Incidence of Headache Following an Unintentional Dural Puncture

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01977898
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arms: 2
• Duration (Months): 88
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Postdural Puncture Headache; Post-Lumbar Puncture Headache; Cerebrospinal Fluid Leaks	Drug: Morphine; Drug: Saline	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Incidence of Post-Dural Puncture Headache Following Unintentional Dural Puncture: A Randomized Trial of Intrathecal Morphine Versus Saline
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Morphine Patients randomized to the treatment group (morphine) will receive preservative-free morphine 0.3 mL (150 mcg) intrathecally.	Drug: 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.; Other Names: Duramorph
Placebo Comparator: Saline Patients randomized to the control group will receive normal saline 0.3 mL intrathecally.	Drug: 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.; Other Names: Normal Saline

Outcome Measures

Primary Outcome Measures

1. Participants Who Report Post Dural Puncture Headaches [5 days]

   Participants who report post dural puncture headaches from delivery to postpartum day 5

Secondary Outcome Measures

1. 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.

2. Treatment Method for Headache [Unintentional dural puncture - Postpartum day 5]

   Treatment method completed for unintentional dural puncture headache.

3. 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.

4. 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.

5. Presenting Day of Headache [Dural puncture to 5 days after delivery]

   Presenting day of headache after unintentional dural puncture

6. 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

7. 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.

8. Intrathecal Catheter Dwell Time [Insertion time to removal in minutes]

   Intrathecal catheter dwell time(time from insertion to time of removal in minutes).

9. Intrathecal Infusion Volume [Time of insertion of catheter to time catheter removed]

   Intrathecal infusion volume in milliliters

10. Mode of Delivery [up to 10 hours after intrathecal catheter placed]

    Mode of delivery of the baby (vaginal delivery or instrumented vaginal delivery)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Feyce Peralta, MD, Northwestern University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 9, 2018

More Information

Publications

• Al-metwalli RR. Epidural morphine injections for prevention of post dural puncture headache. Anaesthesia. 2008 Aug;63(8):847-50. doi: 10.1111/j.1365-2044.2008.05494.x. Epub 2008 Jun 10.
• Angle P, Tang SL, Thompson D, Szalai JP. Expectant management of postdural puncture headache increases hospital length of stay and emergency room visits. Can J Anaesth. 2005 Apr;52(4):397-402.
• Apfel CC, Saxena A, Cakmakkaya OS, Gaiser R, George E, Radke O. Prevention of postdural puncture headache after accidental dural puncture: a quantitative systematic review. Br J Anaesth. 2010 Sep;105(3):255-63. doi: 10.1093/bja/aeq191. Epub 2010 Aug 3. Review.
• Ayad S, Demian Y, Narouze SN, Tetzlaff JE. Subarachnoid catheter placement after wet tap for analgesia in labor: influence on the risk of headache in obstetric patients. Reg Anesth Pain Med. 2003 Nov-Dec;28(6):512-5.
• Banks S, Paech M, Gurrin L. An audit of epidural blood patch after accidental dural puncture with a Tuohy needle in obstetric patients. Int J Obstet Anesth. 2001 Jul;10(3):172-6.
• Carbaat PA, van Crevel H. Lumbar puncture headache: controlled study on the preventive effect of 24 hours' bed rest. Lancet. 1981 Nov 21;2(8256):1133-5.
• Carter BL, Pasupuleti R. Use of intravenous cosyntropin in the treatment of postdural puncture headache. Anesthesiology. 2000 Jan;92(1):272-4.
• Charsley MM, Abram SE. The injection of intrathecal normal saline reduces the severity of postdural puncture headache. Reg Anesth Pain Med. 2001 Jul-Aug;26(4):301-5.
• Choi A, Laurito CE, Cunningham FE. Pharmacologic management of postdural puncture headache. Ann Pharmacother. 1996 Jul-Aug;30(7-8):831-9. Review.
• Choi PT, Galinski SE, Takeuchi L, Lucas S, Tamayo C, Jadad AR. PDPH is a common complication of neuraxial blockade in parturients: a meta-analysis of obstetrical studies. Can J Anaesth. 2003 May;50(5):460-9.
• Cohen S, Amar D, Pantuck EJ, Singer N, Divon M. Decreased incidence of headache after accidental dural puncture in caesarean delivery patients receiving continuous postoperative intrathecal analgesia. Acta Anaesthesiol Scand. 1994 Oct;38(7):716-8.
• Denny N, Masters R, Pearson D, Read J, Sihota M, Selander D. Postdural puncture headache after continuous spinal anesthesia. Anesth Analg. 1987 Aug;66(8):791-4.
• Eldor J, Gozal Y, Lavie A, Guedj P. Late postspinal headache treated with epidural morphine. Anaesthesia. 1990 Dec;45(12):1099.
• Hakim SM. Cosyntropin for prophylaxis against postdural puncture headache after accidental dural puncture. Anesthesiology. 2010 Aug;113(2):413-20. doi: 10.1097/ALN.0b013e3181dfd424.
• Hartopp R, Hamlyn L, Stocks G. Ten years of experience with accidental dural puncture and post-dural-puncture headache in a tertiary obstetric anaesthesia department. Int J Obstet Anesth. 2010 Jan;19(1):118. doi: 10.1016/j.ijoa.2009.06.004. Epub 2009 Nov 28.
• Olesen J, Steiner TJ. The International classification of headache disorders, 2nd edn (ICDH-II). J Neurol Neurosurg Psychiatry. 2004 Jun;75(6):808-11.
• Scavone BM, Wong CA, Sullivan JT, Yaghmour E, Sherwani SS, McCarthy RJ. Efficacy of a prophylactic epidural blood patch in preventing post dural puncture headache in parturients after inadvertent dural puncture. Anesthesiology. 2004 Dec;101(6):1422-7.
• Sudlow C, Warlow C. Posture and fluids for preventing post-dural puncture headache. Cochrane Database Syst Rev. 2002;(2):CD001790. Review. Update in: Cochrane Database Syst Rev. 2013;7:CD001790.

• Responsible Party: Feyce M. Peralta, MD, MS, Assistant Professor in Anesthesiology, Northwestern University
• ClinicalTrials.gov Identifier: NCT01977898
• Other Study ID Numbers: STU00043549
• First Posted: Nov 7, 2013
• Last Update Posted: Nov 17, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Feyce M. Peralta, MD, MS, Assistant Professor in Anesthesiology, Northwestern University: Postdural puncture headache; Intrathecal morphine; Intrathecal catheter; Headache; Labor and delivery; Unintentional dural puncture
• Additional relevant MeSH terms: Post-Dural Puncture Headache; Cerebrospinal Fluid Leak; Headache; Wounds and Injuries; Morphine

Study Results

Participant Flow

Recruitment Details	68 were consented to participate in the study . 2 withdrew and 3 were excluded for non-functional catheter.

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	28	35
COMPLETED	27	34
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Morphine	Saline	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	27	34	61
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	33	32	32
Sex: Female, Male (Count of Participants)
Female	27 100%	34 100%	61 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 7.4%	3 8.8%	5 8.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 3.7%	5 14.7%	6 9.8%
White	24 88.9%	26 76.5%	50 82%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	27 100%	34 100%	61 100%
Ethnicity (Count of Participants)
Hispanic (ethnicity)	7 25.9%	3 8.8%	10 16.4%
Non-hispanic (ethnicity)	20 74.1%	31 91.2%	51 83.6%
Body Mass Index (kg/m^2) (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	29.1	28.9	29.0
Nulliparous (Count of Participants)
Count of Participants [Participants]	5 18.5%	4 11.8%	9 14.8%
Gestational age (weeks) (Weeks) [Median (Full Range) ]
Median (Full Range) [Weeks]	39	39	39
Loss of resistance method (Count of Participants)
Air	16 59.3%	17 50%	33 54.1%
Saline	11 40.7%	17 50%	28 45.9%
Intrathecal catheter depth (cm) (Centimeters (cm)) [Median (Inter-Quartile Range) ]
Insertion	11	11	11
Removal	11	11	11
Unable to aspirate prior to administering study drug (n) (Count of Participants)
Count of Participants [Participants]	4 14.8%	6 17.6%	10 16.4%

Outcome Measures

1. Primary Outcome

Title	Participants Who Report Post Dural Puncture Headaches
Description	Participants who report post dural puncture headaches from delivery to postpartum day 5
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	27	34
Count of Participants [Participants]	21 77.8%	27 79.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.877
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Severity of Post Dural Puncture Headache
Description	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

Outcome Measure Data

Analysis Population Description

21 in the morphine group and 27 in the saline group experienced headaches.

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	21	27
Median (Inter-Quartile Range) [score on a scale]	7	7.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.499
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Treatment Method for Headache
Description	Treatment method completed for unintentional dural puncture headache.
Time Frame	Unintentional dural puncture - Postpartum day 5

Outcome Measure Data

Analysis Population Description

21 in the morphine group and 27 in the saline group experienced unintentional post dural puncture headaches.

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	21	27
Epidural blood patch	11 40.7%	10 29.4%
Oral analgesics	9 33.3%	16 47.1%
Hydration	1 3.7%	1 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.463
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Number of Participants With Cranial Nerve Symptoms
Description	The number of participants who experience cranial nerve symptoms up to 5 days after the unintentional dural puncture.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

21 in the morphine group and 27 in the saline group experienced unintentional dural puncture headaches.

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	21	27
None	13 48.1%	24 70.6%
Visual	1 3.7%	0 0%
Auditory	7 25.9%	3 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.0463
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Repeat Epidural Blood Patch
Description	Repeated epidural blood patch for headache pain after unintentional dural puncture.
Time Frame	After first epidural blood patch to 5 days after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	11	10
Count of Participants [Participants]	1 3.7%	1 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.525
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Presenting Day of Headache
Description	Presenting day of headache after unintentional dural puncture
Time Frame	Dural puncture to 5 days after delivery

Outcome Measure Data

Analysis Population Description

21 in the morphine group and 27 in the saline group experienced headache after unintentional dural puncture.

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	21	27
Day 1	9 33.3%	11 32.4%
Day 2	8 29.6%	8 23.5%
Day 3	1 3.7%	4 11.8%
Day 4	3 11.1%	4 11.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.691
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture.
Description	The duration in days of headaches the participants experience after an unintentional dural puncture
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

21 in the morphine group and 27 in the saline group experienced headache after unintentional dural puncture.

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	21	27
1 day	4 14.8%	8 23.5%
2 day	5 18.5%	9 26.5%
3 day	7 25.9%	4 11.8%
4 day	4 14.8%	5 14.7%
5 day	1 3.7%	1 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.610
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Greatest Level of Headache Pain Experienced With the Unintentional Dural Puncture
Description	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

Outcome Measure Data

Analysis Population Description

21 in the morphine group and 27 in the saline group experienced unintentional post dural puncture headache.

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	21	27
Median (Full Range) [Score on a scale (0=no pain to 10 worst)]	7	7.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.499
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Secondary Outcome

Title	Intrathecal Catheter Dwell Time
Description	Intrathecal catheter dwell time(time from insertion to time of removal in minutes).
Time Frame	Insertion time to removal in minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	27	34
Median (Inter-Quartile Range) [Insertion to removal time in minutes]	418	427

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine, Saline
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.06
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Intrathecal Infusion Volume
Description	Intrathecal infusion volume in milliliters
Time Frame	Time of insertion of catheter to time catheter removed

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	27	34
Median (Inter-Quartile Range) [Milliters]	12.9	16.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Morphine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.31
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

11. Secondary Outcome

Title	Mode of Delivery
Description	Mode of delivery of the baby (vaginal delivery or instrumented vaginal delivery)
Time Frame	up to 10 hours after intrathecal catheter placed

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphine	Saline
Arm/Group Description	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.	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.
Measure Participants	27	34
Vaginal Delivery	24 88.9%	29 85.3%
Instrumented Vaginal Delivery	3 11.1%	5 14.7%

Adverse Events

Time Frame	5 days after delivery of baby.
Arm/Group Title	Morphine		Saline
Arm/Group Description	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.		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.
All Cause Mortality
	Morphine		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/34 (0%)
Serious Adverse Events
	Morphine		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Morphine		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/34 (0%)
Gastrointestinal disorders
New onset nausea	0/27 (0%)	0	0/34 (0%)	0
New onset vomiting	0/27 (0%)	0	0/34 (0%)	0

Limitations/Caveats

The results of our study should only be interpreted in the context of its limitations. Our sample size is small and we stopped the study prior to meeting our original estimated sample size.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.