Incidence of rebound salicylate toxicity following cessation of urine alkalinization

Management of patients with salicylate toxicity frequently requires urine alkalinization to enhance excretion of salicylate. One strategy for determining when to stop urine alkalinization is to wait for two consecutive serum salicylate concentrations to be less than 300 mg/L (2.17 mmol/L) and declining. When alkalinization of the urine ceases, a rebound in serum salicylate concentration can occur from tissue redistribution or delayed gastrointestinal absorption. Whether this can lead to rebound toxicity is not well understood. This was a single-center, retrospective review of cases with a primary ingestion of acetylsalicylic acid reported to the local poison center over a five-year period. Cases were excluded if the product was not listed as the primary ingestion or if there was no serum salicylate concentration documented after discontinuation of intravenous sodium bicarbonate infusion. The primary outcome was the incidence of serum salicylate rebound to a concentration greater than 300 mg/L (2.17 mmol/L) after discontinuation of intravenous sodium bicarbonate infusion. A total of 377 cases were included. Of these, eight (2.1%) had a serum salicylate concentration increase (rebound) after stopping the sodium bicarbonate infusion. All these cases were acute ingestions. Five of the eight cases had rebound serum salicylate concentrations that were greater than 300 mg/L (2.17 mmol/L). Of these five patients, only one reported recurrent symptoms (tinnitus). Prior to stopping urinary alkalinization, the last or the last two serum salicylate concentrations were less than 300 mg/L (2.17 mmol/L) in three and two cases, respectively. In patients with salicylate toxicity, the incidence of rebound in serum salicylate concentration after cessation of urine alkalinization, is low. Even if serum salicylate rebounds to supratherapeutic concentrations, symptoms are often absent or mild. Routine repeat serum salicylate concentrations after urine alkalinization is stopped may be unnecessary unless symptoms recrudesce.

水杨酸盐中毒患者的临床管理通常需采用尿液碱化疗法以提升水杨酸盐的排泄效率。判断尿液碱化疗法终止时机的常用策略为：连续两次检测血清水杨酸盐浓度均低于300mg/L（2.17mmol/L）且呈下降趋势。当尿液碱化疗法停止后，由于组织再分布或胃肠道吸收延迟，血清水杨酸盐浓度可能出现反跳现象，此类反跳是否会引发中毒反弹，目前尚未明确。本研究为单中心回顾性分析，纳入了5年内上报至当地毒物控制中心的、以乙酰水杨酸（acetylsalicylic acid）为主要摄入源的病例。若患者并非以该物质为主要摄入源，或在停用静脉输注碳酸氢钠后未记录血清水杨酸盐浓度，则排除该病例。本研究的主要结局为停用静脉碳酸氢钠输注后，血清水杨酸盐浓度反跳至300mg/L（2.17mmol/L）以上的发生率。最终纳入377例病例。其中8例（2.1%）在停用碳酸氢钠输注后出现血清水杨酸盐浓度升高（即反跳），且均为急性摄入病例。8例反跳病例中，5例的血清水杨酸盐浓度反跳至300mg/L（2.17mmol/L）以上；这5例患者中仅1例出现复发性症状（耳鸣）。在停止尿液碱化疗法前，3例患者的末次血清水杨酸盐浓度、2例患者的末次两次血清水杨酸盐浓度均低于300mg/L（2.17mmol/L）。结果显示，水杨酸盐中毒患者在停止尿液碱化疗法后，血清水杨酸盐浓度反跳的发生率较低；即便反跳至超治疗浓度范围，患者的症状通常也较为轻微或无明显症状。因此，除非患者症状复发，否则在停止尿液碱化疗法后无需常规复查血清水杨酸盐浓度。