ISSN: 2455-3484
Journal of Addiction Medicine and Therapeutic Science
Research Article       Open Access      Peer-Reviewed

Use of a combination of ketamine and dexmedetomidine (Ketodex) in different clinical cases

Somchai Amornyotin*

Department of Anesthesiology and Siriraj GI Endoscopy Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
*Corresponding author: Somchai Amornyotin, Department of Anesthesiology and Siriraj GI Endoscopy Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand; Tel: 66-2-419-7990; Fax: 662-4113256; E-mail: somchai.amo@mahidol.ac.th ; amornyotin.somchai@gmail.com
Published: 20 May, 2020 | Accepted: 05 June, 2020 | Received: 06 June, 2020
Keywords: Ketamine; Dexmedetomidine; Clinical use; Efficacy; Safety

Cite this as

Amornyotin S (2020) Use of a combination of ketamine and dexmedetomidine (Ketodex) in different clinical cases. J Addict Med Ther Sci 6(1): 041-044. DOI: 10.17352/2455-3484.000036

Ketodex is a combination of ketamine and dexmedetomidine. Ketamine, an old intravenous anesthetic, is a non-narcotic and non-barbiturate drug. It has several properties of the ideal anesthetic agent. However, ketamine can produce the psychological adverse effects. Dexmedetomidine has analgesic, amnesic, sedative and anxiolytic properties. A distinct advantage of dexmedetomidine is the maintenance of respiratory force and preserved airway patency. It converges on a natural sleep pathway, activating pathways that promote endogenous non-rapid eye movement sleep to exert its sedative effect. However, dexmedetomidine can produce bradycardia and hypotension. A combination of ketamine and dexmedetomidine has several benefits in the terms of hemodynamic stability, absence of respiratory depression, post-operative analgesia and recovery. Several previous studies have been demonstrated the therapeutic utility of the combination of ketamine and dexmedetomidine.

Introduction

Sedoanalgesic drugs are commonly used for sedation and analgesia in several medical procedures. Generally, physicians utilized these agents by the titration technique. Midazolam and fentanyl are the most common sedoanalgesic drugs. Midazolam has the shortest half-life and duration of action, making it an ideal agent when prolonged sedation is not compulsory. Midazolam could be reversed with flumazenil. Fentanyl is a potent synthetic opioid with rapid onset, short duration of action, and lack of direct of myocardial depressant effects. Ketamine is a neuroleptic anesthetic agent. It produces analgesia, a dissociative anesthetic state, and unpleasant psychomimetic effects. Dexmedetomidine is a specific central alpha 2-adrenergic agonist that decreases central presynaptic catecholamine release. Its properties of sedation, anxiolysis and analgesia make it a valuable adjunct for procedural and intensive care sedation.

Dexmedetomidine does not appear to be the ideal agent for painful procedures. When used together with ketamine, dexmedetomidine may limit the tachycardia, hypertension, salivation, and emergence phenomena from ketamine, whereas ketamine may prevent the bradycardia and hypotension from dexmedetomidine. A combination of ketamine and dexmedetomidine has low incidence of adverse effects, good analgesic, predictable recovery and no cardiorespiratory depression [1]. To date, there is substantial interest in ketodex as an agent for procedural sedation and analgesia. This present review focuses on the clinical uses of a combination of ketamine and dexmedetomidine.

Ketodex

Ketamine is a dissociative anesthetic agent and is stable at room temperature. It works on thalamocortical and limbic N-methyl-D-aspartate (NMDA) receptors [2]. Ketamine stimulates the cardiorespiratory systems. It causes an increase in cerebral blood flow, intracranial pressure and cerebral metabolic rate. It should be avoided in the patients with ischemic heart disease, hypertension and raised intraocular pressures. However, ketamine produces unpleasant psychological effects including hallucinations, nightmares and emergence reactions. Ketamine could use by several administration routes.

Dexmedetomidine is a specific central alpha 2-adrenergic agonist primarily in the locus coeruleus. Its favorable properties are sedation, anxiolysis and analgesia as well as no respiratory depression. Furthermore, it provides a more wakeful sedation than other sedatives. Patients are more arousable and alert when stimulated. The most common adverse effects associated with its use for procedural sedation are hypotension and bradycardia. However, dexmedetomidine as the sole agent has not been similarly successful for some invasive procedures [3]. Dexmedetomidine is generally used by intravenous injection. However, it could be used by intramuscular injection or by oral premedication. Dexmedetomidine seemed to show complete bioavailability after intramuscular injection. It seemed to be well absorbed systemically through oral mucosa, the buccal bioavailability being as high as 82% [4]. A combination of ketamine and dexmedetomidine is used. Currently, there is a rising number of reports regarding to this combination (ketodex).

Clinical uses

Tobias presented a descriptive study of the several reports about the use of a combination of ketamine and dexmedetomidine for procedural sedation [5]. His study showed that ketamine could prevent the decrease of blood pressure and heart rate which had been observed with dexmedetomidine. In addition, dexmedetomidine could prevent the increase of blood pressure and heart rate, salivation and psychological emergence reactions from ketamine. Moreover, ketamine initiated the onset of sedation when evaluated with the use of dexmedetomidine alone. The most effective ketodex regimen was the use of a bolus dose of ketamine 1-2 mg/kg and a bolus dose of dexmedetomidine 1 mcg/kg. This regimen might be followed by an infusion of dexmedetomidine 1-2 mcg/kg/h and a supplemental bolus dose of ketamine 0.5-1 mg/kg as needed [5].

Gunduz and coworkers compared the sedoanalgesic effects of the combination of ketamine and dexmedetomidine with the combination of ketamine and midazolam for dressing changes in burn patients. They concluded that both the combination of ketamine and dexmedetomidine and the combination of ketamine and midazolam for burn patients underwent dressing changes were safe and effective. No serious adverse effects were observed. However, ketodex presented in higher sedation and hemodynamic stability [6]. In addition, the combination of ketamine and dexmedetomidine would help to increase pain relief without over sedation in pediatric patients [7].

One previous study evaluated a combination of ketamine with two different doses of dexmedetomidine for sedation during muscle biopsy in patients with Duchenne muscular dystrophy. This previous study confirmed that a combination of dexmedetomidine and ketamine is safe and effective for moderately painful procedures with limited cardiorespiratory effects [8]. Additionally, the successful use of a combination of ketamine and dexmedetomidine (ketodex) for sedation in a 21-year-old patient with Duchenne muscular dystrophy undergoing bone marrow aspiration and biopsy was also presented by Rozmiarek and colleagues [9]. Another case report of the use of ketodex for sedation in a 9-year-old, 45 kg child with Duchenne muscular dystrophy and a history of egg allergy underwent esophagogastroduodenoscopy (EGD) procedure [10]. The utility of ketodex was also demonstrated in management of the elderly patient who experienced airway obstruction during an EGD procedure under anesthesia secondary to previously undiagnosed tracheomalacia [11].

Generally, ketamine induced hemodynamic response and psychological effects including intraoperative hypertension, tachycardia and unpleasant dreams. Premedication with dexmedetomidine should be reduced these responses. Gupta and coworkers compared the clinical efficacy and safety of dexmedetomidine with midazolam for premedication in 80 normotensive adult patients with ASA class I and II. They suggested that dexmedetomidine premedication was safe and effectively reduced the ketamine-induced hemodynamic response and post-operative psychological effects [12]. Furthermore, ketodex offered better analgesia and cardiorespiratory parameters as well as shorter recovery time [13]. Consequently, Sinha and colleagues compared the effectiveness of the combination of ketamine and dexmedetomidine (ketodex) versus dexmedetomidine alone in awaked fiberoptic intubation. The authors concluded that the use of ketodex offered better intubating conditions, sedation and hemodynamic parameters than the use of dexmedetomidine alone in awaked fiberoptic nasotracheal intubation [14].

Ketodex for electroconvulsive therapy (ECT) was reported by Shams and El-Masry [15]. A combination of ketodex and propofol in ECT procedure had an effective antidepression, less agitation and more patient satisfaction when compared to a combination of ketamine and propofol. Another case report of the use of ketodex for sedation in an elderly patient underwent a painful procedure was published [16]. This case report confirmed ketodex possessed sedative and analgesic properties as well as permitted preservation of airway reflexes and respiratory drive. In addition, it had been reported to lessen the incidence of cognitive dysfunction after the procedure in elderly patients [16] and also could be used to produce additional analgesia in complex regional pain syndrome [17].

Ketodex for various procedures in pediatric patients had been reported. McVey and Tobias utilized a bolus dose of ketamine 2 mg/kg and dexmedetomidine 1 mcg/kg given over 3 min followed by a continuous infusion of dexmedetomidine 2 mcg/kg/h for the first 30 min and followed by 1 mcg/kg/h afterward. Supplemental medication was given by ketamine 0.5 mg/kg as needed. They described that the use of ketodex presented effective procedural sedation in pediatric patients with relatively lower cardiorespiratory adverse effects [18]. The use of ketodex for upper gastrointestinal endoscopies [19] and endoscopic retrograde cholangiopancreatography procedure [20] in pediatric patients was reported.

The use of ketodex for non-cardiac surgery in pediatric patients with cyanotic heart diseases [21,22] and pulmonary embolism with history of pulmonary arterial hypertension with history of PAH and pulmonary embolism were also reported [23]. For cardiac catheterization procedure, ketodex was tried to utilize in this procedure [24]. Another case report of ketodex infusion used for a 15-year-old girl who underwent scoliosis repair surgery with intraoperative wake-up test was presented [25]. Moreover, Goyal and Islam also reported a young girl patient with xeroderma pigmentosum previously anesthetized with delayed recovery, accomplished successfully with intravenous ketodex for a surgical procedure [26].

Furthermore, ketodex could be used by intramuscular injection or by oral premedication. For example, the study of intramuscular ketamine, dexmedetomidine and a combination of both (ketodex) for MRI [27] and the study of Ravipati for burn procedures [28], were also evaluated. The study of Singh demonstrated that oral dexmedetomidine provided more effective sedation and fewer adverse effects than oral ketamine [29]. However, a previous study indicated that ketodex was not superior to a combination of sevoflurane and sufentanil in pediatric patients with obstructive sleep apnea [30].

Conclusion

Ketodex is a combination of ketamine and dexmedetomidine. It is a sedoanalgesic agent for procedural sedation and analgesia. A combination of ketamine and dexmedetomidine has several benefits in terms of hemodynamic stability, absence of respiratory depression, post-operative analgesia and recovery. The most effective regimen seems to be the use of a bolus dose of a 1 mcg/kg of dexmedetomidine and a 1-2 mg/kg of ketamine. This could be followed by 1-2 mcg/kg/hr of dexmedetomidine infusion with supplemental bolus doses of 0.5-1 mg/kg of ketamine as needed. The clinical uses of ketodex have been established in the various studies. Future studies with direct comparisons to the other regimens need to be performed.

  1. Pandit JJ (2011) Intravenous anesthetic agents. Anesth Intens Care Med 12: 144-150.
  2. Amornyotin S (2014) Ketamine: pharmacology revisited. Intern J Anesthesiol Res 2: 42-44. Link: https://bit.ly/2z2DFNP
  3. Amornyotin S (2016) Dexmedetomidine in gastrointestinal endoscopic procedures. World J Anesthesiol 5: 1-14. Link: https://bit.ly/2Ua8JCK
  4. Anttila M, Penttila J, Helminen A, Vuorilehto L, Scheinin H (2012) Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol 56: 691-693. Link: https://bit.ly/2XtM3iK
  5. Tobias JD (2012) Dexmedetomidine and ketamine: an effective alternative for procedural sedation? Pediatr Crit Care Med 13: 423-427. Link: https://bit.ly/3gOBFKa
  6. Gunduz M, Sakalh S, Gunes Y, Kesiktas E, Ozcengiz D, et al. (2011) Comparison of effects of ketamine-dexmedetomidine and ketamine-midazolam on dressing changes of burn patients. J Anesthesiol Clin Pharmacol 27: 220-224. Link: https://bit.ly/2Y0Ypy4
  7. Kayyal TA, Wolfswinkel EM, Weathers WM, Capehart SJ, Monson LA, et al. (2014) Treatment effects of dexmedetomidine and ketamine on postoperative analgesia after cleft palate repair. Cranio Maxillofac Trauma Recon 7: 131-138. Link: https://bit.ly/3czi3X7
  8. Kako H, Corridore M, Kean J, Mendell JR, Flanigan KM, et al. (2014) Dexmedetomidine and ketamine sedation for muscle biopsies in patients with Duchenne muscular dystrophy. Pediatr Anesth 24: 851-856.   Link: https://bit.ly/3dAMZHY
  9. Rozmiarek A, Corridore M, Tobias JD (2011) Dexmedetomidine-ketamine sedation during bone marrow aspirate and biopsy in a patient with Duchenne muscular dystrophy. Saudi J Anesth 5: 219-222. Link: https://bit.ly/2XvEVCp
  10. Raman V, Yacob D, Tobias JD (2012) Dexmedetomidine-ketamine sedation during upper gastrointestinal endoscopy and biopsy in a patient with Duchenne muscular dystrophy and egg allergy. Int J Crit Illn Inj Sci 2: 40-43. Link: https://bit.ly/3gRA0mZ
  11. Atkins JH, Mandel JE, Metz DC (2011) Sudden tracheal collapse during EGD and subsequent anesthetic management with dexmedetomidine-ketamine in a patient with achalasia and tracheomalacia. Case Rep Anesthesiol 2011: 281679. Link: https://bit.ly/2Mv2F3A
  12. Gupta K, Gupta A, Gupta PK, Rastogi B, Agarwal S, et al. (2011) Dexmedetomidine premedication in relevance to ketamine anesthesia: a prospective study. Anesth Essays Res 5: 87-91. Link: https://bit.ly/3eMaRZd
  13. Kose EA, Honca M, Yilmaz E, Batislam E, Apan A (2012) Comparison of effects of dexmedetomidine-ketamine and dexmedetomidine-midazolam combinations in transurethral procedures. Urology 79: 1214-1219. Link: https://bit.ly/2XYIZu5
  14. Sinha SK, Joshiraj B, Chaudhary L, Hayaran N, Kaur M, et al. (2014) A comparison of dexmedetomidine plus ketamine combination with dexmedetomidine alone for awake fiberoptic nasotracheal intubation: a randomized controlled study. J Anesthesiol Clin Pharmacol 30: 514-519. Link: https://bit.ly/2XZhPmL
  15. Shams T, El-Masry R (2014) Ketofol-dexmedetomidine combination in ECT: a punch for depression and agitation. Indian J Anesth 58: 275-280. Link: https://bit.ly/304Jw0g
  16. Ong ET, Thong SY (2014) The use of dexmedetomidine and ketamine for sedation and analgesia in an elderly patient undergoing a painful procedure. OA Case Reports 3: 19. Link: https://bit.ly/2BAlznv
  17. Nama S, Meenan DR, Fritz WT (2010) The use of sub-anesthetic intravenous ketamine and adjuvant dexmedetomidine when treating acute pain from CRPS. Pain Physician 13: 365-368. Link: https://bit.ly/2AHnXbe
  18. McVey JD, Tobias JD (2010) Dexmedetomidine and ketamine for sedation during spinal anesthesia in children. J Clin Anesth 22: 538-545. Link: https://bit.ly/2XvDp3b
  19. Goyal R, Singh S, Shukla RN, Patra AK, Bhargava DV (2013) Ketodex, a combination of dexmedetomidine and ketamine for upper gastrointestinal endoscopy in children: a preliminary report. J Anesth 27: 461-463. Link: https://bit.ly/2MFF6Fn
  20. Ko BJ, Jang JH, Park JW, Lee SC, Choi SR (2012) Procedural sedation with dexmedetomidine for pediatric endoscopic retrograde cholangiopancreatography guided stone retraction. Korean J Anesthesiol 63: 567-568. Link: https://bit.ly/2XusaYQ
  21. Goyal R, Singh S, Bangi A, Singh SK (2013) Case series: Dexmedetomidine and ketamine for anesthesia in patients with uncorrected congenital cyanotic heart disease presenting for non-cardiac surgery. J Anesthesiol Clin Pharmacol 29: 543-546. Link: https://bit.ly/3eMbcuW
  22. Hasan MS, Chan L (2014) Dexmedetomidine and ketamine sedation for dental extraction in children with cyanotic heart disease. J Oral Maxillofac Surg 72: 1920.e1-1920.e4. Link: https://bit.ly/3cwPjOL
  23. Raman V, Tobias JD (2013) Dexmedetomidine and pulmonary hypertension: a case report and review of the literature. J Med Cases 4: 481-484. Link: https://bit.ly/3eSaxs3
  24. Mester R, Easley RB, Brady KM, Chilson K, Tobias JD (2008) Monitored anesthesia care with a combination of ketamine and dexmedetomidine during cardiac catheterization. Am J Ther 15: 24-30. Link: https://bit.ly/2MyyRCR
  25. Penney R (2010) Use of dexmedetomidine and ketamine infusions during scoliosis repair surgery with somatosensory and motor-evoked potential monitoring: a case report. AANA J 78: 446-450. Link: https://bit.ly/3dykA55
  26. Goyal R, Islam MS (2015) Dexmedetomidine and ketamine combination for a patient with xeroderma pigmentosa. J Anesth 29: 457-458. Link: https://bit.ly/375ZOYb
  27. Tammam TF (2013) Comparison of the efficacy of dexmedetomidine, ketamine, and a mixture of both for pediatric MRI sedation. Egypt J Anesth 29: 241-246. Link: https://bit.ly/2AzqX9M
  28. Ravipati P, Reddy PN, Kumar C, Pradeep P, Pathapati RM, et al. (2014) Dexmedetomidine decreases the requirement of ketamine and propofol during burns debridement and dressings. Indian J Anesth 58: 138-142. Link: https://bit.ly/3dsFdj8
  29. Singh C, Pandey RK, Saksena AK, Chandra G (2014) A comparative evaluation of analgosedative effects of oral dexmedetomidine and ketamine: a triple-blind, randomized study. Pediatr Anesth 24: 1252-1259. Link: https://bit.ly/3ctAf4x
  30. Cheng X, Huang Y, Zhao Q, Gu E (2014) Comparison of the effects of dexmedetomidine-ketamine and sevoflurane-sufentanil anesthesia in children with obstructive sleep apnea after uvulopalatopharyngoplasty: an observational study. J Anesthesiol Clin Pharmacol 30: 31-35. Link: https://bit.ly/2U8N11I
© 2020 Amornyotin S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.