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

Wounds and Injuries Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02432456
• Other study ID #: PRO00024679
• Status: Completed
• Phase: Phase 4
• Start date: September 2015
• Est. completion date: August 2018

Study information

• Verified date: January 2020
• Source: Medical College of Wisconsin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Pain
• Fractures, Bone
• Rib Fractures
• Wounds and Injuries

Intervention

Drug:
• 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.
• 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.

Procedure:
• 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.

Drug:
• 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.
• 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)
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Froedtert Memorial Lutheran Hospital	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Medical College of Wisconsin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual Analog Numeric Pain Score	Visual Analog Numeric Pain scores are reported as a single numeric score between 0 and 10. The more severe the pain the higher the number with 10 representing the most severe pain imaginable.	12-24 hours post infusion
Secondary	Visual Analog Numeric Pain Score	Visual Analog Numeric Pain scores are reported as a single numeric score between 0 and 10. The more severe the pain the higher the number with 10 representing the most severe pain imaginable.	24-48 hours post infusion
Secondary	Oral Morphine Equivalent (Narcotic Usage)	This is an analysis of the narcotic utilization during the study. Oral Morphine Equivalents is a means of standardizing narcotic utilization given a multitude of different medications are utilized. Medications are standardized to units (milligrams) or oral morphine for a standardized comparison.	12-24 hours post infusion
Secondary	Oral Morphine Equivalent (Narcotic Usage)	This is an analysis of the narcotic utilization during the study. Oral Morphine Equivalents is a means of standardizing narcotic utilization given a multitude of different medications are utilized. Medications are standardized to units (milligrams) or oral morphine for a standardized comparison.	24-48 hours post infusion
Secondary	Length of Stay	Total hospital length of stay in days up to 365 days.	Total Index Hospitalization up to 365 days
Secondary	Regional Anesthesia Utilization	This is a measure of the Epidural Placement rates. Epidural placement was binary as in patient received or did not receive an epidural infusion catheter for supplemental pain management.	Total Index Hospitalization up to 365 days
Secondary	Respiratory Failure	Respiratory failure within this trial was defined by the need for unanticipated intubation and/or transfer to ICU for respiratory support.	Total Index Hospitalization up to 365 days
Secondary	Hallucination	Hallucinations were documented and confirmed by the treating medical team.	Total Index Hospitalization up to 365 days
Secondary	Oral Morphine Equivalent (Narcotic Usage) in Severely Injured	This is an analysis of the narcotic utilization during the study. Oral Morphine Equivalents is a means of standardizing narcotic utilization given a multitude of different medications are utilized. Medications are standardized to units (milligrams) or oral morphine for a standardized comparison.	Total Index Hospitalization up to 365 days