Association of Intraoperative Opioid Administration With Postoperative Pain and Opioid Use

Abstract

ImportanceOpioids administered to treat postsurgical pain are a major contributor to the opioid crisis, leading to chronic use in a considerable proportion of patients. Initiatives promoting opioid-free or opioid-sparing modalities of perioperative pain management have led to reduced opioid administration in the operating room, but this reduction could have unforeseen detrimental effects in terms of postoperative pain outcomes, as the relationship between intraoperative opioid usage and later opioid requirements is not well understood.ObjectiveTo characterize the association between intraoperative opioid usage and postoperative pain and opioid requirements.Design, Setting, and ParticipantsThis retrospective cohort study evaluated electronic health record data from a quaternary care academic medical center (Massachusetts General Hospital) for adult patients who underwent noncardiac surgery with general anesthesia from April 2016 to March 2020. Patients who underwent cesarean surgery, received regional anesthesia, received opioids other than fentanyl or hydromorphone, were admitted to the intensive care unit, or who died intraoperatively were excluded. Statistical models were fitted on the propensity weighted data set to characterize the effect of intraoperative opioid exposures on primary and secondary outcomes. Data were analyzed from December 2021 to October 2022.ExposuresIntraoperative fentanyl and intraoperative hydromorphone average effect site concentration estimated using pharmacokinetic/pharmacodynamic models.Main Outcomes and MeasuresThe primary study outcomes were the maximal pain score during the postanesthesia care unit (PACU) stay and the cumulative opioid dose, quantified in morphine milligram equivalents (MME), administered during the PACU stay. Medium- and long-term outcomes associated with pain and opioid dependence were also evaluated.ResultsThe study cohort included a total of 61 249 individuals undergoing surgery (mean [SD] age, 55.44 [17.08] years; 32 778 [53.5%] female). Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. In particular, increased fentanyl administration was associated with lower frequency of uncontrolled pain; a decrease in new chronic pain diagnoses reported at 3 months; fewer opioid prescriptions at 30, 90, and 180 days; and decreased new persistent opioid use, without significant increases in adverse effects.Conclusions and RelevanceContrary to prevailing trends, reduced opioid administration during surgery may have the unintended outcome of increasing postoperative pain and opioid consumption. Conversely, improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery.

Opioid use and subsequent delirium risk in patients with advanced cancer in palliative care: a multicenter registry study

“…Previous studies explored the association between opioid use and delirium in individuals with various surgeries and diseases, including hip fractures, neurological injury, pain, infection, fever, and hypotension 4 , 10 , 11 , 30 ; however, investigations focusing on delirium in patients with advanced cancer are limited. A few studies suggested an association between opioid use and the occurrence of delirium in patients with cancer.…”

“…The etiology of delirium in these patients is typically multifactorial, and our prior research identified several risk factors for delirium in patients with cancer, including old age, absence of chemotherapy during hospitalization, hearing impairment, underweight status, current opioid use, and history of delirium and other psychiatric disorders 9 . Opioid prescriptions, in particular, have been identified in various studies as potential triggers of delirium, observed across different surgical and disease groups, including those with neurological injury, pain, infection, fever, and hypotension 4 , 10 , 11 . However, previous studies exploring the association between opioid use and delirium in patients with advanced cancer showed controversy and limited cohort size 12 – 15 .…”

Variation in Intraoperative Opioid Administration by Patient, Clinician, and Hospital Contribution

“…As a result, it is unclear based on current available evidence that opioids administered intraoperatively are associated with surgical outcomes or increased risk for aberrant opioid use postoperatively . Recent studies suggested the importance of understanding qualitative and quantitative aspects of intraoperative opioid administrations for postoperative pain and opioid consumption . Characterizing heterogeneity across clinicians and practices may provide valuable insight to elucidate patterns, improve guidelines, and influence policy change to promote better stewardship of opioids.…”

Letter to the Editor

“…Available evidence indicates that intraoperative opioid administration is associated with total dosage of opioid consumption and pain level in the PACU after surgery. 2 We are concerned that this unknown factor would have biased the main findings of this study.…”