No opioids before scheduled spine – surgery?

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Article for physicians. Preoperative opioid medication can worsen the outcome of surgery. Spine patients in particular are often burdened. The article sheds light on the pathophysiological relationships and shows ways to solve them.

Before you read

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The opioid crisis as an eye opener

Uncritical prescribing of opioid medications has led to a crisis in the U.S. with thousands of drug deaths. Although opioid abuse figures from the U.S. are higher than in other countries ¹https://pubmed.ncbi.nlm.nih.gov/31318808/, it is worthwhile to reconsider opioid medication practices in one’s own patients. However, there are some – perhaps not so well known side effects to be aware of, which are quite worth knowing especially before surgery and even more especially before planned spine surgery.

The purpose of this article is to summarize opioid side effects in chronic use with the goal that perhaps in some patients with planned spine surgery (or other planned surgery), these medications can be discontinued preoperatively. The term opioid is used as a collective term for the natural opiates (morphine) and the synthetic opioids (fentanyl, oxycodone, buprenorphine, etc.). Substance-specific effects cannot be discussed here.

Relationship between opioids preoperatively and postoperatively

I myself first encountered this issue at the SRS Meeting in 2019. ² https://www.srs.org/professionals/online-education-and-resources/past-meeting-archives/annual-meeting/54th-annual-meeting-montreal-canada-september-18-21-2019

Multi-center studies concluded that preoperative opioids medication was the major risk factor for worse pain and function postoperatively in major fusion surgery.³ https://www.sciencedirect.com/science/article/abs/pii/S1529943019302657 Of course, it was also the case that those patients who successfully discontinued opioids postoperatively were also in the group of functionally better patients at the end.⁴ https://www.sciencedirect.com/science/article/abs/pii/S1529943019306370 From my observation, there are few patients who want to keep their opioid medication after surgery. Most would like to get rid of them. This is also consistent with the recommendations of the German LONTS guideline, which recommends rapid de-escalation of acute inpatient pain therapy. ⁵ https://www.schmerzgesellschaft.de/fileadmin/2019/lonts/LONTS_2._Aktualisierung_Empfehlungen_2019.pdf

Side effect pathophysiology of opioids.

However, the side effects of preoperative opioids extend beyond worse intraoperative and postoperative pain control. Everything we fear postoperatively (infections, fractures) seems to be worsened here as well.

Why is that? – how deep does the opiate effect reach into the organism?

• Opioids have an impact on our adrenergic stress management via a reduction of the CRH → ACTH axis. ⁶https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30254-2/fulltext As a consequence, patient cortisol levels are inappropriate to the stress of surgery.
• Opioids have a direct effect on cells of the immune system. ⁷https://www.scielo.br/j/ramb/a/srHBJJwXWxbVmqBGVbCkxvQ/?lang=en&format=pdf Thus, there are opioid receptors on almost every cell of the innate and adaptive immune system. The task here is probably an anti-nociceptive effect in the inflamed peripheral tissue. Drawing conclusions from this for clinical use is difficult due to the diversity of interactions demonstrated. Possibly relevant to practice is that the immunosuppressive effect has been demonstrated only with morphine and fentanyl, but not with oxycodone and tramadol.
• Opioids inhibit the gonadotropin → sex hormone axis in men and women. ⁸https://pubmed.ncbi.nlm.nih.gov/26516462/ Did you know that? Do you educate your patients about the sexual dysfunction to be expected when opioids are prescribed?

These effects occur already with the first administration. In the long term, this mechanism suggests a fixed alteration of the hypothalamic → pituitary axis. Other long-term effects include:

• Osteopenia – due to the effect on sex hormones, as already described. On the other hand, opioids also directly inhibit osteocalcin synthesis in osteoblasts. ⁹ https://pubmed.ncbi.nlm.nih.gov/2342747/
• Obesity due to insulin resistance and diabetes. Again, explainable via hypogonadism-mediated insulin resistance, but possibly via other pathways.¹⁰ https://www.thieme-connect.com/products/ejournals/pdf/10.4103/2321-0656.176570.pdf Overall, the combination of diabetes and opioid use results in significantly increased mortality, irrespective of the pathophysiology ¹¹ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938504/ The interaction probably also works in the opposite direction: diabetic patients (type 1 and 2) need more opioids postoperatively. ¹² https://www.medscape.com/viewarticle/985068#:~:text=People%20with%20type%202%20diabetes,compared%20to%20people%20without%20diabetes

Which of the opioid side effects mentioned have you been already aware of?

Clinical consequences

After this excursion into pathophysiology, I would now like to turn to the clinically proven consequences, the proven opioid-related complications.

Complications in endoprosthesis implantation

In a large American cross-sectional study (2014+2015) of 35,000 patients who had received both total hip and total knee arthroplasty, the following complications were described. ¹³https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060398/ I include the hazard ratio (HR) so that everyone can evaluate the result for themselves. Patients who went into surgery with opioids had

• more wound infections (HR = 1.35, 95% CI = 1.14 – 1.59).
• more revisions (HR = 1.44, 95% CI = 1.21 – 1.71)
• approximately $1,000 higher medical follow-up costs within the current year.

Comparable statements apply to shoulder arthroplasty. ¹⁴ https://www.jshoulderelbow.org/article/S1058-2746(20)30681-9/fulltext

Complications in spinal surgery

Among spine patients, the group of opioid users is the highest, and so is the rate of addiction. ¹⁵https://esmed.org/MRA/mra/article/view/2984 Patients in pain are usually prescribed opioids even before their first consultation with the spine specialist. This procedure is not to be denounced – on the contrary, it underpins the intensity and suffering of the patient clientele. Rather, it is the responsibility of the spine surgeon to design a consistent roadmap for the patient in which the goal clearly includes discontinuation of opioid medication.

From insurance data in the United States on opioid use before and after spinal surgery, it is known that as the duration of preoperative medication increases, the risk for continued postoperative use increases. ¹⁶ https://journals.lww.com/jbjsjournal/Abstract/2018/06060/Sustained_Preoperative_Opioid_Use_Is_a_Predictor.2.aspx

In the cervical spine, a study of 20,000 patients (retrospective insurance data from 2007-2015) showed that preoperative opioid therapy of at least 3 months duration significantly more often results in

• wound healing disorders (odds ratio: 1.32)
• infections (OR: 1.34)
• constipation (OR: 1.11)
• neurological complications (OR: 1.44).
• acute renal failure (OR: 1.24)
• deep vein thrombosis (OR: 1.20)

¹⁷https://pubmed.ncbi.nlm.nih.gov/30973507/ Cervical spine fusions tend to be minor surgeries that usually get patients back in shape faster and usually mobilized with little pain. Thus, if such differences are already evident in such a benign patient population, this is rather an indication of the drug-related side effect and not due to cohort specifics.

The number of publications on complications in the lumbar spine are much more diverse, confirming in essence the complication rates from the cervical spine figures. Due to the mechanical peculiarities of lumbar surgery, this is compounded by the increased implant failure rate. ¹⁸ https://pubmed.ncbi.nlm.nih.gov/32271911/

Discontinuation of opioids 3 months preoperatively leads to a significant reduction in the risks described. ¹⁹ https://journals.lww.com/jbjsjournal/Abstract/2019/03060/Prediction_of_Complications,_Readmission,_and.2.aspx

Complication rates beyond orthopedic surgery.

An increased complication rate due to preoperative opioids medication is also found in colorectal surgery, cardiac surgery, and as an increased [mortality in vascular surgery. ²⁰ Colorectal Surgery, Cardiac Surgery, Vascular Surgery.

What to do?

Opioids are quickly prescribed, but withdrawal from them can be difficult. There is no universal recipe for this and it cannot be discussed here. Preventing an opioid-laden course is the most cost-effective route here, but takes time and thought to identify the right strategy with the patient. At the very least, as surgeons making indications, you should bring the topic of “preoperative discontinuation” to the table in order to optimize your own results.

According to the recommendations of the German S3 guideline on opioids dependence (which can already be present after a few weeks of therapy), withdrawal treatment should be led by a pain specialist. This is definitely to be welcomed from a professional point of view. However, the question arises whether this will be feasible in reality today and in the future. The transition from intended use to dependence is fluid. At this point, allow me to ask how you deal with the de-escalation of opioid medication (completely anonymous survey, please participate so that we get a picture of the reality of care)?

In this regard, the 2021 UK Best Practice Guidelines state that preoperative opioid use should be addressed in a prehabilitation phase, if appropriate.²¹ https://fpm.ac.uk/sites/fpm/files/documents/2021-03/surgery-and-opioids-2021_4.pdf In addition to the precise recording of use, patients should also be psychologically prepared to address fears and expectations – ideally combined with appropriate patient education.

Especially in ERAS programs (Fast Track / Enhanced Recovery), preoperative preparation should play an essential role, as opioids prolonged inpatient stay in almost all clinical trials. ²² https://journals.lww.com/clinicalpain/fulltext/2020/03000/enhanced_recovery_after_surgeryeras_a.11.aspx