Michael Lee

Individual Differences in Psychotic Effects of Ketamine Are Predicted by Brain Function Measured under Placebo

The symptoms of major psychotic illness are diverse and vary widely across individuals. Furthermore, the prepsychotic phase is indistinct, providing little indication of the precise pattern of symptoms that may subsequently emerge. Likewise, although in some individuals who have affected family members the occurrence of disease may be predicted, the specific symptom profile may not. An important question, therefore, is whether predictive physiological markers of symptom expression can be identified. We conducted a placebo-controlled, within-subjects study in healthy individuals to investigate whether individual variability in baseline physiology, as assessed using functional magnetic resonance imaging, predicted psychosis elicited by the psychotomimetic drug ketamine and whether physiological change under drug reproduced those reported in patients. Here we show that brain responses to cognitive task demands under placebo predict the expression of psychotic phenomena after drug administration. Frontothalamic responses to a working memory task were associated with the tendency of subjects to experience negative symptoms under ketamine. Bilateral frontal responses to an attention task were also predictive of negative symptoms. Frontotemporal activations during language processing tasks were predictive of thought disorder and auditory illusory experiences. A subpsychotic dose of ketamine administered during a second scanning session resulted in increased basal ganglia and thalamic activation during the working memory task, paralleling previous reports in patients with schizophrenia. These results demonstrate precise and predictive brain markers for individual profiles of vulnerability to drug-induced psychosis.

Awake insertion of the laryngeal mask airway using topical lidocaine and intravenous remifentanil.

We assessed the use of intravenous remifentanil for the insertion of the laryngeal mask airway in 10 healthy awake volunteers, a technique primarily developed to facilitate functional magnetic resonance imaging studies of anaesthesia. Each volunteer received 200u2003μg glycopyrronium intravenously. Topical airway anaesthesia was effected by 4u2003ml nebulised lidocaine 4%, followed by 12 sprays of lidocaine 10%. Remifentanil was subsequently infused to achieve an initial target effect‐site concentration of 2u2003ng.ml−1; increments of 1u2003ng.ml−1 were allowed with the maximum effect‐site concentration limited to 6u2003ng.ml−1. Insertion of the laryngeal mask airway was successful on the first attempt in all cases. The median (IQR [range]) target effect‐site remifentanil concentration at insertion was 2.5 (2–3 [2–4]) ng.ml−1. All volunteers were co‐operative during the procedure and only one reported discomfort. Sore throat was a complication in all volunteers. We conclude that the technique allows successful insertion of the laryngeal mask airway in healthy awake volunteers under conditions that were safe and reproducible.

Sublingual drug delivery during functional magnetic resonance imaging.

Drs Rahman and Jenkins note that only a few of their cases of obstetric failed intubation had evidence of follow-up [1]. They advise that after a failed intubation women should be told to warn anaesthetists whom they meet in future, and suggest that it is helpful to make a noticeable entry in the patient’s notes and to contact the woman’s general practitioner. However, the need for clear communication with patients, and detailed records to assist with future episodes of anaesthetic care, are not limited solely to cases of difficult intubation. The United Bristol Healthcare Trust has a number of physically separate hospitals with different medical records. In addition, patients regularly use the services of another major hospital Trust in the city. As a result we cannot count on finding a written warning note made in just one medical record. For several years we have had a system in place to produce a letter to the patient and their GP in the event of an anaesthetic problem that might recur during a subsequent anaesthetic. The letter provides details of the occurrence and implications for future management. This coincides with patients’ expectations to be more involved in their own care, and the idea that patients are given copies of any correspondence. Our Information Technology department has recently developed two ‘paperless’ electronic record services. Letters and other records such as discharge summaries are entered onto an electronic document library that is accessible to hospital clinicians as well as participating GP practices. The warning letter is therefore available for the anaesthetist to read at any computer terminal in the Trust. The second aspect is a ‘Clinical Alert Service’. Patients who have been identified as posing an anaesthetic risk are put onto a register. If one of these patients is listed for surgery or admitted to hospital, the anaesthetic department is automatically notified by e-mail. The time in which to plan anaesthesia, including organising equipment and personnel, is therefore considerably extended beyond the preoperative anaesthetic assessment. The national developments in electronic records, although piecemeal at present, can be adapted to benefit anaesthetic clinical risk management.