Persistent Hiccups (Singultus)

Definition and Classification

• Tintinalli's Emergency Medicine, p. 470

Pathophysiology

Causes

Benign / Self-Limited

• Gastric distention (overeating, carbonated drinks)
• Alcohol ingestion (relaxes the inspiration-glottis relationship)
• Sudden temperature change in the stomach

Persistent / Intractable - Organic Causes

• Gastroesophageal reflux / esophagitis
• Gastric distention, peptic ulcer, gastritis
• Pancreatitis, hepatitis, bowel obstruction
• Post-operative gastric dilation or paralytic ileus

• Pneumonia, pleuritis, pericarditis
• Myocardial infarction (inferior wall)
• Mediastinal mass
• Phrenic nerve injury (surgical, neoplastic)

• Lateral medullary (Wallenberg) syndrome - a classic association
• Brainstem tumors or cavernous hemangioma
• Elevated intracranial pressure
• Brainstem encephalitis
• Metabolic encephalopathy (uremia - see "brown dry tongue" as a bedside clue)

• Renal failure / uremia (a well-recognized association - inspect tongue for brown dryness)
• Hyponatremia, hypocalcemia, diabetes

• Dexamethasone and other corticosteroids
• Chemotherapeutic agents
• Tramadol (recently reported - PMID 38299410)
• Benzodiazepines, barbiturates

• Tintinalli's Emergency Medicine, pp. 470-471; Adams & Victor's Neurology, p. 570; S. Das Manual of Clinical Surgery, p. 20

Evaluation

1. History: Duration, triggers, medications (especially dexamethasone), prior surgery, alcohol use
2. Check ear canal: Foreign body (hair) pressing on tympanic membrane - a rare but treatable vagal trigger
3. Ask if hiccups persist during sleep: If yes, organic cause more likely
4. Examine tongue: Brown dry tongue suggests uremia/renal failure - immediate workup indicated
5. Chest X-ray: For any persistent/intractable hiccups
6. Labs: BMP (renal function, electrolytes, glucose), LFTs if warranted
7. Fluoroscopy (not routine ED): Unilateral vs bilateral diaphragm movement - unilateral suggests focal phrenic nerve injury
8. CT chest/abdomen, endoscopy, or CNS imaging based on clinical suspicion

Treatment

Physical Maneuvers (interrupt the vagal arc)

• Remove any foreign body from the external auditory canal
• Swallow a teaspoon of dry granulated sugar (as effective as any other method)
• Sip or quickly drink ice water
• Breath holding / Valsalva / breathing into paper bag (raises CO₂)
• Nasogastric tube decompression (post-operative hiccups from gastric dilation)

Drug Treatment

• Tintinalli's Emergency Medicine, p. 471; Adams & Victor's Neurology, p. 570

Key Clinical Pearls

• Post-op hiccups - think dilated stomach or paralytic ileus; insert NG tube for decompression
• Peritonitis involving the diaphragmatic peritoneum can cause persistent hiccups
• Uremia is a classic systemic cause - brown dry tongue is a bedside clue
• Wallenberg syndrome (lateral medullary infarct) - hiccup is one of its features
• Dexamethasone is a notable drug cause; important in oncology patients
• Psychogenic hiccups resolve during sleep (usually)
• Raising CO₂ (breath-holding, rebreathing) is the physiologic basis for most home remedies

Hematemesis - Upper GI Bleeding

This is a medical emergency. Hematemesis (vomiting fresh blood) signals active upper GI bleeding, which carries an overall mortality of up to 10%.

Definitions - Know Your Terms

• Frameworks for Internal Medicine, p. 215

Causes by Anatomic Site

Esophageal

Gastric

Duodenal

Other

• AV malformation
• Malignancy
• ENT source (epistaxis, oropharyngeal bleeding masquerading as GI bleed)
• Tintinalli's Emergency Medicine, pp. 536-537

Immediate Assessment - ABC First

• Hypotension, tachycardia, decreased pulse pressure, tachypnea
• Syncope, confusion, angina
• Note: Young patients can maintain BP despite large blood loss - don't be falsely reassured. Paradoxical bradycardia can occur even with profound hypovolemia.

• Cirrhosis / chronic liver disease → varices
• Retching before bleeding → Mallory-Weiss
• NSAIDs, aspirin, steroids, anticoagulants → PUD / erosive disease
• Prior aortic graft → aortoenteric fistula
• Alcohol abuse → varices, erosive gastritis, PUD

Risk Stratification Scores

Glasgow-Blatchford Score (GBS) - Pre-endoscopy, predicts need for intervention

• GBS 0 = low risk, consider outpatient management
• GBS ≥ 6 = ~50% likelihood of requiring endoscopic treatment

Rockall Score - Post-endoscopy, predicts mortality

• 0-1 points = 0% mortality
• 5 points = ~10% mortality
• ≥ 8 points = ~40% mortality
• Current Surgical Therapy 14e

Emergency Management

Step 1 - Stabilize

• 2 large-bore IVs immediately
• Type and cross-match; prepare for massive transfusion protocol if severe
• Supplemental oxygen; airway management if altered consciousness
• If intubating: aggressively resuscitate first; use lower induction doses to avoid peri-intubation arrest

Step 2 - Resuscitate

• Isotonic crystalloid initially; avoid overaggressive resuscitation (can worsen some bleeds)
• Blood transfusion thresholds:
  • Hgb < 7 g/dL in most patients
  • Hgb < 9 g/dL in elderly or those with comorbidities (coronary artery disease, etc.)
• Correct coagulopathy: FFP/platelets if INR elevated or platelets < 50,000/µL
• Reverse anticoagulants in life-threatening bleed (except if cardiac stents or prosthetic valves are a concern)

Step 3 - Drug Treatment

Step 4 - Endoscopy (Definitive Diagnosis + Treatment)

• EGD = gold standard for diagnosis AND hemostasis
• Timing:
  • Unstable patients: within 6-24 hours after adequate resuscitation
  • Stable patients: within 12-36 hours
• Endoscopic hemostasis options: epinephrine injection, clips, band ligation, electrocoagulation, argon plasma coagulation, laser photocoagulation

Step 5 - Escalation if Endoscopy Fails

• Repeat endoscopy first
• Angiography + embolization (e.g., gastroduodenal artery in posterior duodenal ulcers)
• Surgery: Consider when hemodynamically unstable with >6 units RBC transfused, or persistent/recurrent bleeding
  • Options for bleeding duodenal ulcer: oversewing alone; oversewing + vagotomy + drainage; vagotomy + antrectomy
• TIPS (transjugular intrahepatic portosystemic shunt): for refractory variceal bleeding
• Balloon tamponade (Sengstaken-Blakemore tube): temporary bridge for variceal hemorrhage
• Tintinalli's Emergency Medicine, pp. 537-539; Frameworks for Internal Medicine, pp. 215-219; Current Surgical Therapy 14e

Connection to the Hiccups

1. Peptic ulcer disease / gastritis - gastric irritation causes both hiccups (vagal stimulation) and bleeding
2. Mallory-Weiss tear - repeated retching from hiccups could cause a longitudinal mucosal tear at the GEJ, producing hematemesis
3. Esophageal varices with cirrhosis - uremia (a hiccup cause) + portal hypertension together are serious
4. Medication-induced - if the patient received dexamethasone (a hiccup cause), it is also ulcerogenic

Focused Approach: Patient with Persistent Hiccups (> 48 hours)

What "Persistent" Tells You

Bedside Assessment - Do These First

History to Take

• Duration - when exactly did it start?
• Recent surgery? - early post-op hiccups = gastric dilation / paralytic ileus → NG tube decompression
• Medications - especially dexamethasone, chemotherapy agents, tramadol, benzodiazepines
• Alcohol use - erosive gastritis, liver disease
• Any neurological symptoms - vertigo, dysarthria, dysphagia, ataxia → suspect Wallenberg syndrome (lateral medullary infarct)
• Known renal disease, diabetes, hypertension

Differential Diagnosis - Ranked by System

Most Common in Clinical Practice

CNS - Must Not Miss

Thoracic

Diaphragmatic / Abdominal

Investigations to Order

Baseline (all patients with persistent hiccups)

• Serum creatinine, BUN, electrolytes - rule out uremia, hyponatremia, hypocalcemia
• Blood glucose - diabetic neuropathy/autonomic
• LFTs - liver disease
• FBC/CBC - infection, anemia
• Chest X-ray - mediastinal mass, pneumonia, diaphragm elevation

If CNS cause suspected

• MRI brain with brainstem sequences - Wallenberg syndrome, tumors (MRI far superior to CT for posterior fossa)
• CT brain - if MRI not immediately available

If GI cause suspected

• Upper endoscopy - GERD, PUD, esophagitis
• CT abdomen/pelvis - subphrenic abscess, pancreatitis, mass

If phrenic nerve injury suspected

• Fluoroscopy - unilateral vs bilateral diaphragm movement

Treatment

Treat the Underlying Cause First

Physical Maneuvers (for symptom relief while investigating)

• Swallow a teaspoon of dry granulated sugar
• Sip/drink ice water quickly
• Breath-holding / Valsalva (raises CO₂, physiologically inhibits hiccup reflex)
• Remove foreign body from ear canal if found

Drug Treatment - Step Up Approach

• Tintinalli's Emergency Medicine, p. 471; Adams & Victor's Neurology, p. 570

Bottom Line for This Patient

Persistent hiccups (> 48 hours) in a male patient (more common in males) needs:

1. Tongue inspection and renal function tests immediately
2. Chest X-ray
3. Neurological exam - any brainstem signs demand urgent MRI
4. Medication review - stop any offending drug (esp. dexamethasone)
5. Symptom control with chlorpromazine or metoclopramide while the workup proceeds
6. Refer to gastroenterology if GI cause likely; neurology if CNS signs present

Reading the Prescription

1. T. Sompraz (Esomeprazole) - 1 tablet OD × 2 weeks, BIF (before food)
2. Syr. Insta-raajt (likely an antacid syrup) - 2-0-2, 2 tsp × 2 weeks
3. T. Ursocol 300mg (Ursodeoxycholic acid / UDCA) - 1-0-1 × 2 weeks
4. Regular Exercise / Breathing
5. Follow-up in 3 weeks - fasting blood tests

Can Prednisone + Augmentin + Montelukast Be Taken WITH This Prescription?

Drug-by-Drug Analysis

1. Prednisone (corticosteroid)

2. Augmentin (Amoxicillin-Clavulanate)

3. Montelukast (Leukotriene receptor antagonist)

• Katzung's Pharmacology, p. 559

Summary Table

One Important Clinical Note

• Esomeprazole (acid suppression)
• Antacid syrup (acid neutralisation)
• UDCA (liver/bile support)

🚨 URGENT - This Patient Needs Hospital NOW

Step 1 - IMMEDIATE Actions (Before Hospital)

Step 2 - What to Tell the ER Team

• Hematemesis (vomiting blood) - fresh/bright red or coffee-ground?
• Persistent hiccups (> 48 hours) - preceding the bleed
• Cough - duration, any blood in sputum?
• Current prescriptions: Sompraz (esomeprazole), Ursocol 300, antacid syrup
• New drugs started: Prednisone, Augmentin (amoxicillin-clavulanate), montelukast
• Underlying condition for which those were prescribed

Why This is High Risk - Clinical Reasoning

The Prednisone Connection

• Gastric mucosal erosion and ulceration
• GI perforation and hemorrhage - especially at high doses or with concurrent NSAIDs
• They mask peritoneal signs - making the clinical picture deceptively quiet

The Cough + Hiccups Connection

• Forceful, repeated coughing and hiccupping can cause a Mallory-Weiss tear - a longitudinal mucosal tear at the gastroesophageal junction. This is the most likely unifying diagnosis here.
• Classic history: repeated forceful effort (cough/hiccup/retch) → hematemesis
• Mallory-Weiss tears account for up to 15% of upper GI bleeding episodes

Differential for THIS Patient

⚠️ Note on Ursocol (UDCA): This drug is used for gallstones, primary biliary cholangitis, or liver disease. If this patient has liver disease, esophageal varices must be actively ruled out - variceal bleeding carries the highest mortality of all upper GI bleeds.

What Will Happen in Hospital

Immediate

• 2 large-bore IV lines
• Type and cross-match blood
• Bloods: FBC, BMP (creatinine, electrolytes), LFTs, coagulation (PT/INR), blood glucose
• IV fluid resuscitation
• IV PPI: Omeprazole/Esomeprazole 80 mg bolus → 8 mg/hr infusion
• If cirrhosis suspected: IV Octreotide 50 µg bolus → 25-50 µg/hr + IV Ceftriaxone 1g

Transfusion

• Transfuse if Hgb < 7 g/dL (or < 9 g/dL if elderly or with cardiac disease)
• Do not wait for lab results if actively bleeding with hemodynamic instability

Definitive

• Upper GI Endoscopy (EGD) within 6-24 hours - diagnosis AND treatment
  • Mallory-Weiss: clips, band ligation, epinephrine injection
  • Ulcer: thermocoagulation, clips
  • Varices: band ligation, sclerotherapy

Airway

• If continued hematemesis with reduced consciousness → elective intubation before endoscopy to prevent aspiration

Medication Changes Going Forward

Bottom Line

Persistent hiccups + cough + hematemesis + prednisone = Go to the emergency department immediately.

The most likely cause is a Mallory-Weiss tear from repeated coughing/hiccupping, possibly compounded by steroid-induced mucosal injury. If the patient is on Ursocol for liver disease, variceal bleeding must be urgently excluded.

This cannot be managed at home. The patient needs IV access, IV PPI, blood tests, and urgent endoscopy.

• Sabiston Textbook of Surgery, p. 2185; Tintinalli's Emergency Medicine, pp. 537-539; Frameworks for Internal Medicine, p. 215

🚨 ESOPHAGEAL VARICEAL BLEEDING - CRITICAL EMERGENCY

Variceal hemorrhage carries in-hospital mortality nearly double that of non-variceal bleeding. In cirrhotics, it is the cause of upper GI bleeding 59% of the time. This patient must be in an ICU-level setting immediately.

IMMEDIATE - Resuscitation Phase

Airway

• Position: Left lateral decubitus
• If ongoing hematemesis + altered consciousness → elective endotracheal intubation before endoscopy to prevent aspiration

Access & Bloods

• Two large-bore IV cannulas (≥18G) or large-bore central access (cordis)
• Blood tests STAT: FBC, coagulation (PT/INR, aPTT), LFTs, BMP (creatinine, electrolytes), blood glucose, blood cultures, cross-match
• Urine output monitoring - insert urinary catheter

Transfusion - RESTRICTED STRATEGY

⚠️ Critical: Over-transfusing in variceal bleeding increases portal pressure and triggers rebleeding. A restrictive strategy (Hgb 7-9 g/dL) reduces rebleeding AND mortality compared to liberal transfusion.

Drug Treatment - Start IMMEDIATELY, Simultaneously

1. Octreotide (Vasoactive Agent) - FIRST PRIORITY

• Dose: 50 µg IV bolus → continuous infusion 25-50 µg/hr for 5 days
• Mechanism: Splanchnic vasoconstriction → reduces portal blood flow and variceal pressure
• Start as soon as variceal bleeding is suspected - do not wait for endoscopy
• Improves initial bleeding control and reduces transfusion requirements

2. Ceftriaxone (Prophylactic Antibiotics) - START BEFORE ENDOSCOPY

• Dose: 1 g IV once daily × 5-7 days
• Why: Cirrhotic patients have impaired immunity + gut bacterial translocation during bleeding
• Prophylactic antibiotics reduce: infections, rebleeding, days in hospital, all-cause mortality
• Ceftriaxone preferred over ciprofloxacin (better coverage, especially if quinolone-resistant organisms likely)

3. PPI (Proton Pump Inhibitor)

• Dose: Omeprazole/Esomeprazole 80 mg IV bolus → 8 mg/hr infusion
• Already on oral Sompraz - switch to IV form now
• Supports clot stability by keeping gastric pH > 6

4. Stop Prednisone

• Immediate - corticosteroids raise portal pressure, cause mucosal erosion, and worsen bleeding
• Discuss alternative with prescribing physician

Endoscopy - Definitive Treatment

• Upper GI Endoscopy (EGD) as soon as patient is resuscitated and stabilized
• Within 12 hours of presentation
• Erythromycin 250 mg IV (infused over 20-30 min) given 20-90 minutes before endoscopy to clear blood/clots from stomach for better visualization

Endoscopic Options

If Endoscopy Fails - Escalation Ladder

Endoscopy (EVL) FAILS
        ↓
Balloon Tamponade (Sengstaken-Blakemore tube)
- Controls bleeding in up to 90% of refractory cases
- TEMPORARY bridge only - max 36 hours
- Risk: aspiration, esophageal perforation, pressure necrosis
        ↓
TIPS (Transjugular Intrahepatic Portosystemic Shunt)
- Stent between portal vein branch and hepatic vein
- Controls bleeding in >90% of endoscopy-refractory cases
- Lowers portal pressure gradient to ≤12 mmHg
- Complications: hepatic encephalopathy (25-30%), renal failure, infection
        ↓
Surgical portosystemic shunt / Liver transplant evaluation

After Bleeding Controlled - Prevent Rebleeding

Drug Review in Context of Variceal Bleeding

Summary - One-Line Priority List

1. 🏥 ICU admission immediately
2. 💉 2 large-bore IVs + blood cross-match
3. 💊 Octreotide 50 µg bolus → 25-50 µg/hr infusion - start now
4. 💊 Ceftriaxone 1 g IV - start before endoscopy
5. 💊 IV PPI (esomeprazole 80 mg bolus → 8 mg/hr)
6. 🩸 Transfuse only if Hgb < 7 g/dL, target 7-9 g/dL - do NOT over-transfuse
7. 🔭 Urgent EGD within 12 hours → band ligation (EVL)
8. ⛔ Stop prednisone
9. 📋 Secondary prophylaxis: carvedilol/propranolol + repeat EVL after discharge

• Harrison's Internal Medicine 22e, p. 1312; Schwartz's Principles of Surgery 11e, pp. 1443-1456; Sabiston Textbook of Surgery; Tintinalli's Emergency Medicine

Drug Decisions for Stable Patient with Known Esophageal Varices

The Earlier Prescription (GI prescription)

The New Prescription (Respiratory prescription)

About the Cough

• ACE inhibitors (a common cough cause) are relatively contraindicated in cirrhosis - check if he is on any
• Chronic cough itself generates repeated Valsalva pressure that can stress varices at the GEJ
• Montelukast and Augmentin will help treat the underlying respiratory cause of cough - which is actually protective (reducing cough = less variceal stress)
• Avoid codeine-based cough suppressants - opiates worsen hepatic encephalopathy in cirrhotic patients

What He Must Do Even Though He's Stable

1. See his gastroenterologist urgently - known varices + hematemesis = needs repeat endoscopy soon to assess variceal grade and whether band ligation (EVL) is needed
2. Start a non-selective beta-blocker (propranolol or carvedilol) if not already on one - this is standard secondary prophylaxis to prevent the next bleed
3. Avoid NSAIDs, aspirin, ibuprofen completely - these shred the gastric mucosa
4. No alcohol whatsoever - if that is a factor in his liver disease
5. Soft diet temporarily - avoid hard, rough foods that can mechanically irritate varices
6. Watch for warning signs and go to ER immediately if:
   • Fresh red blood in vomit again
   • Black tarry stools (melena)
   • Dizziness, fainting, rapid heart rate
   • Abdominal swelling (ascites)
   • Confusion (hepatic encephalopathy)

Summary in One Line Per Drug

• Sompraz ✅ Continue - protective
• Antacid ✅ Continue - safe
• Ursocol ✅ Continue - treating root cause
• Prednisone ⛔ Stop - dangerous in this patient right now
• Augmentin ✅ Continue - safe, treats infection/cough
• Montelukast ✅ Continue - safe, helps cough

Tell the doctor who prescribed prednisone about the esophageal varices and the hematemesis episode - they likely did not have this information and will want to prescribe an alternative. For respiratory conditions in a patient with varices, inhaled corticosteroids (e.g., budesonide inhaler) are far safer than systemic oral prednisone.

Cough Management in a Patient with Cirrhosis + Esophageal Varices

First - What is Causing the Cough?

• Respiratory infection - Augmentin is already covering this
• Asthma / allergic airways - Montelukast is already covering this
• GERD-related cough - very common; his esomeprazole helps this
• Post-nasal drip - allergic cause; montelukast helps

Safe Options for Cough in This Patient

✅ Already on (Continue these)

✅ Can Add (Safe in liver disease)

⛔ Drugs to AVOID in This Patient

Practical Recommendation

1. Continue both - they are treating the underlying cause
2. Add dextromethorphan-guaifenesin syrup (e.g., Benadryl Chesty Forte, Mucinex - confirm no alcohol/codeine content on label) for symptom relief
3. Steam inhalation twice daily - simple, safe, effective for loosening secretions
4. If wheeze/chest tightness is part of the cough - ask the doctor for a salbutamol inhaler or budesonide inhaler instead of oral prednisone
5. Check the label of any OTC cough syrup - if it says "codeine," "pholcodine," or contains alcohol, do not use it

The single most important swap here: if the doctor wanted steroids for respiratory disease, budesonide inhaler replaces oral prednisone safely in this patient. Suggest this to the treating physician.

• Lippincott's Pharmacology; Goldman-Cecil Medicine; Goodman & Gilman's Pharmacology

What to Start Now (He Has Taken Nothing Yet)

✅ START Immediately - The GI Prescription (Safe, Needed)

⛔ DO NOT START - The Respiratory Prescription

For the Cough Right Now

1. Start Augmentin as prescribed - treats the infection causing cough
2. Start Montelukast as prescribed - reduces airway inflammation
3. Steam inhalation twice daily - safe, no drugs, clears airways
4. Warm honey + ginger water - soothes throat naturally
5. No OTC cough syrups until you check the label - anything with codeine or alcohol is dangerous for him

The ONE Thing That Still Needs to Happen

Even though he is stable - he must see his gastroenterologist within the next 24-48 hours about the hematemesis episode.

Known varices + any bleed = needs repeat endoscopy to assess variceal grade, and likely needs to be started on a beta-blocker (propranolol or carvedilol) for long-term prevention of the next bleed.

Do not delay this step just because he is feeling okay right now.