Geriatric Ketamine for Pain Management Study

Elderly patients are making up a greater proportion of the New York State population every
year as the nation's overall population continues to age at a rapid pace. Acute and chronic
pain conditions are very common in the geriatric population and it is well recognized that
pain is undertreated in the elderly. Complicating this important public health problem is
that changes in physiology that occur in the elderly, such as cognitive decline and impaired
ability of the liver and kidney to metabolize medications, render opioid administration
particularly dangerous in the geriatric population. Adverse side effects and increased health
care utilization are well known hazards associated with opioid use in the elderly.

Therefore, development of pain management strategies that include non-opioid pain treatment
modalities has the potential to have a major impact on the health and well-being of New
Yorkers. This study undertakes a novel strategy intended to reduce opioid consumption in the
elderly.

This research project will evaluate the analgesic feasibility and safety of short infusion of
subdissociative dose of intravenous ketamine compared with short infusion of intravenous
morphine for controlling pain in ED patients 65 years of age and older, laying the groundwork
for ketamine to become a safe and viable alternative to opioids in managing geriatric pain in
the ED. The significance of this project being done at Maimonides Medical center is to lay
the foundation to providing safer analgesia in geriatric ED patients and moving towards an
eventual goal of an "opioid-free" ED.

Methods:

Study Design:

This is a prospective, randomized, double-blind trial evaluating and comparing analgesic
effect of Ketamine administered in sub-dissociative doses 0.3 mg/kg as a intravenous infusion
(10 min), and intravenous Morphine given at 0.1 mg/kg as intravenous infusion (10 min) with a
maximum dose of 10 mg. in elderly adults (age 65 and older) with pain in the ED.

Study

Protocol:

Patient screening, enrollment, and data collection will be performed by study investigators
and the research fellow. ED pharmacy investigators will maintain the randomization list which
will be generated prior to commencement of the study, will prepare the medication, and will
deliver it to the nurse caring for the study participant in a blinded fashion.

The study will include patients aged 65 and older presenting to the ED with abdominal, flank,
back, traumatic chest or musculoskeletal pain of five or more on a standard eleven point (0 -
10) numeric rating scale (NRS), and who require opioid analgesia as determined by the
treating ED attending physician.

Exclusion criteria will include altered mental status, allergy to morphine or ketamine,
weight <40kg or >115kg, unstable vital signs (systolic blood pressure <90 or >200 mmHg, heart
rate <50 or >150 beats per minute, non-traumatic chest pain, headache, and respirations <8 or
>30 per minute), past medical history of severe renal or hepatic insufficiency, alcohol or
drug abuse or psychiatric illness; BMI >40; severe COPD

After patients are evaluated by the treating ED physician and determined to meet eligibility
criteria, each patient will be approached by a member of the research team for acquisition of
written informed consent and HIPAA authorization. The on-duty ED pharmacist will prepare
medications according to the two arms of the study: patients receiving 0.1 mg /kg of morphine
; patients receiving 0.3 mg/kg of ketamine.

The medication will be administered using infusion pump with a 10 minute run time.

Patients a priori will will be randomized to either of the two arms. A list will be generated
via SPSS 19.0 from 1 to 90; and SPSS 19.0 will be programmed to randomly assign patients to
either of the two arms at 10 patient blocks. Thus, for example in patients 1 to 10; SPSS will
randomly assign 5 patients to the Ketamine group and 5 patients to the morphine group and so
on for all 90 patients. Therefore, after completion 45 patients will be assigned to the
Ketamine group and 45 to the morphine group. Antonios will then e-mail the list to Nicholas
Filk and pharmacy department who will have the list and when a patient is enrolled in the
study will know which medication to give the patient. Every other investigator and clinician
would be blinded to the randomization assignment.

Study investigators will record pain scores, vital signs, and adverse effects at 0, 30, 60,
90, and 120 minutes.

Patients who report a pain NRS of five or greater and request additional pain relief will be
given fentanyl 0.5 mcg/kg as a rescue analgesic. All data, including gender, demographics,
medical history, and vital signs, will be recorded on data collection sheets and will be
entered into and analyzed via SPSS 19.0.

Development of the randomization list, confirmation of written consent acquisition on all
participants, and statistical analyses will be conducted by the research manager and
statistician, who will be independent of any data collection.

Inclusion Criteria:

- ED patients; 65 years of age and older; abdominal, flank, back, traumatic chest, neck
or musculoskeletal pain; capacity to give verbal or written consent.

Exclusion Criteria:

- ED patients <65 years old; altered mental status; presenting with headache,
non-traumatic chest pain; allergy to morphine or ketamine; weight <40kg or >115kg,
unstable vital signs (systolic blood pressure <90 or >180 mmHg; heart rate <5 or >150
beats per minute; and respirations <8 or >30 per minute), and past medical history of
severe renal or hepatic insufficiency, alcohol or drug abuse or psychiatric illness;
Patients with BMI>40; severe COPD