Dexmedetomidine: Current Role in Burn ICU

G Scibelli, L Maio, M Sasso, A Lanza, G Savoia, G Scibelli, L Maio, M Sasso, A Lanza, G Savoia

Abstract

Dexmedetomidine (DEX) is a relativelyrecent a2-adrenergic agonist which provides sedation, anxiolysis and analgesia with much less respiratory depression than other sedatives. These characteristics have implemented the use of the drug in the ICUs in order to achieve the target of a "arousable sedation", thanks to its significant manageability. Its sedative-analgesic properties are also particularly suitable for use in burn ICUs, both adult and pediatric, which is why the current Guidelines have recognized a central role in the management of these categories of patients. Finally, DEX has showed significant anti-inflammatory effect both in animal models and in preliminary clinical trials, reducing vasopressor requirements and main mediators levels of the systemic inflammatory response involved in sepsis and similar processes, suggesting its use for improved outcome in ICU septic patients.

Keywords: ICU; burns; dexmedetomidine; sepsis.

References

    1. Asmussen S, Maybauer DM, Fraser JF, Jennings K, George S, Maybauer MO. A meta-analysis of analgesic and sedative effects of dexmedetomidine in burn patients. Burns. 2013;39:625–631.
    1. Fagin A, Palmieri T, Greenhalgh D, Sen S. A comparison of dexmedetomidine and midazolam for sedation in severe pediatric burn injury. J Burn Care Res. 2012;33(6):759–63.
    1. Tobias JD. Dexmedetomidine: applications in pediatric critical care and pediatric anesthesiology. Pediatr Crit Care Med. 2007;8:115–31.
    1. Jones JG, Taylor PM. Receptor-specific reversible sedation: dangers of vascular effects. Anesthesiology. 1999;90:1489–90.
    1. Dexmedetomidine on Pediatric Lexi-Drugs. Hudson, OH: Lexi-Comp, Inc.; 2010. [Accessed 1 September 2010]. available from .
    1. Bruno JJ, Warren ML. Intensive care unit delirium. Crit Care Nurs Clin North Am. 2010;22:161–78.
    1. Oschman A, McCabe T, Kuhn RJ. Dexmedetomidine for opioid and benzodiazepine withdrawal in pediatric patients. Am J Health Syst Pharm. 2011;68:1233–8.
    1. Borgeat A, Aguirre J. Sedation and regional anesthesia. Curr Opin Anaesthesiol. 2009;22:678–82.
    1. Cederholm I, Bengtsson M, Bjorkman S, Choonara I, Rane A. Long term high dose morphine, ketamine, and Midazolam infusion in a child with burns. Br J Clin Pharmacol. 1990;30:901–5.
    1. Kariya N, Shindoh M, Nishi S, Yukioka H, Asada A. Oral clonidine for sedation and analgesia in a burn patient. J Clin Anesth. 1998;10:514–17.
    1. Sheridan R, Stoddard F, Querzoli E. Management of background pain and anxiety in critically burned children requiring protracted mechanical ventilation. J Burn Care Rehabil. 2001;22:150–3.
    1. Walker J, MacCallum M, Fischer C, Kopcha R, Saylors R, McCall J. Sedation using dexmedetomidine in pediatric burn patients. J Burn Care Res. 2006;27:206–10.
    1. Sheridan RL, McEttrick M, Bacha G, Stoddard F, Tompkins RG. Midazolam infusion in pediatric patients with burns who are undergoing mechanical ventilation. J Burn Care Rehabil. 1994;15:515–18.
    1. Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, et al. Dexmedetomidine vs. Midazolam for sedation of critically ill patients. JAMA. 2009;301:489–499.
    1. Tan JA, Ho KM. Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med. 2010;36:926–39.
    1. Pasin L, Greco T, Feltracco P, Vittorio A, Neto CN, Cabrini L, et al. Dexmedetomidine as a sedative agent in critically ill patients: a meta-analysis of randomized controlled trials. PLoS One. 2013;8(12):e82913.
    1. Retrouvey H, Shahrokhi S. Pain and the Thermally Injured Patient—A Review of Current Therapies. J Burn Care Res. 2015;36:315–23.
    1. Richardson P, Mustard L. The management of pain in the burns unit. Burns. 2009;35:921–36.
    1. Browne AL, Andrews R, Schug SA, Wood F. Persistent pain outcomes and patient satisfaction with pain management after burn injury. Clin J Pain. 2011;27:136–45.
    1. Pal SK, Cortiella J, Herndon D. Adjunctive methods of pain control in burns. Burns. 1997;23:404–12.
    1. Vanderah TW. Pathophysiology of pain. Med Clin North Am. 2007;91:1–12.
    1. Holtman JR, Jellish WS. Opioid-induced hyperalgesia and burn pain. J Burn Care Res. 2012;33:692–701.
    1. Mahar PD, Wasiak J, O’Loughlin CJ, Christelis N, Arnold CA, Spinks AB, et al. Frequency and use of pain assessment tools implemented in randomized controlled trials in the adult burns population: a systematic review. Burns. 2012;38:147–54.
    1. 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.
    1. Trupkovic T, Kinn M, Kleinschmidt S. Analgesia and sedation in the intensive care of burn patients: results of a European survey. J Intensive Care Med. 2011;26:397–407.
    1. Gray P, Kirby J, Smith MT, Cabot PJ, Williams B, Doecke J, et al. Pregabalin in severe burn injury pain: a double-blind, randomised placebo-controlled trial. Pain. 2011;152:1279–88.
    1. Wong L, Turner L. Treatment of post-burn neuropathic pain: evaluation of pregabalin. Burns. 2010;36:769–72.
    1. Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl. Br J Anaesth. 1992;68:126–31.
    1. Kundra P, Velayudhan S, Krishnamachari S, Lata Gupta S. Oral ketamine and dexmedetomidine in adults’ burns wound dressing - A randomized double blind cross over study. Burns. 2013;39:1150–56.
    1. 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.
    1. 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.
    1. Tobias JD, Berkenbosch JW. Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J. 2004;97:451–5.
    1. Su F, Hammer GB. Dexmedetomidine: pediatric pharmacology, clinical uses and safety. Expert Opin Drug Saf. 2011;10:55–66.
    1. Sheridan RL, Keaney T, Shank E, Cascia G, Martyn JAJ, Weber J. Dexmedetomidine infusion in pediatric burns. J Burn Care Res. 2007;28:S49–S186.
    1. Lin H, Faraklas I, Sampson C, Saffle JR, Cochran A. Use of dexmedetomidine for sedation in critically ill mechanically ventilated pediatric burn patients. J Burn Care Res. 2011;32:98–103.
    1. Shank ES, Sheridan RL, Ryan CM, Keaney TJ, Martyn JA. Hemodynamic responses to dexmedetomidine in critically injured intubated pediatric burned patients: a preliminary study. J Burn Care Res. 2013;34:311–317.
    1. Kamibayashi T, Maze M. Clinical uses of alpha2 adrenergic agonists. Anesthesiology. 2000;93:1345–9.
    1. Mason KP, Lerman J. Dexmedetomidine in children: current knowledge and future applications. Anesth Analg. 2011;113:1129–42.
    1. Kulp GA, Herndon DN, Lee JO, Suman OE, Jeschke MG. Extent and magnitude of catecholamine surge in pediatric burned patients. Shock. 2010;33:369–74.
    1. Goodall M, Stone C, Haynes BW., Jr Urinary output of adrenaline and noradrenaline in severe thermal burns. Ann Surg. 1957;145:479–87.
    1. Falkner B, Roven S, DeClement FA, Bendlin A. Hypertension in children with burns. J Trauma. 1978;18:213–7.
    1. Akrami C, Falkner B, Gould AB, DeClement FA, Bendlin A. Plasma renin and occurrence of hypertension in children with burn injuries. J Trauma. 1980;20:130–4.
    1. Dolecek R, Závada M, Adámková M, Leikep K. Plasma renin like activity (RLA) and angiotensin II levels after major burns. A preliminary report. Acta Chir Plast. 1973;15:166–9.
    1. Afshari R, Maxwell SR, Webb DJ, Bateman DN. Morphine is an arteriolar vasodilator in man. Br J Clin Pharmacol. 2009;67:386–93.
    1. Chang KS, Feng MG, Davis RF. Midazolam produces vasodilation by mixed endothelium-dependent and independent mechanisms. Anesth Analg. 1994;78:710–7.
    1. Stoddard FJ, Jr, Sorrentino EA, Ceranoglu TA, Saxe G, Murphy JM, Drake JE, et al. Preliminary evidence for the effects of morphine on posttraumatic stress disorder symptoms in one- to four-year-olds with burns. J Burn Care Res. 2009;30:836–43.
    1. Stoddard FJ, Todres ID. A new frontier: posttraumatic stress and its prevention, diagnosis, and treatment. Crit Care Med. 2001;29:687–8.
    1. McGhee LL, Slater TM, Garza TH, Fowler M, DeSocio PA, Maani CV. The relationship of early pain scores and posttraumatic stress disorder in burned soldiers. J Burn Care Res. 2011;32:46–51.
    1. Wibbenmeyer L, Sevier A, Liao J, Williams I, Light T, Latenser B, et al. The impact of opioid administration on resuscitation volumes in thermally injured patients. J Burn Care Res. 2010;31:48–56.
    1. Sullivan SR, Friedrich JB, Engrav LH, Round KA, Heimbach DM, Heckbert SR, et al. “Opioid creep” is real and may be the cause of “fluid creep””. Burns. 2004;30:583–90.
    1. Skrupky LP, Drewry AM, Wessman B, Field RR, Fagley RE, Varghese L, et al. Clinical effectiveness of a sedation protocol minimizing benzodiazepine infusions and favoring early dexmedetomidine: a before-after study. Crit Care. 2015;19(1):136.
    1. Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263–306.
    1. Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342:1471–7.
    1. Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomized controlled trial. Lancet. 2008;371:126–34.
    1. Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, et al. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999;27:2609–15.
    1. Quenot JP, Ladoire S, Devoucoux F, Doise JM, Cailliod R, Cunin N, et al. Effect of a nurse-implemented sedation protocol on the incidence of ventilator-associated pneumonia. Crit Care Med. 2007;35:2031–6.
    1. Marshall J, Finn CA, Theodore AC. Impact of a clinical pharmacist-enforced intensive care unit sedation protocol on duration of mechanical ventilation and hospital stay. Crit Care Med. 2008;36:427–33.
    1. Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, et al. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009;37:2527–34.

    1. Agenzia Italiana Del Farmaco (Italian Agency of Drug). Gazzetta Ufficiale Serie Generale (Official Gazette - General Series) n. 4; 07 Gennaio 2016

    1. DAS-Taskforce 2015. Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version. Ger Med Sci. 2015;13
    1. Bayat A, Ramaiah R, Bhananker SM. Analgesia and sedation for children undergoing burn wound care. Expert Rev Neurother. 2010;10(11):1747–59.
    1. Wasiak J, Mahar P, McGuinness SK, Spinks A, Danilla S, Cleland H. Intravenous lidocaine for the treatment of background or procedural burn pain. Cochrane Database Syst Rev. 2012;13:6.
    1. Cuignet O, Pirson J, Soudon O, Zizi M. Effects of gabapentin on morphine consumption and pain in severely burned patients. Burns. 2007;33(1):81–6.
    1. Warncke T, Stubhaug A, Jørum E. Ketamine, an NMDA receptor antagonist, suppresses spatial and temporal properties of burn-induced secondary hyperalgesia in man: a double-blind, crossover comparison with morphine and placebo. Pain. 1997;72(1–2):99–106.
    1. Ilkjaer S, Petersen KL, Brennum J, Wernberg M, Dahl JB. Effect of systemic N-methyl-D-aspartate receptor antagonist (ketamine) on primary and secondary hyperalgesia in humans. Br J Anaesth. 1996;76(6):829–34.
    1. Edrich T, Friedrich AD, Eltzschig HK, Felbinger TW. Ketamine for long-term sedation and analgesia of a burn patient. Anesth Analg. 2004;99(3):893–5.
    1. Field T, Peck M, Krugman S, Tuchel T, Schanberg S, Kuhn C, et al. Burn injuries benefit from massage therapy. J Burn Care Rehabil. 1998;19(3):241–4.
    1. Hernandez-Reif M, Field T, Largie S, Hart S, Redzepi M, Nierenberg B, et al. Childrens’ distress during burn treatment is reduced by massage therapy. J Burn Care Rehabil. 2001;22(2):191–5.
    1. Frenay MC, Faymonville ME, Devlieger S, Albert A, Vanderkelen A. Psychological approaches during dressing changes of burned patients: a prospective randomised study comparing hypnosis against stress reducing strategy. Burns. 2001;27(8):793–9.
    1. Humphries Y, Melson M, Gore D. Superiority of oral ketamine as an analgesic and sedative for wound care procedures in the pediatric patient with burns. J Burn Care Rehabil. 1997;18:34–6.
    1. Branski LK, Al-Mousawi A, Rivero H, Jeschke MG, Sanford AP, Herndon DN. Emerging infections in burns. Surg Infect. 2009;10:389–397.
    1. Geloen A, Pichot C, Leroy S, Julien C, Ghignone M, May CN, et al. Pressor Response to Noradrenaline in the Setting of Septic Shock: Anything New under the Sun—Dexmedetomidine, Clonidine? A Minireview. Biomed Res Int. 2015;2015
    1. Ellis CG, Bateman RM, Sharpe MD, Sibbald WJ, Gill R. Effect of a maldistribution of microvascular blood flow on capillary O2 extraction in sepsis. Am J of Physiol Heart Circ Physiol. 2002;282(1):156–164.
    1. Fink MP. Bench-to-bedside review: cytopathic hypoxia. Critical Care. 2002;6(6):491–499.
    1. Pichot C, Mathern P, Khettab F, Ghignone M, Geloen A, Quintin L. Increased pressor response to noradrenaline during septic shock following clonidine? Anaesth Intensive Care. 2010;38(4):784–785.
    1. Geloen A, Chapelier K, Cividjian A, Dantony E, Rabilloud M, May CN, et al. Clonidine and dexmedetomidine increase the pressor response to norepinephrine in experimental sepsis: a pilot study. Crit Care Med. 2013;41(12):431–438.
    1. Lankadeva YR, Booth LC, Kosaka J, Evans RG, Quintin L, Bellomo R, et al. Clonidine restores pressor responsiveness to phenylephrine and angiotensin II in ovine sepsis. Crit Care Med. 2015;43(7):221–229.
    1. Pichot C, Géloën A, Ghignone M, Quintin L. Alpha-2 agonists to reduce vasopressor requirements in septic shock? Med Hypotheses. 2010;75(6):652–656.
    1. Butler J, Kelly JG, O’Malley K, Pidgeon F. β-adrenoceptor adaptation to acute exercise. J Physiol. 1983;344(1):113–117.
    1. Benedict CR, Rose JA. Arterial norepinephrine changes in patients with septic shock. Circ Shock. 1992;38(3):165–172.
    1. Ramchandra R, Wan L, Hood SG, Frithiof R, Bellomo R, May CN. Septic shock induces distinct changes in sympathetic nerve activity to the heart and kidney in conscious sheep. Am J Physiol Regul Integr Comp Physiol. 2009;297(5):1247–1253.
    1. Dünser MW, Hasibeder WR. Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. J Intensive Care Med. 2009;24(5):293–316.
    1. Huang Y, Lu Y, Zhang L, Yan J, Jiang J, Jiang H. Perineural dexmedetomidine attenuates inflammation in rat sciatic nerve via the NF-κB pathway. Int J Mol Sci. 2014;15(3):4049–59.
    1. Shen J, Fu G, Jiang L, Xu J, Li L, Fu G. Effect of dexmedetomidine pretreatment on lung injury following intestinal ischemia-reperfusion. Exp Ther Med. 2013;6(6):1359–1364.
    1. Chen C, Zhang Z, Chen K, Zhang F, Peng M, Wang Y. Dexmedetomidine regulates inflammatory molecules contributing to ventilator-induced lung injury in dogs. J Surg Res. 2014;187(1):211–8.
    1. Xianbao L, Hong Z, Xu Z, Chunfang Z, Dunjin C. Dexmedetomidine reduced cytokine release during postpartum bleeding-induced multiple organ dysfunction syndrome in rats. Mediators Inflamm. 2013;2013:627831.
    1. Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, et al. Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway. Mediators Inflamm. 2013;2013:562154.
    1. Sugita S, Okabe T, Sakamoto A. Continuous infusion of dexmedetomidine improves renal ischemia-reperfusion injury in rat kidney. J Nippon Med Sch. 2013;80(2):131–9.
    1. Shi QQ, Wang H, Fang H. Dose-response and mechanism of protective functions of selective alpha-2 agonist dexmedetomidine on acute lung injury in rats. Saudi Med J. 2012;33(4):375–81.
    1. Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth. 2008;22(3):221–8.
    1. Zhang X, Wang J, Qian W, Zhao J, Sun L, Qian Y, et al. Dexmedetomidine inhibits tumor necrosis factor-alpha and interleukin 6 in lipopolysaccharide-stimulated astrocytes by suppression of c-Jun N-terminal kinases. Inflammation. 2014;37(3):942–9.
    1. Kawasaki T, Kawasaki C, Ueki M, Hamada K, Habe K, Sata T. Dexmedetomidine suppresses proinflammatory mediator production in human whole blood in vitro. J Trauma Acute Care Surg. 2013;74(5):1370–5.
    1. Peng M, Wang YL, Wang CY, Chen C. Dexmedetomidine attenuates lipopolysaccharide-induced proinflammatory response in primary microglia. J Surg Res. 2013;179(1):219–25.
    1. Lai YC, Tsai PS, Huang CJ. Effects of dexmedetomidine on regulating endotoxin-induced up-regulation of inflammatory molecules in murine macrophages. J Surg Res. 2009;154(2):212–9.
    1. Ueki M, Kawasaki T, Habe K, Hamada K, Kawasaki C, Sata T. The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass. Anaesthesia. 2014;69(7):693–700.
    1. Wang ZX, Huang CY, Hua YP, Huang WQ, Deng LH, Liu KX. Dexmedetomidine reduces intestinal and hepatic injury after hepatectomy with inflow occlusion under general anaesthesia: a randomized controlled trial. Br J Anaesth. 2014;112(6):1055–64.
    1. Kang SH, Kim YS, Hong TH, Chae MS, Cho ML, Her YM, et al. Effects of dexmedetomidine on inflammatory responses in patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2013;57(4):480–7.
    1. Tasdogan M, Memis D, Sut N, Yuksel M. Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis. J Clin Anesth. 2009;21(6):394–400.

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