Parenteral nutrition in intensive care – guidelines and treatment

Nutrition

Trauma and serious illness place extraordinary stress on the body, creating an absolute need for adequate nutrient intake to prevent the body from breaking down and the illness from being prolonged or worsened. Nutrition in anesthesia and intensive care is a basic part of treatment that can be categorized into enteral (via the intestine) and parenteral nutrition (via the bloodstream). Complete intravenous nutrition is commonly referred to as total parenteral nutrition (TPN). The body needs carbohydrates, fats, proteins, minerals, trace elements, and vitamins. TPN typically involves the administration of a fat emulsion, a carbohydrate solution, and an amino acid solution. Parenteral nutrition solutions are usually based on egg, soy, or peanut proteins and a fat emulsion. Fat emulsions are based on soybean oil, corn oil, and egg phospholipids. Electrolytes are added according to daily needs, as well as vitamins like Soluvit and Vitalipid, and trace elements like Tracel. This is often abbreviated as SVT (not to be confused with Sveriges Television). Contraindications for parenteral nutrition include egg, soy, or peanut allergies, severe liver failure, hyperlipidemia, and severe coagulation disorders. If plasma appears 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) generally starts after day 7

Enteral nutrition (EN) should be provided to all ICU patients who are not expected to consume regular food orally within three days. Nutrition should begin within the first 24 hours with a high-protein enteral nutrition solution. During the acute and initial phase of critical illness, 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 meet their nutritional intake goals with EN alone. There is no general indication for immunomodulating solutions in patients with severe illness or sepsis and APACHE II score >15. Glutamine should be supplemented in patients with burns or trauma.

EN should be chosen first for all ICU patients without absolute contraindications. It is beneficial to start early (<24-48 hours) to prevent disruptions to 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 movements, several key benefits are achieved.

There is no strong evidence of mortality benefits with EN compared to PN, but all comparative studies indicate reduced infections, dialysis needs, and costs (Singer et al., Clin Nutr 2009; Kreyman et al., Clin Nutr 2006). PN reliably meets calorie targets, but there is now strong evidence that parenteral nutrition is not entirely beneficial and carries risks in 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 has been associated with late initiation (ICU day 8) of supplemental PN. Therefore, a risk assessment must be made against malnutrition, which carries its own risks for poor wound healing, infections, and ultimately mortality. NRS is automatically calculated in the nutrition calculator to help assess and identify critically ill patients at high risk for malnutrition.

An NRS score ≥ 5 indicates a high risk of malnutrition and the need for early (day 3) supplemental parenteral nutrition, typically with a BMI of <20.5 or <22.5 depending on whether the patient is under or over 70 years of age. In cases of intermediate risk (NRS 3-4), supplemental parenteral nutrition is initiated on ICU day 8.

It is important to aim for the highest possible level of EN even during ongoing PN. High retentions should be actively managed and should only result in reduced or discontinued supply as a last resort. Virtually all patients tolerate some level of EN.

Basic Nutritional Needs

• The basic energy requirement is 25-30 kcal/kg/day, which corresponds to approximately 90 kJ/kg/day.
• The need for glucose is approximately 150-200 g/day.
• The need for fat is about 1-2 g/kg/day, typically 50-200 g/day.
• The need for nitrogen is 0.15-0.20 g/kg/day, 7-20 g N per day for body weight of 45-100 kg. In severe catabolic states, the need for nitrogen is 0.20-0.25 g nitrogen/kg/day.
• Basic fluid requirement is about 30 ml/kg/day. A healthy adult person needs about 1500-2500 ml of water per day.
• Basic electrolyte needs are 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 for Different Patient Categories per Day

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

• Newly arrived, acutely unstable patient
• Massive inotropic need, large volume need, vasopressor need
• SIRS
• Imminent threat of intubation
• 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 need and adrenergic support
• Deep sedation
• Can be started on day 1-2 if not extremely unstable
• Stabilization phase. Resuscitated patient, cardio-respiratory stabilized but with high cardio-respiratory vital function support
• Spinal cord injury patient with reduced metabolism

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

• Stable oxygen need and adrenergic need
• The course begins to reverse
• Plateau phase: The patient has passed the most intense phase of the 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 begins to use their own muscle strength. For example, a patient who is awake and begins to stand or cycle in bed with resistance.

Acute illness induces a catabolic phase followed by a prolonged anabolic phase during recovery. Severe illness increases energy metabolism and oxygen consumption. It also increases gluconeogenesis, lipolysis, and fat oxidation. Additionally, there is retention of water and sodium in the extracellular space, resulting in edema. Increased protein breakdown leads to muscle mass loss and increased nitrogen losses in the urine, as well as decreased glutamine content and reduced protein synthesis in skeletal muscles. Edema impairs organ function, increases the risk of respiratory failure, impairs protein synthesis, and decreases cellular function with failure of vital enzymes. Monitor daily fluid balance with TPN, weigh the patient at least three times a week, and make a clinical assessment of the patient’s nutritional status (SGA class). The patient can be categorized as well-nourished, slightly malnourished, or severely malnourished.

Subjective Global Assessment of Nutritional Status

SGA classification divides patients into three categories:

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

Increased body temperature increases energy needs by about 10% per degree of temperature rise. The energy supply requirement for ICU patients can be calculated using indirect calorimetry or by using standardized nutritional solutions as outlined in the guides in this chapter. In cases of hyperglycemia, insulin is administered according to a specific protocol, and the energy supply is usually not reduced. The goal is to maintain blood glucose between 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 not normally exceed 3 g/kg body weight per 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 TPN.

During parenteral nutrition, body temperature should be monitored daily along with total fluid balance and blood glucose. Nitrogen balance can be calculated if necessary by measuring urea in urine and serum. At least once a week, check serum albumin, phosphate, magnesium, zinc, liver function tests, creatinine, urea, and triglycerides.

Enteral nutrition should be initiated as early as possible in treatment, considering the risks of gastric retention, vomiting, aspiration, intestinal paralysis, and burdening intestinal anastomoses, as well as worsening the patient’s condition. Enteral nutrition should be chosen over parenteral nutrition when possible. Tube feeding generally provides 1 kcal/ml of energy value. If the stomach and intestines need to be relieved, parenteral nutrition administered intravenously is better. Initially, only carbohydrate-rich sugar solutions are given, while the supply of fats and proteins can wait 5-7 days. The timing of the initiation of parenteral nutrition is scientifically controversial. An older practice suggests that if the patient will not be able to eat orally within seven days, parenteral nutrition should be started within 3 to 7 days. Recent findings suggest that, in such cases, it is better to wait seven days, while common practice is to start parenteral nutrition on the third day and only provide glucose solutions on days one and two. A common approach is to use a combination of moderate enteral nutrition plus parenteral support.

Routes of Nutrient 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, intake of clear liquids may be allowed up to about two hours before anesthesia or before surgical or endoscopic procedures. Similarly, postoperatively, clear liquids may be prescribed before solid food intake to see if the intestines can absorb enteral fluids or if gastric retention is present. If gastric retention exceeds 400 ml/day, bowel rest is usually ordered, and nutrition is provided only parenterally.

Examples of clear liquids:

• Clear soup and broth without solid ingredients
• Resorb electrolyte solution
• Orange and apple juice without pulp. Avoid red, purple, or blue drinks
• Clear sports drinks
• Syrup, avoid red, purple, or blue syrup
• Coffee or tea (without milk)
• Water or clear carbonated beverages. Avoid light products

Nutrition Calculator

Follow the link to the nutrition calculator or click on the image.

Parenteral Nutrition

Parenteral nutrition (PN/TPN) is administered when nutritional needs cannot be met through oral and/or enteral nutrition. Where possible, PN should be combined with enteral nutrition. Initiate PN if nutrient intake is less than 50% of the requirement for a prolonged period that cannot be tolerated. Parenteral nutrition solutions consist of various components such as glucose, amino acids, triglycerides, and electrolytes intended for intravenous use. PN reliably meets calorie goals. The amount of nutrition is adjusted according to the patient’s nutritional level and general condition. There is evidence that parenteral nutrition is not entirely beneficial and carries some risks in critically ill patients. Conversely, there is no increased mortality or morbidity with late initiation (ICU day 8) of supplemental PN. Therefore, a risk assessment must be made against malnutrition, with its own risks of poor wound healing, infections, and, ultimately, mortality. PN is normally administered through a central venous catheter (CVC).

• Parenteral nutrition (PN) is generally started after day 7
• Early parenteral nutrition starts on day 3 (NRS ≥ 5)
• Enteral nutrition should be started within 24-48 hours

An NRS score of 5 or higher indicates a high risk of malnutrition, and the indication for early parenteral nutrition exists (day 3), typically with a BMI of <20.5 or <22.5 depending on whether the patient is under or over 70 years old. For intermediate risk (NRS 3-4), supplemental parenteral nutrition is initiated on ICU day 8.

Increased liver values during PN treatment typically indicate ongoing inflammation, steatosis (fat accumulation in liver cells), and/or impaired bile flow (cholestasis) in the liver. One should be particularly observant for cholestasis (i.e., conjugated bilirubin > 20 micromol/L), but even mild elevations in other liver values lasting more than a few days warrant consultation with a gastroenterologist for appropriate management and evaluation of other possible underlying causes. If it is determined that the liver involvement is PN-related, adjustments in the amount and type of fat in the PN solution may be necessary, often in combination with adjustments in glucose and protein content. This type of liver dysfunction that occurs with relatively short-term PN use is generally benign and reversible.

The most serious form of liver disease associated with PN treatment is seen in patients with intestinal failure undergoing long-term PN. This condition is known as “Intestinal Failure Associated Liver Disease” (IFALD) (formerly referred to as “Parenteral Nutrition Associated Liver Disease/Cholestasis,” PNALD/PNAC), a progressive liver disease seen in these patients. The diagnosis is clinical and requires, in addition to intestinal failure and long-term PN, the presence of cholestasis (conjugated bilirubin > 20 micromol/L). The cause is multifactorial, but the risk of developing IFALD can be reduced by using optimally composed PN solutions, primarily in terms of fat composition. Modified fat composition (fish oil-based fat emulsion) in PN is also the basis for treating already developed IFALD.

Preparations

A variety of nutritional solutions are presented below in table format. SmofKabiven may be preferred in cases of liver failure.

Trace Elements and Other Additives

• Cernevit and Tracel are added to SmofKabiven.
• During ongoing CRRT, amino acids and water-soluble vitamins are lost, so protein intake is increased to 1.3-1.5 g/kg ideal body weight/day, along with an extra dose of Solu-Vit.
• Addex Magnesium and Glycophos can be added to SmofKabiven, but the shelf life is only 24 hours. In one liter of glucose, 5% and 10%, a maximum of 20 mmol Magnesium, 40 mmol Glycophos, and 80 Potassium can be added without risk of precipitation. If more Glycophos needs to be added, a maximum of 100 mmol can be added to 1000 ml of fluid without other additives and administered over at least 8 hours. If fluid intake needs to be minimized, e.g., only SmofKabiven and no glucose, 20 mmol Glycophos can be added to 100 ml NaCl over 8 hours. Mg is also given separately: 10-20 mmol in 100 ml sodium chloride solution.
• Betabion should be given at BMI <20 and in cases of alcohol-related problems.
• Zinc in the form of effervescent tablets in an NG tube should be given from day 15 and during Prisma treatment.

Compatibility

Parenteral nutrition solutions can consist of various components such as glucose, amino acids, triglycerides, and electrolytes, making them complex in terms of compatibility. A three-chamber bag contains all of these components, while other nutritional solutions may consist of one or more of these components. The fat emulsion is the weakest link from a physical-chemical perspective. Emulsions require a stable chemical environment regarding pH, electrolyte concentrations, and other charged substances. If a large amount of electrolytes is added or if the addition causes a change in the overall pH of the bag, the emulsion may break, causing fat emboli in small vessels, such as in the lungs. Compatibility information can be found in various mixing databases. The assessment applies to PN solution with the addition of vitamins and trace elements. If further additives are made, a new compatibility assessment must be made by a pharmacist.

Identify Possible Malnutrition

The assessment is primarily clinical. It is indicated by a BMI ≤ 20.5 or 22.5 at age ≥ 70, a history or documented inadequate food intake prehospital or hospital, widespread cancer, anorexia nervosa, obstructive or functional gastrointestinal disease, etc. Use ESPEN’s Nutritional Risk Screening (NRS-2002), which is programmed into the nutrition calculator.

ESPEN’s screening tool for malnutrition, Nutritional Risk Screening (Kondrup et al., Clin Nutr 2003).

The nutrition calculator automatically calculates NRS based on age, nutritional status, and the severity of the illness (degree of catabolic insult). Critically ill ICU patients always receive 3 points. For automatic NRS calculation, and because it is not always possible to obtain a history from ICU patients, point allocation for current nutritional status is rationalized, giving 1 point for BMI <22.5 and 0 points for higher values.

NRS ≤ 4 Points

Intermediate risk of malnutrition. Use nutritional drink or enteral tube feeding (EN). Start/supplement with parenteral nutrition on ICU day 8.

NRS ≥ 5 Points

High risk of malnutrition. If the patient does not achieve at least 80% of their calorie goal (25 kcal/kg/day) with EN, supplement with parenteral nutrition starting on day 3.

Assess Whether the Patient Should Receive Nutrition

Patients who are not expected to meet their own food intake within 3 days need specialized nutritional support (SN). The type of SN is adapted to the patient and clinical status. Special attention should be given to malnourished patients with critical illness.

Calculate Nutritional Parameters

The patient should be weighed and measured upon arrival at the ICU. Exceptions can only be made if the patient can provide their height and weight, or if the information is documented in Melior or on the anesthesia curve. Then use tables, the nutrition calculator, or the formulas below to calculate Body Mass Index (BMI), Ideal Body Weight (IBW), and BMI-corrected IBW (cIBW). Document these values on the daily journal.

Determine Nutrition Level and Caloric Intake

Caloric intake is calculated using BMI-corrected IBW and nutritional levels. This means that “lean” patients receive slightly more calories relative to their current weight. Similarly, overweight patients receive slightly fewer. Determine the nutrition level and plan for an increase over 2-3 days. Levels with explanations are available in the nutrition calculator.

Assess Possible Nutrition Route

Enteral nutrition (EN) should be started if possible within 48 hours. If the patient is already receiving parenteral nutrition (PN) upon arrival at the ICU, continue but repeatedly attempt to start EN unless absolute contraindications exist.

If contraindications to EN exist, or if full EN is not achieved, supplement with PN (sPN). The appropriate time to start sPN depends on the degree of malnutrition risk, as assessed clinically or using NRS-2002. sPN is routinely started on ICU day 8 with NRS ≤ 4; with NRS ≥ 5, sPN starts on ICU day 3.

Compose the Nutrition’s Content

Use the nutrition calculator, which is available as a link on the homepage. Plan the daily amount of calories and distribution of fluids, including other medications. Observe the total amount of water depending on different fluid and medication choices, and adjust with an appropriate glucose solution. The calculation does not need to be saved but can be printed as a work document.

Prescribe in the Daily Journal

The planned preparations and amounts should be prescribed and signed on the daily journal after calculations are completed. The selected nutrition level should be noted along with the planned calorie intake in the nutrition section of the daily journal.

Document the Amount of Energy Administered

Use the nutrition calculator available as a link on the homepage. Record the amount of calories given in the fluid balance list every day.

Follow Up and Adjust

Nutritional goals and prescriptions are adjusted continuously based on the patient’s illness progression. Note that certain medications may contribute to overnutrition.

• Propofol is dissolved in a fat emulsion that contains 1.1 kcal/ml.
• Nimotop infusion is dissolved in alcohol and contains 1.4 kcal/ml.

Nutrition Monitoring

Energy Supply

• The amount of energy supplied is calculated daily using the second sheet of the nutrition calculator.

Nutritional Needs

• Daily assessment of general condition and nutrition level.

Nutritional Deficit

• Discrepancy between prescribed and administered energy. Tracked daily via the calculator and fluid balance list.

Nutritional Surplus

• Signs that metabolism is not functioning adequately.

Weight

• Daily

Electrolytes and Glucose

• 4-6 times per day.
• S-Albumin, S-Magnesium, S-Phosphate twice a week (Monday and Thursday).
• S-Triglycerides once a week (Mondays). Should be <4.

References

1. Caeser et al., N Engl J Med 2011.
2. McClave et al., J Parent Enteral Nutr 2009.

Parenteral Nutrition Solutions

Suggestions for Parenteral Nutrition for Different Body Weights

Lightweight Adult Person 40-60 kg

Normal-weight Adult Person 60-80 kg

Heavyweight Adult Person >80 kg

Constipation

Constipation is a common problem among ICU patients. Critically ill patients receive several medications that negatively affect normal bowel function, primarily opioids. Immobility, reduced consciousness, and the absence of normal food intake inhibit central regulation of the enteric nervous system, gastrointestinal hormones, and normal trophic stimulation of the intestinal mucosa’s function and microstructure. Just like the skeleton and muscles, the intestinal mucosa atrophies quickly, and smooth muscle activity is reduced or stops.

• 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 according to routine. Best effect if both sachets are given with less than 4-6 hours apart. Movicol is an osmotically active laxative that absorbs water in the colon, increases fecal water content, and “softens the stool.” If there is no effect or fecal impaction, the dose is increased, first to 8 sachets per day.
• If fecal impaction or other bowel obstruction cannot be ruled out, order a CT abdomen plain film (CT-BÖS).
• In the second step, consider Laxoberal drops, 10-20 drops are given at 10 p.m. and supplemented with 2 suppositories of Dulcolax the next morning. Repeat daily until results are achieved.
• In the third step, consider Klyx.
• In the fourth step, consider oil enemas. Mix 300 ml of oil with 700 ml of lukewarm water. Start with the patient on their left side, administer 1/3 of the enema, then give 1/3 while in a supine position, and 1/3 on the right side.
• Do not give laxatives to patients with spinal cord injuries or suspected obstructive ileus.
• Be cautious with SAH due to the risk of spasm. Once laxation is achieved, restart the scheme from the beginning.

Gastrointestinal Stimulating Drugs

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 treatment duration 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 the treatment of fecal impaction, up to 8 sachets of Movicol may need to be given 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 in ready-to-drink oral solution form.

Metoclopramid (Primperan®)

Injection solution, 5 mg/ml. Dosage: 2 ml (10 mg) x 3 IV (dose reduction may be necessary in renal insufficiency).

• Promotes gastric emptying
• Counters dopamine’s inhibitory effect on motility
• Increases intestinal sensitivity to acetylcholine
• Increases sphincter tone in the cardia
• Risk of interaction with other medications
• High doses can cause extrapyramidal side effects

Naloxone Hydrochloride

Oral ex tempore preparation 1 mg/ml.

Dosage: 5-8 ml x 3 via NG tube may be tried if the above has not produced the desired effect during concurrent opioid treatment.

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

Methylnaltrexone (Relistor®)

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

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

Laxoberal Drops

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 10 p.m. Stimulates the colon and rectum.

Dulcolax

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

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

If no bowel movement occurs after 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, then give 1/3 while in a supine position, and 1/3 on the right side. Do not administer laxatives to spinal cord-injured patients or in suspected obstructive ileus. Be cautious with SAH due to the risk of spasms.

Other Gastrointestinal Stimulating Drugs

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

Ulcer Prophylaxis

Severe gastrointestinal bleeding (GI bleeding) has been reported in scientific studies in 1.5-8.5% of critically ill patients and has been associated with increased mortality in some studies¹. Recent studies suggest that the risk of GI bleeding may be lower, likely due to improved critical care or better ulcer prophylaxis². Stress ulcers can develop in all critically ill patients within hours due to severe stress, major injury, surgery, shock, or infection. Ulcerations can range from erosive gastritis to perforated ulcers, usually shallow, with minor capillary bleeding, but they can erode into the submucosa and become more severe. Underlying blood vessels can be damaged, causing bleeding, or, in rare cases, perforation of the mucosa. The ulcers likely result from an imbalance between the protective mucosal barrier and acid production in the stomach.

The mucosal barrier contains glycoproteins, providing a physical barrier but also binding bicarbonate, which neutralizes stomach acid. In many critically ill patients, the function of the mucosal layer is impaired due to reduced blood flow. Reflux of bile and uremic toxins may also contribute to mucosal damage³.

Acid production in the stomach is increased in head-injured patients, but probably not in other critically ill patients⁴. Helicobacter pylori infection may be a contributing factor to stress ulcers⁵.

Stress ulcers are most common in the fundus and body of the stomach, but they can also develop in other parts of the gastrointestinal tract, such as the duodenum and distal esophagus⁶.

In a large prospective multicenter study, a significantly increased risk of stress ulcers was seen in patients who were mechanically ventilated for more than 48 hours and/or had coagulopathy, compared to other critically ill patients⁷. Other studies have also indicated increased risk in other serious conditions such as head injury, shock, sepsis, liver and kidney failure, trauma, major burns, organ transplantation, previous upper gastrointestinal bleeding, and high SOFA scores^8–13.

Enteral nutrition itself has a protective effect by buffering stomach acid, increasing mucosal blood flow, and inducing the secretion of cytoprotective prostaglandins and mucus¹⁵.

It is unclear, however, whether pharmacological prophylaxis can be withheld in patients on enteral nutrition^16,17. One study showed that H2 blockers in enterally fed patients actually led to increased mortality¹⁸.

Pharmacological prophylaxis

To reduce the risk of developing ulcers, pharmacological prophylaxis is commonly used in critically ill patients, either administered parenterally or orally. The three main types of drugs used for prophylaxis are proton pump inhibitors (PPIs), histamine-2 receptor blockers, and sucralfate. It is not entirely clear which patients should receive pharmacological prophylaxis and what effect the prophylaxis has. Indications for prophylaxis and drug choice vary across Sweden and internationally. There is no scientific support for routine ulcer prophylaxis in all critically ill patients. Recent studies have shown questionable effects of PPI prophylaxis¹⁹, but they have not shown significant harm either.

Currently, pharmacological ulcer prophylaxis is recommended for patients with:

• More than 48 hours of mechanical ventilation
• Coagulopathy (platelet count <50, INR >1.5x reference value, APTT >2x reference value)
• Gastrointestinal bleeding within the last year
• Traumatic brain injury, traumatic spinal injury, or major burns
• Two of the following: sepsis, intensive care longer than 1 week, occult gastrointestinal bleeding for more than 6 days, corticosteroid therapy (>250 mg hydrocortisone/day)

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

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

Enteral nutrition is likely protective and should be started early, but there is currently not enough evidence to withhold ulcer prophylaxis in high-risk patients even with enteral nutrition.

Ulcer prophylaxis should be evaluated and discontinued when the patient is no longer in a risk group or when intensive care is discontinued.

The three drug types used for prophylaxis are proton pump inhibitors (PPIs), histamine-2 receptor blockers, and sucralfate. PPIs seem to be more effective than H2 blockers in preventing stomach ulcers^20,21, although some studies show otherwise²². The choice of drug often depends on local practices, but proton pump inhibitors are more frequently used in Sweden than other drugs. Sucralfate provides less protection against stress ulcerations but may carry a lower risk of nosocomial pneumonia.

Risks

Ulcer prophylaxis raises the pH in the stomach, allowing bacterial overgrowth in the stomach lining. Through reflux, these bacteria reach the throat, where they can be aspirated into the airways, resulting in pneumonia, a condition known as ventilator-associated pneumonia (VAP). There may be an increased risk of VAP when treating patients with stress ulcer prophylaxis. This risk may be greater with PPIs than with sucralfate and H2 receptor blockers²³. There is also an increased risk of Clostridium difficile gastroenteritis due to the higher pH in the stomach²⁴.

Drugs for Stress Ulcer

Proton Pump Inhibitors

These drugs are substituted benzimidazoles that reduce the secretion of hydrochloric acid by specifically blocking the proton pumps in the parietal cells. Commonly given are omeprazole, esomeprazole, or pantoprazole. The drugs have a similar effect. The drugs are converted to their active form in the acidic environment of the parietal cells, where they inhibit the H⁺/K⁺-ATPase enzyme, i.e., the final step in stomach acid production. This results in inhibition of both basal and stimulated acid secretion in the stomach, independent of the stimulating system such as acetylcholine, histamine, and gastrin²⁵. Omeprazole, like all acid-blocking drugs, may 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 racemate of two enantiomers that specifically inhibits the acid pump in the parietal cell. It has a fast onset of action, and the 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 H⁺K⁺-ATPase enzyme – the acid pump. The effect on the final step of the acid secretion process is dose-dependent and provides very effective inhibition of both basal and stimulated acid secretion, independent of the type of stimulation.

Trade names: Omeprazole®, Losec®, Omecat®, Omestad®, Omezomyl®.

Standard dose: 20-40 mg orally once daily.

Dosage for bleeding ulcers: 40 mg twice daily.

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

Esomeprazole

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

Trade names: Esomeprazole®, Nexium®, Vimovo®.

Standard dose: 40 mg IV once daily; 20-40 mg orally once daily, granules or enteric-coated tablet. Bleeding ulcers: 40 mg IV twice daily.

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

Pantoprazole

Proton pump inhibitor. Available for intravenous and oral use. Virtually complete liver metabolism via P-450, primarily CYP2C19.

Trade names: Pantoprazole®, Pantoloc®.

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

Caution: 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 histamine’s effect on H2 receptors. This leads to reduced activation of parietal cells and inhibits both basal and stimulated acid secretion. Tachyphylaxis occurs over time, with decreased effect on stomach pH. The most common drug is ranitidine. H2 receptor blockers are primarily excreted by the kidneys, likely via active secretion.

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

Standard dose: 50 mg IV 3 times daily or 150 mg orally twice daily as a tablet or oral solution. If S-Creatinine >200 umol/L, CRRT, IHD, give lower dose: 25 mg IV 3 times daily or 150 mg orally once daily.

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

Sucralfate

Sucralfate is alkaline and contains aluminum saccharose sulfate. It binds to the mucosa, providing mechanical protection and stimulating factors in the mucosa that increase its resistance to harmful agents. Preferably given 30 minutes before food intake.

Trade names: Andapsin®. Available as a tablet Andapsin 1 g or oral suspension 200 mg/ml.

Standard dose: 1 g (5 ml) 4 times daily.

Caution: Affects the absorption of other medicines in the gastrointestinal tract, risk of bezoar formation.

Referenser

Nutritional Risk Score