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| ID | Type | Description | Link |
|---|---|---|---|
| ChiCTR-IPR-15007085 | Other Identifier | Chinese Clinical Trial Registry |
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| Name | Class |
|---|---|
| Beijing Tiantan Hospital | OTHER |
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The purpose of this randomized, double-blind and placebo-controlled pilot study is to investigate whether dexmedetomidine when used as an adjuvant to general anesthesia can decrease the harmful effects of anesthesia and surgery on intelligence development in pediatric patients undergoing craniotomy.
General anesthetics and sedatives are administered to millions of children each year to facilitate life-saving surgery and other essential surgical or medical procedures. In the past two decades, mounting evidence from animal and clinical studies have raised concerns that general anesthetics may produce harmful effects in the developing brain and lead to adverse neurodevelopmental outcomes. Factors that may influence the degree of injury include age at the time of drug exposure/surgery and cumulative anesthetic dose.
The Intelligence Quotients of pediatric patients with intracranial tumors are lower when compared with healthy children of same age. The investigators suppose that these patients are more sensitive to the neurotoxic effects of general anesthetics. Dexmedetomidine is an alpha 2-adrenoceptor agonist that provides sedation, anxiolysis, and analgesia, and has been shown to be safe to the brain in animal studies. In clinical studies, the use of dexmedetomidine decreases the consumption of anesthetics and opioids during general anesthesia and suppresses stress response induced by surgery. The investigators hypothesize that dexmedetomidine, when used as an adjuvant to general anesthesia, can reduce the neurotoxic effects of general anesthetics by decreasing anesthetic consumption and inhibiting stress response.
The purpose of this randomized, double-blind and placebo-controlled pilot study is to investigate whether dexmedetomidine, when used as an adjuvant to general anesthesia, can decrease the harmful effects of anesthesia and surgery on intelligence development of pediatric patients undergoing craniotomy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dexmedetomidine group | Experimental | A loading dose of dexmedetomidine (0.5 ug/kg IV infusion in 15 minutes) will be administered after induction of general anesthesia, followed by continuous infusion at a rate of 0.5 ug/kg/h until the closure of the duramater of the brain. |
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| Control group | Placebo Comparator | Normal saline will be administered in the same rate and volume as that in the dexmedetomidine group. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dexmedetomidine | Drug | A loading dose dexmedetomidine (0.5 ug/kg IV infused in 15 minutes) will be administered after anesthesia induction, followed by a continuous infusion at a rate of 0.5 ug/kg/h until the closure of the brain duramater at the end of surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Intelligence Quotient | Tested with Chinese Binet Intelligence Scale | At 3 months after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Time to anesthesia emergence | From end of surgery until reappearance of response to oral orders, assessed up to 24 hours | |
| Time to extubation | From end of surgery until extubation, assessed up to 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Length of stay in hospital after surgery | From end of surgery to 30 days after surgery | |
| Incidence of postoperative complications | From end of surgery to 30 days after surgery | |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dong-Xin Wang, MD, PhD | Peking University First Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital | Beijing | Beijing Municipality | 100034 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25714157 | Background | Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA. Anesthetic neurotoxicity--clinical implications of animal models. N Engl J Med. 2015 Feb 26;372(9):796-7. doi: 10.1056/NEJMp1414786. | |
| 18499599 | Background | Cattano D, Young C, Straiko MM, Olney JW. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg. 2008 Jun;106(6):1712-4. doi: 10.1213/ane.0b013e318172ba0a. |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| D019965 | Neurocognitive Disorders |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| D000077330 | Saline Solution |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| normal saline | Drug | Normal saline will be administered in the same rate, volume and duration as that in the dexmedetomidine group |
|
|
| Depth of sedation at the time of extubation | Assessed with Ramsay sedation scale | Immediately after extubation |
| Emergence agitation | Agitation will be assessed with anesthesia emergence agitation score. | From end of surgery until extubation, assessed up to 24 hours |
| All-cause 30-day mortality |
| At the time of 30 days after surgery |
| All-cause 90-day mortality | At the time of 90 days after surgery |
| 9872743 | Background | Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999 Jan 1;283(5398):70-4. doi: 10.1126/science.283.5398.70. |
| 11303910 | Background | Olney JW, Ishimaru MJ, Bittigau P, Ikonomidou C. Ethanol-induced apoptotic neurodegeneration in the developing brain. Apoptosis. 2000 Dec;5(6):515-21. doi: 10.1023/a:1009685428847. |
| 23722106 | Background | Jevtovic-Todorovic V, Absalom AR, Blomgren K, Brambrink A, Crosby G, Culley DJ, Fiskum G, Giffard RG, Herold KF, Loepke AW, Ma D, Orser BA, Planel E, Slikker W Jr, Soriano SG, Stratmann G, Vutskits L, Xie Z, Hemmings HC Jr. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. Br J Anaesth. 2013 Aug;111(2):143-51. doi: 10.1093/bja/aet177. Epub 2013 May 30. |
| 15386759 | Background | Poggi G, Liscio M, Galbiati S, Adduci A, Massimino M, Gandola L, Spreafico F, Clerici CA, Fossati-Bellani F, Sommovigo M, Castelli E. Brain tumors in children and adolescents: cognitive and psychological disorders at different ages. Psychooncology. 2005 May;14(5):386-95. doi: 10.1002/pon.855. |
| 14527495 | Background | Hernandez MT, Sauerwein HC, Jambaque I, de Guise E, Lussier F, Lortie A, Dulac O, Lassonde M. Attention, memory, and behavioral adjustment in children with frontal lobe epilepsy. Epilepsy Behav. 2003 Oct;4(5):522-36. doi: 10.1016/j.yebeh.2003.07.014. |
| 26016707 | Background | Wang XW, Cao JB, Lv BS, Mi WD, Wang ZQ, Zhang C, Wang HL, Xu Z. Effect of perioperative dexmedetomidine on the endocrine modulators of stress response: a meta-analysis. Clin Exp Pharmacol Physiol. 2015 Aug;42(8):828-36. doi: 10.1111/1440-1681.12431. |
| 26991622 | Background | Li Y, Wang B, Zhang LL, He SF, Hu XW, Wong GT, Zhang Y. Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique. Anesth Analg. 2016 Apr;122(4):1202-10. doi: 10.1213/ANE.0000000000001165. |
| 26446479 | Background | Kim DJ, Kim SH, So KY, Jung KT. Effects of dexmedetomidine on smooth emergence from anaesthesia in elderly patients undergoing orthopaedic surgery. BMC Anesthesiol. 2015 Oct 7;15:139. doi: 10.1186/s12871-015-0127-4. |
| 26005187 | Background | Le Bot A, Michelet D, Hilly J, Maesani M, Dilly MP, Brasher C, Mantz J, Dahmani S. Efficacy of intraoperative dexmedetomidine compared with placebo for surgery in adults: a meta-analysis of published studies. Minerva Anestesiol. 2015 Oct;81(10):1105-17. Epub 2015 May 25. |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
| D000077324 |
| Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |