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Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects.

Sadhasivam S, Zhang X, Chidambaran V, Mavi J, Pilipenko V, Mersha TB, Meller J, Kaufman KM, Martin LJ, McAuliffe J - Pharmacogenomics J. (2015)

Bottom Line: Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid.This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy.Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

ABSTRACT
Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, RD, postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (postoperative anesthesia care unit, PACU) due to RD and PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy.

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Related in: MedlinePlus

The consort diagramillustrates the flow of study participants through this clinical trial. Eligible participants, reasons for exclusions, enrolled and analyzed patients are reported. IRB = institutional review board.
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Figure 1: The consort diagramillustrates the flow of study participants through this clinical trial. Eligible participants, reasons for exclusions, enrolled and analyzed patients are reported. IRB = institutional review board.

Mentions: Children were excluded if they or their parents were non-English speaking. Children allergic to study medications or who had developmental delay, liver or renal diseases, or preoperative pain requiring analgesics (e.g. chronic tonsillitis) were excluded. Due to limited availability of research coordinators for this study, we were not able to recruit all eligible subjects which resulted in convenience sampling (Figure 1).


Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects.

Sadhasivam S, Zhang X, Chidambaran V, Mavi J, Pilipenko V, Mersha TB, Meller J, Kaufman KM, Martin LJ, McAuliffe J - Pharmacogenomics J. (2015)

The consort diagramillustrates the flow of study participants through this clinical trial. Eligible participants, reasons for exclusions, enrolled and analyzed patients are reported. IRB = institutional review board.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492912&req=5

Figure 1: The consort diagramillustrates the flow of study participants through this clinical trial. Eligible participants, reasons for exclusions, enrolled and analyzed patients are reported. IRB = institutional review board.
Mentions: Children were excluded if they or their parents were non-English speaking. Children allergic to study medications or who had developmental delay, liver or renal diseases, or preoperative pain requiring analgesics (e.g. chronic tonsillitis) were excluded. Due to limited availability of research coordinators for this study, we were not able to recruit all eligible subjects which resulted in convenience sampling (Figure 1).

Bottom Line: Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid.This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy.Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

ABSTRACT
Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, RD, postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (postoperative anesthesia care unit, PACU) due to RD and PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy.

Show MeSH
Related in: MedlinePlus