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Approach to Occult GI Bleeding

Definitions - Clarifying the Terminology

• Occult GI bleeding - subacute bleeding that is not clinically visible. It presents as either a positive fecal occult blood test (FOBT) or iron deficiency anemia (IDA), with no hematemesis, melena, or hematochezia. - Sleisenger & Fordtran's Gastrointestinal and Liver Disease
• Obscure GI bleeding - bleeding from a site that is not apparent after routine endoscopic evaluation (EGD + colonoscopy +/- push enteroscopy). Obscure bleeding can itself be either overt (visible blood) or occult (positive FOBT/IDA). - Goldman-Cecil Medicine
• Prevalence context: ~10% of all GI bleeding hospitalizations are from the small bowel (obscure). Of these, 75% originate beyond the reach of a standard endoscope. Iron deficiency has a prevalence of 2-5% among adult men and postmenopausal women, and GI loss is a leading cause.

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Common Causes

Within reach of standard endoscopy (missed initially)

• Cameron ulcers (large hiatal hernia)
• Dieulafoy lesion (aberrant submucosal vessel without ulcer)
• Internal hemorrhoids
• Gastric antral vascular ectasia (GAVE)
• Peptic ulcer disease / H. pylori

Small bowel causes (most common when standard endoscopy is negative)

• Other small bowel causes: NSAID enteropathy, Crohn's disease, celiac disease, radiation enteritis, Meckel's diverticulum, hereditary hemorrhagic telangiectasia (HHT/Osler-Weber-Rendu)

Causes of iron deficiency anemia without GI blood loss

• Celiac disease (malabsorption)
• Atrophic gastritis (decreased absorption)
• Hemolysis
• Menorrhagia (premenopausal women)

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Step-by-Step Diagnostic Approach

Step 1 - Initial Assessment

• Medication history: NSAIDs, aspirin, anticoagulants, steroids
• Prior GI surgeries
• Family history of GI cancer or polyposis
• Skin/mucosal telangiectasias (HHT)
• Symptoms of malabsorption (celiac)
• Menstrual history in premenopausal women

• CBC (microcytic anemia, low Hb)
• Iron studies: serum ferritin (low), transferrin saturation (low), TIBC (elevated)
• CRP/ESR (if inflammatory cause suspected)
• Celiac serology (anti-tTG IgA)
• Reticulocyte count

• All adult men, regardless of age
• All postmenopausal women
• Premenopausal women only after excluding menorrhagia and other non-GI causes

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Step 2 - FOBT-Positive vs. IDA: Different Starting Points

• Colonoscopy is the first step, because FOBT was designed to screen for colorectal cancer (begin at age 45 in average-risk adults per Harrison's)
• If colonoscopy is negative and no IDA/symptoms: no further workup needed per Harrison's
• If IDA or GI symptoms present: proceed to upper endoscopy

• Colonoscopy first (most common source is colorectal lesion)
• Then upper endoscopy + push enteroscopy if colonoscopy is negative
• Take duodenal biopsies during upper endoscopy to exclude celiac disease
• Treat H. pylori if detected (reduces iron absorption and causes microerosions)

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Step 3 - When Standard Endoscopy is Negative (Obscure-Occult)

1. Colonoscopy - if positive: treat. If negative:
2. Push enteroscopy - examines proximal small bowel to ~70 cm past ligament of Treitz. If positive: treat. If negative:
3. Capsule endoscopy (CE) - the key diagnostic tool for small bowel visualization. If positive: proceed to balloon enteroscopy. If negative: supportive care (no aggressive further workup)

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Step 4 - Capsule Endoscopy

• The pivotal investigation once standard endoscopy is unrevealing
• Visualizes the entire small bowel mucosa non-invasively
• Most useful for angiodysplasia, mucosal inflammation, and small tumors
• Yield higher when performed within 2 weeks of acute bleed (while lesion is still active)
• Contraindications: known or suspected bowel obstruction, strictures, swallowing disorder
• After positive capsule: proceed to device-assisted (double-balloon/single-balloon/spiral) enteroscopy for therapeutic intervention

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Step 5 - Deep Enteroscopy (Device-Assisted)

• Double-balloon enteroscopy (DBE) is most common - uses balloon overtube to advance deep into small bowel (>300 cm)
• Can be performed antegrade (per os) or retrograde (per anum)
• Allows both diagnosis and therapy (hemostasis, polypectomy, tattooing)
• Intraoperative enteroscopy reserved for cases where all other modalities fail

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Step 6 - Imaging Modalities

• Multiphasic contrast-enhanced protocol with neutral oral contrast
• One study showed CTE sensitivity 88% vs. capsule endoscopy 38% for identifying small bowel lesions - particularly superior for focal small intestinal tumors (Grainger & Allison)
• Complementary to capsule endoscopy for benign causes (angiodysplasia, inflammation)
• Best combined with CE in clinical practice

• More useful in overt/active bleeding (detects extravasation ≥0.3-0.5 mL/min)
• Less useful in occult/low-grade bleeding (may miss intermittent bleeders)

• Detects bleeding rates as low as 0.1 mL/min
• Used mainly in overt obscure bleeding with rebleed after negative capsule
• Poor anatomic localization - usually followed by angiography

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Step 7 - Angiography and Surgery

• Selective mesenteric angiography: therapeutic (embolization) and diagnostic; requires active bleeding at time of study
• Intraoperative enteroscopy: last resort when all other modalities fail; combined surgical and endoscopic approach

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Special Considerations

When to re-scope before going to capsule endoscopy

• Before labeling bleeding as "obscure," repeat upper endoscopy and colonoscopy, as studies show a lesion is found in up to 25% of cases on repeat examination (missed Dieulafoy, Cameron ulcers, hemorrhoids, GAVE)

H. pylori and iron deficiency

• H. pylori decreases iron absorption and can cause microerosions
• Treat if positive even without obvious ulcer - this alone may resolve IDA in some patients

Celiac disease

• Always biopsy duodenum during upper endoscopy in IDA workup - celiac is a common, easily missed cause of IDA

HHT (Hereditary Hemorrhagic Telangiectasia)

• Autosomal dominant
• Look for telangiectasias on lips, buccal mucosa, tongue, fingernails
• Small bowel AVMs are a major source of recurrent occult bleeding

Medications causing occult blood loss

• NSAIDs: #1 cause of small bowel ulcers/erosions
• Aspirin: gastric erosions
• Anticoagulants/antiplatelets: unmask underlying lesions

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Summary Algorithm - Occult GI Bleed

Positive FOBT or IDA
        |
   Initial labs (iron studies, celiac serology)
        |
   +----|----+
   |         |
FOBT+       IDA
   |         |
Colonoscopy  Colonoscopy first
        |         |
     Negative     Negative
        |         |
    If IDA/Sx → EGD + push enteroscopy
                  |
               Negative
                  |
           Duodenal biopsy (celiac), treat H. pylori if +
                  |
               Still negative
                  |
           Capsule endoscopy
              /        \
           Positive   Negative
              |           |
       Balloon          Supportive
       enteroscopy       care
       (diagnose +       (reassess)
        treat)

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• Goldman-Cecil Medicine International Edition - Chapter 121: Obscure and Occult GI Bleeding
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease - Chapter 20: GI Bleeding
• Grainger & Allison's Diagnostic Radiology - Chapter 21: Occult GI Bleeding
• Harrison's Principles of Internal Medicine (22E, 2025) - Positive FOBT

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Electroconvulsive Therapy (ECT) in Psychiatry

1. Historical Background

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2. Mechanism of Action

Seizure physiology

• A bilateral generalized seizure is necessary for both therapeutic and adverse effects of ECT
• Subconvulsive stimulation is ineffective; the seizure is necessary but not sufficient - its dose relative to seizure threshold also matters
• ECT acts as an anticonvulsant - seizure threshold rises progressively across a treatment course

Neurophysiology

• During seizure: cerebral blood flow, O2 and glucose utilization, and blood-brain barrier permeability increase
• Post-ictally: blood flow and glucose metabolism decrease (most markedly in frontal lobes); the degree of decrease correlates with therapeutic response
• After a successful course: EEG shows massive increase in slow-wave activity over prefrontal cortex in responders; high-intensity bilateral stimulation produces the strongest effect
• EEG typically returns to pretreatment baseline 1 month to 1 year after course completion

Neurotransmitter/receptor changes

• Downregulation of postsynaptic beta-adrenergic receptors (similar to chronic antidepressants, but ECT achieves this faster)
• Enhanced serotonergic transmission (5-HT1A receptor sensitization)
• Increased dopaminergic activity in mesolimbic pathways
• Elevated GABA and endogenous opioid levels
• Increased BDNF (brain-derived neurotrophic factor) - possible contribution to neuroplasticity and antidepressant effect
• Neuroendocrine changes: affects HPA axis, prolactin, thyroid-stimulating hormone

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3. Indications

Primary (First-line) Indications

1. Severe depression with high suicidal risk - ECT works in days vs. weeks for antidepressants
2. Depression with refusal of food/fluid (nutritional emergency - "life-threatening inanition")
3. Catatonia - most dramatic and rapid response; can take as few as 1-4 treatments
4. Severe depression in pregnancy - safe in all trimesters when medications are hazardous
5. Neuroleptic Malignant Syndrome (NMS) - when pharmacotherapy fails

Secondary (After Medication Failure) Indications

1. Major depressive disorder (MDD) - treatment-resistant (failed 2+ adequate antidepressant trials)
2. Bipolar depression - treatment-resistant
3. Mania - severe/refractory; comparable to lithium in RCTs (equal response rates in 1988 trials); requires 8-20 treatments
4. Schizophrenia - as adjunct in treatment-resistant cases or acute exacerbations; 15+ treatments often needed
5. Schizoaffective disorder - particularly when affective component is prominent
6. Parkinson's disease with depression or "on-off" motor fluctuations - ECT has direct dopaminergic effects

Predictors of Good Response to ECT

• Severe melancholic depression
• Psychotic depression (delusional depression responds exceptionally well)
• Catatonic features
• Prior positive response to ECT
• Shorter duration of current episode

Predictors of Poor Response

• Concurrent personality disorder
• Atypical depression
• Long duration of illness
• High levels of anxiety/somatization

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4. Contraindications

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5. Pre-ECT Evaluation

Workup

• CBC, serum electrolytes, urinalysis, LFTs
• ECG (to assess cardiac risk from stimulation-induced autonomic surges)
• Thorough medical history and physical examination
• Anesthesia evaluation

Medications to consider before ECT

• Stop or reduce: benzodiazepines (raise seizure threshold), anticonvulsants (raise seizure threshold, reduce efficacy), lithium (increases risk of post-ECT confusion and prolonged seizures)
• Continue: antihypertensives, cardiac medications, antireflux medications
• Anticholinergics (atropine/glycopyrrolate): may be given pre-procedure to reduce secretions and prevent bradycardia

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6. Technique and Administration

Anesthesia Protocol

1. Anticholinergic premedication - atropine or glycopyrrolate (reduces secretions, prevents bradycardia)
2. Short-acting general anesthetic - methohexital (preferred) or propofol - for rapid induction and short duration
3. Succinylcholine (depolarizing neuromuscular blocker) - to minimize motor convulsions and prevent musculoskeletal injury. A blood pressure cuff can be inflated on one arm prior to succinylcholine to observe the motor seizure in that limb.

Electrode Placement

• High-dose right unilateral ECT (≥6x seizure threshold) achieves equivalent response to bilateral ECT with significantly less cognitive impairment
• Bilateral ECT is preferred in urgent/severe presentations requiring fastest response
• Ultra-brief pulse width bilateral ECT is likely ineffective

Stimulus Parameters

• Modern ECT machines deliver brief pulse (not sine wave) current
• Stimulus measured in millicoulombs (mC) or joules
• Key principle: dose-response relationship - stimulus must be substantially above seizure threshold for right unilateral ECT; for bilateral, even moderately suprathreshold doses are effective
• ~20% of applied charge actually enters the skull to excite neurons (skull impedance is high)

Monitoring the Seizure

• Minimum effective seizure duration: 25 seconds (EEG-monitored)
• EEG monitoring is mandatory; at minimum, electrodes over contralateral hemisphere for unilateral ECT
• Seizure phases: tonic (10-20 sec, plantar extension) → clonic (rhythmic contractions) → postictal suppression (60-90 sec)
• If seizure duration < 25 sec or no seizure: increase stimulus by 25-100%, check electrode contact, consider caffeine sodium benzoate (500-2000 mg IV) to lower seizure threshold

Number and Frequency of Treatments

• Twice-weekly is associated with less memory impairment than three-times-weekly
• Treatment continues until maximal therapeutic response is reached (defined as failure to improve after 2 consecutive sessions)
• If no improvement after 6-10 sessions: switch to bilateral placement and high-density stimulation before abandoning ECT

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7. Adverse Effects

Cognitive Effects (Most Clinically Significant)

• Acute confusion/disorientation - common immediately post-ictal; resolves within 30-60 minutes
• Anterograde amnesia - difficulty forming new memories during the treatment course; typically transient
• Retrograde amnesia - loss of memories from weeks to months surrounding the ECT course; the most persistent side effect
  • Autobiographical memory most affected
  • Usually resolves within weeks-months but can occasionally persist
  • Right unilateral ECT causes significantly less retrograde amnesia than bilateral
• A 2024 meta-analysis (PMID 38101070) found that while ECT causes short-term cognitive impairment, most domains recover at follow-up; autobiographical memory most persistently affected

Cardiovascular Effects

• Immediate bradycardia/asystole (parasympathetic surge with stimulus application) - prevented by anticholinergic premedication
• Followed by tachycardia and hypertension (sympathetic surge from seizure) - typically brief and self-limiting
• ECG changes (ST changes, ectopy) can occur; monitor closely in cardiac patients
• Deaths from ECT are extremely rare: ~1/10,000 treatments (comparable to anesthesia mortality)

Other Adverse Effects

• Headache - most common post-procedure complaint; treat with analgesics
• Muscle aches - from succinylcholine (fasciculations)
• Nausea/vomiting - anesthesia-related; treat with antiemetics
• Prolonged seizure / Status epilepticus (seizure >180 sec) - terminate with IV diazepam 5-10 mg or additional barbiturate anesthetic; requires intubation
• Tardive seizures - spontaneous seizures appearing after ECT, especially in those with pre-existing epilepsy
• Hypomania/mania switch - can occur during ECT for depression, especially in bipolar patients
• Dental/jaw injury - bite block is used to protect teeth

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8. Continuation and Maintenance ECT

Strategies

1. Continuation pharmacotherapy - the 2001 CORE trial demonstrated that nortriptyline + lithium is significantly superior to nortriptyline alone or placebo for 6-month relapse prevention post-ECT
2. Continuation ECT (C-ECT) - weekly then biweekly treatments for 6 months
3. Maintenance ECT (M-ECT) - monthly treatments for patients who relapse despite medications, cannot tolerate medications, or prefer ECT

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9. ECT vs. Ketamine (Recent Evidence)

• Rhee et al. (2022) [PMID 36260324] and Menon et al. (2023) [PMID 37043224] - both concluded ECT demonstrated superior or comparable antidepressant efficacy to ketamine overall, but ketamine had faster onset of action and fewer cognitive side effects. ECT remains the more definitively evidence-based option for severe/treatment-resistant depression.

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10. Special Populations

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11. Summary Table

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• Kaplan & Sadock's Synopsis of Psychiatry - Chapter 22: ECT and Other Brain Stimulation Therapies (primary source)
• Rhee TG et al., JAMA Psychiatry 2022 [PMID 36260324] - Ketamine vs ECT meta-analysis
• Menon V et al., JAMA Psychiatry 2023 [PMID 37043224] - Ketamine vs ECT meta-analysis
• Guo Q et al., Psychiatry Res 2024 [PMID 38101070] - Long-term cognitive effects of ECT