Grade
Diarrhea
1
Increase of < 4 stools per day over baseline; mild increase in ostomy output compared to baseline
2
Increase of 4–6 stools per day over baseline; IV fluid indicated < 24 h; moderate increase in ostomy output compared to baseline; not interfering with ADL
3
Increase of ≥ 7 stools per day over baseline; incontinence; IV fluids ≥ 24 h; severe increase in ostomy output compared to baseline; interfering with ADLs
4
Life-threatening consequences (i.e., hemodynamic collapse)
5
Death
a.
Etiology and pathogenesis
May present any time during conditioning or post-HSCT. The time of onset may assist in identifying potential etiologies, including:
i.
Direct side effect from conditioning and other medications
ii.
Mucositis and intestinal epithelial sloughing
iii.
Infection
iv.
GVHD
v.
Pancreatic insufficiency
vi.
Brush border disaccharidase deficiency
vii.
Malabsorption
viii.
Intestinal thrombotic microangiopathy
ix.
Mycophenolate mofetil (CellCept®) is a very common inciting agent (through direct mucosal toxicity) and may be very difficult to distinguish from GVHD.
b.
Diagnosis
Rule out infection with stool cultures for enteric pathogens. For patients in which diarrhea does not improve after resolution of oral mucositis , consider rectosigmoidoscopy to perform visual inspection and obtain tissue biopsies.
c.
Treatment
i.
Identify and treat the underlying cause.
ii.
Supportive care should focus on hydration and prevention/treatment of electrolyte imbalances.
iii.
Bowel rest/restricted diet (low roughage, low residue; low or no lactose (see Appendix 7).
iv.
Calculate and replace enteral volume losses with isotonic fluid.
v.
Monitor and replace protein losses (albumin, gamma globulin).
vi.
Vitamin K depletion associated with chronic diarrhea is common. If the prothrombin time is elevated, vitamin K should be replaced. The dose is 2.5–25 mg IV or SQ (max 10 mg for children); if prothrombin time is not satisfactory within 6–8 h, the dose may be repeated.
vii.
Loperamide (Imodium®) 2–4 mg po every 6 h or octreotide (Sandostatin®) may be effective to treat or relieve diarrhea associated with conditioning regimen and GVHD. The recommended octreotide regimen varies. A fixed dose of 500 mcg IV every 8 h for 7 days or 50 mcg (2 mcg/kg) IV TID escalated to continuous infusion at 15 mcg/h (1 mcg/kg/hr) have been reported to have some success in control of diarrhea in the HSCT setting.
viii.
Denatured tincture of opium (DTO) has also been used in settings of high-volume diarrhea but should be used with caution as opiate-induced ileus can be observed.
ix.
Antidiarrheal agents should not be used in patients with infectious diarrhea ; negative C. difficile toxin assay should be ascertained prior to the addition of antimotility agents
2.
Gastrointestinal Bleeding
a.
Etiology and pathogenesis
Most cases have diffuse areas of bleeding as opposed to a localized site. Causes of GI bleeding include:
i.
Thrombocytopenia
ii.
Esophageal trauma (from retching)
iii.
Esophagitis
iv.
Colitis
v.
Anal fissures or hemorrhoids
vi.
Viral infections
vii.
GVHD
b.
Diagnosis
Diagnosis is clinical. An esophagogastroduodenoscopy with rectosigmoidoscopy/colonoscopy may aid in identifying the cause of and controlling localized bleeding.
c.
Treatment
If possible, treatment of the underlying disorder should be initiated. Symptom control may be achieved with:
i.
Platelet support to maintain platelets ≥ 50,000/mm3.
ii.
Packed red blood cells (PRBC) transfusion to maintain hematocrit > 28 %.
iii.
Octreotide may provide short-term control.
iv.
Control of localized bleeding with endoscopic cautery or embolization.
v.
If large-volume acute blood loss occurs, consider desmopressin (DDAVP®) ± aminocaproic acid (Amicar®) or tranexamic acid (Lysteda®), providing the patient has no evidence of hematuria.
vi.
The use of recombinant factor VII (NovoSeven®) 90 mcg IV q 2 h to control bleeding in the HSCT setting has not been studied and its routine use is not recommended.
vii.
Consider radiologic assessment with angiography or a red cell nuclear scan to identify areas of active bleeding.
21.3 Hepatobiliary Diseases
1.
Sinusoidal Obstruction Syndrome or Veno-Occlusive Disease (SOS/VOD) of the Liver
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