Methadone is a difficult medicine to assess the efficacy at an initial stage because the blood concentration of it varies greatly among individuals and it takes days to reach a steady state and cannot be increased for 7 days. Nevertheless, there are few reports of blood concentration together with effects after administration of methadone about Japanese cancer patients. In this study, we investigated changes in blood concentration and pain score (NRS), and factors that affect blood concentration. Dose per body weight was only correlated with blood concentration of methadone. In the effective cases, NRS decreased chronologically until the 7th day after treatment initiation, and significantly decreased from the 1st day compared to before treatment initiation, but in the ineffective cases, it tended to decrease until the 3rd day, but there was no change thereafter. The blood concentration increased to 110 ng/ml on the 7th day in the effective cases, and in the ineffective cases, it reached the concentration on the 3rd day. Thus there was no correlation between the blood concentration and the drug efficacy. The individual blood concentrations tended to increase slightly or decrease after the 3rd day, but in only one case, it continued to increase. From the above-mentioned, it was shown that the effect could be judged at an early stage, however, since there was a case in which the blood concentration continued to rise until the 7th day, it was considered that the early dose increase within 7 days after initiation should be performed carefully.

BACKGROUND: The neurotoxicity of general anesthesia to the developing human brains is controversial. We assessed the associations between surgery under general anesthesia in infancy and development at age 1 year using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: In the JECS, 103,062 pregnancies and 104,065 fetuses were enrolled between January 2011 and March 2014. Of the 100,144 registered live births, we excluded preterm or post-term infants, multiple births, and infants with chromosomal anomalies and/or anomalies of the head or brain. Data on surgical procedures under general anesthesia in infancy were collected from self-administered questionnaires by parents at the 1-year follow-up. Developmental delay at age 1 year was assessed using the Japanese translation of the Ages and Stages Questionnaires, Third Edition (J-ASQ-3), comprising five developmental domains. RESULTS: Among the 64,141 infants included, 746 infants had surgery under general anesthesia once, 90 twice, and 71 three or more times. The percentage of developmental delay in the five domains of the J-ASQ-3 significantly increased with the number of surgical procedures. After adjusting for potential confounding factors, the risk of developmental delays in all five domains was significantly increased in infants who had surgery under general anesthesia three times or more (adjusted odds ratios: for communication domain 3.32; gross motor domain 4.69; fine motor domain 2.99; problem solving domain 2.47; personal-social domain 2.55). CONCLUSIONS: Surgery under general anesthesia in infancy was associated with an increased likelihood of developmental delay in all five domains of the J-ASQ-3, especially the gross motor domain at age 1 year. The neurodevelopment with the growth should be further evaluated among the children who had surgery under general anesthesia. TRIAL REGISTRATION UMIN Clinical Trials Registry (number: UMIN000030786 ).
Anesthesia, General ; adverse effects ; Anesthetics, General ; adverse effects ; Child Development ; drug effects ; Cohort Studies ; Female ; Humans ; Infant ; Infant, Newborn ; Japan ; Male