TIVA: Are you using all the tools in your box?€¦ · Taming the Ketamine Tiger Domino, EF. Taming the Ketamine Tiger. Anesthesiology. 2010; 113:678-86 1970s ﬁrst reports of role

TIVA: Are you using all the tools in your box?Thomas Miller CRNA, MSN

Saturday, October 25, 14

Objectives

✤ Using a Case Based Review discuss the evidence for benefits, risk, and costs of:

✤ Remifentanil

✤ Dexmedetomidine

✤ Ketamine


Disclosures

✤ Paid speaker for Mylan pharmaceuticals makers of Remifentanil (no compensation for this educational presentation)

✤ Off label uses or uses for “austere” environments will be discussed


Why TIVA?

✤ Surgery specific benefits or “logistics”

✤ Avoidance of triggering agents

✤ Improved V/Q Matching

✤ Increased mucocilliary transport (Ledowski Anesth Analg 2006;102(5):1427-1430)

✤ Decreased PONV

✤ Decreased emergence delirium

✤ Economics and patient satisfaction


Quality Measures in Hospital Care

✤ Hospital Consumer Assessment of Healthcare Providers and Systems

✤ National, Standardized, Publicly Reported Survey of Patients’ Perspectives

Center for Medicare and Medicaid Services Website


Why not?

✤ Increased Cost

✤ Less titratable

✤ Cumbersome at time

✤ What are your goals?


Case #1 2:45 Lap Chole

✤ 46 y.o. female presenting with biliary colic for Laparoscopic Cholecystectomy

✤ PMH:

✤ HTN and high cholesterol

✤ 5’2 /82kg (BMI: 33)

✤ Previous anesthetics: knee arthroscopy at age 42. No complications. Csxn x2 under spinal

✤ Family hx of MH


Propofol/Remi TIVA

✤ Pre: 2mg Versed IV 4mg Dexamethasone, Scopolamine patch 1.5mg

✤ Induction:

✤ 180 mg Propofol IV

✤ 30 mg Rocuronium IV

✤ 1mg Hydromorphone IV

✤ 75 mcg Remifentanil + 50mg Propofol


Remifentanil

✤ Ultra short acting Fentanyl Analog, mu-opiod agonist

✤ Rapid Onset (30-60 seconds)

✤ Short duration of action (Effective half life: 3-10 minutes/Context sensitive half time: 3 to 6 minutes)

✤ Metabolism independent of renal or hepatic function

✤ Synergistic with other drugs. May reduce requirement of propofol, Midazolam, and Isoflurane by up to 75%

✤ Major Benefits? Concerns?


Maintenance

. An initial dose of 1 mcg/kg may be administered over 30 to 60 secmds.Geriatrics (patienls >65 years): decrease starting dose by 50%: obese patients (>30% of IBW): base startingdose on IBW; palients with renal or hepatic impairment: no dose adiustnenlIBw=ideal body weight; MAC=minimum alveolar concentration.ULTIVA lpackage insertl. Lake Focsi. lL: Bionache Pha.ma USA LLC; 2009.

lJltiidz^(remifentanil HCD-

This table summarizes use qf remifentanil during the induction and maintenance of general anesthesia andfor continuation as an analgesic into the immediate postoperative period.' During induction, remifentanil should be administered at an infusion rate of 0.5 to l mcg/kg/min with a

hypnotic or volatile agent. lf endotracheal intubation is to occur less than 8 minutes after the start of theinfusion of remifentanil, then an initial dose of 7 mcg/kg may be administered over 30 to 60 seconds

' During maintenance of anesthesia, the infusion rate of remifentanil should be decreased as shown in thisdosing table. The rate of administration of remifentanil in adults can be titrated up in 25% to LOO%increments or down in 25%to 50% decrements every 2 to 5 minutes- Bolus doses of 1 mcg/kg may be administered every 2 to 5 minutes in the event of light anesthesia or

transient episodes of intense surgical stress- At infusion rates >1 mcg/kg/min, an increase in the concomitant anesthetic agents should be

considered to increase the depth of anesthesia- For certain patients for whom later transition to longer-acting analgesics is anticipated, infusions of

remifentanil may be continued as an analgesic into the immediate postoperative period in apostoperative care unit or intensive care setting

- lf remifentanil is continued as an analgesic into the immediate postoperative period, it must be done sounder the direct supervision of an anesthesia provider

- Remifentanil should be initially administered by continuous infusion at a rate of O.t mcg/kg/min andmay be adjusted every 5 minutes in 0.025-mcg lkg/min increments. lnfusions greater than 0.2mcg/kg/min are associated with respiratory depression

- Bolus doses of remifentanil for pain management in the postoperative period are not recommended. Please instruct the audience to refer to the dosing guide for additional information including guidance on

dosing in pediatrics. Additionally, there is a backup slide in this deck on pediatric dosing, to address suchquestions

ReferenceULTIVA [package insert]. Lake Forest, lL: Bioniche Pharma USA LLC; 2009.


Remi and Synergy

✤ Bouillon, et al. Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entropy. Anesthesiology. 2004;100 (6): 1353-1372.

✤ Hypnosis : Propofol alone TCI concentration of 8.6mcg per ml VS. Propofol/Remi 0.88 mg per ml

✤ Ablation of response to stimuli: Propofol alone 15 mcg/ml VS. Propofol/Remi 2.5 mg/ml

✤ BIS and EEG/AE: no addiditive effect of Remi (Remi is not a hypnotic agent

✤ Other uses?


Text


Brady et.al. continued. Retrospective review of 49 Charts (PS 1-4) for outpatient elective surgery

✤ Group #1: TIVA with a 20 ml syringe: 5% Dextrose, 5mg/ml Propofol, 25mcg/ml Remifentanil

✤ Induction 1-1.5 mg/ml Propofol

✤ Maint: 25-75 mcg/kg/min Propofol;50/50% Nitrous/Oxygen

✤ Rocuronium as needed

✤ Local Anesthesia and Ketorolac for post operative pain

✤ Group #2: Balanced anesthetic

✤ Induction: Propofol 1-2 mg/kg, Fentanyl 2-5 mcg/kg

✤ Maint.: 50/505 Nitrous/Oxygen, Sevo.

✤ Analgesia as needed in PACU


Results

✤ TIVA Group had shorter PACU time (48.26min vs. 59.62min), 2 patients bypassed PACU

✤ TIVA group had shorter combined OR/PACU times though NOT statistically significant

✤ OR “events” were higher in TIVA group (all bradycardia)

✤ PACU “events” lower in TIVA group (volatile: hypotension, PONV)


Cost?

Drug Cost

PACUCost

TIVA $280.83 $171.80

Balanced $337.42 $207.20


The “Chemical Sympathectomy”

✤ Wormald, PJ.During ESS, Remifentanil-Propofol Based TIVA provides a Significantly Lower Mean Arterial Pressure and a Significantly Improved Surgical Field Compared with Sevoflurane-Fentanyl. Am J Rhinol. 2005; 19(5):514-20

✤ 56 Patients ASA 1-2 undergoing FESS

✤ Sevo-Fent arm maintained 0.8% to 1.8% ET with Fent bolusing up to 7mcg/kg

✤ Remi-Prop arm TCI pump Propofol at 2-4 mg/ml, Remi at 0.2-0.3 mc/kg/min

✤ MAP was mantained between 55-70 mmHg (metoprolol and clonidine)


Thats a lot of work!!

✤ Reconstitute 1mg Remi in 20ml NS (50mcg/ml)

✤ 20 ml syringe of propofol + 100 mcg/remi or 50ml vial +250 mcg Remi. (concentration will be 5mcg/ml of Remi)

✤ 100 mcg/kg/min Propofol = 0.05 mcg/kg/min Remi

✤ Example : 80 kg pt100 mcg/kg/min of propofol= 8 mg/min= 0.8 ml/min=4mcgRemi/min =0.05mcg Remi/kg/min


Case #2The “Challenging” T and A

✤ 14 yo male with developmental delay

✤ PMH: OSA (AHI 11), Obesity (5’2/85kg; 99th percentile), Asthma.

✤ PSH: BMT x2, severe emergence aggitation

✤ Exam: MP 2, cooperative


T and A for the patient with OSA

✤ Surgical Considerations?

✤ Patient Considerations?

✤ More than one way to skin a cat


Dexmedetomidine Infusion

✤ Patel,A et al. Dexmedetomidine for analgesia and prevention of emergence agitation in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy. Anesth Analg 2010; 111(4):1004-10

✤ 122 Patients with OSAS (Ages 2-10 y.o.)

✤ No premed, mask induction, Decadron (0.5mg/kg), PR Tylenol (30-40mg/kg), Roc (0.6mg/kg)

✤ Dex group received 2mcg/kg bolus followed by 0.7mcg/kg/hr

✤ Fentanyl group received 1mcg/kg on induction

✤ Both groups received Fent 0.5 mcg/kg as a “rescue” if necessary


Single Dose Precedex

✤ 90 patients undergoing genitourinary surgery ages 1-10 yo

✤ 3 groups: saline vs. Precedex 0.15mcg/kg vs. Precedex 0.3 mcg/kg

✤ Emergence agitation was 10% in group 3 vs 37% in control

✤ No Delay in discharge time

✤ Dose? Cost?

Ibacache et al. 2004. Single-Dose Dexmetatomidine Reduces Agitation After Sevoflurance Anesthesia in Children. Anesthesia and Analgesia. 98:60-3.


Precedex and Bariatric Surgery

✤ Tufanogullari et al. Dexmedetomidine Infusion During Laparoscopic Bariatric Surgery: The Effect on Recovery Outcome Variables. Anesth Analgesia. 2008. 106:6. 1741-48

✤ Two Fold Study: Assess if there was a reduction in anesthetic and analgesic requirements; determine if the use facilitated the recovery process

✤ 80 morbidly obese patients assigned to 4 groups: Control, Dex 0.2 mcg/kg/hr, Dex 0.4 mcg/kg/hr, Dex 0.8 mcg/kg/hr. (actual BW dosing)

✤ “Standard induction”, then maintenence with inspired Desflurane titrated to MAP value (+/- 25% baseline)

✤ Fentanyl for post op pain until a pain score

Precedex and Bariatric Surgery


Generic Precedex

✤ Hospira holds the patent on Precedex for ICU sedation through 2019; Second patent for use in non-intubated patients and surgical/procedural sedation has already expired

✤ August 18 FDA approved generic Precedex for distribution. Mylan began distribution immediately

✤ Second manufacturer Sandoz (a division of Novartis will begin distribution in December 2014)

✤ August 20th a restraining order on sales was issued

✤ September 8th US District Court in Maryland lifted order

✤ Precedex represented 11 percent of Hospira’s global net sales of $4.1 billion in 2013


Case #3Quick Plastics Case

✤ 46 yo Female for excision of multiple lipomas (back, shoulder, flank)

✤ PMH: HTN, Anxiety/Depression, Obesity,Fibromyalgia, GERD, Smokes 1/2 ppd

✤ PSH: Hysteroscopy with severe PONV, Csxn x2, Knee arthroscopy also with severe PONV.

✤ Meds: Lisinopril, Wellbutrin, Xanax, Oxycodone, Protonix


“Heavy MAC”

✤ Preop: 2mg IV Midazolam, 0.2mg glyco

✤ Induction: 20mg Ketamine, 2mg Midazolam, 50mg Propofol,4mg Decadron

✤ Maint: Propofol/Ketamine infusion (mixed 1mg/ml Ketamine) @ 50-150 mcg/kg/min. LA by surgeon

✤ Emergence: 4mg Ondansetron, 30mg Keterolac


Ketamine

✤ Dissociative Anesthetic

✤ CV: Direct myocardial depressant

✤ Resp: Bronchial smooth muscle relaxation

✤ Neuro: Increases CMR, CBF, ICP


Taming the Ketamine Tiger Domino, EF. Taming the Ketamine Tiger. Anesthesiology. 2010; 113:678-86

✤ 1956 Two Parke Davis scientist synthesized the compound CI-395

✤ Dr. Domino at University of Michigan received the grant to study it

✤ Detroit Receiving Hospital conducted first human trial of CI-395

✤ Studied as a model of schizophrenia at the Lafayette clinic

✤ Further study showed it unsuitable for human anesthesia


✤ A series of short acting derivatives were developed and submitted to Parke Davis

✤ One agent produced excellent anesthesia in Monkeys: CI: 581

✤ August 3, 1964 first doses of Ketamine administered

✤ 1970’s Domino along with the anesthesia department at Michigan attempted to “tame the ketamine tiger”, i.e reduce the emergence delerium

✤ Drug of abuse




✤ 1970s first reports of role in treatment of depression

✤ 1982 Mechanism of Action identified

✤ 1987 NMDA role in “wind up” response and chronic pain

✤ Extensive studies in the last two decades


The “swiss army knife” of narcotics

✤ Roles well described in treating chronic pain

✤ Preemptive analgesia

✤ Reducing postoperative opiod requirements

✤ Prevention of hyperalgesia

✤ Role in treatment of depression

✤ Emergence delerium


Case #4

✤ 2 yo child with complex CHD and pulmonary HTN presents for cardiac cath and lung scan

✤ 11 kg, NKDA

✤ 22g PIV in place

✤ 1 L NC O2 at baseline

✤ Cardiologist requests “avoid positive pressure ventilation please”


Ketamine/Versed TIVA

✤ Rate of infusion is based on dose of Ketamine to maintain GA

✤ 50 ML Syringe: 200mg Ketamine, 5mg Midazolam, + NS.

✤ Start infusion at 1ml/kg/hr..........OR..the patients weight

✤ Equates a dose of Ketamine of 4mg/kg/hr and Versed 0.1mg/kg/hr

✤ For sggitation or breakthrough administer a dose based on Ketamine dosing of 0.5-1mg/kg

✤ Glyco 5mcg/kg adjuvant


Ketamine and Emergence Agitation

Anghelescue et al. 2011. Prevention of Emergence Agitation in Seven Children Recieving Low-Dose Ketamine and Propofol Total Intravenous Anesthesia.

AANA Journal. 79,3:


Ketamine

✤ Khattab et al. Sevoflurane-emergence agitation: Effect of low-dose oral Ketamine premedication in preschool children undergoing dental surgery. Saudi Journal of Anaesthesia. 3;2: 61-66.

✤ 92 preschool children ASA 1 and 2

✤ Recieved oral Midaz 0.5mg/kg or oral Midaz 0.5mg/g + 2mg/kg Ketamine

✤ Postoperative agitation scores and need for rescue (1 mcg/kgof Fent) significantly less in the Ketamine group

✤ Time to discharge?


Emergence Delirium and PTSD

✤ AANA Journal. August 2012 (80:4)

✤ Qualitative survey of CRNAs who had cared for service members suffering TBI and/or PTSD

✤ Identified 5 themes


Service Personnel Emerging from General Anesthesia

✤ Five Themes were identified:

✤ ED exists and in a much higher proportion to the general population

✤ ED was more prevelant in the younger population

✤ TIVA was superior to volatile anesthetics in those patients thought to have TBI or PTSD

✤ Talking to patients before surgery and during emergence was vital for smooth emergence

✤ “There is something “profound” happening in regards to Ketamine and PTSD”


Ketamine, Depression, and PTSDCase#5

✤ 26 yo Male Combative Veteran with refractory PTSD/Depression, suicidal ideations, and insomnia

✤ 5’8; 71kg. NKDA, Otherwise healthy, NPO >8 hours

✤ Received 3mg Midaz. Then “induction” of 70mg propofol and 30mg Lidocaine

✤ 20 minute infusion of 20mcg/kg/min and total of 35mg of Ketamine (0.5mg/kg)

✤ Awake and ambulating 1 hour after infusion stopped.

✤ Results? Womble, A. Effects of Ketamine on a Major Depressive Disorder in a Patient with Post Traumatic Stress Disorder. AANA Journal. 2013. 81:2. 118-20.


Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Clinical Trial

✤ Feder et al. JAMA Psychiatry. April 2014

✤ Glutamate and PTSD

✤ “Peri-Trauma” administration

✤ RCT: 41 patients randomized to receive Ketamine (0.5mg/kg) vs Midazolam (0.045 mg/kg)


Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Clinical Trial

lV Ketamine for Treatment of Chronic PTSD

Figure 1. Consolidated Standards of Reporting Trials Patient Flowchart

2 Dropped out (ketamine)1 Found a job1 Tenlporarily tost to follow-up

1 Removedlrom study duetodetayed-onset sedation (ketamine)

1 Removed from study due to lowbasetine PTSD symptom levets(midazotam)

41 Randomly assigned to ketamine ormidazotam. and received lst infusion

6 Completed study after 1st infusionbecause of sustained improvement2 weeks afLer infusion

l

31 Re(eived 2nd infusion

35 Completed study6 Completed after 1st infusion

29 completed after 2nd infusion

8 Were ineligibte3 Withdrew consent5 Losttofotlow-uD

2 Dropped out1 Received higher-than-expected

kelamine doseI Felt uncomfortJbte during

ketamine infusion

Or,rj,Jr;l lfi lrrlil;"r1hil Research

PTSD indjcates posttraumatrc stressdisorder.

57 Participants screened for eligibility

infusion days, administered ratings at preinfusion baseline and24 hours (day t) after infusion (before patients were dis-charged from the hospital), 48 hours (day z) after infusion, 72hours (day 3) after infusion, and 7 days (day z) after infusion.Ratings were also administered ro and t3 days after infusion,although data analyses focused on the first week after infu-sion owing to the expected duration of ketamine action. Pa-tients were instructed to abstain from takingpsychotropic medications and from using alcohol or substances ofabuse for theduration ofthe trial. As already described, patients who scored5o or higher on the CAPS 2 weeks after the first infusion re-ceived an infusion ofthe second study drug. Patients whosesymptoms remained signiFrcantly improved 2 weeks after in-fusion (indicated by a CAPS score of

Documents

TIVA: Are you using all the tools in your box?€¦ · Taming the Ketamine Tiger Domino, EF. Taming the Ketamine Tiger. Anesthesiology. 2010; 113:678-86 1970s ﬁrst reports of role