In a talk at ACG 2020, the American College of Gastroenterology's annual meeting, held virtually last October, Charles J. Kahi, MD, MS, FACP, offered advice on how to manage acute colonic pseudo-obstruction (ACPO), which occurs in about 100 per 100,000 inpatient admissions a year.
By definition, ACPO is acute dilatation of the large intestine without evidence of mechanical obstruction, said Dr. Kahi, who is a professor of medicine at the Indiana University School of Medicine in Indianapolis. “Its exact mechanism is unknown, but most evidence suggests an alteration in the autonomic innervation of the colon, an imbalance in the sympathetic to parasympathetic control of colonic motility, the sum total of which leads to colonic atony,” he said.
He noted that the syndrome typically occurs in patients who are already hospitalized for severe illness or surgery, those who have had nonsurgical trauma, or those with a significant metabolic imbalance.
Opioids, anticholinergics, antipsychotics, calcium-channel blockers, dopaminergics, and chemotherapy— “essentially anything that can slow down gut motility”—can all cause ACPO, Dr. Kahi said. The other big culprits are metabolic and electrolyte disturbances, particularly those affecting the homeostasis of potassium, calcium, and magnesium, and surgery, particularly orthopedic, gynecologic, cardiothoracic, and abdominal or pelvic procedures, he noted.
The hallmark of ACPO is abdominal distention, “which typically occurs over a few days but can be rapid, over 24 to 48 hours, and those are actually the patients to be most concerned about,” Dr. Kahi said.
Nonspecific abdominal pain is common, and constipation and obstipation occur in about half of patients. However, some patients can experience paradoxical diarrhea due to colonic atony. “They form a large amount of liquid stool in the colon, which essentially seeps out passively, so the presence of liquid bowel movements doesn't rule out the presence of pseudo-obstruction, unlike mechanical obstruction, where there is more frequently obstipation,” he said.
Besides abdominal distention, patients with ACPO have tympany to percussion and bowel sounds on physical exam. “The things to look for are really the alarm signs, so fever, severe tenderness, and peritoneal signs. Obviously, those . . . indicate a more severe clinical course and warrant more intensive therapy and surgical consultation,” Dr. Kahi said.
The most serious adverse events associated with ACPO are ischemia, usually in the right colon, and perforation, Dr. Kahi noted. These complications develop in 3% to 25% of patients. “Cecal diameter of more than 12 cm is usually the cutoff to pay attention to,” he said. “In the presence of complications, the mortality rate from ACPO increases precipitously, from 15% to more than 40%. So it's extremely important to catch patients before they get to this point and obviously to intervene quickly should they develop evidence of ischemia or perforation at any time.”
Patients with ACPO need to be closely monitored with serial exams and a kidney, ureter, bladder X-ray every 12 to 24 hours, Dr. Kahi recommended. Those with ischemia, peritonitis, severe abdominal pain, and a cecal diameter exceeding 12 cm require a stat surgical consult, while a stepwise approach to management can be used in those with uncomplicated ACPO.
That approach starts with identifying and discontinuing predisposing factors, such as medications; treating the underlying condition, such as infection or sepsis; and correcting electrolyte abnormalities. In addition, he said, “There are some active interventions that can be done under the umbrella of conservative measures, and those include keeping the patient NPO (of course, also with adequate hydration) and decompression with a nasogastric tube and rectal tube,” he said. Ambulation can help if the patient is well enough for it, and repositioning in bed can also be useful, he said.
“These measures have to be applied for 48 to 72 hours, again, absent any evidence of clinical deterioration,” Dr. Kahi said. “And the good news is they are successful and the great majority of patients . . . recover with just these conservative low-risk measures.”
Some patients, however, don't respond or have a recurrence, and for them, pharmacologic treatment is the next step, Dr. Kahi said. The mainstay is IV neostigmine, an acetylcholinesterase inhibitor, 2 mg over four to five minutes.
“Keep it in mind even as you're applying the conservative measures, and consider definitely if the cecal diameter reaches or exceeds 12 cm at any time point,” he advised. A meta-analysis of four randomized controlled trials involving 127 patients, published in September 2014 in the Annals of Medicine and Surgery, found that one dose of neostigmine outperformed placebo 89% to 15% in resolving ACPO, with a number needed to treat of one.
“Most patients respond within minutes to one dose of neostigmine if they're going to respond, and it is associated with reduced duration and recurrence of ACPO,” Dr. Kahi said. “This is under the important assumption that you have addressed and are continuing to address other baseline predisposing factors with the conservative measures that we outlined before.”
Because the drug is a parasympathomimetic, it requires continuous cardiac monitoring. “Often that's not an issue because the patient is already in a monitored setting, but if not, that needs to be addressed,” Dr. Kahi said. In addition, atropine is necessary at the bedside to manage any instance of bradycardia when neostigmine is administered.
The only absolute contraindication to neostigmine is the presence of or any suspicion of mechanical obstruction, Dr. Kahi noted. In these cases, he said, “You cannot give a promotility agent, as this can have dire consequences for the patient.” Relative contraindications include bradycardia, reactive airway disease, and renal insufficiency, although some of these can be mitigated with close monitoring, he noted.
Patients who don't respond or respond only partially to the first dose of neostigmine can receive a second dose, usually after 24 hours, Dr. Kahi said. In addition, polyethylene glycol is an important co-intervention. A randomized controlled trial published by Gut in May 2006 showed that it helps decrease the rate of ACPO recurrence after neostigmine or colonoscopic decompression. Polyethylene glycol should be administered daily, either orally or through a gastrostomy tube, Dr. Kahi noted.
There are also newer pharmacologic options available, such as subcutaneous neostigmine, 4.25 mg four times per day, which a study published in Annals of Pharmacotherapy in January 2018 found to be effective for both ACPO and postoperative ileus, with a 1% rate of bradycardia. Neostigmine can also be administered via continuous infusion, 0.4 mg/h.
“It has a similar response rate to the bolus formulation that we're all familiar with, but [with] possibly shorter time to response and less bradycardia,” Dr. Kahi said, citing a study published in the Journal of Intensive Care Medicine in October 2020. “There's not a lot of data to support the superiority of one formulation or mode of administration compared to the other, but that's one other consideration to keep in mind pending additional data.”
Pyridostigmine, another acetylcholinesterase inhibitor, and methylnaltrexone can also be considered, but Dr. Kahi noted that there is little evidence to support their routine use and even less comparing them with neostigmine. “So the bottom line is, while there are variations around the theme of neostigmine, most pharmacologic therapy, with the appropriate precautions that I mentioned, still centers around neostigmine because it is highly effective and relatively safe, particularly in a monitored setting,” he said.
If conservative and pharmacologic measures are unsuccessful, or if neostigmine is contraindicated, the next step is colonoscopic decompression, Dr. Kahi explained. “It's actually done differently than your routine outpatient screening colonoscopy, because reaching the cecum is not the goal, and it has to be done in an unprepped colon,” he said. “That almost goes without saying because it's really not possible to prep a patient with ACPO due to colonic atony.”
He stressed that the procedure should be performed by an experienced endoscopist. The success rate is about 70% to 90%, but recurrence rates are high, up to 40% in some studies. In addition, it has associated complication and mortality rates of 3% and 1%, respectively.
“While there are some studies suggesting that primary colonoscopy decompression is more effective than pharmacologic intervention, because it's an invasive procedure (a very messy procedure to be quite honest), I think most clinicians would prefer neostigmine as first-line therapy in the absence of contraindications,” Dr. Kahi said.
If all of these measures fail, or if there is any evidence of complicated ACPO, surgery is the remaining option, Dr. Kahi said. However, mortality rates in patients with ACPO and ischemia or perforation are high, above 40%, he noted. Some intermediate procedures are available, such as percutaneous placement of a cecostomy tube or an endoscopic-surgical hybrid approach. “But those are reserved for patients who are unable to tolerate standard surgical approaches, such as subtotal colectomy, and, of course, depend on local expertise,” he said.
Dr. Kahi's primary take-home point for physicians dealing with ACPO is very simple: Don't panic. “Most patients do well but have to be monitored very, very closely,” he said. A multidisciplinary approach is vital, with GI services involved early, and complicated ACPO must be distinguished from uncomplicated ACPO. “Most patients respond to conservative measures and/or neostigmine. A minority still need colonoscopic decompression, and if that's needed, expertise is important,” Dr. Kahi said. “Of course, at any time point, patients can change clinical course very rapidly. Remain vigilant for any signs of complicated ACPO.”