Opioids are substances with morphine-like actions. They work by binding to opioid receptors, found principally in the CNS and the gastrointestinal tract. Each opioid has a distinct binding affinity to group(s) of opioid receptors that then determine its pharmacodynamic response. Morphine has been the most commonly used opioid following acquired brain injury (ABI), while fentanyl and its derivatives have gained popularity owing to their more rapid onset and shorter duration of effect (Metz et al. 2000). Controversy persists regarding the effect of opioids on intracranial pressure (ICP) and cerebral perfusion pressure (CPP). It has been reported that opioids can increase cerebral blood flow (CBF), which may lead to an increase in ICP (Bunegin et al. 1989; de Nadal et al. 2000; Marx et al. 1989; Werner et al. 1995).
A total of nine studies examined the efficacy of opioid use in the management of acute ABI. All included studies investigated changes in ICP in response to common opioids, including morphine, fentanyl, sufentanil, remifentanil and alfentanil. Overall, five studies reported increases in ICP after opioid use (Albanese et al. 1993; Albanese et al. 1999; de Nadal et al. 2000; Sperry et al. 1992; Werner et al. 1995), while three found no increase (Engelhard et al. 2004; Karabinis et al. 2004; Lauer et al. 1997), and one reported a decrease (Scholz et al. 1994). However given the high methodological quality of studies reporting ICP elevations following opioid use, we accept that opioid administration results in increased ICP.
Findings suggest that mean arterial pressure (MAP) decreases in response to opioid administration. All but one study reported significant reductions in MAP following opioid use (Engelhard et al. 2004). With regards to CPP however it was more difficult to draw meaningful conclusions due to inconsistencies in its findings, whereby some studies reported a reduction in CPP following opioid use (Albanese et al. 1993; Albanese et al. 1999; de Nadal et al. 2000), while some reported no changes in CPP under similar circumstances (Engelhard et al. 2004; Lauer et al. 1997; Scholz et al. 1994).
Analgesic sedation with opioids is commonly used in conjunction with hypnotic agents such as midazolam or propofol during the acute phase post ABI to reduce nociceptive (pain) stimulation (Albanese et al. 1993; Karabinis et al. 2004; Scholz et al. 1994). In one RCT, the authors investigated whether the timing at which the therapy is initiated influences outcome. To this end, they established two treatment arms: analgesia-based sedation and hypnotic-based sedation. In the former treatment, patients received remifentanil (analgesic) first, followed by propofol and midazolam (hypnotic) if necessary. In the latter group, the order was reversed, with patients receiving propofol or midazolam (hypnotic) first, then either fentanyl or morphine (analgesic). It was found that analgesia-based sedation resulted in significantly faster arousal compared to hypnotic-based sedation, allowing for more prompt neurological assessment of those treated with analgesics first (Karabinis et al. 2004). The findings suggest that administering an opioid as a first-line therapy immediately following an injury may be desirable in the acute management of ABI.
There is Level 1a evidence that opioid administration results in increased intracranial pressure and in decreased mean arterial pressure. Evidence regarding cerebral perfusion pressure, however, is conflicting.
Based on a single RCT, there is Level 2 evidence that administering an opioid prior to administering a hypnotic agent leads to more rapid arousal.
Opioid administration results in increased intracranial pressure and in decreased mean arterial pressure, and thus is not beneficial in the management of acute ABI.
Administering an opioid prior to administering a hypnotic agent results in faster arousal, and thus may be desirable in the acute management of ABI.