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A 50-year-old man of Vietnamese origin presents with vomiting, watery diarrhea, and generalized abdominal pain. He admits to being a heavy drinker but denies any other harmful habits. He does not believe that he has been exposed to anyone ill. His medical history includes intermittent asthma symptoms and seizures. The patient reports that for the past week, he has had a fever, been coughing up phlegm, and has a sharp chest pain on both sides that worsens with breathing.

Day 1: The patient is admitted to intensive care. A physical examination notes severe respiratory distress. He has no fever, but he is tachycardic, hypoxic, and his blood pressure is low at 90/60 mm Hg.

Clinicians intubate the patient, who requires mechanical ventilation. Laboratory tests identify leucopenia, thrombocytopenia, lactic acidosis, and severe transaminitis. Bilateral infiltrates are evident on chest x-ray.

The patient is given intravenous fluids. He also receives broad-spectrum antibiotic treatments for septic shock due to pneumonia – medications include vancomycin, piperacillin tazobactam, oseltamivir, and azithromycin.

However, acute respiratory distress syndrome develops. Clinicians suspect leptospirosis, and he is given meropenem and levofloxacin. Piperacillin, tazobactam, and azithromycin are discontinued.

The patient develops significant agitation – likely related to his respiratory distress – which is treated with propofol, fentanyl, and lorazepam. As the patient shows signs of improvement over the next few days, clinicians begin reducing dosage of these sedatives.

Bronchoscopy identifies Klebsiella pneumoniae and parainfluenza, and antibiotic treatment is de-escalated. Tests for hepatitis, and blood, urine, and spinal fluid cultures are all negative. A computed tomography (CT) scan of the patient's head and transthoracic echocardiography are also normal.

Day 4: At this time, he develops severe agitation and is started on dexmedetomidine.

Day 9: The patient experiences abdominal pain and non-bloody diarrhea, and develops acute abdominal distension and ileus. He is started on intermittent morphine.

Further testing

Abdominal x-ray and CT scan without contrast reveal dilations of the cecum (>15 cm diameter) and the colon (up to 10.1 cm), but no bowel perforation is evident. Clinicians suspect toxic megacolon versus volvulus. Efforts to manage the decompression with nasogastric and rectal tube and aggressive electrolytes and fluid replacement are not successful. Abdominal distention continues to be evident on serial imaging.

Acute onset of ileus is confirmed. The potential of an infectious cause had prompted earlier antibiotic treatment. Other diagnostic considerations include ileus due to metabolic and electrolyte derangement, however, these were aggressively corrected at the time of admission to intensive care.

Day 10: The second of two stool samples taken 1 day apart tests negative for C. difficile toxin A and B and GDH antigen, as well as for ova, parasite, and culture. Several blood cultures also remain negative.

Day 11: Attempted endoscopic decompressions of the colon are not successful. In response to the patient's continuing clinical decline, clinicians perform surgery. This reveals cecal perforation with serosal tear. The patient receives a side-to-side ileocolic anastomosis with diversion loop ileostomy. Pathological findings include patchy transmural suppurative acute and chronic inflammation with ulceration, mucosal necrosis, and serositis. Special stain PAS (Periodic acid-Schiff) reveals focal superficial ulcer with fungal hyphae colonization.

Diagnosis and follow-up

Based on clinical and pathology findings, clinicians identify the likely cause as ischemic colitis and perforation due to acute colonic pseudo-obstruction (ACPO), likely related to the patient's exposure to dexmedetomidine. The patient is able to be taken off mechanical ventilation and discharged to a skilled nursing facility with jejunostomy tube feeding and tracheostomy.

Discussion

Clinicians reporting this ¹ note that while the incidence of ACPO is low, it tends to affects patients with underlying conditions. Awareness and vigilance for this potentially fatal condition is especially important in sedated, ventilated patients in whom symptoms of ACPO could be missed or misinterpreted, delaying diagnosis.

Case authors report etiologies that have been proposed since Ogilvie suggested that bowel dilation in ACPO was related to autonomic imbalance with sympathetic deprivation of the colon.² Many have been proposed. Newer theories favor an excess of the sympathetic over the parasympathetic tone secondary to a reduced parasympathetic innervation to distal colon, the case authors write, leading to a non-functional or atonic segment which therefore results in functional obstruction.^3-5

Autonomic imbalance is also more likely to occur in critically ill patients more prone to increased sympathetic activity. Clinicians of this case suggest that colonic distention at the level of splenic flexure could be due to the overlap of sympathetic and parasympathetic anatomic innervation.

Numerous risk factors are associated with ACPO. As this case illustrates, these include severe infection, electrolyte imbalance, respiratory disorders, and toxic insults such as alcohol abuse and severe illness.

Patients also at increased risk of ACPO include those with cardiac disease; Guillain-Barre syndrome; metabolic disorders such as hypothyroidism, diabetes, liver failure; chronic obstructive pulmonary disease; renal insufficiency; gastrointestinal cancer; severe constipation; intestinal hypoperistalsis; multiple myeloma or amyloidosis; systemic lupus erythematosus; surgery; trauma; spinal cord injury; or burns.

Case authors write that this observed instance of ACPO in the setting of dexmedetomidine use (also seen with clonidine) is thought to occur because alpha-2 agonist receptors reduce peristalsis by activating these receptors in the enteric neurons, resulting in a dose-dependent delay in gastric transit and emptying.^6,7 See Figure for a summary of ACPO's physiopathology.

The clinical presentation of patients with ACPO is similar to small bowel obstruction with abdominal distention, fever, nausea, and emesis (60% of patients), and abdominal pain (80% of patients). Other symptoms like constipation (50%), paradoxical diarrhea (40%), and more rarely, dyspnea, have been reported.

Symptoms can be acute or subacute, ranging from a few days to 1–2 weeks duration, case authors note. The severity of ACPO ranges from mild distention to obstruction, followed by ischemia of the bowel and perforation. Prognosis varies depending on the patient's comorbidities, risk factors, and clinical status.⁸

The key diagnostic challenge involves differentiating small bowel obstruction from ACPO. Typically, abdominal x-ray reveals distended bowel loops with air-fluid levels; use of oral and intravenous contrast is helpful on CT scan.

involves primarily supportive and preventive measures such as correction of electrolyte imbalance and avoidance of predisposing medications. A conservative approach is especially important in patients with intestinal lumen of <12 cm. Adequate fluids intake, walking as early as possible, and knee to chest or prone positioning to promote flatus have been recommended.⁹

In those not responding to initial supportive management, a trial of neostigmine or colonic decompression could be attempted. Neostigmine temporarily increases acetylcholine levels in muscarinic receptors from parasympathetic nervous system, thus promoting contractility and assisting in colon transit. This treatment should be limited to patients with uncomplicated ACPO, and is contraindicated in the presence of colonic ischemia or perforation, pregnancy, severe cardiac arrhythmias, or active bronchospasm.

In patients who are not responding or who are not candidates for neostigmine, colonic decompression may be used. It has a reported success rate of 60%–90% and reported rate of perforation of 1%–3%. Surgical intervention such as tube ostomies or resection should only be used in patients not responding to medical management, or those with ACPO associated perforation or necrosis of the bowel.

Conclusion

Although rare, ACPO is a risk in critically ill patients that deserves awareness and vigilance for possible contributing factors such as electrolyte and fluid imbalance, as well as a medication review and discontinuation of possible contributors. Repeated examinations will assist in early recognition. Clinicians note that to decrease morbidity and mortality in patients with ACPO, management should be multidisciplinary, involving the intensivist, gastroenterologist, and surgery.

References

1. Pérez-Lara JL et al. Acute Colonic Pseudo-Obstruction Caused by Dexmedetomidine: A Case Report and Literature Review. Am J Case Rep 2019; 20: 278-28

2. Ogilvie H. Large-intestine colic due to sympathetic deprivation; A new clinical syndrome. Br Med J, 1948; 2: 671–73

3. Wells C et al. Acute colonic pseudo-obstruction: A systematic review of aetiology and mechanisms. World J Gastroenrol, 2017; 23(30): 5634–44

4. Vanek VW, Al-Salti M. Acute pseudo-obstruction of the colon (Ogilvie's syndrome): An analysis of 400 cases. Dis Colon Rectum, 1986; 29: 203–10

5. Pereira P et al. Ogilvie's syndrome-acute colonic pseu- do-obstruction. J Visc Surg, 2015; 152: 99–105

6. Iirola T et al. Dexmedetomidine inhibits gastric emptying and orocecal transit in healthy volunteers. Br J Anaesth, 2011; 106(4): 522–27

7. Herbert MK et al. Clonidine and dex- medetomidine potently inhibit peristalsis in the Guinea pig ileum in vitro. Anesthesiology, 2002; 97: 1491–99

8. Vogel JD et al. Clinical practice guidelines for colon volvulus and acute colonic pseudo-obstruction. Dis Colon Rectum, 2016; 59(7): 589–600

9. Zhao C Xie T Li et al. Acute colonic pseudo-obstruction with feeding intolerance in critically ill patients: A study according to gut wall analysis. Gastroenterol Res Pract, 2017; 2017: 9574592

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