Skip to main content
SpringerLink
Log in

Dysphagia as a Missing Link Between Post-surgical- and Opioid-Related Pneumonia

  • DYSPHAGIA and PNEUMONIA
  • Published:
Lung Aims and scope Submit manuscript

Abstract

Purpose

Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk.

Methods

Eight healthy adult cats were evaluated to determine changes in airway protection status and for evidence of dysphagia in two experiments. (1) In four female cats, airway protection status was tracked following routine abdominal surgery (spay surgery) plus low-dose opioid administration (buprenorphine 0.015 mg/kg, IM, q8-12 h; n = 5). (2) Using a cross-over design, four naive cats (2 male, 2 female) were treated with moderate-dose (0.02 mg/kg) or high-dose (0.04 mg/kg) buprenorphine (IM, q8-12 h; n = 5).

Results

Airway protection was significantly affected in both experiments, but the most severe deficits occurred post-surgically as 75% of the animals exhibited silent aspiration.

Conclusion

Oropharyngeal swallow is impaired by the partial mu-opioid receptor agonist buprenorphine, most remarkably in the postoperative setting. These findings have implications for the prevention and management of aspiration pneumonia in vulnerable populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Haller L et al (2022) Post-operative dysphagia in anterior cervical discectomy and fusion. Ann Otol Rhinol Laryngol 131(3):289–294

    Article  PubMed  Google Scholar 

  2. Goeze A et al (2022) Post-operative prevalence of dysphagia in head-and-neck cancer patients in the acute care units. Laryngorhinootologie 101(4):320–326

    PubMed  Google Scholar 

  3. Greenberg JA et al (2022) Evaluation of post-operative dysphagia following anti-reflux surgery. Surg Endosc 36(7):5456–5466

    Article  PubMed  Google Scholar 

  4. Hayes M et al (2022) Prevalence, nature and trajectory of dysphagia postoesophageal cancer surgery: a prospective longitudinal study protocol. BMJ Open 12(9):e058815

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nath A et al (2016) Dysphagia after vertical sleeve gastrectomy: Evaluation of risk factors and assessment of endoscopic intervention. World J Gastroenterol 22(47):10371–10379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Skoretz SA et al (2020) A systematic review of tracheostomy modifications and swallowing in adults. Dysphagia 35(6):935–947

    Article  PubMed  PubMed Central  Google Scholar 

  7. Garibaldi RA et al (1981) Risk factors for postoperative pneumonia. Am J Med 70(3):677–680

    Article  CAS  PubMed  Google Scholar 

  8. Arozullah AM et al (2001) Development and validation of a multifactorial risk index for predicting postoperative pneumonia after major noncardiac surgery. Ann Intern Med 135(10):847–857

    Article  CAS  PubMed  Google Scholar 

  9. Kozlow JH et al (2003) Epidemiology and impact of aspiration pneumonia in patients undergoing surgery in Maryland, 1999–2000. Crit Care Med 31(7):1930–1937

    Article  PubMed  Google Scholar 

  10. Chughtai M et al (2017) The epidemiology and risk factors for postoperative pneumonia. J Clin Med Res 9(6):466–475

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chughtai M et al (2017) The incidence of postoperative pneumonia in various surgical subspecialties: a dual database analysis. Surg Technol Int 30:45–51

    PubMed  Google Scholar 

  12. Steffens C et al (2020) The association between prescribed opioid receipt and community-acquired pneumonia in adults: a systematic review and meta-analysis. J Gen Intern Med 35(11):3315–3322

    Article  PubMed  PubMed Central  Google Scholar 

  13. Almirall J et al (2013) Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly. Eur Respir J 41(4):923–928

    Article  PubMed  Google Scholar 

  14. Jean A (2001) Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol Rev 81(2):929–969

    Article  CAS  PubMed  Google Scholar 

  15. Pitts T, Iceman KE (2023) Deglutition and the regulation of the swallow motor pattern. Physiology 38(1):10–24

    Article  Google Scholar 

  16. Gupte T, Knack A, Cramer JD (2022) Mortality from aspiration pneumonia: incidence, trends, and risk factors. Dysphagia 37(6):1493–1500

    Article  PubMed  Google Scholar 

  17. Bateman JT, Saunders SE, Levitt ES (2023) Understanding and countering opioid-induced respiratory depression. Br J Pharmacol 180(7):813–828

    Article  CAS  PubMed  Google Scholar 

  18. Roughan JV, Flecknell PA (2002) Buprenorphine: a reappraisal of its antinociceptive effects and therapeutic use in alleviating post-operative pain in animals. Lab Anim 36(3):322–343

    Article  CAS  PubMed  Google Scholar 

  19. Koehl JL, Zimmerman DE, Bridgeman PJ (2019) Medications for management of opioid use disorder. Am J Health Syst Pharm 76(15):1097–1103

    Article  PubMed  Google Scholar 

  20. Foley KM (1993) Opioids. Neurol Clin 11(3):503–522

    Article  CAS  PubMed  Google Scholar 

  21. Roy S et al (2011) Opioid drug abuse and modulation of immune function: consequences in the susceptibility to opportunistic infections. J Neuroimmune Pharmacol 6(4):442–465

    Article  PubMed  PubMed Central  Google Scholar 

  22. Patel D, Vaezi M (2018) Opioid-induced esophageal dysfunction: an emerging entity with sweeping consequences. Curr Treat Options Gastroenterol 16(4):616–621

    Article  PubMed  Google Scholar 

  23. Patel DA et al (2022) Opioid exposure differentially impacts esophageal body contraction over the lower esophageal sphincter. Gastroenterology 163(2):403–410

    Article  PubMed  Google Scholar 

  24. Savilampi J et al (2014) Aspiration induced by remifentanil: a double-blind, randomized, crossover study in healthy volunteers. Anesthesiology 121(1):52–58

    Article  CAS  PubMed  Google Scholar 

  25. Tagaito Y, Isono S, Nishino T (1998) Upper airway reflexes during a combination of propofol and fentanyl anesthesia. Anesthesiology 88(6):1459–1466

    Article  CAS  PubMed  Google Scholar 

  26. Olfson M et al (2020) Trends in buprenorphine treatment in the United States, 2009–2018. JAMA 323(3):276–277

    Article  PubMed  PubMed Central  Google Scholar 

  27. Shulman M, Wai JM, Nunes EV (2019) Buprenorphine treatment for opioid use disorder: an overview. CNS Drugs 33(6):567–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Elkader A, Sproule B (2005) Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet 44(7):661–680

    Article  CAS  PubMed  Google Scholar 

  29. Davis MP, Pasternak G, Behm B (2018) Treating chronic pain: an overview of clinical studies centered on the buprenorphine option. Drugs 78(12):1211–1228

    Article  PubMed  PubMed Central  Google Scholar 

  30. Robinson SE (2002) Buprenorphine: an analgesic with an expanding role in the treatment of opioid addiction. CNS Drug Rev 8(4):377–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhuang J et al (2017) Mu-opioid receptors in the caudomedial NTS are critical for respiratory responses to stimulation of bronchopulmonary C-fibers and carotid body in conscious rats. Respir Physiol Neurobiol 235:71–78

    Article  CAS  PubMed  Google Scholar 

  32. Maletz SN et al (2022) Nucleus tractus solitarius neurons activated by hypercapnia and hypoxia lack Mu opioid receptor expression. Front Mol Neurosci 15:932189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hardemark Cedborg AI et al (2015) Effects of morphine and midazolam on pharyngeal function, airway protection, and coordination of breathing and swallowing in healthy adults. Anesthesiology 122(6):1253–1267

    Article  CAS  PubMed  Google Scholar 

  34. Frazure M et al (2024) Serotonin therapies for opioid-induced disordered swallow and respiratory depression. J Appl Physiol (1985). https://doi.org/10.1152/japplphysiol.00509.2023

    Article  PubMed  Google Scholar 

  35. Steagall P, Monteiro-Steagall B, Taylor P (2014) A review of the studies using buprenorphine in cats. J Vet Intern Med 28(3):762–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Steagall PV et al (2009) Dose-related antinociceptive effects of intravenous buprenorphine in cats. Vet J 182(2):203–209

    Article  CAS  PubMed  Google Scholar 

  37. Plumb DC (2005) Plumb’s veterinary drug handbook. 2005: Fifth edition. Stockholm, Wis. : PhrmaVet ; Ames, Iowa : Distributed by Blackwell Pub

  38. Holman SD et al (2013) Development, reliability, and validation of an infant mammalian penetration-aspiration scale. Dysphagia 28(2):178–187

    Article  PubMed  Google Scholar 

  39. Rosenbek JC et al (1996) A penetration-aspiration scale. Dysphagia 11(2):93–98

    Article  CAS  PubMed  Google Scholar 

  40. Martin-Harris B et al (2008) MBS measurement tool for swallow impairment–MBSImp: establishing a standard. Dysphagia 23(4):392–405

    Article  PubMed  PubMed Central  Google Scholar 

  41. Tang W et al (2015) Kappa coefficient: a popular measure of rater agreement. Shanghai Arch Psychiatry 27(1):62–67

    PubMed  PubMed Central  Google Scholar 

  42. Shrout PE, Fleiss JL (1979) Intraclass correlations: uses in assessing rater reliability. Psychol Bull 86(2):420–428

    Article  CAS  PubMed  Google Scholar 

  43. Gharavi R et al (2015) Transporter-mediated disposition of opioids: implications for clinical drug interactions. Pharm Res 32(8):2477–2502

    CAS  PubMed  Google Scholar 

  44. Waldhoer M, Bartlett SE, Whistler JL (2004) Opioid receptors. Annu Rev Biochem 73:953–990

    Article  CAS  PubMed  Google Scholar 

  45. Williams JT et al (2013) Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 65(1):223–254

    Article  PubMed  PubMed Central  Google Scholar 

  46. Pasternak GW, Pan YX (2013) Mu opioids and their receptors: evolution of a concept. Pharmacol Rev 65(4):1257–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Pitts T, Iceman KE (2023) Deglutition and the regulation of the swallow motor pattern. Physiology (Bethesda) 38(1):10

    Google Scholar 

  48. Ramirez JM et al (2021) Neuronal mechanisms underlying opioid-induced respiratory depression: our current understanding. J Neurophysiol 125(5):1899–1919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bolser DC, DeGennaro FC (1994) Effect of codeine on the inspiratory and expiratory burst pattern during fictive cough in cats. Brain Res 662(1–2):25–30

    Article  CAS  PubMed  Google Scholar 

  50. Lang IM, Marvig J (1989) Functional localization of specific receptors mediating gastrointestinal motor correlates of vomiting. Am J Physiol 256(1 Pt 1):G92–G99

    CAS  PubMed  Google Scholar 

  51. Blivis D et al (2007) Differential effects of opioids on sacrocaudal afferent pathways and central pattern generators in the neonatal rat spinal cord. J Neurophysiol 97(4):2875–2886

    Article  CAS  PubMed  Google Scholar 

  52. Irnaten M et al (2003) Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus. Neuroscience 116(2):573–582

    Article  CAS  PubMed  Google Scholar 

  53. Rommel N, Hamdy S (2016) Oropharyngeal dysphagia: manifestations and diagnosis. Nat Rev Gastroenterol Hepatol 13(1):49–59

    Article  PubMed  Google Scholar 

  54. Logemann JA (2007) Swallowing disorders. Best Pract Res Clin Gastroenterol 21(4):563–573

    Article  PubMed  Google Scholar 

  55. Logemann JA (1997) Role of the modified barium swallow in management of patients with dysphagia. Otolaryngol Head Neck Surg 116(3):335–338

    Article  CAS  PubMed  Google Scholar 

  56. Donner MW (1985) Radiologic evaluation of swallowing. Am Rev Respir Dis 131(5):S20–S23

    CAS  PubMed  Google Scholar 

  57. German RZ et al (2017) Animal models for dysphagia studies: what have we learnt so far. Dysphagia 32(1):73–77

    Article  PubMed  PubMed Central  Google Scholar 

  58. Lever TE et al (2015) Videofluoroscopic validation of a translational murine model of presbyphagia. Dysphagia 30(3):328–342

    Article  PubMed  Google Scholar 

  59. Harris RA et al (2017) Standardization of a videofluoroscopic swallow study protocol to investigate dysphagia in dogs. J Vet Intern Med 31(2):383–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Stevens M et al (2021) Pathophysiology of aspiration in a unilateral SLN lesion model using quantitative analysis of VFSS. Int J Pediatr Otorhinolaryngol 140:110518

    Article  PubMed  Google Scholar 

  61. Cullins MJ, Connor NP (2019) Reduced tongue force and functional swallowing changes in a rat model of post stroke dysphagia. Brain Res 1717:160–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kobara-Mates M et al (1995) Physiology of oropharyngeal swallow in the cat: a videofluoroscopic and electromyographic study. Am J Physiol 268(2 Pt 1):G232–G241

    CAS  PubMed  Google Scholar 

  63. Sampson S, Eyzaguirre C (1964) Some functional characteristics of mechanoreceptors in the larynx of the cat. J Neurophysiol 27:464–480

    Article  CAS  PubMed  Google Scholar 

  64. Pitts T et al (2013) Coordination of cough and swallow: a meta-behavioral response to aspiration. Respir Physiol Neurobiol 189(3):543–551

    Article  PubMed  Google Scholar 

  65. Karlsson JA, Lanner AS, Persson CG (1990) Airway opioid receptors mediate inhibition of cough and reflex bronchoconstriction in guinea pigs. J Pharmacol Exp Ther 252(2):863–868

    CAS  PubMed  Google Scholar 

  66. Kamei J (1996) Role of opioidergic and serotonergic mechanisms in cough and antitussives. Pulm Pharmacol 9(5–6):349–356

    Article  CAS  PubMed  Google Scholar 

  67. Kamei J et al (1989) Subsensitivity to the cough-depressant effects of opioid and nonopioid antitussives in morphine-dependent rats: relationship to central serotonin function. Pharmacol Biochem Behav 34(3):595–598

    Article  CAS  PubMed  Google Scholar 

  68. Babaei A et al (2019) Chronic daily opioid exposure is associated with dysphagia, esophageal outflow obstruction, and disordered peristalsis. Neurogastroenterol Motil 31(7):e13601

    Article  PubMed  PubMed Central  Google Scholar 

  69. Finnerty CC et al (2013) The surgically induced stress response. JPEN J Parenter Enteral Nutr 37(5 Suppl):21S-S29

    PubMed  PubMed Central  Google Scholar 

  70. Priebe HJ (2016) Pharmacological modification of the perioperative stress response in noncardiac surgery. Best Pract Res Clin Anaesthesiol 30(2):171–189

    Article  PubMed  Google Scholar 

  71. Kohl BA, Deutschman CS (2006) The inflammatory response to surgery and trauma. Curr Opin Crit Care 12(4):325–332

    Article  PubMed  Google Scholar 

  72. Iscoe S (1998) Control of abdominal muscles. Prog Neurobiol 56(4):433–506

    Article  CAS  PubMed  Google Scholar 

  73. Depauw P et al (2019) The significance of intra-abdominal pressure in neurosurgery and neurological diseases: a narrative review and a conceptual proposal. Acta Neurochir (Wien) 161(5):855–864

    Article  PubMed  Google Scholar 

  74. Pitts T et al (2022) Laryngeal and swallow dysregulation following acute cervical spinal cord injury. J Neurophysiol 128(2):405–417

    Article  PubMed  PubMed Central  Google Scholar 

  75. Pitts T et al (2015) Effect of laparotomy on the swallow-breathing relationship in the cat. Lung 193(1):129–133

    Article  PubMed  Google Scholar 

  76. Sanchez MJ et al (2022) Chronic opioid use is associated with obstructive and spastic disorders in the esophagus. Neurogastroenterol Motil 34(3):e14233

    Article  CAS  PubMed  Google Scholar 

  77. Snyder DL, Vela MF (2020) Opioid-induced esophageal dysfunction. Curr Opin Gastroenterol 36(4):344–350

    Article  PubMed  Google Scholar 

  78. Patel D, Callaway J, Vaezi M (2019) Opioid-induced foregut dysfunction. Am J Gastroenterol 114(11):1716–1725

    Article  PubMed  Google Scholar 

  79. Hiss SG, Treole K, Stuart A (2001) Effects of age, gender, bolus volume, and trial on swallowing apnea duration and swallow/respiratory phase relationships of normal adults. Dysphagia 16(2):128–135

    Article  CAS  PubMed  Google Scholar 

  80. Riley LH 3rd et al (2005) Dysphagia after anterior cervical decompression and fusion: prevalence and risk factors from a longitudinal cohort study. Spine 30(22):2564–9

    Article  PubMed  Google Scholar 

  81. Bollschweiler E et al (2008) Prevalence of dysphagia in patients with gastroesophageal reflux in Germany. Dysphagia 23(2):172–176

    Article  PubMed  Google Scholar 

  82. Mori T et al (2022) Association between inflammation and functional outcome in patients with sarcopenic dysphagia. J Nutr Health Aging 26(4):400–406

    Article  CAS  PubMed  Google Scholar 

  83. Huff A et al (2020) Sex-specific vagal and spinal modulation of swallow and its coordination with breathing. PLoS ONE 15(6):e0234194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Fishman MA, Kim PS (2018) Buprenorphine for chronic pain: a systemic review. Curr Pain Headache Rep 22(12):83

    Article  PubMed  Google Scholar 

Download references

Funding

Research reported in this publication was supported by NIH Grants NS110169, HL155721, HL163008, HD110951, NS097781, OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, Rebecca Hammond Endowment and the Commonwealth of Kentucky Challenge for Excellence. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, USA

    Michael Frazure

  2. Department of Neurological Surgery and Kentucky Spinal Cord Injury Research Center, College of Medicine, University of Louisville, Louisville, KY, USA

    Michael Frazure & Dena R. Howland

  3. Department of Speech Language and Hearing Sciences and Dalton Cardiovascular Center, University of Missouri, 701 S Fifth St, Columbia, MO, 65203, USA

    Clinton L. Greene, Kimberly E. Iceman & Teresa Pitts

Authors
  1. Michael Frazure
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clinton L. Greene
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kimberly E. Iceman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dena R. Howland
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Teresa Pitts
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to conception and design of the study. MF, CLG and TP collected data. MF, KEI and TP analyzed data and prepared figures. MF, KEI and TP wrote the initial draft. All authors edited, revised and reviewed the final manuscript.

Corresponding author

Correspondence to Teresa Pitts.

Ethics declarations

Conflict of interest

No conflicts of interest, financial or otherwise, are declared by the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1 (DOCX 27 kb)

Supplementary file 2 (M4V 13074 kb)

Supplementary file 3 (M4V 22300 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frazure, M., Greene, C.L., Iceman, K.E. et al. Dysphagia as a Missing Link Between Post-surgical- and Opioid-Related Pneumonia. Lung 202, 179–187 (2024). https://doi.org/10.1007/s00408-024-00672-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-024-00672-8

Keywords

Search

Navigation