Acute Cardiovascular Collapse Following Glycerin Retention Enema

Andrew Chou; Shih-Hua Lin; Ming-Tso Yan

Acute Cardiovascular Collapse Following Glycerin Retention Enema

by Andrew Chou¹, Shih-Hua Lin^2,3, Ming-Tso Yan^1,4*

¹Division of Nephrology, Department of Medicine, Cathay General Hospital, Taipei, Taiwan

²Division of Nephrology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan

³Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

⁴School of Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan

^*Corresponding author: Ming-Tso Yan, Division of Nephrology, Department of Medicine, Cathay General Hospital, No 280, Section 4, Ren-Ai Road, Daan 104, Taipei, Taiwan

Received Date: 16 March 2024

Accepted Date: 19 March 2024

Published Date: 21 March 2024

Citation: Chou A, Lin SH, Yan MT (2024) Acute Cardiovascular Collapse Following Glycerin Retention Enema. J Urol Ren Dis 09: 1373. https://doi.org/10.29011/2575-7903.001373.

Keywords: Constipation; Hypermagnesemia; Laxatives; Magnesium Salt; Shock

Introduction

Magnesium (Mg²⁺) is second abundant intracellular cation. It is crucial in maintaining cell viability and involved in regulation of multiple enzymes function, nucleic acid synthesis and energy production [1,2]. Hypermagnesemia is a potentially lethal electrolyte abnormality but has long been considered to be rare. With the increasing use of magnesium in diverse clinical conditions including preeclampsia/eclampisa, arrhythmia, severe acute asthma, migraine, constipation or dyspepsia, the prevalence of hypomagnesemia could possibly be underestimated. It may be caused by that serum Mg²⁺ level is not routinely measured in most cases especially in patients without advanced renal failure in light of high efficacy of renal Mg²⁺ excretion. The delay in the recognition of hypermagnesemia may result in a poor outcome and even mortality. Herein, we presented a case with normal renal function who developed lethal hypermagnesemia following 5-day use of oral magnesium oxide.

Case Presentation

A 59-year-old male presented to the emergency department with worsening abdominal bloating for 2 days. He had a history of diabetes mellitus, hypertension and stroke with residual left hemiparesis on regular medications of sitagliptin and amlodipine. Since he was severely constipated with no defecation, 1500 mg of magnesium oxide daily was consumed for 5 days. On arrival, his blood pressure was 118/70 mmHg, pulse rate 89/minute, respiratory rate 20/minute and body temperature 36.3℃. Physical examinations showed reduced bowel movement and his abdomen being apparently distended, tympanic, diffusely tender with no shifting dullness, rebound tenderness or muscle guarding. The rest of physical examinations were unremarkable. Laboratory investigations demonstrated only mild anemia (Hemoglobin 11.3 g/dL) and his serum biochemistries were within the reference range (Table 1). Plain abdominal radiography demonstrated marked and diffuse dilatation of large intestinal loops with fecal impaction. Computed tomography revealed no abdominal emergencies such as intussusception or hollow organ perforation. Therefore, 20-minute retention glycerin enema was undergone twice with intravenous saline administration but minimal amount of stool was defecated.

Item	Unit	Reference	Admission	12 hours	15 hours	25 hours
Hb	g/dL	14-18	11.3
WBC	10^3/μL	4-10	9.08
Platelet	10^3/μL	130-400	178
BUN	mg/dL	8-25	25	38	42
Cr	mg/dL	0.63-1.3	1.28	1.98	1.85
eGFR	mL/min		57.3	38	42
Na⁺	mmol/L	135-145	129	132	133	133
K⁺	mmol/L	3.5-5.3	4.3	3.3		3.6
Ca²⁺	mg/dL	8.5-10	8.5	8.5	8.3	8.8
Phosphate	mg/dL	2.5-4.5	3.2			5.2
Mg²⁺	mg/dL	1.6-2.3	2.1	10.6	13.7	8.7
pH				7.30
PCO₂	mmHg	35-45		45.7
PO₂	mmHg			39.9
HCO₃^-	mmol/L	22-28		22.0

Denote: BUN: Blood Urea Nitrogen; Cr: Creatinine; eGFR: Estimated Glomerular Filtration Rate; Hb: Hemoglobin; WBC: White Cell Count

Table 1: A series of laboratory data at emergency department.

Twelve hours later, he became drowsy and blood pressure dropped to 86/58 mmHg acutely with bradycardia (23/minute). Physical examinations showed bilaterally mild basal rales only. Pertinent serological surveys revealed elevated Cr level (1.98 mg/dL), mild mixed metabolic and respiratory acidosis (pH 7.30, PCO2 45.7mmHg and HCO₃ 22.0 mmol/L), hypokalemia (K⁺ 3.3 mmol/L), and incredible hypermagnesemia (10.6 mg/dL), soon rising to 13.7 mg/dL (Table 2). With serial measurements, serum levels of troponin-T and creatine kinase MB did not elevate. Electrocardiography showed atrial fibrillation with slow ventricular response. Chest radiography revealed slightly increased vascular markings. Cardiac ultrasonography demonstrated ejection fraction rate of 45 % without valvular disorders or pericardial effusion. Saline and calcium gluconate were administered immediately with an implantation of temporary pacemaker, repeated atropine administration as well as continuous vasopressors infusion with dopamine and norepinephrine. However, all those strategies can not correct his bradyarrhythmia with cardiogenic shock. For refusal of transferring to intensive care unit, hemodialysis rather than continuous renal replacement therapy was undergone. Massive saline infusion as replacement solution during hemodialysis, a modality mimicking hemodiafiltration, was performed in our patients. However, poor hemodynamic status caused termination of hemodialysis and Mg²⁺ level was decreased from 13.7 to 8.7 mg/dL post 3-hour hemodialysis with a limited improvement of hemodynamic status. This patient died 10 hours after the first session of hemodialysis.

Patients	Age	Gender	Mg²⁺ salt type	Route	[Mg²⁺]_MAX(mg/dL)		Reference
1	7	Male	MgSO₄	Enema	41.2		[3]
2	89	Male	Mg citrate (34g)	Enema	12.6		[4]
3	4	Male	MgSO₄(100mL)(Fletcher’s MgSO₄ enema)	Enema	14.3		[5]
4	85	Female	MgSO₄(28g)	Enema	18.7		[6]
5	56	Male	MgSO₄ (42.5 g)+ Mg citrate (17.45 g)	Oral	23	+ Charcoal	[7]
6	77	Female	Mg citrate (17.5 g)	Oral	10.3	+ Charcoal	[8]
Our case	59	Male	MgO (1.5 g)	Oral	13.7	+ Glycerin enema

Table 2: Cases with normal renal function but acute fatal hypermagnesemia secondary to a robust Mg²⁺ gut absorption.

Discussion

In view of the difficulty in correcting bradycardia with medications and pacemaker in our patient, arrhythmia secondary to metabolic disturbance especially severe electrolytes imbalance should be considered. For his relatively stationary serum levels of K⁺ and Ca²⁺ as well as acid base status, hypermagnesemia related fetal arrhythmia and cardiogenic shock was diagnosed. Magnesium homeostasis is regulated mainly by the balance between intestinal absorption and renal excretion. Although the majority of Mg²⁺ is absorbed by small intestine in a passive paracellular manner, fine-tuning of Mg²⁺ absorption occurs in colon transcellularly via transporters including apical Transient Receptor Potential Channel Melastatin Member 6 (TRPM6) and TRPM7 as well as basolateral CNNM4 Na⁺-Mg²⁺ exchanger [9]. In kidney, most filtered Mg²⁺ is absorbed paracellularly via claudin 1, 2 in proximal tubule and via claudin 10, 14, 16, 19 in thick ascending limb, respectively. The final renal Mg²⁺ excretion is determined by fine-tuning of renal Mg²⁺ absorption occurring in distal tubule, the last site of nephron to absorb Mg²⁺ by apical TRPM6 channel and basolateral Na⁺-Mg²⁺ exchanger [10,11]. Clinical features of hypermagnesemia usually correlated with serum Mg²⁺ level, varying from asymptomatic, mild gastrointestinal discomforts to conscious change, respiratory depression and fetal arrhythmia. In light of high efficacy of renal Mg²⁺ excretion, Mg²⁺ accumulation in body and lethal hypermagnesemia occurs almost exclusively in patients with advanced renal failure. Other than renal function, the difference in the types of Mg²⁺ salts and the administration routes also contribute to serum Mg²⁺ level. With chronic orally use, almost all types of Mg²⁺ salts have been reported to cause lethal hypermagnesemia progressively but a sudden outset of fatal hypermagnesemia is exclusively caused by an acute large load of Mg²⁺ intravenously, especially in those with normal renal function [12].

Considering the lack of advanced renal failure and intravenous Mg²⁺ administration on admission in our patient, Mg²⁺ responsible for his acute and lethal hypermagnesemia should originate from gut absorption. Several factors have been identified to impact on intestinal Mg²⁺ absorption including gut motility, Mg²⁺ dose, types of Mg²⁺ salt, food constituents and intestinal disorders [13]. To best of our knowledge, only few cases with normal renal function have been reported to have acute lethal hypermagnesemia with Mg²⁺ absorbed from gut following either Mg²⁺salt retention enema or Mg²⁺ -containing active charcoal ingestion. The robust elevation of serum Mg²⁺ level may be caused by very high electrochemical gradient established by Mg²⁺ containing enema solution or uncontrolled massive Mg²⁺ backleak through intestinal mucosa injured by charcoal. Differently, low bioavailability of inorganic Mg²⁺ salt was used in our patient and no Mg²⁺ salt enema was performed. Chronic use of MgO, despite in recommended dose, in our severely constipated patient may result in a significant accumulation of Mg²⁺ in colon. Glycerin enema has been reported to cause acute colitis or colonic mucosa necrosis via direct toxicity to intestinal mucosa or indirectly resulting in mesenteric vasospasm [14].

Therefore, frequent glycerin enema in our patient may cause colonic mucosal injury to disrupt fine-tuning Mg²⁺ absorption. Accumulated Mg²⁺ in colon of our patient could leak through damaged colonic mucosa wildly and massively, like a large bolus of Mg²⁺ load, to cause an acute life-threatening hypermagnesemia. Whether enema solutions contain Mg²⁺ or not, application of enema should be looked before you leap in severely constipated patients with chronic use of oral Mg²⁺-based laxatives even in recommended dose because Mg²⁺ accumulation in gut may be massive but underestimated, best illustrated by our case. In those patients chronically using oral Mg²⁺ cathartics regardless of the dose, signs of hypermagnesemia should be assessed frequently with regular measurement of serum Mg²⁺ level no matter how the renal function is. Early recognition with appropriate management is the key to improve outcome of hypermagnesemia. Discontinuing the use of Mg²⁺ salt is always the first step in the management of hypermagnesemia and usually can correct abnormal serum Mg²⁺ level in those with normal renal function. Volume expansion with saline helps renal Mg²⁺ excretion. Calcium should be administrated in symptomatic patients to antagonize the effect of excessive Mg²⁺ [13]. In patients with advanced renal failure, dialysis may be required and continuous venovenous hemodiafiltration (CVVHDF) is usually more effective in Mg²⁺ removal. Almost 40% reduction of serum Mg²⁺ level within three hours in our patient may suggest low efficacy hemodialysis with replacement fluid may mimic CVVHDF while CVVHDF is not available, but longer treatment time may be required.

Conclusion

Acute and lethal hypermagnesemia still should be considered among patients without intravenous administration of Mg²⁺. Even though enema solution used in severely constipated patients does not comprise Mg²⁺ salt, serum Mg²⁺ level should be closely measured in those with chronic use of Mg²⁺ salt cathartics regardless of renal function and the dose of Mg²⁺ salt.