Nausea, Pain, Pruritus
Conditions
Keywords
morphine, naloxone, pediatrics, adverse effects, pain
Brief summary
This is an investigator initiated dose finding study designed to determine the optimal dose of naloxone to prevent or minimize the most common side effects induced by opioids, namely itching, nausea, and vomiting. Male and female inpatients of the Children's Center of the Johns Hopkins Hospital, who are greater than 6 and less than 18 years of age with acute, moderate to severe pain, and who are to be treated with intravenous Patient controlled analgesia (IVPCA) morphine will be eligible for inclusion in this study. Patients will be recruited by a study investigator prior to the initiation of IVPCA therapy. The majority of patients will be post operative patients, and will start therapy and the investigational drug in the Post Anesthesia Care Unit or the Pediatric Intensive Care Unit. The investigators plan on studying between 10 and 99, male and female patients over a 2 year period.
Detailed description
In patients of all ages, opioids are the cornerstone of management of moderate to severe pain. Regardless of method of administration, all opioids produce unwanted side effects, including pruritus, nausea and vomiting, constipation, urinary retention, cognitive impairment, tolerance, dependence, and (rarely) respiratory depression. Based on the results of a previously completed randomized controlled trial, children and adolescents with moderate to severe pain, are now routinely treated in the Children's Center of the Johns Hopkins Hospital with a low dose naloxone infusion (0.25 mcg/kg/HOUR) whenever morphine intravenous patient controlled analgesia (IVPCA) or parent/nurse controlled analgesia (IVPNCA) is initiated. Although the previous study showed a marked reduction in the incidence and severity of pruritus and nausea, approximately a third of the patients still experience these side effects. The primary purpose of this study is to reduce this failure rate by determining if there is an optimal dose of naloxone to prevent opioid induced side effects as determined by a dose finding classic up down dose escalation method. The second aim is to determine the pharmacokinetics of morphine and naloxone and their metabolites at each of the naloxone infusion rates attempted. The investigators will measure morphine, naloxone, and their metabolites using a liquid chromatographic-electrospray ionization-tandem mass spectrometric method (LC/MS/MS). The final aim is to determine the pharmacogenetics of responders and non-responders using DNA isolated from patient blood. To accomplish this the investigators will need a single blood collection from patients currently being treated with IVPCA morphine and low dose intravenous naloxone.
Interventions
DRUGnaloxone
continuous infusion of naloxone administered in escalating dosing from 0.05 mcg/kg/hr to 1.65 mcg/kg/hour
Sponsors
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients greater than 6 and less than 18 years of age with acute, moderate to severe pain who are to start treatment with IVPCA morphine as inpatients of the Children's Center of the Johns Hopkins Hospital
Exclusion criteria
* patients who require concomitant benzodiazepine administration * allergic to opioids * have been in an investigational drug trial within 1 month * received opioids with in 7 days of the study * parent with psychiatric illness which impairs their ability to provide consent parent who does not speak English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Naloxone Side Effects | 0-48 hours after infusion begins | incidence of nausea, vomiting, pruritus following naloxone infusion |
Countries
United States
Participant flow
Recruitment details
75 participants were consented, but only 64 participants participated in this study and were placed in the experimental arm.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 | 64 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 5 |
Baseline characteristics
| Characteristic | Group 1 |
|---|---|
| Age, Categorical <=18 years | 64 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 12 years STANDARD_DEVIATION 6 |
| Region of Enrollment United States | 64 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 59 |
| serious Total, serious adverse events | 0 / 59 |
Outcome results
Primary
Number of Participants With Naloxone Side Effects
incidence of nausea, vomiting, pruritus following naloxone infusion
Time frame: 0-48 hours after infusion begins
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naloxone | Number of Participants With Naloxone Side Effects | 32 participants |