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1.
World J Pediatr ; 19(2): 170-179, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36399311

RESUMO

BACKGROUND: Pediatric liver transplantation is an important modality for treating biliary atresia. The overall survival (OS) rate of pediatric liver transplantation has significantly improved compared with that of 20 years ago, but it is still unsatisfactory. The anesthesia strategy of maintaining low central venous pressure (CVP) has shown a positive effect on prognosis in adult liver transplantation. However, this relationship remains unclear in pediatric liver transplantation. Thus, this study was conducted to review the data of pediatric living-donor liver transplantation to analyze the associations of different CVP levels with the prognosis of recipients. METHODS: This was a retrospective study and the patients were divided into two groups according to CVP levels after abdominal closure: low CVP (LCVP) (≤ 10 cmH2O, n = 470) and high CVP (HCVP) (> 10 cmH2O, n = 242). The primary outcome measured in the study was the overall survival rate. The secondary outcomes included the duration of mechanical ventilation in the intensive care unit (ICU), length of stay in the ICU, and postoperative stay in the hospital. Patient demographic and perioperative data were collected and compared between the two groups. Kaplan-Meier curves were constructed to determine the associations of different CVP levels with the survival rate. RESULTS: In the study, 712 patients, including 470 in the LCVP group and 242 in the HCVP group, were enrolled. After propensity score matching, 212 pairs remained in the group. The LCVP group showed a higher overall survival rate than the HCVP group in the Kaplan-Meier curves and multivariate Cox regression analyses (P = 0.018), and the HCVP group had a hazard ratio of 2.445 (95% confidence interval, 1.163-5.140). CONCLUSION: This study confirmed that a low-CVP level at the end of surgery is associated with improved overall survival and a shorter length of hospital stay.


Assuntos
Transplante de Fígado , Adulto , Humanos , Criança , Pressão Venosa Central , Doadores Vivos , Estudos Retrospectivos , Prognóstico
2.
Paediatr Anaesth ; 31(6): 702-712, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33715251

RESUMO

BACKGROUND: In pediatric living-donor liver transplantation, lactated Ringer's solution and normal saline are commonly used for intraoperative fluid management, but the comparative clinical outcomes remain uncertain. AIMS: To compare the effect between lactated Ringer's solution and normal saline for intraoperative volume replacement on clinical outcomes among pediatric living-donor liver transplantation patients. METHODS: This single-center, retrospective trial study enrolled children who received either lactated Ringer's solution or normal saline during living-donor liver transplantation between January 2010 and August 2016. The groups with comparable clinical characteristics were balanced by propensity score matching. The primary outcome was 90-day all-cause mortality, and the secondary outcomes included early allograft dysfunction, primary nonfunction, acute renal injury, and hospital-free days (days alive postdischarge within 30 days of liver transplantation). RESULTS: We included 333 pediatric patients who met the entry criteria for analysis. Propensity score matching identified 61 patients in each group. After matching, the lactated Ringer's solution group had a higher 90-day mortality rate than the normal saline group (11.5% vs. 0.0%). Early allograft dysfunction and primary nonfunction incidences were also more frequent in the lactated Ringer's solution group (19.7% and 11.5%, respectively) than in the normal saline group (3.3% and 0.0%, respectively). In the lactated Ringer's solution group, four (6.6%) recipients developed acute renal injury within 7 days postoperatively compared with three (4.9%) recipients in the normal saline group. Hospital-free days did not differ between groups (9 days [1-13] vs. 9 days [0-12]). CONCLUSIONS: For intraoperative fluid management in pediatric living-donor liver transplantation patients, lactated Ringer's solution administration was associated with a higher 90-day mortality rate than normal saline. This finding has important implications for selecting crystalloid in pediatric living-donor liver transplantation. Further randomized clinical trials in larger cohort are necessary to confirm this finding.


Assuntos
Transplante de Fígado , Solução Salina , Assistência ao Convalescente , Criança , Humanos , Soluções Isotônicas , Doadores Vivos , Alta do Paciente , Estudos Retrospectivos , Lactato de Ringer
4.
World J Gastroenterol ; 26(12): 1352-1364, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32256022

RESUMO

BACKGROUND: Pediatric living donor liver transplantation (LDLT) has become the gold standard for patients with end-stage liver disease. With improvements in organ preservation, immunosuppression, surgical and anesthesia techniques, the survival rates and long-term outcomes of patients after LDLT have significantly improved worldwide. However, data on anesthetic management and postoperative survival rate of pediatric LDLT in China are rare. AIM: To review the status of pediatric LDLT in Shanghai and investigate the factors related to anesthetic management and survival rate in pediatric LDLT. METHODS: We conducted a retrospective observational study to investigate the status of pediatric LDLT in Shanghai by reviewing 544 records of patients who underwent pediatric LDLT since the first operation on October 21, 2006 until August 10, 2016 at Renji Hospital and Huashan Hospital. RESULTS: The 30-d, 90-d, 1-year, and 2-year survival rates were 95.22%, 93.38%, 91.36%, and 89.34%, respectively. The 2-year patient survival rate after January 1, 2011 significantly improved compared with the previous period (74.47% vs 90.74%; hazard ratio: 2.92; 95% confidence interval (CI): 2.16-14.14; P = 0.0004). Median duration of mechanical ventilation in the intensive care unit (ICU) was 18 h [interquartile range (IQR), 15.25-20.25], median ICU length of stay was 6 d (IQR: 4.80-9.00), and median postoperative length of stay was 24 d (IQR: 18.00-34.00). Forty-seven (8.60%) of 544 patients did not receive red blood cell transfusion during the operation. CONCLUSION: Pediatric end-stage liver disease (PELD) score, anesthesia duration, operation duration, intraoperative blood loss, and ICU length of stay were independent predictive factors of in-hospital patient survival. Pediatric end-stage liver disease score, operation duration, and ICU length of stay were independent predictive factors of 1-year and 3-year patient survival.


Assuntos
Anestesia/mortalidade , Doença Hepática Terminal/cirurgia , Transplante de Fígado/mortalidade , Anestesia/métodos , Perda Sanguínea Cirúrgica , China , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Lactente , Tempo de Internação , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Duração da Cirurgia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
5.
Acta Neuropathol Commun ; 7(1): 217, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870460

RESUMO

Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adeno-associated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Dor Pós-Operatória/metabolismo , Privação do Sono/metabolismo , Animais , Canais de Cálcio Tipo L/genética , Técnicas de Silenciamento de Genes , Masculino , Neurônios/metabolismo , Neurônios/fisiologia , Ratos Sprague-Dawley
6.
CNS Neurosci Ther ; 18(9): 762-6, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22943142

RESUMO

INTRODUCTION: The delta opioid peptide [D-Ala2, D-Leu5]enkephalin (DADLE) plays a key role in neuronal protection against both hypoxic and ischemic conditions. However, the cellular mechanisms of action of DADLE under these conditions remain unclear. METHODS: Ischemia was simulated with perfusing the brain slices with glucose-free artificial cerebrospinal fluid. Apoptosis was examined using an in situ cell death detection kit and expressed as the percentage of positively labeled neurons relative to total number of neurons. PCR was performed by adding cDNA, 5 pm dNTP, 1 µL Taqase, and primers. PCR products were separated with electrophoresis, stained with ethidium bromide, and visualized under ultraviolet light. AIMS: To investigate the potential effects of DADLE in an ex vivo model of cerebral ischemia/reperfusion. RESULTS: DADLE attenuated lactic dehydrogenase release and neuronal apoptosis in a concentration-dependent manner. The protective effects of DADLE were attenuated by representative selective delta2, but not delta1 opioid antagonists. Treatment with PD98059, a selective inhibitor of ERK kinase (MEK), also blocked the protective effect of DADLE as well as ERK phosphorylation induced by DADLE. CONCLUSIONS: Endogenous opioid peptides could promote cell survival via delta2 opioid receptors, possibly through the downstream MEK-ERK pathway.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Córtex Cerebral/efeitos dos fármacos , Leucina Encefalina-2-Alanina/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Opioides delta/efeitos dos fármacos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
7.
Neurosci Lett ; 431(2): 129-34, 2008 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-18191894

RESUMO

Increasing evidences approve the long-term analgesia effects of intrathecal lidocaine in patients with chronic pain and in animal peripheral nerve injury models, but the underlying mechanism remains elusive. Previous evidences suggest that the activation of the p38 MAPK signaling pathway in hyperactive microglia in the dorsal horn of spinal cord involves in nerve injury-induced neuropathic pain. In this study, we demonstrate that attenuating phosphorylation of p38 MAPK in the activated microglia of spinal cord, at least partly, is the mechanism of intrathecal lidocaine reversing established tactile allodynia in chronic constriction injury model of rats. This finding not only provides a new insight into the mechanisms underlying long-term therapeutic effects of lidocaine on neuropathic pain, but also reveals one more specific drug target for analgesia.


Assuntos
Anestésicos Locais/uso terapêutico , Hiperestesia , Lidocaína/uso terapêutico , Microglia/enzimologia , Doenças do Sistema Nervoso Periférico/complicações , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Constrição Patológica/complicações , Modelos Animais de Doenças , Hiperestesia/tratamento farmacológico , Hiperestesia/etiologia , Hiperestesia/patologia , Injeções Espinhais/métodos , Masculino , Microglia/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Medição da Dor/métodos , Doenças do Sistema Nervoso Periférico/etiologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologia , Fatores de Tempo
8.
Neurosci Lett ; 423(2): 113-7, 2007 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-17689189

RESUMO

Cerebral ischemic insult, mainly induced by cardiovascular disease, is one of the most severe neurological diseases in clinical. There's mounting evidence showing that delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has a tissue-protective effect. However, whether this property is effective to prevent neuronal death induced by forebrain ischemia is not clear. This study was aimed to investigate whether intracerebroventricular (ICV) administration of DADLE has a neuroprotective effect against forebrain ischemia in rats. We found in our study that administration of DADLE 45 min before forebrain ischemia had significant protective effect against CA1 neuronal lose. Further more, we found that DADLE had a dose-dependent protection for improving behavioral retardation revealed by Morris water maze and motor score test, while naltrindole, the antagonist of delta opioid receptor, partially abolished neuroprotective effect of DADLE, which implicated that both opioid and non-opioid systems are involved in ischemic insults and neuroprotection.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Leucina Encefalina-2-Alanina/administração & dosagem , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Animais , Comportamento Animal , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Masculino , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Neurônios/patologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/patologia , Ratos , Ratos Sprague-Dawley
9.
Anesthesiology ; 105(6): 1211-9, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17122584

RESUMO

BACKGROUND: The volatile anesthetic isoflurane induces hypoxia inducible factor (HIF)-1-responsive genes heme oxygenase 1, inducible nitric oxide synthase, and vascular endothelial growth factor (VEGF) expression. Little is known about the extent to which induction of HIF-1alpha is affected by isoflurane. METHODS: Hep3B cells were exposed to isoflurane at various concentrations (0.5-4%) or for different time periods (2-8 h) at 37 degrees C. HIF-1alpha gene expression and transcriptional activity, heme oxygenase 1, inducible nitric oxide synthase, and VEGF gene expression were quantified. RESULTS: Isoflurane induced a time- and concentration-dependent increase in HIF-1alpha protein but not for HIF-1alpha messenger RNA (mRNA) in Hep3B cells. The maximal increase was induced by 2% isoflurane, and the cells incubated with 2% isoflurane for 4-8 h expressed the highest protein. Similarly, HIF-1alpha transcriptional activity was higher in Hep3B cells exposed to 2% isoflurane for 16 h than that in control cells. The combination of 2% isoflurane and desferrioxamine, a hypoxia mimetic, caused a higher level of HIF-1alpha protein than that induced by 2% isoflurane alone. Reoxygenation and inhibitor of proteasome pathway MG132 did not affect the isoflurane-induced HIF-1alpha protein accumulation. Cycloheximide, an inhibitor for protein synthesis, completely abrogated the induction of HIF-1alpha protein by isoflurane. Isoflurane stimulated heme oxygenase 1, inducible nitric oxide synthase, and VEGF mRNA expression in a concentration-dependent manner, and inactivation of HIF-1alpha attenuated the induction of VEGF mRNA by isoflurane. CONCLUSION: Isoflurane can up-regulate HIF-1alpha and enhance HIF-1-responsive genes heme oxygenase 1, inducible nitric oxide synthase, and VEGF mRNA expression in Hep3B cells. The induction of HIF-1alpha by isoflurane does not involve protein degradation but depends on translation pathway.


Assuntos
Anestésicos Inalatórios/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Isoflurano/farmacologia , Actinas/biossíntese , Animais , Western Blotting , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Humanos , Óxido Nítrico Sintase Tipo II/biossíntese , RNA Interferente Pequeno/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/biossíntese
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