Prevention and Treatment of Postoperative Ileus Gum chewing Prevention and Treatment of Postoperative Ileus Lacey N. LaGrone, MD Neuraxial Catheter NSAIDs Ambulation Laparoscopy Opioid antagonists Limit opiates NGT Investigational therapies . . .

Definition Prevention / Treatment Pathophysiologic target Evidence: Yes / No / Maybe

Definition of problem < 12 – 24 hr 5.9 +/- 1.5 d < 12 – 24 hr What gut function is to be expected after laparotomy? < 12 – 24 hr 5.9 +/- 1.5 d Passing flatus / stool correlated well w/ return of colonic myoelectric activity. < 12 – 24 hr Estimated direct health care costs in 2000: > $1,000,000,000

Intervention Neuraxial Catheter Evidence? Yes / No / Maybe

Pathophysiology of ileus: Inhibitory neural reflexes: Noxious spinal afferent signals increase inhibitory sympathetic activity in the GI tract (rats) Limit opiate use Evidence: Midthoracic epidural with local anesthetics, 48-72h postop. 22 trials. Epidural w/ local anesthetics mean time for return of bowel function 24 v. 37h Unclear whether epidural opiates slow bowel function

Nasogastric decompression Intervention Nasogastric decompression Evidence? Yes / No / Maybe

Nasogastric Decompression Pathophysiology of ileus Symptom management Evidence 2010 Cochrane review, 37 studies, 5711 patients. Open procedures, randomization prior to OR Patients w/o routine NGT use had: Earlier return of bowel function [time to flatus] (p<0.00001) Trend toward increased pulmonary complications (p=0.09) Trend toward increased wound infection (p=0.39) Trend toward increased ventral hernia (p=0.09) Anastomotic leak rate the same (p=0.70) Cochrane review. 37 studies.

Intervention Gum chewing Evidence? Yes / No / Maybe

Pathophysiology of ileus Cephalic-vagal stimulation of digestion Increase promotility neural and humoral factors Evidence

Pathophysiology of ileus Cephalic-vagal stimulation of digestion Increase promotility neural and humoral factors Evidence

Intervention Ambulation Evidence? Yes / No / Maybe

Ambulate Control Pathophysiology of ileus “Prokinetic”? Evidence Patients were assigned randomly to one of two groups. Ten patients (group A) followed an ambulatory regimen Transverse starting 12 to 24 hours after operation and the other 25 Tran patients served as controls (group C) and did not ambulate Colon until postoperative day 4. Patients in group A underwent an initial 30- to 45-minute recording session, which was immediately followed by ambulation with assistance. Then they underwent another 60- to 90-minute postambulation recording session. Patients attempted to walk at least 75 yards during the ambulation session, but the distance varied with each patient's condition. Ambulate Control

Intervention Rocking-chair Evidence? Yes / No / Maybe

Pathophysiology of ileus “gentle, rhythmic, repetitive motion of rocking stimulates the vestibular nerves to send signals of pleasure and alertness to the Reticular Activating System, which is the body's “flight or fight” response center” Evidence:

Intervention Opioid antagonists Evidence? Yes / No / Maybe

Pathophysiology of Ileus Opioids Increase resting tone, decrease gastric motility and emptying, increase small intestinal periodic spasms, decrease colonic propulsive movements (5) Receptor specific, mediated at level of enteric nervous system. Evidence: Alvimopan, oral peripherally acting mu-opioid receptor antagonist that has limited ability to cross blood-brain barrier (57), hastens postoperative GI recovery after bowel surgery and TAH (58-62) Time to first passage of stool, tolerance of regular diet, length of hospital stay (63) Concern for cardiovascular or neoplastic complications. FDA: accelerate time to upper and lower GI recovery following partial large or small bowel resection w/ primary anastamosis. Inpatients. (64)

Methylnaltrexone (PAM-OR) (65-67) Approved for opioid-induced constipation. Two phase III trials found no improvement in recovery of gut function or time to discharge (68)

Antiinflammatory pharmacotherapy Intervention Antiinflammatory pharmacotherapy Evidence? Yes / No / Maybe

Pathophysiology of Ileus Inflammation Local macrophages are activated by intestinal manipulation, produce inflammatory response that results in muscle dysfunction. Degree of intestinal manipulation of both small and large intestine is directly related to both amount of dysmotility and degree of neutrophil infiltration into intestinal muscularis. Field effect affecting entire GI tract. Evidence . . .

Highly selective competitive COX-2 antagonist Muscarinic antagonist Bethanechol: muscarinic agonist DFU: Highly selective competitive COX-2 antagonist Increases COX-2, which decreases jejunal contractility Blocked by administration of COX-2 inhibitors

Mast cells play a role Mast cell stabilizers prevent intestinal inflammation and dysmotility, and mast cell deficiencies limit intestinal leukocyte migration

Minimally invasive surgery Intervention Minimally invasive surgery Evidence? Yes / No / Maybe

1 v. 5 cm abdominal muscle-fascia incision Minimally invasive surgery In animals, length of laparotomy correlates w/ ileus. Confounded by decreased postoperative opioid use, tendency towards earlier postoperative feeding. 1 v. 5 cm abdominal muscle-fascia incision 1 v. 5 cm laparotomy Laparotomy with intestinal manipulation

Intervention Duration of operation Evidence? Yes / No / Maybe

Intervention Estimated blood loss Evidence? Yes / No / Maybe

Preemptive anesthesia Intervention Preemptive anesthesia Initiate before surgical injury, adequate to prevent central sensitization, must be maintained postoperatively to prevent inflammatory changes assoc. w/ post-injury hypersensitivity. Gabapentin, dexamethasone, APAP, COX-2 inhibitors, subcu anesthesia Evidence? Yes / No / Maybe

Intervention Bran Bran x 8-10 days preop, more likely to pass flatus w/in 24h (78 v. 5 %)

Intervention Coffee Evidence? Yes / No / Maybe

Pathophysiology of Ileus Cup of coffee stimulates colonic motor activity to the same degree as a high-calorie meal.

Intervention Metoclopramide Evidence? Yes / No / Maybe 100 patients. Scheduled reglan. Average time to PO intake: 3.5 v. 5.0 days. P>0.05.

Intervention Suggestion Evidence? Yes / No / Maybe

P<0.05

Intervention Investigational . . . Evidence? Yes / No / Maybe

Neurohumoral peptides Nitric oxide, vasoactive intestinal polypeptide, substance P act as inhibitory neurotransmitters in the gut which slow gut motility. NO knock-out mice do not get ileus after intestinal manipulation In rats, selective antagonists to VIP, substance P improve ileus (6)

References