Multilevel lumbar spinal fusion and decompression surgeries (LSS) are common and
extremely painful inpatient procedures associated with severe post-surgical pain, high
incidence of CPSP, persistent and excessive opioid use, unsafe opioid prescribing and
development of opioid use disorder (OUD), along with costly immediate postoperative
opioid adverse events (AEs) and long hospital stays. Opioids are still widely used to
manage acute surgical pain and remain a core component of multi-modal analgesic and
enhanced recovery after surgery protocols (ERAS) for painful surgeries. About half of LSS
patients suffer from uncontrolled severe surgical pain and significant adverse opioid
effects due to opioids' narrow therapeutic indices and unpredictable inter-individual
variations in pain perception and opioid responses. Risks associated with perioperative
opioid use include immediate risks (life-threatening respiratory depression (RD),
excessive sedation, postoperative nausea and vomiting (PONV), urinary retention,
constipation, ileus and itching) that frequently delay recovery, require additional
treatment or monitoring, increase cost of care, and prolong hospital stay. Long-term
risks include opioid dependence, opioid-use disorder (OUD), and the consequent personal,
financial and societal fall-out from opioid addiction.
While in the hospital, LSS patients report suboptimal surgical pain (and AEs) with
short-acting opioids such as morphine, hydromorphone, and fentanyl. Post-discharge,
despite receiving additional potent prescribed opioids such as oxycodone for >1-2 weeks
at home, 20-50% of patients develop CPSP, largely due to suboptimal immediate surgical
pain relief (the single greatest risk factor for CPSP). Patients who develop CPSP have
high life-long risks for opioid use and misuse, contributing to the ongoing opioid
epidemic and lost productive life. Poor surgical pain relief and opioid- AEs therefore
result in negative consequences for patients, families, providers, and society, and
constitute significant socio-economic burden. Thus, there is an urgent and unmet clinical
need for a reliable and proactive tool to reduce opioid use and opioid-related AEs,
enhance pain relief and prevent CPSP following painful surgeries.
CPSP is common following LSS: Effective and aggressive acute surgical pain management is
critical to lower risks of developing CPSP. In a large prospective study assessing pain
outcomes from 21 hospitals in 11 European countries (PAIN OUT cohort)120, 11.8% of
patients reported moderate to severe CPSP at 12 months. The three risk factors for CPSP
at 12 months, chronic preoperative pain, type of surgery and percentage of time in severe
acute surgical pain, are very common in LSS patients. Importantly, orthopedic surgery is
associated with 3-fold higher risk for CPSP compared with all other procedures. A 10%
increase in the percentage of time in severe pain on the first postoperative day was
associated with a 30% increase in the incidence of CPSP at 12 months (N=889). LSS is
often associated with severe acute post-surgical pain, a high incidence of CPSP,
excessive and persistent opioid use increasing cost of care significantly with high
worker compensation costs with lost productivity. Thus, there is a clear need for more
effective and safer pain management following LSS to prevent CPSP, risks of lost
productivity, excessive opioid use, misuse, dependence and OUD.
High inter-individual variations in response to opioids can be explained by genetics and
clinical risk factors, yet translational barriers prevent widespread adoption of
genotype-guided care: Our many studies on genetic predictors of postoperative pain and
opioid-related AEs, and published literature from other researchers demonstrate that
genetic and clinical factors are associated with inter-individual variations in pain
control and adverse outcomes with different opioids. Through genotype-based opioid
selection, precision dosing and outpatient tailored opioid prescribing improve outcomes,
there are many translational barriers. An important example is the use of CYP2D6
phenotyping to guide dosing or use of codeine, tramadol, hydrocodone, and oxycodone for
improved safety and efficacy.
OpalGenix intends to revolutionize perioperative opioid and pain management with
proactive and personalized risk prediction algorithms with >70% accuracy in predicting
opioid AEs for precision pain and opioid management. GPS-Opioid will be a 510(k) cleared
medical device that will enable preoperative genotyping of important and patented
polygenetic markers shown to impact clinically and economically meaningful perioperative
opioid and pain outcomes. The polygenetic markers predict opioid AEs better than
single-gene associations: each gene, including CYP2D6, explains only 5-10% of clinical
response variations while polygenetic models have >70% predictive accuracy as they
combine important pharmacodynamics genes with well-known but less important genes
involved in opioid metabolism such as CYP2D6. In addition, polygenetic models account for
the synergistic effects of multiple risk alleles. Uniquely, GPS-Opioid also includes
patented clinical risk factors with polygenetic signatures using a proprietary algorithm
to identify patients at risk for experiencing uncontrolled severe pain, opioid-related
AEs including RD and PONV, prolonged hospital stay, CPSP, opioid dependence and potential
for developing OUD. Integration of GPS-Opioid in EHR, at the point-of-care, will enable
perioperative clinicians with critical information they need to develop a personalized
ERAS pain management plan prior to surgery to proactively minimize/eliminate costly
opioid related adverse events, enhance surgical pain relief and avoid CPSP
