Invasive and noninvasive procedures

Feature Review Article Dexmedetomidine and ketamine: An effective alternative for procedural sedation? Joseph D. Tobias, MD Objectives: Although generally effective for sedation during noninvasive procedures, dexmedetomidine as the sole agent has not been uniformly successful for invasive procedures. To overcome some of the pitfalls with dexmedetomidine as the sole agent, there are an increasing number of reports regarding its combination with ketamine. This article provides a descriptive account of the reports from the literature regarding the use of a combination of dexmedetomidine and ketamine for procedural sedation. Data Source: A computerized bibliographic search of the literature regarding dexmedetomidine and ketamine for procedural sedation. Measurements and Main Results: The literature contains four reports with cohorts of more than ten patients with a total of 122 patients. Two of these studies were prospective randomized trials. Additionally, there are eight single case reports or small case series (six patients or less) with an additional 21 pediatric patients. When used together, dexmedetomidine may prevent the tachycardia, hypertension, salivation, and emergence phenomena from ketamine, whereas ketamine may prevent the bradycardia and hypotension, which has been reported with dexmedetomidine. An additional benefit is that the addition of ketamine to initiate the sedation process speeds the onset of sedation, thereby eliminating the slow onset time when dexmedetomidine is the sole agent. Although various regimens have been reported in the literature, the most effective regimen appears to be the use of a bolus dose of both agents, dexmedetomidine (1 μg/kg) and ketamine (1 2 mg/ kg), to initiate sedation. This can then be followed by a dexmedetomidine infusion (1 2 μg/kg/hr) with supplemental bolus doses of ketamine (0.5 1 mg/kg) as needed. Conclusions: The available literature except for one trial is favorable regarding the utility of a combination of ketamine and dexmedetomidine for procedural sedation. Future studies with direct comparisons to other regimens appear warranted for both invasive and noninvasive procedures. (Pediatr Crit Care Med 2012; 13:423 427) Key Words: dexmedetomidine; ketamine; procedural sedation Invasive and noninvasive procedures remain a component in the management of children with acute and chronic diseases. In recent years there has been a shift in the philosophy regarding procedural sedation given the increasing recognition of the negative aspects of inadequate sedation. Therefore, more patients are being sedated for procedures and the depth of sedation achieved is increasing in certain environments. Regardless of the procedure, there are several options for the agent or agents chosen for sedation. In the general practice of procedural sedation, propofol is a frequently chosen agent because it can be easily titrated by continuous infusion, is generally effective, and allows for rapid From the Departments of Anesthesiology and Pediatrics, Nationwide Children s Hospital and the Ohio State University, Columbus, OH. The author has not disclosed any potential conflicts of interest. For information regarding this article, E-mail: Joseph.Tobias@Nationwidechildrens.org Copyright 2012 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0b013e318238b81c awakening once the procedure is completed. However, in patients with comorbid respiratory or cardiovascular diseases, there may be a relatively high incidence of respiratory effects, including hypotension, hypoventilation, upper airway obstruction, and apnea (1 6). Although these effects are generally dose-dependent and more likely with higher doses as deeper levels of sedation/anesthesia are achieved, there is significant interpatient variability regarding the potential for adverse effects (7). Given these concerns, the search for alternative agents continues. Dexmedetomidine (Precedex; Hospira Worldwide, Lake Forest, IL) exerts its physiologic effects through the α 2 - adrenergic receptor system. Initial Food and Drug Administration approval in the United States for the administration of dexmedetomidine occurred in 1999. At that time, approval was granted for the sedation of adults during mechanical ventilation. Additional approval was granted in 2009 for monitored anesthesia care in adults. Although Food and Drug Administration-approved only for use in adults, dexmedetomidine continues to be used successfully in several different clinical scenarios in infants and children, including procedural sedation (8). Although generally effective for sedation during noninvasive procedures, dexmedetomidine as the sole agent has not been uniformly successful for invasive procedures (9 13). In the first prospective evaluation of dexmedetomidine as the sole agent during an invasive procedure in infants and children, Munro et al (9) reported their experience with dexmedetomidine during cardiac catheterization. After oral premedication with midazolam and the placement of intravenous access, dexmedetomidine was administered as a loading dose of 1 μg/kg over 10 mins, followed by an infusion of 1 μg/kg/hr titrated up to 2 μg/ kg/hr as needed. Five of the 20 patients (25%) moved during local infiltration of the groin, which did not require treatment or interfere with cannulae placement. Twelve (60%) patients received a propofol bolus during the procedure for movement, an increasing bispectral index number, or anticipation of a stimulus. Subsequent studies in the adult population have similarly demonstrated that dexmedetomidine may not be the Pediatr Crit Care Med 2012 Vol. 13, No. 4 423

Table 1. Large case series regarding dexmedetomidine ketamine for procedural sedation in infants and children Author Type of Study and Cohort Size Outcomes Tosun et al (16) Koruk et al (17) Mester et al (18) McVey and Tobias (19) Prospective randomized trial comparing dexmedetomidine ketamine with propofol ketamine sedation in 44 pediatric patients during cardiac catheterization Prospective randomized trial comparing dexmedetomidine ketamine with midazolam-ketamine in 50 pediatric patients for extracorporeal shock wave lithotripsy Retrospective case series using dexmedetomidine and ketamine for sedation during cardiac catheterization. No comparative group was included. The cohort included 16 children ranging in age from 16 mos to 15 yrs Retrospective case series using dexmedetomidine and ketamine for sedation during lumbar puncture for spinal anesthesia. No comparative group was included. The study cohort included 12 children ranging in age from 2 to 9 yrs Sedation managed effectively with both regimens. Patients sedated with ketamine dexmedetomidine required more ketamine (2.03 ± 1.33 vs. 1.25 ± 0.67 mg/kg/hr; p <.01), more frequently required supplemental doses of ketamine (10 of 22 patients vs. 4 of 22 patients), and had a longer recovery time (median time of 45 vs. 20 mins; p =.01). Sedation was equally effective in both groups. Times for eye-opening, verbal response, and cooperation were decreased in the dexmedetomidine ketamine group. The incidence of nausea and vomiting was lower with dexmedetomidine ketamine (4.7% vs. 32%). No patients responded to infiltration of the groin with local anesthetic and placement of the arterial and venous cannulae. Three patients required a supplemental dose of ketamine. In two patients, the dexmedetomidine infusion was decreased because of heart rate changes. Two patients had development of upper airway obstruction that responded to repositioning of the airway. The lumbar puncture for the performance of spinal anesthesia was tolerated in all of the patients. One patient required a decrease of the dexmedetomidine infusion for bradycardia. One patient required a fluid bolus for blood pressure of 68/38 mm Hg. Two patients had upper airway obstruction that resolved with repositioning of the airway. optimal agent for painful procedures. Jalowiecki et al (10) reported that dexmedetomidine was ineffective during colonoscopy in adults and was associated with a high incidence of adverse effects, including a prolonged delay in discharge times. The authors closed the study before completion (12). Similar issues were encountered when comparing dexmedetomidine with midazolam for monitored anesthesia care in adults during cataract surgery (13). In specific clinical scenarios, the response to failures with usual doses (1 2 μg/kg) has been to switch to or to add alternative agents or to increase the dose of dexmedetomidine (14, 15). However, when such dose escalations are attempted, a higher incidence of hemodynamic effects such as bradycardia and hypotension has been noted. Given these issues, the addition of a second agent to dexmedetomidine rather than dose escalations may be the preferred option. Procedural Sedation With Dexmedetomidine and Ketamine. Issues of concern when considering dexmedetomidine as an agent for procedural sedation include a long onset time, limited analgesic effect, and the potential for hemodynamic effects, including bradycardia and hypotension, especially when larger doses are administered. Although limited in number when compared to reports using only dexmedetomidine, there have been several reports in the literature regarding the use of a dexmedetomidine ketamine combination for procedural sedation in the pediatric population (Table 1) (16 19). Two of these reports have been prospective randomized trials with a comparison to another sedation regimen (16, 17). Tosun et al (16) compared a procedural sedation regimen that included dexmedetomidine and ketamine with one that combined propofol and ketamine. The study cohort included 44 children, ranging in age from 4 months to 16 yrs, with acyanotic congenital heart disease undergoing cardiac catheterization. Ketamine (1 mg/kg) and dexmedetomidine (1 μg/kg) were administered over 10 mins, followed by infusions of dexmedetomidine at 0.7 μg/kg/hr and ketamine at 1 mg/kg/hr. In the other arm of the study, propofol (1 mg/kg) and ketamine (1 mg/kg) were administered as the loading dose, followed by a propofol infusion at 100 μg/kg/hr and ketamine at 1 mg/kg/ hr. In both arms of the study, supplemental bolus doses of ketamine (1 mg/kg) were available as needed. Although sedation was effective with both regimens, the propofol ketamine combination was superior. Patients sedated with dexmedetomidine ketamine required more ketamine (2.03 ± 1.33 vs. 1.25 ± 0.67 mg/kg/ hr; p <.01) and more frequently required supplemental doses of ketamine (10/22 patients vs. 4/22 patients). Additionally, the recovery time was longer with dexmedetomidine and ketamine (median time, 45 vs. 20 mins; p =.01). No clinically significant differences in the hemodynamic or respiratory status were noted between the two groups. Koruk et al (17) prospectively compared sedation using dexmedetomidine and ketamine to a regimen using midazolam and ketamine during extracorporeal shock wave lithotripsy in a cohort of 50 pediatric patients who ranged in age from 2 to 15 yrs. Patients received either a bolus dose of dexmedetomidine (1 μg/kg over 10 mins) and ketamine (1 mg/kg) or a bolus dose of midazolam (0.05 mg/kg) and ketamine (1 mg/kg). Patients were then observed by an anesthesiologist who was blinded to which medications they had received. Sedation was equally effective in both groups without clinically significant changes in the hemodynamic and respiratory parameters. Although there was no difference in the time to achieve an Aldrete score of 8, the times for eye opening, verbal 424 Pediatr Crit Care Med 2012 Vol. 13, No. 4

Table 2. Small case series and isolated case reports regarding dexmedetomidine ketamine for procedural sedation Author Type of Study and Cohort Size Dosing Regimen for Dexmedetomidine and Ketamine Outcomes Bozdogan et al (21) Barton et al (22) Luscri and Tobias (23) Irvani and Wald (24) Mahmoud et al (25) Munro et al (26) Rozmiarek et al (27) Corridore et al (28) Sedation during caudal anesthesia in three high-risk infants (ages 5, 6, and 10 mos) with a history of ongoing or recent acute viral upper respiratory infections and congenital heart disease Procedural sedation in six infants (age 3 d to 29 mos) with congenital heart disease Case series of three children with trisomy 21 who required sedation during a magnetic resonance imaging scan for evaluation of sleep apnea 6-yr-old girl with Treacher Collins syndrome and severe micrognathia 4-yr-old, 20-kg boy with a large mediastinal mass and tracheal compression 12-yr-old, 31-kg boy with pulmonary hypertension 21-yr-old, 43-kg man with Duchenne muscular dystrophy with compromised cardiac and respiratory function A 3-yr-old, 14-kg girl with a mediastinal mass and tracheal compression Bolus dose of ketamine (1 mg/kg) dexmedetomidine. The bolus dose of both agents was repeated to achieve a Ramsay sedation scale score of 4. This was followed by a dexmedetomidine infusion at 0.7 1 μg/kg/hr, titrated to maintain a Ramsay sedation scale score of 4 during the surgery Dexmedetomidine was administered at an average dose of 1.5 μg/kg (range, 1 3 μg/kg). Three of the 6 patients (50%) required bolus doses of ketamine (0.3 0.5 mg/kg) because of movement during the procedure Sedation was initiated with a bolus dose of ketamine (1 mg/kg) and dexmedetomidine (1 μg/kg) and maintained by a dexmedetomidine infusion (1 μg/ kg/hr). One patient required a repeat of the bolus doses of ketamine and dexmedetomidine and an increase of the dexmedetomidine infusion to 2 μg/kg/hr A bolus dose of dexmedetomidine 1 μg/kg was followed by a continuous infusion at 1 μg/kg/hr. Once a Ramsay sedation scale score of 5 (sluggish response to glabellar tap) was achieved, three incremental doses of ketamine (0.25 mg/kg) were administered until there was no response to a glabellar tap A loading dose of dexmedetomidine (2 μg/kg) and ketamine (0.5 mg/kg) were administered. Propofol (1 mg/kg) was administered to facilitate placement of an laryngeal mask airway. The anesthetic was maintained with a dexmedetomidine infusion at 2 μg/kg/hr) and ketamine boluses to a total dose of 30 mg Premedication with midazolam (2 mg) and ketamine (15 mg) followed by dexmedetomidine (1 μg/ kg) and an additional dose of ketamine (15 mg). Dexmedetomidine infusion at 1 μg/kg/hr during the procedure and at 0.5 μg/kg/hr for 2 hrs after the procedure Dexmedetomidine was administered as a loading dose of 1 μg/kg along with ketamine (20 mg). This was followed by a dexmedetomidine infusion at 1 μg/kg/hr. An additional 10 mg of ketamine was administered during the procedure Dexmedetomidine (1 μg/kg) and ketamine (1 mg/ kg) were administered over 5 mins followed by a dexmedetomidine infusion at 0.5 μg/kg/min. Additional doses of ketamine (0.3 0.5 mg/kg) were administered every 30 45 mins as needed based on the patient s response to the procedure Caudal epidural block was achieved and surgical procedure was completed without difficulty. No clinically significant change in hemodynamic or respiratory status was noted Effective sedation was achieved and the procedure was completed without incident. No clinically significant change in hemodynamic or respiratory status was noted The scan required that no artificial airway be used so that the exact point of airway obstruction could be identified. Effective sedation was achieved with no significant respiratory or hemodynamic effects. A brief episode of upper airway obstruction occurred in one patient, which responded to repositioning of the airway. All three patients had mild hypercarbia with maximum ETco 2 of 49, 53, and 52 mm Hg Effective sedation for fiberoptic intubation while maintaining spontaneous ventilation Successful completion of the procedure that included biopsy of the anterior mediastinal mass, lumbar puncture, and bone marrow aspiration. Spontaneous ventilation was maintained throughout the procedure. Effective sedation during cardiac catheterization Effective sedation for bone marrow and biopsy Effective sedation for the 135-min procedure that included biopsy of a large anterior cervical lymph node and placement of a percutaneous intravenous central catheter response, and cooperation were decreased in the dexmedetomidine ketamine group. Additionally, the incidence of nausea and vomiting was significantly lower with dexmedetomidine ketamine compared with midazolam ketamine (4.7% vs. 32%). Two other large case series provide us with retrospective information regarding the combination of dexmedetomidine and ketamine for procedural sedation without a comparative group (18, 19). Mester et al (18) retrospectively reviewed the use of dexmedetomidine and ketamine for sedation during cardiac catheterization in 16 children with congenital heart disease, ranging in age from 16 months to 15 yrs old. A bolus dose of ketamine (2 mg/kg) and dexmedetomidine (1 μg/kg) mixed in a single syringe was administered over 3 mins, followed by a continuous infusion Pediatr Crit Care Med 2012 Vol. 13, No. 4 425

of dexmedetomidine at 2 μg/kg/hr for the initial 30 mins and then 1 μg/kg/hr for the duration of the case. No patient responded to infiltration of the groin and placement of the arterial and venous cannulae for cardiac catheterization. Three patients required a supplemental dose of ketamine (1 mg/kg). In two of these patients, the bolus dose of ketamine was administered before changing the vascular cannulae in the middle of the procedure. In two patients, the dexmedetomidine infusion was decreased from 2 to 1 μg/ kg/hr at 12 15 mins instead of 30 mins because of a decrease in heart rate. Two patients had development of upper airway obstruction that responded to repositioning of the airway. No central apnea was noted. Although the Paco 2 was 45 mm Hg in seven patients, the maximum value was 48 mm Hg. More recently, McVey and Tobias (19) described their experience using these agents during lumbar puncture for spinal anesthesia in 12 pediatric patients. The dosing regimen was the same as that reported by Mester et al. The lumbar puncture for the performance of spinal anesthesia was tolerated in all of the patients without movement or the need for supplemental agent. The heart rate decrease was 20% from baseline in 5 of 12 patients, although only one patient required intervention with an early decrease of the dexmedetomidine infusion. One patient had a blood pressure decrease of 20% from baseline. This patient had fasted for over 10 hrs before surgery and had a low blood pressure reading of 68/38 mm Hg that responded to a fluid bolus of 10 ml/kg. Upper airway obstruction in two patients resolved with repositioning of the airway. Additional information regarding the potential utility of a dexmedetomidine ketamine combination is provided by Zor et al (20) in their study of 24 adults undergoing burn dressing changes. A secondary outcome of the study was to find the most effective means of limiting the adverse effects related to the administration of ketamine. Twenty-four adults were randomized into one of three groups. Group 1 received ketamine (2 mg/kg), group 2 received tramadol (1 mg/kg) followed 30 mins later by ketamine (2 mg/ kg) and dexmedetomidine (1 μg/kg), whereas group 3 received tramadol (1 mg/ kg) followed 30 mins later by ketamine (2 mg/kg) and midazolam (0.05 mg/kg). The authors reported improved analgesia and a decreased incidence of adverse effects, including emergence phenomena and hallucinations related to ketamine in patients who received dexmedetomidine (group 2). Additional anecdotal experience in small retrospective case series or individual case reports have consistently demonstrated the utility of dexmedetomidine in conjunction with ketamine for procedures in which a deep level of sedation is required while maintaining spontaneous respiration (Table 2) (21 28). Several of these reports have included patients with significant comorbid conditions, including pulmonary hypertension, upper airway obstruction with sleep apnea, tracheal compression from a mediastinal mass, congenital heart disease, as well as compromised cardiac and respiratory function. These reports, which have included a total of 21 pediatric patients, demonstrate that a dexmedetomidine ketamine combination effectively achieves the desired level of sedation while minimizing the potential for adverse effects. CONCLUSION Given its limited analgesic effects, dexmedetomidine does not appear to be the ideal agent for painful procedures. However, anecdotal experience and a few large series from the literature demonstrate the utility of a combination of dexmedetomidine with ketamine for procedural sedation. When used together, dexmedetomidine may limit the tachycardia, hypertension, salivation, and emergence phenomena from ketamine, whereas ketamine may prevent the bradycardia and hypotension that has been reported with dexmedetomidine (20, 29, 30). Additionally, the addition of ketamine to dexmedetomidine to initiate the sedation process speeds the onset of sedation and eliminates the slow onset time when dexmedetomidine is used as the sole agent with the loading dose administered over 10 mins. When used in such a scenario, the two agents can be coadministered from a single syringe. Although various regimens have been reported in the literature, the most effective regimen appears to be the use of a bolus dose of both agents, dexmedetomidine (1 μg/kg) and ketamine (1 2 mg/kg), to initiate sedation. This can then be followed by a dexmedetomidine infusion (1 2 μg/kg/ hr) with supplemental bolus doses of ketamine (0.5 1 mg/kg) as needed. Although still relatively preliminary, the current literature supports the potential utility of the combination of ketamine and dexmedetomidine for procedural sedation, even in patients with compromised respiratory or cardiac function. When compared with other agents used for procedural sedation, these two agents have limited effects on ventilatory function when compared with other more commonly used agents (4, 31). Future studies may take one of two directions. Because there are no direct comparisons of dexmedetomidine as the sole agent for sedation vs. a dexmedetomidine ketamine combination, this may be one venue. If the dexmedetomidine ketamine combination is superior, then direct comparisons to other commonly used regimens (propofol) appear warranted for both invasive and noninvasive procedures. Given the increased cost of a dexmedetomidine regimen, whenever such studies are performed, attention to the cost-benefits ratio including manpower issues of recovery times should be included. REFERENCES 1. Hertzog JH, Dalton HJ, Anderson BD, et al: Prospective evaluation of propofol anesthesia in the pediatric intensive care unit for elective oncology procedures in ambulatory and hospitalized children. Pediatrics 2000; 106:742 747 2. Hertzog JH, Campbell JK, Dalton HJ, et al: Propofol anesthesia for invasive procedures in ambulatory and hospitalized children: Experience in the pediatric intensive care unit. Pediatrics 1999; 103:e30 3. Cravero JP, Beach ML, Blike GT, et al: The incidence and nature of adverse events during pediatric sedation/anesthesia with propofol for procedures outside the operating room: A report from the Pediatric Sedation Research Consortium. Anesth Analg 2009; 108:795 804 4. Koroglu A, Teksan H, Sagir O, et al: A comparison of the sedative, hemodynamic and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging. Anesth Analg 2006; 103:63 67 5. Mahmoud M, Gunter J, Donnelly LF, et al: A comparison of dexmedetomidine with propofol for magnetic resonance imaging sleep studies in children. Anesth Analg 2009; 109:745 753 6. Brussel T, Theissen JL, Vigfusson G, et al: Hemodynamic and cardiodynamic effects of propofol and etomidate: Negative inotropic properties of propofol. Anesth Analg 1989; 69:35 40 7. Malviya S, Voepel-Lewis T, Tait AR: Adverse events and risk factors associated with the sedation of children by non-anesthesiologists. Anesth Analg 1997; 85:1207 1213 426 Pediatr Crit Care Med 2012 Vol. 13, No. 4

8. Tobias JD: Dexmedetomidine: Applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med 2007; 8:115 131 9. Munro HM, Tirotta CF, Felix DE, et al: Initial experience with dexmedetomidine for diagnostic and interventional cardiac catheterization in children. Pediatr Anesth 2007; 17:109 112 10. Young ET: Dexmedetomidine sedation in a pediatric cardiac patient scheduled for MRI. Can J Anaesth 2005; 52:730 732 11. Heard CMB, Joshi P, Johnson K: Dexmedetomidine for pediatric sedation: A review of a series of cases. Pediatr Anesth 2007; 17:888 892 12. Jalowiecki P, Rudner R, Gonciarz M, et al: Sole use of dexmedetomidine has limited utility for conscious sedation during outpatient colonoscopy. Anesthesiology 2005; 103:269 273 13. Alhashemi JA: Dexmedetomidine vs. midazolam for monitored anaesthesia care during cataract surgery. Br J Anaesth 2006; 96:722 726 14. Mason KP, Zurakowski D, Zgleszewski SE, et al: High dose dexmedetomidine as the sole sedative for pediatric MRI. Paediatr Anaesth 2008; 18:403 411 15. Mason KP, Prescilla R, Fontaine PJ, et al: Pediatric CT sedation: Comparison of dexmedetomidine and pentobarbital. Am J Roentgenol 2011; 196:W194 W198 16. Tosun Z, Akin A, Guler G, et al: Dexmedetomidine-ketamine and propofol-ketamine combinations for anesthesia in spontaneously breathing pediatric patients undergoing cardiac catheterization. J Cardiothor Vasc Anesth 2006; 20:515 519 17. Koruk S, Mizrak A, Gul R, et al: Dexmedetomidine-ketamine and midazolamketamine combinations for sedation in pediatric patients undergoing extracorporeal shock wave lithotripsy: A randomized prospective study. J Anesth 2010; 24:858 863 18. Mester R, Easley RB, Brady KM, et al: Monitored anesthesia care with a combination of ketamine and dexmedetomidine during cardiac catheterization. Am J Ther 2008; 15:24 30 19. McVey JD, Tobias JD: Dexmedetomidine and ketamine for sedation during spinal anesthesia in children. J Clin Anesth 2010; 22:538 545 20. Zor F, Ozturk S, Bilgin F, et al: Pain relief during dressing changes of major adult burns: Ideal analgesia combination with ketamine. Burns 2010; 36:501 505 21. Bozdogan N, Sener M, Caliskan E, et al: A combination of ketamine and dexmedetomidine sedation with caudal anesthesia during incarcerated inguinal hernia repair in three high-risk infants. Pediatr Anesth 2008; 18:1009 1011 22. Barton KP, Munoz R, Morell VO, et al: Dexmedetomidine as the primary sedative during invasive procedures in infants and toddlers with congenital heart disease. Pediatr Crit Care Med 2008; 9:612 615 23. Luscri N, Tobias JD: Monitored anesthesia care with a combination of ketamine and dexmedetomidine during magnetic resonance imaging in three children with trisomy 21 and obstructive sleep apnea. Pediatr Anesth 2006; 16:782 786 24. Iravani M, Wald SH: Dexmedetomidine and ketamine for fiberoptic intubation in a child with severe mandibular hypoplasia. J Clin Anesth 2008; 20:455 457 25. Mahmoud M, Tyler T, Sadhasivam S: Dexmedetomidine and ketamine for large anterior mediastinal mass biopsy. Pediatr Anesth 2008; 18:1011 1013 26. Munro HM, Felix DE, Nykanen DG: Dexmedetomidine/ketamine for diagnostic cardiac catheterization in a child with idiopathic pulmonary hypertension. J Clin Anesth 2009; 21:435 438 27. Rozmiarek A, Corridore M, Tobias JD: Dexmedetomidine-ketamine sedation during bone marrow aspirate and biopsy in a patient with duchenne muscular dystrophy. Saudi J Anaesth 2011; 5:219 222 28. Corridore M, Phillips A, Rabe A, et al: Dexmedetomidine-ketamine sedation in a child with a mediastinal mass. World J Pediatr Cong Heart Surg (in press) 29. Levänen J, Mäkelä ML, Scheinin H: Dexmedetomidine premedication attenuates ketamine-induced cardiostimulatory effects and postanesthetic delirium. Anesthesiology 1995; 82:1117 1125 30. Dilek O, Yasemin G, Atci M: Preliminary experience with dexmedetomidine in neonatal anesthesia. J Anesth Clin Pharm 2011; 27:17 22 31. Koroglu A, Demirbilek S, Teksan H, et al: Sedative, hemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results. Br J Anaesth 2005; 94:821 824 Pediatr Crit Care Med 2012 Vol. 13, No. 4 427