1Total Intravenous Anesthesia:

A Rational Approach to Anesthetic Management

Michael Rieker, DNP, CRNADirector, Nurse Anesthesia Program

Wake Forest University Baptist Medical Center

Objectives

Review drugs and methods in TIVA Discuss how propofol has aided administration of TIVADescribe different equipment that makes administration 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 GADiscuss contraindications to TIVA for GA

Drug administration

Intravenous agents administered by manual bolus on a dose/kg basis is probably as old-fashioned as administration of volatile agents by the Schimmelbusch mask.Armin Holas MD, University of Graz, Austria.

IV Anesthesia History Timeline

Pent

otha

l

Fent

anyl

Keta

min

e, In

nova

rAl

fant

anil,

Suf

enta

nil

Pent

otha

l Inf

usio

n

Prop

ofol

, Rem

i, TC

I

1930 1950 1970 1990

Why Intravenous anesthetics?

SafetyHemodynamic controlRapid titrationAvoid vasodilatation, expansion of gas cavitiesReduced PONVOccupational exposureSmooth emergence, less hangoverAvoid MH riskCost benefit?

Why Intravenous Anesthetics?

Improved mucociliary transportLedowski. Anesth Analg. 2006;102(5):1427-30.

Reduced PONVRohm. Acta Anaesth Scand. 2006 50(1):14-8.

Less effect on hepatic enzymesRohm. Europ J Anaesth. 2005 ;22(3):209-14.

2Advantages of TIVA

Improved V/Q matchingPraetel. Anesth Analg. 2004; 99(4):1107-13

Better preservation of cerebral autoregulation vs. volatile

Ishikawa, Masui. 2003;52(4):370-7

McCulloch Anesthesiology. 2007;106(1):56-64

Reduced stress response.Ledowski Anesth Analg. 2005;101(6):1700-5.

Advantages of TIVA over balanced

Improved surgical field (bleeding)Wormald, P, Am J Rhinology 2005;19 (5): 514.

Volatiles assoc. with inc. inflammation and dec. immune function

Ken Plitt, BIS lecture.

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.

Not a panacea

+ Titratable, but no diff in shivering, PONV, HTN.

Wong AY. Eur JAnaes 2006;23(7):586-90

Cost. (But less PONV)Rohm KD. Acta Anaesthesiologica Scandinavica. 2006;50(1):14-8

Propofol: wonder drug of the 90s

Early (emergence)- Rapid and predictable

Intermediate- Early return of cognitive and psychomotor function. Early time to discharge (?)

Brady. AANA Journal. 2005;73(3):207-10

Low incidence of PONVPurhone. Journal of Clinical Anesthesia. 2006;18(1):41-5.

Recovery profile of propofolStages of recovery after anesthesia

Reduced risk of postoperative vomitingMeta-analysis of studies: propofol vs volatiles

4.0

3.0

2.0

1.0

Allinhalational

agentsIsoflurane

(maintenance)Desflurane

or sevoflurane(maintenance)

3.7 3.7

2.3

70 studiesp < 0.0001

42 studiesp < 0.0001

6 studiesp = 0.003

Reduction in risk of vomiting

after Diprivan(induction and maintenance)

n = 4,074

Sneyd JR et al.Sneyd JR et al. Eur J Anaesthesiol;1998, 15(4), pp 433-445

3Frequency of Side-Effects with Propofol

0.3

0.3

0.4

1.1

1.3

1.9

5.2

0 2 4 6

HTN

Pain

Brady

Hypotension

Excitement

N/V

Pain on Inj

McLeskey et. al. Anesth Analg 1993;77:S3-9

Why infusions?

Avoid over and undershoot of dosageAvoid latency in reaching effect siteReduce workload intraoperativelyContinuous infusions reduce total drug usage by 25-50%More rapid awakeningLess respiratory depressionDischarge times reduced 30%1

1White PF. Use of continuous infusion versus intermittent bolus administration of fentanyl or ketamine during outpatient anesthesia. Anesthesiology. 59(4):294-300, 1983.

Why infusions?

Avoid over and undershoot of dosageAvoid latency in reaching effect site

Latency in reaching effect site

Calculated blood and effect site (brain) concentrations following the bolus administration of propofol, 2.5 mg/kg over 60 seconds

Russell, D. Practical Aspects of Target-Controlled Infusion. AnaesthesiaRounds Oxfordshire, UK, TMG Healthcare Communications Ltd. P. 3.

Why infusions?

Reduce workload intraoperativelyReduce total drug usage by 25-50%

Why infusions?

More rapid awakeningLess respiratory depression

4Why infusions?

Discharge times reduced 30%White PF. Anesthesiology. 1983;59(4):294-300.

Patients met PACU discharge criteria 30 minutes faster with TIVAMontes. Journal of Clinical Anesthesia 2002;14(5):324-8.

Reliability of discharge improvement

Faster readiness, but discharge and cost savings are depending upon system

Montes, Flix 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 anesthesia

RGM, neuromonitors

concentration-controlled vaporizers

open drop ether mask

Best

Better

Good

Titrate to effect-site concentration and response

Deliver MAC level

Strength of pulse

Why now?

Historical perspectiveIntravenous anesthesia

Rapid recovery drugs, target-controlled infusion pumps

Infusion pump

IV bolus

Best

Better

Good

Titrate to effect-site concentration and response

Titrate according to context-specific half-time

Estimate time for recovery, based on t1/2

Why now? TIVA equipment

5Why now? Specific indicationsfor TIVA

Need for precision controlAirway proceduresRemote locationsMH susceptibleNeurosurgeryNeuro monitoringPONV risk

Effect on PONV

PONV similar between Propofol TIVA and Sevo + Dolasetron in high-risk patients. Late PONV 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 30:1539

TIVA (without N2O) equally effective as any anti-emetic as independent factor reducing PONV

Apfel N Engl J Med 350:244151

Disadvantages

Acquisition costsControlled substance accountingSet-up and use greater workload than

vaporizersEarly or late respiratory depressionOpioid side-effects- biliary, muscle rigidity,

GI motility, pruritusAdverse events if IV line disrupted

Infusion administration

Rapid recovery drugs, target-controlled infusion pumps

Infusion pump

IV bolus

Best

Better

Good

Titrate to effect-site concentration and response

Titrate according to context-specific half-time

Estimate time for recovery, based on t1/2

Forget about elimination half-life

A useless measure to guide anesthetic administrationAs many half-lives as distribution

compartmentsTakes no account of time course at effect

sitePentothal- half-life = hours

duration = depends on administration i.e., depends on CONTEXT

6Open three-compartment PK model Context-sensitive half-time

Duration of a drugs effects depends on way its 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. AnaesthesiaRounds Oxfordshire, UK, TMG Healthcare Communications Ltd. p. 10.

Context-sensitive half life vs. necessarydecrease

Shafer SL. Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 74(1):53-63, 1991.

Key effect site concentration levels

0.251251.5Adequate Ventilation

2-81000-400015-60O2 only0.25-1.0100-7501.5-10O2/N2O only0.25-0.5100-3001.5-4N2O/Vapor

Maintenance0.8-1.2400-7508-10O2/N2O only0.4-0.6250-4003-5 ng/mlThiopental

Induction and IntubationSufentanilAlfentanilFentanyl

7Context-sensitive half life vs. necessary decrease

Shafer SL. Varvel JR: Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 74(1):53-63, 1991.

0.25Ventilation

2-8O2 only

0.25-1.0O2/N2O only

0.25-0.5N2O/Vapor

Maintenance

Sufentanilng/ml

But thats the old-fashioned way

Target-controlled infusions eliminate all that thinkingComputer-driven infusion pumps are programmed with pharmacokinetic data for specific drugs in a range of patient types. The anesthetist sets the desired blood level, and the pump does the rest.

Variants of TCI terminology

CATIA- Computer Assisted Total Intravenous AnaesthesiaTIAC- Titration of Intravenous Agents by ComputerCACI- Computer Assisted Continuous InfusionCCIP- Computer Controlled Infusion Pump

TCI equipment

TCI equipment

Pharmacokinetics a validated model with specific parameters for drugAlgorithm(s) to control infusion rateControl unit i.e. software and

microprocessors for aboveInfusion pumpUser interface for input of patient data and

target blood concentration

Key components of a TCI system

8Measured versus calculated blood propofolconcentrations during Diprifusor TCI administration of propofol in 46 patients.

Russell, D. Practical Aspects of Target-Controlled Infusion. AnaesthesiaRoundsOxfordshire, UK, TMG Healthcare Communications Ltd. P. 3.

Software program Commercially available

Diprifusor TCI systems. (a) Graseby 3500.(b) Vial Medical Master TCI(c) Alaris IVAC TIVA TCI(d) Terumo Terufusion TE-

372 TCI TIVA

Diprifusor

Loading dose schemes by Diprifusor

Russell, D. Practical Aspects of Target-Controlled Infusion. Anaesthesia Rounds Oxfordshire, UK, TMG Healthcare Communications Ltd. P. 7

Cardiac induction by Diprifusor

Russell, D. Practical Aspects of Target-Controlled Infusion. AnaesthesiaRounds 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 with Diprifusor target-controlled infusion systems

9TCI Displays TCI Displays

TCI Evaluation Inaccuracies

Limits: age 16-100 for conventional programs. Weight 30-150 kgDoes not account for ethnopharmacology (cannot distinguish a Kenyan African from an Italian)Head injuryConcomitant medsNo problem

HypoalbuminemiaRapid fluid admin

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 monitorTitrate infusions based on context-specific

half-time

Opioid infusion schemes

0.4-1.00.020.01

0.0031.0

0.250.700.20

Infusion Rate g/kg/min

N20/narc1-215analg16Remifentanil

N20/narc0.50.5Bal0.150.15Sufentanil

Bal/N2080160 Analg2040Alfentanil

N20/narc104Bal31Fentanyl

UseBolus g/kg

Plasma Target Conc

(ng/ml)

Drug

10

Propofol context-sensitive dosing

Propofol only TIVA: Induce 2-2.5mg/kg, then infuse:

150-300 g/kg/min first 10 minutes 120-240 10 min to 2 hours75-150 beyond 2 hours

Propofol + 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 g/kg/min

Pre-mixed maintenance infusion400 mg ketamine + 4mg midazolam in 100ml saline

Infuse at 0.5 x weight in kg = ml/hrz = 2mg/kg/hr ketaminez = 0.33 g/kg/min midazolam

Propofol-Ketamine infusion

Extensive use in outpatient (office) settings with outstanding track record for safety and lack of side-effects.

Mix ketamine 2mg/ml of propofolInduce with 1-2mg/kg propofol in mixtureGive additional 0.5-1mg/kg ketamine after asleepInfuse 140-200 g/kg/min first 10 minutes (based on propofol)

100-140 g/kg/min for next 2 hours 80-120 g/kg/min after 2 hours

Remifentanil Infusion

Boon to all types of anesthesiaFast onset and recovery; independent of

infusion durationTurn pump on at 1 g/kg/min

Also start propofol bolus via pump, or wait 30 sec to injectMaintain at 0.1-0.3 g/kg/min for target plasma concentration of 5ng/mlTurn off 5-7 min before extubation. Extubatequickly upon awakening

Propofol-Alfentanil TIVA

Induce Propofol 0.5-1mg/kg Alfentanil 25-50 g/kg

MaintenancePropofol 100-180 g/kg/minAlfentanil 0.5-2 g/kg/min

Dosages loosely suggested; account for level of stimulation and concurrent meds i.e., midazolam

Future of TIVA

Closed-loop anesthesiaDrug advances

S+ ketamine enantiomerPropofol pro-drugNew hypnotics (THRX-918661)

Non-invasive monitoring of propofol blood concentration

11

Its all getting so easy, but maybe tooeasy? The Aneo TIVAS system

Summary

TIVA techniques can provide numerous advantages over volatile-based anesthetics.While equipment set-up and cost is greater than using existing vaporizers, long-term savings can be appreciated.Context-sensitive PK considerations allow safe and effective narcotic dosing.Modern infusion technology and TCI lends control to IV techniques to rival vaporizer use. More info: UK Society for Intravenous Anaesthesiawww.sivauk.org