高血糖高渗状态 (HHS) 通常会在数天至数周内隐匿进展。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com 首次实验室检查的目的是要确诊并评估疾病严重性。 后续检查需要确认潜在的诱发因素,例如感染或者心肌梗死 (MI)。
病史和体格检查
患者通常会有多尿、多饮、多食、无力和体重减轻的表现。[7]Umpierrez GE, Smiley DD. Complications. In: Fonseca V, ed. Clinical diabetes. Philadelphia, PA: Elsevier; 2006:101-8. 入院时,患者常有意识状态改变,[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com 并且与高血糖严重程度和血清渗透压相关。昏迷是 HHS 非常罕见的症状。一般情况下,昏迷与血清渗透压>330-340 mmol/kg (>330-340 mOsm/kg) 相关,并且性质上最常为高血钠性昏迷,而非高血糖性昏迷。
在患者既往病史或现病史中,需要注意的重要因素包括:改变或者遗漏胰岛素治疗、近期感染以及近期或者既往发生了 MI 或卒中,因为这些可能是 HHS 的触发因素或者危险因素。[1]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53.http://care.diabetesjournals.org/content/24/1/131.longhttp://www.ncbi.nlm.nih.gov/pubmed/11194218?tool=bestpractice.com[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com
查看完整的药物史十分重要,尤其是检查近期皮质类固醇、戊烷脒、去羟肌苷、拟交感神经药或者噻嗪类利尿剂,或者二代(非典型)抗精神病药的使用记录,因为这些能影响碳水化合物代谢并且可能促进高血糖危象的发展。[1]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53.http://care.diabetesjournals.org/content/24/1/131.longhttp://www.ncbi.nlm.nih.gov/pubmed/11194218?tool=bestpractice.com[7]Umpierrez GE, Smiley DD. Complications. In: Fonseca V, ed. Clinical diabetes. Philadelphia, PA: Elsevier; 2006:101-8.[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com
血容量不足的体征包括黏膜干燥、皮肤弹性差、心动过速、低血压,严重时出现休克。在老年患者中,皮肤不够充盈可能难以评估血容量不足。对这些患者颊黏膜干燥程度评估可获取更多信息。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31.http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com 因为外周血管舒张,某些患者可能会有轻微的体温过低。[1]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53.http://care.diabetesjournals.org/content/24/1/131.longhttp://www.ncbi.nlm.nih.gov/pubmed/11194218?tool=bestpractice.com[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31.http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com 严重的体温过低往往提示预后不良。[1]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53.http://care.diabetesjournals.org/content/24/1/131.longhttp://www.ncbi.nlm.nih.gov/pubmed/11194218?tool=bestpractice.com[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31.http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com
腹痛在 HHS 中不常见,但在糖尿病酮症酸中毒 (DKA) 中频率较高 (>50%)。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[7]Umpierrez GE, Smiley DD. Complications. In: Fonseca V, ed. Clinical diabetes. Philadelphia, PA: Elsevier; 2006:101-8. 因此,对于高血糖急症患者,如果存在无法解释的腹痛,医生应该考虑 DKA 而不是 HHS 的诊断。[7]Umpierrez GE, Smiley DD. Complications. In: Fonseca V, ed. Clinical diabetes. Philadelphia, PA: Elsevier; 2006:101-8. HHS 患者偶尔可能表现出局灶性神经系统体征(偏盲和轻偏瘫)和癫痫发作(局灶性或全身性)。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[7]Umpierrez GE, Smiley DD. Complications. In: Fonseca V, ed. Clinical diabetes. Philadelphia, PA: Elsevier; 2006:101-8.[8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31.http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com 这种表现经常被误以为是急性卒中。然而,通过液体和胰岛素治疗纠正高血糖,可以快速消除 HHS 患者的这些体征。[7]Umpierrez GE, Smiley DD. Complications. In: Fonseca V, ed. Clinical diabetes. Philadelphia, PA: Elsevier; 2006:101-8.[8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31.http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com 在 HHS 的早期阶段,持续性不全癫痫发作是癫痫发作的一种不常见形式,仅发生在 6% 的 HHS 患者中。[40]Harden CL, Rosenbaum DH, Daras M. Hyperglycemia presenting with occipital seizures. Epilepsia. 1991 Mar-Apr;32(2):215-20.http://www.ncbi.nlm.nih.gov/pubmed/2004625?tool=bestpractice.com 与 HHS 中高血糖相关的癫痫发作通常耐抗癫痫治疗,且苯妥英可能会进一步加剧 HHS。[8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31.http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com
初始检查
首次实验室检查的目的是要确诊并评估疾病严重性。
血糖
血尿素、血氮和肌酐
血清电解质[8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31.http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com
存在高血糖时,由于渗透压导致水从细胞内流向细胞外间隙,通常出现血清钠浓度降低。总钠量不足,为 5-13 mmol/kg (5-13 mEq/kg)。HHS 患者在高血糖的基础上出现高血钠表明血容量严重不足。为了评估钠和水缺乏的严重程度,应计算校正钠浓度,具体算法为:钠浓度检测值+ (血糖浓度-100 mg/dL)/100 mg/dL×1.6 mEq/L。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com 如果存在昏迷症状,最常见的原因是高钠血症而不是高血糖症。
总缺钾量为 4 至 6 mmol/kg (4~6 mEq/kg),是由利尿引起的钾损失升高所致。 尽管全身缺钾,但是血清钾浓度通常升高。 这是由于胰岛素不足、高渗性和酸血症造成大量钾细胞外转移。 住院时的低钾水平提示全身重度缺钾。[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com
血清氯水平通常偏低。 通常缺氯总量为 5 到 15 mmol/kg (5~15 mEq/kg);其继发于钠缺乏。
血清镁水平通常偏低。 通常缺镁总量为 0.5 到 1 mmol/kg (1~2 mEq/kg),这是由利尿引起的镁损失增加而造成的。
血清钙水平通常偏低。 通常缺钙总量为 0.5 到 1 mmol/kg (1~2 mEq/kg),这是由利尿引起的钙损失增加而造成的。
血清磷酸盐水平通常偏低。 全身磷酸盐缺乏总量为 3 到 7 mmol/kg,这是由利尿引起的磷酸盐损失增加而造成的。
血清渗透压浓度
有效血清渗透压浓度的计算公式为:2(测量钠浓度 [mmol/L])+(葡萄糖 [mmol/L])= mmol/kg(2 [测量钠浓度 {mEq/L}]+[葡萄糖 {mg/dL}]/18 = mOsm/kg)。[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com 不需要考虑尿素的浓度,因为尿素是自由渗透的,它的积累不能改变渗透压浓度梯度。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com
所有患者均升高(≥320 mOsm/kg)。
血清或尿酮
β-羟基丁酸是生酮作用的主要产物,乙酰乙酸构成酮的其余部分。随着时间推移,β-羟基丁酸会转化为乙酰乙酸,随尿液排出。测定血清酮体时,硝普钠反应检测不到 β-羟基丁酸。因此,最初发病时通过硝普钠反应测定血清或尿液酮体的结果可能是阴性的,或者在 DKA 纠正后仍为阳性(产生血清中没有酮体或者 DKA 没有纠正的表象)。因此,指南建议,除了使用硝普钠反应检测酮体外,还应尽可能直接测定 β-羟基丁酸。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com[41]Dhatariya KK, Vellanki P. Treatment of diabetic ketoacidosis (DKA)/hyperglycemic hyperosmolar state (HHS): novel advances in the management of hyperglycemic crises (UK versus USA). Curr Diab Rep. 2017 May;17(5):33.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375966/http://www.ncbi.nlm.nih.gov/pubmed/28364357?tool=bestpractice.com
阴离子间隙
阴离子间隙的计算公式为 (Na)-(Cl+HCO3) (mmol/L [mEq/L])[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com
浓度≥10 到 12 mEq/L 预示着阴离子间隙的酸中毒(例如,乳酸或者酮症酸中毒)。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com
血清乳酸
如果伴有乳酸性酸中毒,乳酸的水平会升高。[2]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.http://care.diabetesjournals.org/content/32/7/1335.longhttp://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com
尿液分析
血气分析
动脉血 pH 值通常>7.30;动脉血碳酸氢根>15 mmol/L (>15 mEq/L)。静脉血 pH 值通常比动脉血低 0.03 个单位。一些研究表明,静脉血和动脉血 pH 值之间的差异不足以改变临床管理措施。[41]Dhatariya KK, Vellanki P. Treatment of diabetic ketoacidosis (DKA)/hyperglycemic hyperosmolar state (HHS): novel advances in the management of hyperglycemic crises (UK versus USA). Curr Diab Rep. 2017 May;17(5):33.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375966/http://www.ncbi.nlm.nih.gov/pubmed/28364357?tool=bestpractice.com 此外,静脉 pH 采样更容易、更方便、疼痛更轻。
全血细胞计数 (FBC)
高血糖危象有白细胞增多的现象。 然而,白细胞增多数目>25 x 10^9/L (>25,000/μL) 可能预示着感染,需要进一步的评估。[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com
肝功能试验 (LFT)
其他检查
后续检查需要确认潜在的诱发因素,例如感染或者心肌梗死 (MI),或者尝试其他诊断。
胸部 X 线检查 (CXR)
心电图 (ECG)
如果怀疑心血管疾病(如 MI)为诱发因素或者存在严重的电解质异常时,应该进行此项检测。[1]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001 Jan;24(1):131-53.http://care.diabetesjournals.org/content/24/1/131.longhttp://www.ncbi.nlm.nih.gov/pubmed/11194218?tool=bestpractice.com[15]Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006 Dec;29(12):2739-48.http://care.diabetesjournals.org/content/29/12/2739.longhttp://www.ncbi.nlm.nih.gov/pubmed/17130218?tool=bestpractice.com 还可能存在低钾血症(U 波)或高钾血症(高 T 波)的证据。
心肌酶
血液、尿液或痰液培养