Total Intravenous AnesthesiaTotal Intravenous Anesthesia
A Rational Approach to Anesthetic Management
Michael Rieker, DNP, CRNADi t N A th i PDirector, Nurse Anesthesia Program
Wake Forest Baptist Medical Center
Objectives
Review drugs and methods in TIVA Di h f l h id d d i i t ti fDiscuss how propofol has aided administration ofTIVADescribe different equipment that makesDescribe different equipment that makesadministration of TIVA safe and effectiveList new drugs and drug combinations that are used to improve TIVAOutline medical conditions, disease processes and types of surgery that lend themselves to TIVA for GAtypes of surgery that lend themselves to TIVA for GADiscuss contraindications to TIVA for GA
Drug administration
�Intravenous agents administered by manual bolus on a dose/kg basis is gprobably as old-fashioned as administration of volatileas administration of volatileagents by the Schimmelbusch mask �Schimmelbusch mask.Armin Holas MD, University of Graz, Austria.
Why Intravenous anesthetics?
SafetyHemodynamic controlHemodynamic controlRapid titrationAvoid vasodilatation, expansion of , pgas cavitiesReduced PONVOccupational exposureOccupational exposureSmooth emergence, less hangoverAvoid MH riskCost benefit?
Why Intravenous Anesthetics?
Improved mucociliary transportp y pLedowski. Anesth Analg. 2006;102(5):1427-30.
Reduced PONVRohm. Acta Anaesth Scand. 2006 50(1):14-8.
Less effect on hepatic enzymesp yRohm. Europ J Anaesth. 2005 ;22(3):209-14.
Advantages of TIVA
Improved V/Q matchingPraetel. Anesth Analg. 2004; 99(4):1107-13
Reduced stress response. L d ki A th A l 2005 101(6) 1700 5Ledowski Anesth Analg. 2005;101(6):1700-5.
Improved surgical field (bleeding)Wormald P Am J Rhinology 2005;19 (5): 514Wormald, P, Am J Rhinology 2005;19 (5): 514.
Volatiles assoc. with increased inflammation and decreased immune functionand decreased immune function
Kurosawa Curr Opin Anaesthesiol. 2012;25(3):376.
Optimal technique for neuroanesthesia
Improved extent and duration of cerebral metabolic suppressionsuppression.
Yoon, Kim, & Kim. J Neurosurg Anesthesiol 2012 24(2):146.
Improved CPP, less interference with SSEP, MEP, AEP; Minimal post-op side-effects; potential neuroprotective effects via antioxidant properties.
Hans, P, Current Op Anaes. 2006;19(5):498-503.p ( )
Better preservation of cerebral autoregulation vs. volatile
Ishikawa, Masui. 2003;52(4):370-7
McCulloch Anesthesiology. 2007;106(1):56-64
Not a panacea
+ Titratable, but no diff in shivering, PONV HTNPONV, HTN.
Wong AY. Eur JAnaes 2006;23(7):586-90
No diff in pain; more shivering with TIVANo diff in pain; more shivering with TIVA.Naito, Aya. Comparative study of anesthesia with remifentanil VS fentanyl in terms of postoperative pain
d hi i M i 2009 58 (1) 77and shivering. Masui 2009;58 (1), p. 77.
Cost. (But less PONV)R h KD A t A th i l i S di i 2006 50(1) 14Rohm KD. Acta Anaesthesiologica Scandinavica. 2006;50(1):14-8
Not a panacea
Pre-conditioning/tissue protection from l til i i id ff tvolatiles is a nice side-effect. Landoni, G. "Reducing perioperative myocardial infarction with anesthetic drugs and techniques". Current drug targets 2009;10 (9), p. 858.F ä d f J I t f diti i t l th ti i d dFrässdorf, Jan. Impact of preconditioning protocol on anesthetic-inducedcardioprotection in patients having coronary artery bypass surgery. The Journal of thoracic and cardiovascular surgery 2009;137 (6), p. 1436.
No differences between TIVA and inhalational anesthesia groups with regard to duration of anesthesia, time to discharge from the PACU, bleeding, or incidence offrom the PACU, bleeding, or incidence ofadverse events.
Vlessides, M. Anesthesiology News (07/01/12) Vol. 38, No. 7
Why infusions?
Avoid over and undershoot of dosageAvoid latency in reaching effect siteAvoid latency in reaching effect siteReduce workload intraoperativelyContinuous infusions reduce total drug usage by 25-Continuous infusions reduce total drug usage by 2550%More rapid awakeningLess respiratory depressionDischarge times reduced 30%1
1White PF. Use of continuous infusion versus intermittent bolus administration of fentanyl or ketamine during outpatientWhite PF. Use of continuous infusion versus intermittent bolus administration of fentanyl or ketamine during outpatientanesthesia. Anesthesiology. 59(4):294-300, 1983.
Why infusions?
Avoid over and undershoot of dosageAvoid latency in reaching effect site
Over and undershoot of dosage
Sneyd J R Rigby JonesSneyd J R , Rigby-JonesA E Br. J. Anaesth. 2010;105:246-254
Latency in reaching effect site
Calculated blood and effectblood and effectsite (brain) concentrations following thefollowing thebolus administration of propofol 2 5propofol, 2.5mg/kg over 60 seconds
Russell, D. Practical Aspects of Target-Controlled Infusion. Anaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. P. 3.
Latency in reaching effect siteLatency in reaching effect site
Sneyd J R , Rigby-Jones A E Br. J. Anaesth. 2010;105:246-254
Why infusions?
Reduce workload intraoperativelyR d t t l d b 25 50%Reduce total drug usage by 25-50%
Why infusions?
More rapid awakeningLess respiratory depressionLess respiratory depression
Why infusions?
Discharge times reduced 30%White PF. Anesthesiology. 1983;59(4):294-300.
Patients met PACU dischargePatients met PACU dischargecriteria 30 minutes faster with TIVAMontes. Journal of Clinical Anesthesia 2002;14(5):324-8.
Reliability of discharge improvement
Faster readiness, but discharge and cost i d di tsavings are depending upon system
M Féli R (2002) "C i f l iMontes, Félix R (2002). "Comparison of total intravenous anesthesia and sevoflurane-fentanyl anesthesia for outpatient otorhinolaryngeal surgery." Journal of clinical anesthesia, 14 (5), p. 324.
Why now?
Historical perspectiveInhalation anesthesiaInhalation anesthesia
Good open drop ether mask
Strength of pulse
Better concentration-controlled vaporizers
Deliver MAC level
Best RGM, neuromonitors
Titrate to effect-site concentration and response
Why now?
Historical perspectiveIntravenous anesthesiaIntravenous anesthesiaGood IV bolus Estimate time for
recovery, based on βt1/2
Better Infusion pump Titrate according to context-specific half-time
Best Rapid recovery drugs, t t t ll d
Titrate to effect-site t ti dtarget-controlled
infusion pumpsconcentration andresponse
TIVA equipment
Propofol: wonder drug of the 90’s
Recovery profile of propofolRecovery profile of propofolStages of recovery after anesthesia
Early (emergence)- Rapid and predictable
Intermediate- Early return of cognitive and psychomotor function. Early time to discharge (?)y g ( )
Brady. AANA Journal. 2005;73(3):207-10
Low incidence of PONVLow incidence of PONVPurhone. Journal of Clinical Anesthesia. 2006;18(1):41-5.
Frequency of Side Effects withFrequency of Side-Effects withPropofol
5.2Pain on Inj
1.3
1.9
Excitement
N/V
0 3
0.4
1.1
Pain
Brady
Hypotension
0.3
0.3
HTN
Pain
0 2 4 6
McLeskey et. al. Anesth Analg 1993;77:S3-9
Reduced risk of postoperative vomitingReduced risk of postoperative vomitingMeta-analysis of studies: propofol vs volatiles
Allinhalational
agentsIsoflurane
(maintenance)Desflurane
or sevoflurane
2 0
1.0
agents (maintenance)(maintenance)
2.3Reduction in risk of
3.0
2.0
3.7 3.7
vomitingafter ‘Diprivan’(induction and maintenance)
4.06 studies
p = 0.003
maintenance)
n = 4,074
70 studiesp < 0.0001
42 studiesp < 0.0001 Sneyd JR et al.
Sneyd JR et al. Eur J Anaesthesiol;1998, 15(4), pp 433-445
Why now?
S ifi i di tiSpecific indicationsfor TIVA
Need for precision controlAi dAirway proceduresRemote locationsMH susceptibleNeurosurgeryNeuro monitoringPONV risk
Effect on PONV
PONV similar between Propofol TIVA and Sevo + Dolasetron in high risk patients LateSevo + Dolasetron in high-risk patients. LatePONV was worse in TIVA group.
White, British Journal of Anaesthesia. 98(4):470-6, 2007
PONV similar between TIVA without anti-emetic and volatile + anti-emetic
Paech Anaesth Intensive Care 30:153�9
TIVA (without N2O) equally effective as any anti emetic as independent factor reducinganti-emetic as independent factor reducingPONV
Apfel N Engl J Med 350:2441�51
Effect on cancer recurrence
Volatile anesthetics inhibit natural killer cells and T lymphocytesand T lymphocytesVolatiles also inhibit lymphocyte functions
such as proliferation and cytokine productionsuch as proliferation and cytokine production.Propofol and COX-2 inhibitors may deter
tumor growth & metastasistumor growth & metastasis.Kurosawa, S. Anesthesia in patients with cancer disorders. Curr Opin Anaes. 2012. 25(3):376-84.
Disadvantages
Acquisition costsC ll d b iControlled substance accountingSet-up and use greater workload than
ivaporizersEarly or late respiratory depressionO ffOpioid side-effects- biliary, muscle rigidity,
GI motility, pruritusAd t if IV li di t dAdverse events if IV line disrupted
Infusion administration
Good IV bolus Estimate time for recovery, based on βt1/2
Better Infusion pump Titrate according to context-specific half-time
Best Rapid recovery drugs Titrate to effect siteBest Rapid recovery drugs, target-controlled infusion pumps
Titrate to effect-siteconcentration and response
Forget about elimination half-life
A useless measure to guide anesthetic administrationadministrationAs many half-lives as distribution
compartmentscompartmentsTakes no account of time course at effect
sitesitePentothal- half-life = hours
duration = depends on administration du a o depe ds o ad s a oi.e., depends on CONTEXT
Open three-compartment PK model
Context-sensitive half-time
Duration of a drug�sdrug seffects depends on
it�way it�s administered
Hughes MA. Glass PS. Jacobs J:. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 76(3):334-41, 1992.
Context-sensitive half-time
Sneyd, Recent Advances in Intravenous Anaesthesia. Br J Anaesth 2004 93(5):725-736
Context-sensitive alterations in propofol kinetics
Russell, D. Practical Aspects of Target-Controlled Infusion. Anaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. p. 10.
Context-sensitive half-time- Midaz.
Comparison of context‐sensitive half‐times forremimazolam and midazolam.Midazolam doses = 0.075mg/kg/h; remimazolam doses= 50 mg/h.Anesthesia & Analgesia.115(2):284‐296, August 2012.
Context-sensitive half life vs.half life vs.necessarydecreasedecrease
Shafer SL. Varvel JR: PharmacokineticsPharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 74(1):53-63, 1991.
Key effect site concentration levels
Fentanyl Alfentanil SufentanilInduction and IntubationThiopental 3-5 ng/ml 250-400 0.4-0.6O /N O l 8 10 400 750 0 8 1 2O2/N2O only 8-10 400-750 0.8-1.2MaintenanceN O/Vapor 1 5 4 100 300 0 25 0 5N2O/Vapor 1.5-4 100-300 0.25-0.5O2/N2O only 1.5-10 100-750 0.25-1.0O2 only 15-60 1000-4000 2-8O2 only 15 60 1000 4000 2 8Adequate Ventilation
1.5 125 0.25
Context-sensitive half life vs. necessary decrease
SufentanilSufentanilng/ml
MaintenanceMaintenance
N2O/Vapor 0.25-0.5
O /N O only 0 25 1 0O2/N2O only 0.25-1.0
O2 only 2-8
Ventilation 0 25
Shafer SL. Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 74(1):53-63, 1991.
Ventilation 0.25
But that’s the old-fashioned way…
Target-controlled infusions eliminate all that thinkingthinking�Computer-driven infusion pumps are programmed with pharmacokinetic data for p g pspecific drugs in a range of patient types. The anesthetist sets the desired blood level, and the p mp does the restand the pump does the rest.
TCI equipment
TCI equipment
Key components of a TCI system
Pharmacokinetics � a validated model with specific parameters for drugAlgorithm(s) to control infusion rate�Control unit� i.e. software and
microprocessors for aboveInfusion pumpUser interface for input of patient data and
target blood concentration
Measured versus calculated blood propofolMeasured versus calculated blood propofolconcentrations during ‘Diprifusor’ TCI administration of propofol in 46 patients.
Russell, D. Practical ,Aspects of Target-Controlled Infusion. Anaesthesia RoundsRoundsOxfordshire, UK, TMG Healthcare Communications Ltd. P. 3.
Diprifusor
Software program Commercially available
�Diprifusor� TCI systems. (a) Graseby 3500.(b) Vial Medical �Master TCI�( ) Alaris IVAC TIVA TCI(c) Alaris IVAC TIVA TCI(d) Terumo Terufusion® TE-
372 TCI TIVA
Loading dose schemes by Diprifusor
Russell, D. Practical Aspects of Target-Controlled Infusion. A th i R d O f d hi UK TMG H l hAnaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. P. 7
“Cardiac” induction by Diprifusor
Russell, D. Practical Aspects of Target-Controlled Infusion. Anaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. p. 8.
TCI safety mechanisms
Validated pharmacokineticsCompensation for interrupted infusionAutomatic shutdown in case of malfunctionElectronic tags on pre-filled syringes
(diprivan) to prevent wrong-drug in pump
Tagged prefilled syringes for use withTagged, prefilled syringes for use with‘Diprifusor’ target-controlled infusion systemsy
TCI Displays
TCI Displays
TCI Evaluation
Inaccuracies
Limits: age 16-100 for conventional programs. Weight 30-150 kgWeight 30 150 kgDoes not account for ethnopharmacology (cannot distinguish a Kenyan African from an Italian)Head injuryConcomitant medsNo problem
HypoalbuminemiaRapid fluid adminp
Practical application of TIVA
Select drugs to be used Timing is everything- consider effect site peak
and Co-inductionHigher index of vigilance for recall- reduce
muscle relaxation, awareness monitorf fTitrate infusions based on context-specific
half-time
Drug combinations for TIVA
Opioid infusion schemes
Drug Plasma Target Conc
( / l)
Bolus µg/kg
Infusion Rate µg/kg/min
Use
(ng/ml)
Fentanyl 1 3 0.20 Bal4 10 0 70 N 0/narc4 10 0.70 N20/narc
Alfentanil 40 20 0.25 Analg160 80 1 0 Bal/N20160 80 1.0 Bal/N20
Sufentanil 0.15 0.15 0.003 Bal0.5 0.5 0.01 N20/narc2
Remifentanil 6 1 0.02 analg15 1-2 0.4-1.0 N20/narc
Propofol context-sensitive dosing
Propofol only TIVA: Induce 2-2.5mg/kg, then infuse:infuse:
150-300 µg/kg/min first 10 minutes 120-240 10 min to 2 hours120-240 10 min to 2 hours75-150 beyond 2 hours
Propofol + opioid: Induce 1 5-2mg/kg thenPropofol opioid: Induce 1.5 2mg/kg, then100-150 first 10 minutes 90-140 10 min to 2 hours75-125 beyond 2 hours
Ketamine infusion dosing
Induction: 0.75-2mg/kgInfusion 1-2 mg/kg/hrMidazolam 3-5 mg load, then 0.25 µg/kg/min
Pre-mixed maintenance infusion400 mg ketamine + 4mg midazolam in 100ml saline400 mg ketamine + 4mg midazolam in 100ml saline
Infuse at 0.5 x weight in kg = ml/hr = 2mg/kg/hr ketamine = 0.33 µg/kg/min midazolam
Propofol-Ketamine infusion
Extensive use in outpatient (office) settings with outstanding track record for safety and lack ofoutstanding track record for safety and lack ofside-effects.
Mix ketamine 2mg/ml of propofolInduce with 1-2mg/kg propofol in mixtureg g p pGive additional 0.5-1mg/kg ketamine after asleepInfuse 140-200 µg/kg/min first 10 minutes (based on propofol)propofol)
� 100-140 µg/kg/min for next 2 hours� 80-120 µg/kg/min after 2 hours
Propofol-Ketamine infusion
Reeves JG GlassReeves JG, GlassPSA, Lubarsky DA, McEvoy MD. Intravenous nonopioid anesthetics. In Miller RD. Miller�s Anesthesia 6th ed. 2005
Remifentanil Infusion
Boon to all types of anesthesiaFast onset and recovery; independent of
infusion durationTurn pump on at 1 µg/kg/min
Also start propofol bolus via pump, or wait 30 sec to injectto injectMaintain at 0.1-0.3 µg/kg/min for target plasma concentration of 5ng/mlgTurn off 5-7 min before extubation. Extubate quickly upon awakening
Propofol-Alfentanil TIVA
Induce P f l 0 5 1 /kPropofol 0.5-1mg/kg Alfentanil 25-50 µg/kg
MaintenancePropofol 100-180 µg/kg/minp µg gAlfentanil 0.5-2 µg/kg/min
Dosages loosely suggested; account for level of stimulation and concurrent meds i.e., midazolam
Future of TIVAFuture of TIVA-Esterase Metabolism is in
New hypnotics (THRX-918661/AZD3043)Methoxycarbonyl-etomidateRemimazolam- Sedation with a 6-mg initial
loading dose, then 3-mg doses at >2-minute intervals. Recovery within 16 minutes for 89% of the treated population A th & A l89% of the treated population Anesth & Analg. 2012 Aug;115(2):284-96.
Future of TIVA
Closed-loop anesthesiaDrug advancesDrug advances
S+ ketamine enantiomer Propofol pro-drug
Non-invasive monitoring of propofol blood concentration
It’s all getting so easy but maybe tooIt’s all getting so easy, but maybe tooeasy?
FDA G t P k t A lFDA Grants Premarket ApprovalFor The SEDASYS
May 3, 2013initiation and maintenance of minimal-to-
moderate sedationASA physical status I and II patients > 18
years old colonoscopy and EGDintroduced on a limited basis beginning in
2014
Summary
TIVA techniques can provide numerous advantages over volatile based anestheticsover volatile-based anesthetics.While equipment set-up and cost is greater than using existing vaporizers, long-term savings can be appreciatedappreciated.Context-sensitive PK considerations allow safe and effective narcotic dosing.Modern infusion technology and TCI lends control toModern infusion technology and TCI lends control toIV techniques to rival vaporizer use. More info: UK Society for Intravenous Anaesthesia www sivauk orgwww.sivauk.org