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

Condition(s) targeted: Wounds and Injuries; Rib Fractures

Intervention: Ketamine (Drug); Placebo (Drug); Intercostal Nerve Block (Procedure); Acetaminophen (Drug); Ibuprofen (Drug); Pantoprazole (Drug); Methocarbamol (Drug); Opioid (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Medical College of Wisconsin

Official(s) and/or principal investigator(s):
Thomas Carver, MD, Principal Investigator, Affiliation: Medical College of Wisconsin

Overall contact:
Nathan W Kugler, MD, Phone: 309-251-9952, Email: nkugler@mcw.edu

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: AUCpain

Secondary outcome:

AUCpain

AUCpain

AUCpain

ICU Length of Stay

Length of Stay

Opiate Utilization

Opiate Utilization

Opiate Utilization

Opiate Side Effect Frequency

Regional Anesthesia Utilization

Regional Anesthesia Utilization

Rib Fracture Complication Frequency

Development of Chronic Pain

Detailed description: A prospective randomized, double blinded trial of ketamine use in adult 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. This trial will focus on adult blunt trauma patients who have associated rib fractures. The focus on adult rib fracture patients stems from an injury pattern in which there is a high incidence of prolonged opiate utilization and development of chronic pain. Elderly rib fracture patients are certainly of interest, however, a trial evaluating the benefits of ketamine infusions in this population is best served 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. A total of 60 patients will be enrolled into the trial. The 30 patients randomized to the experimental arm will receive early ketamine infusion therapy at a rate of 0. 15 mg/kg/hr. 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). The 30 patients randomized to the control arm will receive placebo saline solution at a rate equivalent. 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 a minimum of 48 hours with a maximum of 6 days of ketamine/placebo therapy. Following the 48 hour infusion mark, the Regional Anesthesia and Acute Pain Service team will make the clinical decision to continue or cease the ketamine/placebo infusion. 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 IDS department will monitor all trial patients for any adverse event trends. Patients will be followed through the time of discharge.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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. age greater than 65 years 2. history of adverse reaction / intolerance to ketamine therapy 3. elevated intracranial pressure 4. ischemic heart disease defined as active acute coronary syndrome 5. severe, poorly controlled hypertension (Systolic Blood Pressure > 180 mmHg or Diastolic Blood Pressure > 100 mmHg) 6. current opiate agonist/antagonist therapy 7. concurrent use of monoamine oxidase inhibitors (MAOIs) 8. chronic pain or opioid tolerance defined as > 3 weeks of >30mg oral morphine equivalents per day 9. current substance abuse with opiates (prescription and/or heroin) or ketamine 10. Glasgow Coma Scale <13 11. intubation on arrival or need for urgent intubation on arrival 12. inability to delineate pain and/or appropriately communicate with staff 13. history of psychosis 14. three or more psychotropic medications 15. active delirium 16. glaucoma 17. pregnancy 18. prisoners

Nathan W Kugler, MD, Phone: 309-251-9952, Email: nkugler@mcw.edu

Starting date: July 2015
Last updated: April 28, 2015