TIVA different combination of drugs

1. Dr. Tushar M. Chokshi
Area of
Expertise
Other
Highlights
Affiliations
Current
Position
Consultant Private Practicing
Anesthesiologist in Vadodara
(Gujarat, INDIA)
 Sterling Hospital
 Urocare Hospital
 Dhwani ENT Hospital
 Baroda Hospital
30 Years of Experience
TIVA, OFA and NORA
 Uro Anaesthesia
 Lapro Anaesthesia
ENT Anesthesia
Paediatric Anesthesia
 Founder of TIVA and OFA
Face book Groups in INDIA
 National and State Level Speaker
Started Smartphone and Tele-
Anesthesia practice in INDIA
Started Infographics in Anaesthesia

9825062245
chokshitushar@hotmail.com
MD (Anaesthesiology)
https://sites.google.com/site/tusharchokshisite
National
Origami
Teacher
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&
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Happy Go To Lucky Fellow
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1

2. 2
overview

3. It is a technique of
general anesthesia
Totally through
Intravenous Lines
Anesthesia via
Intravenous agents only
No Gas (Even Nitrous Oxide)
or Volatile agents are used
except Oxygen
Given by IV boluses,
in drips, by syringes
or by infusion pumps
Total intravenous anaesthesia (TIVA)
It is a technique of general anaesthesia which uses a combination of
agents given exclusively by the intravenous route without the use of
inhalation agents (Gas Anaesthesia) including Nitrous Oxide, but oxygen,
compressed air or helium are exception
TIVA
3
( TIVA is used in Induction as well as in Maintenance of Anaesthesia)

4. With Endo Tracheal Tubes Without Endo Tracheal Tubes
With Supra Glottic Airways Without Supra Glottic Airways
With Nasal Airways With Oral Airways
Without ETT/SGD/Nasal/Oral Airways 4

5. TIVA
INDICATIONS
Almost in all
surgical procedures
Anaesthesia in non operative
locations where inhalational
anaesthetics are difficult
Airway procedures Remote locations
MH susceptible
Neurosurgery &
Neuro monitoring
PONV risk
Short procedures
CT, MRI,Cardiac
catheterisation
Daycare Surgery Trainee teaching Patient Choice 5

6. Except for a slight
prick in the arm, the
patient is unaware of
having an anaesthetic
No mask over the face
No sudden concentration
of gas or vapour
No risk of MH Less PONV
Patients wake up as it
from natural sleep
Very low incidence of
post operative delirium
Avoid distension air
filled spaces in the
patient’s body- so
better operating
conditions for surgeons
Reduced stress response
Better preservation
of cerebral auto regulation
Less chances of
emergence phenomena
Less operating room
pollution
There should be no smell
of volatile agents at all in
the room, and the patient
is usually most grateful for
not having had his system
saturated with such a drug
6

7. Injection is irreversible Shallow respirations
Possibility of not finding the vein
Not having another
apparatus
to carry on the TIVA
Incidence of awareness
if not given properly
Risk of bacterial contamination
Environmental effect
of plastic waste
Disposables may be costly
Caution in prolonged
procedures
or obese patients
Pain on injection
7

8. TIVA Drugs
8

9. TIVA drugs
with their advantages
• Majority of drugs used for TIVA including Benzodiazepines,
Narcotics, propofol, Ketamine, Etomidate,
Dexmedetomidine, Muscle relaxants, and other adjuvant
drugs are easily available in almost all the Operation
theatres and outside OT
• All these drugs can be given to any subset of population
from Paediatric to Geriatric patients in easily titratable doses
9

10. 1957-1961 Dexamethasone
1886-1990 Magnesium Sulphate
1956 Paracetamol
1973-1988 Diclofenac Sodium
1961-1966 Clonidine
1980-1987 Esmolol
1920-1928 Ephedrine
1971-1985 Mephentermine
1860 Cocaine
1905 Procaine
193--1941 Tetracaine
1943-1949 Lidocaine
1950 Chloroprocaine
1960 Mepivacine
1957 Bupivacine
1980 Ropivacaine
1980 Levobupivacaine
1900 Tubocurarine Chloride
1906-1949 Suxamethonium
1947 Gallamine Triethiodide
1964 Pancuronium
1974-1983 Atracurium
1984 Vecuronium
1984 Mivacurium
1989-1995 Cisatracurium
1994 Rocuronium
1830 Chlorofom
1846 Ether
1920 Trichloroethylene
1956 Halothane
1963-1966 Enflurane
1979 Isoflurane
1970-1987 Desflurane
1971-1990 Savoflurane
1804 Morphine
1937-1943 Pethidine
1960-1968 Fentanil
1974 Sufentanil
1996 Remifentanil
1974 Carfentanyl
1961-1971 Naloxone
2014-2020 Remimazolam
1930-1934 Sodium Thiopental
1962-1964-1970 Ketamine
1964-1972 Etomidate
1977-1989 Propofol
1999 Dexmedetomidine
1901 Atropine
1975 Glycopyrrolate
1964-1979
1981
Metoclopramide
Ranitidine
1980-1991 Ondansetron
1959-1963 Diazepam
1963-1977 Lorazepam
1987 Flumezenil
1975-1990 Midazolam
1772 Nitrous Oxide X
1774 Oxygen
1881 Cyclopropaine X
1898 Xenon X
1996 Atipamazole
1961-1971
1982
Naloxone
Doxapram
1987 Flumezenil
1931 Neostigmine
2007-2015 Sugammdex
1967 Dentrolene
2014-2020 Remimazolam
Anesthesia Adjuvant
IV Anesthetic
Local Anesthetic
Gas
Opioid
Premedication
Inhaltion Anesthetic
Benzodiazepine
Muscle Relaxant
Anti MH Agent
Benzodiazepine Reversal Agent
IV Reversal Agent
Opioid Reversal Agent
Relaxant Reversal Agent
Opioid with Benzodiazepine
I
N
F
O
G
R
A
P
H
I
C
S
A
N
E
S
T
H
E
S
I
A
D
R
U
G
S
O
F
Total 66 Drugs
In Use 45 Drugs
Not
Used
In
TIVA
Not
Used
In
TIVA
10
In TIVA 25 drugs

11. All
Benzodiazepines
Dexmedetomidine
Dexamethasone Magnesium Sulphate
L
i
d
o
c
a
i
n
e
D
i
c
l
o
f
e
n
a
c
P
a
r
a
c
e
t
a
m
o
l
TIVA
DRUGS
TOOL BOX
C
L
O
N
I
D
I
N
E
Opioids 11

12. TIVA Drug Combinations
12
Combination is therapy that uses more than
one medication or modality

13. Why TIVA is given in Combo ?
• Because all anesthetic drugs work through
different mechanisms
• Some drugs are only hypnotic or anesthetic or
analgesic or relaxants
• So, we want complete balanced anesthesia
through TIVA, using two or three drugs in
combo with different mechanism of action
• Combination of TIVA drugs are well established
in journals and literature
13

14. 14
Advantages
of
TIVA
Combo
Drugs work
by different
mechanisms
It decreases
the dose of
individual drug
Combo reduces
side effects all
drugs in mixture
They give complete
balanced anaesthesia
with multiple effects

15. TIVA completes Anesthesia Circle
(with IV anaesthetic drugs)
15

16. 16
What to understand before
mixing any drugs for anesthesia

17. Anesthesia Triangle
The concept of the anesthesia triangle works with Hypnosis, Analgesia, Relaxation –
and their interactions
Any medications entering this prism may result in different interactions:
Pharmaceutical, Pharmacokinetics, Pharmacodynamics, and Thermodynamics by combo
A larger number of incoming drugs leads to increased complexity and more interactions
So, the rule is not mix more than three drugs at time 17
Anesthesia Triangle
• Hypnosis
• Analgesia
• Relaxation
Hypnosis
Analgesia
Relaxation
Anesthesia
Triangle

18. Red
Not compatible
Green
Compatible
Yellow
Non-conclusive
The hidden world of
drug interactions in
anesthesia
Colombian Journal of
Anesthesiology
Volume 45, Issue
3, July–September
2017, Pages 216-223
Alberto
Tafur Betancourt
Conclusion
Drug interactions are
the corner stone of
the anesthesia triangle
and being aware of
those interactions may
contribute to safe
anesthesia
White
Not tested

19. TIVA
KINGDOM
Anaesthesiologist
Fentanyl
Remifentanyl
MgSO4
King
Commanders
Oxygen
Soldier
Here King will decide
their military in battle of
anesthesia whom to
send in combination
Prince is most common
warrior and goes in
every battle
of anesthesia
Prince with one or two
supreme commander
are the best military of King
In absence of prince
two supreme commanders
go to win small battles

20. KETOFOL
Ketamine
+
Propofol
KPD
Ketamine
+
Propofol
+
Dexmedetomidine
KETODEX
or
DEXKET
Ketamine
+
Dexmedetomidine
FP/RP
Fentanyl +
Propofol
or
Remifentanil +
Propofol
PDF
MDF
KETOMED
Propofol + Dex +
Fentanyl
or
Midazolam + Dex +
Fentanyl
or
Ketamine + Midazolam
TIVA : Different Combination
20

21. Ketofol
• First established TIVA combination in 1990
• Ketofol physically compatible & chemically stable in
1:1 mixture in capped syringe upto 3 hrs at room
temperature with exposure to light
• No significant change in pH up to 3 hrs
• No separation, cracking, color change, gas formation
• Widely used by all anesthesiologist across globe
21

22. KPD TIVA (Ketamine, Propofol and Dex)
Mixture in 1:1:1 Dose for TIVA
Combination of all these drugs permit lower dose
of each individual agent for TIVA and reducing
their adverse hemodynamic and respiratory
effects which is very safe and important for
patient and anesthesiologist
The advantage is low dose of each agent as
compared to full dose
Excellent analgesia and anesthesia
 dose of individual
agents
 airway complications
Stable haemodynamics Rapid recovery 22
Used as Bolus, Maintenance and Short case < 30 minutes

23. Ketodex/Dexket
• Ketamine 1mg/kg and Dex 1 mcg /kg (same syringe)
• Useful in Pediatric patients
Ketomed
• Ketamine 1mg/kg and Midazolam 0.1 mcg /kg (same
syringe)
• Useful in NORA procedures
23

24. PROPOFOL & FENTANYL Combo
Combination of Propofol (1% &
2%) with Fentanyl (10 & 50
mcg/ml)
No significant degradation of
emulsion within 20 hrs
Propofol dose reduction by 50%
24

25. RP TIVA (Remifentanyl and Propofol Combo)
 Can be mixed in polypropylene syringes and used up to
36 hours- remifentanil concentration is 50 mcg/ml (1 mg in
20 ml propofol)
 Color and clarity good with pH stable at 3.9 - 4
 Very short acting
Adequate analgesia, satisfactory hemodynamic, rapid
recovery, shorter PACU stay, excellent patient acceptance
 Ideal agents for TCI model
 Synergism- Propofol dose reduction by 50%
 Most widely used TIVA combination with TCI in the world
25

26. 26
Adjuvant Drugs Combo

27. Best Premedication before TIVA induction
DML Mixture
in 10 ml Syringe
Lidocaine ( 1.5 mg/kg, 3 to 5 ml )
D M
L
Given slowly at least for 5 minutes 27

28. Intravenous
Diclofenac Sodium 1 mg/kg
in
Paracetomol 1 gm Infusion
(Always I give before surgical incision)
28
Diclo and Paracetamol Combo

29. For Maintenance
1) KPD mixture 0.5:0.5:0.5 mg:mg:mcg/kg/hr
or
2) Dexmedetomidine 0.7-1 mcg/kg/hr in RL
or
3) Propofol 6-8 mg/kg/hr in 100 ml NS
or
I Stop the infusion drip before 15 minutes of surgery end.
29

30. 30
For postoperative pain relief

31. 31
Fentaketacaine (FLK) drip after major surgery > 3 hrs
Prepared by taking
100 mcg Fentanyl + 100 mg Lidocaine + 100 mg Ketamine in 500 ml RL
And given in dose of 0.5:0.5:0.5 mcg:mg:mg/kg/hr maximum upto 24 hrs.
Ketacaine drip after routine surgery < 3 hrs
Prepared by taking
100 mg Ketamine + 100 mg Lidocaine in 500 ml RL
And given in dose of 0.5:0.5 mg:mg/kg/hr

32. Journal References
32

33. Compatibility of Propofol Injectable emulsion with selected drugs during simulated Y-
site administration
Am J Health Syst Pharm 1997 Jun 1;54(11):1287-92. doi: 10.1093/ajhp/54.11.1287
L A Trissel, D L Gilbert, J F Martinez
The compatibility of a new formulation of Injectable Propofol with selected other drugs during
simulated Y-site injection was studied. Two milliliters of undiluted Propofol Injectable emulsion was
combined with 2 mL of each of 112 other drugs in 5% dextrose injection or 0.9% sodium chloride
injection. The liquids were diluted with 6 mL of particle-free high-performance liquid
chromatography (HPLC)-grade water and centrifuged for 20 minutes. A pipette connected to a
vacuum line was used to remove the fat layer at the top and most of the aqueous phase. The
remaining liquid was diluted with 9 mL of particle-free HPLC-grade water to facilitate visualization of
any precipitate. The liquids were examined with the unaided eye in fluorescent light and with a
Tyndall beam to enhance visualization of small particles. Samples were evaluated during the first 15
minutes and one hour after mixing. Propofol Injectable emulsion was compatible with 98 of the 112
drugs testes. Fourteen drugs demonstrated incompatibilities, including precipitation, gel formation,
and oiling out of cracked emulsions. During simulated Y-site injection, Propofol Injectable emulsion
was compatible with most other drugs tested for one hour at approximately 23 degrees C
33

34. Ketofol: A Combination of Ketamine and Propofol
Department of Anesthesiology and Siriraj GI Endoscvopy Center, Faculty of Medicine
Siriraj Hospital, Thailand
Amornyotin S (2014) Ketofol: A Combination of Ketamine and Propofol. J Anesth Crit
Care Open Access 1(5): 00031. DOI: 10.15406/jaccoa.2014.01.00031
Somchai Amornyotin
Conclusion
Ketofol is a combination of ketamine and propofol. It is an agent of choice for
various procedures. The combination of propofol and ketamine has several
benefits because of hemodynamic stability, lack of respiratory depression, good
recovery and potent post-procedural analgesia. The safety and efficacy of
Ketofol as a sedoanalgesic agent are depended on the dose and the ratio of the
mixture. Therefore, Ketofol should be an ideal combination drug for procedural
sedation. 34

35. Indian J Anaesth. 2014 Mar-Apr; 58(2): 138–142.
doi: 10.4103/0019-5049.130813
Dexmedetomidine decreases the requirement of ketamine and Propofol during
burns debridement and dressings
Prabhavathi Ravipati, Pothula Narasimha Reddy, Chaithanya Kumar, P Pradeep, Rama
Mohan Pathapati andSujith Tumkur Rajasheka
Indian Journal of Anaesthesia, Vol. 58, No. 3, May-June, 2014, pp. 275-280
Clinical Investigatio
Ketofol-Dexmedetomidine combination in ECT
Ragaa El-Masry, Tarek Shams
Department of Public Health, College of Medicine, Mansoura University, Mansoura, Egypt
Department of Anesthesia and ICU, College of Medicine, Mansoura University, Mansoura,
Egypt
Pediatr Cardiol. 2012 Jun;33(5):770-4. doi: 10.1007/s00246-012-0211-1. Epub 2012 Feb 16.
Is the addition of dexmedetomidine to a ketamine-propofol combination in
pediatric cardiac catheterization sedation useful?
Ülgey A, Aksu R, Bicer C, Akin A, Altuntaş R, Esmaoğlu A, Baykan A, Boyaci A
KPD Journal Articles
35

36. Saudi J Anaesth 2010 May-Aug; 4(2): 72–79.
doi: 10.4103/1658-354X.65132
Comparison of two drug combinations in total intravenous anesthesia: Propofol–
Ketamine and Propofol–Fentanyl
Sukhminder Jit Singh Bajwa, Sukhwinder Kaur Bajwa and Jasbir Kaur
Conclusion
the results of this study suggest that both propofol–ketamine and
propofol–fentanyl combinations produce rapid, pleasant and safe
anesthesia with only a few untoward side effects and only minor
hemodynamic fluctuations
36

37. A combination of midazolam and ketamine for procedural sedation and analgesia in
adult emergency department patients
Acad. Emerg. Med. 2000 Mar;7(3):228-35. doi: 10.1111/j.1553-2712.2000.tb01064.x
C R Chudnofsky, J E Weber, P J Stoyanoff, P D Colone, M D Wilkerson, D L Hallinen, F M
Jaggi, M E Boczar, M A Perry
Conclusions
The combination of midazolam and ketamine provides effective procedural
sedation and analgesia in adult ED patients, and appears to be safe
37

38. Comparison of dexmedetomidine and ketamine versus propofol and ketamine
for procedural sedation in children undergoing minor cardiac procedures in
cardiac catheterization laboratory
Vidya Sagar Joshi, Sandeep S Kollu, Ram Murti Sharma
Ann. Card. Anaesth. Oct-Dec 2017;20(4):422-426
Conclusion
Use of dexmedetomidine-ketamine combination is a safe alternative, without
any hemodynamic or respiratory effects during the cardiac catheterization
procedure but with some delayed recovery
38

39. Compatibility of Propofol, Fentanyl, and Vecuronium mixtures designed for
potential use in anesthesia and patient transport
•.
J Clin Anesth. 1996 Jun;8(4):329-36 doi: 10.1016/0952-8180(96)00043-8.
P R Isert, D Lee, D Naidoo, M L Carasso, R A Kennedy
Conclusion
The Propofol, Fentanyl, and Vecuronium mixtures studied were
compatible and stable immediately after mixing
39

40. Propofol and Lidocaine Mixture
The Effect of Mixing Lidocaine with Propofol on the Dose of Propofol Required for
Induction of Anesthesia
Anesthesia & Analgesia: August 2003 - Volume 97 - Issue 2 - p 461-464
doi: 10.1213/01.ANE.0000066357.63011.75
Conclusion
The use of a freshly prepared mixture of Propofol 1%/lidocaine 1% in a 10:1 volume
ratio did not affect the dose of Propofol required for the induction of anesthesia
Tan, Li-Hoon, Mmed (Anaesthesiology)*; Hwang, Nian-Chih, FFARCSI, FAMS
40

41. Conclusion
In healthy premedicated patients undergoing orthopedic surgery, TNA with simplified
infusion rates of a propofol-alfentanil mixture allowed a satisfactory course of anesthesia.
The main advantages are fast awakening and efficient postoperative analgesia. Without
being better than the inhalational technique studied here, TIVA remains a useful technique
in precarious situations and an alternative when medical equipment and volatile agents are
unavailable. 41

42. Methods
42

43. give TIVA Combo
• With a single drug or with a combination of drugs
• Single Syringe Technique with mixture of drugs
or with one drug
• Continuous IV infusion through drips
• With Syringe infusion pumps
• With TCI ( Target Controlled Infusions) machines
• Automated drug delivery through Closed Loop
Systems
43

44. Single Syringe TIVA (SS TIVA)
 No additional investment for TCI or
Closed Loop Systems and no need for
expertise in it.
 Simple syringe or pump can be use for
combo
 Only one syringe is used, with the
advantage of dose titration at a single level
& fixed dose mixtures
 Short procedures can be managed with
intermittent boluses, without a syringe
pump.
 It can be practiced in low dependent set
ups, and outside the operating rooms
44

45. Manually Controlled Infusion (MCI)
 Manual dosing of anaesthetic agents during TIVA
 With fixed infusion rate
 With syringes or with IV drips
45

46. Target Controlled Infusion (TCI)
A target
controlled
infusion is an
infusion
controlled to
achieve a pre
set drug
concentration
in the plasma or
the effect site
Key components of a TCI
infusion
User interface to enter details and
target blood concentration
Software with
pharmacokinetic model, validated
for specific drug to control infusion
rate
Communication between ‘control
unit’ and pump hardware
46

47. Closed Loop Anaesthesia Delivery Systems
or
Automated Total Intra Venous Anaesthesia
A closed-loop system is the ideal means
of automated combo drug delivery
• The Input – Drug delivery (etc. Propofol, Opioids)
• The Output – Evoked Potential, Bispectral
Index (BIS), Blood Pressure, Pulse Rate.
ATIVA/CLADS
47

48. D
Input
Output
48
Computer
Drugs Delivery
Vital Signs

49. iControl-RP (Remifentanyl-Propofol)
iControl-RPR (Remifentanyl-Propofol-Relaxant)
• Auto Robotic TIVA CLADS
• US FDA approved
• Developed in Vancouver at University of British
Columbia in 2015
• By Team of Dr. Ansermino(Pediatric
Anesthesiologist) & Dr. Dumont(Professor of
electrical and computer engineering)
49

50. C
O
N
C
L
U
S
I
O
N
TIVA is a technique of anaesthesia without volatile agents
More than 25 drugs are used in TIVA technique as Premedication, Adjuvants,
Analgesics, Induction and Relaxants
TIVA combination of two or three drugs provides complete anaesthesia
circle
Multimodal analgesia and anaesthesia with TIVA combo are most successful and
widely accepted in anaesthesia practice
Propofol and Ketamine (Ketofol) are most common anaesthesia drugs used
as combo and also with other anaesthetic drugs
Before using any TIVA combo it is necessary to understand their
pharmacodynamics, pharmacokinetics, pharmaceutical and
thermodynamics interactions
50

51. 51