Stirling High School, Stirling, UK.
Pharmacology, Toxicology & Therapeutics, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Clin Toxicol (Phila). 2022 Jun;60(6):672-680. doi: 10.1080/15563650.2022.2054424. Epub 2022 May 5.
Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse effects of phosphate enemas from January 1957 to March 2007 and identified 12 deaths. These were thought due to electrolyte disturbances, heart failure and kidney injury. These data raised concerns about the use of phosphate enemas in routine practice. Newer osmotic-based enema alternatives are now available that do not contain absorbable ions. We sought to review the literature since this review and evaluate the latest data on the toxicity of phosphate-containing enemas. To gain a fuller picture we included case series and larger studies as well as case reports.
To review the toxicity of phosphate enemas, particularly with respect to acute metabolic consequences and their associated clinical features. To identify risk factors for metabolic toxicity and consider whether phosphate enemas should be relatively contra-indicated in specific patient groups.
A systematic literature review was conducted in PubMed, Google Scholar, and Cochrane Reviews (2005-2021) using the search terms 'phosphate enema or sodium phosphate enema' or 'phosphate-based enema' or (phosphate AND enema) or (Fleet AND enema) or 'sodium phosphate laxatives' or 'sodium phosphate catharsis' or 'sodium phosphate cathartic'. Relevant papers were read, and data were extracted.
The searches identified 489 papers of which 25 were relevant: seven papers were case reports or small case series of metabolic abnormalities from the use of phosphate enemas in nine children, six were case reports on 16 adults. Nine papers were large case series or clinical studies that included data on systemic metabolic effects, of varying size from 24 healthy volunteers to a cohort of 70,499 patients. Case reports identified seven adult deaths but none in children. Children most often presented with decreased consciousness (6/9), and tetany (4/9). In adults overall only five cases had clinical features reported, hypotension was seen in four and QT prolongation in two. Treatment was generally symptomatic, with intravenous fluid and calcium salts for electrolyte changes and hypocalcaemia, and vasopressors for severe hypotension. Haemodialysis was used in three children and peritoneal dialysis in one, all of whom survived. In adults, haemodialysis did not prevent death in two of four cases in whom it was used. Common factors underlying toxicity were inappropriately high phosphate dose, or enema retention, both resulting in greater absorption of phosphate. Associated pre-disposing conditions included Hirschsprung disease in children and co-morbidity and renal impairment (2/5) in older adults. Absolute reported changes in serum phosphate or calcium were not accurate indicators of outcome. Larger case series and clinical trials confirm an acute effect of phosphate enemas on serum phosphate, which was related to both dose and retention time. These effects were not seen with non-phosphate preparations. In these cases series, adverse events were rarely reported.
Phosphate enemas are potentially toxic, particularly in young children with Hirschsprung disease and in the elderly with co-morbidity. Raised awareness of the risk of phosphate enemas is still required. Other less toxic enema preparations are available and should be considered in patients at extremes of age. If phosphate enemas are the only clinical option careful monitoring of biochemical sequelae should be undertaken.
含磷酸盐的灌肠剂被广泛应用,可能会引起重要的不良反应。2007 年发表的一篇系统综述报告了 1957 年 1 月至 2007 年 3 月期间关于磷酸盐灌肠剂不良反应的文献,并确定了 12 例死亡病例。这些病例被认为是由电解质紊乱、心力衰竭和肾损伤引起的。这些数据引起了人们对在常规实践中使用磷酸盐灌肠剂的担忧。现在有更新的基于渗透压的灌肠剂替代品,它们不含可吸收的离子。我们试图回顾自该综述以来的文献,并评估关于含磷酸盐灌肠剂毒性的最新数据。为了更全面地了解情况,我们还包括了病例系列和更大规模的研究以及病例报告。
综述磷酸盐灌肠剂的毒性,特别是其对急性代谢后果及其相关临床特征的影响。确定代谢毒性的危险因素,并考虑是否应在某些特定患者群体中相对禁忌使用磷酸盐灌肠剂。
在 PubMed、Google Scholar 和 Cochrane Reviews(2005-2021 年)中进行了系统文献检索,使用的搜索词为“phosphate enema 或 sodium phosphate enema”或“phosphate-based enema”或(phosphate AND enema)或(Fleet AND enema)或“sodium phosphate laxatives”或“sodium phosphate catharsis”或“sodium phosphate cathartic”。阅读相关论文并提取数据。
检索到 489 篇论文,其中 25 篇相关:7 篇论文是关于 9 名儿童使用磷酸盐灌肠剂引起代谢异常的病例报告或小病例系列,6 篇是关于 16 名成人的病例报告。9 篇论文是大型病例系列或临床研究,包括系统代谢效应的数据,规模从 24 名健康志愿者到 70499 名患者不等。病例报告确定了 7 例成人死亡,但儿童中没有死亡。儿童最常出现意识障碍(6/9)和抽搐(4/9)。在所有成年人中,只有 5 例报告了临床特征,4 例出现低血压,2 例出现 QT 延长。治疗通常是对症治疗,包括静脉补液和钙盐治疗电解质紊乱和低钙血症,以及血管加压素治疗严重低血压。3 例儿童接受血液透析,1 例接受腹膜透析,所有患者均存活。在成年人中,4 例中有 2 例使用血液透析未能预防死亡。毒性的共同潜在因素是磷酸盐剂量过高或灌肠保留不当,这两者都会导致磷酸盐吸收增加。相关的易患疾病包括儿童的先天性巨结肠病和老年患者的合并症和肾功能损害(2/5)。血清磷酸盐或钙的绝对变化并不是预后的准确指标。更大规模的病例系列和临床试验证实,磷酸盐灌肠剂会对血清磷酸盐产生急性影响,这与剂量和保留时间有关。非磷酸盐制剂则不会产生这种影响。在这些病例系列中,很少有不良事件报告。
磷酸盐灌肠剂具有潜在毒性,特别是对患有先天性巨结肠病的儿童和患有合并症的老年患者。仍然需要提高对磷酸盐灌肠剂风险的认识。其他毒性较小的灌肠剂制剂可用,应考虑在年龄极端的患者中使用。如果磷酸盐灌肠剂是唯一的临床选择,应仔细监测生化后果。