Gastrointestinal motility disorders in Critically ill patients

Ubaidur Rahaman Senior Resident, Critical Care Medicine, SGPGIMS, Lucknow, India

Advantage of enteral nutrition in critically ill metabolic, immunologic and mucosal barrier protection against bacterial translocation
Post injury hypermetabolic response and magnitude of translocation: prevention by early enteral nutrition. Gianotti L, Nelson JL, Alexander JW, et al. Nutrition. 1994;10:225-231

Early enteral nutrition within 24 hours of admission is recommended

ESPEN guidelines on enteral nutrition: intensive care. Kreymann KG, Berger MM, Deutz NE, et al. Clin Nutr. 2006;25:210-223.

EPIDEMIOLOGY Intolerance to feed: 60% Delayed gastric emptying: 50-80%

Enteral tube feeding in the intensive care unit: factors impeding adequate delivery. McClave SA, Sexton LK, Spain DA, et al. Crit Care Med. 1999;27:1252-1256. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Mentec H, Dupont H, Bocchetti M, et al. Crit Care Med. 2001;29:1955-1961

IMPACT ON PATIENT CARE

Increased complication HAP bacterial translocation leading to sepsis and multi-organ failure Nutritional deficiency Absorption of enterally given drugs Increased hospital stay and mortality

GI MOTILITY- PHYSIOLOGY Peristalsis

reflex wave of contraction in oro-caudal direction in response to stretching of wall by luminal content

Basal electrical activity (BEA)

spontaneous rhythmic fluctuation in membrane potential. Initiated by stellate muscle like pacemaker cells. function is to co ordinate peristaltic activity.

Migrating motor complex

during fasting, cycles of motor activity migrate from stomach to distal ileum. Immediately stopped on ingestion of food. Each MMC consists of Phase I- quiescent period Phase II- irregular contraction Phase III- burst of regular contraction Function unsettled Probably clears stomach and small intestine of luminal contents in preparation for next meal.

GI MOTILITY- PHYSIOLOGY
GASTRIC EMPTYING

FACTORS AFFECTING GASTRIC EMPTYING

Increasing age and female gender- delayed gastric emptying

FOOD
Volume- more volume more rapid emptying caloric density/ unit volume - high caloric density slow gastric emptying Tightly controlled Nutrient delivery- 200 Kcal/ h ( 2-3 Kcal/min) into duodenum osmolality- high osmolalty- slow gastric emptying nutrient content- carb> protien>fat

Intragastric pH- omeprazole delays gastric emptying Temperature- low tempreature- delays gastric emptying
Physio. Res. 2003;1-30

Neurohumoral control of gastrointstinal motility.

MB Hansen

CONTROL AND REGULATION OF GI MOTILITY

Hormonal factors
Cholecystokinin (CCK), peptide tyrosine tyrosine (P YY), motilin, glucagon like peptide (GPP 1) fundal relaxation and inhibit gastric emptying Dopamine decreases gastric emptying and intestinal peristalsis Motilin amplifies and induces MMC activity Opioids and serotonin ( 5HT)

Neural factors ENS---ANS---CNS

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL PATHOPHYSIOLOGY

stomach
absent phase III MMC activity delayed fundal relaxation, prolonged recovery Reduced antral motility increased isolated pyloric activity

Gastroparesis

Diminished functional association between proximal and distal gastric motility

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL PATHOPHYSIOLOGY

Altered GI Motility in Critically Ill Patients: Current Understanding of Pathophysiology, Clinical Impact, and Diagnostic Approach Andrew Ukleja, MD. Nutr Clin Pract. 2010;25:16-25

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

PATHOPHYSIOLOGY

proximal gastric relaxation is delayed fundic wave activity is reduced the recovery of proximal gastric volumes to pre-stimulation levels is delayed.

World J Gastroenterol 2006 July 21; 12(27): 4383-4388

Proximal gastric response to small intestinal nutrients is abnormal in mechanically ventilated critically ill patients
Nguyen N, Fraser R, Chapman M, Bryant R, Holloway R, Vozzo R, Feinle-Bisset

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

PATHOPHYSIOLOGY Abnormal antro-pyloro-duodenal response

Absence of antral activity and frequent isolated pyloric pressure waves

A five minute recording of pressure waves during small intestinal infusion of nutrient

Gut 2005;54:1384-1590

Antro-pyloro-duodenal response to gastric and duodenal nutrient in the critically ill patients.
Chapman M, Fraser R, Vozzo R, Bryant L, Tam W, Nguyen N, Zacharakis B, Butler R, Davidson G, Horowitz M.

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

PATHOPHYSIOLOGY

P <0.01

Plasma CCK concentration during fasting and duodenal stimulation

Crit Care Med 2007; 35: 82-88

intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations.
Nguyen N, Fraser R, Chapman M, Bryant L, Holloway R, Vozzo R, Wishart J, Feinle-Bisset C, Horowitz M.

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

PATHOPHYSIOLOGY
In critical illness association between proximal and distal gastric motility is abnormal
Changes in gastric volume during nutrient infusion Fundic waves(FW) and propagated antral waves(PAW) during fasting and duodenal nutrient stimulation

Intensive Care Med 2008; 34:12461255

Diminished functional association between proximal and distal gastric motility in critically ill patients.
Nguyen NQ, Fraser RJ, Bryant LK, et al. continues

Intensive Care Med 2008; 34:12461255

Diminished functional association between proximal and distal gastric motility in critically ill patients.
Nguyen NQ, Fraser RJ, Bryant LK, et al.

Trans-mural potential difference

Outline of study technique and position of recording assemblies

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

PATHOPHYSIOLOGY

Small intestine
Increased retrograde MMC III activity Persistence of MMC phase III during feeding MMC activity starting in duodenum instead of antrum ileus

Colon
Reduced flushing of nutrient content MMC disorganization: phase I- increased, phase II- decreased, phase III- retrograde

Pseudo-obstruction (Ogilivie syndrome)

Current Opinion in Clinical Nutrition and Metabolic Care 2009, 12:161167

Motility disorders in the ICU: recent therapeutic options and clinical practice
Kerstin D. Rohm, Joachim Boldt, Swen N. Piper.

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

ETIOLOGY AND RISK FACTORS

Surgery Abdominal, head or spinal SIRS/ Sepsis Hypoperfusion- systemic or regional Hypoxaemia Acid- base or electrolyte imbalance Glucose or fluid imbalance Drugs

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

ETIOLOGY AND RISK FACTORS SURGERY
Cannon WB, Murphy FT: The movement of the stomach and intestine in some surgical conditions. Ann Surg 1906, 43:512536.

mechanism

NEURONAL Local manipulation

HUMORAL Macropahage/ monocytes NO, PGs

NO from inhibitory motor neurons

VIP

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

ETIOLOGY AND RISK FACTORS

Drugs Anesthetics- halothane sedatives- midazolam, propofol analgesics- opioids, ketamine Catecholamines alpha agonists- clonidine, dexmedetomidine Calcium channel blockers Proton pump inhibitors

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

ETIOLOGY AND RISK FACTORS

Opioids Fundal relaxation Reduced antral contraction Reduced MMC phase III

Ketamine seems to have no advantage over fentanyl

Schmittner, Vajkoczy, Horn. Effects of fentanyl and S(+) ketamine on cerebral hemodynamics, gastrointestinal motility and need for vasopressors in patients with intracranial pathology: apilot study. J neurosurg Anesthesiol

Propofol showed beneficial gut effects over midazolam.

Nguyen NQ, Chapman MJ, Fraser RJ, et al. The effects of sedation on gastricemptying and intra-gastric meal distribution in critical illness. Intensive Care Med 2008; 34:454460

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

ETIOLOGY AND RISK FACTORS

Hyperglycemia: Gastric feeding was equally successful in diabetics as in non diabetics

Nguyen NZ et al. Gastric feed intolerance is not increased in critically ill patients with type II diabetes. Inten Car Med 2007;33:1740-1745

Normoglycemia attained by intensive insulin therapy seems to minimize feed intolerance in critical illness.
Nguyen et al. the relationship between blood glucose control and intolerance to enteral feeding during critical illness. Inten Car Med 2007;33:2085-2092

Vasopressors decreased antral contractions and orocaecal transit and longer ICU length of stay
Dive A, Foret F, Jamart J, et al. Effect of dopamine on gastrointestinal motility during critical illness. Intensive Care Med 2000; 26:901907.

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

ETIOLOGY AND RISK FACTORS

Fluid balance
Liberal fluid balance prolongs the duration of motility disturbances
and is associated with longer latency to first gastric emptying and first passage of flatus and stool as well as to hospital discharge. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lobo DN, Bostock KA, Neal KR,Perkins AC, Rowlands BJ, Allison SP. Lancet 2002;359:18121818 Effect of intraoperative fluid management on outcome after intraabdominalsurgery. Nisanevich V, Felsenstein I, Almogy G, Weissman C, Einav S, Matot I. Anesthesiology 2005; 103:2532

Dehydration and or hypovolemia may be associated with post operative GI dysfunction

and that increased perioperative fluid administration has been associated with improved indices of gut perfusion and reduced PGID Goal-directed intraoperativefluid administration reduces length of hospital stay after major surgery Gan TJ, Soppitt A, Maroof M, et al. Anesthesiology 2002;97:8206. Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery Mythen MG, Webb AR. Arch Surg 1995;130:4239.

GI MOTILITY DYSFUNCTION IN CRITICALLY ILL

ETIOLOGY AND RISK FACTORS

Co morbidity
Diabetes, thyroid disorders neurological disorders, Collagen vascular disorders Functional GI motility disorders

Substance abuse Alcohol nicotine

Regular use of laxative

ASSESSMENT OF GI DYSMOTILITY
Gastroparesis Gastric residual volume (GRV) Ileus Bowel sounds defecation

tolerance of EN pain and/ or distention, physical exam- distended, tense abdomen, raised IAP passage of flatus and stool, abdominal radiographs

Physiological stool frequency 1-2 evacuations/ day to 1 evacuation Q3-4 day

evidence of bowel motility is not required to initiate enteral feeding

ASSESSMENT OF GI DYSMOTILITY GRV

weak relationship with gastric emptying Depends on position of tube, tube collapsibility, tube size, volume of syringe used Operator performing the test

25% patients with GRV >150ml have normal gastric emptying and do not require prokinetic

In patients with normal gastric emptying GRV- 232-464 ml during enteral feeding @ 25-125ml/hr two large studies in critically ill patients most GRVs <150 ml

Crit Care Clin 26 (2010) 481490

Gastric Residual Volumes in Critical Illness: What Do They Really Mean?

Ryan T. Hurt, Stephen A. McClave.

MANAGEMENT

in critically ill patients mechanism underlying dysmotility are usually complex Relative contribution of control systems to regulation of GI motility varies along the alimentary canal and disease nature and course Propulsive motility occurs only when there is co-coordinated pattern of contraction and relaxation along the length of gut

It is unrealistic one single drug alone is able to promote propulsive motility over entire GI tract

DRUGS

PROKINETIC metocloperamide, Domperidone, Cisapride, Itopride

OPIOID ANTAGONIST Naloxone, Alvimopan, methylnaltrexone MOTILIN AGONIST Erythromycin

AChE INHIBITOR Neostigmine 5HT4 AGONIST tegaserod

PROKINETIC DRUGS

ERYTHROMYCIN IV administration is more potent than oral Effect to facilitate gastric emptying and improving tolerance to enteral feeding has been confirmed in 2 RCTs Effect on colonic transit time is controversial Lack beneficial effect in post op ileus

Microbial resistance no evidence that short term, low dose regimen of erythromycin increases resistance QT prolongation risk increases above plasma level approx 30 mg/ml. this is above level which can be achieved by 100 mg ivi dose. Caution has to be taken in cardiomypathy, CHF, CAD, AFib, bradycardia, hypokalemia, hypomagnesemia

PROKINETIC DRUGS
METOCLOPERAMIDE Effect limited to upper GI tract, no effect on large bowel Beneficial effect on GI transit and enteral feed tolerance when give IV, ineffective when given TNG Duration of post op ileus remains unaltered. NALOXONE may be beneficial in GI motor disturbances that are unrelated to opiate use NEOSTIGMINE Effect remains controversial Found to be ineffective in post op ileus at dose 0.5 mg IMI Q3H total 3 doses. Prompt colonic decompression following orthopedics surgery at dose 2 mg IVI. Acute colonic pseudo obstruction- 2-2.5 mg ivi over 3-3- min caused resolution with a success rate of 80-90%.

PROKINETIC DRUGS

Combination of metocloperamide and neostigmine

Release of ACh by metocloperamide+ inhibition of breakdown by neostigmine Dose should be kept in indicated range and duration of infusion limited to 2 hours. Adverse effects Symptomatic bradycardia Increased tracheo-bronchial secretions and salivation Tracheal suction should be avoided- additional vagal stimulation Contra indication Mechanical bowel obstruction, gastrointestinal ischemia or perforation, pregnancy, uncontrolled arrhythmias, severe bronchospasm

Crit Care Med. 2007 Feb;35(2):483-9.

Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness.
Nguyen NQ, Chapman MJ, Fraser RJ, Bryant LK, Holloway RH.

Kaplan Meier plots comparing the effects

Erythromycin is more effective than metoclopramide in treating feed intolerance But rapid decline in effectiveness renders both treatments suboptimal. Rescue combination therapy is highly effective
further study is required to examine its role as the first-line therapy

ALGORYTHM FOR TREATMENT OF GI DYSMOTILITY Early use of supportive therapeutic options

Stimulant and osmotic laxative Opioid receptor antagonist Reduced use of drugs with inhibitory effect onGI motility

Goal directed specific therapy-PROKINETICS

gastroparesis gastroparesis and Intestinal motor inhibition intestinal motor inhibition without gastroparesis
Clin Nutr 2008; 27:2541

Standardized concept for the treatment of gastrointestinaldysmotility in critically ill patients:current status and future options.
Herbert MK, Holzer P..

ALGORYTHM FOR TREATMENT OF GI DYSMOTILITY

Opioid receptor antagonist Naloxone Impaired gastric emptying 1st line 2nd line 3rd line 1st line After 24 hours Erythromycine Metocloperamide Domperidone Gastroparesis and impaired intestinal motility Erythromycin Metocloperamide + neostigmine 100 mg ivi Q8H for 3 days 10-30 mg ivi + 0.5-1.5 mg ivi Q24H
(in 250 ml NS over 1-2 hours)

3-12 mg PO Q8h 100 mg ivi Q8H for 3 days 10 mg ivi 30-40 mg PO

Impaired intestinal motility without gastroparesis 1st line Ceruletide Metocloperamide + Neostigmine
Clin Nutr 2008; 27:2541

40 mg ivi Q24H
( in 100 ml NS over 30-60 min)

10-30 mg ivi + 0.5-1.5 mg ivi Q24H

(in 250 ml NS over 1-2 hours

Standardized concept for the treatment of gastrointestinaldysmotility in critically ill patients: current status and future options.
Herbert MK, Holzer P

SPECIAL CONSIDERATION FOR USE OF PROKINETICS

Reduce dose Opioids, sedatives, alpha agonist and catecholamines
as soon and as much possible

Only one stimulation per day

Dose should not be increased

Tachyphylaxis, increased stimulation- tetany

If no benefit over use of several consecutive days Holiday of 1 day

Clin Nutr 2008; 27:2541

Standardized concept for the treatment of gastrointestinaldysmotility in critically ill patients: current status and future options.
Herbert MK, Holzer P

recommendations for using GRV in an enteral nutrition protocol

Check GRV Q4h GRV>400 ml EN at the current rate nright lateral decubitus position for 30 minutes nMetocloperamide 10 mg, ivi Q6h; naloxone 8 mg in 10 ml saline TNG Q6h Recheck GRV in 4 hours >400 ml- hold NG feed Recheck GRV every 2 hours GRV < 400 ml- restart NG feeding Tolerance restart at same rate intolerance consider reducing rate by 25 mL/h or to baseline of 25 mL/h
Crit Care Clin 26 (2010) 481490
nContinue

GRV<500 ml- return feed to patient

Gastric Residual Volumes in Critical Illness: What Do They Really Mean?

Ryan T. Hurt, Stephen A. McClave.

FUTURE PHARMACOLOGICAL OPTIONS

5 HT receptor agonist Levosulpiride Renazapride CCK receptor antagonist Cerulein Dexloxiglumide Motilin agonist Alemicinal, Mitemcinal Gherlin receptor agonist TZP-101

PROKINETICS WITHDRAWN FROM MARKET

Itopride lack of efficacy, further development stopped in 2006 by Axcan Pharma Available in Japan, few European countries, India Tegaserod ischemic colitis, cardio toxicity, withdrawn in US in 2007, available in some European countries

ACUTE COLONIC PSEUDO OBSTRUCTION

OGILIVIE SYNDROME
Massive dilatation of colon with obstructive symptoms, in the absence of mechanical obstruction

Ogilvie H. Large-intestine colic due to sympathetic deprivation; a new clinical syndrome. Br Med J 1948; 2:671673.

Risk of ischemia and perforation 3-15% leading to mortality of 50% Advanced age, large ceacal diameter (>10 cm), and duration of distension Supportive measures bowel rest, fluid and electrolyte optimization Rectal tube may be effective Stop drugs delaying motility- opioids, anticholinergics, CCB Laxatives particularly osmotic are contra indicated
continued

ACUTE COLONIC PSEUDO OBSTRUCTION

OGILIVIE SYNDROME

Neostigmine 3 double blind RCT have documented effectiveness

Watch for secretions, bradycardia, hypotension, bronchospasm Risk can be reduced by iv infusion compared to bolus

The benefit derived from one or two doses of neostigmine largely outweigh the risk of administration

Relative contra indication Recent history or signs of perforation or peptic ulcer Myocardial infarction, use of beta blockers Obstructive airway disease S.creatinine>3 mg/dl
Neostigmine for the treatment of the acute colonic pseudo-obstruction.
Ponec RJ, Saunders MD, Kimmey MB. N Engl J Med 1999; 341: 137141

Neostigmine infusion: new standard ofcare for acute colonic pseudo-obstruction?

Amaro R, Rogers AI. Am J Gastroenterol 2000; 95: 304305.

Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure: a prospective, double-blind, placebo-controlled trial.
van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF. Intensive Care Med 2001; 27: 822827.

continued

ACUTE COLONIC PSEUDO OBSTRUCTION

OGILIVIE SYNDROME

Polyethylene glycol (PEG) significant reduction in recurrent caecal dilatation, increased in stool and flatus evacuation, decrease in caecal and colonic diameter reduction in abdominal circumference.
(after initial resolution using neostigmine or decompression)
Effect of polyethylene glycol electrolyte balanced solution on patients with acute colonic pseudo-obstruction after resolution of colonic dilatation: a prospective, randomized, placebo controlled trial. Sgouros SN, Vlachogiannakos J, Vassiliadis K, Bergele C, Stefanidis G, Nastos H et al. Gut 2006; 55: 638642

Endoscopic decompression
Efficacy has not been assessed in RCT Reported to be successful in 80%, Laborious and hazardous High suspicion of ischemia- should be carried out in OT

Surgery
mortality 30-60%

EFFECT OF ENTERLA NUTRITION ON GUT MOTILITY

No evidence that impaired intestinal motility in critically ill improves from enteral nutrition,
either standard formulae or immune modulating formulae or enriched with antioxidant or fiber

Clin Nutr 2008; 27:2541

Standardized concept for the treatment of gastrointestinaldysmotility in critically ill patients: current status and future options.
Herbert MK, Holzer P

NON PROKINETIC THERAPY

Post pyloric feeding Failure of NG feeding and no improvement with prokinetics

Systemic lidocaine administration during induction and peri/post operative period

Epidural anesthesia in post op period

REVIEW OF LITERATURE
Crit Care Med. 2002 Jul;30(7):1429-35.

Gastrointestinal promotility drugs in the critical care setting: a systematic review of the evidence
Booth CM, Heyland DK, Paterson WG

Computerized bibliographic search of published research (1980-2001)

18 studies 6 studies of feeding tube placement, 11 studies evaluating gastrointestinal function 1 study of clinical outcomes

As a class of drugs, promotility agents appear to have a beneficial effect on GI motility in critically ill patients. A one-time dose of erythromycin may facilitate small-bowel feeding tube insertion. metoclopramide appears to increase physiologic indexes of gastrointestinal transit and feeding tolerance. Concerns about safety and lack of effect on clinically important outcomes preclude strong treatment recommendations

REVIEW OF LITERATURE
Crit Care Med. 2000 May;28(5):1408-11.

Metoclopramide for preventing pneumonia in critically ill patients receiving enteral tube feeding: a randomized controlled trial.
Yavagal DR, Karnad DR, Oak JL

Prospective, randomized, controlled trial.

total of 305 consecutive patients requiring placement of a nasogastric tube for >24 hrs.

Metoclopramide delayed the development of nosocomial pneumonia, But it did not decrease its frequency rate No effect on the mortality rate in critically ill patients receiving NG feeding.

REVIEW OF LITERATURE

Crit Care Med 2007; 35(11).

Prokinetic therapy for feed intolerance in critical illness: one drug or two?
Nguyen N, Chapman, M, Fraser, R, Bryant, L, Holloway, RH

Prospective, randomized, controlled trial. Seventy-five mechanically ventilated, medical patients with feed intolerance (GRV >250 mL).

combination therapy- erythromycin 200mg ivi Q12H + metoclopramide 10mg ivi Q6H (n 37) OR erythromycin alone (n 38) Gastric feeding was re-commenced 6-hourly NG aspirates performed. Duration of study- 7 days Successful feeding - GRV<250 mL with the feeding rate >40 mL/hr

continued

Crit Care Med 2007; 35(11).

Prokinetic therapy for feed intolerance in critical illness: one drug or two?
Nguyen N, Chapman, M, Fraser, R, Bryant, L, Holloway, RH

P <0.01 vs erythromycin

combination therapy with erythromycin and metoclopramide is more effective should be considered as the first-line treatment.
Tachyphylaxis was less with combination therapy.
no difference in the length of hospital stay or mortality rate Watery diarrhea was more common with combination therapy but was not associated with enteric infections, including Clostridium difficile.

REVIEW OF LITERATURE
Crit Care Med. 2007 Feb;35(2):483-9.

Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness.
Nguyen NQ, Chapman MJ, Fraser RJ, Bryant LK, Holloway RH.

Prospective, randomized, controlled trial.

90 mechanically ventilated, medical patients with feed-intolerance (GRV 250 ml).

Given either metoclopramide 10 mg ivi Q6H (n=45) or erythromycin 200 mg ivi Q12H (n=45). After the first dose, NG feeding commenced Q6H NG aspirates performed If GRV>or=250 ml, open-label, combination therapy was given. Duration of study- 7 days. Successful feeding-6-hourly GRV<250 mL with a feeding rate>or=40 mL/hr
continued

The only thing that interferes with my learning is my education.

Albert Einstein

HANK OU

Gut 2005;54:1384-1590

Antro-pyloro-duodenal response to gastric and duodenal nutrient in the critically ill patients.
Chapman M, Fraser R, Vozzo R, Bryant L, Tam W, Nguyen N, Zacharakis B, Butler R, Davidson G, Horowitz M.

Aims
n

To characterise antro-pyloro-duodenal motility during fasting, and in response to gastric and duodenal nutrient, n evaluate the relationship between gastric emptying and motility, in the critically ill.

Subjects
Fifteen mechanically ventilated patients from a mixed intensive care unit; 10 healthy volunteers.

Methods
Antro-pyloro-duodenal pressures were recorded during fasting, after intragastric administration (100 ml; 100 kcal), and during small intestinal infusion of liquid nutrient (6 hours; 1 kcal/min). Gastricemptying was measured using a 13C octanoate breath test.

continued

Gut 2005;54:1384-1590

Antro-pyloro-duodenal response to gastric and duodenal nutrient in the critically ill patients.
Chapman M, Fraser R, Vozzo R, Bryant L, Tam W, Nguyen N, Zacharakis B, Butler R, Davidson G, Horowitz M.

Results
In healthy subjects, neither gastric nor small intestinal nutrient affected antro-pyloro-duodenal pressures. In patients, duodenal nutrient infusion reduced antral activity compared with both fasting and healthy subjects Basal pyloric pressure and the frequency of phasic pyloric pressure waves were increased in patients during duodenal nutrient infusion compared with healthy subjects and with fasting Gastric emptying was delayed in patients and inversely related to the number of pyloric pressure waves

Conclusions
Stimulation of pyloric and suppression of antral pressures by duodenal nutrient are enhanced in the critically ill and related to decreased gastric emptying.

continued

Gut 2005;54:1384-1590

Antro-pyloro-duodenal response to gastric and duodenal nutrient in the critically ill patients.
Chapman M, Fraser R, Vozzo R, Bryant L, Tam W, Nguyen N, Zacharakis B, Butler R, Davidson G, Horowitz M.

Measurement of Gastric emptying

13C octanoate breath test 100 ml octanoate was mixed with 100 ml Ensure and instilled into the stomach over five minutes via a nasogastric tube. In patients, end expiratory breath samples were collected from the ventilation tube
using a T adapter (Datex-Engstrom, Helsinki, Finland) and holder for vacutainers (blood needle holder; Reko, Lisarow, Australia), containing a needle (VenoJect; Terumo Corporation, Tokyo, Japan). This technique allowed the reliable filling of collection tubes (Exetainer, Buckinghamshire, UK).

Healthy subjects fully expired into sample tubes for collection of end expiratory breath samples. Breath samples were collected immediately before instillation of the Ensure, every 5 minutes for the first hour, and every 15 minutes thereafter for a further 3 hours. Breath samples were analysed for 13CO2 concentration using an isotope ratio mass spectrometer The 13CO2 concentration in each sample was plotted over time and the area under the recovery curve was used to calculate the gastric emptying coefficient(GEC).

Intensive Care Med 2008; 34:12461255

Diminished functional association between proximal and distal gastric motility in critically ill patients.
Nguyen NQ, Fraser RJ, Bryant LK, et al.

AIM To examine effects of critical illness on the relationship between proximal and distal gastric motor activity during fasting and duodenal nutrient stimulation.

n n

Prospective, case-controlled study.

Ten critically ill patients and ten healthy volunteers.

INTERVENTIONS
: Concurrent proximal gastric (barostat) and antro-pyloro-duodenal (manometry) motility were recorded during fasting and during two 60-min duodenal nutrient infusions (at 1 kcal/min and 2 kcal/min) in random order, separated by a 2-h wash-out period.

continued

RESULTS
Baseline proximal gastric volumes were similar between the two groups. At 10 min nutrient-induced fundic relaxation was lower in patients than healthy subjects In patients the frequency and volume amplitude of fundic waves were also lower. There were fewer propagated antral waves in patients than in healthy subjects during both fasting and nutrient infusion. These were more retrograde, shorter in length and associated with a pyloric contraction. The proportion of fundic waves followed by a distally propagated antral wave was significantly less in patients

CONCLUSIONS
In critical illness, in addition to impairment of proximal and distal gastric motor activity, the association between the two gastric regions is abnormal.

continued

Intensive Care Med 2008; 34:12461255

Diminished functional association between proximal and distal gastric motility in critically ill patients.
Nguyen NQ, Fraser RJ, Bryant LK, et al.

Minimal distending pressure

Trans-mural potential difference

Outline of study technique and position of recording assemblies