Day-of-Surgery Gabapentinoids and Prolonged Opioid Use

A Retrospective Cohort Study of Medicare Patients Using Electronic Health Records

Jessica C. Young, PhD; Nabarun Dasgupta, PhD; Brooke A. Chidgey, MD; Til Stürmer, MD, PhD; Virginia Pate, MS; Michael Hudgens, PhD; Michele Jonsson Funk, PhD

Disclosures

Anesth Analg. 2021;133(5):1119-1128. 

In This Article

Results

We identified 13,958 Medicare patients undergoing major therapeutic surgical procedures between January 1, 2016 and September 16, 2019 who met study inclusion criteria and had 90 days of follow-up (Figure 1; Supplemental Digital Content, Table 1, http://links.lww.com/AA/D593). Overall, 4.2% (exposed) and 6.0% (unexposed) of patients were excluded for having <90 days of follow-up. The majority of patients (94.6% [exposed] and 93.0% [unexposed]), were excluded because they had surgery during the 90-day follow-up. In both cohorts, <0.4% of patients died during the 90-day follow-up (Supplemental Digital Content, Table 2, http://links.lww.com/AA/D593).

Figure 1.

Flow diagram describing cohort inclusion criteria.

The mean age of eligible patients was 72.7 years (SD, 6.0), 57.7% were women, 82.2% reported White race, and 12.4% had opioid orders in the previous 182 days (Table 1). Overall, 21.0% had received preoperative gabapentinoid administration on the day of surgery (84.5% of which was pregabalin). The median dose for pregabalin was 100 mg (interquartile range [IQR], 50–100 mg), while the median dose for gabapentin was 300 mg (IQR, 300–600 mg).

Calendar Trends

The proportion of patients who received preoperative gabapentinoid administration on the day of surgery increased from 7.4% in the first half of 2016 to 28.3% in the first half of 2019 (Table 2).

The observed risk of prolonged opioid use decreased throughout the study period from 1.4 (95% CI, 0.9–2.0) in the first half of 2016 to 0.6% (95% CI, 0.3–0.9) in the first half of 2019. This decreasing trend in prolonged opioid use was larger in patients who received preoperative gabapentinoids, decreasing from 3.7% (95% CI, 0.5–6.8) to 0.3% (95% CI, 0.0–0.8).

Main Analysis

The observed 90-day risk of prolonged opioid use across the study period was 0.91% (95% CI, 0.77–1.08) (Table 3).

Following IPTW adjustment (Supplemental Digital Content, Figure 1, http://links.lww.com/AA/D593), the estimated risk of prolonged opioid use after receiving preoperative gabapentinoids was 1.00% (95% CI, 0.59–1.68). In contrast, in the absence of receipt of preoperative gabapentinoids, the estimated risk of prolonged opioid use was 0.84% (95% CI, 0.66–1.06). Patients receiving preoperative gabapentinoids were not found to be at higher risk of prolonged opioid use compared to those who did not receive gabapentinoids, with an estimated risk ratio of 1.19 (95% CI, 0.67–2.12; Figure 2; Table 3).

Figure 2.

Crude and adjusted risk ratios of prolonged opioid use comparing patients who received preoperative gabapentinoids to those who did not receive preoperative gabapentinoids. CI indicates confidence interval; IPTW, inverse probability of treatment weight.

Models adjusting for calendar time as a continuous variable using a quadratic term and cubic splines had similar results and are presented in Supplemental Digital Content, Table 3, http://links.lww.com/AA/D593. Analysis of interaction between exposure and period (pre-ERAS versus post-ERAS) was not significant (P = .20), and results from stratified analyses are presented in Supplemental Digital Content, Table 4, http://links.lww.com/AA/D593.

Secondary Analysis

There were 4 distinct procedures in which over 30% of patients received preoperative gabapentinoids: colorectal resection, hip arthroplasty, knee arthroplasty, and hysterectomy. The analysis subset of patients undergoing one of these procedures included 2587 patients (Supplemental Digital Content, Table 5, http://links.lww.com/AA/D593). After adjustment via IPTW (Supplemental Digital Content, Figure 2, http://links.lww.com/AA/D593), patients who received preoperative gabapentinoids were at 1.01 (95% CI, 0.30–3.33) times the risk of prolonged use compared to those who did not (Figure 2; Table 3). Among those undergoing surgical procedures for which <30% of patients received perioperative gabapentinoids, exposed patients were at higher risk of prolonged opioid use, with an estimated risk ratio of 2.34 (95% CI, 1.02–5.41) (Supplemental Digital Content, Table 4, http://links.lww.com/AA/D593).

Sensitivity Analyses

Overall, 5084 patients had at least 1 outpatient visit and 1 outpatient medication order in the 182 days before surgery, and 22.2% received preoperative gabapentinoids (Supplemental Digital Content, Table 6, http://links.lww.com/AA/D593). After adjustment (Supplemental Digital Content, Figure 3, http://links.lww.com/AA/D593), patients who received preoperative gabapentinoids were at 1.06 (95% CI, 0.57–1.99) times the risk of prolonged use compared to those who did not receive preoperative gabapentinoids (Figure 2; Table 3). Among those without at least 1 outpatient visit and 1 outpatient medication order in the 182 days before surgery, patients who received preoperative gabapentinoids were at 1.73 (0.57–5.30) times the risk of prolonged opioid use compared to those who did not (Supplemental Digital Content, Table 4, http://links.lww.com/AA/D593).

Bias Analyses

A subset of the population (n = 3446) was linked to Medicare insurance claims. The first quantitative bias analysis adjusted for potential underestimation of prolonged opioid use in the EHR (combined EHR and Medicare data used as the gold standard). The bias-adjRR for the risk of prolonged use comparing patients who received preoperative gabapentinoids to those who did not was 1.45 (95% CI, 0.78–2.17). A second quantitative bias analysis using Medicare insurance claims as the gold standard resulted in a bias-adjRR of 1.48 (95% CI, 0.78–2.27; Supplemental Digital Content, Table 7, http://links.lww.com/AA/D593).

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