Pain Profiles: The GERIKET Trial and Geriatric Analgesia

Written by: David Cisewski, MD (@PainProfiles – EM Resident Physician, Icahn School of Medicine at Mount Sinai) // Edited by: Manpreet Singh, MD (@MPrizzleER), Alex Koyfman, MD (@EMHighAK), and Brit Long, MD (@long_brit)

This edition of Pain Profiles looks at the recent GERIKET trial evaluating subdissociative-dose ketamine in geriatric patients.

Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial

Motov S, Mann S, Drapkin J, et al. Am J Emerg Med. May 2018.

One-liner:

Subdissociative ketamine (SDK) is as efficacious as morphine at controlling acute pain among the  geriatric population but with more side effects.

Study Characteristics:

Clinical question: Is subdissociative ketamine (SDK) a comparably effective non-opioid analgesic alternative among geriatric patients with acute pain presentation to the ED?

Design: Prospective, randomized, double-blind control trial

Setting: Emergency room, Maimonides Hospital, Brooklyn, NY

Patient/Population: >65 yo, with moderate/severe pain (NRS >4), acute (<7d) abdominal, flank, musculoskeletal, or malignant pain.  Patients were excluded if: AMS, morphine/ketamine allergy, unstable vital signs, hx eye/head injury, seizures, intracranial hypertension, severe COPD, chronic pain, renal/hepatic/insufficiency, alcohol/drug abuse, psychiatric illness, opioid use within 4 hours of arrival.

Intervention: Patients enrolled as a convenience sampling were randomized to receive 0.3 mg/kg IV SDK or 0.1 mg/kg IV morphine over 15 min via an infusion pump. Primary outcome – pain reduction at 30 min. Secondary outcomes – adverse events (SERSDA), need for rescue analgesia (0.5 mcg/kg IV fentanyl).

Outcome: 60 patients, approximately 77 years old (77% female) included in the trial. Primary outcome – there was no statistically significant mean difference in pain between between SDK and morphine at 30 min (4.2 vs 4.4;  −0.2; 95% CI −1.93 to 1.46).  Secondary outcome – there was no significant difference between the 2 groups with respect to use of rescue analgesia between SDK and morphine at 30 min ( 7% vs 3%; % difference = 3%; 95% CI −7.6 to 14.3); there was a statistically significant difference observed in the number of patients in the SDK group who reported any adverse effects at 30 min in comparison to morphine (73% vs 37%; 95% CI −13.26% to 60.7%).  [Worth noting, SDK did outperform morphine in analgesic efficacy at 15 min indicating SDK may be the  analgesic of choice for fast onset if side effect profile can be tolerated.]

Conclusion: 0.3 mg/kg SDK over 15 min offers analgesic efficacy comparable to morphine for geriatric patients presenting with acute moderate/severe pain, though with an increased side effect profile.

Quality Assessment:

Well-designed double-blinded RCT (though the ability to blind limited by nystagmus being a common presenting side effect in SDK use). This was a relative small study at 30 patients per arm with discontinuation at the interim analysis.  Limitations include single center study with small sample population selected from a convenience sampling.   The exclusion criteria were numerous, limiting the generalizability of these results to the general ED population.

The Upshot:

Undoubtedly, you can’t be in emergency medicine these days without feeling the ketamine buzz (metaphorically speaking).  Following rigorous advocacy and extensive research, 2017 marked a turning point in which joint policy statements released by American College of Emergency Physicians (ACEP), Emergency Nurses Association (ENA), and the Emergency Medicine Physician Assistants (EMPA) acknowledged SDK as a safe and effective alternative with no added monitoring required for administration.  The American Academy of Emergency Medicine (AAEM) also followed suit in their White Paper on Acute Pain Management in the Emergency Department, stating that SDK should be administered under the same policies as other analgesics (Motov, 2018).  In March 2018, ACEP released a Policy Statement that further acknowledged SDK as a safe and effective analgesic that should be considered part of our pain-management armamentarium in the ED (Annals, 2018).

However, despite the abundance of data, several gaps still remain in our understanding of safe and effective utilization of SDK in our patient population – particularly, its use among older patients (geriatric) in which research had yet to be conducted. The older geriatric population is traditionally more sensitive to medical adverse effects and particularly prone to polypharmacy, requiring caution when administering analgesics.

In steps Sergey Motov. As a proponent of SD for analgesia – and more importantly an advocate for safe and effective pain management – Dr. Motov again provides us the data we need to make an informed decision with SDK use in the elderly population.

• Is SDK an effective analgesic for acute pain in this population? Yes – and in fact the subanalysis found that the analgesic efficacy at 15 minutes post-administration was even moreso.
• Is it safe? Presumably so.  What was surprising from the results – and to the author himself – was a high incidence of side effects (feeling of unreality, dizziness, etc) among the SDK users.  Whether the result of age, changes in metabolism, or polypharmacy, Dr. Motov himself indicates he would consider 0.1 to 0.15 mg/kg IV SDK over 30 minutes to reduce side effects instead of the 15 min infusion used in this and previous studies.

While this is another example of Dr. Motov’s great work supporting use of SDK, specifically for acute pain among the geriatric patient, it was a relatively small patient population with considerable exclusion criteria, and further studies are needed to support his findings, particularly in understanding the side effect profile among the elderly.  As noted by the author himself, if you’re going to give SDK, consider a more conservative approach using a lower dose (0.1-0.15 mg/kg IV) over an extended duration (30 min).

Special thank you to Sergey Motov for his continued persistence in advancing the field of pain management within the emergency setting.

Additional Reading:

• The PharmERToxGuy – Ketamine for Acute Geriatric Pain in the ED
• GEM CAST – Subdissociative Dose Ketamine in Older Adults? – Maybe
• ACEP – Policy Statement: Sub-dissociative dose ketamine for analgesia
• ACEP – Prepared Policy Resource Education Paper (PREP):  “Sub-dissociative Dose Ketamine for Analgesia.” 
• emDOCs – Pain Profiles: Ketamine for Analgesia
• Emergency Physicians Monthly: Motov’s Cocktails: Sub-Dissociative Ketamine
• Sadove MS, Shulman M, Hatano S, Fevold N. Analgesic effects of ketamine administered in subdissociative doses. Anesth Analg. 1971;50(3):452-7. PMID: 5103784