Intraoperative cocktail injection in knee arthroplasty for reduction of postoperative pain.

1. Cocktail
An Antidote for Pain
Anurag Mittal

2. Why Pain Management is Important

3. Why Pain Management is Important
• Pain
– Delays recovery
– Decreases patient satisfaction
– Delays rehabilitation
– Delirium
– Depression

4. Evolution of Perioperative Pain
Management for TKA(Total Knee Arthroplasty)
1980s 1990s 2000s 2010s
IV or IM Narcotics IV Narcotics via patient
controlled analgesia (PCA)
Multi-modal, pre-emptive
analgesia with peripheral
nerve blocks
Multi-modal pre-emptive
analgesia with Peri-
articular Injections

5. Why Use Periarticular Multimodal
Cocktail Injection?
• Significantly reduce
– consumption of analgesics
– infection
– pain after surgery
– intra-articular bleeding
– duration of time required to perform straight-leg
raise
– overall narcotic consumption
– the hospital stay

6. Why Use Periarticular Multimodal
Cocktail Injection? (Cont’d)
• Improve
– range of motion (ROM)
– patient satisfaction rate following surgery
– the time the agents would act locally

7. The Modalities of Decreasing Pain

8. Periarticular Cocktail Injection

9. My Peri-Articular Cocktail Injection
Constituent Epinephrine Ketorolac Ropivacaine Morphine Cefuroxime Normal Saline
Volume 0.3 ml
(1 mg/1 ml)
1 ml
(30 mg/1 ml)
40 ml
(0.75%)
10 ml
(5 mg/5 ml)
750 mg 50 ml
0.9%
In two 50 ml syringes

10. When is it given?
● 1st: After bony cuts
1st 2nd
● 2nd: After implantation of femoral and tibial implants

11. Where is it given? (1st)
Upper left Figure 1.
Lateral capsule
+ Lateral collateral ligament
Upper right Figure 2.
Medial collateral ligament
Lower left Figure 3.
Far medial capsule
Upper right Figure 4.
IC Region
**No injection in Posterolateral capsule
15 ml
15 ml
10 ml 10 ml

12. Where is it given? (2nd)
Upper left figure 1. Superior capsule
Upper middle figure 2. Medial capsule
Upper right figure 3. Anterior capsule
Lower left figure 4. Superior vastus medialis oblique
Lower right figure 5. Inferior vastus medialis oblique
10 ml 10 ml
10 ml
10 ml
10 ml

13. Pharmacological Aspects of
Cocktail Injection Constituents

14. Epinephrine
Group Catecholamine (Sympathomimetic monoamine)
MOA Nonselective agonist of all adrenergic receptors
Increase peripheral resistance via α1 receptor-dependent vasoconstriction
Half-life Less than 5 minutes (IV)
Use in TKA Vasoconstrictor
• Reduce the toxicity of the local anesthetic by reducing the rate the
drug is released into the circulation.
• Reduce intraoperative bleeding and postoperative hemoglobin loss
• Minimize the need for blood transfusion
Side Effect Increased risk of vasoconstriction and sloughing of tissue (Concurrent use
with local anesthetics for injection of areas such as fingers, toes, ears)

15. Ketorolac
Group Potent Nonsteroidal antiinflammatory drug (NSAID)
MOA Blocks prostaglandin complex formation and production through its S-
enantiomeric form.
Half-life S-enantiomer: approximately 2.5 hours (SD±0.4)
R-enantiomer: 5 hours (SD±1.7)
Racemate: 5 to 6 hours
Use in TKA Analgesia that does not possess any sedative or anxiolytic activities
Side Effect Gastrointestinal bleeding, kidney failure (may result in hospitalization
and even fatal outcome)

16. Ropivacaine
Group Amino amide local anesthetic
MOA Increases the threshold for electrical excitation in the nerve
Half-life IV terminal half-life of 1.8 h
Use in TKA Local anesthetic
Side Effect May be chondrotoxic (continuous intra-articular postoperative use)

17. Morphine
Group phenanthrene opioid receptor agonist
MOA Agonists of the μ (main), 🇰, δ
Half-life The plasma half-life is 2-3 hours.
Use in TKA Perioperative analgesia
Side Effect (Acute dose-related effects) Respiratory depression; anorexia, nausea,
vomiting and constipation; euphoria, dizziness, drowsiness and
confusion; dry mouth and spasm of the urinary and biliary tract;
hypotension, bradycardia and palpitations.
Prolonged administration may result in physical dependence.

18. Cefuroxime
Group Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase
(2nd generation)
MOA Binds to specific penicillin-binding proteins (PBPs) located inside the
bacterial cell wall, it inhibits bacterial cell wall synthesis
● Gram positive coverage: Less active compared to 1st generation
cephalosporin (e.g. cephalexin, cefazolin)
● Gram negative coverage: Haemophilus influenza, Enterobacter
aerogenes, Neisseria, Proteus mirabilis, Escheria coli, Klebsiella
pneumonia
● No anaerobic coverage
Half-life Approximately 80 minutes (IM or IV)
Use in TKA Treatment of many different types of bacterial infections
Side Effect Swelling, redness, or pain at the injection site

19. Other Cocktail Injections

20. Other Cocktail Injections - Ranawat
Chitranjan S. Ranawat, M.D.

21. Comparison with Ranawat Injection
Ranawat Cocktail TK Cocktail
Epinephrine 1:1000 (0.3 cc) Epinephrine 0.3 ml (1 mg/1 ml)
Methylprednisolone acetate 40 mg (1 cc) Ketorolac 1 ml (30 mg)
Bupivacaine 0.5% (24 cc) Ropivacaine 40 ml
Morphine sulphate 8 mg (0.8 cc) Morphine 10 ml
Cefuroxime 750 mg (10 cc) Cefuroxime 750 mg
Sodium chloride 0.9% (22 cc) Normal Saline 50 ml
98.1 cc

22. Ketorolac vs. Methylprednisolone
Ketorolac (TK) Methylprednisolone (Ranawat)
Group Potent NSAID for short term use Corticosteroid
Use Anti-inflammatory and analgesic
Cautions (rabbit) Dose-dependent inhibitory
effect on bone repair
Increase the incidence of articular
infection
Mechanical side effects
- Cartilage breakdown
- Loss of elasticity of the
articular cartilage

23. Ropivacaine vs. Bupivacaine
Ropivacaine (TK) Bupivacaine (Ranawat)
Lipophilicity less more
sensory nerve block selectivity more selective selective
CNS toxicity less more
Duration of motor block similar
Analgesic efficacy stronger weaker
Onset of action more rapid delayed
Post-op analgesia time shorter longer
Chondrotoxicity less more

24. Other Modifications of Ranawat Cocktail (1)
0.5% bupivacaine 20 ml
clonidine 150 mcg
morphine 4.5 mg
adrenaline 1000 mcg
Cefuroxime-sodium 1.5 gm
ketorolac 1.5 gm
Prem Kakar, Vinod Gagrani, [...], and Gurpreet Popli, Post-operative analgesia regime following joint replacement, Indian J
Anaesth. 2011 May-Jun; 55(3): 305–306

25. Clonidine
Group imidazole derivative
MOA α2 receptor agonist
● pre-synaptic: inhibit release of neuropeptides that stimulate
nociceptors
● post-synaptic: hyperpolarize and decrease the activity of nociceptive
neurons by releasing inhibitory neurotransmitter
Use in TKA Analgesics
Limitation Intra-articular administration has limited analgesic effect (mild and short
lasting)
Side effect hypotension, bradycardia

26. Other Modifications of Ranawat Cocktail (2)
Morphine sulphate 5 mg
Ketorolac 30 mg
Ropivacaine 0.5% 50-74 kg 200 mg
75-99 kg 300 mg
100-125 kg 400 mg
Epinephrine 50-74 kg 100 mcg
75-99 kg 200 mcg
100-125 kg 300 mcg
Normal Saline to bring quantity to 120 ml
weight-based doses
Mayo clinic Henry Clarke,
M.D. and Mark Spangehl,
M.D., orthopedic
surgeons at Mayo Clinic
in Arizona

27. A nomogram for calculating
the maximum dose of local
anaesthetic, D. J. Williams, J.
D. Walker, Anaesthesia 2014,
69, p.847–853
David Cone, Jane H. Brice,
Theodore R. Delbridge, J.
Brent Myers, Emergency
Medical Services: Clinical
Practice and Systems
Oversight, John Wiley & Sons,
2014. 12. 30, p.409

28. References
• Albert Schweitzer quote https://www.azquotes.com/quote/548046
• Peri-Operative Pain Management for Total Knee Replacements - Mayo Clinic https://www.youtube.com/watch?v=R0Q4adIYF-
Q
• TK Orthopedic Institution Patient Care Protocols
• Tulane Doctors ~ Orthopaedics ~ Total Knee Arthroplasty (TKA)/Knee Arthritis https://medicine.tulane.edu/tulane-
doctors/orthopaedics/problems-conditions/total-knee-arthroplasty-tkaknee-arthritis
• Malone KJ, Matuszak S, Mayo D, Greene P. The effect of intra-articular epinephrine lavage on blood loss following total knee
arthroplasty.Source: Malone, K J. Orthopedics Volume: 32 Issue: 2 (2009-02-01) p. 100. ISSN: 0147-7447
• Drugs.com Ketorolac Injection https://www.drugs.com/pro/ketorolac-injection.html
• Pacifici GM: Metabolism and pharmacokinetics of morphine in neonates: A review. Clinics (Sao Paulo). 2016 Aug;71(8):474-80.
doi: 10.6061/clinics/2016(08)11. [PubMed:27626479]
• World Health Organization, Essential Medicines and Health Products Information Portal
https://apps.who.int/medicinedocs/en/d/Jh2929e/7.html
• Drugbank, Cefuroxime, https://www.drugbank.ca/drugs/DB01112
• Maheshwari, Aditya & Blum, Yossef & Shekhar, Laghvendu & Ranawat, Amar & Ranawat, Chitranjan. (2009). Multimodal Pain
Management after Total Hip and Knee Arthroplasty at the Ranawat Orthopaedic Center. Clinical orthopaedics and related
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• Ranawat Orthopaedics http://www.ranawatorthopaedics.com/
• Ho, Mei-Ling*; Chang, Je-Ken*; Wang, Gwo-Jaw* Antiinflammatory Drug Effects on Bone Repair and Remodeling in Rabbits,
Clinical Orthopaedics and Related Research: April 1995 - Volume 313 - Issue - p 270–278
• Cheng KY, Feng B, Peng HM, et al. The analgesic efficacy and safety of peri-articular injection versus intra-articular injection in
one-stage bilateral total knee arthroplasty: a randomized controlled trial. BMC Anesthesiol. 2020;20(1):2. Published 2020 Jan
4.

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