Hospital Course Continued
The patient continued to have greater than 5 L of output from the ileostomy per day, so the following day the primary team increased the loperamide from 2 mg every 6 hours to 4 mg every 6 hours, added 2 tabs of diphenoxylate-atropine every 8 hours, and made the patient NPO. He continued to require IVFs and frequent electrolyte repletion because of the significant ongoing gastrointestinal losses.
What is the recommended first-line medical therapy for high-output enterostomy/diarrhea?
Anti-diarrheal medications are commonly used in high-output states because they work by reducing the rate of bowel translocation thereby allowing for longer time for nutrient and fluid absorption in the small and large intestine. Loperamide in particular also improves fecal incontinence because it effects the recto-anal inhibitory reflex and increases internal anal sphincter tone [9]. Four RCTs showed that loperamide lead to a significant reduction in enterostomy output compared to placebo with enterostomy output reductions ranging from 22% to 45%; varying dosages of loperamide were used, and ranged from 6 mg per day to 16 total mg per day [10–12]. King et al compared loperamide and codeine to placebo and found that both medications led to reductions in enterostomy output with a greater reduction and better side effect profile in those that received loperamide or combination therapy with loperamide and codeine [13,14]. The majority of studies used a maximum dose of 16 mg per day of loperamide, and this is the maxium daily dose approved by the US Food and Drug Administration (FDA). Interestingly however, loperamide circulates through the enterohepatic circulation which is severely disrupted in SBS, so titrating up to a maximum dose of 32 mg per day while closely monitoring for side effects is also practiced by experts in intestinal failure [15]. It is also important to note that anti-diarrheal medications are most effective when administered 20 to 30 minutes prior to meals and not scheduled every 4 to 6 hours if the patient is eating by mouth. If intestinal transit is so rapid such that undigested anti-diarrheal tablets or capsules are visualized in the stool or stoma, medications can be crushed or opened and mixed with liquids or solids to enhance digestion and absorption.
Hospital Course Continued
The patient continued to have greater than 3 L of ileostomy output per day despite being on scheduled loperamide, diphenoxylate-atropine, and a proton pump inhibitory (PPI), although improved from greater than 5 L per day. He was subsequently started on opium tincture 6 mg every 6 hours, psyllium 3 times per day, the dose of diphenoxylate-atropine was increased from 2 tablets every 8 hours to 2 tablets every 6 hours, and he was encouraged to drink water in between meals. As mentioned previously, the introduction of dietary fiber should be carefully monitored, as this patient population is commonly intolerant of high dietary fiber intake, and hypoosmolar liquids like water should actually be minimized. Within a 48-hour time period, the surgical team recommended increasing the loperamide from 4 mg every 6 hours (16 mg total daily dose) to 12 mg every 6 hours (48 mg total daily dose), increased opium tincture from 6 mg every 6 hours (24 mg total daily dose) to 10 mg every 6 hours (40 mg total daily dose), and increased oral pantoprazole from 40 mg once per day to twice per day.
What are important considerations with regard to dose changes?
Evidence is lacking to suggest an adequate time period to monitor for response to therapy in regards to improvement in diarrheal output. In this scenario, it may have been prudent to wait 24 to 48 hours after each medication change instead of making drastic dose changes in several medications simultaneously. PPIs irreversibly inhibit gastrointestinal acid secretion as do histamine-2 receptor antagonists (H2RAs) but to a lesser degree, and thus reduce high-output enterostomy [16]. Reduction in pH related to elevated gastrin levels after intestinal resection is associated with pancreatic enzyme denaturation and downstream bile salt dysfunction, which can further lead to malabsorption [17]. Gastrin hypersecretion is most prominent within the first 6 months after intestinal resection such that the use of high- dose PPIs for reduction in gastric acid secretion are most efficacious within that time period [18,19]. Jeppesen et al demonstrated that both omeprazole 40 mg oral twice per day and ranitidine 150 mg IV once per day were effective in reducing enterostomy output, although greater reductions were seen with omeprazole [20]. Three studies using cimetidine (both oral and IV formulations) with dosages varying from 200 mg to 800 mg per day showed significant reductions in enterostomy output as well [21–23].