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[NEJM临床决策]:疑似全身性感染患者早期使用抗生素[2/3]
2019年03月05日 临床话题, 模拟诊室 暂无评论

CLINICAL DECISIONS

Early Administration of Antibiotics for Suspected Sepsis

Michael Y. Mi, Michael Klompas, Laura Evans

N Engl J Med 2019; 380:593-596
DOI: 10.1056/NEJMclde1809210

Case Vigenette 病例

A Man with Hypoxemia and a Woman with Acute Kidney Injury

一名低氧血症男性患者及一名急性肾损伤女性患者

Michael Y. Mi, M.D.

Mr. Shui is a 35-year-old man who is brought to the emergency department by ambulance after falling from the crest of a tall wave while surfing. He had been in the water for approximately 10 minutes before a lifeguard reached him and brought him to shore. At that time, he was unconscious and coughing and had a palpable pulse. A friend accompanied him to the nearest community hospital, where you work. The friend thinks that Mr. Shui is generally in good health and takes no medications regularly, but earlier in the day, Mr. Shui mentioned to his friend that he had felt slightly fatigued and had had a persistent cough for 2 days. He drinks alcohol occasionally. He does not smoke tobacco but smokes marijuana regularly.

Shui先生是一名35岁男性患者,因冲浪时从浪峰处摔落被救护车送到急诊。救生员找到患者并将其带至岸边前,患者已在水中约10分钟。那时,患者意识丧失,咳嗽,脉搏可扪及。他的朋友跟他一起在你所工作的最近的社区医院就诊。朋友表示,Shui先生平时身体健康,并未长期服药,但出事当天早上,患者曾提到自己感觉轻度乏力,咳嗽已持续2天。患者偶尔饮酒,不吸烟,但经常吸食大麻。

On examination, his temperature is 36.0°C, blood pressure 98/65 mm Hg, heart rate 110 beats per minute, respiratory rate 24 breaths per minute, and oxygen saturation 90% while he is breathing ambient air. He opens his eyes and moves his limbs in response to commands but is confused and disoriented. Breath sounds are diminished at the base of both lungs. There is a 3-cm laceration on the right side of his scalp. The remainder of the physical examination is unremarkable. The complete blood count is notable for a white-cell count of 12,400 per cubic millimeter. Electrolyte levels, renal function, and liver-function tests are within normal limits. Arterial blood gas analysis reveals a pH of 7.37, partial pressure of oxygen (Po2) of 60 mm Hg, partial pressure of carbon dioxide (Pco2) of 36 mm Hg, and lactate level of 2.2 mmol per liter. A chest radiograph shows bibasilar air-space opacities. Computed tomography (CT) of the head and neck without administration of contrast material shows no acute intracranial abnormalities and no fractures of the cervical spine.

体格检查发现,体温36.0°C,血压98/65 mm Hg,心率110 bpm,呼吸频率24 bpm,吸空气时氧饱和度90%。患者可遵嘱睁眼及活动肢体,但意识模糊,定向力障碍。双肺底呼吸音减低。右侧头皮有3-cm裂伤。其余体格检查没有异常发现。血常规检查白细胞计数12,400/mL。电解质、肾功能及肝功能检查均正常。动脉血气分析pH 7.37,Po2 60 mm Hg,Pco2 36 mm Hg,乳酸水平2.2 mmol/L。胸片显示双侧肺底实变。头颅及颈部CT平扫未发现急性颅内异常,颈椎未见骨折。

Ms. Wilkinson is a 72-year-old woman with a history of hypertension and urgency urinary incontinence who presents to the emergency department with a 1-day history of acute-onset abdominal pain in the left lower quadrant. Before the onset of abdominal pain, she had had constipation for 3 days and had not urinated for 1 day despite her efforts to drink plenty of water. She takes extended-release oxybutynin, at a dose of 30 mg daily, and she was recently given a prescription for hydrochlorothiazide, 25 mg daily. She does not smoke or drink alcohol.

Wilkinson女士是一名72岁女性患者,有高血压及尿潴留病史。患者因急性起病的左下腹疼痛1天到急诊就诊。在腹痛发生前,患者便秘3天,尽管大量饮水,但一整天未排尿。患者服用缓释奥西布宁30 mg qd,近期开始服用双氢克尿塞25 mg qd。患者不吸烟也不饮酒。

Her temperature is 36.7°C, blood pressure 126/75 mm Hg, heart rate 100 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 99% while she is breathing ambient air. On examination, she has tenderness to palpation of the left lower quadrant of the abdomen. She is alert and fully oriented. Cardiac and pulmonary examinations are normal. Laboratory studies show a creatinine level of 2.0 mg per deciliter (180 μmol per liter), anion gap 21 mmol per liter, white-cell count 24,200 per cubic millimeter with a predominance of neutrophils, hematocrit 45.0%, and lactate 3.9 mmol per liter. CT of the abdomen and pelvis with administration of contrast material shows large stool volume in the descending and sigmoid colon without evidence of gastrointestinal wall edema or hypoenhancement. A chest radiograph shows clear lungs without focal consolidations. An indwelling urinary catheter is placed, and 1 liter of urine is drained. Results of urinalysis are within normal limits.

患者体温 36.7°C,血压126/75 mm Hg,心率100 bpm,呼吸频率18 bpm,吸空气时氧饱和度99%。体格检查发现,触诊左下腹时有压痛。患者意识清楚,定向力正常。心肺检查正常。实验室检查发现肌酐2.0 mg/dL (180 μmol/L),阴离子间隙21 mmol/L,白细胞计数24,200/mL,中性粒细胞为主,血球压积45.0%,乳酸3.9 mmol/L。腹部及盆腔增强CT显示降结肠及乙状结肠内大量粪便,没有胃肠道水肿或低密度表现。胸片显示肺部正常,未见局灶实变。患者留置尿管,引流尿液1 L。尿常规检查结果正常。

You are the on-call provider caring for both Mr. Shui and Ms. Wilkinson. You suspect that there may be infections underlying the presentations of both patients, but you are not certain. You believe that early administration of antibiotics to patients with sepsis may save lives, but antibiotics can have serious adverse effects. Your task is to decide whether to administer antibiotics in addition to providing supportive care.

你负责上述两名患者的诊治。你怀疑两名患者的基础病因均可能为感染,但并不确定。你相信早期使用抗生素可能挽救脓毒症患者生命,但抗生素也可以导致严重不良反应。除支持治疗外,你的任务是确定是否应当使用抗生素。

  1. Do not administer antibiotics. 不应使用抗生素
  2. Administer antibiotics immediately. 立即使用抗生素

Option 1 选项1

Do Not Administer Antibiotics 不应使用抗生素

Michael Klompas, M.D., M.P.H.

These two cases encapsulate a common dilemma for clinicians who are trying to implement the recommendation of the Surviving Sepsis Campaign to administer broad-spectrum antibiotics within 1 hour after a patient’s presentation with possible sepsis. Both patients meet Surviving Sepsis Campaign criteria for sepsis and thus immediate administration of antibiotics, because their provider suspects infection and they have organ dysfunction with a Sequential Organ Failure Assessment (SOFA) score of 2 or higher (as defined by the Third International Consensus Definitions for Sepsis and Septic Shock [Sepsis-3]1). Mr. Shui has a SOFA score of 3 (because of confusion and impaired oxygenation); Ms. Wilkinson has a SOFA score of 2 (because of renal dysfunction). The dilemma, of course, is that the evidence for infection is equivocal in both patients and there are alternative explanations for their organ dysfunction. This is not an uncommon scenario. Fewer than 60% of patients admitted to intensive care units with a diagnosis of sepsis are ultimately confirmed to have definite or even probable infection.2

根据挽救脓毒症行动指南,发生可能的脓毒症后一小时内应使用广谱抗生素。对于试图实施这一推荐意见的临床医生而言,上述两个病例代表了常见的难题。两名患者均符合挽救脓毒症行动指南有关脓毒症的诊断标准(根据第三次脓毒症及感染性休克共识定义,可疑感染且出现器官功能障碍,即SOFA评分不低于2分),因此需要立即使用抗生素。Shui先生的SOFA评分为3分(因肾脏功能障碍);Wilkinson女士的SOFA评分为2分(因肾脏功能障碍)。当然,困难之处在于,两名患者的感染证据均不确定,可能有其他病因导致器官功能障碍。这种情况在临床中并不少见。ICU收治的诊断为脓毒症的患者中,不足60%最终确诊为感染或可疑感染。

There are good alternative explanations for both patients’ presentations. Mr. Shui has confusion, impaired oxygenation, diminished breath sounds, leukocytosis, an elevated lactate level, and bibasilar opacities after a possible viral prodrome. These findings are consistent with pneumonia, but his history of nonfatal drowning makes it more likely that his abnormal signs are due to water inhalation, aspiration pneumonitis, and prolonged anoxia. Patients who have had a nonfatal drowning event are at high risk for development of pneumonia, but evidence-based reviews recommend against antibiotic prophylaxis because case series have found no difference in rates of pneumonia or mortality with and without prophylaxis.3 When pneumonia does develop in patients who have had a nonfatal drowning event, the patients often have bacteria and fungi that are resistant to common empirical antibiotic choices. This risk of antibiotic-resistant organisms underscores the wisdom of waiting to see how patients’ conditions evolve and which organisms grow in culture to inform the selection of antibiotics before they are prescribed.

有其他的可能原因导致两名患者的临床表现。在可能的病毒感染前驱症状后,Shui先生出现意识模糊,氧合障碍,呼吸音减低,白细胞升高,乳酸升高,双肺底透光度减低。这些表现符合肺炎,但患者有非致命性溺水病史,因此,其异常体征更可能由于误吸、吸入性肺泡炎及长时间缺氧造成。非致命性溺水患者发生肺炎的风险较高,但循证综述不推荐使用预防性抗生素,因为病例系列研究发现,是否应用预防性抗生素,患者肺炎发生率或病死率并无差异。当非致命性溺水患者发生肺炎时,细菌及真菌往往对常用的经验性抗生素耐药。耐药菌感染的风险表明,密切观察患者病情变化,得到细菌培养结果后再选择抗生素的做法是明智的。

Ms. Wilkinson’s presentation is also not clearly due to infection. Signs that favor infection include tenderness in the left lower quadrant, tachycardia, an elevated lactate level, acute kidney injury, and leukocytosis with a predominance of neutrophils. The history and imaging, however, suggest that these signs are more likely due to constipation and acute urinary retention caused by oxybutynin therapy. Severe constipation and fecal impaction can cause marked inflammatory findings, including fever and leukocytosis, presumably due to bowel-wall compression leading to ischemia.4 Bacterial translocation across the bowel wall is possible but unusual. The CT scan is reassuring insofar as there is no inflammation or abscess. Leukocytosis is not specific for infection; approximately 50% of patients presenting to the emergency department with white-cell counts of 12,000 to 25,000 cells per cubic millimeter have noninfectious conditions.5

Wilkinson女士的临床表现也不一定由感染引起。支持感染的体征包括左下腹压痛,心动过速,乳酸升高,急性肾损伤,白细胞升高且中性粒细胞为主。然而,病史及影像学检查提示,上述表现更可能因便秘以及奥西布宁治疗导致的尿潴留引起。严重便秘及粪便嵌塞能够导致明显的炎症反应,包括发热和白细胞升高,这可能是肠壁压迫导致缺血的后果。也可能发生细菌经肠壁的异位,但这并不常见。CT扫描结果也支持这一判断,因为无炎症或脓肿表现。白细胞增多并非感染的特异性表现;白细胞计数12,000 to 25,000/mL的急诊患者中,约有50%由非感染因素导致。

The Surviving Sepsis Campaign recommends that all patients with sepsis and septic shock should receive antibiotics immediately, but two large observational series and a randomized, controlled trial suggest that rapidity of treatment with antibiotics matters most for patients who have septic shock; the data are equivocal for patients who have sepsis without shock.6-8 The absence of shock in our patients allows us time to gather more data and to observe their clinical trajectories before deciding whether the potential benefits of antibiotics outweigh their risks.9 In Mr. Shui’s case, it will be informative to see whether his pulmonary condition progresses and, if so, whether pulmonary cultures obtained while he is not receiving antibiotics yield pathogenic organisms. If both occur, directed antibiotics will then be warranted. In Ms. Wilkinson’s case, it will be informative to see what happens to her leukocytosis and creatinine and lactate levels if oxybutynin is stopped, the bladder is drained, and bowel movements are encouraged. It is very possible that she will get better with these steps alone.

挽救脓毒症行动推荐所有脓毒症和感染性休克患者应当立即使用抗生素,但是两项大规模观察性研究以及一项随机对照试验提示,抗生素治疗迅速与否对于感染性休克患者非常重要;但是对于未合并休克的脓毒症患者而言结果并不明确。上述两名患者均没有休克表现,因此我们有时间收集更多资料,并观察患者临床表现,然后再确定使用抗生素的益处是否超过其风险。对于Shui先生而言,监测其肺部病变进展情况非常重要。如果肺部病变进展,在应用抗生素前留取的呼吸道标本培养是否能够分离到微生物?如果上述两个问题的答案都是肯定的,那么需要使用针对性抗生素治疗。对于Wilkinson而言,应当在停用奥西布宁,尿液引流及促进肠道运动后,观察白细胞计数、肌酐及乳酸水平的变化情况。采取上述措施后,患者病情很可能改善。

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