|Year : 2014 | Volume
| Issue : 2 | Page : 138-142
Dexmedetomidine decreases the requirement of ketamine and propofol during burns debridement and dressings
Prabhavathi Ravipati1, Pothula Narasimha Reddy1, Chaithanya Kumar1, P Pradeep1, Rama Mohan Pathapati2, Sujith Tumkur Rajashekar2
1 Department of Anaesthesiology and Intensive Care, Narayana Medical College and Super Specialty Hospital, ChinthareddyPalem, Nellore, Andhra Pradesh, India
2 Department of Clinical Pharmacology and Clinical Research, Narayana Medical College and Super Specialty Hospital, ChinthareddyPalem, Nellore, Andhra Pradesh, India
|Date of Web Publication||16-Apr-2014|
Department of Anaesthesiology and Intensive Care Narayana Medical College and Super Specialty Hospital Chinthareddy Palem, Nellore - 524 002, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background and Aims: Dexmedetomidine (Dex), a highly selective α2 -adrenoreceptor agonist, is used for sedation management in various clinical settings and shows anaesthetic-sparing effect. Our aim was to study the effects of Dex on requirements of propofol, ketamine, and intraoperative haemodynamic variations during burns debridement and dressing changes, and compare its effectiveness and safety with combination of ketamine and propofol. Methods: Sixty adult patients posted for elective debridement and dressing were included in the study. Thirty patients received Dex (intramuscular)(IM) 1 μg/kg, 1 h before shifting to the operation theatre while the other thirty did not. Anaesthesia was induced with propofol and ketamine followed by adjusted infusion to achieve a Ramsay Sedation Scale score (RSS) of six in all patients. Intraoperatively haemodynamic parameters were recorded at regular intervals of 5, 15, 30, 45, and 60 min. The mean data between the groups were compared by unpaired t test and medians by Mann-Whitney U test. Within group analysis was performed by using repeated measures ANOVA. P < 0.05 was considered significant. Results: The dose requirement of ketamine and propofol in Dex group was significantly lower when compared to control group (100.5 ± 17.58 mg vs. 231.5 ± 60.39 mg (P < 0.0001) and 127.7 ± 15.47 mg vs. 254 ± 59.22 mg (P < 0.0001) respectively). Additionally, recovery time was lower in the Dex group as compared to the control group, 9.57 ± 1.50 min vs. 11.53 ± 2.56 min (P = 0.0006). Haemodynamic variations were also significantly lower in the Dex group as compared to the control group. Conclusion: Dexmedetomidine (1 μg/kg IM) reduced the requirement of propofol and ketamine, with more stable intraoperative haemodynamics.
Keywords: Burns, dexmedetomidine, drug combinations, debridement and dressing of burns, fentanyl, ketamine, propofol
|How to cite this article:|
Ravipati P, Reddy PN, Kumar C, Pradeep P, Pathapati RM, Rajashekar ST. Dexmedetomidine decreases the requirement of ketamine and propofol during burns debridement and dressings. Indian J Anaesth 2014;58:138-42
|How to cite this URL:|
Ravipati P, Reddy PN, Kumar C, Pradeep P, Pathapati RM, Rajashekar ST. Dexmedetomidine decreases the requirement of ketamine and propofol during burns debridement and dressings. Indian J Anaesth [serial online] 2014 [cited 2018 Oct 16];58:138-42. Available from: http://www.ijaweb.org/text.asp?2014/58/2/138/130813
| Introduction|| |
Patients with burns often present to the operation theatre with different painful conditions that require immediate surgical interventions and anaesthetic agents are needed to provide necessary deep sedation, along with analgesia. Ketamine has been a safe and effective anaesthetic agent for burns dressings with a few limitations such as delayed recovery, emergence phenomenon, and nausea and vomiting.  Propofol is also used due to its favourable pharmacokinetics but it lacks the analgesic property intrinsic to ketamine.  Fentanyl is added to propofol to compliment the analgesic property. Dexmedetomidine (Dex), a highly selective α2 -adrenoreceptor agonist, is used for sedation in various clinical settings and shows an anaesthetic-sparing effect. ,,,, Studies have shown that concomitant dexmedetomidine use may reduce the requirement of propofol and ketamine, with faster postoperative recovery and more stable intraoperative haemodynamics. ,,,, Hence, we evaluated whether Dex affects the requirement for propofol, ketamine and intraoperative haemodynamics during burns debridement and dressing changes, and compared its effectiveness and safety with conventional combination ketamine plus propofol.
| Methods|| |
This prospective, open label study was conducted to assess whether Dex affects the requirement of propofol and ketamine in 60 consenting patients aged between 18-60 years, posted for burns dressing and debridement. Institutional Ethics Committee approved for the study protocol was obtained. Patients were excluded from study with known allergy or contraindications to study drugs, head injury, seizure disorder, and psychological disorders. Written informed consent was obtained from the study participants.
In the Dex group, dexmedetomidine 1 μg/kg IM was given 1 h before induction. The patient was then transferred to the operating room. Monitors (electrocardiography, noninvasive blood pressure (NIBP) and pulse oximeter) were attached and the baseline values were noted.
In both Dex and control groups, patients were premedicated with intravenous glycopyrrolate 0.2 mg, ramosetron 0.3 mg, and fentanyl, 2 μg/kg. All patients were administered bolus dose of ketamine 0.5 mg/kg and propofol 1 mg/kg I.V. in separate syringes. Then the patients received an infusion of 1 mg/kg/h of Ketamine and 100 μg/kg/min of propofol for maintenance in separate i.v lines. The propofol plus ketamine infusion was adjusted to achieve a Ramsay Sedation Scale score (RSS) of 6. As soon as the desired level of sedation was achieved, an appropriate size of laryngeal mask airway (LMA) was inserted and patients were maintained on spontaneous respiration. If patients showed increase in the heart rate, blood pressure, respiratory rate, or body movement on initiation of the surgical procedure was considered as inadequate anaesthesia / analgesia and managed by administering bolus dose of ketamine, 0.25 mg/kg or propofol 0.25 mg/kg through an infusion pump. Blood pressure and heart rate were measured just after placing LMA and at a regular interval of 5, 15, 30, 45, and 60 min.
The study drug infusion was discontinued at the end of the surgical procedure, and total drug consumption was noted. The recovery time (i.e. the time from discontinuation of infusion of the study drug and achievement of RSS score of 3) was also noted. Patients were discharged from the recovery room after attaining an Aldrete Recovery Scale Score of 9/ [as the aldrete score is cosidered to be standard for discharge from recovery room].
Statistical analysis was performed using graph pad prism (Version-4) year 2008. The categorical data were expressed as frequencies and percentages and continuous variables were expressed as mean, median and standard deviation. The categorical variables between the groups were compared using Chi-square test. The mean data between the groups was compared by unpaired t test and Medians by Mann-Whitney U test. Within group analysis was performed by using repeated measures ANOVA. P < 0.05 was considered significant. A sample of 30 patients per group was required to demonstrate an estimated reduction in dose of ketamine and propofol in both the groups, with 99% power to detect the difference and two-sided alpha error of 0.05.
| Results|| |
There was no statistically significant difference in the demographic and clinical characteristics among the two groups [Table 1]. The mean dose of ketamine used in Dex group was significantly less (100.5 ± 17.58 mg) whereas it was 231.5 ± 60.39 mg in the control group (P < 0.0001). Similarly, mean dose of propofol in Dex and control groups were 127.7 ± 15.47 mg and 254 ± 59.22 mg respectively (P < 0.0001) [Figure 1]. Time to recovery was 9.57 ± 1.50 min in the Dex group which was significantly lower than in the control group 11.53 ± 2.56 min (P = 0.0006) [Figure 2].
|Figure 1: Comparison of dose requirement of ketamine and propofol with and without Dexmedetomidine|
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In can be noticed from [Table 2] that in dexmedetomidine group HR, SBP, and DBP varied from 74.23 ± 6.76 to 80.47 ± 9.54 beats/min, 114.8 ± 12.6 to 118.9 ± 5.9 mm Hg and 80.17 ± 8.02 to 76.90 ± 7.16 mm Hg, respectively, whereas in control group HR, SBP, and DBP varied from 97.80 ± 17.70 to 85.60 ± 19.87 beats/min, 137.60 ± 14.33 to 129.37 ± 9.98 mm Hg and 93.60 ± 9.68 to 85.67 ± 9.46 mm Hg [Figure 3] and [Figure 4] starting from 0 min to 60 min.
| Discussion|| |
Dexmedetomidine, by activating pre and postsynaptic α2-receptors of sympathetic system produces vasodilatation.By acting on postsynaptic α2-receptors of vascular smooth muscle cells it produces vasoconstriction. It thereby, shows a biphasic, dose-dependent response on blood pressure and heart rate, characterized by an initial short-term increase in BP followed by a longer lasting reduction in BP and HR. ,,, Most previous investigations have proven the cardiovascular depressive effects of IM Dex at a dose of 2.5 μg/kg, which increases the incidence of hypotension and bradycardia. ,,, However, Virkkila et al. showed that IM Dex 1 μg/kg produced sedation and a reduction of intraocular pressure with minimal haemodynamic side effects when given as premedication before cataract surgery under regional anaesthesia.  According to Markku et al. IM Dex provides complete bioavailability and needs less preoperative monitoring as compared to IV Dex.  Also, Scheinin et al. showed that the intramuscular doses resulted in linearly dose-related plasma concentrations of dexmedetomidine;  henceforth, clearance and half-life remains constant irrespective of its plasma concentration. For all these reasons we evaluated the effect of 1.0 μg/kg IM Dex on the requirement for supplemental propofol and ketamine during anaesthesia for burns debridement and dressing changes.
Despite the limited data, the advantage of adding dexmedetomidine with ketamine is that both balance the haemodynamic and adverse effects of each other. Dexmedetomidine may decrease the incidence of tachycardia, hypertension, salivation, and emergence phenomena from ketamine, while ketamine may prevent the bradycardia and hypotension of dexmedetomidine. , Additionally, ketamine as part of the sedation induction may speed the onset of sedation and eliminate the slow onset time of IM Dex. ,,,
In our study, IM Dex reduced the amount of adjuvant propofol and ketamine needed to maintain a RSS score of 6 and provided more stable haemodynamics without Compromising postoperative recovery. These results are consistent with previous investigations showing a 30-50% reduction in the propofol requirement with concomitant use of Dex in adolescent patients and healthy volunteers. , The sedative effect of Dex is mediated through the locus ceruleus in the brain stem, where Dex decreases sympathetic outflow and increases parasympathetic outflow. ,,, Though Dex, propofol. and ketamine act at different centres of the brain, they show synergism with respect to their sedative effects.
Previous studies showed a possible delay in recovery from propofol anaesthesia with the concomitant use of Dex, probably due to its quite long duration of action. ,,, However, such findings of prolongation of extubation or recovery time profiles were not observed in the present study. Dex, by its propofol sparing effect, may be beneficial for reducing the propofol dosage and avoiding adverse effects such as myocardial depression, metabolic acidosis, impaired platelet aggregation, and extended recovery caused by prolonged and large-dose administration of propofol. ,,,,,,
According to our study, IM dexmedetomidine use does not cause any significant haemodynamic changes. However, we observed a transient increase in BP immediately after shifting the patient inside the operation theatre may be due to patients anxiety and it came down to normal level after giving fentanyl and midazolam premedication. A more constant stable haemodynamics observed during anesthesia induction, surgical incision and throughout the procedure. A significant change in haemodynamics was observed in the control group. There is decreased consumption of propofol and ketamine because of sedo-analgesic, anaesthetic-sparing effect of dexmedetomidine.
Bispectral index could have been a better monitor for assessing awareness and sedation but could not be used due to non-availability. Clinical changes in the heart rate and blood pressure that are nonspecific were used as signs of increased nociception during our study.
| Conclusion|| |
Dexmedetomidine (1 μg/kg IM dose) is a good anaesthetic adjuvant that decreases the requirement of propofol and ketamine during burns debridement and dressings, attenuates sympathoadrenal response, maintains stable intraoperative haemodynamics and adequate duration of analgesia, and also has an excellent recovery profile.
| References|| |
|1.||Krauss B, Green SM. Procedural sedation and analgesia in children. Lancet 2006;367:766-80. |
|2.||Cravero JP, Beach ML, Blike GT, Gallagher SM, Hertzog JH; Pediatric Sedation Research Consortium. 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. |
|3.||Aantaa R, Kanto J, Scheinin M, Kallio A, Scheinin H. Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery. Anesthesiology 1990;73:230-5. |
|4.||Ngwenyama NE, Anderson J, Hoernschemeyer DG, Tobias JD. Effects of dexmedetomidine on propofol and remifentanil infusion rates during total intravenous anesthesia for spine surgery in adolescents. Paediatr Anaesth 2008;18:1190-5. |
|5.||Dutta S, Karol MD, Cohen T, Jones RM, Mant T. Effect of dexmedetomidine on propofol requirements in healthy subjects. J Pharm Sci 2001;90:172-81. |
|6.||Khan ZP, Munday IT, Jones RM, Thornton C, Mant TG, Amin D. Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions. Br J Anaesth 1999;83:372-80. |
|7.||Bulow NM, Barbosa NV, Rocha JB. Opioid consumption in total intravenous anesthesia is reduced with dexmedetomidine: A comparative study with remifentanil in gynecologic videolaparoscopic surgery. J Clin Anesth 2007;19:280-5. |
|8.||Vuyk J, Mertens MJ, Olofsen E, Burm AG, Bovill JG. Propofol anesthesia and rational opioid selection: Determination of optimal EC50-EC95 propofol-opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology 1997;87:1549-62. |
|9.||Glass PS, Hardman D, Kamiyama Y, Quill TJ, Marton G, Donn KH, et al. Preliminary pharmacokinetics and pharmacodynamics of an ultra-short-acting opioid: Remifentanil (GI87084B). Anesth Analg 1993;77:1031-40. |
|10.||Westmoreland CL, Hoke JF, Sebel PS, Hug CC Jr, Muir KT. Pharmacokinetics of remifentanil (GI87084B) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery. Anesthesiology 1993;79:893-903. |
|11.||Kang WS, Kim SY, Son JC, Kim JD, Muhammad HB, Kim SH, et al. The effect of dexmedetomidine on the adjuvant propofol requirement and intraoperative hemodynamics during remifentanil-based anesthesia. Korean J Anesthesiol 2012;62:113-8. |
|12.||Ulgey A, Aksu R, Bicer C, Akin A, Altuntaþ R, Esmaoðlu A, et al . Is the addition of dexmedetomidine to a ketamine-propofol combination in pediatric cardiac catheterization sedation useful?. Pediatr Cardiol 2012;33:770-4. |
|13.||Link RE, Desai K, Hein L, Stevens ME, Chruscinski A, Bernstein D, et al. Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Science 1996;273:803-5. |
|14.||Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, et al. Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science 1987;238:650-6. |
|15.||Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK. Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype. Proc Natl Acad Sci U S A 1988;85:6301-5. |
|16.||Snapir A, Posti J, Kentala E, Koskenvuo J, Sundell J, Tuunanen H, et al. Effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects. Anesthesiology 2006;105:902-10. |
|17.||Bloor BC, Ward DS, Belleville JP, Maze M. Effects of intravenous dexmedetomidine in humans: II. hemodynamic changes. Anesthesiology 1992;77:1134-42. |
|18.||Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, et al. Dexmedetomidine infusion during laparoscopic bariatric surgery: The effect on recovery outcome variables. Anesth Analg 2008;106:1741-8. |
|19.||Scheinin H, Karhuvaara S, Olkkola KT, Kallio A, Anttila M, Vuorilehto L, et al. Pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine. Clin Pharmacol Ther 1992;52:537-46. |
|20.||Virkkilä M, Ali-Melkkilä T, Kanto J, Turunen J, Scheinin H. Dexmedetomidine as intramuscular premedication in outpatient cataract surgery. A placebo-controlled dose-ranging study. Anaesthesia 1993;48:482-7. |
|21.||Anttila M, Penttilä J, Helminen A, Vuorilehto L, Scheinin H. Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol 2003;56:691-3. |
|22.||Yuen VM: Dexmeditomidine: perioperative applications in children. paediatr Anesth 2010:20:256-64. |
|23.||Levänen J, Mäkelä ML, Scheinin H. Dexmedetomidine premedicationattenuates ketamine-induced cardiostimulatory effects and postanesthetic delirium. Anesthesiology 1995;82:1117-25. |
|24.||Zor F, Ozturk S, Bilgin F, Isik S, Cosar A. Pain relief during dressing changes of major adult burns: Ideal analgesic combination with ketamine. Burns 2010;36:501-5. |
|25.||Dilek O, Yasemin G, Atci M. Preliminary experience with dexmedetomidine in neonatal anesthesia. J AnesthClin Pharm 2011;27:17-22. |
|26.||Joseph D, Tobias MD. Dexmedetomidine: Applications in Pediatric Critical Care and Pediatric Anesthesiology. Available from: http://www.pedsanesthesia.org/meetings/Tobias-Dexmedetomidine.pdf. [Last accessed on 2010 Apr 17]. |
|27.||Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology 2000;93:1345-9. |
|28.||Virtanen R, Savola JM, Saano V, Nyman L. Characterization of the selectivity, specificity and potency of medetomidine as an [alpha] 2-adrenoceptor agonist. Eur J Pharmacol 1988;150:9-14. |
|29.||Arcangeli A, D′Alò C, Gaspari R. Dexmedetomidine use in general anaesthesia. Curr Drug Targets 2009;10:687-95. |
|30.||Ohtani N, Kida K, Shoji K, Yasui Y, Masaki E. Recovery profiles from dexmedetomidine as a general anesthetic adjuvant in patients undergoing lower abdominal surgery. Anesth Analg 2008;107:1871-4. |
|31.||Kam PC, Cardone D. Propofol infusion syndrome. Anaesthesia 2007;62:690-701. |
|32.||Fourcade O, Simon MF, Litt L, Samii K, Chap H. Propofol inhibits human platelet ggregation induced by proinflammatory lipid mediators. Anesth Analg 2004;99:393-8. |
|33.||Aoki H, Mizobe T, Nozuchi S, Hiramatsu N. In vivo and in vitro studies of the inhibitory effect of propofol on human platelet aggregation. Anesthesiology 1998;88:362-70. |
|34.||De La Cruz JP, Carmona JA, Paez MV, Blanco E, Sanchez De La Cuesta F. Propofol inhibits in vitro platelet aggregation in human whole blood. Anesth Analg 1997;84:919-21. |
|35.||Burow BK, Johnson ME, Packer DL. Metabolic acidosis associated with propofol in the absence of other causative factors. Anesthesiology 2004;101:239-41. |
|36.||Liolios A, Guerit JM, Scholtes JL, Raftopoulos C, Hantson P. Propofol infusion syndrome associated with short-term large-dose infusion during surgical anesthesia in an adult. Anesth Analg 2005;100:1804-6. |
|37.||Merz TM, Regli B, Rothen HU, Felleiter P. Propofol infusion syndrome-a fatal case at a low infusion rate. Anesth Analg 2006;103:1050. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]
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