Exam 5 Flashcards
Pathophysiology of GERD
Reduced lower esophageal sphincter pressure Direct esophageal irritation Hiatal Hernia Achalasia (lack of motility) Mucosal Resistance Delayed gastric emptying
Conditions that may worsen or cause GERD
Smoking- lowers LES pressure and has acid neutralizing effects of saliva, increases acid production
Obesity (BMI >30)
Physical activity (LES relaxation)
Alcohol- direct irritant
Zollinger- Ellison Syndrome
Very rare, most commonly seen in men aged 50-60
Gastrinomas in pancreas or duodenum secrete large amounts of gastrin , often resulting in peptic ulcers and symptoms of GERD.
Tx- surgery, chemotherapy, high-dose PPI therapy
Suspect if patient has recurrent or refractory PUD or GERD
Associated with frequent diarrhea and duodenal ulcers
GERD complications
Esophagitis (Erosive esophagitis with ulcers occurs when GERD goes untreated)
Barrett’s esophagitis- increases risk of esophageal cancer
Strictures
Anemia
Cancer
Can worsen asthma/precipitate an attack- need to check if patients with frequent asthma exacerbations have GERD (50% do)
Can cause laryngitis
Atypical chest pain
Barrett’s Esophagus
Columnar epithelium replaces squamous epithelial lining during reparative process
This increases the risk of stricture by 30-80%
Increases the risk of cancer by 30-60x
Need endoscopic surveillance
Evaluation of GERD
Take pt history and empiric treatment
- Typically aggravated by meals
- Typically aggravated by recumbent position
- If responds to PPI, the patient likely has GERD
Chest pain needs further evaluation
Typical presentation of GERD
Heartburn
Acid regurgitation
Belching
Bloating
Atypical presentation of GERD
Chest pain Laryngitis/hoarseness Asthma Insomnia Chronic cough Aspiration pneumonia Tooth decay
Alarm S/S of GERD
Needs to be evaluated: Severe dysphagia Odynophagia Weight loss Persistent vomiting Bleeding Hematemesis Anemia
Alternate diagnosis in GERD; Pt presents with chest pain, what could it be?
CAD Gallstones Gastric/esophageal cancer Peptic ulcer disease Esophageal motility disorders Pill induced esophagitis Eosinophilic esophagitis
Diagnostic testing in GERD
Not necessary if PPI resolves symptoms, but symptoms do not always predict the erosive nature of the disease
Consider testing if symptoms persist on PPI or “alarm” symptoms (Endoscopy (EGD))
Endoscopy (EDG)
Necessary to determine: Erosions Rings (Schatzki rings)- mucosal disorder causing esophageal narrowing, common symptom dysphagia Stricutres Barrett's Cancer- need additional biopsy
Treatment goals for GERD
Alleviate or eliminate symptoms
Heal esophagitis
Manage or prevent complications
Maintain remission
Nonpharm treatment of GERD
Elevate head of the bed
Weight loss
Avoid foods that may decrease lower esophageal sphincter pressure (fats, chocolate, alcohol, peppermint, spearmint)
Avoid foods that are direct irritants (spicy foods, OJ, tomato juice, coffee)
Eat small meals and avoid eating prior to sleep
Smoking cessation
Treatment of mild/intermittent heartburn
Lifestyle changes
Antacids
OTC H2RAs
OTC PPIs
Treatment of GERD
Lifestyle changes
Rx-strength H2RAs
Rx PPIs
Treatment of erosive or moderate/severe symptoms
Lifestyle changes
Rx PPIs
High Dose PPIs
Antacids
Only appropriate for intermittent or mild heartburn
Self treat for 2 weeks then see MD
Avoid aluminum and magnesium in CKD patients
Aluminum- constipation
Magnesium- Diarrhea
Tums (calcium carbonate)
DDIs- iron, antibiotics (quinolones, tcn), azoles, separate chelators by 2 hours
Histamine-2 Receptor Antagonists (H2RAs)
Nizatidine, famotidine, ranitidine, cimetidine Famotidine most common Cimetidine many DDI Ranitidine pulled off market May reduce absorption of iron and azoles
Famotidine dosing
Mild- 10-20mg/day
Moderate/Severe- 40-80mg/day BID
Renal dosing if CrCl <50mL/min (give 50% of dose)
AE of H2RAs
HA, dizziness, diarrhea, constipation, fatigue
Increased confusion in elderly (dont use it patients over 75)
Proton Pump Inhibitors
Superior to H2RAs and should be used for erosive diseases
- Reasonable to try first for typical symptoms
All PPIs are equally effective at equal doses and more effective in erosive and nonerosive diseases
OTC PPIs
Omeprazole
Lansoprazole
Esomeprazole
Omeprazole-sodium bicarb
Dont use for more than 14 days
Omeprazole
20mg QD for all indications
Lansoprazole
15mg QD for mild heart burn and GERD
30mg QD for 8 weeks then 15mg QD for erosive disease
Esomeprazole
20mg QD for mild heartburn and GERD
20-40mg QD x8 weeks then 20mg QD for erosive disease
Rabeprazole
20mg QD for GERD and erosive disease
Pantoprazole
40mg QD for GERD and erosive disease
Dexlansoprazole
30mg QD for GERD
60mg QD x8 weeks then 30g QD for erosive disease
Dual delayed-release- first release 1-2 hours after dose, next release 4-5 hours later . Take without regards to meals.
PPI dosing
Start QD, 30 minutes before a meal
In symptoms are uncontrolled may increase to BID dosing (preferred), switch PPIs, or increase dose
PRN dosing only considered after initial treatment course
Omeprazole-Sodium Bicarb (Zegerid)
IR
Doesnt need to be enteric coated because bicarb increases the stomach pH
PPI drug interactions
Iron, azoles (acidic environment needed)
Warfarin- omeprazole only
Clopidogrel- prevents metabolism of clopidogrel due to CYP2C19
PPI AE
HA Dizziness Possible vitamin/mineral deficiencies: B-12 Iron Magnesium Calcium
PPI Concerns
Osteoporosis- inhibition of osteoclast mediated bone resorption (“old bone” not replaced) and inhibition of calcium absorption
Reduced acidity encourages gut microflora growth (C. diff and pneumonia)
Dementia ( Unknown cause, but increased risk)
Reasons for PPI failure
failure- symptoms persist after at least 8 weeks of double dose PPI
Reasons- non-compliance #1 reason
Persistent esophageal acid exposure (hypersecretory state, large hiatal hernia)
Acid-sensitive esophagus
Wrong diagnosis- eosinophilic esophagitis
30-40% of patients will not have good symptoms control
Maintenance PPI therapy
Non-erosive disease- treat initially for a 4-8 week course. Can trial d/c but 2/3rds will relapse
Erosive disease- 8 weeks to heal but typically continue long term
Zollinger-Ellison and Barrett’s- lifelong
GERD therapy adjustments
For nonerosive disease:
Transition to PPI to H2RA ("step down")
Transition from H2RA to PPI ("step up")
Adjust PPI dose, frequency, or switch
Transition from scheduled to PRN
Add bedtime H2RA therapy to daytime PPI therapy for nocturnal symptomsMetoclopramide (Reglan)
Prokinetic agent
-Increases LES pressure and augments gastric emptying
Only use in the presence of proven gastroparesis
5-10mg po TID and HS
CNS AE- Sedation, depression, irritability, EPS, not tolerated in elderly pts
Surgery for GERD
Done if pt:
Will not take medications
Noncompliance to meds or AE
Large hiatal hernia (Nissen fundoplication)
Refractory to meds or worried about long term medication AE
Special populations- Pediatrics and GERD
GERD is fairly common in infants in the first 5 years of life
This is due to developmental immaturity of LES
Non-pharm- changing formula, smaller, more frequent feedings, postural management, parent reassurance
Can safely use H2RAs and PPIs
Special populations- Pregnancy and Lactation and GERD
Pregnancy- have a defective LES and high estrogen and progesterone levels
Tx- lifestyle, TUMS preffered (due to calcium carbonate), H2RA and PPI after TUMS
Do not use omeprazole
Lactation- Antacids and H2RAs safe
Can use PPI but should wait after 6 months of lactation if possible
Counseling Questions for GERD
Duration/frequency of symptoms
Quality and timing of symptoms
Use of alcohol and tobacco
Dietary choices
Medications already tried to treat symptoms and duration of OTC tx
Other disease states present and medications being used
What is the pathophysiology of GERD?
Defective LES pressure or function
-Spontaneous relaxation of LES (more common in recumbent position)
-Increased intra-abdominal pressure-straining, bending over, coughing
Direct esophageal irritation (drugs)
Drugs that worsen GERD
CCB
caffeine
nicotine
Aspirin
Hiatal hernia
When part of the stomach pushes through the diaphragm causing the esophageal sphincter to be permanently open. Food can get trapped in this part of the stomach.
Requires surgical repair
Consider if reflux is not responsive to medication
Pathophysiology of reduced esophageal clearance
Reduced peristalsis (achalasia) Prolongs time refluxed food material is in contact with esophagus
Pathophysiology of mucosal resistance
Esophageal mucosal layer doesnt produce mucus or respond to bicarbonate neutralization.
Happens frequently in the elderly due to decreased saliva
Pathophysiology of delayed gastric emptying
Increased gastric volume increases frequency of reflux as well as amount of refluxate
Common in diabetes
Mucosal defense mechanisms
Bicarbonate- chemical barrier on GI lining. Neutralizes stomach acid
Mucus production- physical barrier
Blood flow to mucosa for healing purposes
Prostaglandins-increases mucus and bicarb production, increases blood flow, decreases gastric acid secretion, limits back diffusion of acid into epithelium
H. pylori
Gram negative bacteria found in most people with peptic ulcer disease.
H. pylori produces ammonia/urease which is toxic to the mucosal barrier. H. pylori produces cytotoxins and mucolytic enzymes
How do NSAIDs cause peptic ulcer disease?
The inhibition of COX1 results in reduced mucus and bicarbonate secretion and impaired platelet aggregation
1st line N/V treatment in chemo
Serotonin receptor blockers
Types of diarrhea
Osmotic Inflammatory Secretory Infectious Altered motility
Osmotic diarrhea
Poorly absorbed intestinal substances (carbs) retain water within the intestine. Carbohydrate malabsorption (lactose intolerance), Mg-containing medications, lactulose, sorbitol Fasting reduces stool volume
Inflammatory diarrhea
Blood, protein, or mucus from an inflamed or ulcerated mucosa
-Ulcerative colitis and Crohns disease
Lactose intolerance
Deficiency of the lactase enzyme
-unabsorbed lactose has an osmotic effect by pulling water into the intestinal lumen
-Can be inherited or acquired
- 3 week trial of diet free of milk and milk products
tx- Dietary changes, probiotics, lactase supplements
Secretory diarrhea
Stimulating substances either increase or decrease absorption of large amounts of water and electrolytes
- Amount exceeds the colons absorptive capacity
Could be due to fat malabsorption, bacterial toxins, pancreatic or intestinal tumors, laxatives, misoprostol, digoxin, colchicine
Fasting does not alter stool volume
Acute infectious diarrhea
Bacterial- C. diff, shigella, E.coli, campylobacter, salmonella
Viral- gastroenteritis
Parasitic- giardia, cryptosporidium
Altered motility
Caused by reduction in contact time with small intestine and premature emptying of the colon
- intestinal resection
- Metoclopramide, erythromycin
Caused by bacterial overgrowth where normal flora replaced (antibiotics, PPI, H2 blockers)
More pathogens will grow due to the inability to digest carbs
Causes of secondary constipation
Hypercalcemia- gut atony
Hypothyroidism- slows digestive contraction
Parkinsons disease- lack of dopamine to stimulate peristalsis
Diabetes- gastroparesis
Secondary medication causes of constipation
Opioids- agonize mu receptors in the GI tract reducing GI motility
Anticholinergics- Inhibit acetylcholine, reducing GI motility
CCBs- Gut smooth muscle relaxation, reduces GI motility
Iron- pulls water into stomach (out of colon); hardens stool; alters motility
IBD
Characterized by inflammation
Ulcerative colitis- confined to rectum and colon; mucosa and submucosa disease
Crohns disease- any part of the GI tract; terminal lumen; transmural disease
Share common etiologies but exact etiology unknown
Pathophysiology of IBD
Alteration of makeup of intestinal microbiota Disruption of mucus layer Dysregulated immune activity Genetic factors Environmental factors
Gut microbiome
1000-1500 different species of bacteria
IBD patients have decreased clostridium and increased campylobacter, shigella, E. coli
Normal intestinal microbiota regulates immune system function by producing substances that reduces TNF-alpha, NF, and LPS activity and promotes regulatory T cell activity
Intestinal immune system
Goblet cells- mucus, keeps bacteria away from intestinal epithelial cells
A-defensins and IgA protect against luminal microbiota
Dendritic cells present antigens to native CD4 T cells
CD4 T cells differentiate into subgroups (T helper cells)
Intestinal epithelium
Provides physical (intercellular junctions and tight junctions) and biochemical barriers to intestinal microorganisms
Produce mucus, maintain and repair barrier, control response to bacteria
Coordinates with innate and adapt immune systems
Intestinal epithelial cells are guided by pattern recognition receptors which detect commensal vs pathogenic microbes and activates immune system if needed
Immunopathophysiology in IBD
Infiltration of lamina by innate and adaptive immune cells (innate first because it regulates homeostasis)
These cells increase levels of inflammatory cytokines (IFN and cytokines), increasing intestinal permeability
Leukocyte infiltration into inflamed intestinal mucosa which contributes to persistent inflammation
Biliary tree
In pancreatitis, anything that blocks a duct effects all organs in the biliary tree.
Gallbladder, pancreas, duodenum
Endocrine pancreas
Insulin and glucagon
Exocrine pancreas
Duct cells
Bicarb, amylase, lipase, protease
Alcohol-induced pancreatitis
> 50g/day alcohol for at least 5 years (4 beers/day)
5% of alcoholics develop pancreatitis
Alcohol increases enzyme production
Alcohol damages acinar cells which can cause premature enzyme activation
Common causes of PUD
NSAIDS
H.pylori
Stress
NSAID caused PUD
Chronic condition Gastric >Duodenal May be asymptomatic Deep ulcers More severe GI bleeding
H. Pylori caused PUD
Chronic condition Duodenal > gastric Epigastric symptoms Superficial ulcers Less severe bleeding
Stress caused PUD
Acute condition Gastric > Duodenal Asymptomatic Most superficial ulcer depth More severe GI bleeding
Uncommon causes of chronic peptic ulcer
Idiopathic Hypersecretion of gastric acid Viral infections Radiation therapy Chemo Infiltrating disease (Crohn's disease) Smoking Psychological stress Potentially alcohol
NSAIDs
Ibuprofen and Naproxen
Aspirin included
Ulcers develop in about 25% of chronic NSAID users (2-4% bleed)
Risk is highest in the first month and persists for the duration (GI mucosa less prepared)
Elderly at highest risk due to age-related changes in gastric mucosal defense
Equal COX1 and COX2 effect
Meloxicam
COX-2 inhibitors
Celecoxib
COX-1 inhibition causes on GI mucosa
Peptic ulcers, GI bleed
COX-1 and 2 inhibition causes on Kidney
Na and H20 retention
Hypertension
Hemodynamic acute kidney injury
COX 1 and 2 inhibition causes on heart
Stroke
MI
COX 2> COX 1
How do COX 1 inhibitors cause mucosal injury and bleeding?
Decreased mucosal blood flow
Reduced mucus and bicarb secretion
Impaired platelet aggregation
How do COX 2 inhibitors cause mucosal injury and bleeding?
Reduced angiogenesis
Impaired healing
Increased leukocyte adherence
Leukocyte activation
Risk factors associated with NSAID induced ulcers
Age >65 Previous peptic ulcer high-dose NSAIDs NSAID + aspirin, bisphosphonates, antiplatelet selective serotonin reuptake inhibitors H.Pylori Cigarette smoking Alcohol
GI prophylaxis for patients on chronic NSAIDs and aspirin
Add PPI or misoprostol
COX-2 inhibitors are less toxic to GI vs NSAIDs, but they inhibit prostacyclin which increases CV risk
Combining COX-2 with aspirin negates any GI benefits
H2RAs not used
Do not typically add PPI for prophylaxis but can in high risk pts
Misoprostol
PGe analog- reduces acid secretion Indicated for patients requiring NSAID therapy to prevent ulceration (secondary to PPIs) Only used in combo with NSAIDs Contraindicated in pregnancy Diarrhea 200mcg 3-4 times daily
What is the major method of toxicity for H. pylori?
Stimulates the inflammatory response (major)
Ammonia is toxic to epithelial cells
Increases pepsin which can degrade mucosa
Complications of PUD
GI Bleeding
GI perforation
Low risk of gastric cancer secondary to H. pylori
Assessment of PUD
Ask about NSAIDs Review meds Review medical history Ask about smoking and alcohol What relieves/worsens S/S of GI bleed
Symptoms of PUD
Pts may be asymptomatic
If no ulcer= nonulcer dyspepsia
Described as burning, fullness, cramping
Can have belching, bloating
N/V, anorexia more common with gastric vs. duodenal
Gastric- food precipitates pain
Duodenal- food relieves pain, but painful 1-3 hours after food
PUD Diagnostic testing
Labs not helpful unless bleeding (reduced hematocrit/hemoglobin and FOB)
H.Pylori testing should be performed in all patients with active PUD
Consider testing H.pylori in patients needing long term NSAID therapy even without PUD
Endoscopy if alarm symptoms
What are PUD alarm symptoms
Elderly, Family h/o GI malignancy, Weight loss, Dysphagia, Bleeding
H. Pylori endoscopic testing
Histology
Culture
Urease
Histology- >95% specificity and sensitivity
Biopsy not recommended for initial diagnosis
Culture is 100% specific
Urease test is >90% sensitive and specific. Biopsy is most common for urease test for rapid results. No H2Ra or PPI for 1-2 weeks or ABX for 4 weeks prior to biopsy.
H. Pylori endoscopic testing Blood antibodies (ELISA) Blood antibodies (IgG) Urea breath test Fecal antigen
ELISA- less accurate than endoscopic tests, but more accurate than office tests. Antibody titers can stay positive for 6 months- 1 year after infection is treated and they are not affected by medications.
IgG-Fingerstick, less accurate than ELISA. Antibody titers can stay positive for 6 months- 1 year after infection is treated and they are not affected by medications. Quick, 15 minutes
Urea breath test- >95% sensitivity and specificity. Tests for ACTIVE infection; results take 2 days. No H2Ra or PPI for 1-2 weeks, no abx for 4 weeks.
Fecal antigen- >95% sensitivity and specificity. Tests for ACTIVE infection; results take 2 days. No H2Ra or PPI for 1-2 weeks, no abx for 4 weeks (may cause false negative, but less important that breath test)
Which H. Pylori test is recommended for post treatment eradication confirmation?
Fecal or breath test
What is the first treatment option for H.pylori induced PUD?
PPI- BID
Tetracycline- 500mg QID
Metronidazole- 500mg TID-QID
Bismuth- 262mg-524mg QID
Duration: 14 days
What is the second treatment option for PUD?
PPI- BID
Clarithromycin- 500mg BID
Metronidazole- 500mg BID
Amoxicillin- 1000mg BID
Duration: 10-14 days (14 preferred)
What do you do with PPI after 14 days of tx for PUD?
May stop after 14 days or continue QD if bleeding ulcer.
Pylera
Combination of bismuth subcitrate, metronidazole, and tetracycline.
Take 3 capsules QID for 10 days with PPI BID
Very expensive, but FDA approved
What is the recommended PUD therapy if no PCN allergy or MCL exposure?
Either
What is the recommended PUD therapy is no PCN allergy but recent MCL exposure?
Bismuth quadruple
What is the recommended PUD therapy if a PCN allergy present?
Bismuth quadruple
What is the recommended PUD therapy if PCN allergy and recent MCL exposure?
Bismuth quadruple
Esomeprazole dosing for NSAID/ASA induced PUD
20mg QD for 4-8 weeks
Lansoprazole dosing for NSAID/ASA induced PUD
15mg QD for 4 weeks (duodenal)
30mg QD for 8 weeks (gastric)
Omeprazole dosing for NSAID/ASA induced PUD
20mg QD for 4-8 weeks (duodenal)
40mg QD for 8 weeks (gastric)
Pantoprazole dosing for NSAID/ASA induced PUD
40mg QD for 4 weeks (duodenal)
40mg QD for 8 weeks (gastric)
Rabeprazole dosing for NSAID/ASA induced PUD
20mg QD for 4 weeks (duodenal)
20mg QD for 6-8 weeks (gastric)
Treatment for NSAID induced PUD
Stop NSAID acutely while ulcer is being treated (8 weeks)
If pt has a bleed on NSAID + PPI do not restart NSAID
Long term tx:
NSAID + PPI/misoprostol
COX-2 inhibitor + PPI in high risk patients
Non-NSAID therapy if possible
Treatment of ASA induced PUD
Typically hold ASA acutely (risk vs benefit if stent patients on DAT)
Long term, if ASA has to be continued
- Add PPI
Do NOT switch to clopidogrel
Sucralfate
Can be added to PPI therapy
“Coats” the ulcer to prevent further acid damage and the GI mucosa to prevent HCl back diffusion.
1g po AC and HS (given QID)
Separate by 2 hours from all other medications
AE: constipation, hypophosphatemia
Stress ulcer prophylaxis
Appropriate for ICU patients, but not general hospital patients
Appropriate for some non-ICU with risk factors
H2RA or PPI IV in ICU (pantoprazole, esomeprazole)
Non-pharm- enteral nutrition
Why do ICU patients get stress ulcers?
Critical illness causes splanchnic hypoperfusion because the body shits down blood flow to organs other than heart and brain.
This causes reduced HCO2 secretion, mucosal blood flow, GI motility, and a disruption of mucosal barrier.
This leads to an acute stress ulcer.
Tx for upper GI bleed
Ensure hemodynamic stability
Volume resuscitation
Correct coagulopathy and/or thrombocytopenia
Endoscopic hemostasis
PPI- high dose bolus vs continuous infusion
Correct underlying cause
S/S GI bleeding
Symptoms related to hypovolemia (orthostasis)
Signs related to hypovolemia ( AKI, hypotension, tachycardia)
Greatly elevated BUN:SCr ration
Reduced hemoglobin and hematocrit
Hematemesis
Hematochezia (bright red blood in stool- lower GI bleed)
Melena (dark blood in stool– upper GI bleed)
Fecal occult blood- either type of bleeding
GI bleeding Tx
Resuscitation- Blood and 0.9% NS Reverse INR if needed and hold meds NOACs- andexanet alpha, Idarcizumab Correct thrombocytopenia if needed PPI infusion- Esomeprazole or pantoprazole 80-mg bolus followed by 8mg/hr IV for 72 hours
Etiologies of N/V
Gastrointestinal processes, infections, acute MI, migraine, vestibular disorders, metabolic disorders, psychiatric disorders, drug withdrawal, post-op, food poisoning
Types of N/V in cancer
Acute- w/in 24 hours
Delayed- begins after 24 hours and may last 120 hours
Anticipatory- learned behavior from poorly controlled N/V
Breakthrough- N/V that occurs despite prophylaxis; requires rescue
Refractory- prophylactic and rescue therapy fails
Which patients receive prophylaxis for N/V before, during, and after chemo?
Low
Moderate
High
What are fluid and electrolyte causes for N/V in cancer patients?
Hypercalcemia (Very common due to PTH secretion of tumors)
Dehydration
What are drug-induced causes of N/V in cancer patients?
Opioids
antibiotics
What are tumor/metastases-related causes of N/V in cancer patients?
GI obstruction Brain melts (tumor spreads to brain)
What are misc. related causes of N/V in cancer patients?
Infection
Radiation therapy
Post-op N/V
Occurs within 24-48 hours after surgery
#1 surgery complications
Triggers- duration of surgery (risk increases by 60% for every 30 minutes)
Anesthetics (inhaled)- use regional anesthetics or IV
Anxiety
PONV risk factors
Female gender
Nonsmoker (smoking induced CYP450 which allows for faster anesthetic metabolism0
H/O motion sickness or PONV
Intraoperative and postoperative opioid use
1 RF= 20%
Moderate risk= 40%
High risk= 60-80%
Nonpharm treatment of PONV
Dietary changes Positioning (vestibular) Relaxation Biofeedback Acupuncture
N/V symptoms
Abdominal pain (pancreatitis, obstruction, PUD)
Diarrhea, myalgias (viral)
Headache, stiff neck, CNS findings (meningitis)
Significant, unintentional weight loss (cancer)
Abrupt symptoms (pancreatitis, appendicitis, gastroenteritis, food poisoning, medications)
After a meal (gastroparesis)
Treatment options for N/V
Antacids Antihistamines-anticholinergics Phenothiazines Dopamine antagonists Serotonin (5HT3) receptor antagonists Neurokinin receptor antagonists Corticosteroids Benzodiazepines Cannabinoids
Antihistamines for N/V
Diphenhydramine
Hydroxyzine 25-50mg PO TID-QID
Meclizine 12.5-25mg PO TID-QID
Scopolamine patch
Adverse reactions: dry mouth, urinary retention, constipation, sedation, ataxia, confusion
Drug interactions: additive anticholinergics and CNS agents
Phenothiazines for N/V
Promethazine (Phenergan)
6.25-25mg PO/SUPP Q6H
6.25-12.5mg IV/IM Q6H
BBW for tissue necrosis in injectable route
Prochlorperazine (Combazine)
AE: Anticholinergic, extrapyramidal symptoms, QT prolongation, sedation (more with promethazine)
Drug interactions: additive anticholinergics and CNS agents
Dopamine antagonists in N/V
Haloperidol
Olanzapine
Droperidol
Metoclopramide
Haloperidol and Olanzapine in N/V
Do not use with metoclopramide Haloperidol- 1-2mg PO Q4H PRN (can be given IM or IV as well) Side effects- Confusion, drowsiness, dystonias, QTc prolongation (especially IV) Olanzapine- 10mg PO (can give IM or IV as well) Side effects- Somnolence, dystonias Better tolerated than haloperidol
Droperidol
Excellent antiemetic but rarely used
BBW for torsades
Side effects similar to that of haloperidol, but also hypotension and tachycardia
Metoclopramide
5-10mg AC and HS (gastroparesis); 10-40mg PO/IV Q6H PRN for chemotherapy
Dosed as high as 1-2mg/kg before chemo
Side effects- Dystonias (including tardive dyskinesia-long term), drowsiness, diarrhea
Reduce dose by 50% for CrCl <40mL/min
Can increase risk of seizures
Should be given before meals
5HT3 Receptor Antagonists for N/V
Dolasetron
Granisetron
Ondansetron
Palonosetron
All have a risk of QTc prolongation (dose dependent)
Ondansetron interacts with strong 3A4 inhibitors
5HT3 Receptor antagonists drug information
Palonosetron has a long half life (QD dosing)
Dolasetron lost FDA approval for CINV due to risk of torsades
Ondansetron carries the most DDI due to substrate for CYP 1A2, 2D6, and 3A4. Watch with amiodarone, quinolones, macrolides, antipsychotics, azoles, and many more
Neurokinin Receptor Antagonists for N/V
Aprepritant (PO), Fosprepitant (IV)
Rolapitant, netuplitant, fosnetupitant- PO
Indicated only for highly emetogenic regimens
Drug interactions- Induces CYP2C9, reduces warfarin efficacy
Inhibitor and substrate of CYP3A4 (use in caution with strong 3A4 substrates (statins, azoles, macrolides)
AE- fatigue, hiccups, weakness
Corticosteroids for N/V
Dexamethasone most common
Utilized in low, moderate, and highly emetogenic regimens
Good for delayed N/V
Avoid in immunotherapies and cellular therapies
Utilizes in non-chemo N/V
Typically used 3-4 days so limited AE, but hyperglycemia, mood disturbances, delayed wound healing, and dyspepsia may be present
Benzodiazepines for N/V
Lorazepam- 0.5-2mg IV/PO Q4-6 H
AE: somnolence, impaired memory and cognition, gait disturbance, irritability
Good for anticipatory N from chemo and anxiety-related N/V
Watch with other CNS depressing drugs
Cannabinoids for N/V
Dronabinol (Marinol)
MOA- opposes serotonin in CTZ
AE- abnormal thinking, appetite stimulation, euphoria, paranoia, may lower seizure threshold, habit-forming
Caution with other CNS depressants
Often used chronically in cancer/AIDS for appetite and nausea
Approaches to treatment in N/V patients
Viral gastroenteritis and other self-limiting conditions
- Identify and treat underlying cause
- Hydration
- PRN promethazine
Gastroparesis -Metoclopramide Erythromycin is secondary -Optimize diabetic control -D/C opioids and anticholinergics
Vertigo
Vomiting after head motion
Meclizine or hydroxyzine
Promethazine second line
Motion sickness
Diphenhydramine, dimenhydrinate, or scopolamine
Chemotherapy- induced N/V high risk regimen
Day 1 (before chemo)- NK-1RA, 5-HT3 RA, and dexamethasone
Day 2- Aprepitant (only if used on day 1) and dexamethasone
Day 3-Aprepitant (only if used on day 1) and dexamethasone
Day 4- Dexamethasone
Olanzapine can be added to each days treatment regimen
How do you reduce baseline risk in post op NV
Use regional anesthesia
Use IV anesthesia (propofol preferred)
Minimize intraoperative and postoperative opioids
Adequate hydration
PONV prophylaxis
Dexamethasone, promethazine at beginning of surgery
Dolasetron, granisetron, ondansetron, droperidol, haloperidol can all be given at end of surgery
Scopalamine patch- prior evening or 4 hours before surgery
Choose 2 of the above if moderate-high risk
PONV treatment
Initially 5HT3 antagonist
If failed prophylaxis choose 1 or 2 agents from a different class
Control pain
Give fluids
N/V in pregnancy
Caused by elevated hCG and estrogen
Hyperemesis gravidarum- requires hospitalization can cause hypokalemia, dehydration, weight loss more than 5%, ketonuria
Treat with Vit B +doxylamine, OTC ginger, dimenhydrinate
If not dehydrated add metoclopramide or ondansetron PO
If dehydrated do IV
What are the types of acute diarrhea?
Osmotic Inflammatory Infectious Secretory Altered motility
Chronic diarrhea
Any of acute, PLUS
diabetes
IBD
Hyperthyroidism
Presentation of diarrhea and potential cause
Typically self-limiting
Stool analysis
Fever? probably infectious
Blood? Pain? Either infectious or inflammatory
Severe dehydration/hemodynamic instability? May need to hospitalize.
Supportive treatment of diarrhea
Treat underlying cause Fluids and electrolytes Oral vs IV fluids depending on severity Can have hypo or hypernatremia Hypokalemia common Bicarb loss with resultant metabolic acidosis
Treatment options for diarrhea
Adsorbents/bulk-forming agents first- pull water out of stool
-polycarbophil, psyllium, methylcellulose, aluminum hydroxide, kaolin-pectin, cholestyramine
Opiate-like agents if bulk forming do not work
Delay onset of intraluminal contents
Loperamide, diphenoxylate- atropine, difenoxin-atropine
Antisecretory agents- bismuth subsalicylate
Ocreotide
Loperamide
Imodium
Agonizes intestinal opioid receptors to slow GI motility
4mg once then 2mg after each unformed stool (max 16mg/day)
Well tolerated
1st line after bulk-forming agents
Diphenoxylate and Difenoxin
Diphenoxylate-atropine (Lomotil) Agonizes central and intestinal opioid receptors to slow GI motility Atropine is used to discourage abuse 5mg PO TID-QID DDI: Do not give with MAOIs, linezolid AE: drowsiness, dizziness, HA
Difenoxin-atropine (Motofen)
Active metabolite of diphenoxylate
Does not cross BBB, non CNS effects
Ocreotide
Somatostatin analog
Blocks serotonin, inhibits intestinal secretion and stimulates intestinal absorption
Used for tumor related secretory diarrhea
Treatment of infectious diarrhea
C.diff
- stop offending agents if possible
- Oral Vanc or fidaxomycin
- Probiotics for prophylaxis
- Fluids
- Do NOT give antidiarrheals
Travelers diarrhea
Diverticulosis and Diverticulitis
Diverticulum- Outpouching of intestinal wall
Diverticulosis- the presence of diverticula
Diverticulitis- the inflamed diverticuli. Acute, left sided abdominal pain, diarrhea or constipation
Bleeding is uncommon
Diverticulitis classification
Complicated- Abscess, obstruction, peritonitis
Uncomplicated- colon wall thickening only
Tx of acute diverticulitis
Abx recommended in complicated. May be reasonable in uncomplicated
If fever or signs of infections use abx
Clear, liquid diet
Pain control
Celiac disease
Inflammatory diarrhea that results in malabsorption
Gluten insensitivity
Evaluate iron, folic acid, B-12 and Vit D
Steroids may be helpful for refractory patients
`Mucositis
Inflammation/ulceration of Gi tract from chemotherapy and/or radiation
Prevent using H2Ra or PPI
Can cause both constipation or diarrhea, but more commonly diarrhea
Tx- Hydration, loperamide, octreotide if loperamide failed
Constipation
Fewer than 3 bowel movements/week
GI causes of constipation
IBS
Diverticulitis
Hemorrhoids
Obstruction (cancer)
Metabolic/endocrine causes of constipation
Diabetes
hypothyroidism
Hypercalcemia
Lifestyle causes of constipation
Pregnancy
Inadequate fluid
Low fiber
Sedentary lifestyle
Neurogenic/Psychogenic causes of constipation
Stroke
Spinal cord/brain injury
Psychiatric diseases
Drug induced constipation
Slow motility- opioids, anticholinergics (antihistamines/phenothiazines, CNS agents, urinary incontinence agents), CCVs, aluminum and calcium antacids, iron
Alarm symptoms of constipation
Hematochezia, melena, family H/O colon cancer, IBD, anemia, weight loss, anorexia, N/V
Colonoscopy if any are present!
Treatment of constipation non-pharm
Increase fluids and fiber
Increase activity
Fiber
Fiber- bulk-forming, increases frequency of defecation by retaining water in intestine and increasing GI motility
Examples- psyllium, methylcellulose and polycarbophil
Laxatives for constipation treatment
Step-wise approach
Bulk-forming (Fiber)
Stool softeners- allows water and lipids to penetrate stool
Osmotic- fluid accumulation/binding, stimulates peristalsis
Stimulant laxatives- mucosal irritation that stimulates peristalsis
Bulk-forming laxatives and onset
Fiber
1-3 days
Softener laxatives and onset
Docusate
1-3 days
Used preventative
Lubricant laxative and onset
Mineral oil
1-3 days
Not used often due to aspiration risk
Osmotic laxatives and onset
Lactulose, sorbitol- 1 day PEG (miralax)- 1 day Mag citrate- 1-6 hours Sodium phosphate- 1-3 hours PEG (GOLYTELY)- Rapid
Stimulant laxatives and onset
Bisacodyl- 1-12 hours
Senna- 6-12 hours
Mag citrate- 1-6 hours
Glycerin suppository- 30 minutes
Dosing:
Psyllium
Docusate
Mineral oil
Psyllium- 4-6g/day
Docusate- 100mg po BID
Mineral oil- 15-45ml po once
Dosing:
Lactulose, sorbitol
PEG (Miralax)
Bisacodyl
Lactulose- 15-30mP QD, or 30 150mL once
PEG (miralax)- 17g QD
Bisacodyl- 10mg PO or PR QD
Dosing: Senna Mag citrate Glycerin supp PEG (GoLYTELY)
Senna- 1-2 tbs PO BID
Mag citrate- 150-300mL PO once
Glycerin supp- Suppository once
PEG(GoLYTELY)- 4000ml once
Lubiprostone
Amitiza
Chronic idiopathic constipation, IBD- constipation, or opioid induced constipation
Activates Cl channels which increase intestinal fluid secretion. Softens stool, increases motility, promotes BM
Not systemically absorbed
Takes 24 hours to 1 week to work
Do not give to patients with GI obstruction
AE- N/D
Dosing- 24mcg BUD (CIC) or 8mg BID (IBS-C)
Linaclotide and Plecanatide
Linzess- liaglutide and Trulance- Plecanatide
Chronic idiopathic constipation or irritable bowel constipation
Increases cGMP which increases Cl and bicarb secretion into intestine which increases intestinal fluid and GI mobility
DO not give to patients with GI obstruction
ADE- Diarrhea
BBBW- dehydration in pediatric patients
Opioid- induced constipation
Opioids agonize mu receptors in gut smooth muscle, reducing GI mobility
Tolerance to this adverse effect does not develop
Use lowest possible opioid dose
Scheduled, stimulant laxatives with routine opioids
-Docusate and senna 2 tabs BID most common
Stimulant must be part of both treatment and prevention regimen
Methylnaltrexone
Relistor Opioid induced constipation Mu receptor antagonist Contraindicated in GI obstruction Oral and SubQ Needs to be renally dosed AE- abdominal pain, gas, N, diarrhea Treatment only, not prevention 450mg QD (PO) 12mg SQ QD
Naloxegol (Movantik)
Naloxone conjugated with a PEG polymer so cant cross BBB Mu receptor antagonist Contraindicated in GI obstruction and strong 3A4 inhibitors Oral AE- abdominal pain Renal dosing Treatment only, not prevention 25mg QD
Naldemedine (Symproic)
Mu receptor antagonist Opioid induced constipation Treatment only not prevention Contraindicated in GI obstruction and strong 3A4 inhibitors Oral AE- abdominal pain Does NOT need renal dosing 0.2mg QD
OIC treatment algorithm
Prevent using stimulant +/- stool softener
Tx- increase dose of stimulant and add stool softener if not on
Opioid reduction
Peripherally acting mu-receptor antagonist
Post Operative Ileus
Use Alvimopan (Entereg)- causes transient inhibition of GI motility after surgery
Selective mu receptor antagonist
BBW- only for short term (15 doses)
Contraindicated in patients taking more than 7 days of opioids prior to alvimopan
Laxative abuse
Trying to maintain daily bowel movements (elderly)
Trying to lose weight
Taking routinely can cause dependence
Can lead to serious health concerns
Aluminum- osteomalacia
Fluid and electrolyte abnormalities
Cathartic colon
Irritable bowel
Affects young women most commonly
S/S- chronic abdominal pain, bloating at least for 3 months
Diarrhea, constipation, or both
Depression and anxiety are common comorbidities
Pain often relieved with defecation
Food is common precipitant
Treatment of IBS with constipation predominant
Fiber
Do not use osmotic laxatives
Lubriprostone, Linaclotide, Tegaserod are last line
Tegaserod is emergency use only due to CV events
Treatment of IBS with diarrhea predominant
Dietary changes
Loperamide not helpful
Alosetron- 5HT3 antagonist, indicated in women, restricted use due to severe AE
Eluxadoline- mixed mu receptor agonist. Causes CNS depression, pancreatitis, hepatitis
Symptom control in IBS
Probiotics- helps bloating and flatulence
Antispasmotics- dicyclomine (Bentyl)- 30mg PO QID, increase to 40mg QID after 1 week. Anticholinergic AE
Peppermint oil has potential benefit
Tricyclic antidepressants- Analgesic effect, not used often
Types of IBD
Ulcerative colitis and Crohns disease
Complications of crohns disease
Inflammation
Stenosis
Fistula
Ulcerative colitis depth and location
Depth- Mucosa and submucosa
Location- Rectum and colon
Ulcerative colitis fistulas, strictures, bleeding
Fistulas- rare
Strictures- rare
Bleeding- common >90%
Ulcerative colitis abdominal pain, distribution, diarrhea, characterization
Abdominal pain- Unusual
Distribution- Continuous
Diarrhea- 10-30%
Characterization- “Steady” disease
Crohns disease depth and location
Depth- Transmural
Location- Terminal ileum, but can occur at any part of the GI tract
Crohns disease fistulas, strictures, bleeding
Fistulas- common
Strictures- common
Bleeding- Common (<50%) but less severe than UC
Crohns disease abdominal pain, distribution, diarrhea, characterization
Abdominal pain- common
Distribution- Discontinuous
Diarrhea- >70%
Characterization- Flares alternating with remission
Local complications of UC
Toxic megacolon- ulceration extends below submucosa (perforation), high fever, elevated WBC, and tachycardia present
Significantly higher risk of colon cancer
Local complications of crohns disease
Hemorrhage
Perforation
Obstruction
Cancer
Systemic complications of both UC and CD
Hematobiliary- fatty liver, hepatitis, cirrhosis, cholangiocarcinoma, gallstones
Joints- arthritis (asymmetric)
Ocular- Iritis and uveitis (blurred vision, eye pain, and photophobia)
Dermatologic- erythema nodosum, pyoderma gangrenosum
Clinical presentation and work up of CD
Abdominal findings- cramping, pain, chronic diarrhea, nausea, vomiting, weight loss
Symptoms related to systemic manifestations- blurred vision, arthritis, skin findings
DC NSAIDS
Colonoscopy
Clinical presentation and work up of UC
Abdominal findings- Pain, hematochezia (blood in stool), need to rule out C. Diff
Symptoms related to systemic manifestations- blurred vision, arthritis, skin findings
DC NSAIDS
Colonoscopy
Pharmacologic treatment for IBD
Aminosalicylates (5-ASA) (first) Corticosteroids Antimicrobials Immunomodulators Biologics (last) Supportive- enteral and parenteral nutrition in severe disease
Sulfasalazine in IBD
Not as commonly used No benefit to sulfa group and contributes to AE Sulfa antibiotic + mesalamine Mesalamine is the active ingredient Avoid in sulfa and aspirin allergies AE- GI disturbances, HA, arthralgias Response correlates with dose Folic acid supplementation needed
Mesalamine derivatives in IBD
Mesalamine
- avoid in ASA allergy
- Oral products- GI AE , HA
- Rectal- flatulence, HA
- If extended or DR, do not open crush or chew
- Give with meals if GI AE
Mesalamine derivatives
- Olsalazine-diarrhea
- Balsalazide- HA, GI
Corticosteroids for IBD
Prednisone 40-60mg/day
Rate of taper depends on dose and duration
Use IV for acute flares (hydrocortisone, methylpresnisolone)
Budesonide (Entocort)- works in terminal ileum. Limited systemic absorption due to extensive first pass metabolism
Steroid AE
Hyperglycemia Hypertension Osteoporosis Acne Fluid retention Weight gain Psychosis Increased susceptibility to infection Cataracts, glaucoma
Antibiotics in IBD
Not used as monotherapy
Metronidazole- 500mg PO Q8H
Interactions- warfarin, disulfiram-like with alcohol
AE- N, metallic taste, paresthesias
Azathioprine/ 6-Mercapropurine in IBD
Azathioprine is metabolized in 6-MP
Drug interactions- allopurinol decreases elimination and can cause significant hematologic toxicity
AE- N, fever, rash, arthralgia, infection, pancreatitis
BBW- myelosuppression, neoplastic disease
6MP- hematologic toxicities, pancreatitis
Methotrexate for IBD
Weekly IM
Bone marrow suppression, folic acid deficiency
BBW- hepatotoxicity, lymphoma, exfoliative dermatitis, diarrhea and ulcerative stomatitis, pulmonary toxicity, increased risk of opportunistic infections, drug clearance is reduced in ascites, renal impairment, and pleural effusions
Cyclosporine in IBD
IV infusion
Drug interactions- statins, macrolides, azoles, diltiazem, verapamil.
AE- nephrotoxicity, hyperlipidemia, HTN
Biologics for IBD
Antibodies to TNF-alpha
Selective adhesion molecule inhibitors
IL12/IL23 inhibitor
JAK inhibitors
Antibodies to TNF-a
Blocks binding to its receptors, decreasing immune response
Infliximab, adalimumab, certolizumab, golimumab
Selective adhesion molecule inhibitors
Blocks adhesion of lymphocytes to epithelium
Natalizumab, vedolizumab
IL12/IL23 inhibitor
Reduces the inflammatory response by blocking the secretion of IL-6, IL-17, and TNF-a
Ustekinumab (Stelara)
JAK inhibitors
JAK signals IL12 and IL23
Tofacitinib
Infiliximab
5mg/kg weeks 0,2, and 6 (induction) then 5mg/kg every 8 weeks for maintenance. Only induction is infusion
BBW- infections (TB, sepsis, fungal and other opportunistic infections), increased risk of lymphoma in adolescent or young adult males (also in receiving AZA or 6MP concomitantly)
Must have TB test before initiating
Infliximab toxicities
Infusion reactions
Premedicate with APAP, diphenydramine, and possibly steroids
Autoimmune reactions- lupus, hemolytic anemia
Adalimumab, certolizumab, and golimumab toxicities
SQ administration- injection site reactions
May worsen/cause HF
Vedolizumab and natalizumab toxicities
May increase risk of infections and liver injuries
Ustekinumab toxicities
Test for TB before initiating
May cause hypersensitivity reactions and increase risk for infections
Tofacitinib toxicities
Test for TB before initiating
Which biologics have a BBW for increasing lymphoma and infection risk?
Infliximab, adalimumab, certolizumab, golimumab
Which biologic has the BBW of PML?
Natalizumab
Which biologics have no BBW?
Vedolizumab, usetkinumab
Which biologic has a BBW for increasing lymphoma, VTE, and infection risk?
Tofacitinib
Treatment of active UC- mild-moderate diseases
Mild-moderate extensive disease- 5-ASA oral agents, corticosteroids (budesonide) if 5-ASA failed
Mild-moderate distal disease- 5-ASA topical agents
Treatment of active UC- severe
Steroids, anti-TNF (refractory to steroids), cyclosporine if hospitalized
Use vedolizumab, tofacitinib, or golimumab as alternative to anti-TNF
Do you use AZA/6MP or antibiotics in active UC?
No
Prevention of relapse of UC
5-ASA agents-oral (dont use with anti TNF)
5-ASA agents- topical if distal disease in combo with oral
AZA/6MP- Especially if anti-TNF was used in combo, effective if steroids were effective or cyclosporine was effective
Can use infliximab, vedolizumab, golimumab, or tofaxitinib if responded to active treatment
Treatment of active CD
Steroids for all (parenteral agents in severe)
Intramuscular MTX
Anti-TNF in moderate to severe disease (including fistulizing), steroid-resistant disease
Natalizumab or vedolizumab only if anti-TNF failed
Ustekinumab- last line if everything as failed
Metronidazole/Cipro if fistulizing
Prevention of relapse CD
AZA/6MP in combo with anti-TNF
Natalizumab, vedolizumab, ustekinumab if worked acutely
Treatment of toxic megacolon
Supportive measures
-Fluids and electrolytes
-D/C meds that slow motility (anticholinergics, opiates)
Empiric Abx- broad spectrum, gram neg anaerobes
High dose IV steroids
Emergent and surgical intervention
Indications for surgery
Life threatening hemorrhage Perforation Cancer Toxic megacolon Failure of or intolerance to maximal medical therapy Obstruction Abscess not amenable to drainage
IBD and pregnancy
Mesalamine and sulfasalazine are acceptable
-All category B (except Asacol, C)
Folic acid should be given with sulfasalazine
Do not use steroids, azathioprine, or mercaptopurine- D
MTX- category X
Infliximab, adalimumab, certolizumab, and golimumab are category B
Acute pancreatitis
Rapid onset, generally no long term complications if patient survives acute attack
Severe abdominal pain
Acutely elevated pancreatic enzymes
Chronic pancreatitis
Multiple attacks without correction of risk factors
-Progressive inflammation and long-standing injury
Anatomical and functional compromise- irreversible
Chronic abdominal pain
Pancreatic enzymes may not be elevated
Causes of acute pancreatitis
Gallstones, alcohol, and hypertriglyceridemia (>1000) most common causes
can also be caused by infections, hypercalcemia, abdominal trauma, IBD, etc.
Medication causes of acute pancreatitis
Azathioprine Estrogens Furosemides Steroids Opiates Sulfonamides Propofol Tetracycline Statins Valproic acid Thiazides ACE-Is
How do ACE-Is cause acute pancreatitis?
Local angioedema
How do estrogen/OC/HRT cause acute pancreatitis?
Microemboli
Hypertriglyceridemia
How do statins cause acute pancreatitis?
Directly toxic
May be related to myalgias/rhabdo
How do diuretics cause acute pancreatitis?
Loops- directly toxic
Thiazides- hypercalcemia, hypertriglyceridemia
How does valproic acid cause acute pancreatitis?
Directly toxic
How do azathioprine, sulfonamides, and tetracyclines cause acute pancreatitis?
Hypersensitivity reactions
These are the same drugs that cause AKI
Clinical presentation of acute pancreatitis
Moderate to severe abdominal pain
-Radiates to upper quadrants or back
-Described as “knife-like”, constant, severe
-Aggravated by eating
N/V
Cullens and Grey-Tuners signs (rare)- blood accumulations
More severe pancreatitis- hypotension, renal failure, fever, diminished bowel sounds, dyspnea and tachypnea
Laboratory findings in acute pancreatitis
Leukocytosis (inflammation vs infection)
Hyperglycemia
Hemoconcentration due to dehydration (Hematocrit, BUN, creatinine all elevated)
Hypocalcemia and Hypoalbuminemia
Elevated C-reactive protein (CRP)
- Good marker for severity buy delayed (72h)
Elevated pancreatic enzymes
Amylase in pancreatitis
60-180units/L
Rise 4-8 hours after initial attack, peak at 24 hours, return to normal over 3-5 days
Not specific to pancreas
Lipase in pacreatitis
<200units/L
Specific to pancreas
Longer half life than amylase so may remain elevated after amylase returns to normal
Takes longer to rise than amylase
What amylase or lipase values are diagnostic of pancreatitis?
> 3x ULN
Elevations do not correlate with etiology or severity of disease
Prognostic criteria pancreatitis
Ransons criteria- specific to pancreatitis, 11 variable assessed on admission and 48 hours later
Apache II score- ICU prognosis predictor, 12 variables within 24 hours, best predictor of severity
CT severity index- measures inflammation and necrosis
Atlanta scoring system-combines all 3, research only
Management of acute pancreatitis
Remove cause or treat underlying condition
Pancreas “rest: clear fluids and advance diet slowly when pain subsides (try to feed in 24 hours). Enteral or parenteral nutrition if npo >5 days
Fluid management
Pain and nausea control
Treat infections
Surgery (cholecystectomy)
G-tube vs J-tube
G-tube is in the stomach
J-tube is in the jejunum
Fluid management for acute pancreatitis
Volume depletion due to “third spacing” of intravascular fluid due to inflammation and increased capillary membrane permeability
Reduction in intravascular volume can lead to reduced perfusion of key organs (acute renal failure, pancreatic necrosis, hemodynamic instability)
Aggressive IV fluids (NS or LR)
-Patients may need >5L fluid in first 12-24 hours
Monitor vital signs, urine output, hematocrit, BUN
Pain and Nausea control for pancreatitis
Narcotics are mainstay
-Hydromorphone (Dilaudid) preferred
Morphine is also reasonable
PCA who need frequent narcotic dosing
Promethazine and serotonin antagonists (Zofran) for N
Infections in pancreatitis
Not common
Prophylactic abx not recommended
Indicated if infected necrosis found
-sterile necrosis should not be treated unless patient deteriorates
-Account for some of the mortality in acute pancreatitis
-Avoid abx if possible.
Octreotide
Potent inhibitor of pancreatic enzyme secretion
May reduce mortality
Reserved for severe acute pancreatitis
Doses studied- 0.1mg SQ Q8H, 0.5mcg/kg/hr by continuous infusion
Complications of acute pancreatitis
Local- acute fluid collection, pancreatic necrosis and abscess, pseudocyst
Systemic- shock, hypotension, acute renal failure, acute respiratory distress syndrome, GI bleeding
Chronic pancreatitis
Chronic pancreatitis cause
Irreversible damage
Alcohol (inflammation-> necrosis -> fibrosis)
Idiopathic
Gallstones are not associated with chronic pancreatitis
Symptoms of chronic pancreatitis
Chronic low-level abdominal pain
Fat malabsorption due to decreased production of enzymes (steatorrhea)
Malnutrition
Weight loss, nausea
Diabetes (bc of lack of insulin production)
Enzymes are typically not elevated
Treatment of chronic pancreatitis
No alcohol! Control of pain Give pancreatic enzymes Insulin if diabetes Smaller, more frequent low-fat meals
Complications of chronic pancreatitis
Malabsorption
Chronic abdominal pain
DM
Pancreatic cancer
Pancreatic enzymes
Treatment for chronic pancreatitis
Amylase, lipase, protease
Helps with malabsorption, steatorrhea, osmotic diarrhea, pain, slows progression
Dose of pancreatic enzymes
Based on lipase content
25000-40000 units lipase per meal, half for snack
Not interchangeable
Lipase in creon, zenpep, pancreaze
Creon- 3,000-24,000 units
Zenpep- 3,000-25,000 units
Pancreaze- 4,200-21,000 units
Lipase in ultresa, viokace, pertzye
Ultreza- 13,900-23,000 units
Viokace- 10,440-20,880
Pertyze- 8000-16,000 units
Pancreatic enzymes counseling points
Avoid in pork allergy
Take with meals or snacks
Do not crush or chew enteric coated formulations
Avoid taking with calcium or magnesium antacids
AE- stomach upset, nausea, diarrhea, hyperuricemia, oral and perianal irritation
Treatment of abdominal pain in chronic pancreatitis
Non-narcotic choices given before meals -tylenol, NSAIDs, Tramadol Pancreatic enzymes -High doses of proteases (non-enteric coated so they work in duodenum) Many patient need narcotics
Pancreatic cancer
Very poor prognosis
Often presents when inoperable or metastasized
5 year survival rate of 5%
Risk factors- smoking, obesity, chronic pancreatitis
Symptoms- abdominal pain, jaundice, weight loss, hyperglycemia
Enteral nutrition
via the gastrointestinal tract
GI tract contains about 75% of its nutrition from the gut mucosa so preferred
Parenteral nutrition
Via the vascular system, usually venous
Limited to 900-1000mOsm/L
For every 1% there are 50mOsm/L
For every 1% AA there are 100mOsm/L
TPN vs PPN
Total parenteral nutrition given through central line
Peripheral parenteral nutrition given through peripheral system
Ileus
Decreased peristalsis resulting in decreased bowel sounds, painful distended abdomen, N, V
-ostomy
New functional opening
Gastric residual
Volume retrieved from the stomach upon aspiration of gastric contents through a gastronomy tube; generally, if >200mL you are intolerant of enteral nutrition
Fistula
Abnormal communication between two epithelial cell lines
Marasmus
Chronic protein and calorie malnutrition Decreased energy intake vs. increased energy expenditure Visceral protein (albumin, prealbumin) production preserved
Kwashiorkor
Acute or chronic protein malnutrition; adequate calorie intake
Decreased synthesis vs decreased intake
Marked depletion of visceral proteins
Why does malnutrition occur with critical illness?
Immune system activates SIRS (systemic inflammatory response syndrome) which causes increased oxygen energy demand, leading to catabolism causing malnutrition
Also, the mobilization of fatty acids, proteins, and glucose causes catabolism leading to malnutrition
Rehabilitation
Loss of skeletal muscle mass; weakness
What are the risks for malnutrition in the ICU?
Stressors- SIRS, infection, trauma
Previous history of malnourished (EtOH)
NPO
Visceral proteins
Synthesized from the liver by dietary amino acids
Prealbumin has a half life of 3 days and is used in acute phase
Weight considerations for nutrition
ABW= IBW + 0.25(ABW-IBW)
If ABW >130% of IBW use adjusted
Nutritionally at-risk adults
Involuntary weight loss of 10% of usual body weight within 6 months or 5% within 1 month
Involuntary loss of 10 pounds within 1 month
BMI less than 18.5
Increased metabolic requirements
Inadequate intake
calorie vs Kcal
calorie- amount of energy required to raise the temp of 1 mL of water by 1 C
Kcal- amount of energy required to raise the temp of 1 L of water by 1 C
How long can you live without food and water?
Food- 60 days
Water- 5-7
Macronutrients
Carbohydrates (Dextrose)- 3.4Kcal/g
Protein (AA)- 4Kcal/g; 0.16g nitrogen
Lipid- 10Kcal
Micronutrients
Vitamins
Minerals
Trace elements
What is the basic composition of nutrition?
Macronutrients
Micronutrients
Electrolytes
Water
Basal energy expenditure vs Resting energy expenditure
Estimate (calculation) based on demographics
REE- measure
Empiric strategy for estimation of energy requirements
Maintenance- 20-25kcal/kg/day
Critically ill- 25-30kcal/kg/day
Trauma- 30-35kcal/kg/day
Burn- 35-50kcal/kg/day
Empiric strategy for estimation of protein requirements
Maintenance- 1-1.5g/kg/day
Critically ill- 1.5-2g/kg/day
Trauma- 2-2.5g/kg/day
Burn- 2-2.5g/kg/day
What is a caloric recipe?
Dextrose 50-60% (max 7g/kg/day)
Protein 20-30% (max 2.5g/kg/day)
Lipids 10-20% (max 2.5g/kg/day)
Daily fluid provisions
Should provide 30-35 mL/kg/day unless contraindicated
Watch for sensible and insensible water loss
Monitor 24 hour in and outs and volume parameters
Potassium
Major intracellular cation (130mEq/L
Normal serum 3.5-5
Require 0.5-1mEq/kg/day
Involved in action potentials, movement of glucose
Magnesium
Fourth major cation (1500mEq total)
Mainly found in bone
Normal serum Mg 1.3-2.1mg/dL
There is an innacurate reflection of intracellular cells, need ionized Mg but not common
Require 20mEq/day (240mg/day)
Involved in ATP-mediated actions, ion transport, calcium channel activity, nerve conduction
Phosphorous
Major intracellular anion (700g total) Predominantly found in bone Normal serum Phos 2.5-4.5mg/dL Poor reflection of total body stores Require 1000mg/day
Involved in cellular energy, resp function, myocardial contractility, glucose utilization
How do you determine if the gut is working?
Succus entericus- 7L/day Oral-1500 Gastric-1500 Duodenal- 1000 Pancreas- 500 Ileum-3000
Assess if pt is having pain or is having bowel movement
When would you use a PPN?
Need nutrition and cant get TPN Acute or chronic bowel obstruction Severe ileus Prolonged inflammatory bowel disease Enteric fistula Severe shock Inability to tolerate enteral route
Timing of nutrition
Earlier the better
burns> trauma> surgery> medicine
After 7 days for well nourished patients, within 24 hours for burns
Within 3-5 days for nutritionally at risk patients
Start at about 25-30% goal rate and titrate
Refeeding syndrome
Electrolyte and fluid abnormalities resulting from reintroduction of energy in the face of chronic or accelerated malnutrition; energy hyper-utilization Hypophosphatemia Hypomagnesemia Hypokalemia Gluconeogenesis (hyperglycemia) Fluid shifts
Prevent by aggressive supplementation of phos, k, mag before and during nutrition
Nutritional endpoints
Weight- Nonspecific
Visceral Proteins- Albumin (half life is too long to evaluate)
Transferin- may be falsely elevated
Prealbumin- preferred
Retinol-binding protein- used due to short half life
Nitrogen balance
If Nin > Nout= anabolic
Approach for providing nutrition support
Assess need and optimal route Estimate protein, caloric, and volume needs Choose enteral or parenteral formula Calculate goal rate and formula Assess risk for refeeding syndrome Initiate treatment
IV electrolyte replacement
Identify cause (diuretics, oral calcium, refeeding syndrome)
Know ICU/hospital policy
Always replace Mg before or with K
Watch renal function and give 50% dose of Mg, K, and phos if needed
Infusion times for electrolytes
K- Central (20meq/L) and peropheral (10meq/L)
Mg- 1g/hr
Phos- 7.5mmol/hr
