Current anesthesia practice in veterinary medicine generally includes use of inhalation anesthesia drugs (isoflurane, sevoflurane, desflurane) to maintain the anesthesia state. These drugs are called “complete anesthetics” in that they produce all the criteria defined as general anesthesia. These criteria are sedation, analgesia, muscle relaxation, and autonomic stability. While inhalant drugs meet all criteria, it is well recognized that they do not meet all criteria equally well. For example, it has been noted that sedation and muscle relaxation may be excellent, but analgesia incomplete. Increasing the dose of an inhalant drug to meet all criteria may expose the patient to additional risk associated with side effects of that drug. For example, it is well known that increasing inhalation concentration results in further physiologic destabilization characterized by myocardial depression, vasodilation, hypotension, and depressed control of breathing.

Recognizing the most challenging anesthesia criterion to achieve is analgesia, recent practice trends have been to reduce inhalation agent level to minimize cardiorespiratory depression and provide additional analgesia with parenterally administered drugs known for their strong analgesic qualities (opioids, ketamine, alpha-2 agonists). Analgesic drugs may be administered as a single dose or intravenously delivered as a constant rate infusion (CRI) following an intravenous “loading” dose. CRI use has been well described in the literature and is frequently incorporated into anesthesia protocols. Adding supplemental analgesia to inhalation anesthesia results in better quality of pain control and improves safety by reducing inhalation drug dose. Supplemental drug administration by intravenous route in addition to inhalation anesthesia has several terms including balanced anesthesia and partial intravenous anesthesia (PIVA).

What Is Total Intravenous Anesthesia (TIVA)?

The practice of creating and maintaining general anesthesia by administration of intravenous drugs is referred to as total intravenous anesthesia (TIVA). Although TIVA is a recent clinical trend, it is not a new concept. The first documented TIVA report was in the dog in 1656. A combination of opium and spirits was administered to produce anesthesia. Further research languished until the commercial release of propofol when it was reported that an intravenous combination of propofol and opioid produced general anesthesia in dogs and humans.

Conceptually, it is easy to understand TIVA in that anesthesia criteria are fulfilled by administration of a drug combination instead of using a single drug [isoflurane, sevoflurane, desflurane] (Table 1). By simultaneously administering several drugs, each with a specific anesthesia characteristic, the sum of administered drugs, rather than the action of an individual drug, produces general anesthesia. Drug interaction is important in that the aggregate effects of infused drugs need to be complementary. Synergism, where the combined effect of drugs is greater than expected, is an important strategic goal in formulating TIVA protocols.

TIVA is currently not mainstream in small animal practice due to perceived complexity and inefficiency based on setup time, equipment required, and math skills. With training and experience, these objections can be easily overcome.

Table 1. TIVA drugs: principal characteristics

TIVA Concepts and Application

In order to plan a TIVA protocol, one must understand the primary characteristics of selected drugs and ensure their composite effect fulfills all criteria for general anesthesia. Drugs which work well in TIVA are those which achieve a rapid therapeutic plasma concentration, have a predictable in vivo behavior (PK-PD) and are rapidly metabolized in a consistent fashion so that in vivo accumulation does not occur.

Practical application requires one to understand that at the beginning of anesthesia, plasma concentration of the selected drug is zero. To establish a therapeutic drug concentration, a “loading” or “bolus” dose of the drug must be intravenously administered. The purpose of administering a loading dose is to immediately establish a clinically effective plasma concentration of the drug (drug dose), which is then sustained by CRI to achieve a drug “steady state.” While this seems simple in principle, it can be challenging to achieve because compartmental redistribution, biotransformation and clearance of a drug begin immediately following administration. The goal is to best “match” delivery rate with compartmental redistribution, biotransformation, and clearance in order to achieve a “steady state” plasma concentration for the duration of anesthesia. This is a dynamic process during the early anesthesia period until the “sweet spot” where infusion rate produces a consistent response is achieved.

In human medicine, common TIVA techniques include a sedative-hypnotic drug (usually propofol) in combination with a potent analgesic drug (alfentanil, remifentanil). This combination produces sedation, analgesia, and muscle relaxation consistent with general anesthesia. Similar strategies may be adopted in companion animal medicine. Drugs which meet these criteria and are currently used for TIVA are listed in Table 1.

Delivery Systems

In order to deliver drugs at a constant rate, dedicated delivery devices are required. A dedicated vascular access point for TIVA drug administration must be established. A short tubing length can be interfaced from the vascular access point to a multichannel infusion manifold or multiple “piggyback” access points. Individual drug “channels” are developed by drawing the desired drug quantity into an appropriate-size syringe and connecting it via small-bore, low-volume infusion tubing to a manifold connection or piggyback site. The drug syringe is then placed in a motorized syringe pump, which is programmed to deliver the drug at a calculated infusion rate. New-generation syringe pumps are programmed to automate the required calculations by selecting TIVA mode on their control panel. This is convenient, but not required, as manual calculation based on weight and drug infusion rate per time unit is easily performed. If syringe pumps are not available, the calculated drug dose can be mixed into fluid and infused using a standard intravenous fluid pump or gravity dripped using a drip controller device. These options are not as accurate as syringe pump delivery nor as flexible when dose adjustment is required.

Monitoring

Patient monitoring during TIVA applies the same principles and equipment used for inhalation anesthesia. Physical monitoring including reflex integrity, muscle tone, eye position, and absence of pain is identical to other general anesthesia monitoring protocols. Eye position is generally ventromedial in dogs with a prominent third eyelid visible. In cats, eye position may be either ventromedial or central. In either species, ocular reflexes noted by palpebral and eyelash brush reflexes are very sluggish or absent. Ear “flick” reflex may be present in cats. Jaw tone is generally present and is slight or moderate in opening resistance based on the characteristics of the administered TIVA drugs. Skeletal muscle on the front and hind legs should have limited “tone” and be relaxed.

It is prudent that the anesthetist understand the physiologic characteristics of drugs selected for TIVA use. This point is no different than understanding in vivo characteristics of isoflurane or sevoflurane. Core physiologic values for heart rate (HR), blood pressure (BP), pulse oximetry (SaO₂) and end-tidal carbon dioxide (ETCO₂) trend similarly to inhalant anesthesia protocols. TIVA drugs do not generally create the degree of hypotension noted with inhalant anesthetic drugs; thus, blood pressure parameters may be higher compared to isoflurane or sevoflurane. Opioids are hemodynamically neutral but may cause respiratory depression. Propofol loading dose can cause a transient drop in blood pressure values and respiratory depression. Slow injection speed for initial loading dose will minimize this effect. Ketamine may cause increased heart rate and respiratory depression following administration. Dexmedetomidine may cause slowing of heart rate.

Central and peripheral nervous systems are monitored by evaluating level of consciousness (LOC) coupled with the above-described reflexes. In addition, deep pain challenge should be performed to determine if the CRI infusion rate is satisfactory for blocking somatic and visceral pain. If neuromuscular blocking drugs are used, the level of neuromuscular blockade may be evaluated using commercially available peripheral nerve stimulators.

Advantages of TIVA vs. Inhalation Anesthesia

Several advantages have been reported in human medicine when TIVA is compared to inhalation anesthesia. TIVA is mainstreamed in neuroanesthesia due to better preservation of neurophysiology and central vascular reflexes compared to inhalation anesthesia. TIVA has demonstrated better recovery quality compared to inhalant anesthesia due to decreased emergence agitation/dysphoria. Less postoperative nausea and vomiting is noted in patients recovering from TIVA compared to inhalation anesthesia. Multicenter studies have shown a reduced postoperative pain medication requirement in TIVA patients compared to inhalation anesthesia.

Environmental pollution and operating room personnel exposure risk from inhalation anesthesia are reduced to zero when TIVA is used. Isoflurane, sevoflurane, and desflurane are chemically classified as substituted halogenated hydrocarbons (CFCs). Chemical analogues include industrial cooling agents (Freon). TIVA reduces exposure to these chemicals which are environmentally harmful and potentially dangerous to personnel in proximity to their administration. By reducing patient, veterinary personnel and environmental exposure, anesthesia is successfully administered with a “greener” outcome.

Disadvantages of TIVA vs. Inhalation Anesthesia

Potential disadvantages of TIVA are personnel training and patient response to parenteral vs. inhalation agents. Equipment setup and perceived complexity may be an initial barrier; however, once embraced, setup time is not significantly different from inhalant anesthesia. TIVA does require a comfort level with math calculations that are required for accurate drug delivery. This is slightly more challenging compared to adjusting a vaporizer setting; however, in principle, it is the same concept. Familiarity with delivery devices, such as syringe pumps, and a comfort level operating these devices are essential. Disposable equipment (intravenous tubing, 3-way valves, vascular manifold) used to deliver TIVA is an additional inventory expense. Additional required supplies, equipment, drugs, and monitors are the same as inhalation anesthesia. The anesthesia machine and breathing circuit is still used for oxygen delivery, carbon dioxide removal, and breathing support during TIVA administration.

TIVA Use in ECC Medicine

TIVA can be useful in ECC patient care. Diagnostic imaging is a natural “fit” because the procedures are short duration and minimally painful. TIVA is an excellent option for CT scans due to the procedure’s short duration and emphasis on sedation and immobility. Similar goals make TIVA an excellent choice for MRI evaluation. TIVA is especially suited for MRI in that supplies are non-ferrous materials and do not pose a hazard under magnetic influence. MRI-compatible infusion pumps are commercially available, making the anesthesia delivery system safe in magnetic fields. TIVA can also be used for ultrasound-guided biopsy of internal organs.

Sedation for emergency procedures is also amenable to TIVA. TIVA is an effective management strategy for severe, refractory status epilepticus patients where anesthesia is the best option for seizure control. Rapid induction using propofol followed by a benzodiazepine and propofol TIVA protocol can effectively manage refractory cases. A similar strategy may be elected to control seizures associated with neuroexcitatory toxins during the decontamination period. When TIVA is used for an extended time period, drug “tolerance” (tachyphylaxis) does occur due to microsomal enzyme induction associated with constant drug exposure. For this reason, it is important that constant monitoring for drug response and patient stability occur during the TIVA period.

TIVA is an excellent option for short-duration anesthesia in emergent patients with incomplete health evaluation. Procedures in which TIVA may be valuable include wound debridement, laceration repair, fracture reduction, splint/bandage application, gastric decompression, and relief of urinary obstruction. TIVA is an excellent option in these cases because it permits the operator to maintain the patient at a consistent sedation/anesthesia level, thereby facilitating time efficiency in task completion. This results in a better quality of sedation/anesthesia with a lower total delivered drug dose compared to intermittent “bolus” doses. This strategy improves patient safety and reduces recovery time.

TIVA is currently used for ventilator patient management. Sedation protocols for ventilator management use TIVA principles with emphasis on sedation and analgesia to achieve artificial airway tolerance and prevent ventilator-patient dyssynchrony during the support period. Agents and protocols used in ventilator management are identical to other TIVA indications.

Table 2. TIVA drug doses

Table 3. Examples of TIVA protocols

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