Total intravenous anaesthesia

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Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, [1] and the common anesthetic agent propofol was licensed in 1986. TIVA is currently employed in various procedures as an alternative technique of general anesthesia in order to improve post-operative recovery.

Contents

TIVA is maintained by intravenous infusion devices and assisted by electroencephalography (EEG) monitoring. These techniques facilitate the use of propofol, etomidate, ketamine, and other intravenous anesthetic agents. During or after TIVA, patients may be subjected to an elevated risk of anesthesia awareness, hyperalgesia and neurotoxicity. [2] Considering these risks, special consideration is given to obese, elderly and pediatric patients.[ citation needed ]

History

In the mid-19th century, specific equipment was developed to enable intravenous anesthesia. Francis Rynd developed the hollow needle in 1845, [1] and Charles Gabriel Pravaz developed the syringe in 1853, [1] which allowed drugs to be administered intravenously.

Using this new mode of delivery, many chemical compounds were tested as intravenous anesthetics. This was pioneered by Pierre-Cyprien Oré in 1872, who reported using chloral hydrate as an intravenous anesthetic. [1] However, these early trials were associated with high mortality. [1] Hedonal was later developed in 1909 for general anesthesia, although with limited success due to its long duration of effect. [3] These insufficiencies encouraged the development of paraldehyde by Noel & Souttar, [4] magnesium sulfate by Peck & Meltzer [5] as well as ethanol by Nakagawa [6] as intravenous anesthetic agents.

Propofol (di-isopropyl phenol) was synthesized by Glen and colleagues in the early 1970s, [7] but its first formulations were temporarily withdrawn due to a number of adverse reactions during clinical studies. [1] In 1983, a lipid emulsion formulation of propofol was available, which carried great potential during clinical trials. [8] It was licensed for use in Europe in 1986 and received FDA approval in the US in 1989. [1] Propofol is now used worldwide with a well-defined pharmacological profile for a variety of medical uses.

Medical uses

TIVA is used to induce general anesthesia while avoiding the disadvantages of volatile anesthesia (and traditional inhalation agents). [9] Intravenous anesthetic agents are titrated at safe doses to maintain stage III surgical anesthesia (unconsciousness, amnesia, immobility, and absence of response to noxious stimulation). [10] The use of TIVA is advantageous in cases where volatile anesthesia is of high risk or is impossible, such as cases involving morbidly obese patients. [11] [12] TIVA has also been used for anesthetic delivery at sites of trauma such as serious accidents, disasters and wars. [1]

The overall goals of TIVA include: [13]

Propofol-based TIVA significantly improves post-operative recovery profile and comfort, minimizes nausea and vomiting, facilitates rapid recovery, greater hemodynamic stability, preservation of hypoxic pulmonary vasoconstriction, reduction in intracerebral pressure, and reduces the risk of organ toxicity. [14] Despite these advantages, it accounts for a small proportion of general anesthetics due to the relatively expensive cost of preparation and maintenance. [15]

Techniques

Dosing considerations

The doses for intravenous sedative-hypnotic and adjuvant agents vary individually. Pharmacodynamic and pharmacokinetic factors need to be considered for each patient (e.g. patients with impaired kidney or liver function, blood abnormalities and myocardial dysfunction, etc.) [16] There are also risks of adverse effects related to doses such as hypotension and respiratory depression. [17] In terms of adjuvant agents, the co-administration of anesthetic drugs from different classes often produce synergistic hypnotic effects. [18] [19] This is especially common for agents acting on gamma-aminobutyric acid (GABA) receptors that are combined with drugs acting on different types of receptors. [20] [21]

The drug interactions between sedative-hypnotic agents and adjuvant agents suggest that dosing regimens cannot be fixed. [19] Instead, dosing should be based on adjusted body weight or estimated lean body weight, especially for obese patients. It is recommended that drug doses be titrated in brief intervals (around 20 to 60 seconds). [22]

Equipment

The delivery of intravenous anesthetics is dependent on different types of infusion devices. Examples of infusion devices include smart pumps, syringe pumps and target-controlled infusion (TCI) devices. [23]

A smart pump used to deliver intravenous agents Infusion pump 2.jpg
A smart pump used to deliver intravenous agents

Smart pumps are commonly used to administer potent anesthetics and various vasoactive drugs such as vasopressors, inotropes, vasodilators, which need to be continuously titrated in the operating room. [24] Smart pumps are advantageous since they administer safe doses with a programmed infusion rate within pre-existing limits based on the institutional standardized medication library. [25]

Syringe pumps are smaller infusion pumps that allow the administration of small amounts of induction agents at a precise rate. [26] The accuracy of syringe pumps is dependent on the selection of syringes during pump programming. Most pumps are able to identify the size of the syringe automatically when the syringe manufacturer's name is input correctly. [27]

Target-controlled infusion (TCI) systems are assisted by computer systems that make use of pharmacokinetic and pharmacodynamic modelling to maintain a target concentration of anesthetic in the brain. [28] [29] TCI requires clinicians to input a target concentration for an anesthetic or other agents, and the computer will calculate the amount of agent required for the input concentration, then the infusion pump will be used to deliver the calculated bolus dose. [30] Subsequently, the computer continuously recalculates how much drug is in the system and influences the amount of drug required to maintain the desired concentration at the effect site. [31]

An EEG recording cap for monitoring awareness EEG Recording Cap.jpg
An EEG recording cap for monitoring awareness

Maintenance

During TIVA, the continuous assessment of heart rate, blood pressure, and state of consciousness is essential when titrating anesthetic agents. [20] [23] Processed electroencephalogram (EEG) monitoring is used to assess anesthetic depth. [32] However, there are 30 seconds of lag time between the subject's state of consciousness and the processed EEG signal. This limits its usefulness during the induction of anesthesia. [20] [21]

Intravenous agents

Propofol, etomidate and ketamine are common intravenous sedative-hypnotic agents for the induction of TIVA. [19] Their highly lipophilic nature allows the rapid onset of anesthesia upon intravenous injection. [17] It also enables penetration through the blood–brain barrier and effective perfusion to the brain. However, the rapid redistribution of these agents from the brain to other muscle and fat tissues causes it to have a short duration of action. Adjuvant agents are typically administered in addition to sedative-hypnotic agents to supplement the induction of TIVA. [17]

Sedative-hypnotic agents

Propofol

Propofol is usually the selected sedative-hypnotic agent to maintain general anesthesia through TIVA because of its rapid onset and offset, beneficial properties and few adverse effects. [33] Its rapid onset of action is due to its high lipid-solubility, rapid redistribution from the brain to other parts of the body, and rapid clearance (20 to 30 mL/kg/minute). [33] Most propofol is conjugated in the liver with pharmacologically inactive metabolites. [33] Although it has a long terminal elimination half-life of 4 to 30 hours, plasma concentrations remain low after the typical induction dose. [33]

Its advantages include “antiemetic, antipruritic, bronchodilatory, and anticonvulsant properties”, [34] which makes it suitable for patients with kidney or liver insufficiency. [35] Potential adverse effects of propofol include hypotension and respiratory depression caused by inadequate dosing, pain on injection, and risk of contamination. [36]

Etomidate

Etomidate is suitable for patients with hemodynamic instability since it does not compromise blood pressure, cardiac output, or heart rate. [37] [38] Its advantages include anticonvulsant properties and hemodynamic stability.  Potential adverse effects include a higher incidence of postoperative nausea and vomiting, transient acute adrenal insufficiency, pain during injection, involuntary myoclonic movements, absence of analgesic effects and mild increases in airway resistance. [37] [39]

Ketamine

Ketamine is suitable for hypotensive patients, or patients with risks of developing hypotension (e.g. those who have hypovolemia, hemorrhage, sepsis or severe cardiovascular compromise). [40] [41] This is because ketamine is associated with increased blood pressure, heart rate and cardiac output. [42] Its advantages include profound analgesic properties, bronchodilation, and the ability to maintain airway reflexes and respiratory drive. [43] It could also be induced via the intramuscular route if TIVA access gets lost. However, its potential adverse effects impact cardiovascular and neurological functions.

Potential adverse effects on cardiovascular activities are listed below: [44]

Potential adverse effects on neurological activities are listed below: [44]

Adjuvant agents

Opioid, lidocaine and midazolam are adjuvant agents frequently administered to minimize pain during the injection of the induction agents. [45] [46] They are also used to lessen the sympathetic stress response, cough reflex during laryngoscopy or intubation, and supplement sedation by synergistic effects. [47] [48] The dose of sedative-hypnotic agents should be reduced due to the synergistic effects when combined with adjuvant agents. [48]

Choice of specific adjuvant agents is dependent upon the patient and procedure-specific factors. [49] Opioid is a commonly administered adjuvant agent as the analgesic component of TIVA. However, when used with propofol, it might exacerbate the adverse hypotensive effects. [48] Other potential adverse effects include respiratory depression, bradycardia, delirium and potential for acute tolerance. [50]

Risks and complications

Accidental awareness during general anesthesia (AAGA)

Patients under TIVA have a higher risk of AAGA. Unlike inhaled anesthetic agents, intravenous agents do not have an indicative end-tidal anesthetic concentration (ETAC) for the monitoring of administered drugs, so the determination of successful delivery is usually left to the anesthetist's clinical judgment. [2]

The high incidence of AAGA with TIVA can be attributed to several factors. Firstly, the target concentration of anesthetic agents required to maintain unresponsiveness is not well understood. [2] Although there have been studies aiming to establish the target concentration of propofol, there is a high degree of variability with the established dosing range. [51] Secondly, intravenous delivery may be impaired by lax monitoring of the intravenous catheter and the insertion site. [2] Thirdly, the use of neuromuscular blockades is a risk factor of AAGA and also hinders communication of distress in the case of accidental awareness. [2]

Opioid-induced hyperalgesia

TIVA techniques which involve the continued administration of opioids (E.g. Remifentanil) at high doses can cause opioid-induced hyperalgesia. [52] This may lead to difficult postoperative pain control, as patients with hyperalgesia experience increased chronic pain and require more analgesics following surgery. [51]

Neurotoxicity

Prolonged anesthetic exposure can result in the death of neural cells and defective synaptogenesis, [53] caused by increased expression of neurologically harmful substances. [2] The resulting neurologic injuries may lead to a persistent subtle decline of cognitive abilities, especially in elderly or very young patients. [2] Animal studies suggest that propofol may have similar neurotoxic properties as it is associated with apoptotic degeneration of oligodendrocytes. [2]

Special populations

Obese patients

Obese patients present technical and physiological challenges to TIVA. Physical tasks such as surgical positioning, intravenous insertion and ventilation are complicated by excess fat. [54] Associated physiological and pharmacological changes include higher susceptibility to hypoxemia, decrease in resting metabolic rate and lower cardiac output per kg body weight. [55] The use of dosing models derived from non-obese patients is therefore unsuitable for obese patients. [56]

Even within the obese population, the large variability between individuals limits the accuracy of pharmacokinetic models in predicting and informing anesthetic titration. [54]

Pediatrics

Infants differ from adults in the consideration of pharmacokinetics, pharmacodynamics and side effects. [57] In terms of pharmacokinetics, protein binding, organ function and body composition are significantly different. [58] Pharmacodynamic effects such as the capacity of target organs to respond to drugs are also changed. [57] Based on this knowledge, doses are adjusted to achieve optimal clinical response and avoid toxicity in pediatric patients. [59] Generally, clearance (drug elimination from the body) is greater in children due to the nonlinear scaling between body size and function. [57]

Elderly patients

Aging is associated with an increase in fat and a reduction in lean body mass and total body water. [60] These factors increase the volume of distribution of lipid-soluble drugs, lower their plasma concentration and delay elimination. [61] Aged patients typically have a higher sensitivity to drug action due to a reduction in the initial drug clearance, resulting in higher plasma concentration and hence greater initial drug effect. [61]

Related Research Articles

General anaesthetics are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompass multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

<span class="mw-page-title-main">Ketamine</span> Dissociative anesthetic and anti-depressant

Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a treatment for depression and pain management. It is a novel compound that was derived from phencyclidine in 1962 in pursuit of a safer anesthetic with fewer hallucinogenic effects.

<span class="mw-page-title-main">Sodium thiopental</span> Barbiturate general anesthetic

Sodium thiopental, also known as Sodium Pentothal, thiopental, thiopentone, or Trapanal, is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of pentobarbital, and an analog of thiobarbital. Sodium thiopental was a core medicine in the World Health Organization's List of Essential Medicines, but was supplanted by propofol. Despite this, thiopental is listed as an acceptable alternative to propofol, depending on local availability and cost of these agents. It was previously the first of three drugs administered during most lethal injections in the United States, but the US manufacturer Hospira stopped manufacturing the drug in 2011 and the European Union banned the export of the drug for this purpose. Although thiopental abuse carries a dependency risk, its recreational use is rare.

<span class="mw-page-title-main">Local anesthetic</span> Medications to reversibly block pain

A local anesthetic (LA) is a medication that causes absence of all sensation in a specific body part without loss of consciousness, as opposed to a general anesthetic, which eliminates all sensation in the entire body and causes unconsciousness. Local anesthetics are most commonly used to eliminate pain during or after surgery. When it is used on specific nerve pathways, paralysis also can be induced.

Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of such action, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which may include dissociation, a general decrease in sensory experience, hallucinations, dream-like states or anesthesia. Despite most dissociatives' main mechanism of action being tied to NMDA receptor antagonism, some of these substances, which are nonselective in action and affect the dopamine and/or opioid systems, may be capable of inducing more direct and repeatable euphoria or symptoms which are more akin to the effects of typical "hard drugs" or common drugs of abuse. This is likely why dissociatives are considered to be addictive with a fair to moderate potential for abuse, unlike psychedelics. Despite some dissociatives, such as phencyclidine (PCP) possessing stimulating properties, most dissociatives seem to have a general depressant effect and can produce sedation, respiratory depression, nausea, disorientation, analgesia, anesthesia, ataxia, cognitive and memory impairment as well as amnesia.

<span class="mw-page-title-main">General anaesthesia</span> Medically induced loss of consciousness

General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of consciousness that renders a patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an analgesic and neuromuscular blocking agent. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway. General anaesthesia is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an intensive care unit or emergency department to facilitate endotracheal intubation and mechanical ventilation in critically ill patients. Depending on the procedure, general anaesthesia may be optional or required. Regardless of whether a patient may prefer to be unconscious or not, certain pain stimuli could result in involuntary responses from the patient that may make an operation extremely difficult. Thus, for many procedures, general anaesthesia is required from a practical perspective.

<span class="mw-page-title-main">Propofol</span> Intravenous medication used in anesthesia

Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was originally approved under the brand name Diprivan. Numerous generic offerings of this formulation now exist. Intravenous administration is used to induce unconsciousness after which anesthesia may be maintained using a combination of medications. It is manufactured as part of a sterile injectable emulsion formulation using soybean oil and lecithin, giving it a white milky coloration.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Remifentanil</span> Synthetic opioid analgesic

Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

In anaesthesia and advanced airway management, rapid sequence induction (RSI) – also referred to as rapid sequence intubation or as rapid sequence induction and intubation (RSII) or as crash induction – is a special process for endotracheal intubation that is used where the patient is at a high risk of pulmonary aspiration. It differs from other techniques for inducing general anesthesia in that several extra precautions are taken to minimize the time between giving the induction drugs and securing the tube, during which period the patient's airway is essentially unprotected.

<span class="mw-page-title-main">Etomidate</span> Short-acting anaesthetic and sedative drug

Etomidate is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardioversion and electroconvulsive therapy. It was developed at Janssen Pharmaceutica in 1964 and was introduced as an intravenous agent in 1972 in Europe and in 1983 in the United States.

<span class="mw-page-title-main">Dexmedetomidine</span> Anxiolytic, sedative, and pain medication

Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation associated with schizophrenia or bipolar I or II disorder.

<span class="mw-page-title-main">Alfaxalone</span> Chemical compound

Alfaxalone, also known as alphaxalone or alphaxolone and sold under the brand name Alfaxan, is a neuroactive steroid and general anesthetic which is used currently in veterinary practice as an induction agent for anesthesia and as an injectable anesthetic. Though it is more expensive than other induction agents, it often preferred due to the lack of depressive effects on the cardiovascular system. The most common side effect seen in current veterinary practice is respiratory depression when Alfaxan is administered concurrently with other sedative and anesthetic drugs; when premedications aren't given, veterinary patients also become agitated and hypersensitive when waking up.

<span class="mw-page-title-main">Medetomidine</span> Chemical compound

Medetomidine is a synthetic drug used as both a surgical anesthetic and analgesic. It is often used as the hydrochloride salt, medetomidine hydrochloride, a crystalline white solid. It is an α2 adrenergic agonist that can be administered as an intravenous drug solution with sterile water.

Procedural sedation and analgesia (PSA) is a technique in which a sedating/dissociative medication is given, usually along with an analgesic medication, in order to perform non-surgical procedures on a patient. The overall goal is to induce a decreased level of consciousness while maintaining the patient's ability to breathe on their own. Airway protective reflexes are not compromised by this process and therefore endotracheal intubation is not required. PSA is commonly used in the emergency department, in addition to the operating room.

<span class="mw-page-title-main">Intravenous regional anesthesia</span>

Intravenous regional anesthesia (IVRA) or Bier's block anesthesia is an anesthetic technique on the body's extremities where a local anesthetic is injected intravenously and isolated from circulation in a target area. The technique usually involves exsanguination of the target region, which forces blood out of the extremity, followed by the application of pneumatic tourniquets to safely stop blood flow. The anesthetic agent is intravenously introduced into the limb and allowed to diffuse into the surrounding tissue while tourniquets retain the agent within the desired area.

Target-controlled infusion (TCI) automates the dosing of intravenous drugs during surgery. After the anesthetist sets the desired parameters in a computer and presses the start button, the system controls the infusion pump, while being monitored by the anesthetist. TCI is as safe and effective as manually controlled infusion.

<span class="mw-page-title-main">Balanced anesthesia</span> Anesthetic technique

Balanced anesthesia is an anesthetic method for surgical patients during their operation. The method was proposed by John Lundy in 1926. The purpose of balanced anesthesia is to use multiple anesthetic agents for a safer general anesthesia and to mitigate the potential adverse side effects which may be caused by the anesthetic agents. The concept of balanced anesthesia is that of applying two or more medications or techniques in order to ease pain, relax the muscles, and have autonomous reflexes suppressed in the patient. In other words, it is an anesthesia method to maintain stable vital signs. There are numerous factors that come into play when the anesthetist decides to use this method of anesthesia. These factors include, but are not limited to: patients' major organ functions, general condition and compensatory capacity. By making use of adequate types and appropriate amounts of agents and accurate anesthesia methods, the anesthetist will promote a successful, safe, and efficient surgery.

<span class="mw-page-title-main">Talmage Egan</span> American academic

Talmage D. Egan is an anesthesiologist, academic, entrepreneur, and author. He is a professor and chair in the department of anesthesiology, and an adjunct professor in the departments of pharmaceutics, bioengineering, and neurosurgery at the University of Utah School of Medicine.

<span class="mw-page-title-main">Ciprofol</span> Intravenous medication used in general anaesthesia

Ciprofol is a novel 2,6-disubstituted phenol derivative that is used for the intravenous induction of general anesthesia. A short-acting and highly selective γ-aminobutyric acid agonist, ciprofol is 4–6 times more potent than other phenol derivatives such as propofol or fospropofol.

References

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