P - ISSN : 2349-6592    |    E - ISSN : 2455-7099
Year : 2016 | Volume : 3 | Issue : 4 | Page : 85-100
Source of Funding:None Conflict of Interest:None
Gastrointestinal (GI) problems occur frequently and are often considered to be just a fact of life in pediatric intensive care units; they do not usually get the importance they deserve. This is substantiated by the fact that gastrointestinal function is not included in any of the scoring systems widely used to assess organ failure in critical illness. Defining gastrointestinal failure or dysfunction is complex; however recent attempts have been made to address acute gastrointestinal injury in critical illness. This review addresses the following common GI issues in PICU: constipation, diarrhea, feeding intolerance and stress ulcer prophylaxis.
Key words :, critical care, constipation, diarrhea, feeding intolerance and stress ulcer prophylaxis
Gastrointestinal (GI) issues are common in critically ill children. GI dysfunction in children may either be a primary presentation (eg. acute pancreatitis, liver failure, variceal bleeding) or part of multisystem disease (eg. ileus, feeding intolerance (FI), constipation, stress ulcer haemorrhage). Most multisystemic GI issues are transient, innocuous and settle within a short period; hence are overlooked as the physician concentrates upon the overwhelming primary illness. However some GI issues (eg: diarrhoea, gastro paresis) are bothersome, lingering and can evolve over days to weeks. A critically ill patient may also develop life threatening GI complications in the course of his illness (eg. acute pancreatitis in sepsis and dengue shock syndrome or gall bladder perforation). In the latter two scenarios, subtle GI symptoms, its progression and clinical examination need to be identified at the bedside by the astute clinician and acted upon. The pathophysiology of GI dysfunction in multisystemic illnesses is incompletely understood and its exact clinical relevance remains controversial. There is little literature of the same in pediatric critical care and adult studies have only recently begun to define these issues in 20121. When describing GI dysmotility it must be remembered that beyond the duodenum the small bowel does not seem to be involved to the same extent as the upper GI tract. Small bowel transit time is largely unaffected by critical illness. Colonic motility disorders are common and lead to both diarrhea and constipation. Increased colonic transit time is commonly seen in postoperative patients (intra-abdominal procedures, narcotics). Alternatively, reduced colonic transit time leading to diarrhoea is also not uncommon in intensive care unit (ICU) patients. Also with advances in technology and newer instruments, the present day intensivist relies more on electronic monitoring of patients and is thus often tempted to perform only a cursory clinical abdominal examination which may be insufficient to detect many GI problems in PICU. In this review, we have addressed few common GI issues in PICU, with respect to definition, brief description and management strategies.
Constipation in PICU:The lazy gut
Difficulty in definition: Transient constipation of short duration in ICU is not defined under the Rome IV criteria, which is meant for childhood chronic constipation. The hurdle in definition is further compounded by the difficulty in establishing limits of normality in the defecatory pattern of children of different races with varying ages and eating habits2,3,4.
Tentative acceptable definition: Working Group on Abdominal Problems (WGAP) from the European Society of Intensive Care Medicine (ESICM) suggested that the term ―paralysis of the lower gastrointestinal (GI) tract‖ be preferred, instead of constipation. They defined this as ―the inability of the bowel to pass stool due to impaired peristalsis‖ and suggested that clinical signs would include absence of stool for three or more consecutive days without mechanical obstruction regardless of bowel sounds1. This definition appears to be sound in ICU settings and has also been used in recent pediatric studies6. Unlike Rome IV criteria, the WGAP-ESICM definition only highlights the frequency and not the consistency of stools (Bristol stool chart scale). In a recent study, 47 critically ill children were analysed for bowel function; a state of ―non-defecation‖ was found for the majority of the time spent in PICU, while patients with hard stools (Bristol stool chart scale,1–2) were seen on only 0.5% of beddays 7 . It might be thus concluded that hard stool is seen in very small proportion of sick children in PICU and usually non defecation is taken as a marker of impaired peristalsis in PICU. Inability to pass stools in PICU setting must be carefully distinguished from paralytic ileus or bowel obstruction despite the considerable overlap. Constipation is primarily a large bowel dysmotility manifested by non-passage of stools, with possible flank distension. The rest of the symptoms (discomfort, nausea etc.) are secondary and subsequent to the above. In research settings, they are proven by a normal orocecal but delayed colonic transit time. In paralytic ileus, the provocating factor (drug, dyselectrolytemia etc) causes abolishment of migratory motor complexes (fasting state) and segmental contractions (fed state) resulting in adynamia of the small bowel primarily. It is manifested by painless generalised distension, feed intolerance, occasional vomiting, non-passage of stools and lack of bowel sounds. Bowel obstruction in contrast is a painfully distended abdomen that worsens with feed, copious bilious aspirates and increased bowel sounds.
Causes : Constipation in critically ill patients is associated with various factors, including immobility, splanchnic hypoperfusion, inflammation, sepsis, cerebral and spinal cord lesions, surgery, delayed administration of enteral nutrition (EN), electrolyte disturbances (eg, hypercalcemia, hypokalemia, hypomagnesemia), and the use of opiate and anticholinergic drugs1,8,9. In a recently conducted study of constipation in critically sick children, the incidence of constipation was 46.7%, which was slightly lower than the figures reported in the majority of studies in critically ill adults6, 8,10. The frequency of constipation was noted mostly in post operative surgical as compared to medical patients. This may be related to the drugs and exposure to anesthesia6,9. PICU settings in general have also been a factor, especially in older children. This is attributable to the lack of privacy and multiple alarms, which makes defecation unconducive 6,11. Pediatric Index of Mortality 2 (PIM2), pediatric risk of mortality (PRISM) clinical severity scores and the need for vasoconstrictor therapy (mostly dopamine) are other major independent risk factors associated with constipation6,12. Acute colonic pseudoobstruction (Ogilvie’s syndrome) is a rare cause of constipation in an acute ill child. It is akin to toxic megacolon in inflammatory bowel diseases and is manifested by a marked dilated cecum (>9 cm on the radiograph) and invariably associated with colonic perforation. This condition is precipitated by sepsis, recent surgery and trauma.
Clinical impact of constipation: Children with constipation usually have associated abdominal distention, and consequently they receive a lower volume of nutrition and more EN (enetral nutrition) interruption6,10. This in turn affects their overall nutritional status. Constipation in critically ill adult patients has been associated with worse outcomes including prolonged ICU length of stay and prolonged mechanical ventilation. Patanwala et al. noted that patients with constipation had more severe illness, as indicated by higher APACHE II scores13. Montejo et al. reported that patients with GI complications, including constipation, had longer ICU stays and higher mortality than those without GI complications14
Management: The routine disimpaction of chronic constipation in a normal child cannot be extrapolated to acute constipation of ICU setting. It is prudent to withhold laxatives unless it is troublesome to patient. The principles of managing constipation in ICU are:
1. Removal of offending medications: Inhibitory drugs for GI motility (e.g. catecholamines, sedatives, opioids) should be discontinued if possible; or dose titration should be considered.15,16,17.
2. Restore enteral nutrition as early as possible if clinically permissible. Theoretically, intermittent feeding seems beneficial as compared to continuous feeding to prevent constipation in ICU patients. Intermittent bolus feeding physiologically causes gastric and colonic distention, leading to increased antro-pyloric pressure waves and motility and thus may help in same.
3. Dyselectrolytemia (hypokalemia, hypomagnesemia, hypercalcemia and hyperglycemia should be corrected
4. Rescue therapy with oral bisacodyl (older child) or lactulose; if constipation is acute, of short duration and bothersome to patient. Lactulose is given with caution as it may aggravate distension.
5. Impacted stools felt on rectal examination should respond to single or multiple phosphate or lactulose enema or bisacodyl suppositories
6. Mineral oils and liquid paraffin are generally avoided in sick obtunded patient due to high chances of gastroesophageal reflux (through nasogastric tube), aspiration and lipoid pneumonia
7. Large doses of magnesium hydroxide are generally avoided in a critically ill patient in the setting of multisystemic problems and precipitation of dyselectrolytemia.
8. In rare settings, oral disimpaction with polyethylene glycol (PEG) is permitted with caution. Preparations that contain balanced electrolytes should be chosen. Purging with PEG should be done under vigilance and cardiac monitoring in ICU settings as it may precipitate dyselectrolytemia in an already compromised and critical milieu. Oral disimpaction is relatively contraindicated in shock and hemodynamic instability. It is best attempted during recovery and transition care. Randomised controlled trials and consensus statements suggest the use of PEG in maintenance therapy for functional constipation18. There are no guidelines yet recommended in acute constipation. However it would be reasonable to use PEG in during recovery for an undefined period shorter than that of chronic constipation (3-6 months) if the provocative factor has been withdrawn prior to start of maintenance therapy. Response at follow-up should guide the physician regarding duration of therapy. PEG should be tapered gradually and not stopped all of a sudden.
9. Prophylaxis of Constipation: Delayed administration of EN contributes to constipation, and probably early EN is the optimal way to prevent constipation in PICU patients. Masri et al. reported that prophylactic use of lactulose 20 ml twice daily for 3 days in critically ill ventilated patients was associated with increased incidence of bowel movement in the first 72 hours compared to no intervention (18% vs 4%, p<0.05)19. Consider starting prophylactic laxative agents, if patient is taking laxatives prior to admission (due to some chronic GI issues).
10. Any underlying disease state or anatomical anomaly should be looked for and managed accordingly. In PICU, the physician can clinically suspect a concomitant acute thyroid or adrenal insufficiency if the constipation fails to respond and child shows poor recovery to standard management of care. Constipation and failure to extubate may be the first sign of myasthenia gravis (rarely seen in children). Acute intermittent porphyria precipitated by and intercurrent illness may present as constipation (autonomic neuropathy) and altered urine colour. The physician would need to refer to the list of contraindicated drugs in each of the above settings.
11. Prokinetics like domperidone, metoclopramide and erythromycin are used to stimulate the upper GI tract (stomach and small bowel), whereas neostigmine stimulates small bowel and colonic motility. Despite the lack of well controlled studies and sufficient evidence, prokinetics are widely used, while few studies suggest a possible role of neostigmine in refractory constipation in critically sick children20,21.
12. Currently there is no proven role of prebiotics, probiotics, prucralopride or lubipristone in management of constipation in the critically ill.
13. It is important to remember that early sitting and mobilization of patients is a cheap and effective way to stimulate gut function.
Diarrhoea in PICU: A different entity
Reaction to diarrhoea is swift in the PICU but adequate awareness is required to eliminate the precipitants of the same. Diarrhoea in a sick PICU patient adds to morbidity by causing hypotension and electrolyte loss; and also increases risk of pressure sores, malnutrition, delayed wound healing; and contamination of wounds and catheters. Kelly et al found that 41% of adult patients develop diarrhoea at approximately 7 days after entry into ICU. 22 In 526 critically ill children who received transpyloric enteral nutrition, 6.4% developed diarrhoea. 23 The occurrence rate of diarrhoea is around 6 per 1000 hospitalized newborn intensive care units. 24
The intestine handles approximately 7-9 litres of fluid per day contributed by oral intake and secretions. The small bowel absorbs 70-80% while the colon absorbs another 15-18%. Diarrhoea in a normal setting will only develop when small intestinal function has been reduced >40% to produce a conspicuous stool volume. In practical terms, a child’s small bowel absorbs twice that of adults and presents 2-3 times more fluid (60 ml/kg vs. 25 ml/kg) to colon. Therefore there is little colonic reserve and reduction of small intestinal function by even 10% in a child can cause diarrhea.25 Sodium and chloride besides water are actively lost from the gut mucosa during diarrhea. Majority of the intestinal transporter pumps are inactivated due to cytotoxic damage or toxin mediated inhibition. Despite failure of these pumps, only the sodium-glucose transporter (SGLT-1) pump located on the mucosal surface remains intact and functional. Through this pump, one molecule of glucose drags one molecule of sodium and consequently 1100 molecule of water to maintain the iso-osmolarity of the absorbate. Glucose and the electrolytes are further released into the bloodstream by GLUT-2, Na-K ATPase pump and K channel. The above rationale forms the basis of rehydration. Diarrhoea results from a relative increase in intestinal luminal osmolality diminished mucosal absorptive capacity, altered motility or a combination of any of the above. Acute onset diarrhoeas in PICU can be due to osmotic causes related to feeds. Transient villous atrophy arises in a state of malnutrition as children have remained nil per oral for days together. The disaccharidases at the tips of the villi are the first to be depleted. Most commonly the lactase enzyme is affected due to its labile structure and decline in function and abdundance (genetic and age-related). Hence lactose (milk) is not broken down to glucose and galactose. Unabsorbed dietary lactose delivered to colon is converted to hydrogen and lactic acid by colonic bacteria. Lactic acid results in decreased stool pH causing perianal excoriation, hydrogen gives explosive (gaseous and noisy) stool and unabsorbed lactose in turn causes osmotic diarrhoea resulting in positive reducing substances if tested. This is the classical manifestation of secondary lactose or carbohydrate intolerance, one of the common causes of diarrhoea in PICU setting. Testing for stool pH and reducing substances may not be needed, when the history is classical and excoriations are clinically evident. Neither the small intestine nor colon can maintain an osmotic gradient. Hence poorly absorbed sugars and polyols (mannitol, sorbitol) remain in the intestinal lumen obligate retention of water to maintain an intraluminal osmolality equal to that of body fluids (about 290 mosm/kg). Therefore, approximately 3.5 mL of water are retained for every 1 mOsm of retained ions or molecules. In osmotic diarrhea, electrolytes account for only a small part of the osmotic activity; unmeasured osmoles resulting from ingestion of a poorly absorbed substance account for most of the osmotic activity, and the calculated osmotic gap will be high. The diarrhoea becomes passive if child is kept fasting for 24-48 h. The second factor that causes osmotic diarrhoea is the osmolality of feeds. Polymeric diets are better tolerated than elemental diet if the villi are intact. Secretory diarrhoea results from mucosal injury results due to viral enteritis most commonly. The virus invades and destroys mature enterocytes which are rapidly replaced by crypt-like cells. These cells lack transport systems and have low levels of Na/K ATPase activity. Hence sodium and water absorption is suboptimal. Secretory diarrhoea fails to respond to fasting in comparison to osmotic diarrhoea. Practically, osmotic and secretory diarrhoea overlap significantly and distinguishing the two in a PICU setting is difficult.26
Definition: Diarrhoea may be defined for practical purposes as a decrease in stool consistency, along with an increase in frequency to more than three bowel movements in 24 hours. Though weighing stool is very important but in the routine practice of PICU it is practically almost impossible and cumbersome. But a general idea of amount is always easy to assess at bedside. Adult literature defines diarrhoea as having three or more loose or liquid stools per day with a stool weight greater than 200–250 g/day (or greater than 250 ml/day).1 The Bristol Stool Chart is probably the most widely used description of stool consistency, with loose or watery stools (Bristol Stool Chart type 5–7) required to constitute diarrhoea.27
Cause: Enteral nutrition is usually considered a common precipitant of diarrhoea in ICU settings. Interestingly, a meta-analysis suggested that the risk of developing diarrhoea was similar in patients receiving either enteral or parenteral nutrition.28 While, a newer study reported that the enteral delivery of more than 60% of energy targets increased the risk of diarrhoea by 1.75 (1.02–3.01), whereas just the presence of enteral nutrition had no impact.29 This data suggest that there may be a small intestinal threshold of nutrient absorption and beyond which, malabsorption and diarrhoea may occur. Diarrhoea in PICU can be caused by various other reasons such as alterations in the colonic response, microbial contamination of enteral nutrition formulas, low-fiber diet, hypoalbuminemia, disturbances of the intestinal flora, increased use of antibiotics and concurrent drug therapy (Table 1). Toxigenic Clostridium difficile seems to be the most common cause for infectious nosocomial diarrhea. Another emerging cause of infectious nosocomial diarrhea other than clostridium difficile is Klebsiella oxytoca.30 Prokinetic drugs may be an added risk factor for diarrhoea in ICU settings. In a study, prokinetic drugs were associated with diarrhoea during intragastric feeding in the critically ill patients: metoclopramide in 32%, erythromycin in 30% and their combination in 49% of study population31. In most patients, diarrhoea was mild and stopped immediately after discontinuing prokinetic therapy. Neutropenic enterocolitis is an important cause of diarrhoea in immunocompromised patients (absolute neutrophil count <500cells/mm3); where a combination of pyrexia (>38.50 C) and abdominal symptoms (pain in right iliac fossa, abdominal distension, diarrhoea) along with typical radiologic findings (gross thickening of ileal and caecal wall with surrounding inflammatory changes) are suggestive.32
Investigate: Initially in PICU settings efforts must be made to distinguish between disease-, food/feeding-, infection- and drug-related diarrhoea. Later on, persistent diarrhoea needs to be addressed by evaluating secretory and osmotic diarrhoea.
1. Symptomatic therapy—replacement of fluids and electrolytes, haemodynamic stabilization and organ protection (e.g. correction of hypovolaemia to prevent impairment of renal function) forms the basic management.
2. Trigger mechanisms need to be discovered and whenever possible stopped (e.g. laxatives, sorbitol, lactulose, antibiotics) or treated (e.g. malabsorption, inflammatory bowel disease). Routine administration of proton pump inhibitors (PPI) in critically ill patients is also associated with increased risk of developing Clostridium difficile–associated diarrhoea in a recent study33. When reviewing medicines for diarrhoea; indication for each medication, including PPI, should be carefully considered.
3. Feeding-related diarrhoea in critically ill patients may require reduction of infusion rate, repositioning of feeding tube, or dilution of nutrition formula. Changing formula by adding soluble fibre helps prolong transit time.34
4. The addition of sodium chloride and trace elements to the formula may counteract the effects of active gastrointestinal water secretion and prevent specific deficiencies.
5. Another approach to treating diarrhoea is to minimize the residue reaching the colon and some authors advocate predigested enteral formulas containing peptides and medium-chain triglycerides rather than whole proteins and long-chain triglycerides. 35,36 Although semi elemental/elemental formulae are very good for absorption and nutrition; there is a theoretical risk of paradoxically worsening diarrhoea due to higher osmolarity as compared to polymeric formulae.
6. Only in cases of severe or recurrent Clostridium difficile associated diarrhoea is oral vancomycin superior to metronidazole. In refractory states, fecal microbiota transplantation is also tried. 1
7. Despite these approaches to modifying the composition of the enteral formula, most importantly, enteral nutrition should not be interrupted or stopped. In the clinical setting, diarrhoea is a frequently cited cause for enteral nutrition to be interrupted or stopped. Reducing the delivery rate, while still achieving target volume is one possibility1. Another option is to reduce enteral nutrition provision and to replace protein and energy with supplementary parenteral nutrition. 37
8. Cholestyramine may be considered in diarrhoea caused by bile acid malabsorption (patients with cholestasis, short bowel syndrome, terminal ileum resection and following cholecystectomy). It needs to be emphasized that cholestyramine can reduce the absorption of enterally administered medications, including metronidazole also.34
9. The use of probiotics in critically ill patients is controversial and still remains to be elucidated which group of patients may benefit from it. Probiotics and prebiotics can possibly reduce diarrhoea, but there are not enough data to recommend their routine use in critically ill patients.38 These agents should be used cautiously, if at all, in premature infants and in patients with any of the following: short bowel syndrome, central catheters, cardiac valve disease, and immunocompromised. In addition, it is important to note that in critically ill patients Saccharomyces boulardii is considered unsafe because of several case reports of fungemia. 39
10. Loperamide is generally not recommended for acute diarrhoea in PICU.
11. Isolation precautions and barrier nursing to prevent nosocomial transmission (especially for C. Difficile) are required for all symptomatic patients with infectious diarrhoea in the ICU.
Feeding Intolerance: The little big problem
Feeding Intolerance (FI) is another commonly encountered GI issue in PICU. Recently in adults The Working Group on Abdominal Problems of the European Society of Intensive Care Medicine has defined FI as ―intolerance of enteral feeding for whatever clinical reason (vomiting, high gastric residual volume, diarrhoea, GI bleeding, etc.)‖1. There is no validated definition for FI in PICU because of several issues, although neonatology and adults have been more proactive in defining the same. 1,40
Diagnosis of FI is complex as several diagnostic symptoms are usually present in any sick child, and different feeding practices in PICU makes it difficult to standardize the definition of FI. Feeding Intolerance in PICU can be presently best defined in 3 ways:
1. Clinical criteria: The presence of abdominal distension, vomiting, GI bleed, abdominal pain, diarrhoea, obvious signs of discomfort.1 The definition of abdominal distension in itself is nonspecific depending on the measure which is taken into account: it can be clinical as increasing abdominal girth or that distension which causes clinical alteration or as dilated loops visualized in radiograph.41
2. Volume based criteria: Gastric residual volume (GRV), this is the most widely accepted criteria for feeding intolerance in PICU 42,43,44. However the accuracy of GRV measurement to predict delayed GE or enteral nutrition (EN) intolerance has not been studied in critically ill children and is not validated. Furthermore, GRV measurement is complicated by a lack of standardization in the GRV threshold to define EN intolerance and in measurement techniques that are affected by patient posture, feeding tube properties ( such as tube type and number of openings, the volume of syringe used etc) and the operator performing the test.46,47,48 Threshold GRVs are usually related to the previous volume of feed given, a volume per kilogram weight or an absolute amount .Volume residual in the gastric aspirate with a volume >50% of the volume administered in the previous 4 h or if gastric aspirate is more than 5ml/kg (max 200ml) is usually considered significant 43,45,48,49. The quality of gastric residuals, namely consistency and colour (clear, milky, bilious, blood stained, and haemorrhagic) and its role in predicting FI is just as inconsistent in the available literature till date.50
3. Nutritional Criteria: FI should be considered present if at least 20 kcal/ kg BW/day via enteral route cannot be reached within 72 h of feeding attempt.1 Newer surrogate markers for gastric emptying (GE) like scintigraphy are being developed but their use is impractical in the PICU. Other techniques like cutaneous electrogastrography, manometry, and the wireless motility capsule are also being studied.51 Ultrasound measurements of the stomach size and antrum cross-sectional area have been used to assess GE.52
What is not feeding intolerance: FI should not be considered as present if enteral feeding is electively not prescribed or is withheld / interrupted due to procedures.1 Intolerance to EN and need to withhold EN during procedural interventions are the most commonly stated reasons for interrupting feeds in the PICU population.45 Absent peristalsis or no bowel sounds heard on cautious abdominal auscultation is of little relevance in ICU settings.41 Also, it should be recognized that presence of bowel sounds does not confirm normal motility, and that reoccurrence of bowel sounds does not correlate with improvement of paralysis. At the same time, a critically sick patient on multiple inotropes, who previously had bowel sounds, and now develops no bowel sounds, should be closely observed as it may be a sign of FI53.
Consequences of feeding intolerance: The lack of consensus on definition makes individual interpretation of signs of FI an uncontrollable variable for discontinuation of enteral feeding and thus affecting overall nutritional status of a sick child. The most common action taken in the face of feed intolerance is to stop feeds or reduce the amount of feed volume.43,45 Suboptimal nutrition, more fasting, delayed attainment of full enteral feeding and prolonged intravenous nutrition supply are all regrettable consequences of FI. Though not evidence based, but the magnitude of FI is deeply influenced by the personal attitude of the clinician.
Risk Factors for FI:
The aetiology of upper gastrointestinal motor dysfunction in critical illness is unclear, but is probably multifactorial. Few important risk factors are highlighted below:
1. Primary diagnosis: Gastric emptying data suggest that there are certain high risk groups for feed intolerance. These include patients with burns, head injuries, sepsis and polytrauma54, 55, 56.
2. Electrolyte imbalance: Hyperglycaemia impairs gastrointestinal motility and GE, which may subsequently lead to feed intolerance.57 Fluid overload and potassium and magnesium derangements have also been associated with slowing of GE.
3. Medications: Many medications used in the critically ill children can potentially influence gastrointestinal motility. Of particular importance are sedatives, analgesics and vasoactive agents. Paralytics or vasoactive agents are often seen as barriers to EN due to their perceived effects on gastrointestinal motility. However, there is limited and equivocal evidence to support the negative effects of these drugs on gastrointestinal motility.58
Vasoactive Medications: High concentrations of circulating catecholamines, either endogenous or exogenous, are common in critically ill patients. Pharmacologically adrenaline reduces gastric emptying by a beta-adrenergic effect. And dopamine has been associated with delayed GE and prolonged small bowel transit time by decreasing antral contractions.59 In a single-center study, a majority of mechanically ventilated children on vasoactive medications were reported to tolerate EN without adverse events. The prevalence of perceived intolerance to EN in this study was 29% only 60.
Opiods: Both endogenous and administered opiates, acting via mu receptors, usually affect upper gastrointestinal motility61. This led to increased use of propofol as a sedative in the critically ill patients as it was believed to cause less slowing of gastrointestinal function. No prospective comparison of propofol and morphine, adjusted for illness severity, has confirmed superiority of propofol on gastric emptying. In addition, propofol has been associated with feed intolerance in head injured patients62. Midazolam, a benzodiazepine often prescribed with an opiate as a combination sedative in the ICU, also reduces gastric emptying and prolongs gastrointestinal transit.
4. Mechanical Ventilation: Manometric studies in critically ill patients requiring mechanical ventilator support have demonstrated decreased gastric motility and diminished activity in the duodenum63. The mechanism by which positive pressure ventilation affects gastric motility is poorly understood and likely multifactorial. Yet, clinical studies in mechanically ventilated children have reported successful EN delivery without adverse effects.43,64
Treatment of FI:
To handle any feeding intolerance in PICU: usual immediate steps by an intensivist are to stop the feed and search for the cause of FI. The intensivist may than restart the feed at previously tolerated rate or may restart trophic feed depending on etiology. Treatment can be broadly divided in 3 ways: 1) Preventive measures 2) Medications 3) Others.
1) Preventive measures:
a) Medications: Avoid or limit use of such medications in PICU that impair motility. Example: restrict use of opiates.
b) Electrolytes: appropriate treatment of hypokalemia, hypocalcaemia, hypomagnesaemia should be carried out, prior to start of feeds.
c) Continuous vs intermittent feed: There is no evidence of superiority of continuous gastric tube feeding over intermittent bolus gastric feeding every 2 hours in terms of tolerance of enteral feedings.65 Except in preterm infants, where continuous gastric feed was associated with lower GRV.66 However, continuous enteral feeding of critically ill adult patients appears to be the standard of care around the world. 67
d) Protocols: Standardized protocols for enteral nutrition in PICU setting need to be developed and followed; with a strategy for minimizing interruptions keeping following points in mind: i). Careful attention to procedure times to prevent prolonged fasting and undue delays in restarting EN ii). Clear communications between PICU team members to ensure timely re-initiation of EN following procedures, eg. following extubation. Iii). Dietician to actively participate in the education of PICU physicians and nursing staff on optimizing EN, troubleshooting GI ―intolerance‖ and to determine alternate causes for feed intolerance.45
There is not enough evidence to recommend the routine use of prokinetic medications or motility agents for EN intolerance in PICU.45 In critically ill children, the most common promotility agents in use are erythromycin and metoclopramide 43, but only erythromycin has been studied for its efficacy in preterm infants68.
3) Others: As GRV mostly defines FI in PICU, few methods are adopted from adult studies, which are not proven or evidence based but many institutes practice it as measures to decrease GRV.69 Few of them are mentioned below:
a. BRE is >30–40°. Maintain a semi-recumbent position with the backrest elevation (shoulders) elevated >30–45.
b. Do not consider automatic cessation of EN until a second high GRV is demonstrated at least four hours after the first.
c. Consider diverting the level of infusion of EN lower in the GI tract (post pyloric). In a study of mechanically ventilated children, postpyloric nutrition was associated with lower GRVs and improved EN delivery when compared with gastric nutrition.70 The benefits of postpyloric nutrition have not been demonstrated in clinical trials, and also postpyloric tube placement needs expertise.
d. Switch to a more calorically dense product to decrease the total volume infused. The risk of diarrhoea may increase due to higher osmolarity of feeds.
e. Verify appropriate placement of feeding tube.
f. Trial of different method of feeding. eg continuous infusion.
g. Consider raising the threshold level or ―cut-off‖ value for GRV for a particular patient.
h. Consider stopping the GRV checks if the patient is clinically stable, has no apparent tolerance issues, and has shown relatively low GRVs for 48 hours. Should the clinical status change, GRV checks can be resumed.
i. Consider a proton pump inhibitor (PPI) in order to decrease volume of endogenous gastric secretions.
Stress Ulcer Prophylaxis in PICU: Is it right to write?
Stress ulcer (SU) prophylaxis is not given to every patient in ICU, but is a relatively common practice among both adult and pediatric intensivists71,72. Stress related GI bleeding is one of the common complications in critically ill patients and it is the main reason for administering SU prophylaxis. Blanket cover with SU prophylaxis is often inappropriately expanded to include non-critically-ill patients in ICU. This preventive approach is mostly attributed to the misconception that acid-suppressive therapy is benign. However SU prophylaxis has been associated with major complications, such as hospital-acquired pneumonia, Clostridium difficile infections73,74 Therefore, an attempt in this brief review, has been made to demarcate a certain high risk children in PICU, who will benefit with this prophylactic intervention.
Recent studies reveal similar incidence of stress related GI bleeding between adult and pediatric intensive care units. The prevalence of GI bleeding ranges from 6 to 50% in pediatric patients, with clinical significant bleeding in only 1.6 to 5.3% of admissions 75, 76, 77. Clinically significant upper GI bleeding is defined as upper GI bleeding associated with hypotension (a spontaneous decrease of more than 20 mm Hg in the systolic blood pressure, an increase of more than 20 beats per minute in the heart rate), need for transfusion ( or a decrease in the hemoglobin of more than 2 g/dL) in the first 24 hours after diagnosis77,78. However, a recent systemic review of SU prophylaxis in critically sick children, found no evidence to support that prophylaxis is better than ―no treatment‖ to decrease the rates of ulcers or erosion or deaths. Furthermore, it also noted there was no evidence to support that prophylaxis decreases the duration of mechanical ventilation or pediatric ICU stay. Also, they did not report any significant increase in the rates of pneumonia or adverse event, when using SU prophylaxis.79 The exact mechanism of development of stress ulcer in critically ill is not completely understood, it may involve decreased mucosal blood flow and subsequent tissue ischemia, resulting in breakdown of mucosal defences, allowing physiological factors to produce injury and ulceration80.
Respiratory failure and coagulopathy are the main risk factors. In a prospective study of more than 2000 adult patients admitted to intensive care units, only 1.5% experienced clinically important GI bleeding. Respiratory failure and coagulopathy were strong, independent risk factors for stress-related hemorrhage. Important bleeding occurred in 3.7% of the 847 patients who had one or both of these risk factors, whereas only 0.1% of 1405 patients without respiratory failure or coagulopathy experienced such bleeding.78 Since the incidence of clinically significant upper GI bleeding is so low in patients with one or no risk factors that SU prophylaxis would be entirely unwarranted in such low risk groups. Pediatric Risk of Mortality score (PRISM II) ≥10 or more recently PRISM III score > 7 have been identified as independent risk factors for GI bleed in PICU77,81. It is also suggested that mechanical ventilation (MV) is another independent significant risk factors of upper GI bleeding in both adult and pediatric ICU's.75,82,83Mechanical ventilation causes decreased cardiac output and splanchnic hypo perfusion. This can result in gastric mucosal injury too 75,81. On the other hand increased production of pro-inflammatory mediators due to ventilator effect can cause mucosal injury of GI tract75,83 Stress ulcer prophylaxis is usually recommended, along with other supportive therapies, in acute respiratory distress syndrome (ARDS) in children84. The recent article on consensus on pediatric ARDS does not mention stress ulcer prophylaxis, wherein these patients are critically ill on mechanical ventilation with sometimes added risk factor of corticosteroid administration85. Stress ulcer prophylaxis is advised as supportive care for children with sep-sis, as per the 2012 Surviving Sepsis Campaign, though it is not a graded recommendation86. But the adult surviving sepsis guidelines have specific indications for SU prophylaxis in high risk septic patients like patients with severe sepsis, septic shock, coagulopathy & on mechanical ventilator for > 48 hours. The other risk factors in PICU where upper GI bleed associated are thrombocytopenia, shock, surgery time >3 hours, trauma, pneumonia , organ failure and corticosteroid administration71,87,88,89, where stress ulcer prophylaxis may benefit. A number of adult studies suggested SU prophylaxis in specific subset of patients in ICU: those on mechanical ventilation >48 hours, coagulopathy( INR >1.5, PTT >2 times control value), platelet count< 50,000/ mm3, thermal injuries>35% body surface area, polytrauma with injury severity score ≥16, traumatic brain injury (GCS ≤10), history of gastric ulceration or bleeding during the year before admission, corticosteroid therapy (>250 mg of hydrocortisone or equivalent daily).88An update on SU prophylaxis suggested pharmacologic intervention in adults admitted to the ICU who have coagulopathy, require mechanical ventilation for 48 hrs, have a history of gastrointestinal ulceration or bleeding within 1 year before admission, or have at least two of the following risk factors: sepsis, ICU stay of 1 week, occult bleeding lasting 6 days, and use of 250 mg of hydrocortisone or the equivalent90. Another guideline in 2008, suggested SU prophylaxis for patients in ICU with coagulopathy, traumatic brain injury, major burn injury, on mechanical ventilator, polytrauma, sepsis, acute kidney injury, high dose steroids91(Table 2). Scoring systems like the Blatchford risk score is widely used and validated in adults, as a risk-stratification tool that can accurately identify patient risk for bleeding using clinical and laboratory variables92. Moreover, the Rockall risk score can also be used but like the above mentioned score; it’s not validated in pediatric age group93.
This section can be further subdivided into 2 sections:
a) Timing and duration b) Medications a) Timing & duration: If stress ulcer prophylaxis is to be initiated, it should be done so at the onset of risk factors. Based on the current literature review, it is unclear when prophylaxis should be discontinued. Although it has been recommended that prophylaxis be continued for at least 7 days, or till there is no risk factors for SU prophylaxis or till the initiation of enteral feeding or throughout the duration of critical illness or intensive care unit stay71,91. These strategies should be individualized based on patient physiology and respective policy of an institute.
b) Medications: (Table 2) Recommendations on agents for SUP are not consistent across all guidelines in both children and adults. Sucralfate, H2 receptor antagonists (H2RA), antacids, and proton pump inhibitors (PPIs) have been used for prophylaxis of stress-induced mucosal damage in pediatric critical care patients. Individual trials including comparative studies and case series have shown each agent to be effective. The Danish Society of Anesthesiology and Intensive Care Medicine; DSIT: Danish Society of Intensive Care Medicine (DASAIM) group recommend using (PPIs) rather than H2RA for SU prophylaxis, while Eastern Association for the Surgery of Trauma (EAST) and National Medical Journal of China (NMJC) group recommend using both PPIs and H2RAs. American Society of Health-System Pharmacists (ASHP) however group do not recommend the use of PPIs. ASHP & NMJC group recommend using antacids for SUP91,94,95,96. With the low incidence of clinically significant bleeds in pediatric ICU, studies intending to demonstrate superiority of one drug class or agent over another usually used a surrogate endpoint of gastric pH 4 or greater to evaluate efficacy of various dosing regimens79. Although published recommendations for pediatric dosing of intravenous H2RAs and PPIs exist for patients with erosive esophagitis and gastroesophageal reflux, these doses may not be appropriate for stress ulcer prophylaxis in the critically ill pediatric patient. However, recent studies indicate they might be benefit with higher doses or continuous infusions97.
i) Antacids & sucralfate: Pediatric patients in PICU do present challenges with regard to drug administration for antacids and sucralfate. Both agents require multiple doses per day, lack intravenous formulations, and may chelate or inhibit absorption of other drugs. Also, a landmark trial in adults by Cook et al. published in 1998, highlighted the inadequacy of sucralfate as compared to ranitidine as stress ulcer prophylaxis in adult ICU. Sucralfate dose is 0.5 gram if weighing <10 kg and 1 gram if weighing >10 kg every 6 hrs98.In addition, aluminium toxicity may be of greater concern, with use of sucralfate, in critical care patients because of the potential risk for renal impairment99.
ii) Histamine receptor antagonists (H2RA): This is the first choice of SU prophylaxis as per a multi centric study in Canadian PICU's and most of the adults ICU's71. The reason stated being optimal efficacy, low cost and easy administration. This group of medications act by inhibiting histamine-stimulated acid secretion by selectively blocking H2-receptor.. Lugo et al studied the pharmacodynamics of ranitidine in critically ill children and found that the maximal inhibition of gastric acid, occurred at 2.3 ± 1.3 hours after intravenous therapy100. The main issue with is development of tolerance and the need for higher doses. Also H2RAs may interact with phenytoin, theophylline, warfarin, beta-blockers, anti-diabetics and some benzodiazepines, thereby prolonging their effect95. The preferred route is intravenous (IV) in PICU settings with a dose ranging from 2 to 4 mg/kg per 24 hours divided every 6 to 8 hours with a maximum dose of 150 mg/d97. Continuous infusion (0.15 mg/kg per hour) on comparison with intermittent bolus doses, had little variation on patients gastric pH.101
iii) Proton pump Inhibitors (PPI): Prescriptions for PPIs have increased greatly among pediatric and infant populations in recent years102. They act by suppressing gastric acid secretion by inhibition of H+ /K+ ATPase pump. Recently, Levy et al prospectively randomized 67 adult patients in ICU who were at high risk for UGIB to either ranitidine or omeprazole prophylaxis and found the rate of clinically significant bleeding in the ranitidine group to be 31% vs only 6% in the omeprazole group102. Apart from good efficacy, another advantage to PPIs is the non development of drug tolerance with its use. Studies in adult patients with UGIB show that intravenous continuous infusions of PPIs can reliably raise and maintain gastric pH at higher levels than intermittent dosing of PPIs104,105. But a recent meta-analysis did not show any advantage of continuous infusion over intermittent therapy of PPIs for high risk bleeding ulcers106 .Although once daily dosing of a PPI is often recommended and appears to be adequate in noncritically ill patients, this dosing regimen may not be effective in critically ill children. Pediatric studies on transplant critically sick children noted that frequent dosing of omeprazole, was needed to maintain optimal gastric pH107,108. Twice daily intravenous PPIs appears to achieve a more alkaline gastric pH (>4) more consistently than once daily intravenous dose97. The dose of intravenous PPI in various studies from pantoprazole, commonly dosed at 1-2 mg/kg per dose every 12 to 24 hours (maximum dose, 40 mg), to lansoprazole, commonly dosed at 1 mg/kg per dose every 12 to 24 hours (maximum dose, 30 mg). There currently are no large studies that prove superiority of proton pump inhibitors to H2RA for stress ulcer prophylaxis, but recent multiple meta analysis in adults conclude that PPIs reduce clinically important bleeding and overt upper GI bleeding, when compared to H2RA as stress ulcer prophylaxis.95,109,110
Potential adverse effects associated with stress ulcer prophylaxis therapy:
1. Infection-related ventilator-associated complication (IVAC): The hypothesis is that SU prophylaxis increases the gastric pH, which facilitates gastric colonisation with pathogenic organisms. The reflux of such gastric content and subsequent aspiration leads to IVAC111. Laheij et al. reported in ambulatory patients, a 1.89 fold increase in the risk of CAP in those taking PPIs versus those who had stopped using PPIs 112. Similar results are shown with the usage of H2RA. In the critically ill, however, data relating intragastric pH and pulmonary infections are inconsistent.
2. Clostridium difficile infection: There is a plausible biological mechanism that acid suppression increases the risk of developing C. difficile colonization, as local immunity is compromised by a higher gastric pH environment. Observational studies have also reported an association between iatrogenic acid suppression and C. difficile-associated diseases113. Another important observational study in adult patients revealed that most of the patients given PPIs for SU prophylaxis in ICU went home on the drug despite there being no indication for its continued usage at discharge114.
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