Dexmedetomidine and Intelligence Development in Pediatric Patients Undergoing Craniotomy

Brain Neoplasms Clinical Trial

Official title:

The Effect of Dexmedetomidine as an Adjuvant to General Anesthesia on Intelligence Development in Pediatric Patients Undergoing Craniotomy: a Randomized, Double-blind and Placebo-controlled Pilot Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02810899
• Other study ID #: 2015[969]
• Secondary ID: ChiCTR-IPR-15007
• Status: Completed
• Phase: Phase 4
• First received: June 8, 2016
• Last updated: September 28, 2016
• Start date: September 2015
• Est. completion date: June 2016

Study information

• Verified date: September 2016
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 12 Years

Eligibility

Inclusion Criteria:

1. Age of 2 years or older, but no more than 12 years;

2. Plan to undergo selective craniotomy under general anesthesia for intracranial tumor resection;

3. Written informed consent signed by legal guardians.

Exclusion Criteria:

1. Refused to participate by the legal guardians;

2. Body weight lower than the 3rd percentile or higher than 97th percentile of the normal body weight reference;

3. American Society of Anesthesiologists physical classification of IV or higher;

4. Unable to complete preoperative intelligence assessment because of coma, dysnoesia, or language barrier;

5. Diagnosed pulmonary disease (including acute respiratory tract infection) or cardiovascular disease (including congenital heart disease, hypertension, hypotension, bradycardia, atrioventricular block, or cardiac insufficiency);

6. Abnormal liver or renal function (liver enzyme or creatinine higher than 1.5 times of the upper normal limit;

7. Other congenital diseases that may affect the development of the nervous system (such as Down's Syndrome);

8. Allergy to dexmedetomidine;

9. Other conditions that are considered unsuitable for study participation by the attending pediatricians or investigators.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Neoplasms

Intervention

Drug:
• dexmedetomidine
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.
• normal saline
Normal saline will be administered in the same rate, volume and duration as that in the dexmedetomidine group

Locations

Country	Name	City	State
China	Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University First Hospital	Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

References & Publications (11)

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. — View Citation

Hernandez MT, Sauerwein HC, Jambaqué 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. — View Citation

Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Olney JW, Ishimaru MJ, Bittigau P, Ikonomidou C. Ethanol-induced apoptotic neurodegeneration in the developing brain. Apoptosis. 2000 Dec;5(6):515-21. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Length of stay in hospital after surgery		From end of surgery to 30 days after surgery	Yes
Other	Incidence of postoperative complications		From end of surgery to 30 days after surgery	Yes
Other	All-cause 30-day mortality		At the time of 30 days after surgery	Yes
Other	All-cause 90-day mortality		At the time of 90 days after surgery	Yes
Primary	Intelligence Quotient	Tested with Chinese Binet Intelligence Scale	At 3 months after surgery	Yes
Secondary	Time to anesthesia emergence		From end of surgery until reappearance of response to oral orders, assessed up to 24 hours	Yes
Secondary	Time to extubation		From end of surgery until extubation, assessed up to 24 hours	Yes
Secondary	Depth of sedation at the time of extubation	Assessed with Ramsay sedation scale	Immediately after extubation	Yes
Secondary	Emergence agitation	Agitation will be assessed with anesthesia emergence agitation score.	From end of surgery until extubation, assessed up to 24 hours	Yes