IN Ketamine vs IN Midazolam and Fentanyl for Laceration Repair

Comparison of Sedation, Pain, and Care Provider Satisfaction Between the Use of Intranasal Ketamine Versus Intranasal Midazolam and Fentanyl During Laceration Repair

Often, repair of the cuts (laceration repair) proves to be traumatic for the children and the parents. Nasal spray (Intranasal/IN) approaches for procedural pain reduction, such as during dental work, have been demonstrated to make drug administration painless and well tolerated. We are comparing IN ketamine to IN midazolam and fentanyl for pain and reducing anxiety during repair of cuts in children.

Study Overview

• Status: Terminated
• Conditions: Laceration of Skin
• Intervention / Treatment: Drug: Ketamine; Drug: Midazolam and fentanyl

Detailed Description

Children frequently present to pediatric emergency center (PEC) with cuts of different body parts. Often, repair of the cuts (laceration repair) proves to be traumatic for the children and the parents alike. Ideally, repair of the cuts should be as painless and free from anxiety as possible. To work towards this goal, different analgesic (pain drugs) and sedative ( to calm patients down) management strategies use intravenous (into the vein), intramuscular ( into the muscle) and, more recently, intranasal (into the nostrils) routes. Unfortunately, intravenous access is hard to establish and may be painful for the child. The intramuscular route is often similarly painful. Due to the rich blood supply and large surface area of the nasal vestibule, intranasally (IN) administered medications are highly absorbed. IN approaches for procedural pain reduction, such as during dental work, have been demonstrated to make drug administration painless and well tolerated, making it an attractive potential alternative to commonly used intravenous and intramuscular approaches. In several small research studies, high doses of intranasal ketamine (9 mg/kg) produce adequate sedation during laceration repair with minimal side effects. A recent study compared IN ketamine, midazolam, fentanyl or combination of these drugs for pain management and urgent analgesia sedation, and demonstrated that they are effective and safe, reporting that ~60% of study participants sustained mild to moderate sedation. Unfortunately, there are not enough studies done to evaluate the sedation effect of IN ketamine for laceration repair. Small studies (Tsze and Nemeth) showed that IN ketamine is an effective alternative but no studies are done to compare combination IN midazolam and fentanyl to IN ketamine. Our null hypothesis is that there is no difference in sedation scores during laceration repair when comparing the use of IN ketamine to IN midazolam and IN fentanyl.

We will recruit a total of 30 pediatric patients (6 months - 10 y age) in a randomized double-blinded pilot study of IN ketamine alone or combined IN midazolam and IN fentanyl for laceration repair, comparing levels of pain and sedation scores using validated pediatric metrics as the primary outcomes. In addition, we will assess comparative nurse and physician satisfaction in each of these two groups. Understanding the relative effectiveness of these two approaches will help us identify a safe, effective, and easily administrable method to manage pain and anxiety, thereby, improving patient experience and outcomes during the often traumatic laceration repair procedure.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital - Royal Oak

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 10 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patients 6 months to 10 years who required laceration repair in the pediatric emergency center.
• Laceration should be less than 5 cm long, require 2 or more sutures and no consult subspeciality consult for repair.
• Topical anesthetic (lidocaine-epinephrine-tetracaine topical solution/XAP) will be applied to all lacerations for 20 minutes duration before giving the intranasal medications.

Exclusion Criteria:

• Age < 6 months
• Documented allergy or adverse effect to ketamine, midazolam or fentanyl
• Epistaxis
• Partial upper airway obstruction
• Oxygen requirement via nasal cannula
• Acute mental status changes (e.g. obtunded or somnolent)
• Documented increased intracranial pressure or increased ocular pressure
• Documented porphyria
• Previously involved in the study
• Parent or patient refusal
• Acutely compromised vitals (hypotension, desaturations, respiratory distress)
• Any known heart disease
• If any previous opioid use for analgesia during the visit
• Need for staples
• Scalp wounds
• General trauma requiring additional sedation
• Patients who received pain medications (acetaminophen or ibuprofen) before laceration repair

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IN ketamine; Intranasal ketamine 3mg/kg (max 100 mg) + saline 0.03 ml/kg (max 2ml)	Drug: Ketamine; Intranasal ketamine 3mg/kg (max 100 mg) + saline 0.03 ml/kg (max 2ml)
ACTIVE_COMPARATOR: IN midazolam and fentanyl; Intranasal midazolam 0.3 mg/kg (max 10 mg) + fentanyl 1.5mcg/kg (max 100 mcg)	Drug: Midazolam and fentanyl; Intranasal midazolam 0.3 mg/kg (max 10 mg) + fentanyl 1.5mcg/kg (max 100 mcg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedation Score	The primary outcome variable is the maximum sedation score as measured by the University of Michigan Sedation Scale. This scale consists of an ordinal scale from 0 being awake and alert and 4 being unarousable. Medians will be calculated for each group.	up to 30 minutes
Proportion of Children With Maximum Sedation Score	The proportion of children who receive a maximum sedation score of either 1 or 2 (without distinguishing between those values)	Up to 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Scores During Laceration Repair	The effect of IN ketamine vs IN midazolam + IN fentanyl on pain scores during laceration repair using either Face, Legs, Activity, Cry, Consolability (FLACC) Scale or Faces Scale pain scale depending for patient age, each a Likert scale from 0 being no pain to 10 being worst pain, median scores for each group	Up to 30 minutes
Nurse and Physician Satisfaction	Nurse and physician satisfaction will be assessed by a survey which will be filled in the end of the sedation. Response to overall experience question score on Likert scale where 1 is poor and 5 is Excellent. Proportion of responders giving answers of 4 or 5 will be calculated.	Up to 30 minutes
Rates of Failure	Rates of failure to repair laceration due to agitation or intolerable pain with the switch to intravenous medications will be compared between two groups. Percentage failure will be reported.	Up to 30 minutes
Change in Vitals	Proportion of children who have any significant change in vitals during analgosedation (any desaturation - Oxygen saturation < 90, and hypotension per age-related norms) will be compared between the two groups.	up to 30 minutes

Collaborators and Investigators

• Sponsor: William Beaumont Hospitals
• Investigators: Principal Investigator: Kelly Levasseur, DO, William Beaumont Hospitals

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 4, 2018
• Primary Completion (ACTUAL): February 6, 2019
• Study Completion (ACTUAL): February 6, 2019

Study Registration Dates

• First Submitted: May 5, 2018
• First Submitted That Met QC Criteria: May 5, 2018
• First Posted (ACTUAL): May 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2021
• Last Update Submitted That Met QC Criteria: July 29, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Pediatric; sedation; analgesia; pain control; intranasal midazolam; intranasal ketamine; intranasal fentanyl
• Additional Relevant MeSH Terms: Wounds and Injuries; Lacerations; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Fentanyl; Midazolam
• Other Study ID Numbers: 2017-363

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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