Objective: Although extensively studied in children, the safety and tolerability of ketone supplementation in adults is unclear, particularly in the acute brain injury population. The purpose of this study was to examine the feasibility and safety of inducing ketosis using an enteric ketogenic formulation and determine its impact on intracranial and cerebral perfusion pressures and metabolic parameters.Methods: Prospective interventional Phase II trial of ventilated critically ill patients with acute brain injury administered a ketogenic feed over a 6 day period.Results: 20 patients were recruited, 5 females and 15 males, 3 with stroke, 2 with subarachnoid haemorrhage and 15 with traumatic brain injury. Feeds were well tolerated with 19 patients completing study. There was a significant increase in both plasma beta-hydroxybutyrate and acetoacetate from 0.24± 0.31 mmol/l and 0.19 ± 0.16 mmol/l to 0.61 ± 0.53 mmol/l (p =0.0005) and 0.52 ± 0.40 mmol/l (p<0.0001) respectively over the 6 day period. Total daily Ketocal® caloric intake was positively correlated with plasma beta-hydroxybutyrate concentrations (p=0.0011). There was no significant correlation between the cerebral hypertension and cerebral hypoperfusion indices and plasma ketone concentrations. In 95% of patients there were no clinically significant changes in acid/base status over the 6 days with pH remaining within normal range.Conclusion: In patients with acute brain injury, an enterally administered ketogenic formulation increased plasma ketone concentrations, was well tolerated, did not impact on cerebral hemodynamics and can be safely administered.Clinical trial registered at the Australian New Zealand Clinical Trials Registry (ACTRN12616000332426)Abbreviations: BHB: betahydroxybutyrate; AcAc: acetoacetate; ABI: acute brain injury; TBI: traumatic brain injury; CSF: cerebrospinal fluid; SAH: subarachnoid injury; CVA: cerebrovascular accidents; ICP: intracranial pressure; CPP: cerebral perfusion pressure; ICU: intensive care unit; EVD: external ventricular device; CHI: cerebral hypoperfusion index; IHI: intracranial hypertension index; GCS: Glasgow Coma Scale.

中文翻译：

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II期研究通过急性脑损伤患者的肠内制剂诱导生酮作用。

目的：尽管在儿童中进行了广泛研究，但成人（尤其是急性脑损伤人群）补充酮的安全性和耐受性尚不清楚。这项研究的目的是检验使用肠溶性生酮制剂诱导酮症的可行性和安全性，并确定其对颅内和脑灌注压力和代谢参数的影响。方法：通风性重症急性脑损伤患者的前瞻性介入性II期临床试验结果：招募了20名患者，共6天。结果：招募了20例患者，女性5例，男性15例，中风3例，蛛网膜下腔出血2例，脑外伤15例。19名完成研究的患者对饲料的耐受性良好。血浆β-羟基丁酸酯和乙酰乙酸酯均显着增加，从0.24±0.31 mmol / l和0.19±0.16 mmol / l增至0.61±0.53 mmol / l（p = 0.0005）和0.52±0.40 mmol / l（p <0.0001 ）分别在6天的时间段内。每日总热量摄入与血浆β-羟基丁酸酯浓度成正相关（p = 0.0011）。脑高血压与脑灌注不足指数和血浆酮浓度之间无显着相关性。在95％的患者中，pH维持在正常范围内，在6天内酸/碱状态没有临床上的显着变化。结论：在急性脑损伤的患者中，肠内生酮制剂可提高血浆酮浓度，耐受性良好，不会影响脑血流动力学并且可以安全地进行治疗。在澳大利亚新西兰临床试验注册中心（ACTRN12616000332426）注册的临床试验缩写：BHB：β-羟基丁酸酯；AcAc：乙酰乙酸；ABI：急性脑损伤；TBI：脑外伤；脑脊液：脑脊液；SAH：蛛网膜下腔损伤；CVA：脑血管意外；ICP：颅内压；CPP：脑灌注压；重症监护病房：重症监护病房；EVD：外部心室设备；CHI：脑灌注不足指数；IHI：颅内高压指数；GCS：格拉斯哥昏迷量表。蛛网膜下腔损伤; CVA：脑血管意外；ICP：颅内压；CPP：脑灌注压；重症监护病房：重症监护病房；EVD：外部心室设备；CHI：脑灌注不足指数；IHI：颅内高压指数；GCS：格拉斯哥昏迷量表。蛛网膜下腔损伤; CVA：脑血管意外；ICP：颅内压；CPP：脑灌注压；重症监护病房：重症监护病房；EVD：外部心室设备；CHI：脑灌注不足指数；IHI：颅内高压指数；GCS：格拉斯哥昏迷量表。