Short- and long-term follow-up of intensive care unit patients after sedation with isoflurane and midazolam--a pilot study

Crit Care Med. 2008 Mar;36(3):801-6. doi: 10.1097/CCM.0B013E3181652FEE.


Objective: To compare memories from the intensive care unit (ICU) and short- and long-term psychological morbidity in patients after sedation with intravenous midazolam or inhaled isoflurane.

Design: Prospective long-term follow-up after randomized controlled trial.

Setting: General ICU at Karolinska University Hospital, Solna, Stockholm.

Patients: Forty patients in need of sedation during ventilator treatment.

Interventions: Patients were randomized to receive isoflurane or midazolam for goal-directed sedation until extubation or for a maximum of 96 hrs.

Measurements and main results: For short-term follow-up, doctors', nurses', and physiotherapists' notes from the 4 days following exposure to the study drugs were reviewed for words indicating adequate or pathologic cognitive and psychological recovery. For long-term follow-up, all 6-month survivors received questionnaires including the ICU Memory Tool (ICU-MT), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), and Well-Being Index. Additionally, several screening questions for previous posttraumatic stress symptoms were included. In the short term follow-up, no significant differences were found between groups. In the long-term follow-up, a trend toward fewer hallucinations/delusions after isoflurane sedation than after midazolam (two of ten isoflurane patients vs. five of seven midazolam patients) was found (p = .06). None of the five solely isoflurane-sedated patients reported hallucinations/delusions from the ICU. There was no difference in groups in long-term psychological morbidity as measured with HADS and IES. Memories of negative feelings in the ICU (ICU-MT) were associated with high HADS and IES scores (Fisher's exact test, p = .02 and p = .01, respectively).

Conclusions: Sedation of ICU patients with isoflurane may result in fewer delusional memories or hallucinations from the ICU compared with more commonly used intravenous sedation. Memories of negative feelings from the ICU were associated with symptoms of depression or anxiety or symptoms indicating posttraumatic stress disorder. Further study of memory and cognitive/psychological recovery after prolonged isoflurane sedation beyond 96 hrs is warranted.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anxiety / chemically induced
  • Cognition Disorders / chemically induced
  • Conscious Sedation*
  • Delusions / chemically induced
  • Depression / chemically induced
  • Female
  • Follow-Up Studies
  • Humans
  • Hypnotics and Sedatives / adverse effects*
  • Hypnotics and Sedatives / therapeutic use
  • Intensive Care Units*
  • Isoflurane / adverse effects*
  • Isoflurane / therapeutic use
  • Male
  • Midazolam / adverse effects*
  • Midazolam / therapeutic use
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Time Factors


  • Hypnotics and Sedatives
  • Isoflurane
  • Midazolam