Grand RoundsGrand Rounds

IVY DIMAYUGA-DE DIOS, M.D.Department of MedicineMakati Medical Center

2 August 2007

IVY DIMAYUGA-DE DIOS, M.D.Department of MedicineMakati Medical Center

2 August 2007

ObjectivesTo present a case in the ICU illustrating the development of ileus/intestinal pseudo-obstruction in the critically ill

To enumerate the risk factors and pathophysiology in the development of ileus/intestinal pseudo-obstruction in critically ill patients

To discuss the management options for ileus/intestinal pseudo-obstruction in the critically ill

The CaseThe Case

admitted for unresponsiveness

2-week history of dizziness, left-sided weakness, vomiting, LOC

diagnosed with Pontine infarct 2complete basilar artery occlusion

comatose, intubated, s/p tracheostomy

treated with Enoxaparine and Co-amoxiclav

H. T., 62/M, (+) HPN

Pertinent PE

BP: 110/70 HR: 88 bpm RR: 20, assisted T: 39.2 °C

pink conjunctivae, anicteric sclerae, (-) NVE, (-) CLAD, (-) TPC, (-) carotid bruits

equal chest expansion, fine crackles left basal lung field

adynamic precordium, good S1 and S2, apex beat displaced 2 cm lateral to 5th ICS LMCL , (-) murmur

abdomen soft, NABS, (-) masses

full and equal pulses, edematous upper and lower extremities

(+) multiple dry, irregularly-shaped erosions with erythematous base and surrounding hyperpigmentation over the L gluteal and L mid-back areas

DRE: (-) masses, lax sphincter tone, full rectal vault, yellowish stool

Pertinent NE

comatose, non-responsive to painful stimuli

pupils 2mm ESRTL

(-) Doll’s eye and corneal reflexes

flaccid extremities

(+)1 DTRs on all extremities

(-) Babinski reflexes

supple neck

Admitting ImpressionPontine infarct 2° to complete basilar artery occlusion

Acute respiratory failure 2° to CVA

Fever, probably 2° to infected decubitus ulcers vs. hospital-acquired pneumonia

Hypertensive cardiovascular disease

Course in the WardsNeurologic

Acute pontine infarct 2° to complete basilar occlusion

Tx: Somazine, Warfarin, Enoxaparine, Cilosatazol

Respiratory

Acute respiratory failure 2° to pontine infarct

Mechanical ventilator: tolerated SIMV weaning off pressure support, maximum PEEP at 10 cm H2O

Infection

Sepsis 2° to hospital-acquired pneumonia; Decubitus ulcers, grade 2

Initial tracheal and blood cultures grew gram negative rods

Tx: broad-spectrum antibiotics; Calmoseptine and Bactroban ointment with duoderm dressing

Course in the Wards

Renal

Dx: Acute renal failure, pre-renal, 2° to sepsis, t/c chronic Kidney Disease 2° to HPN nephrosclerosis; Hypoalbuminemia 2° to poor intake; Third space losses 2° to Hypoalbuminemia

Tx: Hydration, IV human albumin, Nutricomp added to feeding, IV Epoietin

Course in the Wards: Gastrointestinal

Pt admitted with a soft abdomen, NABS, no palpated masses, normal DRE, NGT fed.

OF started at 2000 kcal/day, 222 cc + 50 cc H2O flushing q4°, drip < 1 hour.

Lansoprazole 30 mg OD

2nd HD: increased NGT residuals = 200 cc

Next feeding withheld; OF given via drip x 1 1/2 hours and decreased to 1600 kcal/day, 178 cc + 50 cc H2O flushing q

5th HD: episodes of hiccups

PPI and Domperidone continued; Baclofen given

8th HD: (+) distended abdomen, (+) hypoactive bowel sounds, (+) tympany, soft, adequate BM, no significant residuals

still with intermittent fever; SIMV not tolerated

PFA: Mild gaseous dilatation of some small bowel segments due to ileus.

Domperidone + Omeprazole + Baclofen

11th HD: no BM x 24 hours, (+) hiccups, distended abdomen, hypoactive bowel sounds, (+) tympany, (+) NGT residuals = 150 cc, abdominal girth = 44 cm.

feeding discontinued temporarily → Vamin glucose started

NGT reinserted and hooked to bedside bottle

Laxatives given→ (+) BM

12th HD: (+) BM, ↓abdominal distention and tympany, abdominal girth=40 cm

OF resumed with decreased amount (133 cc q4°) and decreased drip rate (drip for 2 hours, drainage for 1 hour prior to feeding

Iberet discontinued

13th HD: recurrence of fever with severe abdominal distention, hypotension, tachycardia, desaturation, anuria; vasopressors started

Abdomen globular and firm but not tense, absent bowel sounds; serum K normal

OF discontinued

Referred to GI service; Assessment: Generalized ileus probably 2° to mesenteric hypoperfusion due to multiple underlying medical illnesses, to r/o mechanical obstruction

PFA: progression of gaseous distention of the small and large bowels

whole abdominal USG: normal liver, spleen, kidneys; the rest could not be evaluated due to overlying loops of bowel

13th HD...

Tx: conservative GI decompression with NGT and rectal tube insertion

slow fleet enema → (+) BM

Metoclopromide RTC; plan to give Tegaserod but not available

serum K monitoring: no hypokalemia

other plans: imaging (ie, CT scan); endoscopic/surgical decompression

14th HD: abdomen clinically soft, absent bowel sounds, (+) tympany (Pt at this time was still anuric and acidotic; better BP control with vasopressors); (+) coffee-ground and bilious drainage per NGT

PFA: further progression of the gaseously distended small and large bowels; consider a distal colonic obstruction

concern: enlarged cecal diameter 10 cm

PPI dose increased; gastric lavage done

GIT decompression continued; Metoclopromide continued

repeat slow fleet enema → (+) BM

arrested during dialysis

Final DiagnosisMultiple organ failure 2

Septic shock 2hospital-acquired pneumonia

Pontine infarct 2to complete basilar artery occlusion

Acute colonic pseudo-obstruction 2to general medical condition

Hypertensive cardiovascular disease

t/c Chronic Kidney Disease 2 to HPN nephrosclerosis

Hypoalbuminemia 2to poor intake

Decubitus ulcers, grade 2

Discussion: Ileus and Intestinal Pseudo-

obstruction

Discussion: Ileus and Intestinal Pseudo-

obstruction

Enteric Nervous System

a collection of neurons in the GIT that constitutes the “brain of the gut”

can function independently of the CNS

controls the motility, exocrine and endocrine secretions, microcirculation, immune and inflammatory processes

peristalsis - result of a series of local reflexes, each consisting of a contraction of intestinal muscle above an intraluminal stimulus and a relaxation of muscle below the stimulus

interstitial cells of Cajal - nonneural cells that serve as pacemakers responsible for the spontaneous, rhythmic, electrical excitatory activity of GI smooth muscle (slow waves)

Goyal RK et al., NEJM, 1996, 335: 215

Goyal RK et al., NEJM, 1996, 335: 215

Adynamic Ileus

obstipation and intolerance of oral intake resulting from a non-mechanical insult that disrupts the normal coordinated propulsive motor activity of the GIT

abdominal distention, lack of bowel sounds, accumulation of gas and fluids in the bowel and decreased GI passage with delayed or absent defecation

Goyal RK et al., NEJM, 1996, 335: 215Madl C and Druml W. BPRCG, 2003, 17 (3): 445

Ileus vs. Pseudo-obstructionIntestinal ileus - lack of motor activity in the intestine

activity can be inhibited by the selective suppression of excitatory motor reflexes through sympathetic nerves or by sustained intrinsic inhibitory neural overactivity

activation of non-neuronal inducible NOS ⇒↑ nitric oxide

cannot be produced by the generalized suppression of neural activity in the gut

All neural transmission inhibited→ (-) tonic, neurogenic inhibition →unmasks spontaneous, myogenic excitation → increased contractile activity →uncoordinated, non-propulsive activity ⇒ functional bowel obstruction (chronic)

Goyal RK et al., NEJM, 1996, 335: 215

Etiologypost-op ileus - inhibitory neural reflexes and inflammatory processes

opioids

catecholamines

intraperitoneal/retroperitoneal infection

edema/ascites 2° to massive fluid resuscitation

abdominal arterial or venous injury

diffuse inflammation of the intestinal wall (IBD, acute intestinal infections, pseudomembranous colitis)

mesenteric ischemia

intraabdominal/retroperitoneal hematomas

metabolic disturbances (ie, ↓K)

renal function - strong predictor of impairment of intestinal motility

EtiologySepsis on GI motility in ICU patients

Exogenous LPS from gram-negative bacteria

nitric oxide and prostaglandins

cytokines (IL-6, TNF-α, IL-1β): alter the enteric neuromuscular transmission

increased intestinal permeability (increase in the large pores in the intestine despite an overall decreased functional absorptive area) Cullen JJ et al., Dig Dis Sci, 1997, 42: 731-

7Johnston JD et al, Crit Care Med, 1996, 24: 1144-9Overhaus M et al, AJPGL, 2004, 287: G685-694

Pathophysiology

Intestinal dilatation/inflammation ⇒ neutrophils release proteolytic enzymes and cytokines ⇒ release of NITRIC OXIDE ⇒ smooth muscle paralysis aggravating intestinal dilatation

NOS amount and activity correlates significantly with intestinal dilatation

animal studies: NOS inhibitors ⇒ improvement of intestinal dilatation, intestinal contractility and gut luminal pressure

Madl C and Druml W. BPRCG, 2003, 17 (3): 445

Acute colonic pseudo-obstruction: Ogilvie’s syndromeintestinal ileus with massive colon dilatation (usually the cecum and right hemicolon) without mechanical obstruction that develops in hospitalized patients with serious underlying medical or surgical conditions

M > F; >60 y/o

>95% of patients: associated with a predisposing factor or clinical condition

3 most common associations: trauma, infection, cardiac disease

32%: (+) metabolic, cancer, respiratory failure, renal failure

>50%: (+) metabolic imbalance (esp. hypoK, hypoCa, hypoMg) and opiate administration

sole association in <5% of cases

Saunders MD. BPRCG, 2007, 21(4): 671-87Vanek VW et al., Dis Colon Rectum, 1986, 29:203Jetmore AB et al. Dis Colon Rectum, 1992, 35: 1135

Acute colonic pseudo-obstruction: Ogilvie’s syndromeClinical manifestations

abdominal distention → labored breathing

abdominal pain, nausea, vomiting

(+) tympany; (+) bowel sounds in >90%

(+) peritoneal signs: impending perforation

leukocytosis: underlying disease; impending perforation

PFA: dilated colon, often from the cecum to the splenic flexure (occasionally to the rectum)

normal haustral markings

CT scan or gentle water soluble enema: for confirming Dx and excluding mechanical obstruction and toxic megacolonSaunders MD. BPRCG, 2007, 21(4): 671-87

Vanek VW et al., Dis Colon Rectum, 1986, 29:203

Motor input from the CNSParasympathetic

cholinergicexcitatory

Sympatheticadrenergicinhibitory

Vagus Sacral

Distal colonRectum

Upper GITSmall bowelRight colon

⇓⇓

⇓ ⇓

Colon

Celiac and mesenteric ganglia

ACPO: alteration in the autonomic regulation of colonic motor function

transient parasympathetic impairment at the sacral plexus

hyperactivity of inhibitory neurons to the large bowel

colo-colonic reflex: Distention→Mechanoreceptors→reflex via efferent sympathetic nerves targeting the myenteric plexus or smooth muscle layers ➜ inhibition of colonic motilityGoyal RK et al., NEJM, 1996, 335: 215

Saunders MD. BPRCG, 2007, 21(4): 671-87

Differential Diagnosis of Acute Colonic Dilation

Mechanical obstruction

Clostridium difficile infection (Toxic megacolon)

Acute colonic pseudo-obstruction

Saunders MD. BPRCG, 2007, 21(4): 671-87

ACPO vs. mechanical obstruction

(+) crampy abdominal pain

“cut-off sign” (lack of gas in the distal colon or rectum)

small bowel air-fluid levels

ACPO vs. Toxic Megacolon

very ill: (+) fever, tachycardia, abdominal tenderness

(+) history of bloody diarrhea

PFA: (+) “thumbprinting” due to the presence of submucosal edema, or thickening of the colonic wall

flexible sigmoidoscopy: (+) active colitis

Martin B, AACN Adv Crit Care, 2007, 18(2):158-66Mutlu GM et al, Chest 2001,119: 1222-41

Pathophysiology of systemic consequences of ileus

Madl C and Druml W. BPRCG, 2003, 17(3): 445-56

Systemic Consequences

Madl C and Druml W. BPRCG, 2003, 17(3): 445-56

Factors influencing outcome in ACPOSeverity of underlying illness

Increasing age

Cecal diameter (>12 cm)

Duration of colonic distention (>6 days)

Presence of ischemia or perforationSaunders MD. BPRCG, 2007, 21(4): 671-87Eisen GM et al, Gastrointest Endosc, 2002, 56:789

Treatment Options

Supportive measures

Pharmacologic therapy

Colonoscopic decompression

Surgery

Supportive therapy for ACPO

NPO, maintain on IV fluids

Correct fluid and electrolyte imbalances; treat underlying reversible causes; discontinue unnecessary medications

Nasogastric suction

Rectal tube decompression - (+) sigmoid colon and rectal involvement

Limit offending medications

Frequent position changes (ambulate if possible)

Serial PE and abdominal radiographsSaunders MD. BPRCG, 2007, 21(4): 671-87

Supportive therapy for ACPO

successful as the primary treatment in the majority of patients

Sloyer et al on 25 cancer patients with ACPO: 96% improved by clinical and radiologic criteria

retrospective series of 151 patients with ACPO: 77% had spontaneous resolution

initial management of ACPO should be directed towards eliminating or reducing contributory factors

Saunders MD. BPRCG, 2007, 21(4): 671-87Sloyer AF et al. Dig Dis Sci, 1988, 33:1391-96Loftus CG et al. Am J Gastroenterol 2002, 97:3118-22

Pharmacologic agents for ACPO

Gentle enemas

Neostigmine - reversible acetylcholinesterase inhibitor

PEG electrolyte solution

Erythromycin - motilin receptor agonist

Metoclopramide - reverses the inhibitory effects of dopamine on GI motility (more for gastric emptying)

Cisapride, Tegaserod - 5-HT4 receptor agonist

Alvimopan - peripherally-restricted µ-opioid antagonistSaunders MD. BPRCG, 2007, 21(4): 671-87Loftus CG et al. AJG, 2002, 97: 3118Bonacini M et al. J Clin Gastroenterol, 1991, 13:475Sgouros SN et al, Gut, 2006, 55: 638-42

Pharmacologic agents for ACPONeostigmine - the only randomized, double-blind, placebo-controlled therapeutic trial for ACPO

Ponec et al.: (+) clinical response in 91% of patients

van der Spoel et al: 85% of critically ill ventilated patients passed stool

(+) several non-controlled, open label and retrospective series supporting the use of neostigmine for ACPO

Mehta et al.: response to neostigmine more likely in the post-op setting, and less likely in those with electrolyte imbalance or receiving anti-motility agents

Contraindications: mechanical obstruction, ischemia/perforation, severe bronchospasm, pregnancy, uncontrolled cardiac arrhythmias, renal failure

Saunders MD. BPRCG, 2007, 21(4): 671-87Ponec RJ et al. N Engl J Med 1999, 341: 137-41van der Spoel JI et al. Intensive Care Med 2001; 27: 822-27Mehta R et al. J Gastroenterol Hepatol 2006; 21: 459-61

Pharmacologic agents for ACPOPEG solution may decrease the recurrence rate of colonic dilation

Sgouros et al: RCT in 30 ACPO patients with cecal diameter > 10 cm

none in the PEG group had recurrence

significant increase in stool and flatus output, decrease in colonic distention or radiographic measurements, and improvement in abdominal girth

Saunders MD. BPRCG, 2007, 21(4): 671-87Sgouros SN et al. Gut 2006; 55: 638-42

Pharmacologic agents for ACPOErythromycin - successful in a few case reports

Armstrong et al: decompression in 2 patients with ACPO treated for 10 days

Bonacini et al: 1 patient had resolution after 3 days of IV erythromycin therapy

Cisapride and Tegaserod: been employed with some success

withdrawn due to cardiovascular side effectsSaunders MD. BPRCG, 2007, 21(4): 671-87Armstrong DN et al. Lancet 1991; 337: 378Bonacini M et al. J Clin Gastroenterol 1991; 13:475-6MacColl C et al. Gasteroenterology 1990; 98:773-6Camilleri M. Aliment Pharmacol Ther 2001; 15: 277-89

Colonoscopic Decompression for ACPO

role remains controversial: success rates vary from 69-90%

rate of dilation is more important than the absolute diameter of the colon

Indications: initial invasive procedure of choice

failed supportive measures

colonic diameter progressed to 11-13 cm (>10 cm)

significant duration (>3-4 days)

evidence of clinical deterioration or no improvement after 24-48 hours

contraindications to or fail neostigmine

recurrence occurs in 40%Sloyer AF et al. Dig Dis Sci, 1988, 33: 1391Rex DK. Gastroenterologist 1994, 2: 233Geller A et al. Gastrointest Endosc, 1996, 44: 144-50

Geller et al: clinical success is poor (25%) in procedures where a decompression tube was not placed - versus 88%

perforation rate approximates 3%

Sloyer AF et al. Dig Dis Sci, 1988, 33: 1391Saunders MD. BPRCG 2007; 21(4):671-87Geller A et al. Gastrointest Endosc, 1996, 44: 144-50

Invasive strategies for ACPO

Indications

failed medical and endoscopic management

(+) peritonitis, perforation

Percutaneous endoscopic cecostomy

caution: local infection, bleeding

for high surgical risk patients

definitive treatment in a small case series (5 patients) Ramage JI Jr, et al. Gastrointest Endosc,

2003, 57:752

Invasive strategies for ACPO: Surgery

associated with significant mortality and morbidity, likely related to the severity of patients’ underlying conditions

Vanek et al: large retrospective series

179 patients: 6% morbidity rate, 30% mortality rate

Cecostomy: procedure of choice if without perforation or ischemia

Segmental or subtotal resection with either exteriorisation or primary anastomosis - if with perforation or ischemia

Saunders MD. BPRCG 2007; 21(4):671-87Vanek VW and Al-Salti M. Dis Colon Rectum 1986; 29: 203-10

Saunders MD. BPRCG, 2007, 21(4): 671-87Eisen GM et al, Gastrointest Endosc, 2002, 56:789

Surgery/Percutaneous

cecostomy

end end