Handbook of Critical Care Drug Therapy

Editors: Susla, Gregory M.; Suffredini, Anthony F.; McAreavey, Dorothea; Solomon, Michael A.; Hoffman, William D.; Nyquist, Paul; Ognibene, Frederick P.; Shelhamer, James H.; Masur, Henry

Title: Handbook of Critical Care Drug Therapy, 3rd Edition

Copyright 2006 Lippincott Williams & Wilkins

> Table of Contents > Chapter 7 - Gastroenterology, Liver, and Nutrition Therapies

Chapter 7

Gastroenterology, Liver, and Nutrition Therapies

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TABLE 7.1. Gastrointestinal Hemorrhage Available Therapies

Clinical Setting Suggested Therapy Dosage Comments
Acute Treatment
Acute upper GI hemorrhage Omeprazole 40 mg PO/NG q8 12h 5 d Omeprazole is a sustained-release capsule that may be opened, but the contents must not be crushed before administration; the powder for oral suspension should be used in this setting
  Pantoprazole 40 80 mg IV bolus followed by 8 mg/h for 2 3 d  
  H2 antagonists or Vasopressin H2 antagonists: (see Table 7.4)  
    Vasopressin: 0.2 0.3 U/min IV, maximum 0.9 U/min Monitor ECG; use nitroglycerin prophylactically in patients at risk for cardiac ischemia
Acute variceal hemorrhage Octreotide 50 100 g bolus, followed by continuous infusion at 50 100 g/h for 24 48 h More effective in controlling bleeding than vasopressin with less side effects (e.g., headache, chest pain, abdominal pain)
  Vasopressin 0.2 0.3 U/min IV, maximum 0.9 U/min See acute upper GI hemorrhage
Acute lower GI hemorrhage Vasopressin 0.2 0.3 U/min IV, maximum 0.9 U/min See acute upper GI hemorrhage
Prophylaxis
Prophylaxis against stress gastritis H2 antagonists, Sucralfate, proton pump inhibitors, or antacids H2 antagonists: see Table 7.4

Sucralfate: 1 2 g PO/NG q4 6h

Lansoprazole 30 mg IV qd

Pantoprazole 40 mg IV qd

Esomeprazole 20 mg IV qd

Omeprazole 20 mg PO/NG qd

 H2 antagonists and antacids: titrate pH >4; may predispose to nosocomial pneumonia

Sucralfate: no effect on pH

Limited data supporting the use of proton pump inhibitors for stress ulcer prophylaxis

Omeprazole is a sustained-release capsule that may be opened but the contents must not be crushed before administration; the powder for oral suspension should be used in this setting
Prevention of recurrent upper GI hemorrhage H2 antagonists or antacids H2 antagonists: see Table 7.4

Antacids: 30 ml PO/NG q2h (or continuously at 0.5 ml/min)

 See stress gastritis
Prevention of recurrent variceal hemorrhage -blockers Propranolol 10 mg PO qid Titrate to 25% reduction in resting heart rate

Consider sclerotherapy or surgery
ECG, electrocardiogram; GI, gastrointestinal; IV, intravenous; NG, nasogastric; PO, by mouth

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TABLE 7.2. Hepatic Encephalopathy Therapies

Clinical Setting Dosage Comments
Acute hepatic encephalopathya Lactulose: 30 45 ml PO/NG q1h until laxative effect occurs, then 30 45 ml tid

Neomycin: 1.5 6 g/d PO/NG divided q6 8h

 Lactulose retention enema: 300 ml lactulose in 700 ml water or saline PR for 30 60 min q4 6h
Chronic hepatic encephalopathy Titrate dose to 2 3 soft stools/day  
PO, by mouth; PR, per rectum; NG, nasogastric

aElectrolyte correction, avoidance of sedatives and narcotics, and attention to volume status, nutrition, intracranial pressure, and infection are also indicated.

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TABLE 7.3. Antacids

Composition/Preparation Content per 15 ml      
Al+2 Mg+2 SMC Acid Neutralizing Content (mEq per ml) Sodium Content (mg per 15 ml) Dosage
Aluminum Hydroxide Plus Magnesium Hydroxidea,b
Maalox TC 1,800 900 0 5.44 2.40 5 10 ml qid
Maalox 675 600 0 2.66 4.20 10 20 ml qid
Aluminum Hydroxide Plus Magnesium Hydroxidea,b Plus Simethicone
Mylanta 600   60 2.54 2.04 10 20 ml 4 6 d
Mylanta Double Strength 1,200 1,200 120 5.08 3.42 10 20 ml tid
Extra StrengthMaalox Plus 1,500 1,350 120 5.8   10 20 ml qid
Aluminum Hydroxidec,d
AlternaGel 1,800 0 0 3.2 7.50 15 30 ml 3 6 d
Amphojel 960 0 0 2 6.90 10 ml 4 6 d
Magaldrate (Aluminum and Magnesium Oxides)
Riopan

Pluse

 0 0 0 3 0.30 15 30 ml qid
SMC, simethicone

aMagnesium containing antacids may cause diarrhea.

bHypermagnesemia may occur in patients with renal failure who receive magnesium containing antacids.

cAluminum containing antacids may cause constipation.

dAluminum containing antacids may cause hypophosphatemia.

eContains the equivalent of 29% to 40% magnesium oxide and 18% to 26% aluminum oxide.

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TABLE 7.4. Nonantacid Therapies for Gastritis

Therapy Usual Dosage Comments
H2 Antagonists
Cimetidine Intermittent: 300 mg IV q6 8h

Infusion: 37.5 mg/h

PO/NG: 300 mg q6h

 Adverse effects: altered mental status, thrombocytopenia, elevated liver enzymes, many drug interactions
Famotidine Intermittent: 20 mg IV q12h

Infusion: not applicable

PO/NG: 20 mg q12h

 Adverse effects: altered mental status, thrombocytopenia, elevated liver enzymes
Ranitidine Intermittent: 50 mg IV q6 8h

Infusion: 6.25 mg/h

PO/NG: 150 mg q12h

 Adverse effects: altered mental status, thrombocytopenia, elevated liver enzymes
Proton Pump Inhibitors
Esomeprazole PO/NG: 20 40 mg qd Enteric-coated granules in capsule form may be opened, but contents must not be crushed before administration

NG administration: Empty capsule contents into 60 ml syringe and mix with 50 ml water; vigorously shake syringe for 15 s; flush NG tube with additional water after administering granules; do not administer if pellets have dissolved or disintegrated

Do not administer with meals

Adverse effects: headache, nausea, vomiting, diarrhea, abdominal pain, potential drug interactions
Lansoprazole PO/NG: 15 30 mg qd Enteric coated granules in capsule form may be opened, but contents must not be crushed before administration

The contents of the capsule can be emptied into 60 ml of tomato, apple, or orange juice and swallowed immediately

The contents of the oral suspension packet should be mixed with 30 ml of water

The oral disintegrating tablet should be placed on the tongue and allowed to disintegrate with or without water; the tablet should dissolve within a minute and should not be swallowed intact or chewed. Alternatively a 15-mg tablet may be placed into an oral syringe with 4 ml of water or a 30 mg tablet with 10 ml of water; gently shake to allow quick dispersal; after tablet dispersal administer contents; refill syringe with 2 ml water, shake gently, and administer remaining contents

Do not administer with meals
Omeprazole PO/NG: 20 mg qd Sustained-release capsule may be opened, but contents must not be crushed before administration; the powder for oral suspension should be used in this setting

Do not administer with meals
Pantoprazole PO: 40 mg qd Swallow tablets whole, with or without food

Do not split, chew, or crush tablets
Rabeprazole PO: 20 mg qd Swallow tablets whole, with or without food

Do not split, chew, or crush tablets
Other Agents
Sucralfate (a sulfated disaccharide) PO/NG: 1 g qid Sucralfate has no effect on gastric pH

Available as suspension 1 g/10 ml

Tablets may be crushed and dissolved in 30 ml of water for administration through an NG tube

Adverse effects: constipation, hypophosphatemia, bezoar formation especially in patients receiving tube feedings
Other Conditions
Helicobacter pylori Bismuth subcitrate 2 262 mg qid + metronidazole 250 mg tid + amoxicillin 500 mg qid or 1 g bid or Tetracycline 500 mg qid 14 d Alternative regimen:

Clarithromycin 500 mg tid + omeprazole 40 mg qd 14 d
Misoprostol (prostaglandin) PGE1 Prevention of NSAID-induced ulcers: 200 g PO bid-qid

Gastric or duodenal ulcer: 100 200 g PO bid-qid

 Contraindicated in pregnant women

Adverse effects: diarrhea, nausea, abdominal pain
IV, intravenous; NG, nasogastric tube; NSAID, nonsteroidal anti-inflammatory drug; PO, by mouth

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TABLE 7.5. Antiemetics

Agent Usual Indication Dosage Comments
Phenothiazines
Prochlorperazine Postoperative; chemotherapy PO/IM/IV: 5 10 mg q6 8h

PR: 25 mg q12h

 Extrapyramidal effects, drowsiness, blurred vision

Not effective for motion-induced nausea and vomiting
Promethazine Postoperative; motion-induced PO/IM/IV/PR: 12.5 50 mg q4 6h Drowsiness, dry mouth, confusion, blurred vision
Antihistamines
Hydroxyzine Postoperative; motion-induced IM/IV: 25 100 mg q4 6h Drowsiness, dry mouth, confusion, blurred vision
Trimetho-benzamide Postoperative PO: 250 mg tid or qid IM/PR: 200 mg tid or qid Parkinson-like symptoms, drowsiness, blurred vision, hypotension

Less effective than phenothiazines
5-HT3-antagonists     Should not be used for routine nausea and vomiting; traditional antiemetics are the preferred agents
Dolasetron Chemotherapy-induced nausea and vomiting resistant to standard antiemetic regimens IV/PO: 100 mg 30 60 min before chemotherapy Serotonin antagonist

Side effects include diarrhea, headache, constipation

Use for prophylaxis of chemotherapy-induced nausea and vomiting; not effective once vomiting starts
  Postoperative IV: 12.5 mg 15 min before cessation of surgery or as soon as nausea and vomiting presents Conventional antiemetic agents should be tried if single dose ineffective
Ondansetron Chemotherapy-induced nausea and vomiting resistant to standard antiemetic regimens IV: 16 32 mg as a single dose administered 30 min before chemotherapy

PO: 8 mg 30 min before chemotherapy regimens; repeat doses 4 h and 8 h after chemotherapy; then 8 mg tid for 1 2 d

 Serotonin antagonist

Side effects include diarrhea, headache, constipation

Use for prophylaxis of chemotherapy-induced nausea and vomiting; not effective once vomiting starts

Fewer treatment failures with single dose compared to multiple dose
  Postoperative IV: 4 8 mg as a single dose Conventional antiemetic agents should be tried if single dose ineffective
Granisetron Chemotherapy-induced nausea and vomiting resistant to standard antiemetic regimens IV: 10 g/kg IVP starting 30 min before the emetogenic drug

PO: 1 mg bid

 Side effects include headache, asthenia, somnolence, diarrhea, and constipation

May not be effective for delayed onset nausea and vomiting
  Postoperative IV: 20 40 g/kg as a single dose Conventional antiemetic agents should be tried if single dose ineffective
Others
Metoclopramide Chemotherapy PO/IV: 1 2 mg/kg before chemotherapy, followed by 2 mg/kg q2h 2, then q3h 3 Dopamine receptor antagonist

Extrapyramidal effects, drowsiness, fatigue
Scopolamine Prophylaxis against motion-induced nausea and vomiting Topical: 1 patch q72h Belladonna alkaloid

Dry mouth, drowsiness, mental status changes
Dexamethasone Chemotherapy-induced nausea and vomiting resistant to standard antiemetic regimens IV: 10 20 mg before chemotherapy, then 4 8 mg IV/PO q8h 1 5 d postchemotherapy Side effects include mood changes, anxiety, euphoria, hyperglycemia
Lorazepam Chemotherapy-induced nausea and vomiting resistant to standard antiemetic regimens IV: 0.5 1.5 mg/M2 total dose before chemotherapy Useful for anticipatory nausea and vomiting

Side effects include drowsiness, sedation, disorientation, hallucinations, amnesia
IM, intramuscular; IV, intravenous; IVP, IV push; PO, by mouth; PR, per rectum

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TABLE 7.6. Antidiarrheals

Agent Composition Dosage/Adverse Effects Actions/Interactions/Comments
Imodium Loperamide 2 mg capsule, 1 mg/5 ml liquid, 1 mg/ml liquid 4 mg initially, then 2 mg after each loose stool up to 8 mg/d

Bloating, abdominal pain, drowsiness, dizziness, dry mouth, nausea, vomiting

 Drug action: decreases GI motility, may possess antisecretory activity

Drug interactions:a,b

Comments:c
Donnagel, Parepectolin Attapulgite 600 mg per 15 ml 30 ml after each loose bowel movement up to 7 d

Constipation

 Drug action: absorbs bacteria and toxins, reduces water loss

Drug interactions:d

Comments:c
Kaopectate advanced formula Attapulgite 750 mg per 15 ml 30 ml after each loose bowel movement up to 7 d

Constipation

 Drug action: absorbs bacteria and toxins, reduces water loss

Drug interactions:d

Comments:c
Lomotil Diphenoxylate 2.5 mg and atropine 25 g per tablet or per 5 ml syrup 1 2 tabs or 5 10 ml qid

Bloating, abdominal pain, drowsiness, dry mouth, blurred vision, nausea vomiting, urinary retention

 Drug action: reduces GI motility

Drug interactions:a,b

Comments:c
Deodorized tincture of opium (DTO) Opium 10% 0.6 ml qid

Constipation, drowsiness

 Drug action: reduces GI motility

Comments:c

Contains 10 mg of anhydrous morphine per 1 ml
Paregoric Camphorated tincture of opium 5 10 ml qid-qd

Constipation, drowsiness

 Drug action: reduces GI motility

Comments:c

Contains 10 mg of anhydrous morphine per 5 ml
Octreotide Synthetic analogue of endogenous somatostatin 100 600 g/d SC bid-qid

Nausea, cramping, and pain at injection site

 Drug action: blocks release of serotonin and other active peptides; especially useful in watery diarrhea syndromes such as carcinoid tumors and vasoactive intestinal peptide-secreting tumors (VIP-omas)
Pepto-Bismol Bismuth subsalicylate 262 mg per 15 ml 30 ml q30min 1h, up to 8 doses/d

Salicylate toxicity, dark Hemoccult-negative stools

 Drug action: unknown

Drug interactions:d,e
CNS, central nervous system; GI, gastrointestinal; ICU, intensive care unit; SC, subcutaneous

Note: Should be used with caution in any ICU setting until pathogenesis clearly established.

aAdded CNS depressant effects.

bAdded anticholinergic effects.

cShould not be administered in the presence of pseudomembranous colitis.

dDecreased digitalis absorption.

eMay have additive platelet inhibitory effects.

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TABLE 7.7. Infectious Diarrhea Agents of Choice for Common Treatable Pathogens

Organism Primary Therapy Alternative Therapy Comments
Aeromonas hydrophila TMP-SMX

1 DS tablet PO bid 5 d

 Ciprofloxacin 500 mg PO bid 5 d  
Campylobacter jejuni Erythromycin 250 500 mg PO qid 7 d Ciprofloxacin 500 mg PO bid 7 d, or

Doxycycline 100 mg PO bid 7 d

Azithromycin 500 mg PO qd 3 d

 Therapy should begin early in the course of the disease
Clostridium difficile Metronidazole 250 500 mg PO tid 7 14 d Vancomycin 125 mg PO qid 7 14 d, or

Bacitracin 25,000 U PO qid 7 d

Vancomycin 1 g IV q12h

 Relapses should be treated with longer courses of vancomycin
Escherichia Coli
Enterotoxigenic (ETEC) Bismuth subsalicylate 60 ml PO qid 5 d Trimethoprim 200 mg PO bid 5 d  
Entero-adherent (EAEC) TMP-SMX 1 DS tablet PO bid 5 d Ciprofloxacin 500 mg PO bid 5 d, or

Doxycycline 100 mg PO bid 5 d

  
Enterohemorrhagic (EHEC) Ciprofloxacin 500 mg PO bid 5 d    
Entero-invasive (EIEC) Ampicillin 500 mg PO or 1 g IV qid 5 d    
Enteropathogenic (EPEC) TMP-SMX 1 DS tablet PO bid 5 d Neomycin 100 mg/kg/d PO 3 5 d  
0157-H7 None   TMP-SMX may be contraindicated
Food Poisoning

(C. perfringes, S. aureus, B. cereus, Listeria)

 None   Self-limited disease; does not require antibiotic therapy
Salmonella species
Uncomplicated enterocolitis None    
Enteric fever (nontyphoid salmonella) TMP-SMX 1 2 DS tablets PO bid 14 d Ampicillin 2 6 g/d IV/ PO 14 d, or

Ciprofloxacin 500 mg PO bid 14 d, or

Ceftriaxone 1 g IV q12h 14 d, or

Cefotaxime 4 8 g/d IV 14 d, or

Chloramphenicol 3 4 g/d IV 14 d

  
Shigella Ciprofloxacin 500 mg PO bid 3 5 doses Norfloxacin 400 mg PO bid 3 5 d, or

TMP-SMX 1 DS tablet PO bid 3 5 d, or

Ampicillin 0.5 1 g IV/PO qid 3 5 d

 Preferred agents are ciprofloxacin, norfloxacin, or TMP-SMX
Vibrio cholera Doxycycline 300 mg PO 1 d Ciprofloxacin 1 g PO 1 d  
Vibrio parahemolyticus None    
Yersinia enterocolitica Ciprofloxacin 500 mg PO q12h 3 doses Ceftriaxone 2 g IV qd  
DS, double strength; IV, intravenous; PO, by mouth; TMP-SMX, trimethoprim-sulfamethoxazole

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TABLE 7.8. Energy Expenditure Calculations

Method Equation Comments
Indirect calorimetry Patient-specific energy expenditure Requires metabolic cart for determinations
General recommendations Low stress (UUN 5 10 g/d): 20 kcal/kg/d Simple starting point for most patients
  Moderate stress (UUN 10 15 g/d): 25 30 kcal/kg/d Fat 10 kcal/kg/day = 1 g/kg/day
  High stress (UUN >15 g/d): 35 kcal/kg/d Protein 1.5 g/kg/day or adjusted for level of renal function

Maintain glucose infusion rate <5 mg/kg/min
American College of Chest Physicians Guidelines 25 total calories/kg/day

Glucose: 30% to 70% of total calories

Fat: 15% to 30% of total calories

Protein: 10% to 15% of total calories

 Calories based on usual body weight

Glucose: keep blood glucose <225 mg/dl

Fat: keep triglyceride <500 mg/dl

Protein: 1.2 1.5 g/kg/day, keep BUN <100 mg/dl
Hemodynamic equations Energy expenditure (kcal/d) = 95.18 (hemoglobin cardiac output (SaO2 - SvO2) Equation has not been validated prospectively in critically ill patients.

Values of SaO2 and SvO2 are expressed as a decimal
Harris-Benedict equation BEE (kcal/d)

Male = 66 + (13.7 wt in kg) + (5 ht in cm) - (6.8 age in yr)

Female = 655 + (9.6 wt in kg) + (1.7 ht in cm) - (4.7 age in yr)

 Equations tend to underpredict energy expenditure while addition of activity and stress factors tend to overpredict energy expenditure in critically ill patients
  Activity Factors  
  Confined to bed 1.2
  Ambulatory 1.3
  Fever factor 1.13/ C >37
  Injury Factor  
  Surgery 1.1 1.2
  Infection 1.2 1.6
  Trauma 1.1 1.8
  Sepsis 1.4 1.8
BEE, basal energy expenditure; BUN, blood urea nitrogen; UUN, urine urea nitrogen

Nitrogen balance calculation:

Nitrogen balance = Nitrogen in - (nitrogen out + insensible losses)

1 g nitrogen = 6.25 g protein

Nitrogen out = UUN

Insensible losses = 3 4 g/d (increased with diarrhea)

Nitrogen in = protein/6.25

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TABLE 7.9. Fuel Sources (Enteral and Parenteral Formulations)

Fuel Caloric Density Respiratory Quotient (RQ) Comments
Carbohydrate 3.4 kcal/g 1.0 30% to 60% of total nonprotein calories

Maximum infusion rate: 5 mg/kg/min
Fat 9.0 kcal/g 0.7 20% to 40% of nonprotein calories

Usual daily dose: 1g/kg/d
Protein 4.0 kcal/g 0.8 Usually not counted as a calorie source

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TABLE 7.10. Parenteral Nutrition Guidelines

I. Determining Nonprotein Calorie Requirement
A. General guidelines (30 nonprotein kcal/kg/day)
Fat calories 10 kcal/kg/day ____ kg = ____ fat kcal/day (= 1 g/kg/day)
Dextrose calories 20 kcal/kg/day ____ kg = ____ dextrose kcal/day (= 4.1 mg/kg/min),a

OR
B. Indirect calorimetry____ kcal/day RQ*____
   0.33 ____ kcal/day = ____ fat kcal/day
   0.67 ____ kcal/day = ____ dextrose kcal/day
   *Adjust percentage of fat and dextrose calories to achieve an RQ value between 0.8 0.9
II. Determining Protein (Amino Acid) Requirement
A. General guidelines
   1.5 g/kg/day ____ kg = ____ g protein/day OR
B. Disease specific guidelines based on renal function (keep BUN < 100 mg/dl)
   ____ g/kg/day ____ kg = ____ g protein/day
Normal renal function 1.5 g/kg/day
Acute renal failure 0.5g/kg/day
Intermittent hemodialysis 1.0 g/kg/day
Continuous renal replacement therapy 1.5 g/kg/day
III. Solution Formulations
A. Fat volume (20% solution = 2 kcal/ml)
   ____ kcal/____ kcal/ml = ____ ml 20% fat solution*
   *All volumes should be rounded off to the nearest 50 ml
B. Dextrose dose (dextrose 3.4 kcal/g) from Section I above
   ____ kcal/3.4 kcal/g = ____ g dextrose solution
C. Protein dose
   ____ g/d from Section II above
IV. Daily Electrolyte Requirements in Patients with Normal Renal Function
Na 35 150 mEq; K 40 120 mEq; Chloride 100 150 mEq; PO4 15 30 mmolb; Mg 8 24 mEq; Ca Glu 5 20 mEq
V. Additional Additives
Multivitamins, trace elements, regular insulin as needed, H2 blockers, vitamin K as needed
aTo avoid hyperglycemia, order one-half of the total dextrose calories on the first day and advance to full dextrose calories on the second day as tolerated.

bEach ml of sodium phosphate contains 3 mmol PO4-2 and 4 mEq Na+. Each ml of potassium phosphate contains 3 mmol PO4-2 and 4.4 mEq K+.

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TABLE 7.11. Enteral Nutrition Solutions

Enteral Solution Prot (g/L) Carb (g/L) Fat (g/L) Na mEq/L K mEq/L mOsmOs/kg H2O Cal/ml Comments
Criticare HN 38 220 5.3 27 34 650 1.06 Lactose free
Impact 56 130 28 48 33 375 1 Lactose free
Isocal 34 135 44 23 34 270 1.06 Lactose free
Isocal HN 44 123 45 40 41 270 1.06 Lactose free
Osmolite 37 143 37 27 26 300 1.06 Lactose free
Osmolite HN 44 140 35 40 40 300 1.06 Lactose free
Vivonex TEN 38.2 205 2.77 20 20 630 1 Lactose free
Peptamen 40 127.2 39.2 22 32 270 1 For GI impairment
Pulmocare 62 104 92 56 44 475 1.5 For pulmonary patients
Respalor 75 146 70 54 37 580 1.5 For pulmonary patients
Stresstein 70 170 28 56.5 56.4 901 1.2 For moderately and severely stressed patients
TraumaCal 83 195 69 52 36 490 1.5 For moderately and severely stressed patients
Amin-Aid 6.6 124.3 15.7 5 N/A 700 2 For acute or chronic renal failure
Hepatic-Aid II 15 57.3 12.3 5 UK 560 1.2 For chronic liver disease
Travasorb Hepatic 29.4 215.2 14.7 10.2 22.6 600 1.1 For hepatic failure
N/A, Not applicable; UK, unknown

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