Browsing by Author "Packiasabapathy, Senthil"
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Item A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects(Wolters Kluwer, 2021) Sadhasivam, Senthilkumar; Aruldhas, Blessed W.; Packiasabapathy, Senthil; Overholser, Brian R.; Zhang, Pengyue; Zang, Yong; Renschler, Janelle S.; Fitzgerald, Ryan E.; Quinney, Sara K.; Anesthesia, School of MedicineBackground: Intraoperative methadone, a long-acting opioid, is increasingly used for postoperative analgesia, although the optimal methadone dosing strategy in children is still unknown. The use of a single large dose of intraoperative methadone is controversial due to inconsistent reductions in total opioid use in children and adverse effects. We recently demonstrated that small, repeated doses of methadone intraoperatively and postoperatively provided sustained analgesia and reduced opioid use without respiratory depression. The aim of this study was to characterize pharmacokinetics, efficacy, and safety of a multiple small-dose methadone strategy. Methods: Adolescents undergoing posterior spinal fusion (PSF) for idiopathic scoliosis or pectus excavatum (PE) repair received methadone intraoperatively (0.1 mg/kg, maximum 5 mg) and postoperatively every 12 hours for 3-5 doses in a multimodal analgesic protocol. Blood samples were collected up to 72 hours postoperatively and analyzed for R-methadone and S-methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) metabolites, and alpha-1 acid glycoprotein (AAG), the primary methadone-binding protein. Peak and trough concentrations of enantiomers, total methadone, and AAG levels were correlated with clinical outcomes including pain scores, postoperative nausea and vomiting (PONV), respiratory depression, and QT interval prolongation. Results: The study population included 38 children (10.8-17.9 years): 25 PSF and 13 PE patients. Median total methadone peak plasma concentration was 24.7 (interquartile range [IQR], 19.2-40.8) ng/mL and the median trough was 4.09 (IQR, 2.74-6.4) ng/mL. AAG concentration almost doubled at 48 hours after surgery (median = 193.9, IQR = 86.3-279.5 µg/mL) from intraoperative levels (median = 87.4, IQR = 70.6-115.8 µg/mL; P < .001), and change of AAG from intraoperative period to 48 hours postoperatively correlated with R-EDDP (P < .001) levels, S-EDDP (P < .001) levels, and pain scores (P = .008). Median opioid usage was minimal, 0.66 (IQR, 0.59-0.75) mg/kg morphine equivalents/d. No respiratory depression (95% Wilson binomial confidence, 0-0.09) or clinically significant QT prolongation (median = 9, IQR = -10 to 28 milliseconds) occurred. PONV occurred in 12 patients and was correlated with morphine equivalent dose (P = .005). Conclusions: Novel multiple small perioperative methadone doses resulted in safe and lower blood methadone levels, <100 ng/mL, a threshold previously associated with respiratory depression. This methadone dosing in a multimodal regimen resulted in lower blood methadone analgesia concentrations than the historically described minimum analgesic concentrations of methadone from an era before multimodal postoperative analgesia without postoperative respiratory depression and prolonged corrected QT (QTc). Larger studies are needed to further study the safety and efficacy of this methadone dosing strategy.Item Effects of oxycodone pharmacogenetics on postoperative analgesia and related clinical outcomes in children: a pilot prospective study(Taylor & Francis, 2023) Aruldhas, Blessed W.; Quinney, Sara K.; Packiasabapathy, Senthil; Overholser, Brian R.; Raymond, Olivia; Sivam, Sahana; Sivam, Inesh; Velu, Sanjana; Montelibano, Antoinette; Sadhasivam, Senthilkumar; Medicine, School of MedicineBackground: Variability in the pharmacokinetics and pharmacodynamics of oxycodone in children undergoing surgery could be due to genetic polymorphisms. Materials & methods: The authors studied the association between clinical outcomes and pharmacogenes in children undergoing major surgery. A total of 89 children (35 undergoing pectus excavatum repair and 54 undergoing spinal fusion) were recruited. Results: OPRM1 SNP rs6902403 showed an association with maximum pain score and total morphine equivalent dose (p < 0.05). Other polymorphisms in OPRM1 SNP, PXR, COMT and ABCB1 were also shown to be associated with average morphine equivalent dose, length of hospital stay and maximum surgical pain (p < 0.05). Conclusion: This study demonstrates novel associations between the above pharmacogenes and oxycodone's pharmacokinetics as well as postoperative outcomes in children.Item Examining Visiting Student Evaluation Forms(2023-04-28) Rigueiro, Gabriel; Dammann, Erin; Guillaud, Daniel; Packiasabapathy, Senthil; Mitchell, Sally; Yu, CorinnaBackground: Each medical school has clinical evaluation forms with competencies that align with their institutional and course learning objectives. The differences between evaluation forms and the items being assessed presents a challenge for elective course directors to evaluate and complete forms for visiting students. The aim of this project was to compare common characteristics of visiting student evaluation forms presented to an elective course director on Anesthesiology & Perioperative Medicine (APM) in 2022-2023. Materials & Methods: Each medical school has clinical evaluation forms with competencies that align with their institutional and course learning objectives. The differences between evaluation forms and the items being assessed presents a challenge for elective course directors to evaluate and complete forms for visiting students. The aim of this project was to compare common characteristics of visiting student evaluation forms presented to an elective course director on Anesthesiology & Perioperative Medicine (APM) in 2022-2023. Results: Schools (n=33) included ACGME competencies for communication (94%, 31), professionalism (91%, 30), medical knowledge (79%, 26), practice-based improvement (79%, 26), patient care (76%, 25), and systems-based practice (61%, 20) in their evaluation forms. Clinical reasoning skills included history & physical (82%, 27), assessment & plan (79%, 26), differential diagnosis (64%, 21), and charting/note-taking (61%, 20). Additional categories included inter-professionalism (85%, 28), osteopathic principles and practices (64%, 21), self- awareness/receptiveness to feedback (48%, 16), and procedural skills (42%, 14). Formative and summative comments were requested from 94% (31) of schools. Discussion: While many competencies for visiting medical student evaluation forms align with IU School of Medicine evaluations, some subcategories of ACGME core competencies like charting/note-taking are not assessed in the APM elective. Visiting students do not obtain electronic medical record access due to time-prohibitive training requirements, and thus, do not chart during their rotation. Mock paper records for the preanesthetic evaluation history and physical, intraoperative anesthesia record, and postoperative notes and orders could be created as additional assignments to assess students in this skill. Formative/summative comments may or may not comment on the delivery of patient care. Comments frequently discuss teamwork, work ethic, and medical knowledge which are easily evaluated. The time-pressured environment of the OR can limit student opportunity to perform the preoperative anesthetic evaluation. A differential diagnosis during a preoperative history and physical is challenging on the APM elective because patients present to surgery after diagnostic workup. However, differential diagnoses for perioperative symptoms like tachycardia and hypertension could be assessed through Canvas case log discussions. Students currently share an abbreviated written patient presentation with a learning point. They could include perioperative differential diagnoses and treatment plans and share an article from the literature to demonstrate evidence-based learning with more specific questions about systems-based practice. The perioperative environment provides an excellent opportunity to evaluate students in their interprofessional and communication skills working with surgeons, nurses, technicians, assistants, and other learners. Additional questions could be included in the APM evaluation to capture these relationships more fully. Conclusion: Analyzing visiting student evaluations for competencies and skills provides insight into areas for improvement in the APM elective curriculum and clinical evaluation form.Item Gender, genetics, and analgesia: understanding the differences in response to pain relief(Dovepress, 2018-11-08) Packiasabapathy, Senthil; Sadhasivam, Senthilkumar; Anesthesia, School of MedicineGenetic variations and gender contribute significantly to the large interpatient variations in opioid-related serious adverse effects and differences in pain relief with other analgesics. Opioids are the most commonly used analgesics to relieve moderate-to-severe postoperative pain. Narrow therapeutic index and unexplained large interpatient variations in opioid-related serious adverse effects and analgesia negatively affect optimal perioperative outcomes. In surgical, experimental, chronic, and neuropathic pain models, females have been reported to have more pain than males. This review focuses on literature evidence of differences in pain relief due to multiple genetic variations and gender of the patient.Item Genetics of perioperative pain management(Lippincott, Williams & Wilkins, 2018-12) Packiasabapathy, Senthil; Horn, Nicole; Sadhasivam, Senthilkumar; Anesthesia, School of MedicinePURPOSE OF REVIEW: The current review will discuss the current literature on genetics of pain and analgesia, with special emphasis on perioperative setting. We will also discuss pharmacogenetics-based management guidelines, current clinical status and future perspectives. RECENT FINDINGS: Recent literature suggests that the interindividual variability in pain and postoperative analgesic response is at least in part because of one's genetic make-up. Some of the well characterized polymorphisms that are associated with surgical pain and opioid-related postoperative adverse outcomes are described in catechol-O-methyl transferase, CYP2D6 and μ-opioid receptor (OPRM1), ATP-binding cassette subfamily B member 1, ABCC3, organic cation transporter 1 genes. Clinical Pharmacogenetics Implementation Consortium has put forth recommendations on CYP2D6 genotype-based opioid selection and dosing. The list of drug-gene pairs studied continue to expand. SUMMARY: Pharmacogenetic approach marks the dawn of personalized pain medicine both in perioperative and chronic pain settings.Item Guided meditation as an adjunct to enhance postoperative recovery after cardiac surgery: study protocol for a prospective randomized controlled feasibility trial(Biomed Central, 2019-01-11) Packiasabapathy, Senthil; Susheela, Ammu T.; Mueller, Ariel; Patxot, Melissa; Gasangwa, Doris-Vanessa; O’Gara, Brian; Shaefi, Shahzad; Marcantonio, Edward R.; Yeh, Gloria Y.; Subramaniam, Balachundhar; Anesthesia, School of MedicineBACKGROUND: Cardiac surgical procedures are associated with postoperative neurological complications such as cognitive decline and delirium, which can complicate recovery and impair quality of life. Perioperative depression and anxiety may be associated with increased mortality after cardiac surgeries. Surgical prehabilitation is an emerging concept that includes preoperative interventions to potentially reduce postoperative complications. While most current prehabilitation interventions focus on optimizing physical health, mind-body interventions are an area of growing interest. Preoperative mind-body interventions such as Isha Kriya meditation, may hold significant potential to improve postsurgical outcomes. METHODS: This is a prospective, randomized controlled feasibility trial. A total of 40 adult patients undergoing cardiac surgery will be randomized to one of three study groups. Participants randomized to either of the two intervention groups will receive meditative intervention: (1) commencing two weeks before surgery; or (2) commencing only from the day after surgery. Meditative intervention will last for four weeks after the surgery in these groups. Participants in the third control group will receive the current standard of care with no meditative intervention. All participants will undergo assessments using neurocognitive, sleep, depression, anxiety, and pain questionnaires at various time points in the perioperative period. Blood samples will be collected at baseline, preoperatively, and postoperatively to assess for inflammatory biomarkers. The primary aim of this trial is to assess the feasibility of implementing a perioperative meditative intervention program. Other objectives include studying the effect of meditation on postoperative pain, sleep, psychological wellbeing, cognitive function, and delirium. These will be used to calculate effect size to design future studies. DISCUSSION: This study serves as the first step towards understanding the feasibility of implementing a mind-body intervention as a prehabilitative intervention to improve postoperative surgical outcomes after cardiac surgery.Item How do Characteristic Descriptors Relate to Medical Student Performance Ratings on an Anesthesiology Elective: Implications for Letters of Recommendation(2024-04-26) Yu, Corinna; Dijak, Frank; Dammann, Erin; Guillaud, Daniel; Packiasabapathy, SenthilItem Isha Yoga Practices and Participation in Samyama Program are Associated with Reduced HbA1C and Systemic Inflammation, Improved Lipid Profile, and Short-Term and Sustained Improvement in Mental Health: A Prospective Observational Study of Meditators(Frontiers Media, 2021-05-19) Sadhasivam, Senthilkumar; Alankar, Suresh; Maturi, Raj; Williams, Amy; Vishnubhotla, Ramana V.; Hariri, Sepideh; Mudigonda, Mayur; Pawale, Dhanashri; Dubbireddi, Sangeeth; Packiasabapathy, Senthil; Castelluccio, Peter; Ram, Chithra; Renschler, Janelle; Chang, Tracy; Subramaniam, Balachundhar; Anesthesia, School of MedicineBackground: Meditation is gaining recognition as a tool to impact health and well-being. Samyama is an 8-day intensive residential meditation experience conducted by Isha Foundation requiring several months of extensive preparation and vegan diet. The health effects of Samyama have not been previously studied. The objective was to assess physical and emotional well-being before and after Samyama participation by evaluating psychological surveys and objective health biomarkers. Methods: This was an observational study of 632 adults before and after the Isha Samyama retreat. All participants were invited to complete surveys. Controls included household significant others. Surveys were completed at baseline (T1), just before Samyama (T2), immediately after Samyama (T3), and 3 months later (T4) to assess anxiety, depression, mindfulness, joy, vitality, and resilience through validated psychometric scales. Voluntary blood sampling for biomarker analysis was done to assess hemoglobin (Hb), HbA1c, lipid profile, and C-reactive protein (CRP). Primary outcomes were changes in psychometric scores, body weight, and blood biomarkers. Results: Depression and anxiety scores decreased from T1 to T3, with the effect most pronounced in participants with baseline depression or anxiety. Scores at T4 remained below baseline for those with pre-existing depression or anxiety. Vitality, resilience, joy, and mindfulness increased from T1 to T3 (sustained at T4). Body weight decreased by 3% from T1 to T3. Triglycerides (TG) were lower from T2 to T3. Participants had lower HbA1c and HDL at T2, and lower CRP at all timepoints compared with controls. Conclusions: Participation in the Isha Samyama program led to multiple benefits. The 2-month preparation reduced anxiety, and participants maintained lower anxiety levels at 3 months post-retreat. Physical health improved over the course of the program as evidenced by weight loss and improved HbA1C and lipid profile. Practices associated with the Samyama preparation phase and the retreat may serve as an effective way to improve physical and mental health. Future studies may examine their use as an alternative therapy in patients with depression and/or anxiety.Item Methadone-based Multimodal Analgesia Provides the Best-in-class Acute Surgical Pain Control and Functional Outcomes With Lower Opioid Use Following Major Posterior Fusion Surgery in Adolescents With Idiopathic Scoliosis(Wolters Kluwer, 2020-07-27) Ye, Jian; Myung, Karen; Packiasabapathy, Senthil; Yu, Jeffrey S.; Jacobson, Joseph E.; Whittaker, Stephanie C.; Castelluccio, Peter; Drayton Jackson, Meghan; Sadhasivam, Senthilkumar; Anesthesia, School of MedicineIntroduction: Posterior spinal fusion for idiopathic scoliosis is extremely painful, with no superior single analgesic modality. We introduced a methadone-based multimodal analgesia protocol, aiming to decrease the length of hospital stay (LOS), improve pain control, and decrease the need for additional opioids. Methods: We analyzed 122 idiopathic scoliosis patients with posterior instrumented spinal fusion. They were matched by age, sex, surgeon, and the number of levels fused before and after the implementation of the new protocol. This analysis included 61 controls (intrathecal morphine, gabapentin, intravenous opioids, and adjuncts) and 61 patients on the new protocol (scheduled methadone, methocarbamol, ketorolac/ibuprofen, acetaminophen, and oxycodone with intravenous opioids as needed). The primary outcome was LOS. Secondary outcomes included pain scores, total opioid use (morphine milligram equivalents), time to a first bowel movement, and postdischarge phone calls. Results: New protocol patients were discharged earlier (median LOS, 2 days) compared with control patients (3 days; P < 0.001). Total inpatient morphine consumption was lower in the protocol group (P < 0.001). Pain scores were higher in the protocol group on the day of surgery, similar on postoperative day (POD) 1, and lower by POD 2 (P = 0.01). The new protocol also reduced the median time to first bowel movement (P < 0.001), and the number of postdischarge pain-related phone calls (P < 0.006). Conclusion: Methadone-based multimodal analgesia resulted in significantly lower LOS compared with the conventional regimen. It also provided improved pain control, reduced total opioid consumption, and early bowel movement compared with the control group.Item Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children(Future Medicine, 2021-07) Packiasabapathy, Senthil; Aruldhas, Blessed W.; Zhang, Pengyue; Overholser, Brian R.; Quinney, Sara K.; Sadhasivam, Senthilkumar; Anesthesia, School of MedicineAim: Methadone exhibits significant variability in clinical response. This study explores the genetic influence of variable methadone pharmacokinetics. Methods: This is a prospective study of methadone in children undergoing major surgery. CYP2B6 genotyping, plasma methadone and metabolite levels were obtained. Clinical outcomes include pain scores and postoperative nausea and vomiting (PONV). Results:CYP2B6 poor metabolizers (*6/*6) had >twofold lower methadone metabolism compared with normal/rapid metabolizers. The incidence of PONV was 4.7× greater with CYP2B6 rs1038376 variant. AG/GG variants of rs2279343 SNP had 2.86-fold higher incidence of PONV compared with the wild variant (AA). Nominal associations between rs10500282, rs11882424, rs4803419 and pain scores were observed. Conclusion: We have described novel associations between CYP2B6 genetic variants and perioperative methadone metabolism, and associations with pain scores and PONV.