Results of a one-year, retrospective medication use evaluation Joseph Ladd, PharmD PGY-1 Pharmacy Resident BHSF Homestead Hospital
Briefly review ketamine s history, mechanism of action, and unique properties Assess available evidence for its use in low doses for analgesia Discuss ketamine s current use in the Homestead Hospital Emergency Department
Abbreviation Definition Abbreviation Definition ACh Acetylcholine IV Intravenously APAP Acetaminophen LKD Low-dose ketamine BP Blood pressure M Muscarinic receptor CNS Central nervous system MAOI Monoamine oxidase inhibitor ED Emergency Department NMDA N-methyl-d-aspartate GABA γ-aminobutyric acid NN Nicotinic receptor HH Homestead Hospital NSAID Non-Steroidal Anti- Inflammatory Drug HR Heart rate PO By mouth IM Intramuscularly PR Pro-rectally IN Intranasally SL Sublingually
1926: Synthesized as an anesthetic Phencyclidine (PCP) Ketamine 1963: Patented in Belgium for veterinary use 1964: Human testing began 1965: Approved for human use 1969: Ketalar became available 1970: Officially approved by FDA Administered to Viet Nam soldiers
Low-dose ketamine (LDK) < 1 mg/kg The Clinical Basis of Medical ToxicologyGoldfrank's Toxicologic Emergencies, 10e, 2015
N-Methyl-D-Aspartate Activation via glutamate neurotransmitters Activation induces: Hyperalgesia Neuropathic pain Reduced opioid sensitivity http://jralonso.es/wp-content/uploads/2012/12/receptor-nmda.jpg
1 2 3 4 5 May provide effective analgesia Can be given IV, IM, IN, SL, PO, PR Airway responses are protected Minimal cardiovascular effects Rapid onset, short duration of action
Route Dose Onset Peak Duration Intravenous < 1 mg/kg < 1 min 3-5 min 5-10 min Intramuscular 0.5-1 mg/kg 2-5 min ~15 min ~25 min Intranasal 0.5 mg/kg 10 min 20 min 1 hour
Literature
Randomized Controlled Trial at a level I trauma center 45 patients LDK vs. Morphine LDK not superior to Morphine for max change in NRS pain scores Time to max reduction in pain: 5 min for LDK and 100 min for Morphine LDK provided a moderate reduction in pain for 2 hours Conclusion: LDK did not produce a greater reduction in NRS pain scores compared with morphine for acute pain in the ED.
Prospective cohort in pre-hospital setting 27 patients Morphine vs. Morphine + Ketamine Pain scores lower in morphine + ketamine group BP elevated in morphine + ketamine group Conclusion: Morphine + LDK provides adequate pain relief in patients with bone fractures.
Randomized Controlled Trial in a Pediatric ED 260 patients aged 5-15 years requiring fracture/joint reduction LDK q3 minutes + Midazolam vs. Fentanyl + Midazolam Difference in OSBD-R* scores from baseline LDK was not significantly different than Fentanyl *Conclusion: Patients who received ketamine had significant reduction in mean Observational Scale of Behavioral Distress Revised (OSBD-R) scores.
Randomized Controlled Trial in a tertiary care hospital 63 patients aged 14-65 years with fracture/dislocation, incision, drainage LDK every 3 minutes vs. Fentanyl Incidence and severity of adverse events LDK was not significantly different than Fentanyl Conclusion: Subdissociative-dose ketamine is safer than fentanyl for ED procedural sedation and analgesia and appears to have similar efficacy.
Other potential areas of benefit: Sick-cell pain Agitation Burn patients Asthmatics
LDK is versatile and can be administered via many routes < 1 mg/kg IV 0.5 1 mg/kg IM Airway responses are protected Minimal cardiovascular effects Descriptions of increased BP and HR Rapid onset, short duration of action Evidence of relatively equal efficacy to other analgesics
in Homestead Hospital s Emergency Department
Barriers to pain management Subjective nature Regulatory issues Knowledge deficits Fear concerning therapy NSAIDs / APAP limited relief Opioids side effects, dependency, tolerance The Joint Commission 2012 Sentinel Event Alert The American College of Emergency Physicians Ketamine historically used in settings with limited resources Unique safety profile and variety of dosage forms Potential role in pain management
To assess the safety and effectiveness of using LDK for pain management in the emergency department Data used to: Evaluate the use of ketamine in treating mild-to-severe pain in a highvolume community hospital ED Recommend a dosing guideline for its use in the ED
Study Design Observational study Utilizing retrospective medical chart reviews Patients received LDK during a visit to the HH ED Subjects Sample Size: 24 Inclusion Criteria: Admission to the HH ED June 2014 and June 2015 Treatment of acute or chronic mild, moderate, or severe pain with LDK Exclusion Criteria: Administration of 1 mg/kg of ketamine
Instruments The Wong-Baker FACES Pain Rating Scale for children A 1-10 Visual Analogue Scale for adults Provider documentation Procedures Retroactive computerized report generated Identified patients who received ketamine in the ED that year Any patients who did not fit the study criteria were excluded Subjects profiles reviewed by a pre-specified investigator to determine how LDK was used to treat patients pain symptoms Safety was assessed by the incidence of adverse events Effectiveness assed by changes in reported pain-rating scores
Statistical Analysis Descriptive statistics using Microsoft Office Excel 2007 to assess: How LDK was used in the ED For what indications The safety profile of the dosage range being used The effectiveness of LDK in reducing pain
34 orders canceled before administration 114 subjects with orders for ketamine 1 patient refused 55 1 mg/kg 24 Included
Patient Demographics (n=24) Age (yr), average 34.4 Existing Precautions (%) 25 Weight (kg), average 70.5 Coronary Artery Disease (%) 8.3 Sex Heart Failure (%) 8.3 Female (%) 54 Hypertension (%) 20.8 Male (%) 46 Baseline Vital Signs Baseline Pain Score Heart Rate (bpm), average 104 Mild (%) 4.3 Systolic Blood Pressure (mmhg), average 129 Moderate (%) 8.7 Diastolic Blood Pressure (mmhg), average 79 Severe (%) 87 Oxygen Saturation (%), average 99 Post-LDK Pain Score History of Chronic Pain (%) 37.5 None (%) 42.9 History of Opioid Use (%) 37.5 Mild (%) 28.6 Opioid use within the past 24 hours (%) 37.5 Moderate (%) 23.8 Severe (%) 4.8
Indication Average Dosing of LDK by Indication Sickle-cell pain (n=4) (0.41) Reduction procedures (n=5) (0.52) Back pain (n=2) Laceration (n=3) Fracture (n=1) Flank pain (n=2) Burns, 2nd degree (n=1) Abdominal pain (n=6) (0.11) (0.3) (0.24) (0.32) (0.3) (0.8) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Total mg/kg of Ketamine
Pain Rating on a Visual Analogue Scale (0 = no pain; 10 = worse pain imaginable) Change in Pain from Baseline 12 10 8 6 4 2 0 Ketamine alone Adjunctive to Adjunctive to Analgesics Sedatives Avg. Baseline Pain 7.3 8.5 7.6 Avg. Pain at Discharge 1.8 2.5 2.3
Continuous Infusion 15% (n=4) Administration Routes Intranasal 4% (n=1) IV Push 81% (n=22) Coadministered Medications None 18% n=8 Ondansetron 16% n=7 Atropine 2% n=1 Opiate analgesics 21% n=9 Benzodiazepines 5% n=2 Opiates + APAP 7% n=3 Diphenhydramine 5% n=2 Orphenadrine 2% n=1 NSAIDs 12% n=5 Propofol 12% n=5
Incidence of Adverse Drug Events Vomiting 4% (n=1) Decreased SpO 2 4% (n=1) No ADE 92% (n=22) Vomiting Twenty minutes after ketamine administration, a patient vomited yellow bile. Per patient request, ketamine drip was held. Patient was nauseous upon presentation. Decreased SpO2 Three minutes after ketamine administration, oxygen saturation decreased 5% and then returned to baseline after five minutes.
Total average dose: 0.375 mg/kg 8 distinct indications Highest doses for laceration repair; lowest for hairline fracture Ketamine monotherapy Reduced an average baseline pain rating From Severe upon presentation to Mild upon discharge Similar to coadministration with analgesics and sedatives Commonly coadministered medications Opioid and non-opioid analgesics Ondansetron Propofol Data will be used to build a dosing algorithm and protocol
1. Ketamine is a: a. Glutamate agonist b. NMDA agonist c. Glutamate antagonist d. NMDA antagonist
2. Compared to other analgesics, benefits of ketamine include: a. Less respiratory depression b. A rapid onset and short duration of action c. A variety of available dosage forms d. All of the above
3. Generally, low-dose ketamine can be defined as: a. < 0.8 mg/kg b. 1 mg/kg c. < 1 mg/kg d. > 1 mg/kg
1. History of Ketamine. KETAMINE. Accessed October 29, 2015. Available at: http://ketamine.com/history-of-ketamine/. 2. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011;57:449-61. 3. Galinski M, et al. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007;25:385-90. 4. Miller JP, et al. Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial. Am J Emerg Med. 2015;33:402-8. 5. Kennedy RM, et al. Comparison of fentanyl/midazolam with ketamine/midazolam for pediatric orthopedic emergencies. Pediatrics. 1998;102:956-63. 6. Messenger D, et al. Subdissociative-dose ketamine versus fentanyl for analgesia during propofol procedural sedation: a randomized clinical trial. Acad Emerg Med. 2008;15:877-86. 7. Sin B, et al. The use of subdissociative-dose ketamine for acute pain in the emergency department. Acad Emerg Med. 2015;22:251-7.
Joseph Ladd, PharmD PGY-1 Pharmacy Resident BHSF Homestead Hospital JosephL@baptisthealth.net http://4.bp.blogspot.com/_d_z-d2tzi14/s3r2wxdsvni/aaaaaaaabpu/f9avhyef7nm/s640/painfaces7-12.png