Identification of the genetic polymorphisms that could be correlated either with a better clinical response or with a major predisposition of patients to develop tolerance and/or side effects to the treatment with morphine.
Name: morphine chlorhydrate
Description: The drug will be administrated by a bolus 45 minutes before the end of the surgery, with the following modalities: bolus with morphine chlorhydrate 0.15 mg/kg ± 20%. Also acetaminophene 1g and ketoprofen 160 mg (ketorolac 30mg) will be administrated during the operation. At the exit of the operative compartment patients will have an electronic pump (PCA) for 48h with morphine chlorhydrate to be used in boluses by 1 mg with a lock out of 5 mins, max dose 20 mg in 4 hours. Moreover, ketoprofen will be prescribed 160 mg x 2 per day (ketorolac 30mg x 2) (in case of allergy acetaminophene 1g x 3 daily). Postoperative analgesic treatment is lasting 48h for each patient (between starting of the PCA infusion (T0) and the following 48h).Type: DrugGroup A Group B
Description: Valutation of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).
Measure: Assessment of the medium morphine dose (mg/kg/die)in the two groups homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene; group B: both homozygous and heterozygous patients for the less frequent allele Time: first 24 h after surgeryDescription: Frequency of the variants at the loci OPRM1, COMT, UGTs, ESR1, both in patients with NRS ≤4 and in those having NRS >4 at least once during 24 hours.
Measure: Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure Time: during 24 h postsurgeryDescription: Detection of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 though the first 48 hours after surgery.
Measure: Detection of the medium morphine dose Time: First 24 h after surgeryDescription: Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G).
Measure: Pharmacokinetics of morphine with PCA after surgery Time: 48 h after surgeryDescription: Variants frequency at loci OPRM1, COMT, UGTs, ESR1 in the patients with Cmax and AUC of both morphine and M3G-M6G metabolites >2 standard deviations higher than expected population curve ("outliers").
Measure: Variants frequency at loci OPRM1, COMT, UGTs, ESR1 Time: Within 48h after surgeryCohort
There is one SNP
Assessment of the medium morphine dose (mg/kg/die)in the two groups homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene; group B: both homozygous and heterozygous patients for the less frequent allele. --- A118G ---
Valutation of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%).. Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure. --- A118G ---
- Allergies to morphine and derivates Anesthesia Surgery Valuation of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 in the first 24 hours post-surgery in the two groups of patients, A e B. Group A: homozygous patients for the more frequent allele of the polymorphism A118G of OPRM1 gene (about 80%); group B: both homozygous and heterozygous patients for the less frequent allele (about 20%). --- A118G ---