Postoperative Pain
Conditions
Brief summary
To use magnesium sulfate as adjuvant analgesia by implementing a treatment protocol in order to determine whether can benefit pediatric pain in post-operative transplanted patients and decrease overall opioid consumption.
Detailed description
The post-operative ICU course for children receiving liver transplants and TPIAT (total pancreatectomy with islet cell autotransplantation) includes a number of different challenges, one of which includes pain. Pain is treated with both medications and approaches without medications (such as music and other distraction techniques). Opioids are one such effective pain medication which is universally used, however like all medications has risks of certain side effects (such as nausea, constipation, itching, and others). Modern research has searched for other medications and methods to treat pain in both children and adults. In this study, the investigators aim to apply one of these methods that has been shown to be effective in certain operative populations through a medicine called Magnesium-Sulfate, which may be a safe way to decrease the use of other pain medications (specifically opioids). Magnesium is already a physiologic electrolyte the body uses, which are consumed from certain foods. Used as an IV medication to reach higher levels of magnesium can work to decrease pain via its action on specific nerve receptors. Magnesium-Sulfate will be given at the beginning of transplant surgery for consented liver and TPIAT transplant patients, and continue an infusion for 48 hours into their ICU course. The investigators will monitor side effects and treat pain the same way otherwise the care team would without magnesium to determine whether there is any beneficial effect that can be applied to children in the future.
Interventions
DRUGMagnesium sulfate
Magnesium sulfate (MgSO4) will be administered intravenously at induction of anesthesia as a 30-minute bolus dose of 50 mg/kg (maximum 2 grams) in the OR, followed by a 15 mg/kg/hr IV infusion for 48 hours or once the patient has transferred out of the PICU, whichever comes first.
Sponsors
University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Experimental Group: \- Be scheduled for and receive a liver transplant or total pancreatectomy and islet cell autotransplantation Control Group: \- Received a liver transplant or total pancreatectomy and islet cell autotransplantation.
Exclusion criteria
Experimental Group: * Pregnant or unwilling to abstain from sex if not practicing birth control during participation in the study. * Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. * Known allergic reactions to components of the MgSO4 * History of heart block or myasthenia graves in past medical history. * Presence of cardiac pacemaker * Any patient with preoperative creatinine level \> 1.5x upper limit of normal. Control Group: * Any patient who had filed as research-exempt (opt-out of research previously). * Any patient with preoperative creatinine level \> 1.5x upper limit of normal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Opioid Requirement | approximately 7 days | Total opioid requirement during the entire operative and post-operative pediatric intensive care unit (PICU) period will be reported in units of morphine equivalent per body weight. OME/kg is often the recorded value in studies, however the patients had variable PICU courses (i.e. duration in days different between patients, as well as well as admission times altering POD#0 data, etc), so the opioid consumption was standardized to the duration of their course (i.e. OME/kg/d). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OR Opioid Consumption | approximately 7 days | Oral Morphine Equivalent use during Operating Room Procedure OME/kg is often the recorded value in studies, however the patients had variable PICU courses (i.e. duration in days different between patients, as well as well as admission times altering POD#0 data, etc), so the opioid consumption was standardized to the duration of their course (i.e. OME/kg/d). |
| Opioid Side Effect - Delirium/AMS | approximately 7 days | Outcome reported as the count of participants who experience opioid side effects during the entire operative and post-operative pediatric intensive care unit (PICU) period. Delirium or Altered Mental Status |
| Opioid Side Effect - Constipation -- Ileus | approximately 7 days | Outcome reported as the count of participants who experience opioid side effects during the entire operative and post-operative pediatric intensive care unit (PICU) period. Prevalence of Ileus as indicated in Progress Note |
| Opioid Side Effect - Constipation -- Enema Use | approximately 7 days | Outcome reported as the count of participants who experience opioid side effects during the entire operative and post-operative pediatric intensive care unit (PICU) period. Prevalence of enema use for constipation |
| Opioid Side Effect - Constipation -- 1st Stool | approximately 7 days | Postoperative day where first stooled |
| Daily Post-operative Opioid Requirement | Day 1, Day 2, Day 3, Day 4, Day 5 | Daily opioid requirement will be reported in units of morphine equivalent per body weight. |
| Opioid Side Effect - Nausea -- Emeses | approximately 7 days | Postoperative number of emeses as indicator of nausea |
| Opioid Side Effect - Nausea -- Antiemetic Use | approximately 7 days | Number of ondansetron doses |
| Opioid Side Effect - Pruritus | approximately 7 days | Frequency of pruritus as measured by Naloxone gtt use, reported as percentage |
| Opioid Side Effect - Urinary Retention | approximately 7 days | Frequency of urinary retention as measured by straight catheterization requirement, measured in percentage |
| PICU Length of Stay | up to 32 days | Consecutive days in PICU following operation |
| Opioid Side Effect - Bowel Dysmotility -- Feed Initiation | approximately 7 days | Postoperative day where started enteral feeds |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liver Transplant - MgSO4 Liver transplant recipients receiving study intervention (magnesium sulfate infusion) | 2 |
| TPIAT - MgSO4 Total Pancreatecomy with Islet Cell Autotransplantation (TPIAT) recipients receiving study intervention (MgSO4 infusion) | 9 |
| Liver Transplant - Control Review Group Retrospective cohort of liver transplant recipients whom did not receive study intervention | 21 |
| TPIAT - Control Retrospective cohort of TPIAT recipients whom did not receive study intervention | 34 |
| Total | 66 |
Baseline characteristics
| Characteristic | TPIAT - MgSO4 | Liver Transplant - Control Review Group | Liver Transplant - MgSO4 | TPIAT - Control | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 21 Participants | 2 Participants | 34 Participants | 66 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 21 Participants | 0 Participants | 34 Participants | 55 Participants |
| Race (NIH/OMB) White | 8 Participants | 0 Participants | 1 Participants | 0 Participants | 9 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 2 Participants | 21 Participants | 38 Participants |
| Sex: Female, Male Male | 3 Participants | 12 Participants | 0 Participants | 13 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 9 | 0 / 21 | 0 / 34 |
| other Total, other adverse events | 2 / 2 | 7 / 9 | 17 / 21 | 27 / 34 |
| serious Total, serious adverse events | 0 / 2 | 0 / 9 | 0 / 21 | 0 / 34 |
Outcome results
Primary
Total Opioid Requirement
Total opioid requirement during the entire operative and post-operative pediatric intensive care unit (PICU) period will be reported in units of morphine equivalent per body weight. OME/kg is often the recorded value in studies, however the patients had variable PICU courses (i.e. duration in days different between patients, as well as well as admission times altering POD#0 data, etc), so the opioid consumption was standardized to the duration of their course (i.e. OME/kg/d).
Time frame: approximately 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liver Transplant - MgSO4 | Total Opioid Requirement | 3.31 OME/kg/d | Standard Deviation 1.69 |
| TPIAT - MgSO4 | Total Opioid Requirement | 5.27 OME/kg/d | Standard Deviation 2.94 |
| Liver Transplant - Control Review Group | Total Opioid Requirement | 10.2 OME/kg/d | Standard Deviation 8.32 |
| TPIAT - Control | Total Opioid Requirement | 4.1 OME/kg/d | Standard Deviation 2.41 |
Secondary
Daily Post-operative Opioid Requirement
Daily opioid requirement will be reported in units of morphine equivalent per body weight.
Time frame: Day 1, Day 2, Day 3, Day 4, Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liver Transplant - MgSO4 | Daily Post-operative Opioid Requirement | 4.3 OME/kg/d | Standard Deviation 1.28 |
| TPIAT - MgSO4 | Daily Post-operative Opioid Requirement | 5.33 OME/kg/d | Standard Deviation 3.03 |
| Liver Transplant - Control Review Group | Daily Post-operative Opioid Requirement | 14.06 OME/kg/d | Standard Deviation 11.6 |
| TPIAT - Control | Daily Post-operative Opioid Requirement | 4.97 OME/kg/d | Standard Deviation 3.28 |
Secondary
Opioid Side Effect - Bowel Dysmotility -- Feed Initiation
Postoperative day where started enteral feeds
Time frame: approximately 7 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Bowel Dysmotility -- Feed Initiation | 2 day |
| TPIAT - MgSO4 | Opioid Side Effect - Bowel Dysmotility -- Feed Initiation | 2.22 day |
| Liver Transplant - Control Review Group | Opioid Side Effect - Bowel Dysmotility -- Feed Initiation | 2.71 day |
| TPIAT - Control | Opioid Side Effect - Bowel Dysmotility -- Feed Initiation | 2.06 day |
Secondary
Opioid Side Effect - Constipation -- 1st Stool
Postoperative day where first stooled
Time frame: approximately 7 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Constipation -- 1st Stool | 2 day |
| TPIAT - MgSO4 | Opioid Side Effect - Constipation -- 1st Stool | 4 day |
| Liver Transplant - Control Review Group | Opioid Side Effect - Constipation -- 1st Stool | 3.83 day |
| TPIAT - Control | Opioid Side Effect - Constipation -- 1st Stool | 3.76 day |
Secondary
Opioid Side Effect - Constipation -- Enema Use
Outcome reported as the count of participants who experience opioid side effects during the entire operative and post-operative pediatric intensive care unit (PICU) period. Prevalence of enema use for constipation
Time frame: approximately 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Constipation -- Enema Use | 0 Participants |
| TPIAT - MgSO4 | Opioid Side Effect - Constipation -- Enema Use | 2 Participants |
| Liver Transplant - Control Review Group | Opioid Side Effect - Constipation -- Enema Use | 5 Participants |
| TPIAT - Control | Opioid Side Effect - Constipation -- Enema Use | 11 Participants |
Secondary
Opioid Side Effect - Constipation -- Ileus
Outcome reported as the count of participants who experience opioid side effects during the entire operative and post-operative pediatric intensive care unit (PICU) period. Prevalence of Ileus as indicated in Progress Note
Time frame: approximately 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Constipation -- Ileus | 0 Participants |
| TPIAT - MgSO4 | Opioid Side Effect - Constipation -- Ileus | 5 Participants |
| Liver Transplant - Control Review Group | Opioid Side Effect - Constipation -- Ileus | 5 Participants |
| TPIAT - Control | Opioid Side Effect - Constipation -- Ileus | 21 Participants |
Secondary
Opioid Side Effect - Delirium/AMS
Outcome reported as the count of participants who experience opioid side effects during the entire operative and post-operative pediatric intensive care unit (PICU) period. Delirium or Altered Mental Status
Time frame: approximately 7 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Delirium/AMS | 0 Participants |
| TPIAT - MgSO4 | Opioid Side Effect - Delirium/AMS | 5 Participants |
| Liver Transplant - Control Review Group | Opioid Side Effect - Delirium/AMS | 5 Participants |
| TPIAT - Control | Opioid Side Effect - Delirium/AMS | 7 Participants |
Secondary
Opioid Side Effect - Nausea -- Antiemetic Use
Number of ondansetron doses
Time frame: approximately 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Nausea -- Antiemetic Use | 1 antiemetic administrations | Standard Deviation 1.41 |
| TPIAT - MgSO4 | Opioid Side Effect - Nausea -- Antiemetic Use | 11.4 antiemetic administrations | Standard Deviation 11.95 |
| Liver Transplant - Control Review Group | Opioid Side Effect - Nausea -- Antiemetic Use | 2.86 antiemetic administrations | Standard Deviation 4.65 |
| TPIAT - Control | Opioid Side Effect - Nausea -- Antiemetic Use | 10.79 antiemetic administrations | Standard Deviation 9.24 |
Secondary
Opioid Side Effect - Nausea -- Antiemetic Use
Frequency needing any antiemetic use, measure reported in percentage
Time frame: approximately 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Nausea -- Antiemetic Use | 50 percentage |
| TPIAT - MgSO4 | Opioid Side Effect - Nausea -- Antiemetic Use | 89 percentage |
| Liver Transplant - Control Review Group | Opioid Side Effect - Nausea -- Antiemetic Use | 43 percentage |
| TPIAT - Control | Opioid Side Effect - Nausea -- Antiemetic Use | 94 percentage |
Secondary
Opioid Side Effect - Nausea -- Emeses
Postoperative number of emeses as indicator of nausea
Time frame: approximately 7 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Nausea -- Emeses | 0 events |
| TPIAT - MgSO4 | Opioid Side Effect - Nausea -- Emeses | 2.44 events |
| Liver Transplant - Control Review Group | Opioid Side Effect - Nausea -- Emeses | 1.38 events |
| TPIAT - Control | Opioid Side Effect - Nausea -- Emeses | 1.26 events |
Secondary
Opioid Side Effect - Pruritus
Frequency of pruritus as measured by Naloxone gtt use, reported as percentage
Time frame: approximately 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Pruritus | 0 percentage |
| TPIAT - MgSO4 | Opioid Side Effect - Pruritus | 78 percentage |
| Liver Transplant - Control Review Group | Opioid Side Effect - Pruritus | 14 percentage |
| TPIAT - Control | Opioid Side Effect - Pruritus | 59 percentage |
Secondary
Opioid Side Effect - Urinary Retention
Frequency of urinary retention as measured by straight catheterization requirement, measured in percentage
Time frame: approximately 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liver Transplant - MgSO4 | Opioid Side Effect - Urinary Retention | 0 percentage |
| TPIAT - MgSO4 | Opioid Side Effect - Urinary Retention | 22 percentage |
| Liver Transplant - Control Review Group | Opioid Side Effect - Urinary Retention | 10 percentage |
| TPIAT - Control | Opioid Side Effect - Urinary Retention | 18 percentage |
Secondary
OR Opioid Consumption
Oral Morphine Equivalent use during Operating Room Procedure OME/kg is often the recorded value in studies, however the patients had variable PICU courses (i.e. duration in days different between patients, as well as well as admission times altering POD#0 data, etc), so the opioid consumption was standardized to the duration of their course (i.e. OME/kg/d).
Time frame: approximately 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liver Transplant - MgSO4 | OR Opioid Consumption | 2.19 OME/kg/d | Standard Deviation 0.3 |
| TPIAT - MgSO4 | OR Opioid Consumption | 3.6 OME/kg/d | Standard Deviation 2.51 |
| Liver Transplant - Control Review Group | OR Opioid Consumption | 4.69 OME/kg/d | Standard Deviation 1.94 |
| TPIAT - Control | OR Opioid Consumption | 3.24 OME/kg/d | Standard Deviation 1.44 |
Secondary
PICU Length of Stay
Consecutive days in PICU following operation
Time frame: up to 32 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liver Transplant - MgSO4 | PICU Length of Stay | 4.19 days | Standard Deviation 0.42 |
| TPIAT - MgSO4 | PICU Length of Stay | 7.38 days | Standard Deviation 2.92 |
| Liver Transplant - Control Review Group | PICU Length of Stay | 8.47 days | Standard Deviation 6.97 |
| TPIAT - Control | PICU Length of Stay | 7.29 days | Standard Deviation 7.67 |