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TIVA different combination of drugs
Dr. Tushar M. Chokshi is a consultant anesthesiologist practicing privately in Vadodara, India with over 30 years of experience. He has affiliations with several hospitals in Vadodara. His areas of expertise include total intravenous anesthesia (TIVA), uroanesthesia, laparoscopic anesthesia, ENT anesthesia, pediatric anesthesia, and he was the founder of TIVA and OFA Facebook groups in India. He is a national and state level speaker on anesthesia topics and was one of the first to introduce smartphone and teleanesthesia practice as well as infographics in anesthesia in India.
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Introduces Dr. Tushar M. Chokshi, a consultant anesthesiologist with 30 years experience, highlighting expertise in various anesthesia types.
Explains TIVA as a method of general anesthesia using intravenous agents only, detailing its advantages and indications for surgical use.
Discusses potential risks of TIVA including injection complications, awareness risks, and bacterial contamination.
Lists and describes various drugs used in TIVA, their availability, action types, and differentiation between those used in TIVA and not.
Describes the rationale for drug combinations in anesthesia, emphasizing the benefits of achieving balanced anesthesia.
Focuses on the Anesthesia Triangle concept and emphasizes awareness of drug interactions for safe anesthesia.
Uses a metaphor to describe the hierarchy of anesthetic drugs, illustrating the importance of each in achieving effective anesthesia.
Details various established TIVA combinations (e.g., Ketofol) and their compatibility advantages.
Discusses combination therapies for premedication, maintenance, and postoperative relief using specific drug mixtures.
Presents references supporting the use of TIVA and specific drug combinations, highlighting studies and their conclusions.
Summarizes the importance of TIVA in anesthesia, noting its effectiveness without volatile agents and the need for understanding interactions.
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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 [email protected] MD (Anaesthesiology) https://sites.google.com/site/tusharchokshisite National Origami Teacher Visual Storyteller & Vlogger Happy Go To Lucky Fellow Always believe in exchange of Knowledge 1
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- 3. It is atechnique 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 TrachealTubes 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 surgicalprocedures 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 aslight 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 irreversibleShallow 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
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- 9. TIVA drugs with theiradvantages • 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 MagnesiumSulphate 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
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- 12. TIVA Drug Combinations 12 Combinationis therapy that uses more than one medication or modality
- 13. Why TIVA isgiven 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 Itdecreases the dose of individual drug Combo reduces side effects all drugs in mixture They give complete balanced anaesthesia with multiple effects
- 15. TIVA completes AnesthesiaCircle (with IV anaesthetic drugs) 15
- 16. 16 What to understandbefore mixing any drugs for anesthesia
- 17. Anesthesia Triangle The conceptof 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 hiddenworld 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 willdecide 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 establishedTIVA 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/kgand 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 & FENTANYLCombo 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 (Remifentanyland 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
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- 27. Best Premedication beforeTIVA 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 1mg/kg in Paracetomol 1 gm Infusion (Always I give before surgical incision) 28 Diclo and Paracetamol Combo
- 29. For Maintenance 1) KPDmixture 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
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- 31. 31 Fentaketacaine (FLK) dripafter 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
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- 33. Compatibility of PropofolInjectable 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 Combinationof 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 Anaesth2010 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 ofmidazolam 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 dexmedetomidineand 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 LidocaineMixture 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 premedicatedpatients 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
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- 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 AnaesthesiaDelivery 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
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- 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 atechnique 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
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