Critically ill patients receive many drugs during their stay in an intensive care unit (ICU). The agents used most commonly are given to achieve patient comfort. A large variety of drugs are administered to produce anxiolysis, amnesia, analgesia and sleep. Sedative agents are essential to modern intensive care medicine, but both the drugs themselves and an inappropriate level of sedation can have unwanted side effects. It is important that each patient has a different indication for sedation and individual requirements for sedation may change over time. Furthermore, the population of patients in an ICU is generally not uniform. For example, the sedative requirements of a patient ventilated in the prone position may be completely different from those required by a patient who has undergone aortic surgery and is recovering without any problems. Any drug regimen for sedation must also take into account the analgesic requirements of the patient. Opioids will have a synergistic interaction with most sedative drugs.
The most commonly used sedative regimen is administration of midazolam at rates of 0.5-3 ug/kg/min. This has many advantages. It is relatively cheap. When given for short periods of sedation the decrement time is reasonably short. There are few (mild) cardiovascular and respiratory side effects. However, midazolam administration also has some problems. Time to peak effect is relatively long and plasma levels continue to rise even after prolonged administration. The metabolism of midazolam involves glucuronidation. This produces pharmacologically active compounds, which tend to accumulate after prolonged administration. Because they are excreted by the kidney, patients who suffer from renal failure in particular can be at risk for prolonged sedation after cessation of drug administration.
The pharmacokinetic properties of propofol render it theoretically more suitable for sedation in the ICU. The time to peak effect is shorter, due to its faster blood-brain equilibration. The higher clearance and the absence of pharmacologically active metabolites should lead to a quicker recovery of consciousness after stopping the infusion. The safety and efficacy of propofol for sedation in the ICU has been proven in a number of studies1,2,3.
In recent years anesthesiologists have gained experience in administering drugs using target controlled infusion systems (TCI). These systems have been used to provide analgesia, anesthesia and also to provide sedation with or without the use of regional techniques.4 The use of TCI administration of propofol for patient controlled sedation has been described5.
In the literature there are few studies published about postoperative administration of analgesic or sedative drugs using a TCI system. Postoperative analgesia is now widely given by patient controlled devices. Van den Nieuwenhuyzen et al. have described the use of TCI administration of alfentanil in the postoperative phase using a PCA mode6. Their study involved surgical patients on a regular ward. Kenny et al. have described the use of TCI alfentanil after cardiac surgery7. Both report good analgesia using this type of drug administration, albeit at the cost of some adverse effects, most commonly nausea and/or vomiting.
Theoretically, TCI poses many advantages for administering sedative drugs in the ICU. The sedative regime can be tailored to the patient's needs, which may change over time. Difficulties may be encountered because the algorithm incorporated in currently available TCI systems may not be suitable for the population of patients in the ICU. The pharmacokinetic and pharmacodynamic properties of drugs may be different in ICU patients. Especially for long administration of drugs it remains to be seen whether the currently used models are appropriate. To evaluate this we are currently assessing the performance of a commercially available TCI system ('Diprifusor') for use in the ICU.
References
1. Beller et al, Br J of Anaesth 1988;61:583-88
2. Seyde et al, J of Drug Development 1989;2:79-80
3. Aitkenhead et al, Lancet 1989;II:704-09
4. Oei-Lim et al, Br J of Anaesth 1998;80:324-331
5. Irwin et al, Anaesthesia 1997;52:525-530
6. Van den Nieuwenhuyzen et al, Anesth Analg 1995;81:671-9
7. Kenny et al, Br J of Anaesth 1998;80(6):748-51