Opioids and cerebral physiology in the acute management of traumatic brain injury: a systematic review

Abstract

Background: Following traumatic brain injury (TBI), optimization of cerebral physiology is recommended to promote more favourable patient outcomes. Accompanying pain and agitation are commonly treated with sedative and analgesic agents, such as opioids. However, the impact of opioids on certain aspects of cerebral physiology is not well established. Objective: To conduct a systematic review of the evidence on the effect of opioids on cerebral physiology in TBI during acute care. Methods: A comprehensive literature search was conducted in five electronic databases for articles published in English up to November 2017. Studies were included if: (1) the study sample was human subjects with TBI; (2) the sample size was ≥3; (3) subjects were given an opioid during acute care; and (4) any measure of cerebral physiology was evaluated. Cerebral physiology measures were intracranial pressure (ICP), cerebral perfusion pressure (CPP), and mean arterial pressure (MAP). Subject and study characteristics, treatment protocol, and results were extracted from included studies. Randomized controlled trials were evaluated for methodological quality using the Physiotherapy Evidence Database tool. Levels of evidence were assigned using a modified Sackett scale. Results: In total, 22 studies met inclusion criteria, from which six different opioids were identified: morphine, fentanyl, sufentanil, remifentanil, alfentanil, and phenoperidine. The evidence for individual opioids demonstrated equally either: (1) no effect on ICP, CPP, or MAP; or (2) an increase in ICP with associated decreases in CPP and MAP. In general, opioids administered by infusion resulted in the former outcome, whereas those given in bolus form resulted in the latter. There were no significant differences when comparing different opioids, with the exception of one study that found fentanyl was associated with lower ICP and CPP than morphine and sufentanil. There were no consistent results when comparing opioids to other non-opioid medications. Conclusion: Several studies have assessed the effect of opioids on cerebral physiology during the acute management of TBI, but there is considerable heterogeneity in terms of study methodology and findings. Opioids are beneficial in terms of analgesia and sedation, but bolus administration should be avoided to prevent additional or prolonged unfavourable alterations in cerebral physiology. Future studies should better elucidate the effects of different opioids as well as varying dosages in order to develop improved understanding as well as allow for tighter control of cerebral physiology.

Psychotropic and pain medication use in individuals with traumatic brain injury—a Swedish total population cohort study of 240 000 persons

“…In contrast, individuals with mild TBI (ie, concussions) had 10% higher odds of using opioids. Little is known about the long-term consequences of opioid treatment in persons with TBI, 28 however, opioids may increase the risk of cognitive and mental problems in persons with TBI. 29 More studies on the long-term effect of opioids on TBI outcomes, as well as the factors that influence the initiation and continuation of opioid use among persons with TBI, 18 are required.…”

Persistent post-discharge opioid prescribing after traumatic brain injury requiring intensive care unit admission: A cross-sectional study with longitudinal outcome

“…Opioids and benzodiazepines reduce cerebral metabolic oxygen consumption with minimal effects on cerebral perfusion, which makes them ideal agents for the management of TBI. [8–10] However, exposure to opioids for the acute management of TBI may increase risk for dependence and opioid use disorder in these patients. We and others have shown that in-hospital exposure to opioids increases the risk for chronic opioid use in surgical patients [11–13]; with persistent use reported as much as one year after the index admission.…”

Analgesia in the Neurosurgical Intensive Care Unit

“…Different opioids may be used like fentanyl, sufentanil, remifentanil, and morphine. Opioids are beneficial for analgesia, but their bolus administration may increase ICP with associated decreases in MAP and CPP, and should be avoided (29). In the systematic review Wiener and coworkers have found no consistent results between different opioids, and between opioid and non-opioid analgesia in the management of traumatic brain injury regarding their effects on MAP, ICP, or CPP (29).…”

“…Opioids are beneficial for analgesia, but their bolus administration may increase ICP with associated decreases in MAP and CPP, and should be avoided (29). In the systematic review Wiener and coworkers have found no consistent results between different opioids, and between opioid and non-opioid analgesia in the management of traumatic brain injury regarding their effects on MAP, ICP, or CPP (29). Opioid consumption can be reduced by the use of dexmedetomidine for sedation without affecting neurological function (30).…”