# Prospective evaluation of cerebrospinal fluid concentrations of β-Endorphin as a predictor of opioid use after scheduled cesarean delivery

## TL;DR

This study found that pre-surgery levels of a natural painkiller in the spinal fluid of pregnant women did not predict how much opioid pain medication they would need after a cesarean delivery.

## Contribution

The novel contribution is the first prospective evaluation of cerebrospinal fluid β-Endorphin as a predictor of postoperative opioid use after cesarean delivery.

## Key findings

- Preoperative cerebrospinal fluid β-Endorphin concentrations were not associated with total opioid use after cesarean delivery.
- Both cerebrospinal fluid and plasma β-Endorphin concentrations were positively associated with postpartum pain intensity.
- Cerebrospinal fluid and plasma β-Endorphin concentrations were only moderately correlated.

## Abstract

Prior laboratory work indicates that lower endogenous opioid function is associated with greater analgesic and subjective responses to opioid analgesics. We evaluated whether preoperative cerebrospinal fluid (CSF) concentrations of the analgesic endogenous opioid β-Endorphin (BE) were associated with extent of opioid use after cesarean delivery (CD).

We enrolled 136 pregnant women without opioid use or chronic pain who were undergoing CD under spinal or combined spinal-epidural anesthesia. Preoperatively, participants completed validated pain measures and biospecimens were collected to assess BE concentrations in plasma and CSF. Postoperatively, pain intensity at 48 h and 2 weeks postpartum were assessed. We evaluated the association between CSF BE concentrations and total opioid use (in morphine milligram equivalents; MMEs) using linear regression controlling for confounding factors (primary analysis). In secondary analyses, we examined: 1) associations between plasma BE concentrations and total opioid use, and 2) associations between CSF and plasma BE concentrations and secondary outcomes (inpatient versus outpatient opioid use, pain intensity).

Participants completed surveys with 100% response rate. The majority were non-Hispanic white (65%), college educated (58%), had private insurance (71%), and had a prior CD (69%). Psychiatric diagnoses (depression or anxiety) were common, both currently (22%) and in the past (26%). The median total opioid use across inpatient and 2-week postpartum follow-up period was 89.1 mg morphine equivalents (IQR 25–138). Preoperative CSF BE concentrations were not associated with total opioid use (beta = -0.05, SE 0.45, p = 0.64). Similar findings were noted for plasma BE concentrations. CSF BE concentrations were only moderately correlated with plasma BE concentrations (r = 0.38, p < .001). Preoperative CSF and plasma BE concentrations were both positively associated with postpartum pain measures (CSF: at 48 h, beta = 0.19, SE 0.16, p < 0.05; Plasma: at 48 h , beta = 0.02, SE 0.03, p = 0.02, and at 2-weeks, beta = 0.27, SE 0.03, p < 0.01).

Preoperative CSF BE concentrations were not associated with extent of opioid analgesic use after scheduled CD in this cohort of healthy participants. Potential clinical implications are discussed.