Inhalative Sedation

In spite of the generally accepted need for an adequate analgosedation, at present there is no wide consensus neither with intensive care medics nor with the nursing staff as to how and with which substances this condition is best to be achieved and how in the course of intensive care treatment it can be maintained. Evidence-based data for the use of the numerous available sedatives and analgesics in critically ill patients have so far been scarce, which not least is due to the difference of intensive care disease patterns and progression.

In Germany the sedation of intensive care patients nowadays is done mostly by intravenously applicable substances.

Widespread is the use of Propofol for sedation, often also in combination with an opioid such as

• Sufentanil
• Fentanyl or
• Remifentanil.

When used over days or weeks, however, even when short-acting drugs such as Propofol are applied, this will lead to cumulative effects with significantly longer wake-up times which after several days of use may be hours or even days. The so-called Propofol infusion syndrome is a very rare life threatening symptom complex after high-dose or long-lasting Propofol infusion. At present it is not clear yet whether the duration or the level of the dosage will favor the development. Within the scope of a Propofol infusion syndrome signs of increasing cardiac insufficiency and arrhytmia were observed. At the same time a metabolic acidosis occurs and frequently also a rhabdomyolysis which may be accompanied by an acute renal insufficiency and a consecutive renal failure. Hypertriglyceridaemia are another though seldom diagnosed characteristic. Not least because of that the duration of use of Propofol is limited in time.

At the latest 7 days with on-going indication it will be necessary to switch to other substances for analgosedation.

Alternatively used sedatives such as Midazolam from the group of benzodiazepines, however, have per se a considerably longer half-life than Propofol which favors cumulative effects. Moreover, in the enzymatic degradation effective metabolites with even longer half-lives are created. Also, already after short duration of application ceiling effects occur which lead to constant increases of doses, decreasing effectiveness and thereby further accumulation. The weaning from benzodiazepines is also associated with the frequent occurrence of delirious states. Their long-term use is therefore not considered as being unproblematic. These consequences are being counteracted by a combination with Ketamine or barbiturates, but these drugs are also characterized by long clinical duration of action and in individual cases hardly to be estimated.

Longer half-lives not only lead to a poorer controllability of the sedation depth with diminished assessability of the neurological state as well as of the spontaneous breathing capacity of the patient, but they also impede the weaning of the patient from the ventilator. Extended ventilation times increase the rate and gravity of pulmonary complications and with an increase of the sepsis rate, extended stationary stay, considerably higher treatment costs and at long last they are socialized by an increased overall mortality.

For years’ considerable efforts are therefore being made to counteract this viscious circle by therapeutic interventions such as daily wake-up maneuvers and medication rotations. Newer substances such as the recently introduced Dexmedetomidin, are advertised under the aspect of gaining advantages over established substances in long-term use but could not live up to the expectations. Moreover, they are not suitable for every patient and all degrees of sedation.