Enteral Nutrition English

Nutrition for Intensive Care Patients

Trauma and severe illness place extraordinary demands on the body, requiring adequate nutrient intake to prevent the body from breaking down and to avoid prolonging or worsening the illness. Nutrition within anesthesia and intensive care is a basic part of treatment and can be categorized into enteral (via the intestines) and parenteral nutrition (via the blood). Total intravenous nutrition is commonly referred to as total parenteral nutrition (TPN). The body needs supplements of carbohydrates, fats, proteins, minerals, trace elements, and vitamins. In TPN, solutions of a fat emulsion, a carbohydrate solution, and an amino acid solution are usually given. Parenteral nutrition solutions are usually based on egg, soy, or peanut proteins, as well as a fat emulsion. Fat emulsions are based on substances such as soybean oil, corn oil, and egg phospholipids. Electrolytes are added according to daily needs, along with vitamins (e.g., Soluvit and Vitalipid) and trace elements (e.g., Tracel). This combination is often shortened to SVT (not to be confused with Sveriges Television). Contraindications for parenteral nutrition may include egg, soy, or peanut allergy, or severe liver failure, hyperlipidemia, and severe coagulation disorders. If the plasma is milky or opalescent during TPN treatment, the planned infusion should be stopped.

• Enteral nutrition should be started within 24-48 hours
• Early TPN starts on day 3
• Parenteral nutrition (PE) usually starts after day 7

Enteral nutrition should be provided to all ICU patients who are not expected to eat normal food orally within three days. Nutrition should be initiated within the first 24 hours with a protein-rich enteral nutritional solution. During the acute and early phases of critical illness, an exogenous energy supply exceeding 20-25 kcal/kg body weight/day should be avoided, while during the recovery phase, the goal should be 25-30 kcal/kg body weight/day. Supplemental parenteral nutrition remains a reserve tool and should only be given to patients who do not reach their nutritional intake goal solely with EN. There is no general indication for immunomodulatory solutions in patients with severe illness or sepsis and APACHE II scores > 15. Glutamine should be supplemented for patients suffering from burns or trauma.

EN should be prioritized for all ICU patients without absolute contraindications. There is value in starting early (< 24-48 hours) to counteract disruptions in normal gut flora, which can lead to translocation and sepsis, as well as poorer outcomes for EN due to diarrhea or constipation. If EN is established early in intubated patients with a protected airway, without gastric retention, and ideally with bowel movement, several significant advantages can be achieved:

There is no strong evidence for mortality benefits with EN compared to PN, but all comparative studies point to reduced infections, dialysis needs, and costs (Singer et al., Clin Nutr 2009; Kreyman et al., Clin Nutr 2006). While PN achieves caloric goals predictably, there are now strong indications that parenteral nutrition is not solely beneficial but may pose risks for critically ill patients (Caeser et al., N Engl J Med 2011; McClave et al., J Parent Enteral Nutr 2009). Conversely, no increased mortality or morbidity is seen with the late start (ICU day 8) of supplemental PN. Therefore, a risk assessment must be made against malnutrition, which carries its own risks of poorer wound healing, infections, and, ultimately, mortality. To aid assessment and identify critically ill patients with a particularly high risk of malnutrition, NRS is calculated automatically in the nutrition calculator.

At NRS ≥ 5, there is a high risk of malnutrition and an indication for early (day 3) supplemental parenteral nutrition, typically at BMI < 20.5 or < 22.5 depending on age under or over 70. At intermediate risk (NRS 3-4), supplemental parenteral nutrition is started on ICU day 8.

Note that the goal should always be to achieve the highest possible level with EN even during ongoing PN. High gastric retention should be actively managed and only as a last resort should intake be reduced or stopped. Virtually all patients tolerate some level of EN.

Basic Nutritional Needs

• Basic energy requirement is 25-30 kcal/kg/day, corresponding to about 90 kJ/kg/day.
• Glucose requirement is approximately 150-200 g/day.
• Fat requirement is approximately 1-2 g/kg/day, normally 50-200 g/day.
• Nitrogen requirement is 0.15-0.20 g/kg/day, 7-20 g N per day for a body weight of 45-100 kg. In severe catabolic conditions, nitrogen requirement is 0.20-0.25 g nitrogen/kg/day.
• Basic fluid requirement is about 30 ml/kg/day. A healthy adult requires about 1500-2500 ml of water per day.
• Basic electrolyte requirement is approximately 80 mmol sodium, 40 mmol potassium, 20 mmol magnesium, and 20 mmol phosphate per day.

Daily Needs

• Fluids 25-30 ml/kg
• Glucose 3 g/kg
• Electrolytes (mmol): 80 Na, 40 K, 20 Mg, 20 Phosphate

Energy Needs in Different Patient Categories Per Day

Nutrition Level 0: 5-10 kcal/kg/day (20-30% of indirect calorimetry). Resuscitation phase.

• Newly admitted acutely unstable patient.
• Massive inotropic needs, large volume requirements, vasopressor needs.
• SIRS.
• Imminent intubation threat.
• Patient not expected to require full nutrition.
• Only crystalloid fluid replacement with 5-10% glucose.

Nutrition Level 1: 15-20 kcal/kg/day (~50% of indirect calorimetry)

• Unstable but no imminent respiratory or circulatory threat.
• Continued high oxygen needs and adrenergic support.
• Deep sedation.
• Should be started on day 1-2 if not extremely unstable.
• Stabilization phase. Resuscitated patient, cardio-respiratorily stabilized but with high cardio-respiratory vital function support.
• Spinal cord injured patient with reduced metabolism.

Nutrition Level 2-3: 20-25 kcal/kg/day (~65-80% of indirect calorimetry). Weaning phase.

• Stable oxygen and adrenergic needs.
• Turning point in the course.
• Plateau phase: Patient has passed the most intense phase of illness and can now begin weaning from ventilator and pressor support.
• Nutrition goal for most ICU patients.

Nutrition Level 4: 30-35 kcal/kg/day (100% of indirect calorimetry)

• Recovery and mobilization phase with increasing mobilization.
• The transition from the catabolic to the anabolic phase of critical illness can only occur when immobilization ceases, and the patient voluntarily starts using their own muscle strength. For example, an awake patient begins standing or bed cycling with resistance.

Acute illness induces a catabolic phase followed by a prolonged anabolic phase during recovery. Severe illness involves increased energy turnover and oxygen consumption. It also leads to increased gluconeogenesis, lipolysis, and fat oxidation. Additionally, water and sodium retention occurs in the extracellular space, leading to edema. There is increased protein breakdown with loss of muscle mass and increased nitrogen losses in the urine, along with reduced glutamate content and reduced protein synthesis in skeletal muscle. Edema impairs organ function, increases the risk of respiratory failure, reduces protein synthesis, and impairs cellular function with failure of vital enzymes. Daily fluid balance should be monitored during TPN, with the patient weighed at least three times per week, and a clinical assessment of the patient’s nutritional status (SGA class) should be performed. The patient can be categorized as well-nourished, slightly malnourished, or severely malnourished.

Subjective Global Assessment of Nutritional Status

SGA classification divides the patient into 3 categories.

• SGA Class A: Well-nourished
• SGA Class B: Slightly malnourished
• SGA Class C: Severely malnourished

Increased body temperature raises energy needs by approximately 10% per degree of temperature increase. The need for energy supply in critically ill patients can be calculated using indirect calorimetry or by using standardized nutrition solutions, as referenced in guides in this chapter. In case of hyperglycemia, insulin is administered according to a specific protocol, but energy supply is usually not reduced. The target blood glucose level is 5-9 mmol/L. Parenteral nutrition solutions should not be administered at a rate higher than 2-3 ml/kg/hour. The amount of intravenously administered fat should generally not exceed 3 g/kg body weight/day (150-300 g/day). The maximum recommended infusion rate is 1.6 ml/min, which corresponds to an infusion time of at least 5 hours for 500 ml of TPN.

During parenteral nutrition, temperature should be monitored daily, along with total fluid balance and blood glucose levels. Nitrogen balance can be calculated if needed by monitoring urea in urine and serum. Weekly monitoring of S-Alb, S-Phosphate, S-Mg, S-Zn, liver tests, S-Creatinine, S-Urea, and S-Triglycerides is recommended.

If possible, enteral nutrition should be used as early as possible in the treatment, taking into account the risk of gastric retention, vomiting, aspiration, intestinal paralysis, burdening of intestinal anastomoses, and worsening of the patient’s condition. Enteral nutrition should be chosen over parenteral nutrition whenever feasible. Tube feedings typically provide 1 kcal/ml of energy value. If the stomach and intestines need to be relieved, parenteral nutrition administered intravenously is a better option. Initially, only carbohydrate-rich sugar solutions are given, while fat and protein supplementation can wait for 5-7 days. The timing for starting parenteral nutrition is scientifically controversial. An old practice suggests that if the patient is unable to eat orally within seven days, parenteral nutrition should be initiated within 3 to 7 days. New findings suggest that it may be better to wait seven days, while common practice is to start parenteral nutrition on the third day and give only glucose solutions on days one and two. A common approach is to use a combination of moderate enteral nutrition plus parenteral support.

Routes of Nutritional Administration

• Orally (liquid or solid food)
• Nasogastric tube
• Nasoduodenal tube
• Nasojejunal tube
• Gastrostomy
• Jejunostomy
• Intravenous nutrition
• Total parenteral nutrition (TPN)
• Peripheral parenteral nutrition (PPN)

Clear Liquids

During preoperative fasting, clear liquids can sometimes be tolerated up to about 2 hours before anesthesia or surgical or endoscopic procedures. Similarly, postoperatively, the intake of clear liquids may be prescribed before solid food to assess whether the gut can absorb enteral fluid or if gastric retention is present. If gastric retention exceeds 400 ml/day, bowel rest and only parenteral nutrition are usually prescribed.

Examples of clear liquids:

• Clear soup and broth without solid components
• Resorb fluid replacement
• Orange and apple juice without pulp (avoid red, purple, or blue liquids)
• Clear sports drinks
• Juice, avoid red, purple, or blue juice
• Coffee or tea (without milk)
• Water or clear carbonated drinks (avoid diet products)

Enteral Nutrition

Enteral nutrition (EN) should be prioritized for all ICU patients without absolute contraindications. There is value in starting early (< 24-48 hours) to counteract disruptions in the normal gut microbiota, which can lead to translocation and sepsis, as well as poorer conditions for EN success due to diarrhea or constipation.

If EN is established early in intubated patients with a protected airway, without gastric retention and preferably with bowel movement, several significant advantages are achieved:

• The risk of aspiration during or after extubation can be assumed to be significantly lower.
• Tube feeding can be restarted earlier after extubation.
• The absorption of oral medications via the tube can be assumed to work well.

There is no strong evidence for mortality benefits with EN compared to PN, but all comparative studies point to reduced infections, dialysis needs, and costs (Singer et al., Clin Nutr 2009; Kreyman et al., Clin Nutr 2006). With PN, calorie goals are achieved predictably, but there are now strong indications that parenteral nutrition is not solely beneficial but may pose risks of harm in critically ill patients (Caeser et al., N Engl J Med 2011; McClave et al., J Parent Enteral Nutr 2009). Conversely, there is no increased mortality or morbidity with the late start (ICU day 8) of supplemental PN. Therefore, a risk assessment must be made against malnutrition, with its own risks of poorer wound healing, infections, and ultimately mortality. To facilitate assessment and identify critically ill patients at high risk of malnutrition, NRS is automatically calculated in the nutrition calculator.

At NRS over 5, there is a high risk of malnutrition and an indication for early (day 3) supplemental parenteral nutrition, typically at BMI < 20.5 or < 22.5 depending on age under or over 70. At intermediate risk (NRS 3-4), supplemental parenteral nutrition starts on ICU day 8.

Note that the goal should always be to achieve the highest possible level with EN even during ongoing PN. High retention levels should be treated actively and only as a last resort lead to reduced or stopped supply. Virtually all patients tolerate some level of EN.

Practical Steps for Enteral Nutrition

• The head of the bed should be elevated 30-45° during tube feeding.
• Start EN in sedated, consciousness-impaired, or neurologically disabled patients with a Salem or Vygon tube only after the appropriate position is verified by X-ray. For skull base and facial fractures, the tube is inserted orally.
• Check tube position by injecting air with a syringe and listening with a stethoscope over the stomach for sounds. The position is checked during each feeding and before administering medication.
• Aspirate from the tube 3 times a day (1 time/shift) at regular intervals. If more than 200 ml is aspirated, consider administering metoclopramide (Primperan).
• Document aspiration testing and any interventions as codes in the daily journal.
• To reduce the risk of misadministration, medication should only be given with a large tube syringe or a purple 10 ml syringe, with a specially designed connection, in the side port of the set. After giving crushed tablets in the tube, flush it with 30 ml of water.
• If tube feeding is paused in a patient with a concurrent insulin regimen, the insulin infusion must be adjusted accordingly and blood sugar monitored.
• For commercially prepared tube formulas and continuous delivery, the recommended hang time is 24 hours. If the product is in powder form, mixed with water, or transferred to another container, the hang time is 4 hours after preparation.
• Switch to a nutrition tube when the patient is fully nourished and shows no retention. The position of the nutrition tube should be checked with contrast X-ray after placement. Mark the position with a marker.
• The continuous feeding pause must not exceed 2 hours. If longer, the set and formula must be discarded. If the system is interrupted, flush out a few ml of the formula and disinfect the connections with 70% alcohol before restarting the feeding.
• For continuous feeding, the set can be used for 1 day (new formula bag – new set). Mark the set with the date and time.
• Before airway intervention, surgery in the prone position, or open gastrointestinal surgery, enteral feeding is stopped 6 hours before anesthesia starts (refer to intensive care anesthesia preoperative fasting guidelines). Adjust insulin infusion and increase glucose supply accordingly!
• For radiological examination, angiography, ICU transport, or other surgeries, enteral nutrition is stopped when the patient is taken from the ICU. Adjust or stop insulin infusion and increase glucose supply accordingly!
• For transportation outside the hospital, EN is stopped upon ambulance arrival, and glucose solution is prescribed in advance. Stop insulin infusion if applicable. Document the type and level of nutrition for the receiving hospital. Do not revert to PN unless the transport exceeds 6 hours.

Intermittent Enteral Nutrition (IEN)

IEN can be considered after well-established continuous EN to facilitate mobilization and transition to a normal tube feeding routine on the ward, particularly for diabetics where the natural continuation is meal-time insulin with extra doses and long-acting insulin. Intermittent feeding is also thought to be beneficial for restoring natural gastrointestinal function and circadian rhythm.

• Enteral nutrition starts within 24-48 hours.
• Divide the established daily dose into 3 meals.
• Consider switching to a formula with different energy content so that the daily volume can be translated into the standard volume of 500 ml x 3, based on the patient’s current gastrointestinal function.
• Prescribe the full or fractional volume of a tube feed bag, preferably at 08:00 – 13:00 – 18:00.
• A suitable infusion rate is generally 250-500 ml over 2-3 hours, but may need adjustment based on the patient’s gastrointestinal function and surgical circumstances.
• Check gastric residual volume before each meal and follow standard recommendations.
• PE nutrition typically starts after day 7.

Avoid Enteral Nutrition When

• Intra-abdominal compartment syndrome.
• Intestinal ischemia/perforation/obstructive ileus.
• Imminent intubation/tracheostomy.
• Imminent abdominal surgery.

EN is possible but with caution when:

• Impaired consciousness.
• Non-invasive ventilation.
• Swallowing dysfunction.

Diarrhea

• Pause or discontinue laxatives unless it is constipation-caused diarrhea.
• Let EN continue. Nutrient absorption is adequate despite diarrhea. Try switching to GI-control.
• Use a rectal tube to protect perianal skin from erosion.
• For frequent watery diarrhea, Clostridium culture should be taken. If positive, antibiotics should be changed, and treatment should be done with Metronidazole orally, in severe cases Vancomycin.

Gastric Retention (GRV)

GRV is usually checked 3 times a day. High retention volumes are a signal to treat with motility-stimulating medications; the maximum limit is 200 ml.

Gastric Retention Volume (GRV) < 200 ml every 8 hours

1) Return the aspirated amount
2) Increase EN the next day
3) Decrease PN or Glucose at the corresponding infusion rate.

GRV > 200 ml every 8 hours

1) Return 200 ml
2) Optimize = minimize opioid administration.
3) Administer metoclopramide (Primperan).
4) Continue EN at the same rate.

If GRV > 200 ml every 4 hours

1) Discard the aspirate.
2) Optimize opioid infusion.
3) Reduce the intake by 10 ml/h.

If continued GRV > 200 ml every 4 hours

1) Discard the aspirate.
2) Provide nutrition via PN to the prescribed energy level.
3) Aim to maintain low-dose EN at 10 ml/h.
4) Make regular attempts every 24-48 hours to increase EN again, by 10 ml/h each time.
5) Consider jejunal tube.

Nutritional Solutions and Suggestions

Lightweight Adult 40-60 kg

Normal Weight Adult 60-80 kg

Heavy Weight Adult > 80 kg

Nutritional Drinks

Nutritional Drinks for Oral Use

Energy Value and Content of Protein, Glucose, and Lipids (per 100 ml solution)

Constipation Prophylaxis

Constipation is a common problem among ICU patients. Critically ill patients receive multiple medications that negatively affect normal bowel function, especially opioids. Immobilization, reduced consciousness, and lack of normal food intake inhibit central regulation of the enteric nervous system, gastrointestinal hormones, as well as normal trophic stimulation of the intestinal mucosa’s function and microstructure. Just like bones and muscles, the intestinal mucosa quickly atrophies, and smooth muscle activity decreases or ceases.

• Start enteral nutrition early. As soon as the patient is stabilized, preferably at the first regular round.
• Continuously reassess opioid administration, sedation, and mobilization regimen.
• Moventig 25 mg x 1 is given to counteract opioid-induced constipation.
• Movicol 2 sachets per day are given as routine. Best effect if both sachets are taken within 4-6 hours. Movicol is an osmotically active laxative
  
  that absorbs water in the colon, increases fecal water content, and “loosens the stool.” If ineffective or fecal impaction occurs, increase the dose stepwise to 8 sachets per day.
• If fecal impaction or other bowel obstruction cannot be ruled out, order a CT of the abdomen (BÖS).
• Consider Laxoberal drops in the second instance, 10-20 drops given at 22:00, supplemented with 2 suppositories of Dulcolax the following morning. Repeat this daily until results are achieved.
• Consider Klyx in the third instance.
• Consider oil enema in the fourth instance. Mix 300 ml of oil with 700 ml of lukewarm water. Start with the patient on the left side, administer 1/3 of the enema, and then give 1/3 in the supine position and 1/3 on the right side.
• Do not administer laxatives to spinal cord injured patients or when bowel obstruction is suspected.
• Be cautious in cases of subarachnoid hemorrhage with spasm risk. Once laxation is achieved, follow the schedule again from the beginning.

Gastrointestinal Stimulants

Movicol

Sachets containing a dose granulate (macrogol) to counteract constipation. Movicol is a laxative for temporary treatment of constipation in adults, adolescents, and the elderly. It is not recommended for children under 12 years. The duration of treatment with Movicol for temporary constipation is normally about 2 weeks.

Dosage: 1 sachet dissolved in 125 ml (1/2 glass) of water given 1-3 times daily, depending on the severity of constipation. For fecal impaction, up to 8 sachets of Movicol may be required per day. Each sachet is dissolved in 125 ml (1/2 glass) of water. The 8 sachets should be taken within 6 hours for up to 3 days if necessary. Movicol is also available as a ready-to-drink oral solution.

Metoclopramide (Primperan^®)

Injection solution, 5 mg/ml. Dosage: 2 ml (10 mg) x 3 IV (may lower the dose in case of renal insufficiency).

• Promotes gastric emptying.
• Counteracts dopamine’s inhibitory effect on motility.
• Sensitizes the intestines to acetylcholine.
• Increases sphincter tone in the cardia.
• Risk of interaction with other medications.
• High doses may cause extrapyramidal side effects.

Naloxone Hydrochloride

Oral ex tempore preparation 1 mg/ml. Dosage: 5-8 ml x 3 via tube can be tried if the above has not produced the desired effect during concurrent opioid treatment.

• Counteracts opioids’ inhibitory effect on gastrointestinal motility by blocking opioid effects on intestinal receptors.
• Reduces the risk of nosocomial pneumonia.
• Naloxone is absorbed from the gastrointestinal tract but is metabolized in the liver.
• Should not be given in cases of severe liver failure. May cause systemic effects with opioid antagonism due to reduced liver metabolism.

Methylnaltrexone (Relistor^®)

Selective opioid antagonist. Injectable solution 12 mg/0.6 ml. Dosage: 8-12 mg x 1 SC is primarily indicated for opioid-induced constipation in cancer patients. No studies are available on ICU patients, but it likely has a similar effect to oral Naloxone.

• Only peripheral action, does not reverse central opioid effect.
• Reduces oro-rectal transit time.

Laxoberal Drops (Cilaxoberal^®)

Oral drops, solution 7.5 mg/ml, 10–20 drops (5-10 mg) per day 2 days after starting enteral nutrition. 10-20 drops are given at 22:00. Stimulates the colon and rectum.

Dulcolax

Suppositories (10 mg) or tablets (5 mg) (Bisacodyl) 10 mg in the morning after starting enteral nutrition. Can be repeated daily until results are achieved.

On day seven, a Klyx (rectal solution 1mg/ml+250mg/ml) may also need to be given, along with starting oral solution Lactulose (670 mg/ml) 30 ml x 1.

If no stool has been passed in 10-12 days, consider an oil enema. Mix 300 ml of oil with 700 ml of lukewarm water. Start with the patient on the left side, administer 1/3 of the enema, and then give 1/3 in the supine position and 1/3 on the right side. Do not administer laxatives to spinal cord injured patients or in cases of suspected obstructive bowel paralysis. Be cautious in cases of subarachnoid hemorrhage with spasm risk.

Other Gastrointestinal Stimulants:

• Dulcolax^®, tablets 5 mg
• Pursennid Ex-Lax^®, dragee tablet 12 mg, 20 pieces in blister pack
• Microlax^® Rectal solution, 12 x 5 milliliters tube
• Inolaxol^® Granules in sachet, 50 pieces in sachets
• Resource Active, ready-to-drink solution with prunes, 200 ml
• Vi-Siblin^® Granules, 610 mg/g, 500 grams in a bag
• Lunelax^® Powder for oral suspension, 100 sachets in a box
• Resulax^® (Sorbitol), rectal solution 8.5 g, 4 pieces in a tube
• Frukt & Fibrer tablets, dietary fiber, 30 pcs
• Duphalac^® oral solution, 670 mg/ml in a 1000-milliliter bottle
• Laxido Orange Powder for oral solution, 20 sachets
• Relaxit^® Suppository, 20 pieces in blister pack
• DulcoSoft^® (macrogol) sachets, 20 pcs 4000
• Prune juice from the pharmacy, ready-to-drink juice that can be given for constipation. One pack equals about 15 prunes. Dosage from age 7: one pack of 200 ml per day for occasional discomfort.

Ulcer Prophylaxis

Severe gastrointestinal bleeding (GI bleeding) has been reported in scientific studies in 1.5-8.5% of ICU patients and, in some studies, has been shown to be associated with increased mortality. In more recent studies, the risk of GI bleeding appears to be lower, probably due to generally better intensive care or improved ulcer prophylaxis.

Stress ulcers can develop in all critically ill patients within hours due to severe stress, serious injury, surgery, shock, or infection. Ulcers can range from erosive gastritis to perforated ulcers, and they are often superficial, with minor capillary bleeding, but can erode into the submucosa and become more profound. Underlying vessels can be damaged, causing bleeding, or in rare cases, perforation of the mucosa. The ulcers likely result from an imbalance between protective mucus membranes and acid production in the stomach.

The mucus membrane contains glycoproteins, which provide physical protection but also bind bicarbonate, neutralizing the acid in the stomach. In many critically ill patients, the function of the mucus layer is impaired due to reduced blood flow. Reflux of bile and uremic toxins can contribute to damaging the mucosa.

Increased acid production is observed in patients with head trauma but probably not in other critically ill patients. Helicobacter pylori infection may be a contributing factor to stress ulcers.

Stress ulcers are most common in the fundus and corpus of the stomach but can also occur in other parts of the gastrointestinal tract, such as the duodenum and distal esophagus.

A large prospective multicenter study showed a significantly increased risk of stress ulcers in patients who had been in mechanical ventilation for over 48 hours and/or had coagulopathy, compared to other ICU patients. There are also studies pointing to increased risk in other severe conditions, such as head trauma, shock, sepsis, liver and kidney failure, trauma, severe burns, organ transplantation, previous upper GI bleeding, and high SOFA scores.

Enteral nutrition has a protective effect by buffering stomach acid, increasing mucosal blood flow, and inducing the secretion of cytoprotective prostaglandins and mucus.

However, it is uncertain whether one can forego pharmacological prophylaxis despite ongoing enteral nutrition. One study has shown that H₂ blockers in patients receiving enteral nutrition actually led to increased mortality.

Ulcer Prophylaxis

To reduce the risk of developing ulcers, pharmacological prophylaxis is commonly used in ICU patients, either given parenterally or orally. The three main types of medications used for prophylaxis are proton pump inhibitors (PPI), histamine-2 receptor blockers, and sucralfate. The indications for prophylaxis and the choice of medications vary across Sweden and internationally. There is no scientific support for routine administration of ulcer prophylaxis to all ICU patients. Recent studies have shown questionable effectiveness of PPI prophylaxis but have not demonstrated significant harm either.

Currently, pharmacological ulcer prophylaxis is recommended for patients with:

• Respiratory support for over 48 hours.
• Coagulopathy (platelets < 50, INR > 1.5 times the reference value, APTT > 2 times the reference value).
• Gastrointestinal bleeding in the last year.
• Traumatic brain injury, traumatic spinal cord injury, or major burns.
• Two of the following: sepsis, ICU stay longer than 1 week, occult gastrointestinal bleeding > 6 days, corticosteroid treatment (>250 mg hydrocortisone/day).

For other patients, an individual assessment should be made, taking the patient’s risk factors into account.

The choice of prophylaxis can be based on local guidelines, but oral medications should be used if the patient tolerates them.

Enteral nutrition is probably protective and should be initiated early, but today there is not enough knowledge to withhold ulcer prophylaxis in at-risk patients despite enteral nutrition.

Ulcer prophylaxis should be evaluated and discontinued when the patient no longer belongs to a risk group or when intensive care ends.

The three types of medications used for prophylaxis are proton pump inhibitors (PPI), histamine-2 receptor blockers (H2 blockers), and sucralfate. It appears that PPIs are more effective than H2 blockers in preventing ulcers; however, some studies show the opposite. The choice of medication often depends on local routines, but PPIs are more frequently used in Sweden than other medications. Sucralfate provides less protection against stress ulcers but may pose a lower risk for nosocomial pneumonia.

Risks

Ulcer prophylaxis leads to a higher pH in the stomach, which allows bacterial overgrowth in the gastric mucosa. Through reflux, these bacteria can reach the pharynx, where they may be aspirated into the airways, potentially resulting in pneumonia (ventilator-associated pneumonia, VAP). There may be an increased risk of VAP when treating patients with prophylaxis against stress ulcers, and this risk may be higher with PPIs than with sucralfate and H2 blockers. There is also an increased risk of Clostridium difficile gastroenteritis due to the elevated pH in the stomach.

Medications Against Stress Ulcers

Proton Pump Inhibitors

These medications are substituted benzimidazoles that reduce acid secretion by specifically blocking the proton pumps in the parietal cells. Commonly used medications include omeprazole, esomeprazole, or pantoprazole. The medications are converted into their active form in the acidic environment of the parietal cells, where they inhibit the H⁺/K⁺-ATPase enzyme, the final step in gastric acid production. This results in inhibition of both basal and stimulated acid secretion, independent of stimulating systems such as acetylcholine, histamine, and gastrin. Omeprazole, like all acid-blocking medications, can reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. Another side effect may be hypomagnesemia.

Omeprazole

Proton pump inhibitor. Available as enteric-coated capsules and enteric-coated tablets.

Omeprazole is a racemic mixture of two enantiomers that specifically inhibits the acid pump in parietal cells. It has a fast onset of action, and its effect on acid secretion is reversible with daily administration.

Omeprazole is a weak base that is concentrated and converted to its active form in the highly acidic environment of the parietal cell’s secretory channels, where it inhibits the enzyme H⁺K⁺-ATPase – the acid pump. The effect on the final step of the acid secretion process is dose-dependent and provides highly effective inhibition of both basal and stimulated acid secretion, regardless of the type of stimulation.

Brand names: Omeprazole^®, Losec^®, Omecat^®, Omestad^®, Omezomyl^®.

Standard dose: 20-40 mg orally once daily.

Dosage for bleeding ulcers: 40 mg twice daily.

Caveats: Possible dose adjustment in severe liver failure, possible clinical interaction with clopidogrel (reduced effect), interactions with certain HIV medications and azoles.

Esomeprazole

Proton pump inhibitor, S-isomer of omeprazole. Available for intravenous and oral use. Fully metabolized via P450, mainly by CYP2C19. Can be used during pregnancy.

Brand names: Esomeprazole^®, Nexium^®, Vimovo^®.

Standard dose: 40 mg IV once daily; 20-40 mg orally once daily (granules or enteric-coated tablets). Dosage for bleeding ulcers: 40 mg IV twice daily.

Caveats: Possible dose adjustment in severe liver failure, potential clinical interaction with clopidogrel (reduced effect), interaction with certain HIV medications and azoles.

Pantoprazole

Proton pump inhibitor. Available for intravenous and oral use. Almost fully metabolized in the liver via P-450, mainly by CYP2C19.

Brand names: Pantoprazole^®, Pantoloc^®.

Standard dose: 40 mg IV once daily; 20-40 mg orally once daily as enteric-coated tablets. Dosage for bleeding ulcers: 40 mg IV twice daily.

Caveats: Possible dose adjustment in severe liver failure, interaction with certain HIV medications, rifampicin, and St. John’s Wort.

Histamine-2 Receptor Blockers (H2 Blockers)

H₂-receptor blockers are chemically substituted aminoalkylfurans that competitively block the effects of histamine on H₂ receptors. This leads to reduced activation of the parietal cells and inhibits both basal and stimulated acid secretion. Tachyphylaxis can occur over time, with a reduced effect on gastric pH. The most common medication is ranitidine. H₂ receptor blockers are excreted mainly through the kidneys, likely via active secretion.

Brand names: Ranitidine^®, Inside Brus^®, Rani-Q^®, Stomacid^®, Zantac^®, Zantac Brus^®.

Standard dose: 50 mg IV three times daily or 150 mg orally twice daily as tablets or oral solution. If serum creatinine > 200 umol/l, CRRT, IHD, give a lower dose: 25 mg IV three times daily or 150 mg orally once daily.

Caveats: Risk of bradycardia with rapid infusion, possible dose adjustment in severe liver failure.

Sucralfate

Sucralfate is alkaline and contains aluminum sucrose sulfate. It binds to the mucosa, providing mechanical protection and stimulating factors that increase the mucosa’s resistance to harmful agents. Should be given 30 minutes before food intake.

Brand name: Andapsin^®. Available as tablets (Andapsin 1 g) or oral suspension (200 mg/ml).

Standard dose: 1 g (5 ml) four times daily.

Caveats: May affect the absorption of other medications in the gastrointestinal tract, risk of bezoar formation.

Literature

Nutritional Risk Score

Neostigmine

Neostigmine is a cholinesterase inhibitor that increases the concentration of acetylcholine, counteracting the effects of muscle-relaxing agents, and muscle activity and strength return after muscle relaxation during anesthesia. It is used to reverse the effects of non-depolarizing muscle relaxants at the end of anesthesia. Neostigmine can also be used to stimulate bowel peristalsis in cases of bowel paralysis and to increase muscle activity in myasthenia gravis. Neostigmine administration is preceded by intravenous administration of an anticholinergic (atropine sulfate or glycopyrrolate). Neostigmine is then given in doses of 0.5-2.5 mg (0.2-1 ml) intravenously. In rare cases, doses up to 5 mg (2 ml) may be required. The injection should be given slowly and with caution.

Concentration: 2.5 mg/ml IV.

Dosage

30-70 µg/kg. Standard dose for reversal: 2.5 mg = 1 ml. If the effect is insufficient, a half standard dose can be repeated (after 10-15 minutes) = 0.5 ml.

Routinely combined with an anticholinergic, such as atropine or glycopyrrolate, to prevent bradycardia and bronchospasm.

• Neostigmine 2.5 mg + 0.5 mg gly
  
  copyrrolate (Robinul) (1 ml).
• Neostigmine 2.5 mg (1 ml) + 0.5 mg atropine (1 ml).

Dosage for constipation: 1-2.5 mg IV.

Precautions

When combined with beta blockers, bradycardia and hypotension may occur.

Naloxone Hydrochloride Orally

Naloxone hydrochloride counteracts the inhibitory effect of opioids on bowel peristalsis by blocking my-receptors in the intestinal wall. Opiates inhibit bowel peristalsis by releasing acetylcholine in the parasympathetic nervous system, which increases muscle tone, reduces fluid secretion, and decreases bowel movements. Naloxone is absorbed from the gastrointestinal tract but is metabolized in the liver and does not produce systemic effects, only local effects in the intestine. Counteracting constipation can reduce the risk of nosocomial pneumonia during intensive care. Naloxone can be used in conjunction with other constipation treatments such as Movicol and Laxoberal drops.

Dosage: 5-8-10 ml x 3 via tube.

Indication: Opioid-induced constipation.

Concentration: 1 mg/ml (extemporaneous preparation).

Warning: Naloxone should not be given in severe liver failure, as it can cause systemic effects with central opioid antagonism due to reduced liver metabolism.

Methylnaltrexone (Relistor)

Opioid antagonist for parenteral use (subcutaneous injections) against opioid-induced constipation. Methylnaltrexone is a quaternary amine that cannot cross the blood-brain barrier and therefore acts selectively on intestinal receptors, producing no systemic effects but only local effects in the intestines. Relistor is primarily indicated in cancer patients but can also be used in ICU patients with opioid-induced constipation. Few studies have been conducted on ICU patients, but it likely has the same clinical effect as oral Naloxone. Opiates inhibit bowel peristalsis by releasing acetylcholine in the parasympathetic nervous system, increasing muscle tone, reducing fluid secretion, and decreasing bowel movements. Methylnaltrexone increases bowel transit and reduces oro-rectal transit time. It can be used in conjunction with other constipation treatments such as Movicol and Laxoberal drops.

Dosage: 8-12 mg once daily subcutaneously.

Indication: Opioid-induced constipation.

Concentration: Injectable solution 12 mg/0.6 ml.

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