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Severe hyponatremia and seizures after bowel preparation with low-volume polyethylene glycol plus ascorbic acid solution
Abstract
The widely used polyethylene glycol (PEG)-based solutions have been proven effective for bowel preparation when 4 L of the solution is administered before colonoscopy. However, large volumes of the solutions are generally poorly tolerated. A new PEG-based solution consisting of 2 L of PEG and a high dose of ascorbic acid has recently become available. Electrolyte abnormalities caused by PEG-based solutions have rarely been reported. We report on a case of acute severe hyponatremia with associated generalized tonic-clonic seizures after bowel preparation with a low-volume PEG plus ascorbic acid solution in a 74-year-old woman with no history of seizures. She took a beta blocker, an angiotensin-converting enzyme inhibitor, and glimepiride for hypertension and diabetes mellitus. She showed general weakness, nausea, agitation, muscle cramping, and seizures after ingestion of the PEG plus ascorbic acid solution. Her serum sodium level was 112 mEq/L. Her symptoms improved after intravenous administration of hypertonic saline. Physicians should pay attention to screening for electrolytes and development of neurological symptoms during bowel preparation.
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Hyponatremia, the most common electrolyte disorder, has been rarely reported as causing rhabdomyolysis. Osmotic demyelination syndrome (ODS), a demyelinating disease of the central pons and/or other areas of the brain, is infrequently reported as associated with rapid correction of hyponatremia. This paper reports a case of ODS after correction of severe hyponatremia complicated by rhabdomyolysis. A 47-year-old female with a history of chronic alcoholism presented herself at the hospital with altered consciousness after three days of nausea and vomiting. She was on a thiazide diuretic for essential hypertension. Her blood tests upon her hospital admission showed hyponatremia (Na+ 98 mEq/L), hypokalemia (K+ 3.0 mEq/L), and elevation of her serum creatine phosphokinase (3,370 IU/L) with an increase in her serum myoglobin level 11,267 ng/mL). She was treated with intravenous fluid therapy that included isotonic and hypertonic salines along with potassium chloride. She became more alert, and her neurological condition gradually improved after the first five days of her therapy. On the ninth day after her admission, she developed progressive quadiaresis associated with dysarthria, dysphagia, and dystonia despite the resolution of her hyponatremia. Magnetic resonance imaging of her brain on 16th day revealed symmetrical areas of signal hyperintensity in her central pons, basal ganglia, and precentral gyrus in T2-weighted images, which are consistent with ODS. Her neurological symptoms steadily improved after six weeks with only supportive treatment and rehabilitation.
4 liters of polyethylene glycol (PEG) solution is commonly used to evacuate the colon before colonoscopy. This substance, however, is known to cause electrolyte abnormalities such as hyponatremia. Seizures caused by hyponatremia associated with bowel preparation have only rarely been reported. We report the case that a 75-year-old woman with no prior history of seizures was developed severe hyponatremia (112 mEq/L) with generalized tonic-clonic seizure and mental change after ingestion of 4L of PEG solution. Past medical history was notable for thiazide diuretics. Her symptoms are improved during intravenous administration of hypertonic saline for the correction of hyponatremia. Patients with impaired ability to excrete free water those with renal insufficiency, hypothyroidism, mineralocorticoid deficiency, liver cirrhosis, or heart failure as well as those taking drugs which including thiazide diuretics, NASIDs, and ACE inhibitors have risk of hyponatremia following bowel preparation for colonoscopy. We conclude that physicians should check patient's condition and electrolyte abnormalities before colonoscopy procedures.
Ingestion of large volumes of a balanced electrolyte solution has previously been shown to be an effective method of cleaning the colon for diagnostic studies. However, in this paper we have shown that total gut perfusion with such a solution results in absorption of 2400 ml water and 375 meq of sodium over 3 hr, which is the approximate time required to clean the colon by this technique. This might be hazardous to patients who are unable to readily excrete a salt and water load. We, therefore, designed a solution containing mainly sodium sulfate that was associated with only trivial amounts of water and sodium absorption or secretion during total gut perfusion. This new solution might be useful in colon cleansing before colonoscopy, barium enema, and surgery. In addition, such a solution may have some therapeutic indications, including bowel cleaning in patients with hepatic encephalopathy or as a rapid washout technique for ingested toxins.
There are many published trials of colon cleansing regimens for colonoscopy but no clear consensus regarding relative performance.
To identify high quality controlled trials comparing two or more bowel preparation regimens and to compare efficacy and tolerability.
A comprehensive systematic review was carried out to identify candidate studies. Quality appraisal was carried out on all identified studies. Results were meta-analysed where possible and qualitatively compared if not.
Eighty-two studies qualified for analysis. Polyethylene glycol and sodium phosphate were the most frequently investigated preparations. There was no significant efficacy difference between the two, but sodium phosphate was better tolerated. Sodium picosulphate/magnesium citrate, a commonly prescribed preparation, was investigated in four studies, with no clear benefit over other regimens demonstrated. Safety was not recognized as a problem in the randomized controlled trials. Published case series demonstrate that sodium phosphate is associated with the highest risk of clinically significant electrolyte disturbances.
Shortcomings in study design limit the value of many of the studies. Based on these results, no single bowel preparation emerges as consistently superior. New preparations are required that combine better efficacy and tolerability, in addition to rigorous new validated study designs, allowing unequivocal comparisons to be made.
Bowel preparation is critical for the efficacy and safety of colonoscopy. Poor patient tolerance to bowel preparation has been associated with the high amount of fluid administered. A 2-L polyethylene glycol (PEG) solution containing ascorbic acid has been recently developed.
To compare the efficacy, safety and acceptability of 2-L PEG+ascorbic acid vs 4-L PEG for colonoscopy.
We designed a single blind randomized non-inferiority study in order to compare the two bowel preparations. A blinded assessment of cleansing was made by the endoscopist according to the Aronchick scale. Acceptability was assessed by questionnaire. Intention-to-treat (ITT) and per-protocol (PP) analysis were reported.
Overall, 169 patients (PP: 166) were selected for the 2-L PEG+ascorbic acid and 170 (PP: 166) for the 4-L PEG. When rating global bowel cleansing at ITT, an excellent-good level was reported in 84.6% (PP: 86.2%) of patients who received 2-L PEG+ascorbic acid and 75.3% (PP: 77%) of patients who received 4-L PEG (p=0.04). Acceptability rate favoured 2-L PEG+ascorbic acid vs 4-L PEG (83% vs 76%; p=0.02).
2-L PEG+ascorbic acid, completed with an additional L of clear fluids, provided bowel cleansing which appeared to be more effective and acceptable than 4-L PEG.
Polyethylene glycol (PEG) is a commonly used bowel preparation for colonoscopy. Unfortunately, the standard large-volume solution may reduce patient compliance. Split-dosing of PEG has been studied in various randomized, controlled trials (RCTs). However, results have been conflicting.
We conducted a meta-analysis to assess the role of split-dose PEG versus full-dose PEG for bowel preparation before colonoscopy.
Multiple databases were searched (January 2011). RCTs on adults comparing full-dose and split-dose of PEG for bowel preparation before colonoscopy were included and analyzed by calculating pooled estimates of quality of bowel preparation, preparation compliance, willingness to repeat the same preparation, and side effects by using odds ratio (OR) by fixed and random-effects models.
Literature search.
Per RCTs.
Satisfactory bowel preparation, willingness to repeat same bowel preparation, patient compliance, and side effects.
Five trials met inclusion criteria (N = 1232). Split-dose PEG significantly increased the number of satisfactory bowel preparations (OR 3.70; 95% CI, 2.79-4.91; P < .01) and willingness to repeat the same preparation (OR 1.76; 95% CI, 1.06-2.91; P = .03) compared with full-dose PEG. Split-dose PEG also significantly decreased the number of preparation discontinuations (OR 0.53; 95% CI, 0.28-0.98; P = .04) and nausea (OR 0.55; 95% CI, 0.38-0.79; P < .01) compared with full-dose PEG.
Limited number of studies.
The use of a split-dose PEG for bowel preparation before colonoscopy significantly improved the number of satisfactory bowel preparations, increased patient compliance, and decreased nausea compared with the full-dose PEG.
Virtually all investigators now agree that self-induced water intoxication, symptomatic hospital-acquired hyponatremia, and hyponatremia associated with intracranial pathology are true emergencies that demand prompt and definitive intervention with hypertonic saline. A 4- to 6-mmol/L increase in serum sodium concentration is adequate in the most seriously ill patients and this is best achieved with bolus infusions of 3% saline. Virtually all investigators now agree that overcorrection of hyponatremia (which we define as 10 mmol/L in 24 hours, 18 mmol/L in 48 hours, and 20 mmol/L in 72 hours) risks iatrogenic brain damage. Appropriate therapy should keep the patient safe from serious complications of hyponatremia while staying well clear of correction rates that risk iatrogenic injury. Accordingly, we suggest therapeutic goals of 6 to 8 mmol/L in 24 hours, 12 to 14 mmol/L in 48 hours, and 14 to 16 mmol/L in 72 hours. Inadvertent overcorrection owing to a water diuresis may complicate any form of therapy, including the newly available vasopressin antagonists. Frequent monitoring of the serum sodium concentration and urine output are mandatory. Administration of desmopressin to terminate an unwanted water diuresis is an effective strategy to avoid or reverse overcorrection.
Screening colonoscopy exposes healthy patients to the risk of serious adverse events associated with bowel preparation. Randomized controlled trials are not an effective method for evaluating this risk.
To search published literature in order to characterize the risk of adverse events associated with oral polyethylene glycol (PEG) or sodium phosphate (NaP).
A systematic review identified case reports of any serious events associated with PEG or NaP. Reports to the Food and Drug Administration (FDA) were also examined.
Fifty-eight publications of significant events in 109 patients using NaP and 22 patients using PEG were identified. As the total number of prescriptions issued is unknown, rates for the two agents cannot be directly compared. Most commonly reported were electrolyte disturbances, renal failure and colonic ulceration for NaP and Mallory-Weiss tear, electrolyte disturbances and allergic reactions for PEG between January 2006 and December 2007; there were 171 cases of renal failure reported to the FDA following use of NaP and 10 following PEG.
Adverse events following bowel preparation are uncommon, but potentially serious. Given that many of these patients are healthy individuals undergoing screening, the benefit/risk ratio must be carefully considered when deciding which preparation to prescribe in individual patients.
A case of colonoscopy-induced hyponatraemic encephalopathy led us to study the risk of hyponatraemia after gastrointestinal endoscopy. We assessed 40 patients before and after colonoscopy. 20 gastroscopy patients served as controls. Our findings show a high incidence (7.5%) of hyponatraemia after colonoscopy, in association with raised serum concentrations of arginine vasopressin. Physicians should be aware of this complication, since it may contribute to psychological and neurological symptoms after colonoscopy.
Screening for colorectal cancer clearly reduces colorectal cancer mortality, yet many eligible adults remain unscreened. Several screening tests are available, and various professional organizations have differing recommendations on which screening test to use. Clinicians are challenged to ensure that eligible patients undergo colorectal cancer screening and to guide patients in choosing what tests to receive.
To critically assess the evidence for use of the available colorectal cancer screening tests, including fecal occult blood tests, sigmoidoscopy, colonoscopy, double-contrast barium enema, and newer tests, such as virtual colonoscopy and stool-based molecular screening.
All relevant English-language articles were identified using PubMed (January 1966-August 2002), published meta-analyses, reference lists of key articles, and expert consultation.
Studies that evaluated colorectal cancer screening in healthy individuals and assessed clinical outcomes were included. Evidence from randomized controlled trials was considered to be of highest quality, followed by observational evidence. Diagnostic accuracy studies were evaluated when randomized controlled trials and observational studies were not available or did not provide adequate evidence. Studies were excluded if they did not evaluate colorectal screening tests and if they did not evaluate average-risk individuals.
Randomized controlled trials have shown that fecal occult blood testing can reduce colorectal cancer incidence and mortality. Case-control studies have shown that sigmoidoscopy is associated with a reduction in mortality, and observational studies suggest colonoscopy is effective as well. Combining fecal occult blood testing and sigmoidoscopy may decrease mortality and can increase diagnostic yield.
The recommendation that all men and women aged 50 years or older undergo screening for colorectal cancer is supported by a large body of direct and indirect evidence. At present, the available evidence does not currently support choosing one test over another.
Central pontine myelinolysis (CPM) was described by Adams and colleagues in 1959 as a disease affecting alcoholics and the malnourished.' The concept was extended from 1962 with the recognition that lesions can occur outside the pons, so-called extrapontine myelinolysis (EPM). In 1976 a link between these disorders and the rapid correction of sodium in hyponatraemic patients was suggested, and by 1982 substantially established. in this review we discuss the clinical, pathological, and aetiological features of the disease, the dilemma facing clinicians treating patients with severe hyponatraemia, and treatment opportunities.
Oral sodium phosphate and sodium picosulfates/magnesium citrate are commonly used to evacuate the colon and rectum before colonoscopy or colorectal surgery. These substances, however, are known to cause electrolyte abnormalities. Seizures caused by electrolyte abnormalities associated with bowel preparation have only rarely been reported. We report the cases of three patients with no prior history of seizures, who had their first seizure associated with hyponatremia following ingestion of sodium phosphate or sodium picosulfates/magnesium citrate combination. Care must be taken with patients with a low seizure threshold and those with possible chronic sodium depletion, such as patients on thiazide diuretics, who are undertaking bowel preparation with oral sodium phosphate or sodium picosulfates/magnesium citrate combination.
Elective colonoscopy is used increasingly to screen at risk patients for colonic malignancy. Bowel preparation quality is a critical factor for successful screening. Preparations used include high doses of potent laxatives, e.g. sodium phosphate solution or high volume polyethylene glycol. Because of constraints and limited patient acceptability, there remains a need for a more acceptable bowel preparation with at least equivalent cleansing to existing preparations.
To determine if a 2-L polyethylene glycol solution with electrolytes and ascorbic acid (polyethylene glycol + ascorbic acid) produces equivalent bowel cleansing to sodium phosphate solution, and is acceptable to patients and well tolerated.
This was a single blind, parallel group, equivalence study comparing polyethylene glycol + ascorbic acid with sodium phosphate solution in 352 patients undergoing elective colonoscopy. A blinded, independent expert scored a video recording of each colonoscopy. Patients completed a questionnaire reporting acceptability of the bowel preparation process.
Clinically successful bowel preparation was reported in 72.5% of cases prepared using polyethylene glycol + ascorbic acid and in 63.9% of cases prepared using sodium phosphate solution (treatment difference +8.6%, 95% confidence interval -2.3%, +19.4%). The new solution was well accepted and better tolerated than sodium phosphate solution.
The new 2-L solution of polyethylene glycol + ascorbic acid was at least as efficacious as sodium phosphate solution with comparable efficacy and a better tolerability profile.
Patient compliance with screening recommendations for colorectal cancer remains low, despite a 90% survival rate achieved with early detection. Bowel preparation is a major deterrent for patients undergoing screening colonoscopy. More than half of patients taking polyethylene glycol electrolyte lavage solution and sodium phosphate preparations experience adverse events, such as nausea and abdominal pain. Many adverse events may be associated with dehydration, including rare reports of renal toxicity in patients taking sodium phosphate products. Addressing dehydration-related safety issues through patient screening and education may improve acceptance of bowel preparations, promote compliance and increase the likelihood of a successful procedure.
To evidence safety issues associated with bowel preparation are generally related to inadequate hydration.
Dehydration-related complications may be avoided through proper patient screening, for example, renal function and comorbid conditions should be considered when choosing an appropriate bowel preparation. In addition, patient education regarding the importance of maintaining adequate hydration before, during and after bowel preparation may promote compliance with fluid volume recommendations and reduce the risk of dehydration-related adverse events.
Proper patient screening and rigorous attention by patients and healthcare providers to hydration during bowel preparation may provide a safer, more effective screening colonoscopy.
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