opioid free anaesthesia by dr tushar chokshi

1. Opioid Free Anesthesia
(OFA)
Opioid Free -Total Intra Venous Anesthesia
(OF-TIVA)
Dr. Tushar Chokshi
Anesthesiologist
VADODARA
The Future Modern Anaesthesia

2. • I have no financial relationships with any commercial
interest related to the content of this presentation
• I will discuss many medications with my experience
and recent developments in OFA
• OFA is one of the technique for providing anesthesia
• OFA is a scientifically based & systematic treatment to
the surgical patient in para operative period

3. Lecture Outline
• Introduction
• History
• Definition
• Why and How OFA / Opioid Epidemic in Medicine
• Opioid Risk/Use/Abuse/Side Effects/Complications
• Opioid epidemic in Anaesthesia
• OFA Goals
• OFA – Benefits
• Methods of OFA
• OFA Indications and Contraindications
• Multimodal and Intravenous drugs for OFA and their Infographics
• Standard OFA Induction and Maintenance
• My experience & techniques of OFA and OF-TIVA with economics
• Conclusion
• Take Home message
• My Verdict
• Cartoons
• Thanks
• Join ISOFA (Indian Society for Opioid Free Anesthesia) FB group

4. INTRODUCTIO
N
The practice of
anesthesia requires a
full spectrum of drugs
from which an
anesthetic plan can
be implemented to
achieve a desired
level of surgical
anesthesia, analgesia,
amnesia and muscle
relaxation and opioid
is one of drug
Opioid Free
Anesthesia (OFA) is a
technique where no
intra-operative
systemic, neuraxial, or
intracavitary opioid is
administered during
the anesthetic period
OFA became possible
- An alternative to opioid
Anesthesia
- Providing benefits to
selective group of patients
- Facilitates postoperative
analgesia with no opioids
- Enhances recovery after
surgery (ERAS)
The epidemic of opioid
abuse is increasing,
and the number of
deaths secondary to
opioid overdose is also
increasing
For patient safety,
anesthetists have
started to develop
protocols centered on
minimizing or even
avoiding opioids for
their patients
altogether
But
So
OFA
New Normal

5. HISTORY of Opioid Use
1962
to
2000
> 1950
1950
To
1962
2000
To
2020
However, over the last twenty years,
many studies have questioned this
practice, highlighting the many unknown
side effects of opioids
In 1962, in Belgium, the use of
fentanyl, the first synthetic opioid for
use in anaesthesia
The use of natural opiates, such as
opium, is more than millennial
The history of synthetic opioids begins
after 1950, with the development of the
so-called 'modern' anaesthetic techniques
So,
Opioid-free
anesthesia
(OFA) were
developed in
parallel with a
better
understanding
of
perioperative
pain and has
emerged as a
new
technique and
branch of
anesthesia

6. DEFINITION of OFA
It is a technique in anesthesia portfolio with
simple cocktail of drugs without opioids
In other words,
It is Multimodal Anesthesia and Analgesia
without opioids in Para Operative period

8. Opioid Epidemic in Medicine
In the late 1990s, with
reassurance of pharma
companies healthcare
providers began to prescribe
opioids at greater rates and
addiction/abuse started
Opioid overdoses accounted
every year more than 1 lac
deaths and estimated 40% of
opioid overdose deaths
involved a prescription opioid
Since, 2000 increase in opioid
use, misuse, and overdose
started and “opioid crisis”, or
“opioid epidemic”, began in the
USA, spread to Europe, and
extended to Asia
Destructive consequences of the
opioid epidemic were included-
increases in opioid misuse,
related overdoses and rising
incidence of opioid use and
misuse during pregnancy
So, increased prescription of opioid medications led to widespread
misuse of both prescription and non-prescription opioids in medicine

9. Because of this Opioid Epidemic
Opioid Overdose Death
Increased

10. US Data

11. USA 2018 DATA

12. 1990 the first wave
began with increased
prescribing of opioid, with
overdose deaths
involving prescription
opioid (natural and semi-
synthetic opioid) increasing
since at least 1999
2010 the second wave
began with rapid
increases in overdose
deaths
involving heroin
2013 the third wave
began with significant
increases in overdose
deaths involving synthetic
opioid, particularly
involving fentanyl
noted in Medicine

13. MORPHINE DERIVATIVES
During the 20th century, the following morphine
derivatives were developed
1916: Oxycodone (Germany)
1924: Hydromorphone (Germany)
1932: Pethidine (1st synthetic – Germany)
1937: Methadone (Germany)
1960: Piritramide (Janssen - Belgium)
1963: Pentazocin (USA)
1963: Tramadol (Germany)
1965: Buprenorphine (USA)
1971: Butorphanol (USA)
1979: Nalbuphin (USA)
Others are
Fentanyl
Alfentanil
Remifentanyl
Sufentanyl
Etorphin
Carfentanyl
Oleceridine

14. What are the Opioid Risk Effects
• Respiratory depression *****
• Need for post-op ventilation with ventilator associated pneumonia*
• Addiction***
• Nausea & Vomiting****
• Gastrointestinal dysfunction, Ileus
• Pruritus**
• Urinary retention***
• Opioids and Cancer (?)
Dozens of publications are available concerning opioid use in anesthesia
causes cancer growth, recurrence, and metastasis (Opioid Tumor)
• Opioid-induced Hyperalgesia (most common even in single dose)*******
• Misuse, Abuse and Overuse****
Hyperalgesia means abnormally heightened sensitivity to pain

17. 1.
2.
3.
4.
Patient becomes more sensitive to
certain painful stimuli
Patients have a prolonged period of
hypersensitivity to pain
State of nociceptive sensitization caused by
exposure to opioids
It occurs even after single dose of an opioid
Remifentanil > Fentanyl > Morphine
Opioid Induced Hyperalgesia (OIH)
Ketamine reduces opioid induced hyperalgesia

18. But some OPIOID benefits also
there
• First
Haemodynemic stability
• Second
Analgesia and Little Sedation

19. There were no
control after
discharged from our
care and patients are
taking self opioids
Acute tolerance and
hyperalgesia
increased opioid
requirement in post
operative opioid
How Anesthesiologists are
responsible for overdose?
First exposure of
opioid to patient
in preoperative
period
Finally it cause abuse
and sometime death

20. Opioid analgesic
overdose can have
life-threatening
toxic effects in
multiple organ
systems
Normal
pharmacokinetic
properties are often
disrupted during an
overdose and can
prolong intoxication
dramatically
The duration of action
varies among opioid
formulations, and
failure to recognize such
variations can lead to
inappropriate treatment
decisions, sometimes
with lethal results
Opioid Epidemic in Anesthesia
Opioid analgesic overdose leading to opioid
toxicity has Three features in anesthesia
1 2 3

21. Why Opioids are/were
used in Anesthesia ?
• Opioids are primarily used, initially because of their
safe intraoperative profile
e.g. Minimal cardiac depression
• Blunting of pain transmission
• To provide postoperative pain control

22. Side Effects are
more and lethal
Uses are for pain
and alternatives
are available
OPIOIDS

23. Why To Avoid Opioids
• Negative side effect profile
– Respiratory depression, N/V, Pruritus, Urinary retention
• Opioids suppress the immune response
– Suppression of Natural Killer cells
• Cause cognitive/sleep dysfunction
• Increased risk for addiction postoperatively
• Increased risk of chronic pain with opioid
administration

24. Change the Habit / No compulsion
Now
- We know the problems with opioids
- We know there are alternatives & effective modalities
available
Yet we choose………..

25. Common Misconceptions for using
OFA
• Need multiple infusions --------------------(NO)
• Patients will be in pain-----------------------(Not at all)
• Expensive---------------------------------------(Never)

26. So
Why should we administer
Opiates/Opioids/Narcotics?
Start
OFA practice

27. Millions Dollar Question
What are the alternatives to Opioid
?
Replacing opioids with other analgesics will not
only reduce the development of opioid
addiction but will also lead to better
perioperative outcomes and enhanced patient
recovery (ERAS)

28. Opioid free anesthesia becoming a new paradigm

29. And
first concept of
OFA
came in 1990

30. Main Goals of OFA
in
Nine words only

31. Barry Friedberg, USA
(Inventor of Ketofol in 26th March 1992)
Grandfather of OFA
26 years only OFA practice
(BIS)
(Ketamine)
(Opioid)
No much anesthesia
No less anesthesia
Only Brain FOG
(BIS value around 55-60)
Main aim in OFA is
anesthetized brain should
not come to know
about the pain during
skin incision
Goals of OFA
In
Nine words only
Friedberg’s Triad

33. OFA completes Anesthesia Circle

34. OFA BENEFITS
 Stable hemodynamics intraoperatively
 No respiratory depression
No addiction except for ketamine
Less need for post op ventilation
No nausea and vomiting
No gastrointestinal dysfunction and ileus
No Pruritus
No urinary retention
Prevention of chronic pain

35. Advantages of OFA
The European society for perioperative care of patient (ESPCOP)

36. 17 Benefits of
OFA
OFA

37. Mechanism of Action
of
OFA Drugs

38. Non Opioid Drugs
PG-inhibitors

39. Management
of
Central
Sensitization
Management
of
Peripheral
Sensitization
Prevention
of
OIH
Weight
based dosing
of
drugs(IBW)
Methods Of OFA
1 2 3 4

40. Management of
Central Sensitization
• Propofol and Etomidate
• Substance P inhibition
– Clonidine (a2-adrenoreceptor agonist)
– Dexmedetomidine (Strong a2-adrenoreceptor agonist)
• Glutamate antagonist
– Ketamine (NMDA antagonist)
– N2O (NMDA antagonist)
– Magnesium (NMDA antagonist)
– Gabapentinoids (Pregabalin)

41. Management of
Peripheral Sensitization
• Local Anesthetics
– Peripheral nerve blocks
– Lidocaine infusion
• Steroids
– Dexamethasone
• NSAIDS
– Diclofenac sodium
– Paracetamol

42. OFA Indications
with its advantages

43. OFA Contraindications
• Absolute
- Allergy to any adjuvant drugs
• Relative
- Disorders of autonomic failure
- Cerebrovascular disease
- Critical coronary stenosis or acute coronary ischemia
- Heart block / extreme bradycardia
- Non-stabilized hypovolemic shock or polytrauma patients
- Acute bleeding with significant blood loss
- Elderly patients on beta-blockers
- ASA - 4 patients

45. Multimodal drugs in OFA
with their advantages
• Majority of drugs used for OFA including Benzodiazepines,
Propofol, Ketamine, Etomidate, Dexmedetomidine, Muscle
Relaxants, and other adjuvants are easily available in almost
all the OT and outside OT
• And All these drugs can be given to any subset of population
in any surgical procedure without opioids

46. 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
1774 Oxygen
1881 Cyclopropaine
1898 Xenon
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 AgentIV 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

47. All
Benzodiazepines
Dexmedetomidine
Dexamethasone Magnesium Sulphate
L
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e
D
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P
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m
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l
OFA
DRUGS
TOOLBOX
C
L
O
N
I
D
I
N
E

48. Universal Weapon
For
Anesthesiologist
Anti-Emetic and Anti-Nauseatic
Anti-Inflammatory
Analgesic Effect
Anti Shivering
Increase Quality of Recovery
No effect on sepsis and sugar in single dose

49. DEXAMETHASONE
 Universal Friend 
Anti Nauseatic & Anti Emetic
Early Discharge from Anaesthesia
Anti Inflammatory
Weak anti pyretic effect
Anti Edema drug
Anti Shivering
Systemic Analgesic Effect
Increase Quality of Recovery
 Synthetic
Glucocorticoids with
minimal mineralocorticoid
activity
 Most potent anti
inflammatory than
Hydrocortisone and
prednisolone
 Biological half-life is 3 hours
 Metabolism in liver with
inactive metabolites
 Renal excretion upto 65%
in urine within 24 hours
Readily available
 Price is very cheap 
 Most ideal perioperative agent 
 Superior to ondensetron to reduce PONV 
 Reduce opioid Consumption 
 Decrease Analgesic effect upto 24 hours 
 Always to be given prior to surgery 
 Best TIVA and OFA adjuvant 
 Great psychological effect 
 Prevents any allergic reaction 
Dose Schedule
 PONV – 0.1 mg/kg (IV) 
 Anti Inflammatory – 0.2 mg/kg(IV) 
 Analgesic – 0.1 mg/kg(IV) 
 Epidural -- 8 to 10 mg 
 Blocks – 0.1 mg/kg 
 S/A - 8 mg 
Mechanism of Actions
 Depletion of γ-aminobutyric acid (GABA)
stores and reduction of blood brain barrier
to emetogenic toxins,
 Inhibition of central prostaglandins and
serotonin
 Membrane stabilizing effect on nerves and
on spinal cord
Dexona IN DM
 4 mg is
ideal dose
8 -10 mg dose
Increase around
25 mg/dl
glucose postop
upto 24 hrs
Dexona in Sepsis
Does not
increase any
risk of wound
infection with
or without DM
in any surgical
procedure
Acute Side Effect
Flushing
Perineal Itching
Dexona
Is the only
adjuvant in
anesthesia
given
irrespective of
age, sex,
disease or ASA
status
Safe in
Onco Anesthesia
Avoid in
Psychiatric patients
Be careful in
Immuno compromised
patients
Improves
Cognitive function
In Elderly
8
8 8
8
8
8 8
8

51. In spinal Anesthesia
Dose : 50 -100 mg
Old Wine in New Bottle Best Adjuvant in TIVA
Intravenous Oxygen for AnaesthesiologistOMg OMg
As Anesthesia Adjuvant
Dose : 30-50 mg/kg
Direct depressant on myocardial
and vascular smooth muscles
Anti-arrhythmic
Reduces systolic blood pressure
Decrease pulmonary vascular
resistance
Bronchodilator
Reduce excitability of nerves
As an Anticonvulsant
Reverse the cerebral vasospasm
Reduces the release of
acetylcholine at NMJ
Terminates muscular contraction
Causing skeletal muscles relaxation
(Versatile Drug)
Friend
Philosopher
Guide
For
Anesthesiologist
Potassium levels must be normal
Extreme caution in patients
with myasthenia gravis or other
neuromuscular disease
In renal impairment
In digitalized patients
Monitor renal function,
blood pressure, respiratory rate,
and deep tendon reflex
In Local Anesthetic Block
Dose : 50 – 250 mg
Pre-Emptive
Analgesic
Analgesic effect of
MgSO4 is due to
inhibition of calcium
channels and
NMDA receptors
Reduce the dose
requirement for
opioids, anaesthetics
and muscle relaxants
and part of MMA
Both in hypo and hyper
Magnesemia
Hyperventilated patients
Avoid in Geriatric and
Pediatric patients as far as
possible
In electrolyte disturbance
Avoid excessive use of
volatile agents with MgSO4
(500 mg /ml)
BURP
Antidote for Magnesium is
Calcium

52. Best Companion of Anesthesiologist
Lidocaine
Analgesic & Anti Hyperalgesic
Anti Inflammatory
Reduced opioid analgesic consumption
Anti Arrhythmic
Improvements in patient’s outcomes
Decrease Aerosol and Droplets during Extubation

53. Intravenous
Lidocaine
(Magic Drug)
Best Adjuvant in TIVA
Lidocaine is metabolized in the liver and excreted by the kidneys
Permanent member of Multi Model Anaesthesia & Analgesia
Analgesic
 Anti Arrhythmic
 Anti Cancer drug
 Anti Hyperalgesic
 Anti Inflammatory
 Reduces the release of cytokines
 Improvements in patient’s outcomes
 Reduced opioid analgesic consumption
 Reduce Volatile anesthetic consumption
 Decrease Laryngospasm and Laryngeal Edema
Decrease Aerosol and Droplets during Extubation
Class-1b Antiarrhythmic Amide Local Anesthetic
Most beneficial
 In painful Propofol/Etomidate Inj.
 Both in Acute and Chronic pain
 Abdominal Surgery
 Neuro surgery
 TIVA and OFA
 Onco surgery
 ENT surgery
 In ERAS
Most ideal drug to blunt airway reflexes
and sympathetic responses to
laryngoscopy and tracheal intubation
Mechanism of Action
 Blocks sodium ion channels on
the cell membranes and stabilizes
the membrane
 In neural tissues, lidocaine inhibits
the generation, transmission and
propagation of neural impulses
 At the level of the spinal reflex,
it blocks the afferent and/or
efferent parts of the reflex arc
The pharmacological effect of IV lidocaine
involves multiple pathways (peripheral
and central) and mechanisms (direct and
indirect) for pain relief
Dose Schedule
 A bolus of 1–2 mg/kg followed by
an infusion of 1–2 mg/kg/h with IBW
 From Pediatric to Geriatric
 Do not exceed a maximum dose
of 100 mg bolus or 100 mg/h
The target plasma concentration for
therapeutic effect is between 2.5 and
3.5 μg/ml
 CNS toxicity occurs in > 5 μg/ml
 CVS toxicity occurs in > 10 μg/ml
Post Operative IV Lidocaine
Use of lidocaine for up to 24 h
has significant decrease in pain
 Reduced analgesic requirements
 A faster return of GI function
An overall reduction in side effects
 Maximum post op infusion can be
given upto 3 to 5 days till the bowel
function returns normal and pain is well
Controlled
 Multi Para monitoring is must
during post op IV lidocaine
Practical Consideration
The concomitant use of IV lidocaine
with another regional anaesthesia
technique (e.g., epidural, TAP block)
requires careful consideration and is
probably best avoided because of
possible local anaesthetic toxicity
IV lidocaine is a component of every
laparoscopic procedure, irrespective of
its duration, invasiveness and desired
outcomes
 IV lidocaine is Useful to relieve PDPH
IVlidocainealways,toorderedbyAnesthesiologists
InHigh-RiskPatientsIVLidocainedosemustbereduced
Invention
1943
First Marketed
1949

54. Ketamine
NMDA antagonist
- Key role and main drug in OFA, without this drug OFA is incomplete
- Best analgesic, amnesic and opioid sparing effect
- Dose less than 0.5 mg/kg reduces postoperative analgesic needs and especially seen in
opioid-tolerant patients
- It has anti-hyperalgesic and anti-tolerance effects.
Most popular drug for anesthesiologist across globe since 50 years
Brahmashtra
for anesthesiologist in pain relief

55. Main Features
 Rapid-acting general anesthetic
 Produce profound analgesia
 Normal pharyngeal-laryngeal reflexes
 Slightly enhanced skeletal muscle tone
 Cardiovascular and respiratory stimulation
 Transient and minimal respiratory depression.
Contraindications
> Angina, Stroke and very high blood pressure
Psychiatric disorders, Uncontrolled Epilepsy
In raised intraocular pressure & Eye injury
Acute Porphyria
 Age less than 3 months
 Traceal and Laryngeal Surgery
- Bioavailability – 93 -100 %
- Protein binding - 53.5%
-Distribution half-life 1.95 min
- Half Life - 186 minutes
- Elimination - urine 91 % , 3 %
in feces and 6 % unchanged
- Clearance rate - 95 L/h/70kg
Mechanism of action
 Interacts with N-methyl-D-aspartate (NMDA) receptors,
opioid receptors, monoaminergic receptors, muscarinic
receptors and voltage sensitive Ca ion channels
 Does not interact with GABA receptors
 Selectively depress the thalamoneocortical system before
significantly obtunding the more ancient cerebral centers and
pathways (reticular-activating and limbic systems)
- Water and Lipid Soluble
- Oral ketamine broken down by
bile acids
- Undergoes hepatic Metabolism
- It can be mixed with any TIVA
drugs
- Compatible with all IV fluids
Other uses
> Emergency Dept.
> Asthma
> Seizures
>Pain management
> Depression
> Vet Anesthesia
Invented in 1962 ---- NMDA receptor antagonist with Dissociative Anesthesia ---- Approved in 1970
Most Popular Anesthetic Drug of Anesthesiologists
Ketamine• I V Effect
Starts -2 min
Last – 25 min
• IM Effect
Starts – 5 min
Last – 4-6 hrs
• Oral – 30 min
C13H16ClN
O
More
Analgesia
&
Less
Anesthesia
M/A
Main Actions
 Increase BP
 Increase Salivation
 Bronchodilation
 Hallucination
 Agitation
 Catatonia
 Prevent opioid
induced
Hyperalgesia
 Best agent
in Post anesthetic
shivering
Post
Ketamine
Double vision
& Nystagmus
are very
common
Dose Schedules
0.1-0.3 mg/kg – Analgesia
0.2-05 mg/kg – Recreational
0.4-0.8 mg/kg -- Partially dissociated
1-2 mg/kg – Fully Dissociated
1-2 mg/kg /IV – Procedural Sedation
4-8 mg/kg/IM – Procedural Sedation
0.1-0.2 mg/kg/hr – Postop Pain Relief
(Infusion maximum 3 days only)
IV Bioavailability -100 %
IM Bioavailability – 93 %
Dose Schedules
10 mg/kg /Oral – As Sedative
Premedication(Bioavailability – 20 %)
0.7-0.9 mg/kg – Intrathecal (S/A)
0.2 mg/ml – Epidural for Postop pain
Intra nasal 0.5-1 mg/kg (Bio-50%)
Intrarectal 0.5-1 mg/kg (Bio-30%)
Sublingually 0.5 -1 mg/kg (Bio-30%)
Inhalation 0.5-1 mg/kg
Topical Gel – 1% ketamine with
other drugs
Ketamine is
the only
drug which
Is given by
all routes
In body
U
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•Increase HR, high BP(20 %)
•Increased intracranial pressure
• Transient reddening of the skin
• Reduced appetite, nausea
• Increased salivation, vomiting
•Pain, eruptions or rashes at the injection site
• Tonic-Clonic movements
• Double vision , involuntary eye movements,
• Increased bronchial secretions
• Anaphylaxis and Dependence
• Cognitive Deficits
• Emergence reaction
Side
Effect
Pharmacokinetics
•Rapid onset and short duration of action
• Initially distributed to highly perfused brain tissues
• Crosses Blood Brain barrier
• Undergoes extensive redistribution
• Major metabolite are norketamine
and dehydronorketamine
Combination
• Ket+Propofol(Ketofol)
• Ketamine+Dex(Dexket)
• Ketamine+Fentanyl
• Ketamine+Midazolam
• Ketamine+Diazepam
• Ket+Prof+Dex (KPD)
WHO List of Essential Medicine

56. PROPOFOL
Invented in 1977 In Use 1989Switch On & Switch Off Anaesthesia
Only Hypnosis, Anaesthesia & No Analgesia
Propofol 1 % (10mg/ml) Propofol 2 % (20mg/ml)
Milk of Amnesia Also used in Veterinary Medicine for anaesthesia
Addiction and
Propofol Infusion
Syndrome with
long-term use
Milky White SolutionWHO Essential Medicine
Only given by
IV Route Slowly
No other routes
are indicated
Pharmacodynamics
Three compartment linear model
with compartments representing
Plasma, Rapidly equilibrating tissues,
and Slowly equilibrating tissues
Indications
 Initiation and maintenance of
Monitored Anesthesia Care
(MAC) sedation
 Combined sedation and
regional anesthesia
 Induction of General
Anesthesia
 Maintenance of General
Anesthesia
 Intensive Care Unit (ICU)
sedation of intubated,
mechanically ventilated patients
 Lie Detector test
Compatibility with other Drugs
 Ketamine
 Midazolam
 Dexmedetomidine
 Fentanyl / Remifentanil
 Lidocaine / Dexamethasone
Compatibility with other fluids
 5 % Glucose
 5 % Dextrose Saline
 0.9 % NaCl
 Ringer Lactate
 Paracetamol Infusion
 Minimum Dilution 2 mg/ml
Different Doses ( IV)
Induction
Children – 3-3.5 mg/kg
 Adult – 2-2.5 mg/kg
 Geriatric – 1-1.5 mg/kg
 ASA III & IV - 1 mg/kg
Maintenance
 Children - 0.125-0.3 mg/kg/min
 Adult - 0.1-0.2 mg/kg/minute
 Geriatric - 0.05-0.1 mg/kg/min
 ASA III & IV - 0.05 mg/kg/min
Maximum Maintenance
 6-10 mg/kg/hr(Roberts regime)
ICU Patient (Maximum 10 days)
 0.01-0.05 mg/kg/minute
TCI Model : Marsh, Diprifusor
Schinder, Kataria and Paedfusor
Common Side Effects
Hypotension
 Apnea lasting 30-60 seconds
 Abnormal Movement
 Injection site burning/pain
 Respiratory acidosis
 Hypertriglyceridemia
 Rash and Itching
 Arrhythmia and Bradycardia
 Cardiac Output decreased
 Bronchospasm / Edema
 Phlebitis /Allergic Reaction
 Pancreatitis
Asystole/Cardiac Arrest
 Seizures
Contraindications
 Documented Hypersensitivity
 Egg allergy
 Soybean/Soy allergy
Cautions
 Bronchial Asthma
 Pt. with long term NSAIDs
 Severe Hypovolemia or Shock
 EF < 30 % with Cardiac Disease
 Severe hepatic dysfunction
 Severe renal Impairment
 Long term infusion
 GI bleeds, ulcers, perforation
 Pregnancy and Lactation
Mechanism of Action
 Works by increasing GABA
mediated inhibitory tone in the CNS
 Decreases the rate of dissociation
of the GABA from the receptor,
thereby increasing the duration of
the GABA-activated opening of the
chloride channel with resulting
hyper polarization of cell membrane
The endocannabinoid system
may contribute significantly to
propofol‘s anesthetic action and
to its unique properties
 Causes a prominent reduction in
the brain's information
integration capacity
Pharmacokinetics
 Formula : C12H18O
 Molar mass : 178.275 g·mol−1
 Protein binding : 95–99%
 Metabolism :
Liver glucuronidation
 Onset of action : 15–30 seconds
 Elimination half-life: 1.5–31 hr
 Duration of action : 5–10 min
 Excretion: Renal
 Renal clearance : 120 ml/min
S
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Pre filled Syringes 10 ml/20 ml
10 ml/20 ml 1 % as Bulb/Ampoule
50/100 ml 1 % or 2% Bulb MCT/LCT
Propofol contains Soya oil, MCT,
glycerol, egg lecithin, sodium hydroxide,
oleic acid and water for injections
Changed
Anesthesia
Practice
Over
Dose
Death
Main Drug in TIVA
Most
widely
used
drug
In
world

57. Dexmedetomidine
• Dexmedetomidine has hypnotic,
sedative, and analgesic
properties and is estimated to be
7-10 times more potent than
clonidine
• Most ideal anesthetic agent with
all the properties of anesthesia
• Has got opioid sparing effect
• Dexket/Ketodex combination is
becoming very popular in
Pediatric OFA
• Patients sedated, but, arousable,
alert and respond without
uncomfortable
• They may quickly return to
sedation again
• Conscious Sedation as natural
sleep
• This drug is becoming widely
popular in all part of world in all
anesthesia techniques
(An alpha-2 agonist)

58. Sedation
Anxiolysis DEXMEDETOMIDINE
Analgesic
Anaesthetic
FDA
December 1999
Market
August 2000
 Agonist of α2-adrenergic receptors 
 Most ideal anesthetic agent available 
M/A
Induces sedation by decreasing
activity of noradrenergic neurons
in the locus ceruleus in the brain
stem, thereby increasing the
activity of inhibitory gamma-
aminobutyric acid (GABA) neurons
in the ventrolateral preoptic
nucleus
 Popular in pediatric TIVA with ketamine 
 Patients sedated, but arousable, alert and respond without
uncomfortable like conscious sedation 
No effect on
Respiratory
System
 Transient Hypertension followed by Hypotension 
No Direct
effect on
Myocardium
IOP
Insulin Release
 Overdose may cause 1st or 2nd degree AV Block 
- Nasal - ~ 84 % bioavailability
Indications
Pre Anaesthetic sedation (IM/IV)
As Induction Agent
In maintenance of Anaesthesia
As adjuvant in TIVA
Intra thecal with Regional Ane.
In Post Operative Analgesia
As ICU sedation(only for 24 hrs)
Relative Contraindication
 Infusion over 24 hours
 In pre existing severe bradycardia
 Brady dysrhythemia
 Patient with < 30% EF
 Partial or Complete AV block
 In patients more than 65 y of age,
a higher incidence of bradycardia and
hypotension
Compatibility
- 0.9% sodium chloride in water
- 5% dextrose in water
- 20% mannitol
- Lactated Ringer's solution
- 100 mg/ml MgSo4 solution
- 0.3% potassium chloride solution
- With other Anesthetic agents e.g.
Propofol, Ketamine, Etomidate
Available as Ampoules or Bulb
50 mcg / 0.5ml
100 mcg / 1 ml
200 mcg / 2ml
Sileo Gel for Dogs
(Dexmedetomidine Oromucosal Gel)
0.09 mg/ml, 3 ml syringe
(BIPHASIC BLOOD PRESSURE RESPONSE) (BRADYCARDIA IS BECAUSE OF DOUBLE EFFECT)
(DECREASE OPIOID REQUIREMENT BY 50 %)
(BETTER THAN CLONIDINE IN ALL ASPECTS)

60. Clonidine
(An alpha-2 agonist)
• Analgesic properties are due
to both peripheral and
central a2-
adrenoreceptor agonism
• Avoid in patients with:
– Bradyarrthymias
– severe AS
– Coronary artery
– Renal patients require
less dose
• Long half life up to 18 hours
with both PO and IV dose
• PO dose:
– 3-5mcg/kg (IBW) given
1-2 hours preop
• Bioavailbility is 75-
95%
• IV dose:
– Give 1.5mcg/kg (IBW) on
induction
• Total dose 3mcg/kg,
should not exceed
• Dose may be given
over 30 minutes
before preop

61. Paracetamol
• Preemptive analgesic
• Has got opioid sparing
effect
• Loading dose is 30 mg/kg
and maximum not to
exceed 2 gm
• Very innocent drug in OFA
and can be repeated at
every 6 to 12 hours interval
in dose of 1000 mg
• Excellent adjuvant in
Pediatric OFA
Diclofenac Sodium
• Powerful NSAID in OFA
with analgesia and anti-
inflammatory action
• Best is given in single dose
of 1.5 mg/Kg IV slowly and
maximum is 150 mg
• Use aqueous solution only
• Caution with renal, hepatic,
pulmonary and heart
failure patients
Always give both drugs before surgical
incision to inhibit prostaglandin receptors

62. (Opioid sparing adjunct) (Gives central analgesia)

63. MOKA ICECUBES
A Novel Combination of Oral Premedication
for Paediatric Patients
in OFA practice
One Icecube Contains
Midazolam 2 ml ------ 2 mg
Ondansetron 2 ml ---- 4 mg
Ketamine 2 ml -------- 100 mg
Atropine 2 ml ---------- 1 mg
Dose is given as follows
2-5 Year ---- 1 ice cube
5-10 Year --- 2 ice cubes
10-15 Year -- 3 ice cubes
MOKA ice cube is novel
mixture of Midazolam,
Ondansetron, Ketamine
and Atropine
One hour after oral
premedication, all
paediatric patient are
calm, cool, quiet,
sleepy
No crying,
rowdiness, injection
fear or anxiety in
both patient as well
as in parents

64. In short in OFA
Dexamethasone given before induction to general anaesthesia in dose 0.1 mg/kg has
antiemetic effect and can reduce opioid consumption in the first 24 h
Paracetamol has analgesic and antipyretic effect and given preemptively has shown to
be effective in the postoperative treatment of pain with less opioid consumption in the
first 24 h after surgery and less nausea and vomiting and Together with the NSAID is the
first analgesic of choice for treatment of acute pain
Analgesic doses of lignocaine needed in the perioperative period are 1–2 mg/kg as a
bolus dose, continuing with intravenous continuous infusion from 1–2 mg/kg/h, which
are clinically effective
Ketamine and magnesium sulphate are both N-methyl D-aspartate (NMDA) antagonists.
Ketamine is most effective given as a bolus dose 0.5 mg/kg during induction to general
anaesthesia and to be continued in the peri- and postoperative period in dose 0.25
mg/kg up to 48 h in major abdominal operations, with reduction on postoperative
opioid consumption
Magnesium sulphate given as a continuous i.v. infusion potentiates analgesia after
surgery and reduces the need for opioids in the postoperative period.

65. So OFA gives
Fast Track Enhanced Recovery
• With Good Safety Profile ( Early Recovery)
• Excellent Cost efficient ( Decrease hospital stay)
• User Friendly (Easily accepted)
• Better outcome ( Early ambulation)
• Early oral hydration and Minimum parenteral fluids (No opioid, No Antiemetics)
Minimal Invasive Anaesthesia

66. Some OFA RISK with these
drugs
# Bradycardia with dexmedetomidine
# Hepatic damage with paracetamol
# Bleeding, renal impairment and bronchospasm with
diclofenac sodium
# Hallucinations, tachycardia and addiction with
ketamine
# Tinnitus, seizures and cardiac arrest with lidocaine
# Sedation with dex
# Hypotension with magnesium

67. The European society for perioperative care of patient
(ESPCOP)

68. The European society for perioperative care of patient
(ESPCOP)

69. Standard OFA Induction
10 minutes prior to induction
Sympathetic Block
Dexmedetomindine 0.3 mcg/kg IBW (20-
30 mcg)
1 minute prior to induction
Hypnotic and rapid stress block –
Lidocaine 1.5 mg /kg ( 100 mg)
Induction
Hypnotic and stress block
Propofol 2.5 mg/kg IBM (200mg)
Rapid preload reduction
Magnesium Sulfate 40 mg / kg IBW (2.5 g)
Anti-inflammatory agents
before surgery
Dexamethasone 8-10 mg
Diclofenac 75 – 150 mg
Paracetamol – 1 gm
NMDA Antagonist
Ketamine 50-100 mg (bolus / slow infusion /
end of surgery)
On standby
Beta-Blocker – Esmolol / Metoprolol
Calcium channel blocker – Nicardipine 1–5 mg
Ephedrine 3–9 mg / Mephentermine 15-30 mg
Phenylephrine 10 – 30 mcg
Anticholinergic, Antiemetic and Antacid as per choice of anesthetist
And Neuromuscular Blocking drugs if needed for surgery

70. Standard OFA Maintenance
Sympathetic Block
Dexmedetomidine 0.5 – 1 mcg/kg/h
Clonidine 150 mcg
Local Anesthetics
Lidocaine 1 – 2 mg / kg /h
Magnesium Sulfate :
2.5 – 10 mg / kg IBW/ h
Inhalation Agent (If required)
Sevoflurane / Desflurane
0.6 – 0.8 MAC with BIS around 50%
Propofol infusion
higher dose than TIVA required
(6-8 mg/kg/hr)
NMDA block
Ketamine 0.1-0.2 mg/kg/hr
IV Paracetamol: 1000 mg
Post Operative Analgesia
(not more than 24 hrs)
Lidocaine 1-2 mg/kg/hr
Ketamine 0.1-0.2 mg/kg/hr
Block Anesthesia
Local Infiltration

71. MY
OF–TIVA
(Opioid Free –TIVA)
Technique

72. Best Premedication in COVID pandemic to avoid
aerosol and droplets before OFA 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

73. Intravenous
Diclofenac Sodium 1 mg/kg
and
Paracetomol 1 gm Infusion
(Always I give before surgical incision)

74. KPD TIVA
Mixture in 1:1:1 mg:mg:mcg/kg 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
 dose of individual
agents
 airway complications
Stable haemodynamics Rapid recovery
As Induction, Maintenance and in Short procedure < 30 min
(Ketamine, Propofol and Dexmedetomidine)
Excellent Analgesia and Anesthesia

75. For Maintenance
Dexmedetomidine 0.7-1 mcg/kg/hr in RL
or
Propofol 6-8 mg/kg/hr in 100 ml NS
and
I Stop the infusion drip 15 minutes before at end of surgery

76. OFA

77. For post Operative Pain
Relief
Local Infiltration or Respective Nerve Blocks
No Opioid at all in Post Op period
Ketamine and Lidocaine drip for 12-24 hours
depends upon surgery (KetaCaine Drip)
Paracetamol 1 gm every 12 hrs IV
Diclofenac Sodium 1 mg/kg every 12 hrs IV
VAS is almost Zero or < 10 %
(Ketamine 0.1- 0.2 mg/kg/hr + Lidocaine 1 mg/kg/hr with Monitoring
1
2
3
4
No

78. Pearls of my
OFA
Practice
In my 80 % practice I use
KPD mixture In all
OFA cases
For Intra Op maintenance I use Dex infusion
or Propofol infusion depends upon surgery,
surgical time and vital parameters
Started practice of Opioid Free Multi
Model Analgesia and Anesthesia with
Ketamine, Propofol, Dexmedetomidine
(KPD) with help of other adjuvants in OFA
I am using Nitrous
oxide and any
volatile agents
only in 20 % cases

79. So
My Economics of Drugs
in OFA

80. Name of Drug Form Strength Cost (Rs.) Remark
Glycopyrrolate 1 ml ampoule 0.2 mg 25 2 ampoule
Ondensetron 2 ml ampoule 4 mg 10 1 ampoule
Dexamethasone 2 ml amp/bulb 8 mg 10 1 amp/bulb
MgSO4 2 ml ampoule 1 gm 10 1 amp
Paracetamol 3 ml ampoule 450 mg 20 2 ampoule
Diclofenac Aqua 1 ml ampoule 75 mg 25 1 ampoule
Lidocaine IV 30 ml bulb 21.3 mg/ml
Total 640 mg
50 1 bulb
Etamsylate/Trenexa 2 ml ampoule 125 mg 25 1 ampoule
Propofol 20 ml bulb 200 mg 300 2 bulb
Suxamethonium 10 ml bulb 500 mg 50 2 ml
Ketamine 10 ml bulb 500 mg 100 3 - 4 ml
Dexmedetomidine 1 ml amp 100 mcg 350 1 ml
Esmolol 10 ml bulb 100 mg 250 3 – 4 ml
Atracurium / Neostigmine 5 ml / 5 ml amp 50 mg / 2.5 mg 250 + 25 5 ml – 5 ml
Total 15
drugs in
my OFA
Toolbox
This is
example
of routine
case lasting
for 90-120
minutes
e.g.
Lap. Chole.
or
Lap. TLH
or
Mastoid.
Total cost
is only
1500 Rs.
for my
OF TIVA
No Volatile
agent is
used
Rs. 1500

81. Surgical Procedures under OFA
• From OT to Outside OT(NORA)
• From Pediatric to Geriatric patients
• From any Surgical to Medical Specialty

82. The European society for perioperative care of patient
(ESPCOP)

83. My Tips For Starting
OFA
• Do not administer
Opioids
• Communicate in Doubt
• Educate Yourself
• Keep Update with Latest

84. CONCLUSION
• Do we really need opioids in anesthesia? No
• Opioid crisis/epidemic became a known reality since 1990, so
the concept of opioid-reduced, and eventually opioid-free
anesthesia started
• Opioid Free anesthesia is the future of anesthesia
• It is slowly but surely being considered the best way to give GA
• There are very few contraindications for opioid free anesthesia
• Multimodal anesthesia and analgesia with no opioid use is
becoming popular and new normal method in OFA and OF-TIVA
• Replacing opioids with other analgesics will not only reduce
the development of opioid addiction but will also lead to
better perioperative outcomes and enhanced patient recovery

85. Take Home Message
• Opioids can be replaced by multi drugs to avoid complications of opioids
• Postoperative pain management without opioids are viable truth
• Ketamine is the main key role in OFA (Preempt Ketamine)
• Don’t give Ketamine alone, always combine with Propofol or Dexmedetomidine
• Don’t exceed Ketamine more than 200 mg intraop, in any surgery under in OFA
• No bolus Propofol more than 2 mg/kg in OFA
• Ketamine laryngospasm is not common, but whatever we see is light anesthesia
induction causing laryngospasm and treatment is IV lidocaine 2 mg/kg
• NMDA receptors are antagonized with Ketamine / MgSO4 / Dexmedetomidine
in OFA
• You don’t have to be worry, if your OFA is perfect than better outcome without
pain and PONV (ERAS)
• To reduce intraop blood pressure use Esmolol, with its multiple effect in OFA
• Dexamethasone, MgSO4 and Lidocaine(DML) are three main friends in OFA
• NSAIDs and Paracetamol are best adjuvant in OFA for postop pain relief

86. OFA will be a game changer in high risk patients,
especially Geriatric, COPD & Obese patients
Let's begin
Opioid sparing or opioid free anesthesia with
technique of Multimodal Anesthesia and Analgesia
By reducing opioid-related adverse effects, OFA aims to
enhance optimal perioperative analgesia through
reducing pain scores and enabling earlier mobilization
with enhanced rehabilitation, faster discharge and
improved patient satisfaction

87. 1
2
3

88. 1
2
3
4

89. Start
IT IS

90. In this era patient wants Opioid Free Anesthesia
If not than start Opioid sparing Anaesthesia

91. In 2020 My Friends
OFA is not humbug

92. 92
II won’t use OFA
I can’t use OFA
I want to use OFA
How do I use OFA
I will try to use OFA
I can use OFA
I will use OFA
Yes I have used OFA

93. Thank You
Join
Face book Group of
“Indian Society for Opioid Free Anesthesia”
(I SOFA)
chokshitushar@hotmail.com
https://sites.google.com/site/tusharchokshisite