You are asked to review a 25-year-old patient with severe diarrhoea. He is two weeks post-allogeneic hematopoietic stem cell transplant.

  1. List four likely causes. (20% marks)
  1. Outline your assessment and management. (80% marks)

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College answer

Causes

Drugs: promotility agents, antibiotics
Infection – multiple possible organisms
Radiation
Neutropenic enterocolitis
VHD

Outline your assessment and management

ABC

History:

Details of the indication for and type of transplant – esp. HLA matching etc.
Details of pre-transplant chemo/radiation etc.

Course and complications post-transplant
Whether engraftment has occurred
Medication history – esp. antibiotics

Details related to diarrhoea – associated with pain, blood etc,

Examination:

General physical with specific attention to Volume status

Abdominal examination – signs of peritonitis Signs of GVHD: rash, liver tenderness

Investigations:

Standard blood tests -FBC, Electrolytes, LFT’s, Cultures Stool culture including C difficile PCR

Plain AXR CT abdomen

Sigmoidoscopy +- biopsy

Discussion

Management

Fluid resuscitation – volume loss replaced by saline or balanced salt solution
Electrolyte replacement – as required but particularly potassium and magnesium

Nutrition – general enteral nutrition is satisfactory but TPN may be required where whole bowel rest is required

Antidiarrheal – loperamide can be used once infectious cause has been excluded
Anti-secretory – octreotide – particularly in early GvHD

Infection control, contact proportions

Treatment of underlying cause e.g. GVHD, C Diff.

Discussion

This question is functionally quite similar to Question 11 from the first paper of 2014, except in 20144 this patient was a 65-year-old male, 18 days following BMT for multiple myeloma, and who clearly has some serious abdominal pathology.

The causes of diarrrhoea in a bone marrow transplant recipient are so vastly numerous that they require a table to manage them:

Causes of Diarrhoea in the Bone Marrow Transplant Recipient

Infectious

Non-Infectious

Viruses

  • Rotavirus
  • Norovirus
  • Adenovirus
  • Cytomegalovirus

Bacteria:

  • Clostridium difficile
  • Shigella
  • Salmonella
  • Campylobacter
  • E.coli
  • Aeromonas

Parasites

  • Giardia
  • Cryptosporidium
  • Microsporidium

Fungi

  • Candida

Immunosuppressant therapy

  • Cytotoxic drugs
  • Tacrolimus
  • Whole-body irradiation

Consequences of BMT

  • Neutropenic enterocolitis
  • Graft vs host disease

ICU therapy

  • Pro-motility agents
  • High caloric feeds
  • Lactulose
  • Opioid withdrawal
  • Broad spectrum antibiotics

Assessment:

  • Supportive assessment:
    • A) - assessment of the urgent need for intubation
    • B) - Support of ventilation:
           - may be tachypnoeic if compensating for a metabolic acidosis
    • C) - Haemodynamic assessment: fluid resuscitation +/- vasopressors
    • E) - investigation of electrolyte abnormalities: EUC, CMP, ABG
    • F)- Monitoring of urine output and renal function; CRRT support as indicated
    • G)- assessment of the need for surgical consultation (is there peritonitis?)
      Also, assessment of the patient's nutritional state
  • Specific investigations:
    • Blood cultures
    • Stool sample for
      • Culture
      • Ova/cyst/parasite microscopy
      • C.difficile toxin PCR
    • CT abdomen (looking for evidence of colitis): it will reveal such nasties as neutropenic enterocolitis (in the BMT recipient) as well as the pneumatosis of C.difficile infection and gut ischaemia. A plain abdominal xray is almost never useful. Hamdeh et al (2016) report a false negative rate of 48%.
    • CMV quantitative titer (perhaps this is CMV colitis?)
    • Colonoscopy and biopsy

Management:

  • Supportive management
    • Fluid resuscitation, electrolyte replacement and haemodynamic control with vasopressors as needed
    • TPN if enteral nutrition is clearly inadequate
  • Specific management:
    • Antibiotics empirically
    • Loperamide if the diarrhoea is not infectious
    • Octreotide if it is definitely secretory
  • Targeted therapy for cause of diarrhoea:
    • Metronidazole for C.difficile, etc
    • High dose steroids for GVHD
    • Albendazole or ivermectin for parasitic infections

References

References

UpToDate have a good article on acute diarrhoea for the paying customer.

Kelly, T. W. J., M. R. Patrick, and K. M. Hillman. "Study of diarrhea in critically ill patients." Critical care medicine 11.1 (1983): 7-9.

Wiesen, Patricia, Andre Van Gossum, and Jean-Charles Preiser. "Diarrhoea in the critically ill." Current opinion in critical care 12.2 (2006): 149-154.

Ferrie, Suzie, and Vivienne East. "Managing diarrhoea in intensive care."Australian Critical Care 20.1 (2007): 7-13.

Pawlowski, Sean W., Cirle Alcantara Warren, and Richard Guerrant. "Diagnosis and treatment of acute or persistent diarrhea." Gastroenterology 136.6 (2009): 1874-1886.

Schiller, Lawrence R. "Diarrhea." Medical Clinics of North America 84.5 (2000): 1259-1274.

Timothy A. Woods. "Diarrhea." Chapter 88 in: Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990.

Guerrant, Richard L., et al. "Practice guidelines for the management of infectious diarrhea." Clinical infectious diseases 32.3 (2001): 331-351.

Cox, George J., et al. "Etiology and outcome of diarrhea after marrow transplantation: a prospective study." Gastroenterology 107.5 (1994): 1398-1407.

Hamdeh, Shadi, et al. "Clinical approach to diarrheal disorders in allogeneic hematopoietic stem cell transplant recipients." World Journal of Hematology 5.1 (2016): 23-30.