A Dose Finding Study of Remifentanil and Propofol for Lumbar Punctures in Children

The Minimum Effective Dose of Remifentanil When Co-administered With Propofol for Lumbar Puncture in Children: A Dose-finding Study

This study will examine whether the combination of two anaesthetic medications, propofol and remifentanil, is suitable for short duration surgical procedures, providing a shorter recovery time and fewer side effects than either drug used alone.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Hematologic Diseases
• Intervention / Treatment: Drug: Remifentanil; Drug: Remifentanil

Detailed Description

Propofol is the primary medication used by anesthesiologists at HSC to provide sedation for lumbar puncture. Propofol provides amnesia, anxiolysis, and hypnosis, but because propofol has no analgestic properties patients often respond to the pain of LP needle insertion. To ensure patient immobility, the dose of propofol is often increased, resulting in a duration of action that is excessive for lumbar puncture. Remifentanil is an ultra-short acting opioid which can be used to provide analgesia and sedation for short painful procedures with minimal residual pain. However, when used as the sole agent, remifentanil is associated with a high incidence of respiratory depression and/or arterial oxygen desaturation and does not provide amnesia or anxiolysis. The combination of propofol and remifentanil may be particularly suitable for short duration procedures, providing a shorter recovery time and fewer side effects than either drug used alone.

The objective is to determine the minimum effective dose of remifentanil required to prevent movement for insertion of a lumbar puncture needle when co-administered with propofol. The results obtained from this study will be used in a future study of the recovery characteristics of propofol and remifentanil in children undergoing lumbar puncture.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of a hemato-oncological disorder
• Scheduled to undergo a lumbar puncture
• Aged 4-11 years
• Male or female
• Unpremedicated
• Willing and able to provide informed consent (or informed consent by parents)

Exclusion Criteria:

• Children who are known or suspected to be difficult to ventilate by face mask
• Children who are deemed medically unfit to receive either of the two study medications
• Children who are obese (weight for height > 95th percentile,
• Children who do not have an indwelling intravenous line

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propofol 4 mg/kg group; First patient in this arm will receive a bolus of propofol 4 mg/kg followed by remifentanil 0.5 mcg/kg. Subsequent patients randomized to this arm will receive propofol 4 mg/kg but the dose of remifentanil will be determined using the Dixon up-and-down method (i.e. based on the response of the previous patient)	Drug: Remifentanil; The first patient in this group will receive 4 mg/kg propofol and 0.5 ug/kg respectively. The dose of remifentanil in subsequent patients will be determined by the Dixon up-and-down method.; Drug: Remifentanil; The first patient in this group will receive 2 mg/kg propofol and 1.0 ug/kg respectively. The dose of remifentanil in subsequent patients will be determined by the Dixon up-and-down method.
Experimental: Propofol 2 mg/kg group; First patient in this arm will receive a bolus of propofol 2 mg/kg followed by remifentanil 1 mcg/kg. Subsequent patients randomized to this arm will receive propofol 2 mg/kg but the dose of remifentanil will be determined using the Dixon up-and-down method (i.e. based on the response of the previous patient)	Drug: Remifentanil; The first patient in this group will receive 4 mg/kg propofol and 0.5 ug/kg respectively. The dose of remifentanil in subsequent patients will be determined by the Dixon up-and-down method.; Drug: Remifentanil; The first patient in this group will receive 2 mg/kg propofol and 1.0 ug/kg respectively. The dose of remifentanil in subsequent patients will be determined by the Dixon up-and-down method.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose of Remifentanil Required to Prevent Movement in Response to Lumbar Puncture Needle Insertion	Minimum effective dose (Dixon methodology) and ED98 required to prevent movement during lumbar puncture needle insertion	Movement measured at the time of lumbar puncture needle insertion.

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of Adverse Events.	Followed for the length of the procedure.

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Publications and helpful links

General Publications

• Hayes JA, Lopez AV, Pehora CM, Robertson JM, Abla O, Crawford MW. Coadministration of propofol and remifentanil for lumbar puncture in children: dose-response and an evaluation of two dose combinations. Anesthesiology. 2008 Oct;109(4):613-8. doi: 10.1097/ALN.0b013e31818629f3.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Actual): December 2, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: pediatrics; anesthesia; propofol; remifentanil; spinal puncture; dose finding
• Additional Relevant MeSH Terms: Hematologic Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: 1000007479

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No