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

Authors

  • Stefano Cattaneo, MD
  • Pablo Ingelmo, MD
  • Luigia Scudeller, MD, PhD
  • Manuela De Gregori, PhD
  • Dario Bugada, MD
  • Marco Baciarello, MD
  • Maurizio Marchesini, MD
  • Giovanni Alberio, MD
  • Marco Normanno, MD
  • Gloria Saccani Jotti, MD
  • Tiziana Meschi, MD
  • Guido Fanelli, MD
  • Massimo Allegri, MD

DOI:

https://doi.org/10.5055/jom.2017.0372

Keywords:

daily rhythm, postoperative pain, patient-controlled analgesia

Abstract

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.

Author Biographies

Stefano Cattaneo, MD

Department of Anesthesia, McGill University, Montreal, Québec, Canada.

Pablo Ingelmo, MD

Allan Edwards Research Center for Pain, Department of Anesthesia, Montreal Children's Hospital, McGill University, Montreal, Québec, Canada

Luigia Scudeller, MD, PhD

Clinical Epidemiology and Biostatistics Unit, Scientific Direction, IRCCS Policlinic San Matteo Foundation, Pavia, Italy

Manuela De Gregori, PhD

Pain Therapy Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Dario Bugada, MD

Department of Surgical Science, University of Parma, Parma, Italy

Marco Baciarello, MD

Department of Surgical Science, University of Parma, Parma, Italy; Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliera Universitaria Parma, Parma, Italy

Maurizio Marchesini, MD

Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliera Universitaria Parma, Parma, Italy

Giovanni Alberio, MD

Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliera San Gerardo, Monza, Italy

Marco Normanno, MD

Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliera San Gerardo, Monza, Italy

Gloria Saccani Jotti, MD

Faculty of Medicine, Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T), University of Parma, Parma, Italy

Tiziana Meschi, MD

Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy

Guido Fanelli, MD

Department of Surgical Science, University of Parma, Parma, Italy; Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliera Universitaria Parma, Parma, Italy.

Massimo Allegri, MD

Department of Surgical Science, University of Parma, Parma, Italy; Anesthesia, Intensive Care and Pain Therapy Service, Azienda Ospedaliera Universitaria Parma, Parma, Italy

References

Gan TJ, Habib AS, Miller TE, et al.: Incidence, patient satisfaction, and perceptions of post-surgical pain: Results from a US national survey. Curr Med Res Opin. 2014; 30(1): 149-160.

Allegri M, Clark MR, De Andres J, et al.: Acute and chronic pain: Where we are and where we have to go. Miner Anestesiol. 2012; 78(2): 222-235.

Apfelbaum JL, Chen C, Mehta SS, et al.: Postoperative pain experience: Results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003;

(2): 534-540.

McNicol ED, Ferguson MC, Hudcova J: Patient controlled opioid analgesia versus non-patient controlled opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2015; 6: Cd003348.

Barletta JF, Senagore AJ: Reducing the burden of postoperative ileus: Evaluating and implementing an evidence-based strategy. World J Surg. 2014; 38(8): 1966-1977.

Myles PS, Wengritzky R: Simplified postoperative nausea and vomiting impact scale for audit and post-discharge review. Br J Anaesth. 2012; 108(3): 423-429.

Pasero C: Assessment of sedation during opioid administration for pain management. J Perianesth Nurs. 2009; 24(3): 186-190.

McQuay HJ, Poon KH, Derry S, et al.: Acute pain: Combination treatments and how we measure their efficacy. Br J Anaesth. 2008; 101(1): 69-76.

Grass JA: Patient-controlled analgesia. Anesth Analg. 2005; 101(5 suppl): S44-S61.

Oderda G: Challenges in the management of acute postsurgical pain. Pharmacotherapy. 2012; 32(9 suppl):6S-11S.

Theodoraki K, Staikou C, Fassoulaki A: Postoperative pain after major abdominal surgery: Is it gender relatedϿ. An observational prospective study. Pain Pract. 2014; 14(7): 613-619.

Gagliese L, Gauthier LR, Macpherson AK, et al.: Correlates of postoperative pain and intravenous patient-controlled analgesia use in younger and older surgical patients. Pain Med. 2008; 9(3): 299-314.

De Gregori M, Garbin G, De Gregori S, et al.: Genetic variability at COMT but not at OPRM1 and UGT2B7 loci modulates morphine analgesic response in acute postoperative pain. Eur J Clin Pharmacol. 2013; 69(9): 1651-1658.

Diatchenko L, Robinson JE, Maixner W: Elucidation of muopioid gene structure: How genetics can help predict responses to opioids. Eur J Pain Suppl. 2011; 5(2): 433-438.

Aubrun F, Bunge D, Langeron O, et al.: Postoperative morphine consumption in the elderly patient. Anesthesiology. 2003; 99(1): 160-165.

Belfer I, Segall SK, Lariviere WR, et al.: Pain modality- and sex-specific effects of COMT genetic functional variants. Pain. 2013; 154(8): 1368-1376.

Allegri M, De Gregori M, Niebel T, et al.: Pharmacogenetics and postoperative pain: A new approach to improve acute pain management. Miner Anestesiol. 2010; 76(11): 937-944.

Costantini R, Affaitati G, Fabrizio A, et al.: Controlling pain in the post-operative setting. Int J Clin Pharmacol Ther. 2011; 49(02): 116-127.

Grantcharov TP, Rosenberg J: Vertical compared with transverse incisions in abdominal surgery. Eur J Surg. 2001; 167(4): 260-267.

Lee CW, Ho IK: Sex differences in opioid analgesia and addiction: Interactions among opioid receptors and estrogen receptors. Mol Pain. 2013; 9:45.

Paller CJ, Campbell CM, Edwards RR, et al.: Sex-based differences in pain perception and treatment. Pain Med. 2009; 10(2): 289-299.

Krizo JA, Mintz EM: Sex differences in behavioral circadian rhythms in laboratory rodents. Front Endocrinol. 2014; 5: 234.

Ballantyne JC, Carr DB, Chalmers TC, et al.: Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials. J Clin Anesth. 1993; 5(3): 182-193.

Gogenur I, Wildschiotz G, Rosenberg J: Circadian distribution of sleep phases after major abdominal surgery. Br J Anaesth. 2008; 100(1): 45-49.

Auvil-Novak SE: A middle-range theory of chronotherapeutic intervention for postsurgical pain. Nurs Res. 1997; 46(2): 66-71.

Boscariol R, Gilron I, Orr E: Chronobiological characteristics of postoperative pain: Diurnal variation of both static and dynamic pain and effects of analgesic therapy. Can J Anaesth. 2007; 54(9): 696-704.

Graves DA, Batenhorst RL, Bennett RL, et al.: Morphine requirements using patient-controlled analgesia: Influence of diurnal variation and morbid obesity. Clin Pharm. 1983; 2(1): 49-53.

Closs SJ: Patients' night-time pain, analgesic provision and sleep after surgery. Int J Nurs Stud. 1992; 29(4): 381-392.

Chassard D, Bruguerolle B: Chronobiology and anesthesia. Anesthesiology. 2004; 100(2): 413-427.

Auvil-Novak SE: The chronobiology, chronopharmacology and chronotherapeutics of pain. Annu Rev Nurs Res. 1999; 17: 133-153.

Labrecque G, Vanier MC: Biological rhythms in pain and in the effects of opioid analgesics. Pharmacol Ther. 1995; 68(1): 129-147.

Bruguerolle B, Labrecque G: Rhythmic pattern in pain and their chronotherapy. Adv Drug Deliv Rev. 2007; 59(9-10): 883-895.

Fillingim RB, Gear RW: Sex differences in opioid analgesia: Clinical and experimental findings. Eur J Pain. 2004; 8(5): 413-425.

Kissin I: Patient-controlled-analgesia analgesimetry and its problems. Anesth Analg. 2009; 108(6): 1945-1949.

Chassard D, Duflo F, de Queiroz Siqueira M, et al.: Chronobiology and anaesthesia. Curr Opin Anaesthesiol. 2007; 20(3): 186-190.

Barreca T, Siani C, Franceschini R, et al.: Diurnal betaendorphin changes in human cerebrospinal fluid. Life Sci. 1986; 38(24): 2263-2267.

Vescovi PP, Rastelli G, Volpi R, et al.: Circadian variations in plasma ACTH, cortisol and beta-endorphin levels in normal-weight bulimic women. Neuropsychobiology. 1996; 33(2): 71-75.

Puig MM, Laorden ML, Miralles FS, et al.: Endorphin levels in cerebrospinal fluid of patients with postoperative and chronic pain. Anesthesiology. 1982; 57(1): 1-4.

Yan L, Silver R: Neuroendocrine underpinnings of sex differences in circadian timing systems. J Steroid Biochem Mol Biol. 2016; 60: 118-126.

Burns JW, Hodsman NB, McLintock TT, et al.: The influence of patient characteristics on the requirements for postoperative analgesia. A reassessment using patient-controlled analgesia. Anaesthesia. 1989; 44(1): 2-6.

McDowell AL, Fransen KM, Elliott KS, et al.: Sex differences and the impact of chronic stress and recovery on instrumental learning. Neuroscience J. 2015; 2015: 697-659.

Cheng HG, Phillips MR: Secondary analysis of existing data: Opportunities and implementation. Shanghai Arch Psychiatry. 2014; 26(6): 371-375.

Dahan A, Kest B, Waxman AR, et al.: Sex-specific responses to opiates: Animal and human studies. Anesth Analg. 2008; 107(1): 83-95.

Published

03/01/2017

How to Cite

Cattaneo, MD, S., P. Ingelmo, MD, L. Scudeller, MD, PhD, M. De Gregori, PhD, D. Bugada, MD, M. Baciarello, MD, M. Marchesini, MD, G. Alberio, MD, M. Normanno, MD, G. S. Jotti, MD, T. Meschi, MD, G. Fanelli, MD, and M. Allegri, MD. “Sex Differences in the Daily Rhythmicity of Morphine Consumption After Major Abdominal Surgery”. Journal of Opioid Management, vol. 13, no. 2, Mar. 2017, pp. 85-94, doi:10.5055/jom.2017.0372.