular fibrillation cardiac arrest reduces death and neurological morbidity with negligible adverse events. This provides the first irrefutable evidence that outcome can be favourably altered in humans with widely applicable neuroprotection protocols. How far hypothermic protection can be extended to global ischaemia of other aetiologies remains to be determined. All available evidence suggests an adverse response to hyperthermia in ischaemic or post-ischaemic brain. Management of other physiological values can have dramatic effects in experimental injury models and this is largely supported by available clinical data. Hyperoxaemia may be beneficial in transient focal ischaemia but deleterious in global ischaemia. Hyperglycaemia causes exacerbation of most forms of cerebral ischaemia and this can be abated by restoration of normoglycaemia. Studies indicate little, if any, role for hyperventilation. There is little evidence in humans that pharmacological intervention is advantageous. Anaesthetics consistently and meaningfully improve outcome from experimental cerebral ischaemia, but only if present during the ischaemic insult. Emerging experimental data portend clinical breakthroughs in neuroprotection. In the interim, organized large-scale clinical trials could serve to better define limitations and efficacy of already available methods of intervention, aimed primarily at regulation of physiological homeostasis.
Assuntos
Hipóxia-Isquemia Encefálica/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Anestésicos/uso terapêutico , Glicemia/fisiologia , Dióxido de Carbono/sangue , Humanos , Hipotermia Induzida , Fármacos Neuroprotetores/uso terapêutico , Oxigênio/sangue , Pressão ParcialRESUMO
Apolipoprotein E (apoE) modifies glial activation and the CNS inflammatory response in an isoform-specific manner. Peptides derived from the receptor-binding region of apoE have been demonstrated to maintain the functional activity of the intact protein, and to improve histological and functional deficits after closed head injury. In the current study, APOE2, APOE3, and APOE4 targeted replacement (TR) mice expressing the human apoE protein isoforms (apoE2, apoE3 and apoE4) were used in a clinically relevant model of closed head injury to assess the interaction between the humanized apoE background and the therapeutic apoE mimetic peptide, apoE(133-149). Treatment with the apoE-mimetic peptide reduced microglial activation and early inflammatory events in all of the targeted replacement animals and was associated with histological and functional improvement in the APOE2TR and APOE3TR animals. Similarly, brain beta amyloid protein (Abeta)(1-42) levels were increased as a function of head injury in all of the targeted replacement mice, while treatment with apoE peptide suppressed Abeta(1-42) levels in the APOE2TR and APOE3TR animals. These results suggest a pharmacogenomic interaction between the therapeutic effects of the apoE mimetic peptide and the human apoE protein isoforms. Furthermore, they suggest that administration of apoE-mimetic peptides may serve as a novel therapeutic strategy for the treatment of acute and chronic neurological disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Apolipoproteínas E/metabolismo , Encefalite/tratamento farmacológico , Traumatismos Cranianos Fechados/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Animais , Apolipoproteína E2/metabolismo , Apolipoproteína E3/metabolismo , Apolipoproteínas E/química , Apolipoproteínas E/genética , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Encefalite/metabolismo , Encefalite/fisiopatologia , Gliose/tratamento farmacológico , Gliose/fisiopatologia , Gliose/prevenção & controle , Traumatismos Cranianos Fechados/metabolismo , Traumatismos Cranianos Fechados/fisiopatologia , Humanos , Camundongos , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/fisiologia , Fragmentos de Peptídeos/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/uso terapêutico , Placa Amiloide/efeitos dos fármacos , Placa Amiloide/metabolismo , Resultado do TratamentoRESUMO
Apolipoprotein E (apoE) is a 34-kD protein with multiple biological properties. Recent clinical and preclinical observations implicate a role for apoE in modifying the response of the brain to focal and global ischemia. One mechanism by which apoE might exert these effects is by reducing glutamate-induced excitotoxic neuronal injury associated with ischemic insults. We demonstrate that human recombinant apoE confers a mild neuroprotective effect in primary neuronal-glial cultures exposed to 100 microM N-methyl-D-aspartate. Furthermore, a peptide derived from the receptor-binding region of apoE (residues 133-149) maintained a significant helical population as assessed by circular dichroism, and completely suppressed the neuronal cell death and calcium influx associated with N-methyl-D-aspartate exposure. Neuroprotection was greatest when the peptide was added concurrently with N-methyl-D-aspartate; however, a significant protection was observed when peptide was preincubated and washed off prior to N-methyl-D-aspartate exposure. These results suggest that one mechanism by which apoE may modify the CNS response to ischemia is by partially blocking glutamate excitotoxicity. Moreover, small peptide fragments derived from the receptor-binding region of apoE have enhanced bioactivity compared with the intact holoprotein, and may represent a novel therapeutic strategy for the treatment of brain ischemia.
Assuntos
Apolipoproteínas E/farmacologia , Agonistas de Aminoácidos Excitatórios/toxicidade , N-Metilaspartato/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Sequência de Aminoácidos , Animais , Apolipoproteínas E/química , Apolipoproteínas E/genética , Isquemia Encefálica/tratamento farmacológico , Células Cultivadas , Técnicas de Cocultura , Mimetismo Molecular , Dados de Sequência Molecular , Neuroglia/citologia , Neurônios/citologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Neurocognitive dysfunction is a common complication of cardiac surgery using cardiopulmonary bypass (CPB). Elucidating injury mechanisms and developing neuroprotective strategies have been hampered by the lack of a suitable long-term recovery model of CPB. The purpose of this study was to investigate neurologic and neurocognitive outcome after CPB in a recovery model of CPB in the rat. METHODS: Fasted rats (n = 10) were subjected to 60 min of normothermic (37.5 degrees C) nonpulsatile CPB using a roller pump and a membrane oxygenator. Sham-operated controls (n = 10) were not subjected to CPB. Neurologic outcome was assessed on days 1, 3, and 12 after CPB using standardized functional testing. Neurocognitive outcome, defined as the time (or latency) to finding a submerged platform in a Morris water maze (an indicator of visual-spatial learning and memory), was evaluated daily from post-CPB days 3-12. Histologic injury in the hippocampus was also evaluated. RESULTS: Neurologic outcome was worse in the CPB versus the sham-operated controls at all three measurement intervals (P < 0.001). The CPB group also had longer water maze latencies compared with the sham-operated controls (P = 0.004), indicating significant neurocognitive dysfunction after CPB. No difference in histologic injury between groups was observed. CONCLUSIONS: CPB caused both neurologic and neurocognitive impairment in a rodent recovery model. This model could potentially facilitate the investigation of CPB-related injury mechanisms and possible neuroprotective interventions.
Assuntos
Ponte Cardiopulmonar/efeitos adversos , Transtornos Cognitivos/etiologia , Doenças do Sistema Nervoso/etiologia , Anestesia , Animais , Gasometria , Temperatura Corporal , Transtornos Cognitivos/patologia , Hemodinâmica , Masculino , Aprendizagem em Labirinto/fisiologia , Doenças do Sistema Nervoso/patologia , Oxigênio/sangue , Ratos , Ratos Sprague-Dawley , Análise de Sobrevida , Natação/fisiologiaRESUMO
Magnetic resonance imaging (MRI)-based volume measurements of brain structures are useful indicators of pending cognitive decline in humans suffering from neurodegenerative diseases. Transgenic mouse models that mimic the clinical conditions of these disorders have been developed. Noninvasive methods that can follow progression and regression of relevant pathology in these mice are therefore in great demand. In this study we tested whether high-resolution MRI (micro-MRI) in a mouse model of neurodegeneration (cerebral ischemia) could reliably track development of brain atrophy. We first established that diffusion imaging at a spatial resolution of 1.6 x 10(-3) mm(3) allowed superior visualization of forebrain, ventricles, and dorsal hippocampus in the mouse brain compared to either T2*- or T1-weighted MR imaging. Using this predetermined protocol we subsequently scanned C56BL/6J (C57) and ApoE-deficient (ApoE(-/-)) mice before and after ischemia. Four groups were studied: C57/sham (n = 9), ApoE(-/-)/sham (n = 9), C57/ischemia (n = 9), and ApoE(-/-)/ischemia (n = 11). All mice received a baseline 3D diffusion scan. One week later C57/ischemia and ApoE(-/-)/ischemia mice were exposed to 10 min of ischemia and scanned again on the 3rd and 30th postischemic day. The C57/sham and ApoE(-/-)/sham mice served as controls and were scanned at corresponding time points. Diffusion images of ApoE(-/-)/ischemia mice on the 3rd postischemic day revealed multiple localized high signal intensity areas. An increase in ventricle and a decrease in dorsal hippocampal volumes (which included the associated cortex laterally) at 30 days confirmed brain atrophy in C57 mice after ischemia. Excessive mortality of ApoE(-/-)/ischemia mice restricted statistical analysis, but ventricle enlargement postischemia was demonstrated. Our results show that volume changes in the brain of a 30-g mouse can be tracked by micro-MRI in a model of neurodegeneration. Clearly the ability to follow progression of pathology in mice will greatly aid our understanding of neurodegenerative diseases and facilitate the many possibilities to intervene pharmacologically.
Assuntos
Apolipoproteínas E/deficiência , Isquemia Encefálica/patologia , Encéfalo/patologia , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Microscopia , Doenças Neurodegenerativas/patologia , Animais , Atrofia , Mapeamento Encefálico , Ventrículos Cerebrais/patologia , Modelos Animais de Doenças , Hipocampo/patologia , Imageamento Tridimensional , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes Neurológicos , Prosencéfalo/patologiaRESUMO
STUDY OBJECTIVES: To compare patients' functional ability in the 24-hour postoperative period following a remifentanil compared to a hypnotic-fentanyl-treated anesthesia regimen using a 24-Hour Functional Ability Questionnaire. DESIGN: Prospective, 1:1 single-blind, randomized, controlled effectiveness study. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2438 patients (1496 outpatients and 942 inpatients) 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness of > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous remifentanil (0.5 microg/kg/min for induction and intubation; with the infusion rate decreased to 0.25 microg/kg/min after intubation) or fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given in the remifentanil patients and at the discretion of the anesthesiologists in the fentanyl patients. MEASUREMENTS: A validated set of measurements of functional ability, rather than more traditional clinical psychological methods, to compare the recovery of patients from remifentanil- and fentanyl-treated anesthetic regimens up to 24 hours after surgery. MAIN RESULTS: Remifentanil was statistically superior to fentanyl for the four functional assessments evaluated: walking without dizziness, thinking clearly, concentration, and communicating effectively. These differences reflect events occurring within the first 24 hours after anesthesia and surgery. CONCLUSIONS: A remifentanil-treated anesthetic demonstrated earlier return to some functions than a fentanyl-treated technique. Although functional assessment is a field that is still in its infancy, a questionnaire to assess functional ability during the 24 hours after anesthesia may provide more practical information about anesthetic recovery than previously used, traditional psychomotor evaluations.
Assuntos
Analgésicos Opioides/farmacologia , Anestesia , Fentanila/farmacologia , Piperidinas/farmacologia , Humanos , Período Pós-Operatório , Estudos Prospectivos , Remifentanil , Método Simples-Cego , Fatores de TempoRESUMO
STUDY OBJECTIVE: To compare the responses to, and hemodynamics associated with surgical stress, recovery profiles, and anesthesiologists' satisfaction following balanced general anesthesia using either remifentanil or fentanyl in a large-scale population. DESIGN: Prospective, 1:1 single blind, randomized, controlled effectiveness study in which patients received either remifentanil or fentanyl in combination with a hypnotic-based anesthesia regimen of either isoflurane or propofol. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2,438 patients (1,496 outpatients and 942 inpatients), 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous (IV) remifentanil (0.5 microg/kg/min for induction and intubation, with the infusion rate decreased to 0.25 microg/kg/min after intubation) or IV fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were either propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given to the remifentanil patients and, at the anesthesiologists' discretion, in the fentanyl patients. MEASUREMENTS: Vital signs, adverse events, and emergence profiles were assessed and recorded. Recovery profile was assessed by recording time spent in the postanesthesia care unit and step-down recovery unit, number and timing of adverse events, timing and dosage of rescue medications, and time to eligibility for discharge (to home or to hospital room). Anesthesiologists' satisfaction with the anesthetic regimen was assessed at the end of surgery. MAIN RESULTS: Remifentanil-treated patients exhibited lower systolic and diastolic blood pressures (by 10-15 mmHg) and lower heart rates (by 10-15 bpm) intraoperatively compared to the fentanyl-treated patients. This difference promptly disappeared on emergence. Remifentanil-treated patients responded to verbal command, left the operating room, and (for outpatients) were discharged home sooner than fentanyl-treated patients. Anesthesiologists rated the predictability of response to intraoperative titration, assessment of hemodynamic profiles, and the quality of anesthesia higher in the remifentanil-treated patients. CONCLUSIONS: This study confirms previous observations on the hemodynamic properties associated with remifentanil and extends these to a wider context than previously reported. These characteristics provide clinicians with an alternative in opioid-based anesthesia.
Assuntos
Analgésicos Opioides/farmacologia , Fentanila/farmacologia , Hemodinâmica/efeitos dos fármacos , Piperidinas/farmacologia , Adulto , Idoso , Anestesia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/epidemiologia , Estudos Prospectivos , Remifentanil , Método Simples-Cego , Fatores de TempoRESUMO
BACKGROUND: Volatile anesthetics are known to ameliorate experimental ischemic brain injury. A possible mechanism is inhibition of excitotoxic cascades induced by excessive glutamatergic stimulation. This study examined interactions between volatile anesthetics and excitotoxic stress. METHODS: Primary cortical neuronal-glial cultures were exposed to N-methyl-D-aspartate (NMDA) or glutamate and isoflurane (0.1-3.3 mM), sevoflurane (0.1-2.9 mM), halothane (0.1-2.9 mM), or 10 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate (MK-801). Lactate dehydrogenase release was measured 24 h later. In other cultures, effects of volatile anesthetics on Ca++ uptake and mitochondrial membrane potential were determined in the presence or absence of NMDA (0-200 microM). RESULTS: Volatile anesthetics reduced excitotoxin induced lactate dehydrogenase release by up to 52% in a dose-dependent manner. At higher concentrations, this protection was reversed. When corrected for olive oil solubility, the three anesthetics offered equivalent protection. MK-801 provided near-complete protection. Ca++ uptake was proportionally reduced with increasing concentrations of anesthetic but did not account for reversal of protection at higher anesthetic concentrations. Given equivalent NMDA-induced Ca++ loads, cells treated with volatile anesthetic had greater lactate dehydrogenase release than those left untreated. At protective concentrations, volatile anesthetics partially inhibited NMDA-induced mitochondrial membrane depolarization. At higher concentrations, volatile anesthetics alone were sufficient to induce mitochondrial depolarization. CONCLUSIONS: Volatile anesthetics offer similar protection against excitotoxicity, but this protection is substantially less than that provided by selective NMDA receptor antagonism. Peak effects of NMDA receptor antagonism were observed at volatile anesthetic concentrations substantially greater than those used clinically.
Assuntos
Anestésicos Inalatórios/farmacologia , N-Metilaspartato/antagonistas & inibidores , Neuroglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Cálcio/metabolismo , Células Cultivadas , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Ácido Glutâmico/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Neuroglia/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
Providing intraarticular analgesia with a continuous infusion of local anesthetic via a disposable infusion pump has gained popularity. Despite the prevalence of this technique, data comparing this method of analgesia to conventional regional anesthesia are not available. We present a prospective study that compared a single-dose interscalene block with a single-dose interscalene block plus continuous intraarticular infusion of local anesthetic. Forty patients scheduled for shoulder arthroscopy were entered in this prospective, double-blinded study. All patients received an interscalene brachial plexus block as their primary anesthetic. Patients were randomly assigned to 1 of 2 groups: 1. interscalene block with 1.5% mepivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.5% ropivacaine at 2 mL/h, or 2. interscalene block with 0.5% ropivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.9% saline (placebo) at 2 mL/h. Postoperative infusions were maintained for 48 h. Visual analog scale pain scores and postoperative oxycodone consumption were measured for 48 h. Visual analog scale scores at rest and with ambulation in the Mepivacaine/Intraarticular Ropivacaine group were reduced when compared with the Ropivacaine/Saline group (rest: P = 0.003, ambulation: P = 0.006). Oxycodone consumption was also decreased (28 +/- 21 mg vs 44 +/- 28 mg, P = 0.046), respectively. We conclude that a brachial plexus block with 1.5% mepivacaine and a continuous intraarticular infusion of 0.5% ropivacaine at 2 mL/h provides improved analgesia for minor surgery at 24 and 48 h versus a single-injection interscalene block with 0.5% ropivacaine.
Assuntos
Amidas , Anestésicos Locais , Plexo Braquial , Bloqueio Nervoso , Adulto , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Bombas de Infusão , Injeções Intra-Articulares , Masculino , Mepivacaína/uso terapêutico , Oxicodona/uso terapêutico , Medição da Dor , Estudos Prospectivos , RopivacainaRESUMO
Oxidative stress is known to play an important role in the response of brain to traumatic insults. We tested the hypothesis that increased extracellular superoxide dismutase (EC-SOD) expression can reduce injury in a mouse model of closed head injury. Neurologic, cognitive, and histologic outcomes were compared between transgenic mice exhibiting a fivefold increase in EC-SOD activity and wild-type littermate controls. Severe or moderate transcranial impact was induced in anesthetized and physiologically controlled animals. After severe impact, transgenic mice had better neurological outcome at 24 hr postinjury (p = 0.038). Brain water content was increased, but there was no difference between groups. Moderate impact resulted in predominantly mild neurologic deficits in both groups at both 24 hr and 14 days postinjury. Morris water maze performance, testing cognitive function at 14-17 days after trauma, was better in EC-SOD overexpressors (p = 0.018). No differences were observed between groups for histologic damage in hippocampal CA1 and CA3. We conclude that EC-SOD has a beneficial effect on behavioral outcome after both severe and moderate closed head injury in mice. Because EC-SOD is believed to be predominantly located in the extracellular space, these data implicate an adverse effect of extracellular superoxide anion on outcome from closed head injury.
Assuntos
Comportamento Animal/fisiologia , Traumatismos Cranianos Fechados/enzimologia , Traumatismos Cranianos Fechados/psicologia , Superóxido Dismutase/biossíntese , Animais , Western Blotting , Contagem de Células , Cognição/fisiologia , Espaço Extracelular/enzimologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Traumatismos Cranianos Fechados/patologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Transgênicos , Estresse Oxidativo/fisiologiaRESUMO
Reactive oxygen species contribute to ischemic brain injury. This study examined whether the porphyrin catalytic antioxidant manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) reduces oxidative stress and improves outcome from experimental cerebral ischemia. Rats that were subjected to 90 min focal ischemia and 7 d recovery were given MnTE-2-PyP(5+) (or vehicle) intracerebroventricularly 60 min before ischemia, or 5 or 90 min or 6 or 12 hr after reperfusion. Biomarkers of brain oxidative stress were measured at 4 hr after postischemic treatment (5 min or 6 hr). MnTE-2-PyP(5+), given 60 min before ischemia, improved neurologic scores and reduced total infarct size by 70%. MnTE-2-PyP(5+), given 5 or 90 min after reperfusion, reduced infarct size by 70-77% and had no effect on temperature. MnTE-2-PyP(5+) treatment 6 hr after ischemia reduced total infarct volume by 54% (vehicle, 131 +/- 60 mm(3); MnTE-2-PyP(5+), 300 ng, 60 +/- 68 mm(3)). Protection was observed in both cortex and caudoputamen, and neurologic scores were improved. No MnTE-2-PyP(5+) effect was observed if it was given 12 hr after ischemia. MnTE-2-PyP(5+) prevented mitochondrial aconitase inactivation and reduced 8-hydroxy-2'-deoxyguanosine formation when it was given 5 min or 6 hr after ischemia. In mice, MnTE-2-PyP(5+) reduced infarct size and improved neurologic scores when it was given intravenously 5 min after ischemia. There was no effect of 150 or 300 ng of MnTE-2-PyP(5+) pretreatment on selective neuronal necrosis resulting from 10 min forebrain ischemia and 5 d recovery in rats. Administration of a metalloporphyrin catalytic antioxidant had marked neuroprotective effects against focal ischemic insults when it was given up to 6 hr after ischemia. This was associated with decreased postischemic superoxide-mediated oxidative stress.
Assuntos
Antioxidantes/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Infarto Cerebral/prevenção & controle , Metaloporfirinas/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Aconitato Hidratase/metabolismo , Animais , Antioxidantes/química , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Encéfalo/patologia , Isquemia Encefálica/etiologia , Catálise , Infarto Cerebral/etiologia , DNA/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Fumarato Hidratase/metabolismo , Infarto da Artéria Cerebral Média/complicações , Injeções Intravenosas , Injeções Intraventriculares , Masculino , Metaloporfirinas/química , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/enzimologia , Necrose , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
BACKGROUND: Volatile anesthetics decrease ischemic brain injury. Mechanisms for this protection remain under investigation. The authors hypothesized that volatile anesthetics serve as antioxidants in a neuronal-glial cell culture system. METHODS: Primary cortical neuronal-glial cultures were prepared from fetal rat brain. Cultures were exposed to iron, H2O2, or xanthine-xanthine oxidase for 30 min in serum-free media containing dissolved isoflurane (0-3.2 mm), sevoflurane (0-3.6 mm), halothane (0-4.1 mm), n-hexanol, or known antioxidants. Cell damage was assessed by release of lactate dehydrogenase (LDH) and trypan blue exclusion 24 h later. Lipid peroxidation was measured by the production of thiobarbituric acid-reactive substances in a cell-free lipid system. Iron and calcium uptake and mitochondrial depolarization were measured after exposure to iron in the presence or absence of isoflurane. RESULTS: Deferoxamine reduced LDH release caused by H2O2 or xanthine-xanthine oxidase, but the volatile anesthetics had no effect. Iron-induced LDH release was prevented by the volatile anesthetics (maximum effect for halothane = 1.2 mm, isoflurane = 1.2 mm, and sevoflurane = 2.1 mm aqueous phase). When corrected for lipid solubility, the three volatile anesthetics were equipotent against iron-induced LDH release. In the cell-free system, there was no effect of the anesthetics on thiobarbituric acid-reactive substance formation in contrast to Trolox, which provided complete inhibition. Isoflurane (1.2 mm) reduced mean iron uptake by 46% and inhibited mitochondrial depolarization but had no effect on calcium uptake. CONCLUSIONS: Volatile anesthetics reduced cell death induced by oxidative stress only in the context of iron challenge. The likely reason for protection against iron toxicity is inhibition of iron uptake and therefore indirect reduction of subsequent intracellular oxidative stress caused by this challenge. These data argue against a primary antioxidant effect of volatile anesthetics.
Assuntos
Anestésicos Inalatórios/farmacologia , Antioxidantes/farmacologia , Neuroglia/efeitos dos fármacos , Animais , Cálcio/metabolismo , Células Cultivadas , Feminino , Peróxido de Hidrogênio/farmacologia , Ferro/metabolismo , Ferro/farmacologia , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/farmacologia , Neuroglia/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury.
Assuntos
Dano Encefálico Crônico/etiologia , Ponte Cardiopulmonar/efeitos adversos , Animais , Temperatura Corporal , Ponte Cardiopulmonar/instrumentação , Ecocardiografia Transesofagiana , Desenho de Equipamento , Masculino , Modelos Animais , Desempenho Psicomotor , Ratos , Ratos Sprague-DawleyRESUMO
Continuous interscalene brachial plexus blockade traditionally requires a hospital stay for local anesthetic infusion, and achieving consistent catheter insertion may be difficult. Incorporating long-acting pain relief from a continuous peripheral nerve block, with a reliable method of catheter insertion, and a self-contained infusion system would be a valuable asset for short-stay care. We compared the efficacy of single injection interscalene brachial plexus blockade to a continuous peripheral nerve block, with an insulated Tuohy system and a disposable infusion pump. Forty adult patients scheduled for open rotator cuff repair were entered in this randomized, double-blinded, placebo-controlled study. Patients received an interscalene brachial plexus blockade and a continuous peripheral nerve catheter as their primary anesthetic and then, were assigned to receive one of two different postoperative infusions: either 0.2% ropivacaine at 10 mL/h via a disposable infusion pump or normal saline at 10 mL/h via a disposable infusion pump (n = 18-20 per group). Visual analog pain scores and postoperative morphine consumption were measured for 24 h. The ropivacaine group showed less pain than the placebo group (P: = 0.0001) between 12 and 24 h after the initial injection of local anesthetic. In addition, initial interscalene blockade was successful in all patients and all redosed catheters were functional after 24 h with the continuous catheter insertion system. We conclude that it is possible to achieve a high rate of successful catheter placement and analgesia by using the continuous catheter insertion system and a disposable infusion pump in the ambulatory setting. This method of analgesia may offer improved pain relief after outpatient rotator cuff repair.
Assuntos
Plexo Braquial , Bloqueio Nervoso/instrumentação , Adolescente , Adulto , Amidas/sangue , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/sangue , Cateterismo/instrumentação , Cateterismo/métodos , Método Duplo-Cego , Feminino , Humanos , Bombas de Infusão , Masculino , Morfina/administração & dosagem , Morfina/uso terapêutico , Procedimentos Ortopédicos , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Ropivacaina , Ombro/cirurgiaRESUMO
BACKGROUND: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide. METHODS: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25 microgram. kg-1. h-1. 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion. RESULTS: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures. CONCLUSIONS: The results indicate that improved histologic-behavioral outcome provided by isoflurane anesthesia cannot be explained by differential vasodilative effects of the anesthetic states before, during, or after severe forebrain ischemia. This study also shows severe postischemic delayed hypoperfusion that was not affected by choice of anesthetic or the presence of trimethaphan. Mechanisms other than effects on periischemic CBF must be responsible for beneficial effects of isoflurane in this model.
Assuntos
Anestésicos Inalatórios/farmacologia , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Isoflurano/farmacologia , Prosencéfalo/irrigação sanguínea , Anestésicos Intravenosos/farmacologia , Animais , Bloqueio Nervoso Autônomo , Isquemia Encefálica/tratamento farmacológico , Circulação Cerebrovascular/fisiologia , Interações Medicamentosas , Fentanila/farmacologia , Bloqueadores Ganglionares/farmacologia , Masculino , Antagonistas Nicotínicos/farmacologia , Óxido Nitroso/farmacologia , Prosencéfalo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Trimetafano/farmacologiaRESUMO
UNLABELLED: This study prospectively determined whether there was a learning curve with the use of remifentanil, as indicated by decreased hemodynamic variability, improved recovery profile, and decreased incidence of opioid-related adverse events with increasing experience. Patients undergoing diverse surgical procedures (outpatient [n = 1340] and inpatient [n = 560]) were enrolled by investigators (n = 190) who had no previous experience with remifentanil use. Each investigator enrolled 10 patients. A standardized protocol for administration of remifentanil was used. Data were analyzed to determine differences between the first three patients and the last three patients enrolled for each anesthesiologist in the study. There were no differences in hemodynamic variables between the first triad and the last triad in either outpatients or inpatients. Requirements for hypnotic drugs and the doses of remifentanil used were also similar between groups. Analgesic medications administered at the end of surgery and in the postanesthesia care unit (PACU) were similar between groups, except that the last triad in the outpatient group received smaller doses of fentanyl compared with the first triad. Times to response to verbal command, tracheal extubation, and operating room discharge did not differ between groups. However, patients in the last triad undergoing outpatient surgery had shorter times to eligibility for PACU discharge, but times to eligibility for discharge home did not differ. The overall incidence of all adverse events (i.e., hypotension, hypertension, muscle rigidity, respiratory depression, apnea, nausea, and vomiting) was less in the last triad as compared with the first triad. When analyzed separately, only the incidence of vomiting (in the outpatient group) was decreased in the last triad as compared with the first triad. This study suggests that there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of PACU stay. IMPLICATIONS: This study demonstrated that anesthesiologists rapidly acquire the ability to use remifentanil with limited experience. However, there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of postanesthesia care unit stay.