ABSTRACT
Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory. Correspondingly, dopamine (DA) content shows the reverse characteristic change to MIF with a time-dependent curve in post-surgical behavior. The levels of both MIF and DA are reversed by the MIF tautomerase inhibitor ISO-1, and a negative relationship exists between MIF and DA. The reversed role of ISO-1 also affects tyrosine hydroxylase expression. Furthermore, CCI induces Th promoter CpG site methylation in the L-SC and VTA areas, and this effect could be abated by ISO-1 administration. G9a/SUV39H1 and H3K9me2/H3K9me3 enrichment within the Th promoter region following CCI in the L-SC and VTA was also decreased by ISO-1. In cultured dopaminergic neurons, rMIF enhanced the recruitment of G9a and SUV39H1, followed by an increase in H3K9me2/H3K9me3. These molecular changes correspondingly exhibited alterations in Th promoter CpG site methylation and pain behaviors. In summary, MIF functions as a braking factor in curbing dopaminergic descending inhibition in peripheral nerve injury-induced hypersensitivity by mediating Th gene methylation through G9a/SUV39H1-associated H3K9 methylation.
ABSTRACT
JUSTIFICATIVA E OBJETIVOS: A hipotensão materna associada à raquianestesia no parto cesáreo é a complicação mais frequente e problemática, com sérios riscos para a mãe e comprometimento do bem-estar neonatal. Nesse contexto, o volume efetivo de cristaloides por via intravenosa como uma estratégia de prevensão ainda não foi estimado. MÉTODOS: Oitenta e cinco parturientes com estado físico ASA I/II submetidas à cesariana seletiva foram selecionadas e 67 mulheres elegíveis foram designadas para receber uma pré-carga de cristaloides com 2 mL de bupivacaína hiperbárica a 0,5% (10 mg) mais 50 µg de morfina. O volume de cristaloides foi determinado por um método sequencial up-and-down. Os cristaloides foram infundidos a uma taxa de 100 a 150 mL.min-1 antes da anestesia espinal. O volume inicial de cristaloides foi de 5 mL.kg-1. Os dados do efeito do volume foram ajustados para o modelo sigmoidal de máxima eficácia e a mediana do volume efetivo (VE50) e seu intervalo de confiança (IC) de 95% foram calculados usando a estimativa de máxima verossimilhança e a regressão logística de Firth corrigida. RESULTADOS: Sessenta e sete parturientes completaram o estudo e foram analisadas. Vinte e oito pacientes (41,8%) desenvolveram hipotensão, com queda da pressão arterial sistólica (PAS) superior a 20% do valor basal. O VE50 de cristaloides foi de 12,6 mL.kg-1 (IC 95%, 11,6 a 14,8 mL.kg-1). Com a correção de Firth, a probabilidade conjunta do volume efetivo de cristaloides a 13 mL.kg-1 foi de 50,2% (IC 95%, 30,0% a 83,1%). CONCLUSÕES: O VE50 estimado da pré-carga de cristaloides necessário para prevenir a hipotensão induzida por anestesia espinhal em parto cesáreo é de 13 mL.kg-1 (valor aproximado). Porém, a profilaxia ou terapia com vasoconstritores também deve ser preparada e administrada no momento oportuno.
BACKGROUND AND OBJECTIVES: Spinal anesthesia-associated maternal hypotension in Cesarean delivery is the most frequent and troublesome complication, posing serious risks to mothers and compromising neonatal well-being. The effective volume of intravenous crystalloid as the preventive strategy in this context has not been estimated. METHODS: Eighty-five parturients with ASA physical status I/II undergoing elective Cesarean delivery were screened and 67 eligible women were assigned to receive pre-spinal crystalloid loading. Hyperbaric 0.5% bupivacaine 2 mL (10 mg) plus morphine 50 µg was given to all patients. The volume of crystalloid was determined by an up-and-down sequential method. The crystalloid was infused at a rate of 100-150 mL.min-1 prior to the spinal anesthetic injection. The initial volume of crystalloid was 5 mL.kg-1. Volume-effect data were fitted to a sigmoidal maximum efficacy model and the median effective volume (EV50) and corresponding 95% confidence interval (95% CI) were estimated using maximum likelihood estimation and logistic regression with Firth's correction. RESULTS: A total of 67 subjects completed the study and were analyzed. Twenty-eight (41.8%) patients developed hypotension with their systolic blood pressure (SBP) decreasing > 20% of baseline. The EV50 of crystalloid were 12.6 mL.kg-1 (95% CI, 11.6 to 14.8 mL.kg-1). With Firth's correction, the pooled probability of an effective preventive volume of crystalloid at 13 mL.kg-1 was 50.2% (95% CI, 30% to 83.1%). CONCLUSIONS: The estimated EV50 of the preloaded crystalloid required to prevent spinal anesthesia-induced hypotension in a Cesarean section is, approximately, 13 mL.kg-1. However, prophylactic or therapeutic vasoconstrictors should also be prepared and administered at an appropriate time.
JUSTIFICATIVA Y OBJETIVOS: La hipotensión materna asociada a la raquianestesia en el parto por cesárea es la complicación más común y problemática, acarreando serios riesgos para la madre y para el compromiso del bienestar neonatal. En ese contexto, el volumen efectivo de cristaloides por vía intravenosa como una estrategia de prevención todavía no ha sido estimado. MÉTODOS: Fueron elegidas ochenta y cinco parturientes con estado físico ASA I/II sometidas a la cesárea selectiva, y 67 mujeres elegibles fueron designadas para recibir una precarga de cristaloides con 2 mL de bupivacaína hiperbárica al 0,5% (10 mg) más 50 µg de morfina. El volumen de cristaloides quedó determinado por un método secuencial up-and-down. Los cristaloides fueron administrados a una tasa de 100 a 150 mL.min-1 antes de la anestesia espinal. El volumen inicial de cristaloides fue de 5 mL.kg-1. Los datos del efecto del volumen se ajustaron para el modelo sigmoidal de máxima eficacia y la mediana del volumen efectivo (VE50). El intervalo de confianza (IC) de 95% fue calculado usando la estimación de máxima verosimilitud y la regresión logística de Firth para la corrección. RESULTADOS: Sesenta y siete parturientes completaron el estudio y fueron analizadas. Veinte y ocho pacientes (41,8%) desarrollaron hipotensión, con una caída de presión arterial sistólica (PAS) superior al 20% del valor basal. El VE50 de cristaloides fue de 12,6 mL.kg-1 (IC 95%, 11,6 a 14,8 mL.kg-1). Con la corrección de Firth, la probabilidad conjunta del volumen efectivo de cristaloides a 13 mL.kg-1 fue de 50,2% (IC 95%, 30,0% a 83,1%). CONCLUSIONES: El VE50 estimado de la precarga de cristaloides necesario para prevenir la hipotensión inducida por anestesia espinal en el parto por cesárea es de 13 mL.kg-1 (valor aproximado). Sin embargo, la profilaxis o terapia con vasoconstrictores también debe ser preparada y administrada en el momento oportuno.
Subject(s)
Humans , Female , Pregnancy , Cesarean Section/instrumentation , Hypotension/complications , Anesthesia, Spinal/instrumentation , Bupivacaine/administration & dosage , Morphine/administration & dosageABSTRACT
Objective To investigate the effect of preemptive parecoxib on blood coagulation in patients undergoing abdominal hysterectomy. Methods This was a randomized, double-blind controlled study. Seventy ASA Ⅰ or Ⅱ patients aged 38-56 yr weighing 50-75 kg undergoing abdominal hysterectomy under combined spinal-epidural anesthesia were randomized to one of 2 groups (n=35 each): parecoxib group (group P) received intravenous parecoxib 40 mg/2 ml at 20 min before anesthesia and control group (group C) received normal saline 2 ml instead of parecoxib. Both groups received patient-controlled intravenous analgesia (PCIA) with butorphanol after surgery. The PCIA solution contained butorphanol 0.2 mg/kg and ondansetron 4 mg in normal saline 100 ml.The PCIA was set up with background infusion 2 ml/h, incremental dose 2 ml, and lockout interval 15 min. VAS score was used to assess the intensity of pain (O= no pain, 10 = worst pain). Venous blood samples were taken before and at 30 min and 2 h after parecoxib or normal saline administration for coagulation test and platelet count.The postoperative ambulation time and adverse response were recorded. Butorphanol consumption per hour during postoperative analgesia and total consumption of butorphanol within 24 h after operation were also recorded. Results Compared with those before parecoxib administration, prothrombin time and thrombin time in group C and thrombin time in group P were significantly prolonged and fibrinogen concentration was significantly lower in group C at 30 min after parecoxib administration (P＜ 0.05), but no significant difference was found in the other parameters of blood coagulation and platelet count at 30 min after parecoxib administration in group P ( P＞0.05).The fibrinogen concentration was significantly higher, the incidence of postoperative nausea and vomiting was significantly lower, the postoperative ambulation time was significantly shorter, and butorphanol consumption per hour during postoperative analgesia and total consumption of butorphanol within 24 h after operation were significantly lower in group P than in group C ( P＜0.05 ), but there was no significant difference in the other parameters of blood coagulation and platelet count between group P and group C ( P ＞ 0.05 ). Conclusion Preemptive parecoxib 40 mg can enhance blood coagulation in patients undergoing abdominal hysterectomy.