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 [1].
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 [2].
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 [3]. 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 [4]. 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 [5]. 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 [6]. 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 [7]. 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 [8].
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 [9].
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 [10].
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 [11]. 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 [10].
1.
Stevens MH, White PF. Monitored anesthesia care. In Miller RE, ed.
Anesthesia 4th edition. New York: Churchill Livingstone, 1994; 1465-1480
2. White PF, Vasconez LO, Mathes SA, Way WL,
Wender LA. Comparison of midazolam and diazepam
for sedation during plastic surgery. Plast Reconstr Surg 1988; 81: 703-10
3. Mackenzie N, Grant IS. Propofol for
intravenous sedation. Anaesthesia 1987; 42: 3-6
4. Smith I, White PF, Nathanson M, Gouldson R.
Propofol: an update on its clinical uses. Anesthesiology
1994; 81: 1005-43
5. Rosa G, Conti G, Orsi P et al. Effects of
low-dose propofol on central respiratory drive, gas exchanges and respiratory pattern. Acta Anaesth
Scand 1992; 36: 128-36
6. Smith I, Monk TG, White PF et
al. Propofol infusion during regional anesthesia: sedative, amnestic and anxiolytic properties. Anesth Analg
1994; 79: 313-9
7. White PF, Negus JB. Sedative infusions
during local and regional anesthesia: a comparison of midazolam and propofol. J Clin Anesth 1991; 3: 32-9
8. Holas A, Faulborn J. Propofol versus
diazepam for sedation of patients undergoing ophthalmic surgery in regional anaesthesia. Anaesthesist 1993;
42: 766-772
9. Casati A, Fanelli G, Casaletti E, Colnaghi
E, Cedrati V et al. Clinical assessment of target- controlled infusion of propofol during
monitored anesthesia care. Can J of Anesthesia 1999; 46: 235-39
10. Holas A, Krafft P, Marcovic M, Quehenberger F.
Remifentanil, propofol or both for conscious sedation
under regional anaesthesia. Eur J of Anaesth 1999; 16: in press
11. Philip BK. The use of
remifentanil in clinical anaesthesia. Acta Anaesth Scand 1996; 40: Suppl.109,
170-173