Ketamine Infusion Therapy for the Management of Acute Pain in Adult Rib Fracture Patients

NCT ID: NCT02432456

Last Updated: 2020-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2018-08-31

Brief Summary

This study will evaluate the effectiveness of ketamine infusions in the management of acute pain resulting from broken ribs suffered following a blunt trauma. Half of patients will receive the institutional standard of care and a placebo infusion (no active medication). The other half of patients will receive the institutional standard of care and a ketamine infusion. All subjects and staff will be blinded as to whether they are receiving placebo or ketamine.

Detailed Description

A prospective randomized, double blinded trial of ketamine use in adult and elderly blunt trauma patients with associated rib fractures admitted to the trauma service will be conducted. Examples of blunt mechanisms include assault, falls, motor vehicle collisions, motorcycle crashes, motor vehicle pedestrian collisions, crush injuries, and bicycle accidents. The experimental arm of the trial will receive ketamine infusion therapy while the control arm receives saline placebo infusions at an equivalent rate. All patients will be managed with adjunct therapy including opiates in accordance with the institutional thoracic trauma protocols. Two separate trials based on patient age are included in this study. Elderly rib fracture patients are certainly of interest but will be evaluated as a distinct entity given the discrete differences in the complications of rib fractures and the goals of therapy.

All blunt trauma patients with associated rib fractures will be screened. All patients will be enrolled into the institutional standard thoracic trauma pathway. All individuals will undergo Intercostal Nerve Block (ICNB) in the Emergency Department or on admission to the Intensive Care Unit. In addition to scheduled medications per institutional thoracic trauma protocols, all patients will receive adjunct opiate therapy. Patients will be screened by the clinical and pharmacy staff following the diagnosis of rib fractures for eligibility. Patients enrolled into the trial will be randomized into either the experimental or control arm of the trial. The Investigational Drug Services (IDS) department will randomize all enrollees and handle administration of all trial drugs. The infusate will be mixed by the IDS department and all bags will be labeled "Ketamine / Placebo." The IDS department will have unique bag identifiers, which will allow them to identify which bags have active ketamine and which are placebo in case of emergency.

Patients will be randomized in a 1:1 fashion for experimental and control arms. Those enrolled in the experimental arm will receive early ketamine infusion therapy at a fixed infusion rate. For those enrolled in the adult trial the infusion rate will be 2.5 mcg/kg/min while those in the elderly trial will receive infusions at 2.0 mcg/kg/min. All ketamine infusions will be calculated based on ideal body weight (IBW), unless actual body weight is less than ideal. IBW will be calculated for males as 50kg + 2.3*(number of inches above 5 feet) and for women as 45.5kg + 2.3*(number of inches over 5 feet). Patients randomized to the control arm will receive placebo saline solution at an equivalent rate. Time zero will be defined as the time at which the "ketamine / placebo" infusion is begun. For inclusion in the trial, initiation of ketamine / placebo infusions must take place within 6 hours of presentation to Froedtert Memorial Lutheran Hospital (FMLH). Ketamine infusion therapy will be continued for 48 hours. At 6-8 hours post-ICNB all subjects will be assessed for need for repeat ICNB. Need for repeat ICNB will be defined by a thoracic specific numeric pain score greater than seven. Between eight and ten hours post-ketamine infusion initiation, subjects who have thoracic specific pain scores above seven will be evaluated for epidural placement by the Regional Anesthesia and Acute Pain Service.

A subject will be allowed to remove himself/herself from the trial or be un-blinded should he/she, pharmacy, anesthesia, and/or surgical staff deem it medically necessary. Medical necessity would be determined by inability to treat the patient appropriately without knowledge of trial assignment; otherwise the assumption of treating staff will be all patients have received ketamine. All adverse events will be recorded and if necessary subjects will be un-blinded in the event of a serious adverse event. The trauma and anesthesia teams along with the inpatient clinical pharmacists will monitor all trial patients for any adverse event trends. Patients will be followed through the time of discharge.

Conditions

Wounds and Injuries; Rib Fractures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo Infusion

Subjects in this arm will receive the institutional standard of care for rib fractures along with a placebo (NaCl) infusion.

All patients will undergo Intercostal Nerve Blockade with administration of scheduled medications including acetaminophen, ibuprofen, pantoprazole, and methocarbamol. All subjects will receive adjunct opioids.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Individuals enrolled into the control arm of the trial will receive a normal saline placebo infusion at a rate equivalent to the dosage of ketamine in the experimental arm.

Intercostal Nerve Block

Intervention Type: PROCEDURE

All individuals enrolled into the trial will undergo an Intercostal Nerve Blockade as a part of the institutional standard of care for rib fractures. This procedure will be performed according to current standard protocols in the Emergency Department or on admission.

Acetaminophen

Intervention Type: DRUG

All patients admitted to the hospital will be placed on scheduled acetaminophen 1000mg PO q 6 hours unless signs of liver disease/impairment or creatinine clearance \< 35ml/min at which point dosage would be reduced to 650mg q 8 hours. Individuals unable to take oral medications would be placed on intravenous acetaminophen.

Ibuprofen

Intervention Type: DRUG

All patients will be placed on scheduled Ibuprofen or an equivalent NSAID at dosage of 600mg every 6 hours. Patients must have a Glomerular Filtration Rate \> 60 ml/min with no contraindications to NSAID therapy (e.g. Aspirin use, allergy/sensitivity, concurrent ACE inhibitor use, other nephrotoxins, etc)

Pantoprazole

Intervention Type: DRUG

All individuals on scheduled Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy will receive scheduled pantoprazole at 40mg daily. Individuals unable to take medications orally will be placed on intravenous therapy. Individuals with previous reaction or intolerance to pantoprazole will be placed on an equivalent proton pump inhibitor.

Methocarbamol

Intervention Type: DRUG

All individuals enrolled in the trial will be placed on scheduled methocarbamol 500 mg orally every 6 hours while admitted. Individuals with previous intolerance to methocarbamol will be placed on a pharmacy directed equivalent.

Opioid

Intervention Type: DRUG

All individuals will receive as needed opiate therapy as an adjunct to the scheduled medications and "ketamine/placebo" solution. Choice in opiate therapy will be at the discretion of the attending trauma faculty. Dosage and adjustments will be in accordance with the institutional policy on appropriate opiate dosage adjustment.

Ketamine Infusion

Subjects in this arm will receive the institutional standard of care for rib fractures along with a ketamine infusion.

All patients will undergo Intercostal Nerve Blockade with administration of scheduled medications including acetaminophen, ibuprofen, pantoprazole, and methocarbamol. All subjects will receive adjunct opioids.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

All individuals randomized to the experimental arm of the trial will receive early ketamine therapy (within 6 hours of admission) at a rate of 0.15 mg/kg/hr dosed based on ideal body weight. Individuals in the control arm will receive our standard of care for thoracic trauma patients, however, they will receive an additional placebo infusion of normal saline.

Intercostal Nerve Block

Intervention Type: PROCEDURE

All individuals enrolled into the trial will undergo an Intercostal Nerve Blockade as a part of the institutional standard of care for rib fractures. This procedure will be performed according to current standard protocols in the Emergency Department or on admission.

Acetaminophen

Intervention Type: DRUG

All patients admitted to the hospital will be placed on scheduled acetaminophen 1000mg PO q 6 hours unless signs of liver disease/impairment or creatinine clearance \< 35ml/min at which point dosage would be reduced to 650mg q 8 hours. Individuals unable to take oral medications would be placed on intravenous acetaminophen.

Ibuprofen

Intervention Type: DRUG

All patients will be placed on scheduled Ibuprofen or an equivalent NSAID at dosage of 600mg every 6 hours. Patients must have a Glomerular Filtration Rate \> 60 ml/min with no contraindications to NSAID therapy (e.g. Aspirin use, allergy/sensitivity, concurrent ACE inhibitor use, other nephrotoxins, etc)

Pantoprazole

Intervention Type: DRUG

All individuals on scheduled Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy will receive scheduled pantoprazole at 40mg daily. Individuals unable to take medications orally will be placed on intravenous therapy. Individuals with previous reaction or intolerance to pantoprazole will be placed on an equivalent proton pump inhibitor.

Methocarbamol

Intervention Type: DRUG

All individuals enrolled in the trial will be placed on scheduled methocarbamol 500 mg orally every 6 hours while admitted. Individuals with previous intolerance to methocarbamol will be placed on a pharmacy directed equivalent.

Opioid

Intervention Type: DRUG

All individuals will receive as needed opiate therapy as an adjunct to the scheduled medications and "ketamine/placebo" solution. Choice in opiate therapy will be at the discretion of the attending trauma faculty. Dosage and adjustments will be in accordance with the institutional policy on appropriate opiate dosage adjustment.

Interventions

Ketamine

All individuals randomized to the experimental arm of the trial will receive early ketamine therapy (within 6 hours of admission) at a rate of 0.15 mg/kg/hr dosed based on ideal body weight. Individuals in the control arm will receive our standard of care for thoracic trauma patients, however, they will receive an additional placebo infusion of normal saline.

Intervention Type: DRUG

Placebo

Individuals enrolled into the control arm of the trial will receive a normal saline placebo infusion at a rate equivalent to the dosage of ketamine in the experimental arm.

Intervention Type: DRUG

Intercostal Nerve Block

All individuals enrolled into the trial will undergo an Intercostal Nerve Blockade as a part of the institutional standard of care for rib fractures. This procedure will be performed according to current standard protocols in the Emergency Department or on admission.

Intervention Type: PROCEDURE

Acetaminophen

All patients admitted to the hospital will be placed on scheduled acetaminophen 1000mg PO q 6 hours unless signs of liver disease/impairment or creatinine clearance \< 35ml/min at which point dosage would be reduced to 650mg q 8 hours. Individuals unable to take oral medications would be placed on intravenous acetaminophen.

Intervention Type: DRUG

Ibuprofen

All patients will be placed on scheduled Ibuprofen or an equivalent NSAID at dosage of 600mg every 6 hours. Patients must have a Glomerular Filtration Rate \> 60 ml/min with no contraindications to NSAID therapy (e.g. Aspirin use, allergy/sensitivity, concurrent ACE inhibitor use, other nephrotoxins, etc)

Intervention Type: DRUG

Pantoprazole

All individuals on scheduled Non-Steroidal Anti-Inflammatory Drug (NSAID) therapy will receive scheduled pantoprazole at 40mg daily. Individuals unable to take medications orally will be placed on intravenous therapy. Individuals with previous reaction or intolerance to pantoprazole will be placed on an equivalent proton pump inhibitor.

Intervention Type: DRUG

Methocarbamol

All individuals enrolled in the trial will be placed on scheduled methocarbamol 500 mg orally every 6 hours while admitted. Individuals with previous intolerance to methocarbamol will be placed on a pharmacy directed equivalent.

Intervention Type: DRUG

Opioid

All individuals will receive as needed opiate therapy as an adjunct to the scheduled medications and "ketamine/placebo" solution. Choice in opiate therapy will be at the discretion of the attending trauma faculty. Dosage and adjustments will be in accordance with the institutional policy on appropriate opiate dosage adjustment.

Intervention Type: DRUG

Other Intervention Names

NaCl Placebo Solution; Rib Block; Tylenol; Advil, Motrin; Protonix; Robaxin; opiate, narcotic

Eligibility Criteria

Inclusion Criteria

1. age greater than 18 years

2. rib fractures following recent trauma with admission to Froedtert Memorial Lutheran Hospital

Exclusion Criteria

1. history of adverse reaction / intolerance to ketamine therapy

2. elevated intracranial pressure

3. ischemic heart disease defined as active acute coronary syndrome

4. severe, poorly controlled hypertension (Systolic Blood Pressure > 200 mmHg or Diastolic Blood Pressure > 100 mmHg)

5. current opiate agonist/antagonist therapy

6. concurrent use of monoamine oxidase inhibitors (MAOIs)

7. chronic pain or opioid tolerance defined as > 3 weeks of >30mg oral morphine equivalents per day

8. current substance abuse with opiates (prescription and/or heroin) or ketamine

9. Glasgow Coma Scale <13

10. Intubation on arrival or need for urgent intubation on arrival

11. inability to delineate pain and/or appropriately communicate with staff

12. history of psychosis

13. three or more psychotropic medications

14. active delirium

15. glaucoma

16. pregnancy

17. prisoners

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Nathan Kugler

Lead Research Resident

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas W Carver, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Countries

United States

References

Carver TW, Kugler NW, Juul J, Peppard WJ, Drescher KM, Somberg LB, Szabo A, Yin Z, Paul JS. Ketamine infusion for pain control in adult patients with multiple rib fractures: Results of a randomized control trial. J Trauma Acute Care Surg. 2019 Feb;86(2):181-188. doi: 10.1097/TA.0000000000002103.

Reference Type: DERIVED

PMID: 30376537 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO00024679

Identifier Type: -

Identifier Source: org_study_id