Cerebrospinal Fluid Leaks, Postdural Puncture Headache, Post-Lumbar Puncture Headache
Conditions
Keywords
Postdural puncture headache, Intrathecal morphine, Intrathecal catheter, Headache, Labor and delivery, Unintentional dural puncture
Brief summary
The purpose of this study is to evaluate the use of intrathecal morphine administration following an unintentional dural puncture, to decrease the incidence of post dural puncture headaches (PDPH) in obstetric patients.
Detailed description
Unintentional dural puncture is a known risk of neuraxial techniques, occurring in roughly 1% of all epidural catheter placements. The incidence of post dural puncture headaches(PDPH) after unintentional dural puncture (UDP) is 50-80%. A PDPH is defined as a headache that occurs following a dural puncture, worsens within 15 minutes after sitting or standing and improves within 15 minutes after lying, with at least one of the following: neck stiffness, tinnitus, hypacusia, photophobia, or nausea. The headache develops within 5 days after dural puncture and resolves either spontaneously within 1 week or within 48 hours after effective treatment of the spinal fluid leak. The rates of PDPH following unintentional dural puncture with placement of an intrathecal catheter will be compared in two groups: intrathecal morphine (treatment) versus intrathecal saline (control) administered 1-2 hours after delivery, followed by immediate catheter removal. Patients randomized to the treatment group (morphine) will receive preservative-free morphine 0.3 mL (150 mcg) intrathecally. Those randomized to the control group will receive normal saline 0.3 mL intrathecally. After administration of intrathecal morphine, all patients will have their respirations monitored every hour for a period of 12 hours and then every two hours for a period of 12 hours. On postpartum days 1-5, all patients will be visited daily while inpatient and/or contacted by phone after discharge from the hospital. PDPH can lead to significant morbidity and negatively impact patient satisfaction with postpartum recovery. Along with headache, patients may develop cranial nerve palsy during the postpartum period leading to permanent disability. In addition, new mothers are unable to bond with their babies due to headache and associated symptoms of nausea, vomiting and limited mobility secondary to pain. Therefore, an effective intervention to decrease the risk of PDPH after UDP would be useful.
Interventions
DRUGMorphine
The drug will be prepared in tuberculin syringes. After thoroughly sanitizing the catheter port with a Chloroprep wipe and allowing adequate time for drying of the Chloroprep, the anesthesiologist will first attach a 3-mL syringe to the catheter port and aspirate to a volume of 1 mL. This syringe will then be removed from the port. The study drug will then be administered through the intrathecal catheter via the tuberculin syringe. The 3-mL syringe containing the aspirate will then be injected via the catheter, effectively flushing the study drug through the catheter. The intrathecal catheter will be removed immediately following the injection.
DRUGSaline
The drug will be prepared in tuberculin syringes. After thoroughly sanitizing the catheter port with a Chloroprep wipe and allowing adequate time for drying of the Chloroprep, the anesthesiologist will first attach a 3-mL syringe to the catheter port and aspirate to a volume of 1 mL. This syringe will then be removed from the port. The study drug will then be administered through the intrathecal catheter via the tuberculin syringe. The 3-mL syringe containing the aspirate will then be injected via the catheter, effectively flushing the study drug through the catheter. The intrathecal catheter will be removed immediately following the injection.
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Postpartum patients following vaginal delivery * Unintentional dural puncture * Functioning intrathecal catheter * Patients must be 18 years of age or older * English speaking.
Exclusion criteria
* History of previous PDPH * Body mass index BMI \> 40 kg/m2 * History of obstructive sleep apnea (OSA) * Morphine allergy * Patients who receive Cesarean delivery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Report Post Dural Puncture Headaches | 5 days | Participants who report post dural puncture headaches from delivery to postpartum day 5 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Post Dural Puncture Headache | Time of unintentional dural puncture to postpartum day 5 | Severity of post dural puncture headache on a numerical rating scale 0= no pain and 10= worst pain imaginable from the time of delivery to postpartum day 5. |
| Treatment Method for Headache | Unintentional dural puncture - Postpartum day 5 | Treatment method completed for unintentional dural puncture headache. |
| Number of Participants With Cranial Nerve Symptoms | 5 days | The number of participants who experience cranial nerve symptoms up to 5 days after the unintentional dural puncture. |
| Repeat Epidural Blood Patch | After first epidural blood patch to 5 days after delivery | Repeated epidural blood patch for headache pain after unintentional dural puncture. |
| Intrathecal Infusion Volume | Time of insertion of catheter to time catheter removed | Intrathecal infusion volume in milliliters |
| Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 5 days | The duration in days of headaches the participants experience after an unintentional dural puncture |
| Greatest Level of Headache Pain Experienced With the Unintentional Dural Puncture | 5 days | Greatest reported headache pain associated with unintentional dural puncture reported on a scale of 0= no pain to 10= worst pain imaginable. |
| Intrathecal Catheter Dwell Time | Insertion time to removal in minutes | Intrathecal catheter dwell time(time from insertion to time of removal in minutes). |
| Mode of Delivery | up to 10 hours after intrathecal catheter placed | Mode of delivery of the baby (vaginal delivery or instrumented vaginal delivery) |
| Presenting Day of Headache | Dural puncture to 5 days after delivery | Presenting day of headache after unintentional dural puncture |
Countries
United States
Participant flow
Recruitment details
68 were consented to participate in the study . 2 withdrew and 3 were excluded for non-functional catheter.
Participants by arm
| Arm | Count |
|---|---|
| Morphine Patients randomized to the treatment group (morphine) will receive preservative-free morphine 0.3 mL (150 mcg) intrathecally.
Morphine: The drug will be prepared in tuberculin syringes. After thoroughly sanitizing the catheter port with a Chloroprep wipe and allowing adequate time for drying of the Chloroprep, the anesthesiologist will first attach a 3-mL syringe to the catheter port and aspirate to a volume of 1 mL. This syringe will then be removed from the port. The study drug will then be administered through the intrathecal catheter via the tuberculin syringe. The 3-mL syringe containing the aspirate will then be injected via the catheter, effectively flushing the study drug through the catheter. The intrathecal catheter will be removed immediately following the injection. | 27 |
| Saline Patients randomized to the control group will receive normal saline 0.3 mL intrathecally.
Saline: The drug will be prepared in tuberculin syringes. After thoroughly sanitizing the catheter port with a Chloroprep wipe and allowing adequate time for drying of the Chloroprep, the anesthesiologist will first attach a 3-mL syringe to the catheter port and aspirate to a volume of 1 mL. This syringe will then be removed from the port. The study drug will then be administered through the intrathecal catheter via the tuberculin syringe. The 3-mL syringe containing the aspirate will then be injected via the catheter, effectively flushing the study drug through the catheter. The intrathecal catheter will be removed immediately following the injection. | 34 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Non functioning catheter | 1 | 1 |
Baseline characteristics
| Characteristic | Saline | Morphine | Total |
|---|---|---|---|
| Age, Continuous | 32 Years | 33 Years | 32 Years |
| Body Mass Index (kg/m^2) | 28.9 kg/m^2 | 29.1 kg/m^2 | 29.0 kg/m^2 |
| Ethnicity Hispanic (ethnicity) | 3 Participants | 7 Participants | 10 Participants |
| Ethnicity Non-hispanic (ethnicity) | 31 Participants | 20 Participants | 51 Participants |
| Gestational age (weeks) | 39 Weeks | 39 Weeks | 39 Weeks |
| Intrathecal catheter depth (cm) Insertion | 11 Centimeters (cm) | 11 Centimeters (cm) | 11 Centimeters (cm) |
| Intrathecal catheter depth (cm) Removal | 11 Centimeters (cm) | 11 Centimeters (cm) | 11 Centimeters (cm) |
| Loss of resistance method Air | 17 Participants | 16 Participants | 33 Participants |
| Loss of resistance method Saline | 17 Participants | 11 Participants | 28 Participants |
| Nulliparous | 4 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 24 Participants | 50 Participants |
| Region of Enrollment United States | 34 participants | 27 participants | 61 participants |
| Sex: Female, Male Female | 34 Participants | 27 Participants | 61 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Unable to aspirate prior to administering study drug (n) | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 34 |
| other Total, other adverse events | 0 / 27 | 0 / 34 |
| serious Total, serious adverse events | 0 / 27 | 0 / 34 |
Outcome results
Primary
Participants Who Report Post Dural Puncture Headaches
Participants who report post dural puncture headaches from delivery to postpartum day 5
Time frame: 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Morphine | Participants Who Report Post Dural Puncture Headaches | 21 Participants |
| Saline | Participants Who Report Post Dural Puncture Headaches | 27 Participants |
Comparison: A sample size of 65 patients in each group would be required to achieve 80% power to detect this difference between intrathecal morphine and saline administration . Sample size of 64 per group achieve 80% power to detect a difference between the group proportions of 0.25. The proportion in the treatment group is assumed to be 0.5 under the null hypothesis and 0.25 under the alternative hypothesis. The proportion in the control group is .05.The significance level of the test was targeted at .05.p-value: 0.877Fisher Exact
Secondary
Greatest Level of Headache Pain Experienced With the Unintentional Dural Puncture
Greatest reported headache pain associated with unintentional dural puncture reported on a scale of 0= no pain to 10= worst pain imaginable.
Time frame: 5 days
Population: 21 in the morphine group and 27 in the saline group experienced unintentional post dural puncture headache.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Morphine | Greatest Level of Headache Pain Experienced With the Unintentional Dural Puncture | 7 Score on a scale (0=no pain to 10 worst) |
| Saline | Greatest Level of Headache Pain Experienced With the Unintentional Dural Puncture | 7.5 Score on a scale (0=no pain to 10 worst) |
p-value: 0.499Wilcoxon (Mann-Whitney)
Secondary
Intrathecal Catheter Dwell Time
Intrathecal catheter dwell time(time from insertion to time of removal in minutes).
Time frame: Insertion time to removal in minutes
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Morphine | Intrathecal Catheter Dwell Time | 418 Insertion to removal time in minutes |
| Saline | Intrathecal Catheter Dwell Time | 427 Insertion to removal time in minutes |
p-value: 0.06Wilcoxon (Mann-Whitney)
Secondary
Intrathecal Infusion Volume
Intrathecal infusion volume in milliliters
Time frame: Time of insertion of catheter to time catheter removed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Morphine | Intrathecal Infusion Volume | 12.9 Milliters |
| Saline | Intrathecal Infusion Volume | 16.2 Milliters |
p-value: 0.31Wilcoxon (Mann-Whitney)
Secondary
Mode of Delivery
Mode of delivery of the baby (vaginal delivery or instrumented vaginal delivery)
Time frame: up to 10 hours after intrathecal catheter placed
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Morphine | Mode of Delivery | Vaginal Delivery | 24 Participants |
| Morphine | Mode of Delivery | Instrumented Vaginal Delivery | 3 Participants |
| Saline | Mode of Delivery | Instrumented Vaginal Delivery | 5 Participants |
| Saline | Mode of Delivery | Vaginal Delivery | 29 Participants |
Secondary
Number of Participants With Cranial Nerve Symptoms
The number of participants who experience cranial nerve symptoms up to 5 days after the unintentional dural puncture.
Time frame: 5 days
Population: 21 in the morphine group and 27 in the saline group experienced unintentional dural puncture headaches.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Morphine | Number of Participants With Cranial Nerve Symptoms | None | 13 Participants |
| Morphine | Number of Participants With Cranial Nerve Symptoms | Visual | 1 Participants |
| Morphine | Number of Participants With Cranial Nerve Symptoms | Auditory | 7 Participants |
| Saline | Number of Participants With Cranial Nerve Symptoms | None | 24 Participants |
| Saline | Number of Participants With Cranial Nerve Symptoms | Visual | 0 Participants |
| Saline | Number of Participants With Cranial Nerve Symptoms | Auditory | 3 Participants |
p-value: 0.0463Chi-squared
Secondary
Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture.
The duration in days of headaches the participants experience after an unintentional dural puncture
Time frame: 5 days
Population: 21 in the morphine group and 27 in the saline group experienced headache after unintentional dural puncture.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Morphine | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 2 day | 5 Participants |
| Morphine | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 4 day | 4 Participants |
| Morphine | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 3 day | 7 Participants |
| Morphine | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 5 day | 1 Participants |
| Morphine | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 1 day | 4 Participants |
| Saline | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 5 day | 1 Participants |
| Saline | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 1 day | 8 Participants |
| Saline | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 2 day | 9 Participants |
| Saline | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 3 day | 4 Participants |
| Saline | Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture. | 4 day | 5 Participants |
p-value: 0.61Wilcoxon (Mann-Whitney)
Secondary
Presenting Day of Headache
Presenting day of headache after unintentional dural puncture
Time frame: Dural puncture to 5 days after delivery
Population: 21 in the morphine group and 27 in the saline group experienced headache after unintentional dural puncture.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Morphine | Presenting Day of Headache | Day 1 | 9 Participants |
| Morphine | Presenting Day of Headache | Day 2 | 8 Participants |
| Morphine | Presenting Day of Headache | Day 3 | 1 Participants |
| Morphine | Presenting Day of Headache | Day 4 | 3 Participants |
| Saline | Presenting Day of Headache | Day 4 | 4 Participants |
| Saline | Presenting Day of Headache | Day 1 | 11 Participants |
| Saline | Presenting Day of Headache | Day 3 | 4 Participants |
| Saline | Presenting Day of Headache | Day 2 | 8 Participants |
p-value: 0.691Wilcoxon (Mann-Whitney)
Secondary
Repeat Epidural Blood Patch
Repeated epidural blood patch for headache pain after unintentional dural puncture.
Time frame: After first epidural blood patch to 5 days after delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Morphine | Repeat Epidural Blood Patch | 1 Participants |
| Saline | Repeat Epidural Blood Patch | 1 Participants |
p-value: 0.525Chi-squared
Secondary
Severity of Post Dural Puncture Headache
Severity of post dural puncture headache on a numerical rating scale 0= no pain and 10= worst pain imaginable from the time of delivery to postpartum day 5.
Time frame: Time of unintentional dural puncture to postpartum day 5
Population: 21 in the morphine group and 27 in the saline group experienced headaches.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Morphine | Severity of Post Dural Puncture Headache | 7 score on a scale |
| Saline | Severity of Post Dural Puncture Headache | 7.5 score on a scale |
p-value: 0.499Wilcoxon (Mann-Whitney)
Secondary
Treatment Method for Headache
Treatment method completed for unintentional dural puncture headache.
Time frame: Unintentional dural puncture - Postpartum day 5
Population: 21 in the morphine group and 27 in the saline group experienced unintentional post dural puncture headaches.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Morphine | Treatment Method for Headache | Epidural blood patch | 11 Participants |
| Morphine | Treatment Method for Headache | Oral analgesics | 9 Participants |
| Morphine | Treatment Method for Headache | Hydration | 1 Participants |
| Saline | Treatment Method for Headache | Epidural blood patch | 10 Participants |
| Saline | Treatment Method for Headache | Oral analgesics | 16 Participants |
| Saline | Treatment Method for Headache | Hydration | 1 Participants |
p-value: 0.463Chi-squared