A 22-year-old male was admitted to the emergency room in a comatose state due to shock after being transferred from another hospital where he was being treated with high doses of antipsychotic medications for an acute psychotic episode from drug abuse. Imaging showed severe dilation of the intestines without obstruction or free air. The patient underwent surgery where necrosis of the right colon was found. The diagnosis was acute megacolon (Ogilvie's syndrome) likely caused by the antipsychotic medications, which is a known but rare risk. Literature review showed antipsychotics like clozapine can cause gastrointestinal hypomotility and this case highlights the need to monitor for constipation from these drugs.

1. Case presentation
Dr. Roni Rozen
Wolfson medical center, Gastroenterological institute

2.  22 Y.O. male was admitted to Wolfson emergency room, in a state of
coma and shock – low BP, tachycardia and respiratory distress.
 The patient was transferred to ER from Abarbanel Hospital, where he
was admitted 2 days before with an acute psychotic episode
secondary to illicit drug abuse.
 During the hospitalization the patient was treated with high dose
antipsychotics like Clozapine, Seroquel and Entumin.
 Prior to deterioration the patient complained about abdominal pain.
Case review

3. Work up at admission
 Clinical examination : altered mental status , BP 80/50 , Pulse 150 ,
RR 22, O2 Saturation 94%, Fever 38° C.
 Abdomen: peritoneal signs, marked distention, absent bowel sounds.
 Lab. tests : PH 6.9, Lactate 9, WBC 19000, NEUT 85%, Creatinine 2, Urea
96, Potassium 6, Sodium 135, normal LFT’s, INR 1.12.
 Abdominal X ray : severe colonic dilatation without evidence of fecal
impaction or free air.
 CT scan : severe small and large bowel loops dilatation,
no evidence of free air, obstruction or volvulus, mild ascites.

4. CT scan

5. Any ideas?

6. Alam HB et al. N Engl J Med 2009;361:1487-1496.
Differential Diagnosis of Abdominal Distention and Shock.

7. Possible etiologies
 Acute megacolon (Ogilvie’s syndrome) : acute dilatation of the colon in the
absence of mechanical obstruction
- abnormal intestinal motility due to antipsychotic/ illicit drugs/electrolytes
 Toxic megacolon : colonic distention (>6 cm), inflammation and septic shock
- IBD
- Clostridium difficile colitis
 Abdominal compartment syndrome : colonic distention, shock and organ
failure with sustained intraabdominal pressure above 20 mmHg
- Critically ill patients (including with septic shock)

8.  The patient was stabilized with vasopressors, fluid resuscitation and
taken to urgent explorative laparotomy.
 On laparotomy massive ischemia of right colon including hepatic
flexure was noted, patient underwent subtotal colectomy and
protective ileostomy with mucous fistula.
 After laparotomy patient was transferred to ICU .
Management

9. Pathology report
 Large bowel with ischemic changes , hemorrhagic necrosis of the
mucosa (predominantly) and submucosa (focally), unremarkable
appendix.
 No clear evidence of colitis, granulomas or evidence of IBD.
 No obstructive condition was detected.

10. Diagnosis
In the absence of colonic inflammation or obstruction -
the diagnosis is acute megacolon, also known as
Ogilvie’s syndrome

11. Follow up
 One month after admission including recurrent septic episodes,
tracheostomy and prolonged rehabilitation the patient was
discharged with Zyprexa (olanzapine) treatment.
 Remained under gastroenterological and surgical follow up
 3 months after discharge the patient was well, underwent normal
colonoscopy before ileostomy closure was performed.

12. Clozapine induced gastrointestinal
hypomotility (CIGH)
Literature review

13. Literature review
 102 cases of Clozapine and Colonic hypo motility/ toxic megacolon
in New Zealand and Australia between 1967-2007.
 Prevalence 0.3 %
 Mortality rate of 27.5%.
 High morbidity mostly due to large bowel resection.
 Risk factors : recent Clozapine ingestion, especially high dose, concomitant use
of anticholinergic medications , or other hypomotility inducers such as opiates
and bowel surgery
Life- Threatening Clozapine-induced gastrointestinal hypomotility:
an analysis of 102 cases Palmer SE et al. J Clin Psychiatry 2008

14. Literature review - continued
 Review of 43,000 patients treated with Clozapine between 1992-
2013
 160/43,000 reported as having serious GI hypo motility
 29 patients died (7/10,000), while regulators report 1/10,000
Clozapine induced GI hypomotility: 22 year Bi-national pharmacovigilance study
Palmer SE et al. CNS DRUGS 2017

15. Literature review - continued
 Review of three large case series with 104 cases
 38% mortality
 Mean daily Clozapine dose 453 mg, Median age 40, 79% male
 Four patients were re-challenged with Clozapine, two developed
recurrency
Clozapine induced GI hypomotility: A potentially life threatening adverse event, literature review
West S. et al. Gen Hosp Psychiatry 2017

16. Literature review - continued
 Comparison of colonic transit time between patients treated and not
treated with antipsychotics using radiopaque marker.
 Control patients had 23h. of median colonic transit time vs. Clozapine
treated patients, which had median transit time of 104h.
 80% of Clozapine treated patients had colonic hypomotility,
compared with none of other antipsychotics.
 Pre-emptive laxative treatment is recommended with Clozapine.
Clozapine-treated patients have marked GI hypomotility, A cross sectional study
Every-Palmer S. et al. Ebiomedicine 2016

17. Take home message
 Consider Clozapine (or high dose antipsychotic medications) as a
possible etiology for acute megacolon
 Consider treatment for preexisting constipation before
administration of Clozapine/antipsychotic medications
 Consider complaints like constipation and abdominal distention in
patients taking high dose antipsychotic as alarm sign for life
threatening complications
 Early aggressive intervention is warranted in acute megacolon

18. Thank you!