Analgesia for anticoagulated patients requires substituting gabapentin for ibuprofen

To the Editor

Older Brazilians with various cardiovascular disorders (e.g., atrial fibrillation, venous thrombosis, pulmonary embolia) are often provided long-term treatment with a vitamin K antagonist (i.e., warfarin) or direct acting oral anticoagulants (DAOAs) such as dabigatran, apixaban¹ . Many members of this patient cohort often require complex dental implant procedures with anticipated moderate to severe post-operative pain. This scenario heralds a number of clinical dilemmas. Non-steroidal anti-inflammatory medications (NSAIDs) and specifically ibuprofen are most commonly prescribed for their analgesic effects but may not provide adequate pain relief² , ³ . Secondly, NSAIDs adversely effect platelet function and when concurrently administrated with an anticoagulant medication be it a vitamin K antagonist or a DAOA there are enhanced risks of significantly bleeding. Thirdly, there are both societal concerns regarding the addictive properties and diversion of opioid medications as well as the need for Brazilian dentists to adhere to a set of stringent recommendations as to how the medications are to be administered as well as legal regulations (Regulamento Técnico sobre substâncias e medicamentos sujeitos a controle especial) set in place limiting their prescribing⁴ - ⁶ .

Thus, our interest was peaked when coming upon two prospective, double-blinded, placebo-controlled studies. The first demonstrating that an orally administered preoperative dose of gabapentin (600mg.) significantly (p=0.004) decreased the need for post-operative “narcotic rescue” pain medication administration among patients undergoing rhinoplasty and endoscopic sinus surgery⁷ . The second demonstrating that the perioperative administration of gabapentin (1,200mg. preoperatively and 600 mg. 3 times a day postoperatively) to patients having total hip arthroplasty increased by 24% (H.R. 1.24; 95% CI, 1.20-1.54) the rate of opioid cessation after surgery⁸ .

Gabapentin’s perioperative anti-inflammatory effects result from its ability to reduce pro-inflammatory mediators (e.g., TNF-α, IL β, and IL-6) and up-regulate anti-inflammatory cytokine IL-10). Its acute (nociceptive) pain analgesic effect, by binding to calcium channels thereby inhibiting the influx of calcium into nerve endings thus decreasing excitatory neurotransmitter release in the central and peripheral nervous systems. Concomitantly, analgesia is also believed garnered from gabapentin’s activation of the descending noradrenergic pain inhibitory system⁹ , ¹⁰ .

In summary, our review of the medical literature suggests that patients concurrently receiving anticoagulant medications and presenting for dental implant surgery be administered oral gabapentin 600mg. one hour prior to surgery in order to decrease the inflammatory (painful) surgical insult (i.e., pre-emptive analgesic effect) and that the post-operative regimen consist of gabapentin 600mg combined with acetaminophen 500mg. every 6 hours as needed for pain control.

The institution of our suggested regimen however should be held in abeyance until consultation with the patient’s physician for patients having renal impairment or those having chronic obstructive pulmonary disease (COPD). These admonitions specifically because gabapentin is not metabolized in the body and is eliminated solely by renal clearance, therefore, toxic levels may arise in those with chronic kidney disease and because respiratory depression may arise in those with COPD because gabapentin acts centrally. Furthermore, patients need to be advised that gabapentin administration has been associated with somnolence resulting in impaired driving capabilities as well as dizziness increasing the propensity of falling.

References

• ¹
  Marcolino MS, Polanczyk CA, Bovendorp AC, Marques NS, Silva LA, Turquia CP, et al. Economic evaluation of the new oral anticoagulants for the prevention of thromboembolic events: a cost-minimization analysis. São Paulo Med J. 2016 Jul-Sep;134(4):322-9. doi: 10.1590/1516-3180.2016.0019260216.
  » https://doi.org/10.1590/1516-3180.2016.0019260216
• ²
  Pereira GM, Cota LO, Lima RP, Costa FO. Effect of preemptive analgesia with ibuprofen in the control of postoperative pain in dental implant surgeries: A randomized, triple-blind controlled clinical trial. J Clin Exp Dent. 2020 Jan;12(1):e71-e78. doi: 10.4317/medoral.56171.
  » https://doi.org/10.4317/medoral.56171
• ³
  Cruz AJSD, Santos JS, Pereira Júnior EA, Ruas CM, Mattos FF, Castilho LS, et al. Prescriptions of analgesics and anti-inflammatory drugs in municipalities from a Brazilian Southeast state. Braz Oral Res. 2020 Dec;35:e011. doi: 10.1590/1807-3107bor-2021.vol35.0011.
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• ⁴
  Maia LO, Daldegan-Bueno D, Fischer B. Opioid use, regulation, and harms in Brazil: a comprehensive narrative overview of available data and indicators. Subst Abuse Treat Prev Policy. 2021 Jan;16(1):12. doi: 10.1186/s13011-021-00348-z.
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• ⁵
  Brazilian Ministry of Health. Ordinance No. 834, of May 14, 2013. Redefines the National Committee for the Promotion of Rational Use of Medicines within the scope of the Ministry of Health. Brasília: Brazilian Ministry of Health; 2013 [cited 2022 Jan 27]. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/gm/2013/prt0834_14_05_2013.html Portuguese.
  » https://bvsms.saude.gov.br/bvs/saudelegis/gm/2013/prt0834_14_05_2013.html
• ⁶
  Brazilian Ministry of Health. Ordinance No 344, of May 12, 1998. Approves the Technical Regulation on substances and medicines subject to special control. Brasília: Brazilian Ministry of Health; 2013 [cited 2022 Jan 27]. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/svs/1998/prt0344_12_05_1998_rep.html Portuguese.
  » https://bvsms.saude.gov.br/bvs/saudelegis/svs/1998/prt0344_12_05_1998_rep.html
• ⁷
  Kazak Z, Meltem Mortimer N, Sekerci S. Single dose of preoperative analgesia with gabapentin (600 mg) is safe and effective in monitored anesthesia care for nasal surgery. Eur Arch Otorhinolaryngol. 2010 May;267(5):731-6. doi: 10.1007/s00405-009-1175-5.
  » https://doi.org/10.1007/s00405-009-1175-5
• ⁸
  Hah J, Mackey SC, Schmidt P, McCue R, Humphreys K, Trafton J, et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort: a randomized clinical trial. JAMA Surg. 2018 Apr;153(4):303-11. doi: 10.1001/jamasurg.2017.4915. Erratum in: JAMA Surg. 2018 Apr 1;153(4):396.
  » https://doi.org/10.1001/jamasurg.2017.4915
• ⁹
  Chincholkar M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review. Br J Anaesth. 2018 Jun;120(6):1315-34. doi: 10.1016/j.bja.2018.02.066.
  » https://doi.org/10.1016/j.bja.2018.02.066
• ¹⁰
  Anfuso CD, Olivieri M, Fidilio A, Lupo G, Rusciano D, Pezzino S, et al. Gabapentin attenuates ocular inflammation: in vitro and in vivo studies. Front Pharmacol. 2017 Apr;8:173. doi: 10.3389/fphar.2017.00173.
  » https://doi.org/10.3389/fphar.2017.00173

• Data Availability
  Datasets related to this article will be available upon request from the corresponding author.

Edited by

Editor: Altair A. Del Bel Cury

Data availability

Data Availability

Datasets related to this article will be available upon request from the corresponding author.

Publication Dates

• Publication in this collection
  28 Aug 2023
• Date of issue
  2023

History

• Received
  24 Apr 2022
• Accepted
  10 June 2022