Induction of potentially lethal hypermagnesemia, ischemic colitis, and toxic megacolon by a preoperative mechanical bowel preparation: report of a case

The patient was a 67-year-old man. He had experienced bloody stool and anal pain for
1 year and then visited our hospital. Colonoscopic examination showed a locally advanced
type 2 rectal tumor that had invaded the subserosal layer at the Rb portion, and a
CT scan revealed several swollen lymph nodes. There was no sign of metastasis to other
organs. The patient’s past medical history was significant for hypertension and slight
renal dysfunction (blood urea nitrogen (BUN), 10 mg/dL; creatinine, 1.23 mg/dL; and
eGFR was 52.8, chronic kidney disease (CKD) stage 3a). To reduce the size of the tumor,
we treated the patient with four courses of neo-adjuvant chemotherapy with the SOX
regimen (TS-1 120 mg/body and oxaliplatin 80 mg/m
²
), and he completed the treatment without any adverse events. Preoperative examination
revealed that the tumor had decreased more than 30 % in diameter, and the response
was regarded as a “partial response” by RECIST criteria 6]. There was no obstruction, and minimal tumor at the rectum by colonoscopy, and his
nodes had also decreased by CT scan. He was admitted to undergo a laparoscopic abdominoperineal
resection, and, for mechanical bowel preparation (MBP), he received 34 g of magnesium
citrate (Magcorol P®; containing 2.71 g of magnesium (Mg)) orally at 2:00 PM, day
0. Three hours later, he had only scant excrement, and he felt abdominal distention
and muscle weakness in his legs. In spite of additional anthraquinone laxatives, he
could not get excrement. On day 1, at 2:00 AM, he was lethargic and did not respond
well to verbal stimuli. His systolic blood pressure (BP) was less than 55 mmHg, and
his heart rate (HR) was 75/min (Fig. 2). The electrocardiogram showed the findings of first-degree atrioventricular block,
prolonged PR interval (0.281 ms), and slightly prolonged QRS interval (0.118 ms).
Intravenous epinephrine and dopamine were started to restore normal BP, but the effect
was limited, and the BP soon fell again. Next, the patient was transferred to the
intensive care unit (ICU) and was intubated. Under dopamine (10 ?g/kg/min), dobutamine
(5 ?g/kg/min), and norepinephrine (0.7 ?g/kg/min), his systolic BP was 75/40 mmHg,
his HR was 70/min, and his abdomen was soft but distended and tympanic, but there
was no muscular defense. Emergency CT and abdominal X-ray examinations revealed diffuse
and marked dilatation of the large-bowel loops, with fecal impaction 6 cm in diameter
at the sigmoid colon (Fig. 1), and no free air in the abdominal cavity. His head CT scan was of normal finding,
as was his echocardiography findings. Digital rectal palpation revealed no anal or
rectal stenosis, and there was enough room to pass the stool. We drained the fecal
impaction by intestinal lavage and a transanal tube (12 Fr silicone tube). A stool
culture revealed normal flora and no C. difficile or other toxigenic bacteria. A large volume of liquid excrement was removed, but
his abdomen was still distended, and his BP was still low, even though several catecholamines
were on board. At first, our diagnosis was functional fecal ileus with an infection
due to “bacterial translocation,” and we thought that the patient developed septic
shock. Despite his markedly low BP, his HR was not increased; relative bradycardia
continued. Then, the presence of hypermagnesemia was suspected. The patient’s serum
Mg level on day 3 was 6.4 mg/dL, and blood drawn at day 1 showed a markedly elevated
serum Mg concentration of 16.3 mg/dL (Fig. 2). The serum Mg level at admission was normal (1.8 mg/dL), and the diagnosis of symptomatic
hypermagnesemia was confirmed. Calcium gluconate was infused to antagonize the effects
of hypermagnesemia. To reduce the serum Mg concentration, we performed temporary hemodialysis.
After 2 days, hemodialysis and daily intestinal lavage enabled the serum Mg level
to decrease to almost the standard level, and the patient’s hemodynamics also dramatically
improved. Intravenous catecholamines were gradually withdrawn, and the patient was
extubated at day 5. Though his hemodynamics were improved, and the inflammation was
gone, his abdomen remained distended. On day 15, colonoscopy revealed that the mucous
membrane was sloughed and the sigmoid colon had an ulcer that covered the entire circumference,
similar to the severe stage of IBD (Fig. 3). The examination could not progress beyond the sigmoid descending colon junction
because stenosis of the descending colon made it too tight for the scope to pass.
On day 32, a contrast enema examination revealed notable stenosis on the left side
of the transverse colon to the descending colon (Fig. 4). These findings confirmed the diagnosis of ischemic colitis. The patient tried oral
intake, but just a liquid nutritional supplement caused a stomachache and bloody diarrhea.
Subsequently, he ingested only liquid water and was given intravenous alimentation.
While waiting for recovery of his general condition, on day 52, he underwent laparoscopic
abdominoperineal resection with left-side colectomy with D3 lymph node dissection.
Laparoscopic observation revealed that the entire transverse colon and descending
colon were severely narrowed. Pathological findings showed advanced rectal cancer,
and at the transverse colon and descending colon, a longitudinal ulcer on the opposite
of the mesenteric attached side, and severe stenosis with massive invasion of inflammatory
cells within the whole thickness of the colon wall. The findings were comparable to
those of ischemic colitis (Fig. 5). The patient had a good postoperative course and was able to eat normal foods. He
was discharged on day 72 (postoperative day 20) without any postoperative complications.

Fig. 1. Clinical course and value of the patient. Mg magnesium, HR heart rate, SBP systolic blood pressure, DBP diastolic blood pressure

Fig. 2. Abdominal X-ray examination revealed 6-cm dilatation of the sigmoid colon with fecal
impaction

Fig. 3. Colonoscopy showed a severe ulcer and pseudomembrane at the descending colon

Fig. 4. Contrast enema examination revealed significant stenosis on the left side of the transverse
colon to the descending colon

Fig. 5. Pathological findings showed advanced rectal cancer and significant atrophic changes
and a longitudinal ulcer at the transverse colon and descending colon. The findings
were compatible to ischemic colitis

Discussion

Magnesium (Mg) is the fourth most abundant cation in the human body and the second
most abundant intracellular cation, with 67 % in bone, 31 % in intracellular spaces,
and 1–2 % found extracellularly 7]. Mg homeostasis is dependent mainly on gastrointestinal absorption and renal excretion,
and the kidney is the main organ involved in Mg regulation. Renal Mg excretion is
very efficient because the thick ascending limb of Henle has the capacity to completely
reject Mg reabsorption under conditions of hypermagnesemia 8]. Even in the presence of decreased renal function, the serum Mg level is regulated
by a reduction in the gastrointestinal absorption of Mg 9]. Therefore, hypermagnesemia is most frequently seen in conjunction with renal insufficiency
and ingestion of Mg-containing drugs or in patients with small-bowel hypomotility
disorder. Moreover, hypermagnesemia can decrease bowel motility by blocking myenteric
neurons and interfering with excitation-contraction coupling of smooth muscle cells
10]. In addition, hypermagnesemia can block the peripheral and autonomic nervous systems
via anatomization of calcium effects, suppression of acetylcholine release, and reduction
of postsynaptic membrane responsiveness and depress the conduction system of the heart
and sympathetic ganglia 11]. Thus, the clinical manifestations of hypermagnesemia vary according to the serum
Mg concentration. Hypotension, nausea, vomiting, facial flushing, urinary retention,
and ileus occur at levels ranging from 5 to 8 mg/dL, while the absence of the deep
tendon reflex and somnolence and complete heart block occur at 9–12 mg/dL. Respiratory
depression, paralysis, and complete heart block occur at levels 15 mg/dL, and cardiac
arrest occurs in asystole at levels 20 mg/dL 12], 13]. However, the peak serum Mg concentration does not correlate with mortality or the
severity of intestinal complications 14], 15]. Although our case showed some manifestations of severe hypermagnesemia, we did not
recognize these manifestations until day 3 because his clinical manifestations were
concurrence of hypermagnesemia, ischemic colitis, and severe shock. Equivalent to
CKD stage 3a, during preoperative chemotherapy in our case, renal function was maintained,
and there were no abnormalities of serum electrolytes, even Mg. The patient presented
with a serum creatinine level of 1.19 mg/dL on day 0 before laxative intake, which
was a completely normal value at hospitalization, and there was no stenosis, including
rectal, at the site of the tumor. However, a Mg laxative administered as part of the
preoperative preparations reduced and weakened his colonic motility in inverse proportions
with increased serum Mg, and his colon became dilated such that a lot of Mg might
have been absorbed. Finally, the level to which the serum Mg had increased became
critical. Treatment for hypermagnesemia requires increasing renal Mg excretion through
intravenous diuretics, and sometimes, hemodialysis is effective when kidney function
is impaired and the patient is symptomatic from hypermagnesemia. In this case, drainage
of fecal impaction by intestinal lavage was also effective to reduce the intra-bowel
Mg concentration.

Distention of the colon due to decreased bowel motility could lead to continuous ischemia
of the entire thickness of the bowel wall and ultimately induce necrosis of a part
of the colon. Ischemia due to dilation of the colon may be provoked when there is
an increase in intraluminal pressure to more than 50 mmHg 16]. Acute colonic ischemia has a high mortality rate, depending on the cause of the
event, the degree of ischemia, and the extent of ischemic bowel. Ischemic colitis
is likely to develop in the left colon, including the splenic flexure and sigmoid
colon, because of its arterial anatomical features. In our case, the left side of
the transverse colon and the descending colon became gangrenous, as ischemic colitis,
despite the fact that the sigmoid colon, which is located anatomically close to the
inferior mesenteric artery, showed normal findings.

Toxic megacolon is a rare but severe and potentially fatal complication of colonic
inflammation. Most often, it is associated with IBD 17] specifically ulcerative colitis and, to a much lesser extent, Crohn’s disease 18]. Ischemia and amebic colitis may also produce a toxic megacolon pattern 19]. Its main characteristics are radiographic evidence of total or segmental colonic
distension of 6 cm. In this case, the patient had received an amount of magnesium
sodium, and despite the fact that it was the result of laxative intake, he could not
use his bowels. Orally ingested Mg had stayed in the intestine much longer, and intestinal
absorption of Mg might have been enhanced. Initially, hypermagnesemia occurred and
caused bowel hypomotility. Prolonged hypotension and a pressure effect of fecal impaction
on the intestinal circulation could have induced intestinal ischemia, and the patient
developed toxic megacolon. Although a portion of the toxic megacolon recovered from
a severe condition to almost normal digestive function, the damage to his left colon
was serious, and hard sclerotic changes occurred. Finally, he required resection,
and surgery for rectal cancer was performed simultaneously. To our knowledge, this
is the first case report to show that administration of mechanical bowel preparation
can lead to the development of three rare complications: hypermagnesemia, ischemic
colitis, and toxic megacolon.