Hypnotics in the ICU
Lars Berggren MD PhD
Assoc professor
Intensive Care Unit
University Hospital
S-701 85 Örebro
Sweden
Critically ill patients are often given sedatives to promote patient comfort. The aims are often expressed as decreased anxiety and agitation, promotion of amnesia, improved sleep and facilitation of ventilator therapy. Guidelines for the use of hypnotics and sedation have been developed (1). However, strict indications for sedation and the administration of hypnotics in the intensive care setting are poorly defined. Further more, several factors may contribute to the apparent need of sedation such as, hypoxemia, hypoglycemia, hypercapnia, pain, sepsis and circulatory insufficiency. Achieving an appropriate balance between the apparent need of analgesia, sedation, the physiological disturbances and the needs of the care is challenging. There are obvious and rapidly changing needs of the patient, but often the administration of hypnotics is regarded as pure routine. ICU physicians to often regard problems of patient comfort, anxiety and pain as solely a nursing problem and as such leave it to the attending nursing staff. No ideal sedative regime, specific drug or “golden standard” suitable to all patients have been identified. Surprisingly few high quality sedation studies deal with primary patient outcome variables like morbidity, mortality, and length of ICU and hospital stay.
Standard care
Deep sedation in the critically ill patient has been reported to induce immunosuppression decrease gastrointestinal motility and depress cardiorespiratory function with prolonged time on the ventilator. Also, the problems with accumulation, tolerance and altered drug metabolism are obvious. On the other hand, inadequately little sedation may increase sympathetic nervous activity and cause fear, anxiety and agitation, thus interfering with life-sustaining treatment. In order to achieve a desired predetermined level of sedation some sort of sedation scale is mandatory.
Today, standard care to reduce time on ventilator, should comprise intermittent sedation rather than continuous (2), daily interruption of sedation (3) and the use of nurse implemented sedation protocols (4). However, the compliance to these findings is not universal in the clinical setting. In a recent study in Scandinavian intensive care units describing practical and pharmacological routines only 15 % of ICUs used daily interruptions. Written guidelines for sedation were used in 41 % of the units and weaning protocols in 15 %. The most used sedative agents were, not surprisingly, propofol followed by midazolam (5). Midazolam and other benzodiazepines as well, may have extensively prolonged metabolism and duration, while propofol may induce both hemodynamic instability and serious metabolic disorders. However, it must be emphasized, that both drugs are safe and effective for prolonged sedation even in severely ill patients. Nevertheless, only a minority of sedative agents have been rigorously evaluated and compared in randomized double-blind controlled trails.
Alpha-2 agonists
Dexmedetomidine is a new highly selective and potent alpha-2 agonist. It was approved for short term ICU-sedation (< 24 h) by the US food and Drug Administration in 1999 (Precedex, Abbott Labs). Clonidine, another alpha-2 agonist, has been shown to spare general anesthetic and narcotic requirements perioperatively and also has potent prophylactic effect on alcohol withdrawal syndrome (6). Dexmedetomidine has sympatholytic effects, reduces narcotic and sedative requirements and no respiratory depressant effect. The sedative effect seems to be of a special quality. Even deeply sedated patients can be easily aroused (7), the sedation resembling natural sleep and might be described as sedation without cognitive impairment. This specific effect might also have impact on the development of ICU delirium and other sleep deprivation induced psychotic reactions. However, this has to be confirmed in future studies.
Prolonged isoflurane sedation
Isoflurane has been successfully used for sedation of ventilator treated ICU patients. However, most high-flow ICU ventilators are not constructed to provide efficient and cost-effective inhalation of anesthetic gasses. The practical and technical problems are considerable. To facilitate the application of isoflurane sedation in the ICU setting a new technical device has been developed. The Anesthetic Conserving Device (AnaConDa, Hudson RCI) is a modified heat-moisture-exchanger for simple and gas sparing administration of anesthetic gases. It has been shown to provide adequate isoflurane sedation with significantly shorter wake-up times after long-time administration (96 h) as compared with midazolam (10). It seems that even extended administration of isoflurane is devoid of accumulation and prolonged sedation.
Conclusion
Certain routines, nurse based sedation protocols, targeted sedation to predetermined end-points, daily interruptions of sedation and avoidance of neuromuscular blocking agents have been shown to decrease morbidity, time on ventilator and ICU length of stay. These procedures seem to be more important than the choice of sedative agent. However, with newer drugs and applications the concept of ICU sedation might change towards more titrable drugs like isoflurane and “natural” sleep inducing drugs like dexmedetomidine.
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