A novel step‐down infusion method of barbiturate therapy: Its safety and effectiveness for intracranial pressure control. Issue 2 (22nd February 2021)

• Record Type: Journal Article
• Authors: Yamakawa, Yukako; Morioka, Motohiro; Negoto, Tetsuya; Orito, Kimihiko; Yoshitomi, Munetake; Nakamura, Yukihiko; Takeshige, Nobuyuki; Yamamoto, Masafumi; Takeuchi, Yasuharu; Oda, Kazutaka; Jono, Hirofumi; Saito, Hideyuki
• Is Part Of: Pharmacology research & perspectives. Volume 9:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-02-22
• Subjects: barbiturate -- cerebral perfusion pressure -- intracranial pressure -- step‐down infusion -- traumatic brain injury; Pharmacology -- Periodicals; Drug development -- Periodicals; 615.105
• DOI: 10.1002/prp2.719
• Languages: English
• ISSNs: 2052-1707

Abstract

Abstract: Intracranial pressure (ICP) has to be maintained quite constant, because increased ICP caused by cerebrovascular disease and head trauma is fatal. Although controlling ICP is clinically critical, only few therapeutic methods are currently available. Barbiturates, a group of sedative‐hypnotic drugs, are recognized as secondary treatment for controlling ICP. We proposed a novel "step‐down infusion" method, administrating barbiturate (thiamylal) after different time point from the start of treatment under normothermia, at doses of 3.0 (0–24 h), 2.0 (24–48 h), 1.5 (48–72 h), and 1.0 mg/kg/h (72–96 h), and evaluated its safety and effectiveness in clinical. In 22 patients with severe traumatic brain injury or severe cerebrovascular disease (Glasgow coma scale ≤8), thiamylal concentrations and ICP were monitored. The step‐down infusion method under normothermia maintained stable thiamylal concentrations (<26.1 µg/ml) without any abnormal accumulation/elevation, and could successfully keep ICP <20 mmHg (targeted management value: ICP <20 mmHg) in all patients. Moreover the mean value of cerebral perfusion pressure (CPP) was also maintained over 65 mmHg during all time course (targeted management value: CPP >65 mmHg), and no threatening changes in serum potassium or any hemodynamic instability were observed. Our novel "step‐down infusion" method under normothermia enabled to maintain stable, safe thiamylal concentrations to ensure both ICP reduction and CPP maintenance without any serious side effects, may provide a novel and clinically effective treatment option for patients with increased ICP. Abstract : The novel "step‐down infusion" method of barbiturate therapy was proposed and evaluated in this study, and could maintain a stable concentration of thiamylal in normothermic patients, achieving both ICP reduction and CPP maintenance without any serious side effects such as hypotension or hypokalemia.