Rambam Medical Center, Haifa, Israel.
Corresponding author: Dr Ivan Gur, Department of Internal Medicine C, Rambam Medical Center, 4 HaAlia Street, Haifa 3109601, Israel,
Diving Hyperb Med. 2024 Sep 30;54(3):168-175. doi: 10.28920/dhm54.3.168-175.
The effects of methylphenidate, a stimulant often prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD), on the development of central nervous system oxygen toxicity (COT) have not been experimentally evaluated.
The records of all pure-oxygen-rebreather divers evaluated at our institution from 1975-2022 were assessed. Cases of COT were defined as a new onset of tinnitus, tunnel vision, myoclonus, headache, nausea, loss of consciousness, or seizures resolving within 15 minutes from breathing normobaric air, and matched 4:1 with similar controls. Any medications issued to the diver in the preceding three months, including methylphenidate, were recorded. In the animal arm of this study, male mice were exposed to increasing doses of methylphenidate orally, with subsequent exposure to hyperbaric O₂ until clinically evident seizures were recorded.
Seventy-five cases of COT were identified in divers, occurring at a median of 80 (range 2-240) minutes after dive initiation at a median depth of 5 m (2-13). Hypercarbia was documented in 11 (14.7%) cases. Prescription of methylphenidate in the preceding three months was not associated with increased risk (OR 0.72, 95% CI 0.16-3.32) of COT. In mice, increasing methylphenidate exposure dose was associated with significantly longer mean COT latency time being 877 s (95% CI 711-1,043) with doses of 0 mg·kg⁻¹; 1,312 s (95% CI 850-1,773) when given 0.75 mg·kg⁻¹; and 1,500 s (95% CI 988-2,012) with 5 mg·kg⁻¹ (F = 4.635, P = 0.014).
Observational human data did not demonstrate an association between methylphenidate and an increased risk of COT. Methylphenidate exposure in mice prolongs COT latency and may have protective effects against COT.
哌醋甲酯是一种常用于治疗注意力缺陷多动障碍（ADHD）的兴奋剂，但其对中枢神经系统氧中毒（COT）发展的影响尚未通过实验进行评估。
评估了 1975 年至 2022 年期间在我们机构接受纯氧再呼吸潜水员评估的所有记录。COT 病例定义为新出现耳鸣、隧道视觉、肌阵挛、头痛、恶心、意识丧失或癫痫发作，在呼吸常压空气后 15 分钟内缓解，并且与类似的对照组 4:1 匹配。记录潜水员在过去三个月中服用的任何药物，包括哌醋甲酯。在这项研究的动物部分，雄性小鼠口服接受递增剂量的哌醋甲酯，随后暴露于高压氧中，直到记录到明显的临床发作。
在潜水员中发现了 75 例 COT 病例，在潜水开始后中位数 80 分钟（范围 2-240 分钟），中位数深度为 5 米（2-13 米）发生。在 11 例（14.7%）病例中记录到高碳酸血症。在过去三个月内开哌醋甲酯处方与 COT 风险增加无关（OR 0.72，95%CI 0.16-3.32）。在小鼠中，哌醋甲酯暴露剂量的增加与 COT 潜伏期的平均时间明显延长相关，0mg·kg⁻¹剂量时为 877s（95%CI 711-1,043）；0.75mg·kg⁻¹剂量时为 1,312s（95%CI 850-1,773）；5mg·kg⁻¹剂量时为 1,500s（95%CI 988-2,012）（F=4.635，P=0.014）。
观察性的人类数据并未显示哌醋甲酯与 COT 风险增加之间存在关联。小鼠中哌醋甲酯的暴露延长了 COT 的潜伏期，可能对 COT 具有保护作用。
