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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.
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%).
In order to avoid the bias related to alterations in metabolism, patients with Cmax and AUC of morphine (and metabolites M6G and M3G) >2 standard deviation higher than expected population curve ("outliers") will be excluded for the primary purpose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Homozygous patients,using PCA administration with morphine chlorhydrate for postoperative analgesia, for the more frequent allele of the polymorphism A118G of OPRM1 gene |
| |
| Group B | Both homozygous and heterozygous patients,using PCA administration with morphine chlorhydrate for postoperative analgesia, for the less frequent allele of the polymorphism A118G of OPRM1 gene |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| morphine chlorhydrate | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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%). | first 24 h after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Variants at the loci OPRM1, COMT, UGTs, ESR1,towards median pain measure | 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. | during 24 h postsurgery |
| Detection of the medium morphine dose |
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Inclusion criteria:
Exclusion criteria:
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Pazients scheduled for major abdominal or urological surgery with postoperative pain control by PCA morphine administration
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| Name | Affiliation | Role |
|---|---|---|
| Massimo Allegri, MD | IRCCS Policlinico San Matteo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Azienda Ospedaliera San Gerardo | Monza | 20052 | Italy | |||
| Fondazione IRCCS Policlinico San Matteo |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28829523 | Derived | Cattaneo S, Ingelmo P, Scudeller L, Gregori M, Bugada D, Baciarello M, Marchesini M, Alberio G, Normanno M, Jotti GS, Meschi T, Fanelli G, Massimo A. Sex differences in the daily rhythmicity of morphine consumption after major abdominal surgery. J Opioid Manag. 2017 Mar/Apr;13(2):85-94. doi: 10.5055/jom.2017.0372. | |
| 26902643 | Derived |
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genes OPRM1, COMT, UGTs, ESR1
|
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Detection of the medium morphine dose (mg/kg/die) necessary to maintain NRS<4 though the first 48 hours after surgery. |
| First 24 h after surgery |
| Pharmacokinetics of morphine with PCA after surgery | Pharmacokinetic study of both morphine and its principal active and/or toxic metabolites (M3G and M6G). | 48 h after surgery |
| Variants frequency at loci OPRM1, COMT, UGTs, ESR1 | 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"). | Within 48h after surgery |
| Detection of the possible side effects. | 72 h postopratively |
| Detection of the association between M3G/M6G ratio and polymorphisms of UGTs (and possible side effects). | within 72 h postoperatively |
| Pavia |
| 27100 |
| Italy |
| De Gregori M, Diatchenko L, Ingelmo PM, Napolioni V, Klepstad P, Belfer I, Molinaro V, Garbin G, Ranzani GN, Alberio G, Normanno M, Lovisari F, Somaini M, Govoni S, Mura E, Bugada D, Niebel T, Zorzetto M, De Gregori S, Molinaro M, Fanelli G, Allegri M. Human Genetic Variability Contributes to Postoperative Morphine Consumption. J Pain. 2016 May;17(5):628-36. doi: 10.1016/j.jpain.2016.02.003. Epub 2016 Feb 21. |