Sedative Anaesthetic

Propofol

Propofol reduces anxiety and tension, and promotes relaxation and sleep or loss of consciousness. Propofol provides loss of awareness for short diagnostic tests, surgical procedures, and supplements other types of general anesthetics. It is fast acting and metabolized quickly. Its beneficial effects occur via decreases in peripheral vascular tension resulting in potential neuroprotective effects. Experimental results have shown positive effects on cerebral physiology including reductions in CBF, cerebral oxygen metabolism, EEG activity, and ICP (Adembri et al. 2007).

The American Association of Neurological Surgeons recommends propofol use for the control of ICP, but on an individual basis. The EBIC also recommends the use of propofol for the control of ICP, but not for improvement in mortality or 6 month outcome. Caution is recommended in the administration of high-dose propofol as it can produce significant morbidity (Bratton et al. 2007). 

Table: Effects of Propofol in the Management of Acute ABI

Discussion

In one RCT, propofol sedation was compared to morphine for safety and efficacy (Kelly et al. 1999). Patients in the propofol group tended to display reduced ICP levels, and showed less need for neuromuscular blocking agents, benzodiazepines, pentobarbital, and CSF drainage (Kelly et al. 1999). When propofol was compared to dexmedetomidine there were no significant differences between the two sedatives based on the physiologic measures assessed (James et al. 2012). Results of these studies suggest that propofol is a safe, acceptable, and possibly desirable as an alternative to opiate-based sedation (Kelly et al. 1999) and/or relatively expensive sedatives such as dexmedetomidine (James et al. 2012).

In a study conducted by Stewart et al. (1994), propofol was reported to provided sedation similar to a combination of midazolam and morphine, with no differences in six month outcomes between groups. Farling et al. (1989) also reported that propofol provided safe and effective sedation. Due to the size of the studies and their poor methodological scores further study is warranted.

Conclusion

There is Level 1b evidence that propofol may help to reduce intracranial pressure and the need for other sedative interventions when used in conjunction with morphine.

 

Propofol helps to reduce intracranial pressure and the need for other sedative interventions when used in conjunction with morphine.

 

Midazolam

Midazolam, another benzodiazepine, works by slowing activity in the brain to allow for relaxation and sleep. Midazolam has been found to reduce CSF pressure in patients without intracranial mass lesions as well as decrease CBF and cerebral oxygen consumption (McClelland et al. 1995). For a more detailed discussion of midazolam please refer to Modules 10 and Module 16.

Table: Effects of Midazolam in the Management of Acute ABI

Discussion

Infusions of midazolam or propofol were reported to provide similar quality sedation in patients with severe head trauma, although propofol was associated with a high incidence of hypertriglyceridemia (Sanchez-Izquierdo-Riera et al. 1998). In both studies evaluating midazolam and ICP, no significant difference was seen after midazolam administration (Papazian et al. 1993; Sanchez-Izquierdo-Riera et al. 1998). However, hypotension was related to increased doses of midazolam (Davis et al. 2001) and decreases in MAP resulting in decreased CPP (especially in patients with initial ICP ≤ 18 mmHg; Papazian et al. 1993). The study by Sanchez-Izquierdo-Riera et al. (1998) measured ICP, CPP and MAP in all patients and reported no between group differences. However, they did not report comparisons with baseline values making it unclear whether or not midazolam resulted in any negative effects. Based on current evidence, hypotension should be monitored as a potential side effect for midazolam.

Conclusion

There is Level 2 evidence that midazolam has no effect on intracranial pressure but conflicting evidence regarding its effect on mean arterial pressure and cerebral perfusion pressure. 

 

Midazolam has no effect on intracranial pressure but may result in systemic hypotension.