Vet Times The website for the veterinary profession https://www.vettimes.co.uk 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 intravenous anaesthesia, looking at the advantages compared with inhalational methods, such as reduced occupational hazards Summary Inhalational agents are the mainstay of veterinary anaesthetic maintenance. In the medical field there has been interest in total intravenous anaesthesia (TIVA), where intravenous agents provide the three main aspects of surgical anaesthesia: unconsciousness, muscle relaxation and analgesia. This article reviews the advantages of TIVA compared with inhalational anaesthesia in small animals, including reducing occupational hazards associated with chronic exposure to inhalational agents. The benefits of TIVA for airway procedures, neuroanaesthesia, in patients requiring mechanical ventilation and in those with a known or suspected mutation for malignant hyperthermia, are discussed. In addition, commonly available anaesthetic, sedative and analgesia drugs 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 has been much interest in total intravenous anaesthesia (TIVA), where IV agents provide the 1 / 15
three main aspects of surgical anaesthesia: unconsciousness, muscle relaxation and analgesia. 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 is released into the atmosphere, potentially contributing to global warming (Irwin et al, 2009). The halogenated chlorofluorocarbons, including halothane, isoflurane and sevoflurane, are thought to be potentially damaging to the ozone layer (Irwin et al, 2009). There are also health concerns about the effects of chronic exposure to these agents in hospital staff. Nitrous oxide may be linked to bone marrow disorders via reduction in vitamin B12 levels (Ferner et al, 2014) and is thought to be teratogenic. Experimentally in rats, it caused increased rates of spontaneous abortion and congenital 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 still controversy in the literature. Most studies finding a link between exposure to anaesthetic agents and health problems have been retrospective questionnaire-based studies (Burm, 2003). These studies have been criticised for bias and lack of control of many potential confounding factors in hospital 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 to the potential risk, it would be best practice to minimise or eliminate occupational exposure. Times when 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, prep room to operating theatre and in recovery, where patients are exhaling anaesthetic gases directly into the surrounding area. The use of TIVA would eliminate these potential risks from the work environment. Another advantage of TIVA is a reduction in postoperative nausea and vomiting. It has been shown in human literature that induction and maintenance of anaesthesia with propofol is associated with significantly 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 contributing to inappetence or anorexia sometimes seen after general anaesthesia. Procedures involving the airway, such as bronchoscopy, laryngeal and pharyngeal surgery, pose particular challenges for anaesthetic maintenance. Difficulties and interruptions in access to the airway for delivery of inhalational agents lead to fluctuations in the plane of anaesthesia and potential for exposure of staff to these agents during the procedure. TIVA would allow for a more stable plane of anaesthesia throughout. 2 / 15
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 in intracranial pressure. The skull is a fixed volume containing brain tissue, cerebrospinal fluid and blood. An increase in the volume of one component will firstly cause a reduction in volume of the others. Once no further compensation can be achieved, intracranial pressure will rise, eventually leading to brain herniation (Figure 1). Animals presenting with space occupying brain lesions or inflammatory brain disease are at risk of raised intracranial pressure. All halogenated agents cause dose-dependent vasodilation, which increases the volume of blood in the skull, potentially leading to an increase in intracranial pressure in high-risk patients. Also, cerebral blood flow is normally controlled by cerebral metabolic rate; a reduction in cerebral metabolic rate will lead to a reduction in cerebral blood flow. While halogenated inhalant anaesthetics will reduce cerebral metabolic rate, they alter this autoregulation and cerebral blood flow does not reduce as expected and may actually increase, further compounding increases in intracranial pressure. Propofol has been shown to maintain cere bral blood flow autoregulation, reduce cerebral metabolic rate and reduce intracranial pressure (Artru et al, 1992). TIVA protocols with propofol are widely used in medical neuroanaesthesia (Chui et al, 2014). Alfaxalone may be an alternative to propofol, but studies into its use are lacking. Patients in the intensive care unit receiving mechanical ventilation or patients with pre-existing pulmonary disease may also benefit from TIVA. A number of indications for mechanical ventilation in small animals include severe hypoxaemia despite oxygen therapy, severe hypoventilation and excessive work of breathing (Hopper and Powell, 2013). Animals with severe hypoventilation, and where 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 regulatory mechanism that occurs when low partial pressure of oxygen detected in the alveoli results in constriction of the adjacent pulmonary arterioles. The aim is to divert blood away from poorly ventilated 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 vasodilatory effects can also contribute to hypotension in already compromised patients and therefore these agents are not recommended during long-term mechanical ventilation, requiring the use of injectable sedative and anaesthetic drugs. Halogenated inhalational agents, including isoflurane and sevoflurane, can trigger malignant hyperthermia (Visoiu et al, 2014). Malignant hyperthermia is an inherited channelopathy that leads to hypercapnia, hyperthermia, metabolic acidosis, hyperkalaemia and cardiac arrhythmias, which, if untreated, can be fatal. Animals with known or suspected malignant hyperthermia mutation, such as 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 3 / 15
where siblings or parents have had previous anaesthetic problems or an unexplained anaesthetic death, 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 intravenous anaesthesia (PIVA), where a low dose of an inhalational agent is used. The concept of incorporating a number of different drugs to provide balanced anaesthesia has been around for a long time and enables administration of much lower concentrations of inhalational anaesthetics, thereby reducing detrimental side effects (Duke, 2013). Examples of this technique would be severely painful animals, where a combination of analgesics may be required to control pain, and critically ill animals, where the haemodynamic alterations from inhalational agents may not be well tolerated. Ideal TIVA agent IV anaesthetic agents are administered by continuous infusion, either at a constant rate or varied depending 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 to provide the best conditions for anaesthesia. Drugs used for TIVA/ PIVA techniques Propofol 4 / 15
Propofol can be used for both induction and maintenance of general anaesthesia. It is short acting and rapidly metabolised, making it suitable for IV infusion. Recoveries in dogs are reported to be smooth (Suarez et al, 2012) and relatively short (Musk and Flaherty, 2007). Infusions are not recommended 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). Slow recoveries are thought to be because propofol is largely metabolised in the liver by glucuronidation and 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 of the normal baroreceptor-mediated tachycardia response to this (Claeys et al, 1988). High infusion rates 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 as opioids, can reduce requirements for propofol (Muir et al, 2003; Beier et al, 2008) by providing analgesia and therefore reducing cardiovascular side effects. Alfaxalone Alfaxalone is also suitable for induction and maintenance of anaesthesia, being short acting and rapidly metabolised. It is suitable for maintenance in cats as metabolism does not rely on glucuronidation 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 may occur 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 the amount used may help to reduce side effects. Opioids These drugs, particularly the mu agonists, are excellent analgesics and can reduce the amount of anaesthetic agent needed to maintain anaesthesia, but they do not produce unconsciousness so cannot be used as TIVA agents alone. Morphine, fentanyl and remifentanil have all been shown to reduce requirements for anaesthetic agents and maintain cardiovascular stability in dogs (Muir et al, 2003; Beier et al, 2008; Covey-Crump and Murison, 2008). Methadone, a licensed mu agonist in dogs and cats, can be substituted for morphine in TIVA protocols, but studies involving methadone infusions are lacking. Fentanyl a short-acting, potent, mu agonist is probably more suited to continuous infusion than the longer acting opioids, morphine or methadone, as there will be less accumulation over time. The main side effects of opioid administration are bradycardia and respiratory depression (Dugdale, 2010). Propofol and remifentanil have been used concurrently without significant bradycardia in dogs (Musk and Flaherty, 2007; Beier et al, 2008). However, hypoventilation or apnoea has been reported (Kurum et al, 2013) and manual or mechanical ventilation may be 5 / 15
required. Alpha-2 adrenergic agonists Alpha-2 adrenergic agonists provide sedation, analgesia and muscle relaxation, making them useful additions to a balanced anaesthetic protocol. Concerns about the cardiovascular effects of these drugs may limit their use; they initially cause peripheral vasoconstriction, hypertension and baroreceptor-mediated bradycardia, followed by a parasympathetic-mediated further reduction in heart rate (Sinclair, 2003). The combined effects of increased systemic vascular resistance and bradycardia significantly reduce cardiac output (Sinclair, 2003). Medetomidine and the active isomer dexmedetomidine have both been used in low-dose infusions to reduce isoflurane requirements without significant reduction 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 antiarrhythmic. However, when given intravenously it causes a significant reduction in inhalational anaesthetic 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 thought to be due to central analgesic effects, the mechanisms of which are not totally understood. It is not recommended for use in cats due to severe cardiovascular depression seen when used as an infusion (Pypendop and Ilkiw, 2005). Ketamine Ketamine is an N-methyl D-aspartate (NMDA) receptor antagonist, which can be used to provide analgesia, particularly for chronic pain. NMDA receptors are activated following prolonged noxious stimulation and increase sensitivity to noxious stimuli, leading to central sensitisation (Dugdale, 2010). Ketamine has been shown to reduce requirements for inhalational anaesthetic agents when used alone and in combination with other agents including morphine, dexmedetomidine and lidocaine in dogs (Muir et al, 2003, Gutierrez-Blanco et al, 2013). It has also been used in combination 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 via a breathing system attached to an anaesthetic machine. An ability to provide ventilation, either manually (by squeezing the reservoir bag) or via a mechanical ventilator, is also required. 6 / 15
The aforementioned drugs may be used in various combinations to provide a balanced anaesthesia of unconsciousness, analgesia and muscle relaxation. Dosages of more commonly used IV agents are in Table 2, when combining drugs is sensible to use the lower end of the dose ranges. Syringe drivers (Figure 3) will provide more accurate administration of drugs. However, where these are not available, drugs can be added to IV fluid bags and infused using a giving set. Table 3 gives some 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 plain fluids and administer them at the rate needed rather than increasing the rate of the fluid containing drugs as this may lead to overdose. Some of the drugs mentioned in this article are not licensed for veterinary use. Diluting drug concentrations with saline is also an unlicensed use of these drugs and cannot guarantee the correct concentration of drug is present throughout; therefore, informed owner consent should be gained before use. These dose charts are just for guidance and vets should use their own clinical judgment 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 red blood cells, Veterinary Surgery 24(3): 277-282. Artru A A et al (1992). Electroencephalogram, cerebral metabolic and vascular responses to 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 by use of a target-controlled infusion system for maintaining anesthesia in dogs, American Journal 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 and Research Clinical Anaesthesiology 17(1): 147-161. Chui J et al (2014). Comparison of propofol and volatile agents for maintenance of anaesthesia 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 and maintained 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 of anaesthesia 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 to Practice. Wiley-Blackwell, Chichester: 8-16. 7 / 15
Duke T (2013). Partial intravenous anesthesia in cats and dogs, Canadian Veterinary Journal 54(3): 276-282. Ferner R E et al (2014). The adverse effects of nitrous oxide, Adverse Drug Reaction Bulletin 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-ketaminedexmedetomidine during ovariohysterectomy in dogs, Veterinary Anaesthesia and Analgesia 40(6): 599-609. Herbert G L et al (2013). Alfaxalone for total intravenous anaesthesia in dogs undergoing ovariohysterectomy: a comparison of premedication with acepromazine or dexmedetomidine, 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, Expert Opinion in Drug Safety 8(4): 474-483. Kurum B et al (2013). Comparison of propofol-remifentanil and propofol-fentanyl anaesthesia during ovariohysterectomy in dogs, Journal of the Faculty of Veterinary Medicine Kafkas University 19(suppl A): A33-40. Lennon P F and Murray P A (1996). Attenuated hypoxic pulmonary vasoconstriction during isoflurane anaesthesia is abolished by cyclooxygenase inhibition in chronically instrumented dogs, Anesthesiology 84(2): 404-414. Muir W W et al (2003). Effects of morphine, lidocaine, ketamine, and morphine-lidocaineketamine drug combination on minimum alveolar concentration in dogs anesthetised with isoflurane, 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 with variable 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 recovery from 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 lidocaine administered 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 dogs undergoing ovariohysterectomy, Canadian Veterinary Journal 54(9): 864-868. Schwartz A et al (2014). Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy, Veterinary Anaesthesia and Analgesia 41(5): 480-490 doi:10.1111/vaa.12144. Seliskar A et al (2007). Total intravenous anaesthesia with propofol or propofol/ketamine in spontaneously 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 8 / 15
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 of anaesthesia with propofol or inhalational agents, European Journal of Anaesthesiology 15(4): 433-445. Suarez M A et al (2012). Comparison of alfaxalone and propofol administered as total intravenous anaesthesia for ovariohysterectomy in dogs, Veterinary Anaesthesia and Analgesia 39(3): 236-244. Uilenreef J J et al (2008). Dexmedetomidine continuous rate infusion during isoflurane anaesthesia 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 of isoflurane in dogs, Veterinary Anaesthesia and Analgesia, 31(4): 264-271. Vettorato E (2013). Prolonged intravenous infusion of alfaxalone in a cat, Veterinary Anaesthesia 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, Anaesthesia and Analgesia 118(2): 388-396. 9 / 15
Figure 1. Intracranial pressure-volume curve, showing increase in pressure as volume increases. 10 / 15
Figure 2. Schematic diagram showing the mechanism of hypoxic pulmonary vasoconstriction. Low alveolar partial pressure of oxygen (30mmHg) results in constriction of the adjacent pulmonary arterioles, diverting pulmonary blood past alveoli with higher partial pressures of oxygen (100mmHg). 11 / 15
Figure 3. Example of syringe driver for TIVA with propofol. 12 / 15
Table 1. Advantages and disadvantages of TIVA 13 / 15
Table 2. Drug dosages for infusion intra-operatively with syringe drivers 14 / 15
Table 3. Volumes to add to 500ml bag of normal saline for infusion at 2ml/kg/hr 15 / 15 Powered by TCPDF (www.tcpdf.org)