Track topics on Twitter Track topics that are important to you
The use of methadone to provide analgesia may be increasing due to advantages compared to other commonly used opioid analgesic drugs. While efficacy of methadone has been reported in adults, there is a paucity of information in neonates and infants. In the latter population, fentanyl and morphine are most commonly used for opioid analgesia following major surgery, while methadone is frequently used for weaning of opioid dependent and tolerant patients, in spite of the paucity of knowledge of methadone pharmacology in this population. There are several clinical problems associated with fentanyl and morphine, and methadone may offer superior efficacy with fewer side effects than these agents. We propose to study the pharmacokinetics (PK) and pharmacodynamics (PD) of methadone in neonates and infants in the intensive care unit following cardiac surgery.
Fentanyl will be administered for intraoperative analgesia by the treating anesthesiologist in a dose range of 25 - 50 mcg/kg. No other intraoperative opioids will be given.
Subjects will receive intravenous methadone or morphine ("study drug") delivered by an initial IV "bolus" injection followed by a nurse-administered patient controlled analgesia (PCA) device for postoperative pain for a period of 24 hours. The initial dose of study drug will be 0.2 mg/kg IV administered following admission to the ICU after surgery. The study drug will then be given at a dose of 0.035 mg/kg IV as needed q30min via PCA. The study drug may be increased or decreased in increments of 20-25% according to the discretion of the investigator as needed to maintain a FLACC pain assessment tool < 4. Subjects will also receive lorazepam 0.025 mg/kg IV q2hr as needed for agitation as indicated by specific criteria. The study drug will be discontinued after 24 hours to facilitate "wash out" sampling and determination of elimination half-life. Beginning at 24 hours, fentanyl will be used for analgesia at an equianalgesic dose to be determined by the investigator based upon the current PCA "study drug" dose.
Measurements and Monitoring:
- Blood samples will be obtained for measurement of concentrations of methadone (methadone group) and morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide (morphine group), prior to administration of initial bolus dose (t = 0) and t = 5 min, 15 min, 30 min, 60 min, 2 hrs, 4 hrs and 6 hrs; thereafter, blood samples will be obtained for measurement every 6 hrs for up to 90 hrs according to availability of vascular access for phlebotomy.
- Continuous monitoring: temperature (rectal), electrocardiogram, heart rate, systemic arterial blood pressure, central venous blood pressure, respiratory rate, oxygen saturation (pulse oximetry)
- Intermittent recording (q1hr): urine output
- Lab Tests (at baseline[prior to study procedures] and 24 hours after initial dose of study medication): arterial blood gas tensions, arterial lactate, Hb/Hct, BUN/Cr, glucose, AST, ALT
- 12 lead ECG at hour 24 for determination of QTc.
- The Faces, Legs, Activity, Cry, Consolability (FLACC) Scale recoded every hour, and preceding every study medication PCA dose for 24 hours.
- Subject follow up at 90 hours to record time of extubation, re-intubation if necessary, and reason for re-intubation.
Primary Endpoints: Pharmacokinetics of methadone and morphine, including its metabolites (morphine-3-glucuronide and morphine-6-glucuronide)
- Pain scores (FLACC) during the 24 hours study period
- Amount of study drug administered during the 24-hour dosing period
- Changes in heart rate, systemic arterial blood pressure and laboratory test values
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Methadone or Morphine
Stanford University School of Medicine
Published on BioPortfolio: 2014-08-27T03:14:57-0400
This is a randomized Phase II study testing the effectiveness of the combination of morphine and methadone versus morphine alone in relieving pain. A second goal is to further evaluate any...
Primary Objective: To determine whether the addition of low dose methadone to morphine(in the methadone group) has a lower dose escalation index as compared to the morphine alone(in the m...
RATIONALE: Methadone, morphine, or oxycodone may help relieve pain caused by cancer. It is not yet known whether methadone is more effective than morphine or oxycodone in treating pain in ...
The investigators propose to compare analgesia by methadone and ketamine with a combination of morphine and ketamine in orthopedic surgery patients with moderate to severe pain. The invest...
The purpose of this study is to compare methadone with morphine in the management of moderate to severe cancer pain.
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Depending on its pathophysiological mechanism, it may be classified into nociceptiv...
Acute pain management in opioid-dependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalg...
Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or othe...
The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy rat...
The objective of this review was to assess the existent evidence for the use of methadone as first line therapy in cancer pain management.
A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Methadone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)
A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration.
An opioid analgesic with actions and uses similar to those of MORPHINE, apart from an absence of cough suppressant activity. It is used in the treatment of moderate to severe pain, including pain in obstetrics. It may also be used as an adjunct to anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1092)
An opioid analgesic structurally related to METHADONE and used in the treatment of severe pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1070)
An opioid analgesic used similarly to MORPHINE in the control of moderate to severe pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1097)
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...
Pain is defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. Some illnesses can be excruci...