Constipation and ileus in the critically ill

The college asked about constipation ( a variation on the theme of gut dysmotility) in Question 17 from the first paper of 2016. Colonic pseudo-obstruction was asked about in Question 7 from the first paper of 2018.  Gut dysmotility and prokinetic agents are discussed elsewhere, and that topic is kept separate because the discussion there is more about improving the tolerance of incoming enteral feeds. Improving the exit of those feeds is the topic of this chapter. The best short introduction to the topic is probably the 2015 article by JL Vincent and JC Preiser.

Broadly speaking, constipation is associated with inadequate nutrition due to poor feed tolerance, delayed ventilator weaning and slower ICU progress, with some authors reporting an increased ICU stay. The therapy scales up from simple things (stopping the constipating drugs and mobilising the patient) all the way to neostigmine infusion and manual disimpaction.

Definitions of constipation and ileus

ESICM have a working group or subcommittee for just about everything ( I am sure they have a team specifically authorised to categorise injuries arising from being sucked into an aircraft engine). These definitions for gut problems have been adapted from their 2012 statement.

• Constipation in the historic literature has been defined as "failure of the bowel to open for three consecutive days" (eg. used by Mostafa et al, 2001). ESICM support this cut-off, but suggest that ICU patients cannot use the normal colloquial definition of constipation ("uncomfortable or infrequent bowel movements, hard stool and painful defecation") and recommend we instead use the term "paralysis of lower GI tract". CICM still call it constipation in Question 17 from the first paper of 2016. A rose by any other name, etc.
• Ileus (or "paralytic ileus", or  "pseudo-obstruction", as separate from "post-operative ileus" and actual bowel obstruction) is the occurrence of intestinal blockage in the absence of an actual physical obstruction.
• "Ogilvie's syndrome" or colonic pseudo-obstruction obviously is the same as above, but specific to the colon. 

Risk factors for constipation in the ICU

According to Nassar et al, (2009), constipation occurred in 69.9% of the patients who stayed for loger than 3 days in the ICU. In other studies, it ranges from 5% to 83% (Azevedo et al, 2013) Factors associated with constipation may include a long list:

Modifiable ICU-related risk factors

• Delayed enteral nutrition (delayed for longer than 24 hrs) - although early enteral nutrition has also been blamed, and in fact in ICU patients nasogastric nutritional formula is at least as likely to cause constipation as diarrhoea ( Montejo et al, 1999).
• Reduced mobility
• Deep sedation
• Heavy opiate use
• Anticholinergic drug side effects
• Calcium channel blockers
• The use of paralysing infusions
• Electrolyte disturbance, eg.hypokalemia hypercalcemia and hypomagnesemia
• Dehydration, inadequate fluid resuscitation (or excess diuresis)
• Hypotension (SBP under 90mmHg - Gacouin et al, 2010)
• Hypoxia (P/F ratio under 150 - also Gacouin et al)

Non-modifiable disease risk factors

• Abdominal surgery
• Severe illness
• Paralysis (eg. spinal cord injury) 
• Prior alcohol or cannabis use
• Nicotine withdrawal

Consequences of constipation

Constipation seems to be associated with numerous adversities for the critically ill patient:

• Increased ICU length of stay (Mostafa et al, 2001)
• Slower weaning (or failure to wean) from mechanical ventilation (Mostafa et al, 2001)
• Agitation and delirium (Smonig et al, 2016)
• Worse organ system failure severity scores (Gacouin et al, 2010)
• Increased mortality (Gacouin et al, 2010)

Consequences of constipation may include:

• Abdominal distension
• Vomiting and aspiration
• Increased intra-abdominal pressure
• Reduced nutritional intake
• Bacterial hyperproliferation and translocation through the gut mucosa
• Bowel obstruction
• Bowel perforation
• Gut ischaemia

This is probably a reasonable place to discuss the pointlessness of auscultating bowel sounds in ICU patients. The practice of trying to distinguish normal from pathological bowel sounds has been nicely debunked by van Bree et al (2018), who determined that the reliability of this examination manoeuvre in discriminating ileus from non-ileus  was approximately as accurate as tossing a coin.

Radiological features of ileus and colonic pseudo-obstruction

• Chest Xray: to rapidly exclude bowel perforation, looking for gas under the diaphragm
• Abdominal Xray: findings identical to mechanical obstruction, i.e. dilated bowel loops
• CT of the abdomen: findings: gaseous dilatation of the colon with no stricture, mass or clear transition point. A "smooth transition" may be seen, which is a slight discrepancy in diameter between the proximal and distal bowel loops - less than 50% (Choi et al, 2008).

Management options

• Stool softeners:
  • Coloxyl (docusate)
• Stimulant laxatives:
  • Sennocot
• Bulk-forming "soluble fibre" laxatives
  • Soy polysaccharide
  • Hydrolyzed guar (often already mixed with the NG formula)
  • Pectin
  • Psyllium
• Osmotic laxatives:
  • Lactulose
  • Polyethylene glycol
  • Sodium picosulfate (which forms magnesium citrate in the bowel)
  • Magnesium sulfate
• Enemas
  • "Microlax" 5ml sodium citrate/sorbitol enema
  • "Fleet" 118ml sodium phosphate enema
• Prokinetics and promotility agents are discussed in greater detail elsewhere; in brief:
  • Erythromycin
  • Neostigmine
• Opiate antagonists
  • Naloxone (enterally)
  • Methylnaltrexone
• Novel and experimental therapies:
  • Lubiprostone, a selective chloride channel-2 activator

An approach to the constipated ICU patient:

Tier one therapies and investigations:

• Abdominal X-ray to exclude "true" bowel obstruction"
• Electrolytes and biochemistry to rule out and correct any electrolyte disturbance
• Fluid management review to ensure euvolaemia and adequate hydration
• Attention to primary pathology (eg. shock, hypoxic respiratory failure) - if this is being treated well and is getting better, patience may be all that is required.
• Drug chart audit to ensure exposure to opiates, anticholinergics and calcium channel blockers is minimised
• Mobility: physiotherapy for limbs, sit out of bed in a chair, etc
• Stool softeners, stimulants and bulk-forming laxatives:
  • Docusate
  • Sennocot
  • Soluble fibre

Tier two therapies and investigations: Assuming bowel obstruction and megacolon are ruled out

• Osmotic laxatives:
  • Lactulose
  • Polyethylene glycol
• PR examination:  this may have a therapeutic effect
• Enema
• Prokinetics, eg. erythromycin
• Opiate antagonists, eg. methylnaltrexone

Tier three therapies and investigations: assuming all of the above are ineffective, or impossible to implement

• Abdominal CT  to investigate for possible abdominal pathology unseen on AXR
• Neostigmine infusion
• Manual disimpaction
• Surgical decompression

An approach to management of colonic pseudo-obstruction:

Supportive

• Nil by mouth
• Correct electrolytes
• Ensure the patient is well-hydrated
• Nasogastric tube on free drrainage or low wall suction
• Rectal tube to gravity drainage
• Limit anti-motility medications, such as opiates and anticholinergic agents
• Mobilise the patient and sit them out ouf bed

Pharmacological (pro-motility) management

• Oral or nasogastric naloxone
• Methylnaltrexone
• Enema
• Erythromycin
• Neostigmine

Interventional (decompressive) management

• Sigmoidoscopy
• Colonoscopy 
• Surgical decompression
• Caecostomy 
• Colectomy, ileostomy, and Hartmann procedure

Advantages of surgical decompression are:

• You release the pressure, which reduces the extraintestinal effects (eg. abdominal compartment syndrome and respiratory failure)
• The improved perfusion of the gut should lead to improved gut function

The disadvantages are:

• More anaesthetic (therefore, more ileus)
• Unless there are adhesions to release, this does not fix the underlying problem (possibly makes it worse)
• By reperfusing the gut, you could cause a "septic shower", creating haemodynamic instability

Neostigmine for ileus

This is a therapy supported by a small number of RCTs, all of which in turn had a small number of patients, such that when Valle & Godoy (2014) tried to do a meta-analysis on this, they turned up only 127 patients. A single dose of neostoigmine seemed to resolve colonic pseudo-obstruction in 89.2% of patients. In ICU patients, Van der Spoel et al (2001) used a continuous infusion of 0.4-0.8mg/hr, with similar results (they put 5mg in 50ml syringes and started the infusion at 4ml/hr, in case you are wondering) 

Arguments for aggressive management of constipation

• It is a preventible cause of delayed ventilator weaning and longer ICU stay
• Numerous studies have associated constipation with poorer outcomes
• Management options are largely cheap and benign
• Consequences of untreated constipation may be lifethreatening
• Arguments against the aggressive management of constipation are either theoretical (complaining about study methodology or heterogeneity of definitions) or arising from sloth (the constantly defecating patient is more difficult to care for from a nursing point of view).

Arguments against aggressive management

• Constipation may be relatively harmless. In the cohort oberved by  Nassar et al, (2009), constipation was not associated with greater intensive care unit or hospital mortality, length of stay, or days free from mechanical ventilation. Obviously, these findings are not replicted by all authors. As seen above,  Mostafa et al (2001) performed a very similar study, with similar definitions, and arrived at completely different conclusions.
• The definition of constipation is far from scientific, as the three day cutoff is quite arbitrary. It is well known that ICU patients open their bowels infrequently. In the group who were declared "not constipated" by standard criteria (Guerra et al, 2013) the mean time until bowels opened was approximately 2.8 days on average.
• The association of constipation with worse outcomes may be merely reflective of its association with severe illness (i.e. patients whose illness is more severe also have more constipation, and - on an unrelated note- they also die more often and have a longer stay in ICU).
• Abdominal distension may worsen with laxative use
• Fluid losses will increase with more frequent liquid stools
• Electrolyte derangement may develop due to high volume diarrhoea resulting from laxative use
• Liquid stools can become difficult to manage from a nursing workload point of view, as well as in terms of infection control and wound contamination
• Bowel perforation or hyperphosphataemia may result from the excessive use of enemas