A real-world systematic review of the forensic implications regarding serum testing in compliance monitoring

Authors

  • Robert G. Salazar Pharmacological Management, California Advanced Pain and Spine Specialists, Fresno, California, USA
  • Tyler F. Salazar Pharmacological Management, California Advanced Pain and Spine Specialists, Fresno, California, USA

DOI:

https://doi.org/10.18203/issn.2454-2156.IntJSciRep20251455

Keywords:

Centers of disease control, Intrathecal opioid therapy, Morphine milligram equivalent, Opioid toxicity, Serum opioid levels

Abstract

The purpose of this systematic review is to study the correlation between the daily dose of oral opioids/ intrathecal opioids and resultant serum levels in relation to established blood toxicity levels used forensically. Between April 2018 and October 2022, serum opioid test results of 1,583 patients were analyzed from our clinical private practice.  A broad literature search was conducted with the key words, “Blood concentrations of opioids”, which returned 7,993 results in PubMed. A smaller search was performed in PubMed with the key words, “cytochromes that metabolize opioids”, which yielded 1,387 results. Additionally, a confidential Excel spreadsheet was created by the American Institute of Toxicology Laboratories in Denton, Texas and was provided to our clinical practice. Simple linear regression was performed in Excel to determine the correlation coefficient, R-squared value, for each prescribed opioid. The result was an unexpected weak correlation between the daily opioid dose and serum concentration. The most surprising finding is an “overlap” between measured serum levels of all opioid groups with the toxic range in Baselt. In conclusion, the endpoint of opioid prescribing should focus on maximizing activities of daily living and achievement of functional goals utilizing serum level analysis, tempered by Centers of Disease Control guidelines. Serum testing can suppress physician vulnerability created by patients dying, (who were taking prescribed opioids). Future research analyzing the concentration of oral opioids in the cerebrospinal fluid in comparison to the concentration of opioids in the cerebrospinal fluid in the same patient after intrathecal opioid monotherapy would be interesting.

Metrics

Metrics Loading ...

References

Alpert A, Evans WN, Lieber EMJ, Powell D. Origins of the Opioid Crisis and its Enduring Impacts. Quart J Economics. 2022;2:1139-79. DOI: https://doi.org/10.1093/qje/qjab043

Leung PTM, Macdonald EM, Dhalla IA, Juurlink DA. A 1980 Letter on the Risk of Opioid Addiction. N Engl J Med. 2017;376:2194-5. DOI: https://doi.org/10.1056/NEJMc1700150

Gunn J. Schwilke E. The Value of Blood Analysis for Complaince Monitoring. Pract Pain Mana. 2011;3:16-8.

Bohnert AS, Valenstein M, Bair MJ, Ganoczy D, McCarthy JF, Ilgen MA, et al. Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths. JAMA. 2011;305:1315-21. DOI: https://doi.org/10.1001/jama.2011.370

Deer TR. Gunn J. Blood Testing in Chronic Pain Management. Pain Physician. 2015;2:157-61. DOI: https://doi.org/10.36076/ppj/2015.18.E157

Baselt R.C. Disposition of Toxic Drugs and Chemicals in Man. 12th ed. Seal Beach (CA): Biomedical Publications. 2020.

Ferner RE. Post-mortem clinical pharmacology. Br J Clin Pharmacol. 2008;66:430-43. DOI: https://doi.org/10.1111/j.1365-2125.2008.03231.x

Heiskanen T, Langel K, Gunnar T, Lillsunde P, Kalso EA. Opioid Concentrations in Oral Fluid and Plasma in Cancer Patients With Pain. J Pain Symptom Manag. 2020;3:524-32. DOI: https://doi.org/10.1016/j.jpainsymman.2014.09.004

Palmer RB. Fentanyl in postmortem forensic toxicology. Clin Toxicol. 2010;2:771-84. DOI: https://doi.org/10.3109/15563650.2010.525514

Davis GG, Cadwallader AB, Fligner CL, Gilson TP, Hall ER, Harshbarger KE. Recommendations for the investigation, diagnosis and certification of deaths related to opioid and other drugs. Am J Forensic Med Pathol. 2020;41(3):152-9. DOI: https://doi.org/10.1097/PAF.0000000000000550

Skopp G. Preanalytic aspects in postmortem toxicology. Forensic Science Int. 2004;142:75-100. DOI: https://doi.org/10.1016/j.forsciint.2004.02.012

Pounder DJ, Jones GR. Post-Mortem Drug Redistribution. A Toxicological Nightmare. Forensic Sci Int. 1990;45: 253-263 DOI: https://doi.org/10.1016/0379-0738(90)90182-X

Ummenhofer WC, Arends RH, Shen DD, Bernards CM. Comparative Spinal Distribution and Clearance Kinetics of Intrathecally Administered Morphine, Fentanyl, Alfentanil and Sufentanil. Anesthesiol. 2000;92(3):739-753 DOI: https://doi.org/10.1097/00000542-200003000-00018

Brogan SE, Sindt JE, Jackman CM, White J, Wilding V, Okifuji A. Prospective association of serum opioid levels and clinical outcomes in patients with cancer pain treated with intrathecal opioid therapy. Anesthesia Analgesia. 2020;130:1035-44. DOI: https://doi.org/10.1213/ANE.0000000000004276

Schultz DM, Orhurhu V, Khan F, Hagedorn JM, Abd-Elsayed AA. Patient satisfaction following intrathecal targeted drug delivery for benign chronic pain: results of a single-center survey study. Neuromodulation. 2020;23:1009-17. DOI: https://doi.org/10.1111/ner.13167

Downloads

Published

2025-05-23

How to Cite

Salazar, R. . G., & Salazar , T. F. (2025). A real-world systematic review of the forensic implications regarding serum testing in compliance monitoring. International Journal of Scientific Reports, 11(6), 222–229. https://doi.org/10.18203/issn.2454-2156.IntJSciRep20251455

Issue

Section

Systematic Reviews