Inhaled sedation with isoflurane in the intensive care unit

Patients in the Intensive Care Unit (ICU) may experience distress and pain, for which they are often prescribed sedative and analgesic drugs, sometimes at the cost of clinically significant side effects, such as prolonged wake-up time, drug or solvent toxicity and withdrawal. The search for the ideal sedation regimen for these patients in ongoing.

Isoflurane - an inhaled anaesthetic - has sedative properties in subanaesthetic concentrations and is theoretically appealing as an ICU sedative but modem ICU ventilators are not compatible with currently available vaporizers. The Anesthetic Conserving Device / AnaConDa® (ACD) - a modified heat-moisture exchanger, with features permitting infusion of isoflurane from a standard syringe pump and rebreathing of exhaled isoflurane, has been developed for high-flow ventilation anaesthesia. This novel method has been studied in the anaesthesia setting but not for isoflurane sedation in the ICU.

The feasibility of isoflurane via the ACD for sedation in ICU patients was evaluated and sedation efficacy was compared with that of intravenous midazolam. Environmental aspects and agent-saving properties of the method were studied, as well as the potential benefit and limitations of ACD use in paediatric patients. The Bispectral indexTM (BIS), a non-invasive EEG-derived numerical measure of anaesthetic and sedative depth, was evaluated as a predictor of clinically assessed sedation depth for isoflurane sedation and for midazolam sedation. Short-term recovery, long-term memories and psychological recovery in patients receiving isoflurane or midazolam were studied.

Wake-up times after isoflurane sedation via the ACD were significantly shorter than after midazolam. Few minor practical problems related to ACD use occurred and no adverse hepatic or renal effects related to either sedative were observed. Ambient isoflurane concentrations were low and well below recommended exposure limits. The novel method was useful in paediatric patients but required adapted placement in the breathing circuit to avoid increased dead-space in smaller children. BIS did not predict sedation depth well enough to replace clinical scoring during isoflurane or midazolam sedation. Patient follow-up did not reveal any differences in short-term recovery but significantly fewer patients reported delusions hallucinations after isoflurane sedation than after midazolam sedation.

In conclusion, this thesis demonstrates that isoflurane via the ACD is efficacious for sedation of ICU patients, with shorter wake-up times than with midazolam. The use of the ACD for isoflurane delivery in the ICU is feasible, environmentally safe and reduces agent consumption compared with conventional vaporizer delivery. In paediatric ICU sedation, placement of the ACD in the inspiratory limb of the breathing circuit is necessary if the device is used in smaller children. BIS monitoring can not reliably replace clinical assessment of sedation depth in non-paralyzed ICU patients. Isoflurane sedation does not appear to have any serious negative psychological or cognitive effects compared to intravenous sedation and may possibly reduce the risk of delusions and hallucinations in the ICU.

List of scientific papers

I. Sackey PV, Martling CR, Granath F, Radell PJ (2004). Prolonged isoflurane sedation of intensive care unit patients with the Anesthetic Conserving Device. Crit Care Med. 32(11): 2241-6.
https://pubmed.ncbi.nlm.nih.gov/15640636

II. Sackey PV, Martling CR, Nise G, Radell PJ (2005). Ambient isoflurane pollution and isoflurane consumption during intensive care unit sedation with the Anesthetic Conserving Device. Crit Care Med. 33(3): 585-90.
https://pubmed.ncbi.nlm.nih.gov/15753751

III. Sackey PV, Martling CR, Radell PJ (1970). Three cases of PICU sedation with isoflurane delivered by the 'AnaConDa'. Paediatr Anaesth. 15(10): 879-85.
https://pubmed.ncbi.nlm.nih.gov/16176317

IV. Sackey PV, Granath F, Radell PJ, Martling CR (2006). Does the Bispectral Index predict sedation depth better during isofl urane than midazolam sedation in ICU patients? [Submitted]

V. Sackey PV, Carlsward C, Martling CR, Sundin O, Radell PJ, (2006). Short- and long-term follow-up of ICU patients after sedation with isoflurane and midazolam a pilot study. [Manuscript]