Clinical trial NCT02432456: Ketamine Infusion Therapy for the Management of Acute Pain in Adult Rib Fracture Patients
Official title: Ketamine Infusion Therapy for the Management of Acute Pain in Adult Rib Fracture Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Wounds and Injuries
Rib Fractures
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2015-05-04
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Visual Analog Numeric Pain Score
timeFrame: 12-24 hours post infusion
Secondary outcomes:
measure: Visual Analog Numeric Pain Score
timeFrame: 24-48 hours post infusion
measure: Oral Morphine Equivalent (Narcotic Usage)
timeFrame: 12-24 hours post infusion
measure: Oral Morphine Equivalent (Narcotic Usage)
timeFrame: 24-48 hours post infusion
measure: Length of Stay
timeFrame: Total Index Hospitalization up to 365 days
measure: Regional Anesthesia Utilization
timeFrame: Total Index Hospitalization up to 365 days
measure: Respiratory Failure
timeFrame: Total Index Hospitalization up to 365 days
measure: Hallucination
timeFrame: Total Index Hospitalization up to 365 days
measure: Oral Morphine Equivalent (Narcotic Usage) in Severely Injured
timeFrame: Total Index Hospitalization up to 365 days
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Thomas W Carver, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.