von Rosenstiel N, von Rosenstiel I, Adam D
University Children's Hospital, Munich, Germany.
Paediatr Drugs. 2001;3(1):9-27. doi: 10.2165/00128072-200103010-00002.
Sepsis and septic shock constitute an important cause of morbidity and mortality in critically ill children. Thus, the systemic response to infection and its management remains a major challenge in clinical medicine. Apart from antibiotic administration, the majority of available therapies are limited to supportive strategies, although considerable efforts are being undertaken to devise innovative approaches that modulate host inflammatory responses. In suspected sepsis, 2 or 3 days' empiric antibiotic therapy should begin immediately after cultures have been obtained without awaiting results. Antibiotics should be re-evaluated when the results of the cultures and susceptibility tests are available. The initial antibiotic (combination) is determined by the likely causative agent, susceptibility patterns within a specific institution, CNS penetration, toxicity, and the patient's hepatic and renal function. The likely offending micro-organism in turn depends primarily on the patient's age, coexistence of any premorbid condition leading to impaired immune response, and the presenting signs and symptoms. Close attention to cardiovascular, respiratory, fluid and electrolyte, haematological, renal and metabolic/nutritional support is essential to optimise outcome. Fluid resuscitation is of utmost importance to overcome hypovolaemia on the basis of a diffuse capillary leak. Monitoring and normalisation of the heart rate is essential. In case of nonresponse to fluid resuscitation, inotropic and vasoactive agents are commonly used to increase cardiac output, maintain adequate blood pressure and enhance oxygen delivery to the tissue. Because respiratory distress syndrome is seen in about 40% of critically ill children with septic shock, increased inspired oxygen is essential. To provide optimal relief from respiratory muscle fatigue and facilitate the provision of positive airway pressure, early intubation and mechanical ventilation should be considered. Renal support is essential to avoid prolonged renal shutdown in hypoperfusion states. Haematological support comprises replacement therapy of clotting factors to overcome disseminated intravascular coagulation. Metabolic support may include glucose support, extraction of ammonia from the body and recognition of liver dysfunction. Nutritional support may modify the inflammatory host response, and early enteral feeding can improve outcome in critical illness. To date, glucocorticoid and non-glucocorticoid anti-inflammatory agents have not shown significant benefit in septic patients.
脓毒症和脓毒性休克是危重症儿童发病和死亡的重要原因。因此,对感染的全身反应及其管理仍是临床医学中的一项重大挑战。除了使用抗生素外,大多数现有疗法仅限于支持性策略,尽管人们正在付出巨大努力来设计调节宿主炎症反应的创新方法。在疑似脓毒症时,应在获取培养物后立即开始2或3天的经验性抗生素治疗,无需等待结果。当培养物和药敏试验结果出来后,应对抗生素进行重新评估。初始抗生素(联合用药)由可能的病原体、特定机构内的药敏模式、中枢神经系统渗透性、毒性以及患者的肝肾功能决定。反过来,可能致病的微生物主要取决于患者的年龄、任何导致免疫反应受损的基础疾病的共存情况以及所呈现的体征和症状。密切关注心血管、呼吸、液体和电解质、血液学、肾脏以及代谢/营养支持对于优化治疗结果至关重要。液体复苏对于克服基于弥漫性毛细血管渗漏的低血容量至关重要。监测并使心率恢复正常至关重要。如果对液体复苏无反应,常用强心剂和血管活性药物来增加心输出量、维持足够的血压并增强组织的氧输送。因为约40%的脓毒性休克危重症儿童会出现呼吸窘迫综合征,增加吸入氧至关重要。为了最佳缓解呼吸肌疲劳并便于提供气道正压,应考虑早期插管和机械通气。肾脏支持对于避免在低灌注状态下出现长时间的肾衰竭至关重要。血液学支持包括凝血因子替代疗法以克服弥散性血管内凝血。代谢支持可能包括葡萄糖支持、从体内清除氨以及识别肝功能障碍。营养支持可能会改变宿主的炎症反应,早期肠内喂养可改善危重症的治疗结果。迄今为止,糖皮质激素和非糖皮质激素抗炎药在脓毒症患者中尚未显示出显著益处。