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Chronic Opioid Use After Surgery


"Risks Associated with Opioid Use after Surgery

The adverse effects of prescription opioids are well documented. The presence of tolerance and physical dependence can occur even at prescribed doses. Opioids are associated with immunosuppression and opioid-induced endocrinopathy (sexual dysfunction, depression, decreased energy). Opioids are implicated in opioid-induced hyperalgesia or increased pain sensitivity despite increasing doses of opioids. This hyperalgesia has been demonstrated with exposure to both short- and long-term opioids.

Opioid-related adverse effects can manifest as a multitude of symptoms after surgery ranging from sedation, respiratory depression, delirium, ileus, to the paradoxical worsening of pain with higher opioid doses. The significance of these opioid-related adverse effects cannot be understated. The primary mechanism of opioid fatality involves opioid-induced respiratory depression and subsequent hypoxia, hypercapnia, and cardiorespiratory arrest. Pulmonary conditions such as chronic obstructive pulmonary disease, and concurrent use of CNS depressants including benzodiazepines or antidepressants potentiate the risk of opioid-induced respiratory depression and overdose after surgery.-Postoperative opioid-induced respiratory depression often occurs within the first 24 hours, and leads to death or severe brain damage in the majority of patients. Thus, measures to limit postoperative opioid use may help to decrease the morbidity and mortality resulting from opioid-related adverse events. These adverse effects are likely to accumulate as patients take opioids for longer lengths of time after surgery.

Particularly concerning, is the association between preoperative opioid use and increased postoperative morbidity and mortality. In a cohort of 200,005 patients undergoing elective surgery, 8.8% of patients were using opioids prior to surgery, preoperative opioid use was associated with longer hospital stays, a higher rate of 30-day readmission, and increased healthcare expenditures at 90-,180-, and 365 days after surgery. Similarly, long-term opioid use was associated with an increased risk of knee revision in the first year following total knee arthroplasty in a cohort of veterans. As patients taking opioids prior to surgery often require higher postoperative doses for extended periods of time, it is possible that these heightened postoperative opioid requirements increase vulnerability to a multitude of opioid-related adverse effects. Alternatively, chronic opioid use may be associated with a number of psychosocial characteristics that impede physical function and recovery after surgery.

Concerns regarding persistent opioid use after surgery include misuse, abuse, addiction and diversion. Of patients surveyed in outpatient neurosurgery or orthopedic clinics of a tertiary academic medical center, 14.7% reported using opioids without a prescription, in greater amounts, or longer than prescribed, far exceeding the national prevalence of opioid misuse of 1.9% amongst US adults. The potential for misuse and diversion is highlighted by research reporting that the majority of patients keep their unused opioids rather than disposing of them after surgery. As provider overprescribing for acute pain is a primary source of diversion in America, efforts to limit excess perioperative opioid prescribing may be warranted.

Serious consequences of perioperative opioid misuse and dependence include increased inpatient mortality (OR 3.7, 95% CI 2.7–5.1), aggregate morbidity (OR 2.3, 95% CI 2.2–2.4), and resource utilization. In a cohort of patients scheduled for a variety of operations (thoracotomy, total knee replacement, total hip replacement, radical mastectomy, and lumpectomy), preoperative opioid use was associated with an increased risk for opioid misuse after surgery. Future work to characterize risks factors for the transition from therapeutic use to misuse are warranted in patients undergoing surgery given the increased morbidity, mortality, and healthcare costs associated with perioperative opioid misuse.

Persistent or Chronic Opioid Use After Surgery

Opioids prescribed during and after surgery may trigger long-term use in patients regardless of whether or not they are opioid-tolerant, taking opioids regularly prior to surgery, or ever been exposed to opioids in the past.,, Even opioids prescribed for low-pain, outpatient, or short-stay surgeries increase the risk of persistent opioid use,, and over 60% of people receiving 90 days of continuous opioid therapy remain on opioids years later. Patients receiving an opioid prescription after short-stay surgeries have a 44% increased risk of long-term opioid use. Even prescribing opioids at hospital discharge to previously opioid naïve patients is a risk factor for chronic opioid use 1 year after discharge (AOR=4.9, 95% CI 3.22–7.45). Surgery is an important stimulus for chronic opioid use even amongst those who are opioid naïve prior to surgery. Given the likely transition from acute to long-term opioid use after surgery, measures to curb the duration of postoperative opioid use may be necessary to limit the risks of perioperative opioid exposure.

The incidence of prolonged opioid use after surgery varies based on preoperative patient characteristics and the type of surgery a patient undergoes. In a retrospective analysis of 641,941 opioid naïve patients undergoing surgery, and 18,011,137 opioid naïve nonsurgical patients, the incidence of chronic opioid use amongst non-surgical patients was 0.136% (95% CI, 0.134%−0.137%). The highest incidence of chronic opioid use occurred after total knee arthroplasty (1.41%, 95% CI, 1.29%−1.53%). After controlling for age, sex, and preoperative medication use (antidepressants, antipsychotics, benzodiazepines), patients undergoing total knee arthroplasty, open cholecystectomy, total hip arthroplasty, simple mastectomy, laparoscopic cholecystectomy, open appendectomy, and cesarean delivery were at significantly increased risk for chronic opioid use after surgery. Risk factors for chronic opioid use after surgery amongst opioid naïve patients included male sex, age greater than 50 years, preoperative use of benzodiazepines, preoperative use of antidepressants, depression history, alcohol abuse history, and drug abuse history. Similarly, in a retrospective cohort of 36,177 opioid naïve patients undergoing minor (e.g. varicose vein removal, laparoscopic cholecystectomy, laparoscopic appendectomy, hemorrhoidectomy, thyroidectomy, transurethral prostate surgery, parathyroidectomy, and carpal tunnel surgery) or major (e.g. ventral incisional hernia repair, colectomy, reflux surgery, bariatric surgery, and hysterectomy) operations, the rates of new persistent opioid use varied between 5.9–6.5%. The incidence in a non-operative control cohort was only 0.4%. Risks factors for new persistent opioid use after surgery included preoperative tobacco use, alcohol and substance abuse disorders, mood disorders, anxiety, and preoperative pain disorders. The higher incidence of new persistent opioid use noted in this second study may relate to defining the outcome as any opioid prescription filled between 90 and 180 days after the surgical procedure, whereas the first study defined chronic opioid use as 10 or more prescriptions, or more than a 120 days’ supply of an opioid within the first year following surgery excluding the first 90 days.

Regardless of whether or not patients are taking opioids prior to surgery, undergoing surgery in and of itself is a risk factor for instigating persistent and chronic opioid use after surgery. When examining the surgical population as a whole, including patients taking opioids prior to surgery, postoperative chronic opioid use ranges from 9.2 to 13%., In the context of the current opioid crisis, measures to decrease the overall prevalence of chronic opioid use after surgery will decrease opioid-related adverse events including opioid misuse, abuse, addiction, diversion, respiratory depression and overdose."


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