Download Free Medical KETAMINE - Whats Old is New Again PowerPoint Presentation

KETAMINE - Whats Old is New Again PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical presentation on Neurology, which is titled "KETAMINE - What’s Old is New Again", to know about Ketamine.

Tags : Neurology, Ketamine

Published on : Aug 23, 2021 | Views : 1755 | Downloads : 5

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

KETAMINE - What’s Old is New Again Mary Wojnakowski, CRNA, PhD Director Nurse Anesthesia Program Midwestern University
Slide 2-

WHATS OLD…..
Slide 3-

“DISSOCIATIVE ANESTHETIC” Produces an atypical behavioral state. State of sedation Immobility Amnesia Marked analgesia Feeling of dissociation from the environment Without true unconsciousness
Slide 4-

HISTORY Ketamine was first synthesized in 1962 in an attempt to find a safer anesthetic alternative to PCP, which was more likely to cause hallucinations and seizures. The drug was first used on American soldiers during the Vietnam War. In the recent past its use on humans has been dramatically curtailed because of exaggerated concern about its potential to cause emergence phenomena including out-of-body experiences in clinical practice.
Slide 5-

ORGANIC CHEMISTRY Phencyclidine derivative
Slide 6-

Ketamine is racemic Has two steroisomers R- and S+ Have different anesthetic potencies (1:3-4) but similar kinetics
Slide 7-

Its R- and S+ stereoisomer have different binding affinities. (S)-Ketamine has about four times greater affinity for the PCP site of the NDMA receptor than (R)-Ketamine (in guinea pig brain). The S form also seems to be better at inducing the drowsiness than the R form.
Slide 8-

Soluble in aqueous solutions Does not require a lipid solvent like propofol or etomidate Produces profound analgesia at subanesthetic doses. pH is 3.5 to 5.5 (pKa 7.5) Highly lipid soluble 12-35% plasma protein bound 44% nonionized at physiologic pH
Slide 9-

PHARMACODYNAMICS Dosing: Sedation/Analgesia IV: 0.5 – 1.0 mg/kg IM/ rectal: 2.5 – 5.0 mg/kg PO: 5 – 6 mg/kg Induction IV: 1.0 – 2.5 mg/kg IM/ rectal: 5 – 10 mg/kg Infusion 15-80 mcg/kg/min Augment with diazepam IV 2 -5 mg or midazolam IV 1 -2 mg Epidural/ Caudal 0.5 mg/kg Dilute in saline or local anesthetic (1 mL/kg)
Slide 10-

Cardiovascular system: Direct myocardial depressant Overriden by the central sympathetic stimulation, neurolal release of catecholamines, & inhibition of neuronal uptake of catecholamines. Increase in systemic arterial pressure Increase in heart rate Increase in cardiac output Pulmonary system: Bronchial smooth muscle relaxant As effective as inhalational agents in preventing bronchospasm Increase in pulmonary arterial pressure Increases aalivary & tracheobronchial secretions
Slide 11-

Neurological system: Seizure threshold is not altered Increase in cerebral metabolism, blood flow, & ICP Other: Increases uterine tone without adverse effects on uterine blood flow Does not release histamine
Slide 12-

PHARMACKINETICS Onset of action: IV <30 seconds IM/ rectal 3 – 4 minutes Peak effects: IV 1minute IM/ rectal 5 – 20 minutes PO 30 minutes Duration of action: IV 5 - 15minute IM/ rectal 12 – 25 minutes Epidural 4 hours Metabolism: Demethylation & hydroxylation by hepatic CYP One of the produced metabolites is active Norketamine (Metabolite I) Has a potency of 30% of the parent drug & longer half-life
Slide 13-

NEUROPHARMACOLOGY Ketamine, is primarily a non-competitive glutamate NMDA receptor antagonist. At low doses, the analgesia effects of ketamine are mediated by antagonism on the NMDA receptors. Evidence for this is reinforced by the fact that naloxene, an opioid antagonist, does not reverse the analgesia. Studies also seem to indicate that ketamine is 'use dependent' meaning it only initiates its blocking action once a glutamate binds to the NMDA receptor.
Slide 14-

At high doses, ketamine has also been found to bind to opioid mu receptors and sigma receptors. This indicates that loss of consciousness at high doses may be partially due to binding at the opioid mu and sigma receptors.
Slide 15-

The effects seem to occur mainly in the hippocampal formation and in the prefrontal cortex. This evidence along with the NMDA receptor's connection with the memory formation process explains ketamine's profound effects on memory and thought.
Slide 16-

WHATS NEW…
Slide 17-

Strong pain stimuli activate NMDA receptors and produce hyperexcitability of dorsal root neurons. This induces central sensitization, wind-up phenomenon, and pain memory. Ketamine, a noncompetative antagonist of NMDA receptors, can prevent the induction of central sensitization caused by stimulation of peripheral nociception as well as blocking the wind-up phenomenon.
Slide 18-

Multimodal Analgesia Simultaneous use of multiple analgesic methods or drugs.
Slide 19-

Review of the Current Literature…
Slide 20-

Ketamine as an Adjunct Analgesic
Slide 21-

Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. The Cochrane Database of Systematic Reviews. 2006; 3; 1-61. N = 37 trials (2240 participants) Methods: Search from 1966-2004 Randomized, controlled trials being treated with perioperative ketamine or placebo Results & Conclusion: Subanesthetic doses of ketamine reduce rescue analgesia requirements, pain intensity, PCA morphine consumption, PONV. Adverse effects were mild or absent.
Slide 22-

Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI, Chauvin M. Remifentanil-induced postoperative hyperanalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005; 103: 147-55 Methods: N = 75 Major upper abdominal surgery Treatment groups: Intraoperative remifentanil at 0.05 mcg/kg/min Intraoperative remifentanil at 0.40 mcg/kg/min Intraoperative remifentanil at 0.40 mcg/kg/min Ketamine 0.5 mg/kg just after incision followed by infusion at 5 mcg/kg/min until skin closure then 2 mcg/kg/min for 48 hours Results: Hyperanalgesia in group 2 was greater compared to the other two groups No difference between group 1 and 3 Conclusion: Large doses of intraoperative remifentanil triggers postoperative hyperanalgesia This hyperanalgesia is prevented by small-dose ketamine NMDA pain-facilitator process
Slide 23-

Adam F, Chauvin M, DaManoir B, Langlois M, Sessler DI, Fletcher D. Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty. Analgesia & Anesthesia. 2005;100: 475-80. N = 40 Elective total knee arthroplasty with general anesthesia & continuous femoral nerve block Methods: Treatment groups Ketamine 0.5 mg/kg bolus before skin incision followed by infusion at 3 mcg/kg/min until emergence from anesthesia followed by infusion at 1.5 mcg/kg/min for 48 hours Placebo Results & Conclusions: Group 1 required less morphine, reached 90 ° flexion more rapidly. No difference in side effects
Slide 24-

Ketamine for Preemtive Analgesia
Slide 25-

Kwok RFK, Lim J, Chan MTV, Gin T, Chiu KY. Preoperative ketamine improves postoperative analgesia after gynecologic laparoscopic surgery. Anesthesia & Analgesia. 2004; 98: 1044-9. N = 135 Methods Treatment groups Preincision group * Ketamine IV 0.15 mg/kg immediately before induction of anesthesia Postoperative group * Ketamine IV 0.15 mg/kg after wound closure Placebo group Results & Conclusions: Group 1 had lower pain scores, longer time to first request for analgesia, & lower morphine consumption No difference r/t hemodynamic variables or side effects
Slide 26-

Ketamine with Local Anesthetics
Slide 27-

Suzuki M, Haraguti S, Sugimoto K, Kikutani T, Shimuda Y, Sakamoto A. Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy. Anesthesiology. 2006; 105: 111-9. N = 50 Methods: Treatment groups: Continuous epidural infusion of ropivacaine & morphine with IV ketamine at 0.05 mg/kg/hr Placebo Epidual inplace for 2 POD; ketamine infusion for 3 POD Results: Ketamine group has lower pain scores Ketamine group had lower baseline pain scores at 1 & 3 months Placebo group was still taking pain medications. Conclusions: Very-low-dose ketamine potentiated morphine-ropivacine analgesia and reduced post-thoracotomy pain.
Slide 28-

Ketamine and Brain Injury
Slide 29-

Himmelseher S, Durieux ME. Revising a dogma: Ketamine for patients with neurological injury? Anesthesia & Analgesia. 2005; 101:524-34. N = 79 trials (> 500 participants) Methods: Search from 1994-2004 Randomized controlled trials Nonrandomized controlled or cohort trials Results & Conclusions: Ketamine does not increase ICP when used with controlled ventilation, co-administration of a GABA receptor agonist, and without nitrous oxide. Hemodynamic stimulation induced by ketamine improved cerebral perfusion. In the lab: Ketamine has neuroprotective effects S(+)- ketamine has neuroregenerative effects NOTE: improved outcomes were only reported with brief recovery observation intervals Neurotoxic effects noted after large doses
Slide 30-

Erb TO, Ryhult SE, Duitmann E, Hasler C, Luetschg J, Frei F. Improvement of motor-evoked potentials by ketamine and spatial facilitation during spinal surgery in a young child. Anesthesia & Analgesia. 2005; 100: 1634-6. Case study Child serves as own control Methods: First attempt (No MEP’s could be recorded) Propofol 50-100 mcg/kg/min Remifentanil 2 mcg/kg/min Second attempt (MEP’s could be obtained) Ketamine 20 mg bolus followed by infusion of 4 mg/kg/hr Remifentanil 2 mcg/kg/min Results & Conclusions: Ketamine-based anesthesia improves the signal quality of MEP’s.
Slide 31-

Stereoisomers of Ketamine
Slide 32-

Lahtinen P, Kokki H, Hakala T, Hynynen M. S(+)-ketamine as an analgesic adjunct reduces opioid consumption after cardiac surgery. Anesthesia & Analgesia. 2004; 99:1295-1301. N = 90 Pain management after sternotomy Methods: Treatment groups: 75 mcg/kg bolus followed by infusion at 1.25 mcg/kg/min for 48 hours Placebo Results & Conclusions: Group 1 consumed less oxycodone, and had higher patient satisfaction scores. Pain scores did not differ at rest or deep breathing Side effects did not differ.
Slide 33-

Hanouz JL. Zhu L. Persehaye E. Massetti M, Babatasi G, Khayat A, Ducouret P, Plaud B, Gerard JL. Ketamine preconditions isolated human right atrial myocardium: roles of adenosine triphosphate-sensitive potassium channels and adrenoceptors. Anesthesiology. 2005; 102: 1190-6. Examined the effects of ketamine and its S(+) isomer on isolated human myocardium submitted to hypoxia-reoxygenation. Ketamine enhanced recovery of force of contraction at the end of the reoxygenation period. Ketamine preconditions the myocardium via activation oo adenosine triphosphate-sensitive potassium channels & stimulation of alpha- and beta-adrenergic receptors.
Slide 34-

Argiriadou H, Himmelseher S, Papagiannopoulou P, Georgiou M, Kanakoudis F, Giala M, Kochs E. Improvement of pain treatment after major abdominal surgery by intravenous S(+)- ketamine. Anesthesia & Analgesia. 2004; 98: 1413-8. N = 45 Lower abdominal surgery with epidural and general anesthesia Methods: Premedicated with oral diazepam 0.15 mg/ kg Treatment groups: Single IV injection at 0.5 mg/kg before incision Single IV injection at 0.5 mg/kg before incision Intraoperative IV injection at 0.2 mg/kg every 20 minutes until 30 minutes before end of surgery 3) Placebo Results & Conclusions: Group 2 had lower pain scores, required less additional analgesics, and reported greater patient satisfaction No psychotomimetic side effects were noted
Slide 35-

Martindale SJ, Dix P, Stoddaet PA. Double-blind randomized controlled trial of caudal versus intravenous S(+)-ketamine for supplementation of caudal analgesia in children. British Journal of Anaesthesia. 2004; 92:344-7. N = 60 Caudal block during general anesthesia for hernia repair or orchidopexy Methods: Treatment groups: Caudal bupivacaine 0.25% 1 mL/kg Caudal bupivacaine 0.25% 1 m/kg with S(+)-ketamine 0.5 mg/kg Caudal bupivacaine 0.25% 1 m/kg plus IV S(+)-ketamine 0.5 mg/kg Results: Group 2 had a longer time to first analgesia requirement and a lower total drug requirement overall No difference between group 1 & 3 No difference between group concerning side effects Conclusion: Principle analgesic effect of caudal S(+)-ketamine results from a local neuroxial rather than systemic effect.
Slide 36-

Ketamine and the Pediatric Patient
Slide 37-

Dalens BJ, Pinard AM, Letourneau DR, Albert NT, Truchon RJY. Prevention of emergence agitation after sevoflurane anesthesia for pediatric cerebral magnetic resonance imaging by small doses of ketamine or nalbuphine adminnistered just before discontinuing anesthesia. Anesthesia & Analgesia. 2006; 102: 1056-61. N = 90 6 mo to 8 years scheduled for cerebral MRI under general anesthesia Methods: Treatment groups: At end of procedure received: Ketamine 0.25 mg/kg Nalbuphine 0.1 mg/kg Placebo Results & Conclusions: Group 3 was most agitated at all times Group 1 & 2 more obtunded at 5 and 10 minutes BUT all groups met discharge criteria at 30 minutes Group 1& 2 were more awake and quiet (Most in group 1; all in group 2)
Slide 38-

Migita RT, Klein EJ, Garrison MM. Sedation and analgesia for pediatric fracture reduction in the emergency department: a systematic review. Archives of Pediatric & Adolescent Medicine. 2006; 160: 46-51. N = 8 studies (1086 participants) Assess safety & efficacy of various forms of analgesia and sedation Results: Ketamine-midazolam was more effective & had fewer side effects than fentanyl-midazolam or propofol-fentanyl.
Slide 39-

Other Studied Uses of Ketamine
Slide 40-

Saricaoglu F, Dal D, Salman AE, Doral MN, Kilinc K, Aypar U. Ketamine sedation during spinal anesthesia for arthroscopic knee surgery reduced the ischemia-reperfusion injury markers. Anesthesia & Analgesia. 2005;101: 904-9. N = 30 Arthroscopic knee surgery with tourniquet under spinal anesthesia with 12.5 mg bupivacaine Methods: Treatment groups: Midazolam 0.01 mg/ kg Ketamine infusion at 0.5 mg/kg/hr to end of surgery 2) Midazolam 0.01 mg/kg Results & Conclusions: Group 1 had lower MDA & HPX levels after reperfusion Ketamine attenuates lipid peroxidation which results in tissue injury
Slide 41-

McDaniel WW, Sahota AK, Vyas BV, Laguerta N, Hategan L, Oswald J. Ketamine appears asociated with better word recall than etomidate after a course of 6 electroconvulsive therapies. J ECT. 2006; 22: 103-6. N = 10 ECT for severe depression Methods: Patients served as their own controls Treatment groups: Etomidate 0.3 mg/kg Ketamine 1.0 mg/kg Results : Group 2 had less impairment of short-term memory loss Conclusion: The effect of ECT on memory is mediated by glutamate at NMDA receptors NMDA receptor antagonists may offer protection from memory dysfunction
Slide 42-

Dal D, Honca KM, Akinci SB, Basgul E, Aypar U. Efficacy of prophylactic ketamine in preventing postoperative shivering. British Journal of Anaesthesia. 2005; 95: 189-92. N = 90 Undergoing general anesthesia for an anticipated duration of 60-180 minutes Methods: Treatment groups (administered 20 min before end of surgery): Pethidine 20 mg Ketamine 0.5 mg/kg Placebo Results: Fewer patients in group 1 & 2 were shivering on arrival in the recovery room Time to first analgesic requirement was less in group 1 & 2 Conclusions: Low dose ketamine is effective in preventing postoperative shivering
Slide 43-

Poyhia R, Vainio A. Topically administered ketamine reduces capsaicin-evoked mechanical hyperalgesia. Clinical Journal of Pain. 2006; 22: 32-6. N = 9 Assess the effect of topically applied ketamine Methods: Treatment groups: 1) Applied 1 mL of Ketamine gel (50 mg/mL) 2) Placebo Applied to bilateral forearms 10 minutes before intradermal injection of capsaicin (250 mcg) Results: Intensity & unpleasantness of mechanical hyperalgesia was less with ketamine No side effects were noted Conclusion: Preemptive topical ketamine reduces central sensitization secondary to its absorption into circulation
Slide 44-

IN CONCLUSION…
Slide 45-

ppt slide no 45 content not found