Toxicity of phosphate enemas – an updated review

Figures & data

Figure 1. Flow chart of the data retrieval process.

Table 1. Case reports of adverse effects of phosphate enemas 2005–2021. A. Children and B Adults.

Author (year) [reference number]	Age (gender)	Associated morbidity	Enema vol (PO4 dose 1.38 mmol/ml)	Serum PO4 concentration mmol/L (ref range)	Serum Ca concentration mmol/L (ref range)	Na^+ concentration mmol/L (ref range)	K^+ concentration mmol/L (ref range)	Creatinine concentration μmol/L (ref range)	Specific treatment for metabolic disorder
A. Children
Butani (2005) [17]	11y (m)	End stage renal disease 2ry to neurogenic bladder	2 × ‘adult Fleet enemas’; dose 3.3 mmol/kg	6 (0.77–1.61)	1.38 (2.20–2.65)	Not reported	Not reported	Not reported	Haemodialysis, IV Ca gluconate, dopamine.
Biebl et al. (2009) [11]	13y (m)	Costello syndrome and chronic constipation	4 × 125 ml	17.75 (0.95–1.75)	0.56 (2.20–2.70)	171 (136–146)	Not reported	373 (27–62)	IV fluid
Kostic et al. (2010) [16]	8 days (f)	Neonate (Medication error)	Fleet enema 35 ml/kg; Wt 2.85 kg	9.17 (1.0–2.5)	0.72 (2.15–2.94)	151 (130–145)	5.2 (4–7)	99.9 (26.5–62)	IV slow Ca gluconate 10% (2 ml/kg slow; 8 ml/kg over 24 h). Flow through peritoneal dialysis.
Ladenhauf et al. (2012) [12]	5y (m)	Chronic constipation	Not stated	6.03 (1.1–1.98)	0.36 (2.12–2.62)	Not reported	Not reported	Not reported	Intravenous calcium gluconate, lactate Ringer's solution, fluids
	4y (m)	Chronic constipation		4.76 (1.1–1.98)	0.44 (2.12–2.62)	Not reported	Not reported	Not reported	Intravenous calcium gluconate, lactate Ringer's solution, fluids
	2y (f)	Hirschsprung's disease		5.5 (1.1–1.98)	0.4 (2.12–2.62)	Not reported	Not reported	Not reported	Intravenous calcium gluconate, lactate Ringer's solution, fluids
Becknell et al. (2014) [13]	4y (m)	Anorectoplasty imperforate anus	240 ml	21.3 (1.32–1.91)	0.6 (2.0–2.63)	155 (Not reported)	3.0 (Not reported)	Not reported	IV CaCl, HCO3, & fluid, haemodialysis
Marek et al. (2015) [14]	6 months (m)	Undiagnosed Hirschsprung's disease, with magacolon	Not stated	19.95 (1.15–2.15)	1.23 (2.17–2.62)	154 (131–140)	Not reported	Not reported	Haemodialysis.
Sanchez et al. (2017) [15]	2y (f)	Chronic constipation	59 ml	12.24 (NA)	1.05 (NA)	155 (Not reported)	2.3 (Not reported)	47.7 (Not reported)	IV Ca gluconate & fluids, furosemide.
B. Adults
Carl et al. (2007) [18]	79y (f)	Mild sigmoid diverticular disease	118 ml	2.65 (0.8–1.55)	‘Normal’	‘Normal’	‘Normal’	‘Normal’	IV Saline
Kosseifi et al. (2008) [19]	77y (m),+	CCF, diabetes.	798 ml	5.17 Not reported	1.2 (2.1–2.55)	Not reported	Not reported	Not reported	IV Saline
Hsu and Wu (2008) [22]	81y (m)	Post-surgery	118 ml	6.3 (0.8–1.5)	1.3 (2.0–2.5)	149 (134–148)	3.5 (3.0–3.8)	707 (35–124)	Haemodialysis
Ori et al. (2012) [20] (Results are presented in the same order in each column)	77y (f), 89 y (m)+ 70 y (f), 89 y (f)+, 61 (f)+ 77 (f), 89 (m), 83 (f)+, 80(m), 80(m), 88(m)+	None detailed	Individual dose not specified. 8 received a ‘standard’ dose. 3 ‘high’ 500–798ml.	7.1, 4.26, 10.11, 11.56, 14.54, 3.9, 2.52, 1.71, 5.78, 2.07, 3.07 (0.87–1.45)	1.28, 1.1, 1.08, 1.05, 0.5, 1.63, 1.6, 2.18,1.9, 2.05, 2.08 (NA)	Not reported	Not reported	Not reported	IV resuscitation; haemodialysis in 2 cases who died.
Szoke et al. (2012) [21]	90y (m)+	Heart and kidney failure	240 ml	9.69 (0.81–1.45)	0.93 (2.13–2.63)	155 (135–145)	2.7 (3.5–5.0)	492.4 (61.9–106.1)	Intravenous calcium gluconate
Di Mario et al. (2021) [23]	73y (m)	Hypertension, diabetes, stage 3 b renal failure	Repeated phosphate enemas for 3 days	8.0	1.6	140	3.9	345	Haemodialysis

Deaths are marked with a +. All results have been converted to SI units when quoted in other units in the original papers. Comparative mass units are presented in the text.

Table 2. Clinical trials and large case series reporting use of phosphate enemas.

Author (Yr) [reference number]	Type of study	Population	Agents and dose	Outcome
Anderson et al. (2019) [26]	Retrospective comparative chart review	768 children; median 6.2 y receiving enemas 396 phosphate	Sodium phosphate (3.1 ml/kg): Combination docusate, Mg Citrate, mineral oil, sodium phosphate: Soap.	Assessment based on time to defecate, ADR’s only abdominal pain.
Ainley et al. (2005) [27]	Cohort study. Pre-test/post-test design	100 colonoscopy outpatients aged 19–89 y (48 f)	Fleet Enema (45 mL given 12-hr apart)	PO4 mM 0.91–2.81 (Normal 0.8–1.6) hyperphosphataemia 45%, Ca^+ 2.07–2.46 mmol/L (Normal 2.15–2.6) hypocalcaemia 16%
Sàdaba et al. (2006) [29]	RCT (open-label)	24 participants aged 36–68 y (12 m & 12 f)	Enema Casen (250 ml) v no therapy	Active: PO4 5.6 mg/dL (SD 1.3, range 3.6–8.5) hyperphosphatemia (16.7%); placebo 3.7 mg/L (SD 0.3, range 2.7–4.6 mmol/L p < 0.01 active v placebo
Jacobson et al. (2010) [30]	RCT (open-label)	45 participants aged > 50 y	Fleet Enema (117 ml) and Enema Casen (224 ml)	No differences between preparations. Hyperphosphatemia in 10 of 40 with data, related to retention time.
Hansen et al. (2011) [31]	Retrospective comparative chart review	96 paediatric ED patients (45 bm & 51 f)	Milk and Molasses enema (240 ml) and Sodium phosphate Enema (59/118 ml)	Emesis, diarrhoea, fatigue and abdominal pain and distention - (64%) had ADR with PO4 enema & (36%) Milk and molasses
Niv et al. (2013) [32]	2-phase cohort study (retrospective then prospective)	555 ED patients (269 in 1st phase, 286 in 2nd), mostly aged > 65 y	Fleet Enema (1st phase) and Easy Go enema (2nd phase)*	Hyperphosphatemia, perforation-NaP (1.4%) Easy Go(0%), phosphate nephropathy and death- NaP (3.9%) Easy Go(0.7%)
Alami et al. (2015) [28]	Cohort study. Pre-test/ post-test design	100 inpatients aged 75–100 y (52 f 48 m)	Sodium phosphate enema (113 ml)	Serum calcium (IQR) pre: 2.32 (0.12); post: 2.34 (0.13) mmol/L Serum phosphate 1.14 (0.39) 1.16 (0.42) mmol/L. Hyperphosphataemia (6%) and hypocalcaemia (2%)
Schaefer et al. (2016) [33]	Cohort study (retrospective)	70,499 outpatients receiving aged 50–89 y	Sodium phosphate enema and Polyethylene glycol (PEG): doses not stated	eGFR decline over 15 months - phosphate enema (4.5%) PEG (3.4%) p < 0.001; OR 1.4 (95% CI 1.1–1.8) for long term eGFR decline PO4 vs PEG. No acute injury risk.
Dagan et al. (2017) [34]	Case control (retrospective)	412 patients of whom 206 received a single phosphate enema	Sodium phosphate 3 mmol/ml in 15 ml	Renal and electrolyte function on routine blood tests over 3 days. No changes were identified.

Abbreviations: RCT, randomized controlled trial; ADR, Adverse Drug Reaction.

*Dose was 59 mL for patients under 11 years and 118 mL for patients 11 years and over. Comparative mass units are presented in the text.

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