Case presentation

Dr. Roni Rozen

Wolfson medical center, Gastroenterological institute

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

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.

CT scan

Any ideas?

Alam HB et al. N Engl J Med 2009;361:1487-1496.

Differential Diagnosis of Abdominal Distention and Shock.

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)

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

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.

Diagnosis

In the absence of colonic inflammation or obstruction -

the diagnosis is acute megacolon, also known as

Ogilvie’s syndrome

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.

Clozapine induced gastrointestinal

hypomotility (CIGH)

Literature review

Literature review

102 cases of Clozapine and Colonic hypo motility/ toxic megacolonin 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

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

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 reviewWest S. et al. Gen Hosp Psychiatry 2017

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

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

Thank you!