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Benefits of total intravenous anaesthesia in dogs and cats

Author : KATHERINE ROBSON

Categories : Vets

Date : November 17, 2014

KATHERINE ROBSON BVSc, CertAVP(VA), MRCVS discusses the interest in total intravenousanaesthesia, looking at the advantages compared with inhalational methods, such as reducedoccupational hazards

Summary

Inhalational agents are the mainstay of veterinary anaesthetic maintenance. In the medical fieldthere has been interest in total intravenous anaesthesia (TIVA), where intravenous agents providethe three main aspects of surgical anaesthesia: unconsciousness, muscle relaxation andanalgesia.

This article reviews the advantages of TIVA compared with inhalational anaesthesia in smallanimals, including reducing occupational hazards associated with chronic exposure to inhalationalagents. The benefits of TIVA for airway procedures, neuroanaesthesia, in patients requiringmechanical ventilation and in those with a known or suspected mutation for malignanthyperthermia, are discussed. In addition, commonly available anaesthetic, sedative and analgesiadrugs that can be used in TIVA protocols are described, along with some suggested doses.

Key words

anaesthesia, analgesia, dogs, cats, intravenous agents

INHALATIONAL agents are the mainstay of veterinary anaesthetic maintenance. There hasbeen much interest in total intravenous anaesthesia (TIVA), where IV agents provide the

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three main aspects of surgical anaesthesia: unconsciousness, muscle relaxation andanalgesia.

This change has been driven partly by concerns about occupational hazards of inhalational agents.Nitrous oxide is a greenhouse gas that cannot be adsorbed by charcoal. Therefore, waste gas isreleased into the atmosphere, potentially contributing to global warming (Irwin et al, 2009).

The halogenated chlorofluorocarbons, including halothane, isoflurane and sevoflurane, are thoughtto be potentially damaging to the ozone layer (Irwin et al, 2009). There are also health concernsabout the effects of chronic exposure to these agents in hospital staff. Nitrous oxide may be linkedto bone marrow disorders via reduction in vitamin B12 levels (Ferner et al, 2014) and is thought tobe teratogenic. Experimentally in rats, it caused increased rates of spontaneous abortion andcongenital abnormalities in offspring (Vieira et al, 1980).

Chronic exposure to halogenated agents may be linked to increased incidence of hepatic disease,renal disease and immunological abnormalities (Irwin et al, 2009). However, there is stillcontroversy in the literature. Most studies finding a link between exposure to anaesthetic agentsand health problems have been retrospective questionnaire-based studies (Burm, 2003). Thesestudies have been criticised for bias and lack of control of many potential confounding factors inhospital personnel, including high work stress, exposure to radiation and long working hours (Burm,2003).

Health problems associated with chronic exposure to inhalational agents remain unclear. Due tothe potential risk, it would be best practice to minimise or eliminate occupational exposure. Timeswhen there is greater exposure include: mask inductions, using uncuffed endotracheal tubes,disconnection of the patient from the breathing system to move to another area – for example, preproom to operating theatre – and in recovery, where patients are exhaling anaesthetic gases directlyinto the surrounding area. The use of TIVA would eliminate these potential risks from the workenvironment.

Another advantage of TIVA is a reduction in postoperative nausea and vomiting. It has been shownin human literature that induction and maintenance of anaesthesia with propofol is associated withsignificantly less postoperative nausea and vomiting compared with isoflurane (Sneyd et al, 1998).Although veterinary patients are unable to communicate feelings of nausea, it could be contributingto inappetence or anorexia sometimes seen after general anaesthesia.

Procedures involving the airway, such as bronchoscopy, laryngeal and pharyngeal surgery, poseparticular challenges for anaesthetic maintenance. Difficulties and interruptions in access to theairway for delivery of inhalational agents lead to fluctuations in the plane of anaesthesia andpotential for exposure of staff to these agents during the procedure. TIVA would allow for a morestable plane of anaesthesia throughout.

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Patients presenting with neurological disease is another group where TIVA may have advantages.Goals of neuroanaesthesia are to maintain oxygen delivery to the brain and avoid increases inintracranial pressure. The skull is a fixed volume containing brain tissue, cerebrospinal fluid andblood. An increase in the volume of one component will firstly cause a reduction in volume of theothers. Once no further compensation can be achieved, intracranial pressure will rise, eventuallyleading to brain herniation (Figure 1).

Animals presenting with space occupying brain lesions or inflammatory brain disease are at risk ofraised intracranial pressure. All halogenated agents cause dose-dependent vasodilation, whichincreases the volume of blood in the skull, potentially leading to an increase in intracranial pressurein high-risk patients. Also, cerebral blood flow is normally controlled by cerebral metabolic rate; areduction in cerebral metabolic rate will lead to a reduction in cerebral blood flow. Whilehalogenated inhalant anaesthetics will reduce cerebral metabolic rate, they alter this autoregulationand cerebral blood flow does not reduce as expected and may actually increase, furthercompounding increases in intracranial pressure.

Propofol has been shown to maintain cere bral blood flow autoregulation, reduce cerebralmetabolic rate and reduce intracranial pressure (Artru et al, 1992). TIVA protocols with propofol arewidely used in medical neuroanaesthesia (Chui et al, 2014). Alfaxalone may be an alternative topropofol, but studies into its use are lacking.

Patients in the intensive care unit receiving mechanical ventilation or patients with pre-existingpulmonary disease may also benefit from TIVA. A number of indications for mechanical ventilationin small animals include severe hypoxaemia despite oxygen therapy, severe hypoventilation andexcessive work of breathing (Hopper and Powell, 2013). Animals with severe hypoventilation, andwhere they are exhausted due to excessive work of breathing, are also likely to be hypoxaemic,especially if breathing room air. Hypoxic pulmonary vasoconstriction (HPV) is a regulatorymechanism that occurs when low partial pressure of oxygen detected in the alveoli results inconstriction of the adjacent pulmonary arterioles. The aim is to divert blood away from poorlyventilated areas of lung towards better ventilated areas, thereby improving gas exchange (Figure 2).Halogenated inhalational agents have been shown to attenuate HPV (Lennon and Murray, 1996)resulting in lower oxygenation of arterial blood and worsening hypoxaemia. Their vasodilatoryeffects can also contribute to hypotension in already compromised patients and therefore theseagents are not recommended during long-term mechanical ventilation, requiring the use ofinjectable sedative and anaesthetic drugs.

Halogenated inhalational agents, including isoflurane and sevoflurane, can trigger malignanthyperthermia (Visoiu et al, 2014). Malignant hyperthermia is an inherited channelopathy that leadsto hypercapnia, hyperthermia, metabolic acidosis, hyperkalaemia and cardiac arrhythmias, which, ifuntreated, can be fatal. Animals with known or suspected malignant hyperthermia mutation, suchas those with a previous adverse anaesthetic event (for example, unexplained hyperthermia,increased muscle tone during anaesthesia or sudden increase in end-tidal carbon dioxide) or

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where siblings or parents have had previous anaesthetic problems or an unexplained anaestheticdeath, may be at risk from malignant hyperthermia and TIVA would be preferred in these patients(Brunson and Hogan, 2004; Table 1).

PIVA

An alternative to TIVA, where no inhalational agents are used, would be partial intravenousanaesthesia (PIVA), where a low dose of an inhalational agent is used. The concept ofincorporating a number of different drugs to provide “balanced anaesthesia” has been around for along time and enables administration of much lower concentrations of inhalational anaesthetics,thereby reducing detrimental side effects (Duke, 2013). Examples of this technique would beseverely painful animals, where a combination of analgesics may be required to control pain, andcritically ill animals, where the haemodynamic alterations from inhalational agents may not be welltolerated.

Ideal TIVA agent

IV anaesthetic agents are administered by continuous infusion, either at a constant rate or varieddepending on the clinical signs of the animal. Desirable properties of TIVA drugs include:

• rapid onset of action and smooth induction;

• short duration of action;

• rapid metabolism;

• no active metabolites;

• rapid clearance from the body so accumulation does not occur;

• smooth, excitement-free recovery;

• little or no effect on cardiovascular parameters; and

• provides unconsciousness, muscle relaxation and analgesia.

Unfortunately, no agents fulfil all these criteria; therefore, a combination of agents is often used toprovide the best conditions for anaesthesia.

Drugs used for TIVA/ PIVA techniques

Propofol

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Propofol can be used for both induction and maintenance of general anaesthesia. It is short actingand rapidly metabolised, making it suitable for IV infusion. Recoveries in dogs are reported to besmooth (Suarez et al, 2012) and relatively short (Musk and Flaherty, 2007). Infusions are notrecommended in cats; they have been shown to cause Heinz body anaemia (Andress et al, 1995)and can lead to prolonged recoveries, after only 30 minutes of infusion (Pascoe et al, 2006). Slowrecoveries are thought to be because propofol is largely metabolised in the liver by glucuronidationand cats have a poor ability to metabolise compounds this way (Pascoe et al, 2006).

Propofol reduces systemic vascular resistance and can lead to low blood pressure via reduction ofthe normal baroreceptor-mediated tachycardia response to this (Claeys et al, 1988). High infusionrates may be needed to maintain anaesthesia for surgery as propofol has no analgesic effects.High rates may be associated with haemodynamic problems. The use of other agents, such asopioids, can reduce requirements for propofol (Muir et al, 2003; Beier et al, 2008) by providinganalgesia and therefore reducing cardiovascular side effects.

Alfaxalone

Alfaxalone is also suitable for induction and maintenance of anaesthesia, being short acting andrapidly metabolised. It is suitable for maintenance in cats as metabolism does not rely onglucuronidation and it does not produce prolonged recoveries (Vettorato, 2013). However,myoclonus and opisthotonus has been reported in cats recovering from alfaxalone anaesthesia(Schwartz et al, 2014). Cardiovascular stability is good, but in dogs hypoventilation or apnoea mayoccur at higher infusion rates necessitating manual or mechanical ventilation (Herbet et al, 2013).As with propofol, alfaxalone has no analgesic effect and use of other agents to decrease theamount used may help to reduce side effects.

Opioids

These drugs, particularly the mu agonists, are excellent analgesics and can reduce the amount ofanaesthetic agent needed to maintain anaesthesia, but they do not produce unconsciousness socannot be used as TIVA agents alone. Morphine, fentanyl and remifentanil have all been shown toreduce requirements for anaesthetic agents and maintain cardiovascular stability in dogs (Muir etal, 2003; Beier et al, 2008; Covey-Crump and Murison, 2008). Methadone, a licensed mu agonist indogs and cats, can be substituted for morphine in TIVA protocols, but studies involving methadoneinfusions are lacking. Fentanyl – a short-acting, potent, mu agonist – is probably more suited tocontinuous infusion than the longer acting opioids, morphine or methadone, as there will be lessaccumulation over time.

The main side effects of opioid administration are bradycardia and respiratory depression(Dugdale, 2010). Propofol and remifentanil have been used concurrently without significantbradycardia in dogs (Musk and Flaherty, 2007; Beier et al, 2008). However, hypoventilation orapnoea has been reported (Kurum et al, 2013) and manual or mechanical ventilation may be

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required.

Alpha-2 adrenergic agonists

Alpha-2 adrenergic agonists provide sedation, analgesia and muscle relaxation, making themuseful additions to a balanced anaesthetic protocol. Concerns about the cardiovascular effects ofthese drugs may limit their use; they initially cause peripheral vasoconstriction, hypertension andbaroreceptor-mediated bradycardia, followed by a parasympathetic-mediated further reduction inheart rate (Sinclair, 2003).

The combined effects of increased systemic vascular resistance and bradycardia significantlyreduce cardiac output (Sinclair, 2003). Medetomidine and the active isomer dexmedetomidine haveboth been used in low-dose infusions to reduce isoflurane requirements without significantreduction in cardiac output or tissue perfusion in healthy dogs (Uilenreef et al, 2008; Rioja et al,2013). Recoveries when using alpha-2 agonist infusions were reported to be good (Uilenreef et al,2008; Rioja et al, 2013).

Lidocaine

Lidocaine is a sodium channel blocker primarily used for local anaesthesia and as an anti-arrhythmic. However, when given intravenously it causes a significant reduction in inhalationalanaesthetic requirements with minimal associated cardiovascular side effects in dogs (Muir et al,2003; Valverde et al, 2004; Gutierrez-Blanco et al, 2013). This anaesthetic sparing effect is thoughtto be due to central analgesic effects, the mechanisms of which are not totally understood. It is notrecommended for use in cats due to severe cardiovascular depression seen when used as aninfusion (Pypendop and Ilkiw, 2005).

Ketamine

Ketamine is an N-methyl D-aspartate (NMDA) receptor antagonist, which can be used to provideanalgesia, particularly for chronic pain. NMDA receptors are activated following prolonged noxiousstimulation and increase sensitivity to noxious stimuli, leading to central sensitisation (Dugdale,2010). Ketamine has been shown to reduce requirements for inhalational anaesthetic agents whenused alone and in combination with other agents including morphine, dexmedetomidine andlidocaine in dogs (Muir et al, 2003, Gutierrez-Blanco et al, 2013). It has also been used incombination with propofol to provide TIVA in dogs (Seliskar et al, 2007).

Administration

TIVA still requires the airway to be secured with an endotracheal tube and provision of oxygen viaa breathing system attached to an anaesthetic machine. An ability to provide ventilation, eithermanually (by “squeezing” the reservoir bag) or via a mechanical ventilator, is also required.

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The aforementioned drugs may be used in various combinations to provide a “balancedanaesthesia” of unconsciousness, analgesia and muscle relaxation. Dosages of more commonlyused IV agents are in Table 2, when combining drugs is sensible to use the lower end of the doseranges.

Syringe drivers (Figure 3) will provide more accurate administration of drugs. However, where theseare not available, drugs can be added to IV fluid bags and infused using a giving set. Table 3 givessome guidance on the doses needed to add to a 500ml bag of fluid for an infusion rate of 2ml/kg/hr. If increased fluid therapy is required it is advisable to attach a second drip line with plainfluids and administer them at the rate needed rather than increasing the rate of the fluid containingdrugs as this may lead to overdose.

• Some of the drugs mentioned in this article are not licensed for veterinary use. Diluting drugconcentrations with saline is also an unlicensed use of these drugs and cannot guarantee thecorrect concentration of drug is present throughout; therefore, informed owner consent should begained before use. These dose charts are just for guidance and vets should use their own clinicaljudgment when administering any veterinary medicines.

• This article was reviewed by Eva Rioja Garcia.

References

Andress J L et al (1995). The effects of consecutive day propofol anaesthesia on feline redblood cells, Veterinary Surgery 24(3): 277-282.Artru A A et al (1992). Electroencephalogram, cerebral metabolic and vascular responsesto propofol anaesthesia in dogs, Journal of Neurosurgical Anaesthesiology 4(2): 99-109.Beier S L et al (2008). Effect of remifentanil on requirements for propofol administered byuse of a target-controlled infusion system for maintaining anesthesia in dogs, AmericanJournal of Veterinary Research 70(6): 703-709.Brunson D B and Hogan K J (2004). Malignant hyperthermia: a syndrome not a disease, Veterinary Clinics of North America Small Animal Practice, 34(6): 1,419-1,433.Burm A G L (2003). Occupational hazards of inhalational anaesthetics, Best Practice andResearch Clinical Anaesthesiology 17(1): 147-161.Chui J et al (2014). Comparison of propofol and volatile agents for maintenance ofanaesthesia during elective craniotomy procedures: systematic review and meta-analysis, Canadian Journal of Anaesthesia, 61(4): 347-356.Claeys M A et al (1988). Haemodynamic changes during anaesthesia induced andmaintained with propofol, British Journal of Anaesthesia 60(1): 3-9.Covey-Crump G L and Murison P J (2008). Fentanyl or midazolam for co-induction ofanaesthesia with propofol in dogs, Veterinary Anaesthesia and Analgesia 35(6): 463-472.Dugdale A H A (2010). Pain. In Dugdale A H A (ed), Veterinary Anaesthesia Principles toPractice. Wiley-Blackwell, Chichester: 8-16.

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Duke T (2013). Partial intravenous anesthesia in cats and dogs, Canadian VeterinaryJournal 54(3): 276-282.Ferner R E et al (2014). The adverse effects of nitrous oxide, Adverse Drug ReactionBulletin 285: 1,099-1,102.Gutierrez-Blanco E et al (2013). Evaluation of the isoflurane-sparing effects of fentanyl,lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine during ovariohysterectomy in dogs, Veterinary Anaesthesia andAnalgesia 40(6): 599-609.Herbert G L et al (2013). Alfaxalone for total intravenous anaesthesia in dogs undergoingovariohysterectomy: a comparison of premedication with acepromazine ordexmedetomidine, Veterinary Anaesthesia and Analgesia 40(2): 124-133.Hopper K and Powell L L (2013). Basics of mechanical ventilation for dogs and cats, Veterinary Clinics of North America Small Animal Practice 43(4): 955-969.Irwin M G et al (2009). Occupational exposure to anaesthetic gases: a role for TIVA, ExpertOpinion in Drug Safety 8(4): 474-483.Kurum B et al (2013). Comparison of propofol-remifentanil and propofol-fentanylanaesthesia during ovariohysterectomy in dogs, Journal of the Faculty of VeterinaryMedicine Kafkas University 19(suppl A): A33-40.Lennon P F and Murray P A (1996). Attenuated hypoxic pulmonary vasoconstriction duringisoflurane anaesthesia is abolished by cyclooxygenase inhibition in chronicallyinstrumented dogs, Anesthesiology 84(2): 404-414.Muir W W et al (2003). Effects of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetised withisoflurane, American Journal of Veterinary Research 64(9): 1,155-1,160.Musk G C and Flaherty D A (2007). Target-controlled infusion of propofol combined withvariable rate infusion of remifentanil for anaesthesia of a dog with patent ductus arteriosus, Veterinary Anaesthesia and Analgesia 34(5): 359-364.Pascoe P J et al (2006). The effect of the duration of propofol administration on recoveryfrom anaesthesia in cats, Veterinary Anaesthesia and Analgesia 33(1): 2-7.Pypendop B H and Ilkiw J E (2005). Assessment of the hemodynamic effects of lidocaineadministered IV in isoflurane anaesthetised cats, American Journal of Veterinary Research 66(4): 661-668.Rioja E et al (2013). Clinical use of a low-dose medetomidine infusion in healthy dogsundergoing ovariohysterectomy, Canadian Veterinary Journal 54(9): 864-868.Schwartz A et al (2014). Minimum infusion rate of alfaxalone for total intravenousanaesthesia after sedation with acepromazine or medetomidine in cats undergoingovariohysterectomy, Veterinary Anaesthesia and Analgesia 41(5): 480-490doi:10.1111/vaa.12144.Seliskar A et al (2007). Total intravenous anaesthesia with propofol or propofol/ketamine inspontaneously breathing dogs premedicated with medetomidine, Veterinary Record 160(3):85-91.Sinclair M D (2003). A review of the physiological effects of alpha-2- agonists related to the

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clinical use of medetomidine in small animal practice, Canadian Veterinary Journal 44(11):885-897.Sneyd J R et al (1998). A meta-analysis of nausea and vomiting following maintenance ofanaesthesia with propofol or inhalational agents, European Journal of Anaesthesiology15(4): 433-445.Suarez M A et al (2012). Comparison of alfaxalone and propofol administered as totalintravenous anaesthesia for ovariohysterectomy in dogs, Veterinary Anaesthesia andAnalgesia 39(3): 236-244.Uilenreef J J et al (2008). Dexmedetomidine continuous rate infusion during isofluraneanaesthesia in canine surgical patients, Veterinary Anaesthesia and Analgesia 35(1): 1-12.Valverde A et al (2004). Effect of lidocaine on the minimum alveolar concentration ofisoflurane in dogs, Veterinary Anaesthesia and Analgesia, 31(4): 264-271.Vettorato E (2013). Prolonged intravenous infusion of alfaxalone in a cat, VeterinaryAnaesthesia and Analgesia 40(5): 551-552.Vieira E et al (1980). Effect of low concentrations of nitrous oxide on rat fetuses, Anaesthesia and Analgesia, 59(3): 175-177.Visoiu M et al (2014). Anaesthetic drugs and onset of malignant hyperthermia, Anaesthesiaand Analgesia 118(2): 388-396.

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Figure 1. Intracranial pressure-volume curve, showing increase in pressure as volume increases.

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Figure 2. Schematic diagram showing the mechanism of hypoxic pulmonary vasoconstriction. Lowalveolar partial pressure of oxygen (30mmHg) results in constriction of the adjacent pulmonaryarterioles, diverting pulmonary blood past alveoli with higher partial pressures of oxygen(100mmHg).

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Figure 3. Example of syringe driver for TIVA with propofol.

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Table 1. Advantages and disadvantages of TIVA

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Table 2. Drug dosages for infusion intra-operatively with syringe drivers

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Table 3. Volumes to add to 500ml bag of normal saline for infusion at 2ml/kg/hr

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