LONG WAY ALI PRYNE PHARMD, BCPS VALLEY VIEW HOSPITAL, GLENWOOD - PowerPoint PPT Presentation

SPECIAL K: A LITTLE GOES A LONG WAY ALI PRYNE PHARMD, BCPS VALLEY VIEW HOSPITAL, GLENWOOD SPRINGS, CO

DISCLOSURES • Nothing to disclose

OBJECTIVES 1. Compare differing doses of ketamine for indications such as sedation, analgesia, and depression. 2. Analyze recently published literature regarding ketamine and esketamine use. 3. Discuss treatment plans for safe administration and monitoring of ketamine.

BACKGROUND • Administration of ketamine in Alaska limited to provider only • RN not able to provide deep sedation • Nursing advisory

MECHANISM OF ACTION • Produces a cataleptic-like state in which the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. • Ketamine is a noncompetitive NMDA receptor antagonist that blocks glutamate.

MECHANISM OF ACTION • Low (subanesthetic) doses produce analgesia, and modulate central sensitization, hyperalgesia and opioid tolerance. Reduces polysynaptic spinal reflexes.

ASSESSMENT QUESTION Select all approved routes of administration  Intranasal  Intravenous/Intraosseous  Intramuscular  Oral  Rectal  Endotracheal

ADMINISTRATION • Oral, IM, IV, IN or Rectal

Ketamine Slow infusion vs IV push (Clattenburg et. al.) Purpose Low dose ketamine (0.3 mg/kg) IV push (IVP) vs slow infusion (SI) (over 15 min) Methods Prospective, randomized, double blind, double dummy, placebo controlled Moderate to severe pain in ED Primary outcome = side effects only – not efficacy Psychoperceptual SE w/in 60 min of administration Used SERDSA (side effects rating scale for dissociative anesthetics) Data 59 participants, 86.2% IVP vs 70% SI; not significant 75.9% IVP vs 43.4% SI; statistically significant No difference in analgesia effect Discussion Small study, not validated scale Conclusions Similar rate of SE, less severe w/ SI IVP = higher risk of “bothersome” SE Considerations Limited external validity Blinded – attempted to limit bias

Pharmacokinetics Onset of action: IV: 30 seconds IM: ~4 minutes IN: ~10 minutes Oral: ~30 minutes Duration: IV:~10 minutes IM: 15-25 minutes IN: Up to 60 minutes Protein binding: 27 % Metabolism: Four varying metabolites Hepatic via N-dealkylation (norketamine) - ~30 % as potent as ketamine Bioavailability: IM: 93% IN: 35-50% Oral: 20-30% Half-life: Alpha ~10-15 minutes, Beta 2.5 hours Time to peak, plasma: IM: 5-30 minutes IN: 10-15 minutes Oral: ~30 minutes Excretion: Urine 91%, feces 3%

SPECIAL CONSIDERATIONS • Psychedelic/dissociative effects • Nystagmus • Protruding tongue, exaggerated mouth movements • Hypertonia

SPECIAL CONSIDERATIONS • Head trauma/bleeds – increases ICP and intraocular pressure • Schizophrenia – even if stable on medications • Cardiac decompensation • Pharynx/larynx/bronchial abnormalities** • Bladder dysfunction • Tachycardia/arrythmias

ASSESSMENT QUESTION • T/F: Ketamine is commercially available only as 50 mg/mL and 100 mg/mL.

SAFETY CONSIDERATIONS • ISMP high risk medication • Concentration/math errors • “ Ketofol ” – mix of propofol and ketamine • Generally 1:1

COMPOUNDING Infusion • Dilute 50 or 100 mg/mL with D5W or NS to final concentration of 1-2 mg/mL • Do NOT use 10 mg/mL • Do not mix w/ barbituates (i.e. PHENobarbital, PENTobarbital) or diazepam • Generally send full vial for IV push, intranasal or IM routes

VIAL SIZES x x

PATIENT CASE A 34 y/o M is transported to the ER after a MVC. No PMH and NKDA. He had a positive LOC, airbags did not deploy, GCS of 9, and is beginning to not protect his airway. MD would like to proceed with RSI and looks to you for recommendations… • What other information do you want to know? • Why would you advocate for/against ketamine?

ADVERSE REACTIONS • Cardiovascular: tachycardia, hypertension • CNS: dependence, hypertonia, increased ICP • Dermatologic: rash • Endocrine/metabolic: diabetes insipidus • Gastrointestinal: nausea, sialorrhea • Genitourinary: bladder dysfunction, cystitis, urgency • Neuromuscular: laryngospasm • Ophthalmic: diplopia, increased intraocular pressure, nystagmus • Respiratory: apnea, respiratory depression

Ketamine Safety: PTSD (Highland et. al.) Purpose Determine if ketamine SE increase risk for PTSD in combat casualty care. X Methods Evaluated those medically evacuated from combat (paired) PCL (PTSD checklist scores) w/in 365 days of injury, if positive and severity Ketamine >7 days before evaluation Matched cohort n(1:1, and 1:4) Data N=1158, 107 got ketamine Primary outcome: OR=1.28 95% CI (0.48-3.47) p = .62 Secondary outcome: mean difference 1.98 95% CI (-.99 – 4.96) p = .19 Discussion Varying times between assessment, ketamine administration, and injury Low power Unknown if received in field (just at medical center post injury) Conclusions Medical and surgical care provided in service members does not appear to increase risk for PTSD Considerations Small sample size Accounted for confounders fairly well

SEDATION

KETAMINE DOSING: SEDATION • Adults • IV: 1-2 mg/kg • IM: 4-5 mg/kg, may repeat 2-5 mg/kg if needed • Pediatrics • IV: 1-2 mg/kg • IM: 4-5 mg/kg • Intranasal: 3-6 mg/kg* • Oral: 5 mg/kg *

Ketamine Procedural Sedation (Yin et. Al.) Purpose Optimal agent combined w/ propofol for sedation in elderly patients undergoing gastrointestinal endoscopy Methods ketamine w/ propofol dexmedetomidine w/ propofol sufentail w/ profofol saline w/ propofol Data See next page Discussion Well done study (prospective, blind, large single center) No major biases Conclusions Lower rates of bradycardia, hypoxia, and hypotension Considerations Only studied elderly patients (60-80 years old) short procedures (<40 min) weren’t in poor physical status (per ASA classifications)

Ketamine Intubation sedation (Shahtahmasebi et. al.) Purpose Does ketamine administration impact intubation rates in the transport of patients w/ behavioral disturbances Methods Pre and post ketamine protocol introduction Selected patients transferred from remote areas of Australia Intubation rates and adverse event Ketamine failure = adverse event Data N=340 patients, 129 had an intervention See next page for results AE = 18 ketamine and 50 I+V (difference of -0.43, p = <0.00001 CI -0.58 to -0.28) Discussion 92.5% were mental health/substance abuse Selection bias Conclusions Ketamine reduced intubation rates in patients w/ behavioral disturbances on transport Reduces adverse reactions, but does have risks Considerations Included all post protocol = real life May require intubation for other illness/low GCS Lower cost?

Ketamine Adjunct sedation in vented patients (Groetzinger et. al.) Purpose Ketamine use as adjunct sedation in mechanically vented patients Methods Retrospective review between 2012-2016, on continuous infusion Dosing, effect on other sedatives, total sedative use, Sedation-Agitation Scale (SAS), ADRs and hemodynamics Excluded if paralyzed or ketamine for <6 hours Data N=91, median dose= 0.41 mg/kg/hr, duration = 2.8 days 63% reduction or discontinuation of alternative sedative 7.7% had ADR = discontinuation Increase in SAS at goal 61% vs 55% p =0.001 Discussion Descriptive report No standard protocol for dosing Selection bias (only started in 65% of patients Conclusions Acceptable adjunct sedation in critically ill patients Considerations Attempt for light sedation 30% of adults may experience emergence reactions, only 2% in this study

Ketamine Adjunct sedation (Pruskowski et. al.) Purpose Ketamine as adjunct sedation/analgesia in trauma patients Methods Retrospective chart review – must have sedation, not just acute pain Determine time at RASS goal and alternative sedation doses Changes 72 hours before or 72 hours after initiation Data N=36, mostly white men w/ blunt trauma Decreased opioid and propofol use Increased dexmedetomidine and ziprasidone use Did not change time at goal RASS Discussion Trade off? Less opioid use for psychosis AE Conclusions Ketamine infusions may not be the best choice for trauma patients Considerations Single center, small study Did not confound for TBI, substance withdrawal or psychiatric disorders

ANALGESIA Painless

KETAMINE DOSING: ANALGESIA • Adults • IV: 0.2-0.8 mg/kg bolus followed by 1 mcg/kg/minute • Intranasal: acute pain 0.5-1 mg/kg • Pediatrics • IV • IM • Intranasal