Two Dose Neuraxial Morphine for Prevention of Postdural Puncture Headache
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Columbia University
- Enrollment
- 44
- Locations
- 4
- Primary Endpoint
- Number of Participants With Postdural Puncture Headache
Study Overview
Brief Summary
Neuraxial analgesia (most commonly continuous epidural or combined spinal epidural) is the most effective modality available for pain relief during labor. Accidental dural puncture (ADP) with a large bore epidural needle and the resulting post-dural puncture headache (PDPH) is one of the most significant sources of anesthesia-related morbidity in parturients.
Epidural blood patch (EBP) is the gold standard for treatment of PDPH, and although almost always effective, can result in another ADP, as well as low back pain and lower extremity pain. For this reason, effective measures to prevent PDPH when ADP occurs would be highly valuable. One small study in which 50 women were randomly allocated to receive 2 epidural injections of morphine or saline, demonstrated a beneficial effect of epidural morphine in decreasing the incidence of PDPH.
This study aims to determine the efficacy of 2 doses of neuraxial (either epidural (EPID) or intrathecal) preservative-free morphine (PFM) to prevent headache after ADP in parturients.
Detailed Description
This will be a prospective, randomized, double blind clinical trial. Subjects will be ASA I and II women (per American Society of Anesthesiologists Physical Status Classification System or ASA) aged 18 years and older, who are known to have had ADP with an epidural needle during placement of neuraxial labor analgesia, and have either an intrathecal catheter or epidural catheter in situ. Patients will be randomized to either receive PFM or placebo (sterile normal saline (NS or SAL)).
For patients with an epidural catheter, the group "EPID PFM" will receive 3 mg (6 ml) of PFM, followed by 3 ml of sterile normal saline to be administered through the epidural catheter. The placebo group, "EPID NS", will receive 6 ml of sterile normal saline via the epidural catheter followed by another 3 ml NS. For patients with an intrathecal catheter, the group, "IT PFM" will receive 200 micrograms (mcg) (0.4 ml) of preservative-free morphine, followed by a flush of the catheter with 2 ml of sterile saline. The placebo group will receive 0.4 ml and then 2 ml of sterile normal saline through the intrathecal catheter. Sixteen to 24 hours after receiving the first study drug, patients in all groups will be visited by an investigator, and then daily thereafter during the hospital admission. They will be evaluated for the presence of headache, analgesia requirements, need for EBP and the severity of opioid side effects. As long as the patient is afebrile, has not been experiencing severe opioid side effects and the catheter is in place and intact, the patient will then receive the identical study drug (for a total of two doses). The epidural/intrathecal catheter will be removed immediately after the second administration of the study drug.
After discharge, the patient will be followed up once daily by telephone for up to a minimum of 5 days after receiving the last dose of the study drug if they remain headache free, and for a minimum of 3 days after resolution of PDPH.
Statistical Design:
This will be a prospective randomized double blind clinical trial. The primary outcome will be the incidence of PDPH at 48 hours after ADP. The primary outcome of the trial is the incidence of PDPH at 48 hours after ADP. We will consider a difference in incidence of PDPH between the placebo and treatment groups of 25 % to be significant, based on the findings of Al Metwalli et al. (Anaesthesia. 2008; 63(8):847-50), and the meta-analysis by Heesen et al. (Int J Obstet Anesth. 2013 ; 22(1):26-30).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subjects will be ASA I and II women aged 18 years and older, who are known to have had accidental dural puncture with an epidural needle during placement of neuraxial labor analgesia, and have either an intrathecal catheter or epidural catheter in place.
Exclusion Criteria
- •Past history of headache syndromes- such as migraine and cluster headaches
- •History of chronic pain syndromes
- •Chronic opioid use
- •Illicit drug use - e.g. marijuana, heroin
- •Allergy to morphine
- •Intrapartum or postpartum fever ≥ 38 ° C
- •Coagulopathy
- •Accidental removal of the epidural or intrathecal catheter
Arms & Interventions
EPID PFM
The group "EPID PFM" will receive 3 mg (6 ml) of preservative-free morphine, followed by 3 ml of sterile normal saline, to be administered through the epidural catheter.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Intervention: Morphine (Drug)
EPID PFM
The group "EPID PFM" will receive 3 mg (6 ml) of preservative-free morphine, followed by 3 ml of sterile normal saline, to be administered through the epidural catheter.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Intervention: Sterile normal saline (Drug)
EPID SAL
The placebo group, "EPID NS", will receive 6 ml of sterile normal saline via the epidural catheter followed by another 3 ml NS. Sixteen to 24 hours after receiving the first study drug,the patient will then receive the identical study drug (for a total of two doses).
Intervention: Sterile normal saline (Drug)
IT PFM
The group, "IT PFM" will receive 200 micrograms (mcg) (0.4 ml) of preservative-free morphine via the intrathecal catheter, followed by a flush of the catheter with 2 ml of sterile saline.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Intervention: Morphine (Drug)
IT PFM
The group, "IT PFM" will receive 200 micrograms (mcg) (0.4 ml) of preservative-free morphine via the intrathecal catheter, followed by a flush of the catheter with 2 ml of sterile saline.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Intervention: Sterile normal saline (Drug)
IT SAL
The placebo group IT SAL will receive 0.4 ml and then 2 ml of sterile normal saline through the intrathecal catheter.Sixteen to 24 hours after receiving the first study drug, the patient will then receive the identical study drug (for a total of two doses).
Intervention: Sterile normal saline (Drug)
Outcomes
Primary Outcomes
Number of Participants With Postdural Puncture Headache
Time Frame: 48 hours after accidental dural puncture
The primary outcome will be the incidence of postdural puncture headache at 48 hours after accidental dural puncture. This will be determined by a face to face questionnaire and the severity of headache will be rated according to a verbal rating scale (0 -10).
Secondary Outcomes
- Number of Participants in Need for Epidural Blood Patch(48 hours after accidental dural puncture)
Investigators
Richard M. Smiley
Professor of Anesthesiology
Columbia University