Aims. The purpose of this study was to use pharmacogenetics to determine the frequency of genetic variants in our total knee arthroplasty (TKA) patients that could affect postoperative pain medications. Pharmacogenetic testing evaluates patient DNA to determine if a drug is expected to have a normal clinical effect, heightened effect, or no effect at all on the patient. It also predicts whether patients are likely to experience side effects from medicine. We further sought to determine if changing the multimodal programme based on these results would improve pain control or reduce side effects. Methods. In this pilot study, buccal samples were collected from 31 primary TKA patients. Pharmacogenetics testing examined genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of non-steroidal anti-inflammatory drugs and opioids. We examined the frequency of genetic variants to any of the medications we prescribed including celecoxib, hydrocodone, and tramadol. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen, and the study group received a customized regimen based on the pharmacogenetic results. For the first ten postoperative days, patients recorded pain scores, medication, and side effects. Results. Genetic variants involving one or more medications in the multimodal pain protocol occurred in 13 of the 31 patients (42%). In total, eight patients (26%) had variants affecting more than one of the medications. For the 25 patients who recorded pain and medication logs, the mean pain levels and morphine equivalents (MEQs) consumed in the first ten days were higher in the control group than in the custom-guided group (p = 0.019 for pain and p = 0.655 for MEQ). Conclusion. Overall, 42% of patients had a variant involving one of the pain medications prescribed in our perioperative pain program for TKA. Ongoing research will help determine if using these data to modify a patient’s medication will improve outcomes. Cite this article: Bone Joint J 2020;102-B(6 Supple A):73–78

Introduction. Pharmacogenetics evaluates a patient's DNA to determine if a particular drug is expected to have a normal clinical effect, heightened effect, or no effect at all on a patient. It may also predict which patients are most likely to experience side effects from the medications. The purpose of this study was to use pharmacogenetic testing to determine how frequently total knee arthroplasty (TKA) patients have genetic variants to standard postoperative pain medications. We further sought to determine if changing the multimodal program based on these results would improve pain control and reduce side effects. Methods. In this prospective, randomized study, buccal cheek swab samples were collected from 31 primary TKA patients. Pharmacogenetics testing was performed on the samples to examine genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of NSAIDs and opioids. We examined the frequency of a genetic variant to one of the multimodal medications we prescribe including celecoxib, hydrocodone, and tramadol. Subjects included 9 men and 22 women. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen; the study group received a customized regimen based on the pharmacogenetic results. For the first 10 postoperative days patients recorded pain scores, amount of pain medication taken, and any side effects experienced. Results. Genetic variations to one or more medications in our standard postoperative pain management protocol occurred in 13 of the 31 patients (42%). 8 patients (26%) had a variation of gene CYP2C9 affecting celecoxib. 11 patients (35%) had a variation of gene OPRM1 and/or CYP2D6 affecting the response to hydrocodone. 4 patients (13%) had a variation of gene CYP2D6 that altered their response to tramadol. Of the 31 patients tested, only 18 (58%) had no genetic variants related to the pain medications we routinely prescribe. 8 patients (26%) had variants affecting more than one of the medications. (Table 1, below) Both the average pain levels and morphine equivalents consumed in the first 10 days were higher in the control group than in the study group. Conclusion. 42% of patients in this study demonstrated a pharmacogenetic variant to one of the commonly used multimodal pain medications. Our early data suggests that customizing pain regimens based on this information can help reduce pain and the amount of pain medication used postoperatively. For figures, tables, or references, please contact authors directly

Malignant hyperthermia (MH) is a pharmacogenetic disorder, potentially lethal, due to the exposure to anesthetic drugs that triggers, a high increase of corporal temperature, progressive muscular stiffness, severe rabdomiolisis and death due to cardiac dysfunction. Many research works relate Malignant Hyperthermia to muscular illnesses or to the King Syndrome. Through this study we present the incidence of MH in patients with congenital vertebrae malformations. (CVM). The objective is to establish the incidence of the MH in patients who were operated on CVM and to alert about this association. 1029 patients with CVM were treated between 1972 and 2000. 390 with congenital vertebrae malformation were operated on. 3 patients (0.76%) (1 girl and 2 boys) developed MH while they underwent surgical treatment for the CVM. 1 patient presented an isolated congenital vertebrae malformation. 1 patient presented King Syndrome and the other presented Robert Syndrome. Only 1 elevated amount of preoperative CPK was found (the are no reports on the others). No muscular biopsy was done to test sensitivity. Two of them were biopsied for a post episode study. At the surgical moment, any patients reported personal or familiar antecedents of MH. No deaths were reported, although it is considered as a potentially lethal disorder. We found no reports in the literature in this subject. Most of the bibliographic data belonged to anesthesiologists or geneticists. Our approach as spine surgeons leaded us to the detailed analysis of this studies and the 0.76% (3 out of 390) incidence suggested us to have an alert attitude when facing patients with surgical MVC and take the necessary precautions