Sex differences in the daily rhythmicity of morphine consumption after major abdominal surgery

J Opioid Manag. Mar/Apr 2017;13(2):85-94. doi: 10.5055/jom.2017.0372.


Objective: The sex of the patients has been shown to affect postoperative pain and morphine consumption; still a clear understanding able to explain the reasons behind this difference struggles to emerge. Our research aimed to investigate one specific aspect of the variability in morphine consumption between sexes. Previous studies have shown that circadian rhythm can influence opioid consumption. Furthermore, circadian rhythm is different between female and male. Our analysis investigated the presence of differences in daily rhythmicity of morphine consumption between males and females.

Design: This is a secondary analysis of data collected during 2 years long multicenter clinical trial (NCT01233752).

Settings: Clinical data were collected in two Italian hospitals: IRCCS Foundation Policlinico S. Matteo (Pavia) and San Gerardo Hospital (Monza).

Patients: The authors recorded data about morphine consumption in 157 patients who underwent major abdominal surgery, who received morphine intravenous patient-controlled analgesia (IV-PCA) as postoperative analgesia.

Interventions: The authors analyzed the daily periodicity of effective boluses delivered by morphine IV-PCA with Poisson multilevel models, adjusted by the time of start for each pump. An effective bolus was defined as a correctly delivered bolus of 1 mg of morphine. The authors also evaluated the interactions among the time of the day and sex, age (</≥55 y), and body mass index (BMI;</≥30 kg/m2).

Main outcome measure(s): Differences in sex of morphine consumption rhythms over the 24 hours of the day.

Results: Morphine consumption showed a statistically significant daily periodicity (p < 0.001) in our study population. Consumption was higher around 2 AM (rate 0.4 mg/min·patient) and lower around 12 PM (rate 0.05 mg/min·patient). Global consumption was not associated with the pump start time, age, or sex. The daily periodicity of morphine consumption was different between males and females (p = 0.004), with males consuming more morphine during the night.

Conclusions: Our analysis confirmed the presence of daily rhythm for morphine consumption in patients treated with IV-PCA morphine after major abdominal surgery. A difference in the daily periodicity was observed between sexes. No difference emerged in daily periodicity for the categories of age and BMI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Cavity / surgery*
  • Administration, Intravenous
  • Aged
  • Analgesia, Patient-Controlled / statistics & numerical data*
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / therapeutic use
  • Circadian Rhythm*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morphine / administration & dosage*
  • Morphine / therapeutic use
  • Pain, Postoperative / drug therapy*
  • Sex Characteristics*


  • Analgesics, Opioid
  • Morphine

Associated data