Evaluating Dexmedetomidine: A Viable Non-Opioid Alternative to Remifentanil in Anesthesia and Perioperative Care

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Introduction

Fentanyl and its analogs, such as remifentanil, sufentanil, and alfentanil, are vital components of modern anesthesia and pain management, valued for their rapid onset, potent analgesic effects, and ability to maintain hemodynamic stability during surgical procedures. These agents are crucial for achieving the necessary balance of unconsciousness, analgesia, and autonomic stability in patients undergoing surgery. However, the increasing incidence of fentanyl shortages has forced healthcare providers to seek alternative therapeutic options. Among these, dexmedetomidine, a selective alpha-2 adrenergic agonist, has emerged as a promising substitute, particularly in scenarios where fentanyl analogs are unavailable or in limited supply. In light of recent shortages of fentanyl, particularly remifentanil, it is crucial to evaluate dexmedetomidine as a reliable alternative for perioperative and critical care management.¹

Clinical Impact of Drug Shortages

The clinical consequences of opioid drug shortages, particularly those involving essential anesthetic agents like remifentanil, are profound. A 2023 retrospective study conducted at a tertiary care hospital in Vienna revealed the significant repercussions of a nationwide remifentanil shortage. During this period, patients in perioperative intensive care units (ICUs) experienced longer durations of mechanical ventilation (risk ratio [RR] 2.19; 95% confidence interval [CI] 2.14 to 2.24; p< 0.001), extended ICU stays (p< 0.001), prolonged non-invasive ventilation periods (p< 0.001), and longer overall hospital stays (p< 0.001) compared to those treated when remifentanil was readily available. The shortage also led to an increased need for secondary tracheostomy (p< 0.001), underscoring the adverse effects of such shortages on critical care outcomes. These findings highlight the urgent need for vigilant monitoring and the development of alternative strategies to mitigate the negative impacts of drug shortages on patient care².

However, the anesthesiology community faces even broader challenges due to shortages of perioperative medications, including opioids and anesthetics. Regrettably, an increased potential for medication errors, prolonged recovery times, and decreased patient satisfaction have been observed during these shortages. Emphasizing the ethical responsibility of clinicians to inform patients about drug shortages is crucial, along with prioritizing shared decision-making to enhance patient engagement and satisfaction. By involving patients in the decision-making process and considering their values and preferences, healthcare providers can make more informed and personalized treatment decisions, particularly when standard medications are in short supply^2,3.

Potential of a Non-Opioid Alternative: Dexmedetomidine

In response to the challenges posed by these shortages, the anesthesiology community has turned to alternative agents like dexmedetomidine. This shift is reflected in several recent studies that evaluate the efficacy and safety of dexmedetomidine in various clinical settings.

For instance, a 2023 meta-analysis (N= 543) compared the effectiveness of dexmedetomidine and remifentanil for controlled hypotension during general anesthesia. The analysis found no significant differences between dexmedetomidine and remifentanil in terms of surgical field scores (mean difference [MD] -0.03; 95% CI -0.39 to 0.33; p= 0.86), blood loss (MD 4.07; 95% CI -7.95 to 16.09; p= 0.51), or hemodynamic parameters such as minimum mean arterial pressure (MD 0.24; 95% CI -1.65 to 2.13; p= 0.80) and heart rate (MD 0.42; 95% CI -1.33 to 2.17; p= 0.64). Both agents were effective in achieving controlled hypotension and satisfactory surgical conditions. However, dexmedetomidine was associated with a significantly lower visual analog score in the post-anesthesia care unit (PACU) (MD -1.01; 95% CI -1.25 to -0.77; p< 0.00001) and reduced incidence of shivering (odds ratio [OR] 0.22; 95% CI 0.08 to 0.60; p= 0.003), nausea, and vomiting (OR 0.34; 95% CI 0.13 to 0.89; p= 0.03) compared to remifentanil. Conversely, remifentanil had a shorter extubation time (MD 3.34; 95% CI 0.75 to 5.93; p= 0.01), highlighting a trade-off between faster recovery and improved postoperative comfort⁵.

Further supporting dexmedetomidine's potential, another recent meta-analysis (N= 1,309) found that general anesthesia with dexmedetomidine led to significantly lower postoperative pain scores (MD -0.7; 95% CI -1.2 to -0.2; p= 0.004) and reduced opioid consumption at 24 hours (MD -4.6 mg morphine equivalents; 95% CI -7.7 to -1.4; p= 0.004). Similarly, this study also observed fewer episodes of hypotension, shivering, and postoperative nausea and vomiting. However, despite these benefits, dexmedetomidine was found to be associated with longer extubation times (MD 4.9 minutes; 95% CI 0.8 to 9.1; p= 0.02) and extended recovery area stays (MD 8.9 minutes; 95% CI 4.4 to 13.4; p< 0.0001), which could impact its use in settings where quick recovery is paramount⁶.

In a different surgical context, a retrospective study (N= 42) comparing dexmedetomidine and remifentanil for sedation during Descemet's membrane endothelial keratoplasty under locoregional anesthesia found that those receiving dexmedetomidine reported higher satisfaction scores (p< 0.01 for patients; p< 0.001 for surgeons) and deeper sedation levels without compromising respiratory function. Specifically, 62% of patients in the dexmedetomidine group achieved a Ramsay score of 3 (responding only to commands) compared to 23% in the remifentanil group, while 77% of remifentanil patients had a Ramsay score of 2 (cooperative and oriented) compared to 38% in the dexmedetomidine group (p< 0.02). These results suggest that dexmedetomidine could be a favorable option for sedation in procedures requiring locoregional anesthesia, despite its association with more pronounced decreases in systolic blood pressure (mean decrease of 25 ± 13 mm Hg vs. 11 ± 16 mm Hg; p= 0.002)⁷.

Interestingly, additional available evidence analyzing dexmedetomidine during endobronchial ultrasound-guided transbronchial needle aspiration also found that dexmedetomidine resulted in fewer respiratory adverse events (0 [interquartile range (IQR), 0 to 0.5] episodes per patient) compared to remifentanil (2 [IQR 0 to 5] episodes per patient; p= 0.001). Nevertheless, dexmedetomidine was associated with a longer recovery time (10 [IQR 3 to 37.5] minutes) compared to remifentanil (3 [IQR 3 to 5] minutes; p< 0.001). This indicates that while dexmedetomidine may reduce respiratory complications, its longer recovery period might make it less suitable for outpatient procedures⁸. Similarly, patients administered dexmedetomidine experienced significantly lower pain scores at 30 minutes post-procedure (4.0 ± 1.9 vs. 6.1 ± 2.0; p< 0.001) and required fewer rescue analgesics compared to those who received remifentanil (25% vs. 66.7%; p< 0.001).

Overall, dexmedetomidine has consistently outperformed remifentanil, demonstrating superior outcomes and even exhibiting a propofol-sparing effect, which suggests a distinct advantage over other alpha-2 agonists, such as clonidine. With its faster onset, shorter duration of action, and higher potency, dexmedetomidine is particularly effective in perioperative care, making it a superior alternative to remifentanil for managing postoperative pain and reducing opioid-related side effects ^9,10.

Conclusions

Available evidence indicates that the ongoing shortage of remifentanil and other fentanyl analogs poses significant challenges to anesthetic and pain management practices, with potentially severe implications for patient outcomes. The shortage has led to extended mechanical ventilation durations, prolonged ICU stays, and increased procedural complications, such as the need for secondary tracheostomy, emphasizing the need for vigilant monitoring and alternative therapies during drug shortages¹. Dexmedetomidine, a selective alpha-2 adrenergic agonist, has emerged as a promising alternative, offering effective sedation and analgesia, reducing postoperative pain and opioid-related side effects, and maintaining hemodynamic stability, though it presents challenges such as longer extubation times and a higher incidence of bradycardia^{2,3,4,5,6,7,8,9}. While it shows promise, careful consideration of its risks and continued research are essential to optimize its use and mitigate the impact of drug shortages on patient care, ensuring that both safety and efficacy are maintained in these critical clinical settings⁹. 

 

Parameter	Dexmedetomidine	Remifentanil	References
Sedative Effectiveness	Effective sedation with deeper levels in certain procedures	Effective sedation, typically with faster recovery	[7,8]
Analgesic Effectiveness	Lower postoperative pain scores; reduced opioid consumption	Effective analgesia, standard in many protocols	[6,9]
Hemodynamic Stability	Maintains hemodynamic stability; notable for hypotensive effects	Maintains stability; quicker recovery from hypotensive effects	[5,7]
Respiratory Adverse Events	Fewer respiratory adverse events, but longer recovery times	More respiratory events, but quicker discharge	[8]
Postoperative Recovery	Longer extubation times and PACU stays	Shorter extubation times and quicker recovery	[5,6]
Side Effects	Lower incidence of shivering, nausea, vomiting; higher incidence of bradycardia	Less bradycardia, but higher incidence of shivering, nausea, vomiting	[5,6,7,8]
Propofol-Sparing Effect	Sparing effect observed, which may reduce the need for propofol	Not typically associated with a propofol-sparing effect	[9]
Patient/Surgeon Satisfaction	Higher satisfaction in certain procedures (e.g., DMEK)	Standard satisfaction Often favored for quick recovery	[7]
Considerations
·      Dexmedetomidine offers advantages like reduced postoperative pain and fewer opioid-related side effects but may lead to longer recovery times and increased bradycardia risk. ·      Dexmedetomidine's role as an effective alternative during fentanyl analog shortages highlights its importance, but careful monitoring and risk assessment are crucial.

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References:

• Smith G, D'Cruz JR, Rondeau B, et al. General Anesthesia for Surgeons. [Updated 2023 Aug 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493199/
• Klaus DA, de Bettignies AM, Seemann R, Krenn CG, Roth GA. Impact of a remifentanil supply shortage on mechanical ventilation in a tertiary care hospital: a retrospective comparison. Crit Care. 2018;22(1):267. Published 2018 Oct 26. doi:10.1186/s13054-018-2198-3
• Ammar MA, Sacha GL, Welch SC, et al. Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages. J Intensive Care Med. 2021;36(2):157-174. doi:10.1177/0885066620951426
• Nimmo AF, Absalom AR, Bagshaw O, et al. Guidelines for the safe practice of total intravenous anaesthesia (Tiva): joint guidelines from the association of anaesthetists and the society for intravenous anaesthesia. Anaesthesia. 2019;74(2):211-224. https://doi.org/10.1111/anae.14428
• Xu N, Chen L, Liu L, Rong W. Dexmedetomidine versus remifentanil for controlled hypotension under general anesthesia: A systematic review and meta-analysis. PLoS One. 2023;18(1):e0278846. Published 2023 Jan 17. doi:10.1371/journal.pone.0278846
• Grape S, Kirkham KR, Frauenknecht J, Albrecht E. Intra-operative analgesia with remifentanil vs. dexmedetomidine: a systematic review and meta-analysis with trial sequential analysis. Anaesthesia. 2019;74(6):793-800. doi:10.1111/anae.14657
• Mencucci R, De Vitto C, Cennamo M, Pierucci S, Adembri C. Dexmedetomidine versus remifentanil monitored anesthesia care during endothelial keratoplasty: a retrospective study. Cornea Open. 2023;2(3):e0014. doi:10.1097/coa.0000000000000014
• St-Pierre P, Tanoubi I, Verdonck O, et al. Dexmedetomidine Versus Remifentanil for Monitored Anesthesia Care During Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Randomized Controlled Trial. Anesth Analg. 2019;128(1):98-106. doi:10.1213/ANE.0000000000003633
• Koo JM, Chung YJ, Lee M, Moon YE. Efficacy of Dexmedetomidine vs. Remifentanil for Postoperative Analgesia and Opioid-Related Side Effects after Gynecological Laparoscopy: A Prospective Randomized Controlled Trial. J Clin Med. 2023;12(1):350. Published 2023 Jan 2. doi:10.3390/jcm12010350
• Hughes LM, Irwin MG, Nestor CC. Alternatives to remifentanil for the analgesic component of total intravenous anaesthesia: a narrative review. Anaesthesia. 2023;78(5):620-625. doi:10.1111/anae.15952

  

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