Armin Holas. Department of Anaesthesiology and Critical Care, University Hospital, Graz; Austria
Intravenous sedation is a valuable adjunct during surgery under regional anaesthesia. In many cases, only light sedation is required, with patients remaining in verbal contact with their anaesthesiologists throughout the entire surgical procedure. Therefore, this kind of sedation is known as ”conscious sedation” or ”monitored anaesthesia care” (MAC) and is defined as a specific anaesthesia service involving monitoring of vital signs provided during a planned procedure in connection with loco-regional anaesthesia .
The goal of conscious sedation for surgery under regional anaesthesia is to enhance patient comfort, to include preservation of protective airway reflexes, to avoid painful stimuli and to help maintain haemodynamic stability during the whole surgical procedure.
The centrally active adjuvant drugs available to optimize surgical conditions for both patient and surgeon include benzodiazepines (midazolam), sedative doses of hypnotic agents (propofol) and short acting opioid analgesics (remifentanil). Although transmucosal administration may become more popular in the near future, the intravenous route is the most popular approach at the present time. An understanding of the pharmacokinetic and -dynamic effects of the commonly used sedative, anxiolytic and analgesic drugs is essential in order to achieve optimal surgical conditions and acceptable patient outcome when using sedation-based techniques.
All benzodiazepines have the ability to produce anxiolysis, as well as varying degrees of amnesia and sedation. Benzodiazepine-induced central nervous system depression is dose-dependent and can vary from light sedation to deep unconsciousness. Diazepam (0.1 - 0.2 mg/kg iv.), the prototypic drug for many years, is characterised by a long elimination half-life of about 50 hours, which may result in delayed recovery and possible postoperative re-sedation, due to active metabolites and entero-hepatic recirculation. Therefore, its use as a sedative agent has been reduced for several years because of its poor control of the desired sedative level. Furthermore, the effects of diazepam are particulary intensified with older patients, on whom local anaesthetic techniques are frequently used.
Midazolam (0.05 - 0.1 mg/kg; 0.03 - 0.2 mg/kg/h) is now the most popular benzodiazepine because it is water soluble and does not cause veno-irritation or pain when injected. It is a more rapid-acting agent than diazepam with a relatively short elimination half-life of about 2 - 4 hours. Thus, midazolam allows a more predictable recovery after brief procedures. However, midazolam requires careful intravenous titration to the desired sedative result to minimize side effects resulting from inadvertent overdosage. In many studies, midazolam has a more rapid onset and also produces more profound perioperative amnesia, anxiolysis and sedation than diazepam .
Propofol is commonly used in subhypnotic dosages for conscious sedation in combination with local anaesthesia, mainly because it is a short acting, easily controllable and individually titrable hypnotic and sedative agent . These pharmacokinetic properties result in a quick recovery from the effects of a single bolus-dose, as well as following a continuous infusion. Propofol’s rapid onset and short duration of action ensures prompt responsiveness to changes in its infusion rate, with optimal titration achieved by using a variable-rate infusion. Furthermore, propofol has a very low incidence of undesirable side-effects when used in sedative dosages . Its use is rarely associated with excitatory phenomena or involuntary movements, and there is a low incidence of postoperative nausea and vomiting (PONV). Of particular importance, low-dose infusions of propofol have very little depressant effect on cardiovascular and respiratory variables . Nevertheless, monitoring of oxygen saturation is recommended and supplemental oxygen via nasal cannulae (4l/min) should be given throughout the surgical procedure.
Propofol is well investigated as a sedative agent in the field of regional anaesthesia for ophthalmic, orthopaedic, or urological surgery: In the most comprehensive trial conducted for conscious sedation with propofol, loading doses of 0.2 - 0.5 mg/kg and maintenance dosages of 0.5 - 4 mg/kg/h are recommended . In randomised comparative studies (mean doses for maintenance: 1.7 - 3.5 mg/kg/h) propofol demonstrated a smaller amnesic effect for the early postoperative period than midazolam and was associated with a quicker recovery . Propofol is particularly beneficial for ophthalmic procedures (0.8 - 3 mg/kg/h) not only because of its sedative properties but also because of its ability to decrease the intraocular pressure and low incidence of PONV .
Target-controlled infusion is a logical approach to the development of improved administration techniques for an intravenous anaesthetic agent. A TCI-system for propofol uses an open three-compartment pharmocokinetic model to predict the necessary initial bolus-dose and following infusion rates to achieve and maintain a given predicted blood concentration. Therefore, a TCI-system allows a more rapid adjustment of the propofol blood concentration according to individual need than a manually controlled infusion. Alteration of sedation level is easy to achieve with TCI as changes made to either ”deepen” or ”lighten” the level of sedation result in patients achieving the desired sedation score within a few minutes. For conscious sedation with TCI, dosages of propofol at target concentrations of 0.4 - 1.0 (1.2) µg/ml are useful, also dependent on the age of patient and the kind of premedication .
While opioid analgesics can be used as the sole supplement to local anaesthesia, they do not produce reliable sedation in the absence of considerable respiratory depression. Therefore, opioids are often used in combination with sedative drugs to supplement analgesia produced by local anaesthetics .
Remifentanil is the first representative of a new class of esterase metabolized opioid drugs, resulting in a short context-sensitive half-time of about 3.5 min. Therefore, remifentanil allows a more precise intraoperative titration and has a more predictable offset of effect than traditional opioids. Remifentanil does not accumulate even during prolonged infusion. For conscious sedation with remifentanil, infusion rates of 0.025 - 0.1 µg/kg/min are recommended titrated to individual needs . Especially combined with propofol at lower dosages, remifentanil provides superior anlagesia during the performance of nerve blockade, thereby enhancing patient comfort during the surgical procedure without compromising haemodynamic stability or respiratory depression .
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