Maintenance of anaesthesia

General anaesthesia can be described as the reversible loss of conscious awareness and response to noxious stimuli. The maintenance phase follows induction and precedes emergence. Maintenance of anaesthesia is achieved with inhalational or intravenous anaesthetic agents. Considering that induction of anaesthesia can also be achieved with inhalational or intravenous agents, a transition from one to another may be necessary, most commonly from intravenous induction to inhalational maintenance.

Inhalational Anaesthetic Agents: inhalational anaesthetic agents are the most commonly used drugs for maintenance. Examples from modern practice include sevoflurane, isoflurane and desflurane, often given in combination with nitrous oxide. Table 1 highlights the most important physiochemical properties of inhalational agents.

The blood:gas partition coefficient is a measure of solubility in blood. It is directly linked to the rate of equilibration of alveolar with inspired concentrations of the agent. While this is a major determinant of anaesthesia onset and offset time, it also plays a role when depth of anaesthesia needs to be altered during maintenance.

The oil:gas partition coefficient is a measure of lipid solubility. It is an indicator of potency and is inversely related to the minimum alveolar concentration (MAC). The MAC is the alveolar concentration of an anaesthetic at equilibrium, at which 50% of the population will fail to respond to a surgical skin incision. Although anaesthesia is related to the partial pressure of an inhalational agent in the brain rather than its percentage concentration in alveoli, MAC can be measured and therefore is accepted as an index of potency. It also allows a single point (at 1 MAC) comparison between agents. Factors that affect MAC are described in Table 2.

During maintenance, inhalational agents are delivered in combination with a mixture of oxygen and air, or a mixture of oxygen and nitrous oxide. Nitrous oxide has declined in popularity, mainly because of its greenhouse gas effect. Nonetheless, it remains in clinical use because of several useful features. It has a MAC-sparing effect. It also has a ‘concentration effect’ and a ‘second gas effect’, which allow for faster onset of inhalational anaesthesia.

The use of ‘low-flow’ anaesthesia in a circle system reduces the requirement for both oxygen and inhalational anaesthetic agents. This is cost saving and reduces environmental pollution. During maintenance of anaesthesia, the inhalational agent uptake is largely constant because the patient's compartments can be regarded as saturated. Crucially, the aim is to keep the target concentration in the effect compartment (the brain) at a constant level. Oxygen consumption during anaesthesia corresponds to the patient's metabolic consumption. It can be assumed to be largely constant and estimated in ml/minute at 3.5 times the body weight. Continuous monitoring of the inspired oxygen concentration, as well as measuring the expiratory end-tidal anaesthetic agent concentration in the breathing system is mandatory. The anaesthetist controls the end-tidal concentration of anaesthetic agents by dialling the vaporizer and adjusting fresh gas flow. ‘End-tidal control’ is a gas delivery option in the newest anaesthesia machines that automatically adjusts the level of delivered agent. The anaesthetist sets target end-tidal oxygen concentration, minimum flow rate and end-tidal anaesthetic concentration. The system applies a proprietary algorithm to automatically adjust fresh gas flow and anaesthetic concentration to ensure that the patient's uptake of oxygen and inhalational agent is maintained at the correct level.

Intravenous anaesthetic agents Maintenance of anaesthesia solely by intravenous anaesthetic agents is called total intravenous anaesthesia (TIVA). Agents used for TIVA can be any combination of hypnotics with or without analgesics, all with short context-sensitive half-time (CSHT). CSHT is the time taken for the drug concentration to reduce by half once an infusion designed to maintain a constant plasma concentration is stopped. The most commonly used drug is propofol (alone or in conjunction with remifentanil or dexmedetomidine), due to fast onset and offset times. Remifentanil is an ultra-short-acting mu-type-opioid receptor agonist. It is considered relatively context-insensitive as it has the unique property of allowing prolonged infusions without drug accumulation. Dexmedetomidine has recently gained popularity for use during TIVA. It acts as an agonist at the α2 adrenoreceptors and reduces hypnotic and opioid requirements. Dexmedetomidine is associated with minimal respiratory depression. Following a loading dose of 1 microgram/kg over 10 minutes, the maintenance infusion is generally initiated at 0.6 micrograms/kg/hour and titrated to achieve desired clinical effect with doses ranging from 0.2 micrograms/kg/hour to 1 microgram/kg/hour.

After an intravenous bolus, the plasma concentration of a typical drug follows an exponential decline in three distinct phases, giving a ‘three-compartment model’. The drug is distributed between the central compartment and two compartments which equilibrate rapidly (muscle) and slowly (fatty tissue). Theoretically, when the compartments reach steady-state concentration, the infusion rate should match elimination only.

Drug infusions for TIVA may be given either manually (input ml/hour by anaesthetist) or using a target-controlled infusion (TCI). Manual infusion regimes are prone to error, a fact that was highlighted in the fifth National Audit Project Report (NAP5). Traditionally, the manual infusion regimen for propofol was calculated using the Roberts method: a 1.5 mg/kg loading dose was followed by an infusion of 10 mg/kg/hour reduced to 8 mg/kg/hour and 6 mg/kg/hour every 10 minutes. A modern alternative is a programmed TCI syringe driver that solves complex equations of the distribution of drug between compartments in an algorithm that calculates the rate of infusion. Examples include the Marsh and Schnider models, and others (Table 3). They calculate the bolus dose and speed of the subsequent infusion required to maintain the targeted plasma drug concentration (Cpt) or targeted effect site concentration (Cet). Plasma concentrations of propofol required to produce loss of consciousness are between 4 micrograms/ml and 8 micrograms/ml. Adequate analgesia with remifentanil is achieved with 3–8 ng/ml but it may require doubling for stimulating procedures. Propofol and remifentanil used in combination tend to show synergism therefore target concentrations need to be adjusted and titrated to the clinical effect.

At present, in clinical practice, there is no method available for measuring real time plasma drug concentrations during TIVA akin to the end tidal volatile agent concentration during inhalational. All target concentrations are calculated, not measured. Contemporary TCI pumps maintain three superimposed infusions, one at a constant rate to replace drug elimination and two exponentially decreasing infusions to replace drug removed from the central compartment to peripheral compartments of distribution.

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