Pharmacogenetics-guided analgesics in major abdominal surgery

Further benefits within an enhanced recovery protocol

Anthony J. Senagore, Bradley J. Champagne, Eslam Dosokey, Justin Brady, Scott R. Steele, Harry L. Reynolds, Sharon L. Stein, Conor P. Delaney

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Objective Effective, narcotic sparing analgesia is a major component of Enhanced Recovery Protocols (ERP), however the risk of poor analgesia and opioid related side effects (ORADE) remains an issue related to poor outcomes and satisfaction, and is strongly related to the risk of narcotic dependence after surgery. A variety of genes can impact narcotic and non-steroidal (NSAID) drug efficacy including: the CYP family (drug metabolism-narcotics and NSAID), or COMT/ABCB1/OPRM1 (functional receptor and transport activity for analgesia vs side effects). The purpose of this study was to perform the first assessment of the impact of a pharmacogenetics (PGx) guided selection of analgesics following major abdominal surgery within an ERP. Methods A consecutive series of open and laparoscopic colorectal resections or major ventral hernia repair (PGx group) had a guided analgesic protocol based upon assessment of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, COMT, OPRM1, and ABCB1 genes. Study patients were compared to a recent historical series of patients (H group) managed using our well validated ERP. The primary outcome measure was the Overall Benefit of Analgesia Score (OBAS). Pain scores were also assessed. Results The data demonstrated a similar mix of procedures and gender between groups and more than half of the PGx group had revised analgesia from the standard ERP. The PGx group demonstrated significantly lower OBAS scores (p = 0.0.1) from POD1 (3.8 vs 5.4) through POD 5 (3.0 vs 4.5) Analgesia was also superior for the PGx group from POD1 through POD 5 (p = 0.04). Conclusion Pharmacogenetics guidance resulted in frequent modifications of the analgesic program, resulting in excellent analgesia with a 50% reduction in narcotic consumption, and a reduced incidence of analgesic related side effects compared to our standard ERP. These data suggest further improvement in ERP resulting from a patient centric analgesic, reduced narcotic regimen which provides early and durable pain control with fewer narcotic related side effects.

    Original languageEnglish (US)
    Pages (from-to)467-472
    Number of pages6
    JournalAmerican Journal of Surgery
    Volume213
    Issue number3
    DOIs
    StatePublished - Mar 1 2017

    Fingerprint

    Pharmacogenetics
    Analgesia
    Analgesics
    Narcotics
    Cytochrome P-450 CYP3A
    Non-Steroidal Anti-Inflammatory Agents
    Ventral Hernia
    Opioid-Related Disorders
    Pain
    Cytochrome P-450 CYP1A2
    Cytochrome P-450 CYP2D6
    Herniorrhaphy
    Pharmaceutical Preparations
    Opioid Analgesics
    Genes
    Outcome Assessment (Health Care)
    Incidence

    Keywords

    • CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, COMT, OPRM1, and ABCB1
    • Enhanced recovery
    • Overall Benefit of Analgesia Score (OBAS)
    • Pharmacogenetic testing

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Senagore, A. J., Champagne, B. J., Dosokey, E., Brady, J., Steele, S. R., Reynolds, H. L., ... Delaney, C. P. (2017). Pharmacogenetics-guided analgesics in major abdominal surgery: Further benefits within an enhanced recovery protocol. American Journal of Surgery, 213(3), 467-472. https://doi.org/10.1016/j.amjsurg.2016.11.008

    Pharmacogenetics-guided analgesics in major abdominal surgery : Further benefits within an enhanced recovery protocol. / Senagore, Anthony J.; Champagne, Bradley J.; Dosokey, Eslam; Brady, Justin; Steele, Scott R.; Reynolds, Harry L.; Stein, Sharon L.; Delaney, Conor P.

    In: American Journal of Surgery, Vol. 213, No. 3, 01.03.2017, p. 467-472.

    Research output: Contribution to journalArticle

    Senagore, AJ, Champagne, BJ, Dosokey, E, Brady, J, Steele, SR, Reynolds, HL, Stein, SL & Delaney, CP 2017, 'Pharmacogenetics-guided analgesics in major abdominal surgery: Further benefits within an enhanced recovery protocol', American Journal of Surgery, vol. 213, no. 3, pp. 467-472. https://doi.org/10.1016/j.amjsurg.2016.11.008
    Senagore, Anthony J. ; Champagne, Bradley J. ; Dosokey, Eslam ; Brady, Justin ; Steele, Scott R. ; Reynolds, Harry L. ; Stein, Sharon L. ; Delaney, Conor P. / Pharmacogenetics-guided analgesics in major abdominal surgery : Further benefits within an enhanced recovery protocol. In: American Journal of Surgery. 2017 ; Vol. 213, No. 3. pp. 467-472.
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    abstract = "Objective Effective, narcotic sparing analgesia is a major component of Enhanced Recovery Protocols (ERP), however the risk of poor analgesia and opioid related side effects (ORADE) remains an issue related to poor outcomes and satisfaction, and is strongly related to the risk of narcotic dependence after surgery. A variety of genes can impact narcotic and non-steroidal (NSAID) drug efficacy including: the CYP family (drug metabolism-narcotics and NSAID), or COMT/ABCB1/OPRM1 (functional receptor and transport activity for analgesia vs side effects). The purpose of this study was to perform the first assessment of the impact of a pharmacogenetics (PGx) guided selection of analgesics following major abdominal surgery within an ERP. Methods A consecutive series of open and laparoscopic colorectal resections or major ventral hernia repair (PGx group) had a guided analgesic protocol based upon assessment of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, COMT, OPRM1, and ABCB1 genes. Study patients were compared to a recent historical series of patients (H group) managed using our well validated ERP. The primary outcome measure was the Overall Benefit of Analgesia Score (OBAS). Pain scores were also assessed. Results The data demonstrated a similar mix of procedures and gender between groups and more than half of the PGx group had revised analgesia from the standard ERP. The PGx group demonstrated significantly lower OBAS scores (p = 0.0.1) from POD1 (3.8 vs 5.4) through POD 5 (3.0 vs 4.5) Analgesia was also superior for the PGx group from POD1 through POD 5 (p = 0.04). Conclusion Pharmacogenetics guidance resulted in frequent modifications of the analgesic program, resulting in excellent analgesia with a 50{\%} reduction in narcotic consumption, and a reduced incidence of analgesic related side effects compared to our standard ERP. These data suggest further improvement in ERP resulting from a patient centric analgesic, reduced narcotic regimen which provides early and durable pain control with fewer narcotic related side effects.",
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    T1 - Pharmacogenetics-guided analgesics in major abdominal surgery

    T2 - Further benefits within an enhanced recovery protocol

    AU - Senagore, Anthony J.

    AU - Champagne, Bradley J.

    AU - Dosokey, Eslam

    AU - Brady, Justin

    AU - Steele, Scott R.

    AU - Reynolds, Harry L.

    AU - Stein, Sharon L.

    AU - Delaney, Conor P.

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    N2 - Objective Effective, narcotic sparing analgesia is a major component of Enhanced Recovery Protocols (ERP), however the risk of poor analgesia and opioid related side effects (ORADE) remains an issue related to poor outcomes and satisfaction, and is strongly related to the risk of narcotic dependence after surgery. A variety of genes can impact narcotic and non-steroidal (NSAID) drug efficacy including: the CYP family (drug metabolism-narcotics and NSAID), or COMT/ABCB1/OPRM1 (functional receptor and transport activity for analgesia vs side effects). The purpose of this study was to perform the first assessment of the impact of a pharmacogenetics (PGx) guided selection of analgesics following major abdominal surgery within an ERP. Methods A consecutive series of open and laparoscopic colorectal resections or major ventral hernia repair (PGx group) had a guided analgesic protocol based upon assessment of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, COMT, OPRM1, and ABCB1 genes. Study patients were compared to a recent historical series of patients (H group) managed using our well validated ERP. The primary outcome measure was the Overall Benefit of Analgesia Score (OBAS). Pain scores were also assessed. Results The data demonstrated a similar mix of procedures and gender between groups and more than half of the PGx group had revised analgesia from the standard ERP. The PGx group demonstrated significantly lower OBAS scores (p = 0.0.1) from POD1 (3.8 vs 5.4) through POD 5 (3.0 vs 4.5) Analgesia was also superior for the PGx group from POD1 through POD 5 (p = 0.04). Conclusion Pharmacogenetics guidance resulted in frequent modifications of the analgesic program, resulting in excellent analgesia with a 50% reduction in narcotic consumption, and a reduced incidence of analgesic related side effects compared to our standard ERP. These data suggest further improvement in ERP resulting from a patient centric analgesic, reduced narcotic regimen which provides early and durable pain control with fewer narcotic related side effects.

    AB - Objective Effective, narcotic sparing analgesia is a major component of Enhanced Recovery Protocols (ERP), however the risk of poor analgesia and opioid related side effects (ORADE) remains an issue related to poor outcomes and satisfaction, and is strongly related to the risk of narcotic dependence after surgery. A variety of genes can impact narcotic and non-steroidal (NSAID) drug efficacy including: the CYP family (drug metabolism-narcotics and NSAID), or COMT/ABCB1/OPRM1 (functional receptor and transport activity for analgesia vs side effects). The purpose of this study was to perform the first assessment of the impact of a pharmacogenetics (PGx) guided selection of analgesics following major abdominal surgery within an ERP. Methods A consecutive series of open and laparoscopic colorectal resections or major ventral hernia repair (PGx group) had a guided analgesic protocol based upon assessment of CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, COMT, OPRM1, and ABCB1 genes. Study patients were compared to a recent historical series of patients (H group) managed using our well validated ERP. The primary outcome measure was the Overall Benefit of Analgesia Score (OBAS). Pain scores were also assessed. Results The data demonstrated a similar mix of procedures and gender between groups and more than half of the PGx group had revised analgesia from the standard ERP. The PGx group demonstrated significantly lower OBAS scores (p = 0.0.1) from POD1 (3.8 vs 5.4) through POD 5 (3.0 vs 4.5) Analgesia was also superior for the PGx group from POD1 through POD 5 (p = 0.04). Conclusion Pharmacogenetics guidance resulted in frequent modifications of the analgesic program, resulting in excellent analgesia with a 50% reduction in narcotic consumption, and a reduced incidence of analgesic related side effects compared to our standard ERP. These data suggest further improvement in ERP resulting from a patient centric analgesic, reduced narcotic regimen which provides early and durable pain control with fewer narcotic related side effects.

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    KW - Overall Benefit of Analgesia Score (OBAS)

    KW - Pharmacogenetic testing

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