Epidural morphine improves postoperative analgesia in patients after total knee arthroplasty: A randomized controlled trial

Abstract

Background: Patients after total knee arthroplasty (TKA) often develop moderate to severe pain. This study compared the analgesic effect of low-dose epidural morphine vs. a comparable saline injection in patients following TKA surgery.

Methods: This randomized, double-blinded, and placebo-controlled trial was conducted in a tertiary hospital in Beijing between July 1, 2017 and May 30, 2018. One hundred and ten patients following TKA under combined spinal-epidural anesthesia were randomized to receive either epidural morphine (2 mg diluted to 5 ml normal saline, the epidural morphine group) or placebo (5 ml normal saline, the placebo group). For all patients, single-injection femoral nerve block was performed, and a supplementary patient-controlled intravenous analgesia pump was provided. The severity of pain was assessed with the numerical rating scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) at 6, 12, 24, 36, and 48 hours after surgery. The primary endpoint was moderate to severe pain (NRS pain score ≥4) within 48 hours after surgery.

Results: The percentage with moderate to severe pain within 48 hours was lower in the epidural morphine group than in the placebo group (58.2% [32/55] with epidural morphine vs. 76.4% [42/55] with placebo; OR 0.43, 95% CI 0.19-0.98; p = 0.042). Furthermore, the cumulative morphine consumption within 48 hours was lower (18.4±6.1 mg vs. 22.4±7.3 mg; p = 0.002) whereas the mental component summary score of 30-day quality of life was higher (63.8±2.9 vs. 61.9±4.2; p = 0.008) in the epidural morphine group than in the placebo group.

Conclusions: For patients following TKA, the addition of epidural morphine to single-injection femoral nerve block improves the quality of analgesia within 48 hours, without increasing adverse events.

Trial registration: ClinicalTrials.gov NCT03203967.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flow diagram of the study.

TKA, total knee arthroplasty; CKD, chronic kidney disease; ASA, American Society of Anesthesiologists; PCIA, patient-controlled intravenous analgesia.

Fig 2

The NRS pain scores at rest (A) and with movement (B). The pain score with movement at different time-points were significantly lower in the epidural morphine group than in the placebo group (P = 0.020 [mixed-effects maximum likelihood regression model]). The box and whiskers plots show medians, interquartile ranges and outer ranges, and individual points mean mild outliers (o, which are outside 1.5 times of interquartile range) and extreme outliers (*, which are outside 3 times of interquartile range). NRS, numerical rating scale.

Fig 3

The percentages with moderate to severe pain at rest (A) and with movement (B). The percentage with movement at different time-points were significantly lower in the epidural morphine group than in the placebo group (P = 0.016 [mixed-effects logistic regression model]).

Fig 4

The numbers of required (A) and given (B) boluses of the PCIA pump. The numbers of both required and given boluses during different time-intervals were significantly less in the epidural morphine group than in the placebo group (P = 0.017 and 0.005, respectively [mixed-effects maximum likelihood regression model]). The box and whiskers plots show medians, interquartile ranges and outer ranges, and individual points mean mild outliers (o, which are outside 1.5 times of interquartile range) and extreme outliers (*, which are outside 3 times of interquartile range). PCIA, patient-controlled intravenous analgesia.