Ignite Creation Date:
2024-05-06 @ 2:31 AM
Last Modification Date:
2024-10-26 @ 11:20 AM
Study NCT ID:
NCT02067520
Status:
COMPLETED
Last Update Posted:
2016-01-08
First Post:
2014-01-30
Brief Title:
Intrathecal Hydromorphone for Cesarean Section
Sponsor:
Thomas Jefferson University
Organization:
Thomas Jefferson University
Study Overview
Official Title:
Intrathecal IT Hydromorphone for Cesarean Section CS A Dose Finding Study
Status:
COMPLETED
Status Verified Date:
2016-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Introduction
Cesarean section CS is usually performed under spinal with preservative free morphine for pain relief but the investigators have a severe shortage of this formulation of morphine Hydromorphone is a narcotic which acts peripherally and centrally to decrease pain It has been used in spinals for postoperative pain relief and in pain pumps for relief of chronic pain No randomized controlled studies have evaluated intrathecal IT hydromorphone for post CS pain
Methods
This is a randomized double-blind controlled trial utilizing the up-down sequential allocation method12 to find the best dose of IT hydromorphone that provides pain relief following CS Patients will be given a morphine PCA pump for additional pain relief Our first patient will receive 200 mcg of IT hydromorphone Pain nausea and itching will be evaluated at 4 8 12 and 24 hours following the CS via numeric rating scales vomiting and morphine use per hour will be recorded Success will be a median morphine usage of less than or equal to 1mghour in the following 16 hours If a success the next patient will be given 10 mcg less IT hydromorphone if a failure she will receive 10 mcg more The study will end after 5 successes
Objective
The primary objective is to find the optimal dose of IT hydromorphone for pain relief following CS The secondary objectives are to define the incidence and severity of hydromorphones side effects and determine the duration of analgesia
Cesarean section CS is usually performed under spinal with preservative free morphine for pain relief but the investigators have a severe shortage of this formulation of morphine Hydromorphone is a narcotic which acts peripherally and centrally to decrease pain It has been used in spinals for postoperative pain relief and in pain pumps for relief of chronic pain No randomized controlled studies have evaluated intrathecal IT hydromorphone for post CS pain
Methods
This is a randomized double-blind controlled trial utilizing the up-down sequential allocation method12 to find the best dose of IT hydromorphone that provides pain relief following CS Patients will be given a morphine PCA pump for additional pain relief Our first patient will receive 200 mcg of IT hydromorphone Pain nausea and itching will be evaluated at 4 8 12 and 24 hours following the CS via numeric rating scales vomiting and morphine use per hour will be recorded Success will be a median morphine usage of less than or equal to 1mghour in the following 16 hours If a success the next patient will be given 10 mcg less IT hydromorphone if a failure she will receive 10 mcg more The study will end after 5 successes
Objective
The primary objective is to find the optimal dose of IT hydromorphone for pain relief following CS The secondary objectives are to define the incidence and severity of hydromorphones side effects and determine the duration of analgesia
Detailed Description:
SpecificAims Cesarean section CS is usually performed under spinal anesthesia with preservative free morphine added for pain relief but currently the investigators have a severe shortage of this formulation of morphine Hydromorphone is a narcotic which has been used in spinals for acute postoperative pain relief and in pain pumps for relief of chronic pain The investigators hypothesize that a dose between 25 and 200 mcg of IT hydromorphone will provide pain relief for at least 16 hours following CS with the need for minimal rescue medication and therefore may be a reasonable alternative to IT morphine
Background and Significance Cesarean section is usually performed under spinal anesthesia using bupivacaine Intrathecal preservative free morphine is often added to decrease postoperative pain for 12-24 hours with only the need for minor rescue medication a significant intravenous and oral opioid sparing effect This allows earlier mobilization and interaction with familyinfant of these hypercoagulable patients With the critical shortage of this formulation of morphine we must find an alternative medication Hydromorphone is a narcotic which acts peripherally and centrally to decrease pain It has been used in spinal anesthetics for acute postoperative pain relief and in pain pumps for relief of chronic pain Currently hydromorphone is not approved for intrathecal administration by the FDA but pain practitioners commonly prescribe hydromorphone for intrathecal pumps and have so for years The most recent Poly Analgesic Consensus Conference PACC of 2012 included IT hydromorphone as an acceptable opioid for chronic use Its inclusion for the management of neuropathic and nociceptive pain infers hydromorphones relative neurologic safety as it is used in much higher doses than for cesarean section The investigators reviewed the literature to learn if IT hydromorphone has been used for post CS pain relief and if so at what dose A retrospective chart review comparing IT hydromorphone to fentanyl after CS and a case report of IT hydromorphone for a repeat CS were all the investigators found34 No randomized controlled studies exist
Our study will find the optimal dose of IT hydromorphone for pain relief following cesarean section as well as delineate the incidence and severity of side effects and how long the drug lasts This information is critical as no other viable alternatives currently exist to replace IT morphine in this capacity
Preliminary StudiesProgress Report
The spinal anesthetic including the IT hydromorphone will be performed by a competent anesthesia resident or attending residents on the obstetric anesthesia service the principal investigator or one of the co-investigators Our CS rate is about 31 of 2100 deliveries per year and most 80 are done under spinal
Research Design and Methods
This is a randomized double-blind controlled trial utilizing the up-down sequential allocation method continual reassessment12 to find the best dose of IT hydromorphone that provides pain relief following CS Spinal anesthetic containing the specified dose of IT hydromorphone will be administered in the OR by the anesthesia resident or attending
After consent is obtained the first patient will be assigned to a dose of 200 mcg of IT hydromorphone Although the dose of IT hydromorphone equivalent to that of IT morphine for post cesarean section pain is not known some sources suggest that 50 - 100 mcg of IT hydromorphone may be similar to 100 - 200 mcg of IT morphine5-8 After preliminary observations using varying doses of IT hydromorphone for post CS analgesia the investigators observed that average and median morphine consumption in the following 16 hours was not markedly decreased until a dose of 200 mcg IT hydromorphone was reached 40 observational patients to date no increased side effects The investigators now use this dose routinely on labor and delivery so the investigators have chosen this as a starting dose The spinal anesthetic will also include 15mg of hyperbaric bupivacaine All patients will be provided with a morphine patient controlled analgesia PCA pump in the post-anesthesia care unit PACU for additional pain relief At 4 8 12 and 24 hours following the CS the patient will rate her pain degree of nausea and itching with verbal numeric rating scales pain 0 - 10 nausea and itching 0 - 5 and the investigators will record the incidence of vomiting These verbal numeric rating scales are commonly used at Thomas Jefferson for any patient using IV PCA pumps for postoperative pain The investigators will also obtain a validated quality of recovery scale from each patient Standard nursing orders include monitoring respiratory rate every 1 hour for 6 hours then every 2 hours for 6 hours for signs of respiratory depression use of pulse oximetry and administration of naloxone if needed These orders are currently standard for all patients receiving IT preservative free morphine and are in an order set in Jeff Chart The PCA pump will be queried the next day to evaluate the number of attempts and actual use of morphine in the first 16 hours postoperatively The data will be compiled and analyzed by our statistician Success will be defined as a median dose of less than or equal to 1mghour of morphine usage in the following 16 postoperative hours If a patient is determined to be a success the next patient will be assigned to a dose of IT hydromorphone that is 10 mcg less than the previous patient If the first patient is a success the second patient will receive 190 mcg of IT hydromorphone If a patient is deemed a failure the next patient will receive a dose of IT hydromorphone that is 10 mcg higher than the previous patient If the first patient is a failure the second patient will receive 210 mcg of IT hydromorphone Our goal is to stop the study when the investigators get 5 points of success using the lowest concentration of IT hydromorphone resulting in a median dose of less than or equal to 1mghr of morphine consumption in the 16 hours post-operatively
Statistical Methods This is a randomized double-blind controlled trial utilizing the up-down sequential allocation method of Dixon and Massey12 On the basis of previous non-probability sequential dosing studies with binary outcomes success vs failure the investigators estimate on enrolling 40-50 patients9-11 Using the referenced studies the investigators estimate a minimum of 10 independent negative-positive up-and-down deflections in the study Our goal is to stop the study when the investigators get 5 points of success using the lowest concentration of IT hydromorphone resulting in less than or equal to 1mghr of morphine consumption for 16 hours post-operatively
All data will be analyzed using the Statistical Package for the Social Sciences SPSS software Version 210 IBM Corporation The continuous data will be reported as mean standard deviation SD Tests of significance include the t test for independent samples Wilcoxon rank-sum test for non-parametric data and Chi-square or Fishers exact test for frequency count data Repeated measurements pain scores nausea scores will be analyzed by repeated measure analysis of variance where normally distributed with further paired comparisons at each time interval performed using the t-test A P value 005 will be considered significant A dose response curve will also be created to determine the effective dose in 95 of patients ED95 and effective dose in 50 of patients ED50 for the patient population
1 The investigators would like to enroll at least 40 - 50 patients as needed
2 PCA pump attempts and usage for 16 hours pain medication adjuncts used verbal numeric rating scores for nausea itching and pain incidence of vomiting and respiratory rate recorded every one hour will be obtained
3 The patient will be approached if she meets inclusion criteria when she is admitted to the labor floor on the morning of her scheduled CS The study will be explained to her the possible risks benefits and alternatives will be discussed she will be given the opportunity to ask questions and if she agrees the consent will be signed The dose of IT hydromorphone will be determined and made up by our statistician physician The spinal anesthetic will be administered to the patient in the operating room and the CS will proceed as usual Data will be collected over the next 16 hours according to the above research design
4 Risks of any narcotic medication include analgesia drowsiness mental clouding changes in mood euphoria or dysphoria respiratory depression cough suppression decreased gastrointestinal motility nausea vomiting increased cerebrospinal fluid pressure increased biliary pressure pinpoint constriction of the pupils increased parasympathetic activity and transient hyperglycemia There is also the risk that the study drug is ineffective at controlling post CS pain
5 Standard nursing orders will include monitoring respiratory rate every 1 hour for 6 hours then every 2 hours for 6 hours for signs of respiratory depression use of pulse oximetry and administration of naloxone if needed These orders are currently standard for all patients receiving IT preservative free morphine and are in an order set in Jeff Chart They allow early recognition of andor minimize the risk of respiratory depression should it occur Also the dosages the investigators will use are well below documented safe doses of this drug for the IT route All patients will be provided with a morphine patient controlled analgesia PCA pump in the postanesthesia care unit PACU for additional pain relief whether or not the study drug is effective
6 Potential benefit of the study is pain relief in the postoperative period following CS Our usual medication is currently unavailable or in critically limited supply
7 The side effect profiles for our standard drug IT morphine and the study drug IT hydromorphone are similar Delayed respiratory depression and itching are more notable with IT morphine than described with IT hydromorphone so this may be beneficial The duration of action of IT hydromorphone may not be as long as that of IT morphine
This study poses minimal risk This is a dose finding study The dosages the investigators will use are well below documented safe doses of this drug for the IT route
Background and Significance Cesarean section is usually performed under spinal anesthesia using bupivacaine Intrathecal preservative free morphine is often added to decrease postoperative pain for 12-24 hours with only the need for minor rescue medication a significant intravenous and oral opioid sparing effect This allows earlier mobilization and interaction with familyinfant of these hypercoagulable patients With the critical shortage of this formulation of morphine we must find an alternative medication Hydromorphone is a narcotic which acts peripherally and centrally to decrease pain It has been used in spinal anesthetics for acute postoperative pain relief and in pain pumps for relief of chronic pain Currently hydromorphone is not approved for intrathecal administration by the FDA but pain practitioners commonly prescribe hydromorphone for intrathecal pumps and have so for years The most recent Poly Analgesic Consensus Conference PACC of 2012 included IT hydromorphone as an acceptable opioid for chronic use Its inclusion for the management of neuropathic and nociceptive pain infers hydromorphones relative neurologic safety as it is used in much higher doses than for cesarean section The investigators reviewed the literature to learn if IT hydromorphone has been used for post CS pain relief and if so at what dose A retrospective chart review comparing IT hydromorphone to fentanyl after CS and a case report of IT hydromorphone for a repeat CS were all the investigators found34 No randomized controlled studies exist
Our study will find the optimal dose of IT hydromorphone for pain relief following cesarean section as well as delineate the incidence and severity of side effects and how long the drug lasts This information is critical as no other viable alternatives currently exist to replace IT morphine in this capacity
Preliminary StudiesProgress Report
The spinal anesthetic including the IT hydromorphone will be performed by a competent anesthesia resident or attending residents on the obstetric anesthesia service the principal investigator or one of the co-investigators Our CS rate is about 31 of 2100 deliveries per year and most 80 are done under spinal
Research Design and Methods
This is a randomized double-blind controlled trial utilizing the up-down sequential allocation method continual reassessment12 to find the best dose of IT hydromorphone that provides pain relief following CS Spinal anesthetic containing the specified dose of IT hydromorphone will be administered in the OR by the anesthesia resident or attending
After consent is obtained the first patient will be assigned to a dose of 200 mcg of IT hydromorphone Although the dose of IT hydromorphone equivalent to that of IT morphine for post cesarean section pain is not known some sources suggest that 50 - 100 mcg of IT hydromorphone may be similar to 100 - 200 mcg of IT morphine5-8 After preliminary observations using varying doses of IT hydromorphone for post CS analgesia the investigators observed that average and median morphine consumption in the following 16 hours was not markedly decreased until a dose of 200 mcg IT hydromorphone was reached 40 observational patients to date no increased side effects The investigators now use this dose routinely on labor and delivery so the investigators have chosen this as a starting dose The spinal anesthetic will also include 15mg of hyperbaric bupivacaine All patients will be provided with a morphine patient controlled analgesia PCA pump in the post-anesthesia care unit PACU for additional pain relief At 4 8 12 and 24 hours following the CS the patient will rate her pain degree of nausea and itching with verbal numeric rating scales pain 0 - 10 nausea and itching 0 - 5 and the investigators will record the incidence of vomiting These verbal numeric rating scales are commonly used at Thomas Jefferson for any patient using IV PCA pumps for postoperative pain The investigators will also obtain a validated quality of recovery scale from each patient Standard nursing orders include monitoring respiratory rate every 1 hour for 6 hours then every 2 hours for 6 hours for signs of respiratory depression use of pulse oximetry and administration of naloxone if needed These orders are currently standard for all patients receiving IT preservative free morphine and are in an order set in Jeff Chart The PCA pump will be queried the next day to evaluate the number of attempts and actual use of morphine in the first 16 hours postoperatively The data will be compiled and analyzed by our statistician Success will be defined as a median dose of less than or equal to 1mghour of morphine usage in the following 16 postoperative hours If a patient is determined to be a success the next patient will be assigned to a dose of IT hydromorphone that is 10 mcg less than the previous patient If the first patient is a success the second patient will receive 190 mcg of IT hydromorphone If a patient is deemed a failure the next patient will receive a dose of IT hydromorphone that is 10 mcg higher than the previous patient If the first patient is a failure the second patient will receive 210 mcg of IT hydromorphone Our goal is to stop the study when the investigators get 5 points of success using the lowest concentration of IT hydromorphone resulting in a median dose of less than or equal to 1mghr of morphine consumption in the 16 hours post-operatively
Statistical Methods This is a randomized double-blind controlled trial utilizing the up-down sequential allocation method of Dixon and Massey12 On the basis of previous non-probability sequential dosing studies with binary outcomes success vs failure the investigators estimate on enrolling 40-50 patients9-11 Using the referenced studies the investigators estimate a minimum of 10 independent negative-positive up-and-down deflections in the study Our goal is to stop the study when the investigators get 5 points of success using the lowest concentration of IT hydromorphone resulting in less than or equal to 1mghr of morphine consumption for 16 hours post-operatively
All data will be analyzed using the Statistical Package for the Social Sciences SPSS software Version 210 IBM Corporation The continuous data will be reported as mean standard deviation SD Tests of significance include the t test for independent samples Wilcoxon rank-sum test for non-parametric data and Chi-square or Fishers exact test for frequency count data Repeated measurements pain scores nausea scores will be analyzed by repeated measure analysis of variance where normally distributed with further paired comparisons at each time interval performed using the t-test A P value 005 will be considered significant A dose response curve will also be created to determine the effective dose in 95 of patients ED95 and effective dose in 50 of patients ED50 for the patient population
1 The investigators would like to enroll at least 40 - 50 patients as needed
2 PCA pump attempts and usage for 16 hours pain medication adjuncts used verbal numeric rating scores for nausea itching and pain incidence of vomiting and respiratory rate recorded every one hour will be obtained
3 The patient will be approached if she meets inclusion criteria when she is admitted to the labor floor on the morning of her scheduled CS The study will be explained to her the possible risks benefits and alternatives will be discussed she will be given the opportunity to ask questions and if she agrees the consent will be signed The dose of IT hydromorphone will be determined and made up by our statistician physician The spinal anesthetic will be administered to the patient in the operating room and the CS will proceed as usual Data will be collected over the next 16 hours according to the above research design
4 Risks of any narcotic medication include analgesia drowsiness mental clouding changes in mood euphoria or dysphoria respiratory depression cough suppression decreased gastrointestinal motility nausea vomiting increased cerebrospinal fluid pressure increased biliary pressure pinpoint constriction of the pupils increased parasympathetic activity and transient hyperglycemia There is also the risk that the study drug is ineffective at controlling post CS pain
5 Standard nursing orders will include monitoring respiratory rate every 1 hour for 6 hours then every 2 hours for 6 hours for signs of respiratory depression use of pulse oximetry and administration of naloxone if needed These orders are currently standard for all patients receiving IT preservative free morphine and are in an order set in Jeff Chart They allow early recognition of andor minimize the risk of respiratory depression should it occur Also the dosages the investigators will use are well below documented safe doses of this drug for the IT route All patients will be provided with a morphine patient controlled analgesia PCA pump in the postanesthesia care unit PACU for additional pain relief whether or not the study drug is effective
6 Potential benefit of the study is pain relief in the postoperative period following CS Our usual medication is currently unavailable or in critically limited supply
7 The side effect profiles for our standard drug IT morphine and the study drug IT hydromorphone are similar Delayed respiratory depression and itching are more notable with IT morphine than described with IT hydromorphone so this may be beneficial The duration of action of IT hydromorphone may not be as long as that of IT morphine
This study poses minimal risk This is a dose finding study The dosages the investigators will use are well below documented safe doses of this drug for the IT route
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None