Calcium Replacement in Massive Transfusion

Massive Transfusion: VitaCal Calcium Replacement

Purpose

• Prevent or treat transfusion-associated hypocalcemia during massive hemorrhage resuscitation.
• Citrate in transfused blood products binds ionized calcium. Monitor and correct ionized calcium during ongoing bleeding and transfusion.

Proposed Local VitaCal Rule

• VitaCal concentration: 400 mg per ampule.
• After 4 units of PRBCs: give 2.5 ampules of VitaCal.
  • Calculation: 2.5 × 400 mg = 1,000 mg = 1 g calcium gluconate.
• After 8 units of PRBCs: give 5 ampules of VitaCal.
  • Calculation: 5 × 400 mg = 2,000 mg = 2 g calcium gluconate.
• Reassess ionized calcium, ECG, hemodynamics, and the ongoing transfusion rate. Do not use a fixed schedule as a substitute for clinical monitoring.

Evidence Base

• Rajesh et al. performed a retrospective, single-center Level III cohort study of trauma patients receiving low-titer O whole blood (LTOWB) and calcium prehospital or within 4 hours of arrival.
• In adjusted analysis, at least 1 g calcium chloride per 2 units of LTOWB was associated with lower odds of 24-hour mortality.
• The study found no significant association for calcium gluconate in the subgroup with greater LTOWB requirements.
• The authors concluded that prospective validation is needed.

Important Interpretation Limit

• The published threshold is calcium chloride per LTOWB, not calcium gluconate per PRBC.
• 1 g calcium gluconate is not pharmacologically equivalent to 1 g calcium chloride. Calcium chloride provides more elemental calcium per gram.
• Therefore, the proposed “2.5 VitaCal ampules after 4U PRBC” rule is a local operational adaptation, not a direct dose conversion from the cited study.
• Confirm the institutional massive transfusion protocol, the exact VitaCal formulation, line-access requirements, and ionized-calcium targets before adopting it as a standing order.

Practical Bedside Checklist

• Activate hemorrhage control and balanced resuscitation in parallel.
• Send or obtain serial ionized calcium when available.
• Give calcium using appropriate IV access and cardiac monitoring according to local medication policy.
• Watch for severe hypocalcemia, including hypotension, reduced myocardial contractility, prolonged QT interval, or arrhythmia.
• Reassess after each transfusion cycle and adjust to ionized calcium and clinical status.

Summary Takeaway

• Proposed local rule: VitaCal 400 mg/ampule, 2.5 ampules after 4U PRBCs and 5 ampules after 8U PRBCs.
• Evidence-supported threshold studied: at least 1 g calcium chloride per 2U LTOWB in a retrospective trauma cohort.
• Do not claim direct equivalence between the VitaCal PRBC rule and the calcium-chloride LTOWB study threshold.

Reference

Rajesh A, Barry L, Limon D, et al. Aggressive calcium chloride dosing reduces early mortality in trauma patients receiving whole blood resuscitation. Journal of Trauma and Acute Care Surgery. 2026;101(1):57-64. doi: 10.1097/TA.0000000000005009

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Evidence scope: retrospective single-center trauma cohort using LTOWB.

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome: Lecture Notes

Definition and Clinical Significance

• Neuroleptic malignant syndrome (NMS) is a life-threatening syndrome associated with dopamine antagonism or abrupt withdrawal of dopaminergic therapy.
• Suspect NMS when relevant medication exposure is followed by:
  • Fever
  • Generalized lead-pipe rigidity
  • Altered mental status
  • Autonomic instability

Triggers and Risk Factors

• Relevant triggers include:
  • Antipsychotics
  • Metoclopramide
  • Prochlorperazine
  • Promethazine
  • Abrupt withdrawal of dopaminergic therapy
• Factors that increase risk include:
  • Rapid dose escalation
  • Dehydration
  • Agitation requiring intramuscular injections
  • Neurologic disease

Diagnosis and Differential Diagnosis

• NMS is a clinical diagnosis. No laboratory test confirms it.
• Levenson criteria use fever and rigidity plus at least 2 additional features:
  • Altered mental status
  • Tachycardia
  • Tachypnea
  • Leukocytosis
  • Elevated creatine kinase (CK)
• Obtain a medication history while evaluating competing immediately life-threatening diagnoses.
• Key differential diagnoses:
  • Serotonin syndrome: commonly develops within minutes to hours after exposure and features hyperreflexia and spontaneous or inducible clonus.
  • NMS: commonly evolves over days to weeks, with reduced reflexes and no clonus.
  • Malignant hyperthermia: follows anesthetic exposure.

Evaluation and Monitoring

• Obtain and monitor:
  • CK
  • Renal function
  • Urine output
  • Electrolytes
  • Acid-base status
  • Electrocardiogram (ECG)
• Rhabdomyolysis may cause myoglobinuria, acute kidney injury, hyperkalemia, hyperphosphatemia, hypocalcemia, and arrhythmias.
• A urine dipstick positive for blood without red blood cells may indicate myoglobin, not hematuria alone.

Immediate Management

• Stop all antipsychotics and other dopamine antagonists immediately.
• Begin supportive care in parallel:
  • Intravenous hydration
  • Active cooling
  • Cardiorespiratory monitoring
  • Serial temperature, CK, renal function, electrolytes, and urine-output assessment
• Benzodiazepines are listed as first-line medication for agitation and muscle relaxation.

Escalation and Disposition

• If response is inadequate, the local source lists dantrolene or bromocriptine as escalation options.
• Amantadine or dopamine replacement are listed as adjunctive choices.
• Severe rigidity with respiratory compromise may require intubation and neuromuscular paralysis.
• Refractory cases may require electroconvulsive therapy.
• Suspected NMS warrants hospital admission, typically intensive care.

Clinical Pitfalls and Takeaway

• Avoid delayed recognition.
• Do not treat fever without removing the trigger.
• Avoid anchoring on infection before considering NMS.
• Medication choices and doses require review against current institutional toxicology, pharmacy, and critical-care protocols.

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This educational summary does not establish medication dosing or replace institutional protocols.

Diabetic Ketoacidosis Management

Diabetic Ketoacidosis: Treat Ketones, Not Just Glucose

Diagnostic Framework

• DKA requires all three of the following:
  • Diabetes history or glucose at least 200 mg/dL.
  • Ketosis.
  • Metabolic acidosis.
• Prefer blood beta-hydroxybutyrate when available.
  • A value at least 3.0 mmol/L supports DKA.
  • Neither glucose alone nor an anion gap alone establishes the diagnosis.

Common Triggers

• Infection.
• Missed insulin or new diabetes.
• Myocardial infarction, stroke, or pancreatitis.
• Steroids.
• SGLT2 inhibitors.

Initial Resuscitation and Monitoring

• Use balanced crystalloids when available. Normal saline remains acceptable when balanced fluids are unavailable.
• Reassess serially:
  • Hemodynamics and urine output.
  • Electrolytes.
  • Glucose and acid-base status.

Potassium Before Insulin

• Potassium determines whether insulin can safely begin.
• If potassium is below 3.5 mEq/L:
  • Hold insulin.
  • Replace potassium first.
• If potassium is 3.5 to 5.0 mEq/L:
  • Add 20 to 30 mEq potassium to each liter of intravenous fluid.
• If potassium exceeds 5.0 mEq/L:
  • Withhold initial replacement.
  • Monitor closely.
• Aim for potassium 4 to 5 mEq/L.

Insulin and Dextrose Strategy

• Once potassium is safe, use intravenous insulin.
• Target a glucose decline of 50 to 70 mg/dL each hour.
• When glucose falls below 200 mg/dL:
  • Add dextrose.
  • Continue insulin until ketosis and acidosis resolve.
• Give basal insulin 2 to 4 hours before discontinuing the intravenous insulin infusion.

Biochemical Resolution

• The endpoint is biochemical resolution, not euglycemia.
• When beta-hydroxybutyrate is available, resolution requires:
  • Plasma ketones below 0.6 mmol/L.
  • Venous pH at least 7.30 or bicarbonate at least 18 mmol/L.
  • Glucose ideally below 200 mg/dL.
• Do not use anion-gap normalization as the primary endpoint. Saline-related hyperchloremic acidosis can persist after ketone clearance.

SGLT2-Associated Euglycemic DKA

• Euglycemic DKA may occur with glucose below 200 mg/dL.
• Stop the SGLT2 inhibitor on admission.
• Add dextrose early so insulin can continue until ketosis and acidosis resolve.

Practical Takeaway

• Key point: Treat ketone clearance and metabolic-acidosis resolution, not glucose alone.
• This adult educational summary does not replace local DKA, ICU, perioperative, or endocrinology protocols.

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YouTube: https://youtu.be/UUGJjt5h4FY

Trephination of Subungual Hematoma

Overview

• Trephination is the controlled creation of a small opening in the nail plate to decompress a painful subungual hematoma.
• A subungual hematoma is blood trapped beneath a fingernail after trauma.
• Decompression can rapidly relieve pressure and throbbing pain.
• The procedure is most useful when the hematoma is painful and the nail plate is intact and adherent to the nail bed.

Preprocedure Assessment

• Examine and document:
  • Neurovascular status.
  • Sensation and range of motion.
  • Nail stability.
  • Lacerations and contamination.
  • Evidence of fracture.
• Consider radiographs after a crush injury or with significant tenderness.
• Seek hand-surgery assessment rather than simple trephination when there is:
  • A displaced fracture.
  • A disrupted or avulsed nail plate.
  • Gross contamination.
  • A suspected complex nail-bed laceration.

Procedure

• Obtain consent and clean the nail.
• Anesthesia is often unnecessary because decompression is brief, but a digital block can be offered.
• Create 1 or more small openings over the hematoma with electrocautery or a sterile needle.
• Avoid excessive depth and contact with the nail bed.
• Allow blood to drain. Gentle pressure may help.
• Irrigate when needed and apply a nonadherent dressing.

Aftercare and Follow-up

• Keep the digit clean and dry.
• Change the dressing as instructed.
• Use elevation, ice, and analgesia as needed.
• Drainage may continue for 24 to 48 hours.
• Routine antibiotics are generally not required for an uncomplicated injury. Management may change with an open fracture, contamination, immunocompromise, or bite injury.
• Address tetanus status when indicated.
• Advise urgent reassessment for increasing pain, redness, warmth, swelling, pus, fever, numbness, or impaired motion.
• The nail may remain discolored or eventually shed. Regrowth takes months.

Clinical Takeaway

• Simple trephination is a focused decompression procedure for a painful subungual hematoma with an intact, adherent nail plate.
• Evaluate for associated fracture, nail disruption, contamination, and complex nail-bed injury before proceeding.
• Local protocols and specialist advice should guide atypical injuries.

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YouTube: https://www.youtube.com/watch?v=o5ppLYMHdjg

CSF Patterns in Suspected Meningitis

Core Principle

• Interpret cerebrospinal fluid (CSF) findings as a physiologic pattern, not as a single laboratory value.
• Record and interpret:
  • Opening pressure
  • Fluid appearance
  • Leukocyte count and differential
  • Protein
  • CSF glucose with a paired serum glucose value
  • Microbiology
  • Lactate
• Integrate the CSF profile with illness timing, host factors, examination findings, and clinical severity.

Bacterial Meningitis

• Typical CSF pattern:
  • Elevated opening pressure
  • Turbid or purulent fluid
  • Neutrophilic pleocytosis, often greater than 1,000 cells per microliter
  • Protein greater than 100 mg/dL
  • Low CSF glucose or a CSF-to-serum glucose ratio below 0.4
  • Elevated lactate
• Gram stain is often positive, but a negative result does not neutralize a dangerous clinical syndrome.
• Do not delay treatment when bacterial meningitis is clinically suspected.

Viral Meningitis

• Typical CSF pattern:
  • Clear fluid
  • Normal or mildly elevated opening pressure
  • Lymphocytic pleocytosis
  • Mildly elevated protein
  • Normal glucose
  • Normal lactate
• Clinical pearl:
  • Early viral disease may be neutrophil-predominant before the expected lymphocytic pattern develops.
  • A single CSF snapshot is less reliable than serial clinical reasoning and pathogen-directed testing.

Tuberculous and Fungal Meningitis

• Shared CSF features may include:
  • Lymphocytic pleocytosis
  • Low glucose
  • Elevated protein
  • Elevated lactate
• Tuberculous meningitis may produce very high opening pressure and protein concentrations, sometimes greater than 1,000 mg/dL.
• A negative tuberculosis polymerase chain reaction result does not exclude tuberculous meningitis because sensitivity is limited.
• Fungal evaluation may include culture and cryptococcal antigen testing.
• A very high opening pressure with a positive cryptococcal antigen result supports cryptococcal meningitis.

Special Findings

• CSF eosinophilia shifts the differential toward:
  • Parasitic infection
  • Coccidioidomycosis
  • Drug reaction
• When red cells contaminate CSF, use a rough correction of 1 white blood cell per 250 to 500 red blood cells rather than overcalling pleocytosis.

Empiric Therapy and Practical Takeaways

• The provided local source lists ceftriaxone, vancomycin, and ampicillin as empiric therapy for suspected adult central nervous system infection.
• Ampicillin provides Listeria coverage in immunocompromised or other risk groups.
• Steroid use is scenario-specific, particularly when pneumococcal or tuberculous meningitis is suspected.
• Follow local protocols for empiric treatment and adjunctive therapy.

Summary Takeaway

• Use the full CSF pattern and the clinical context to distinguish bacterial, viral, tuberculous, fungal, and other causes of meningitis.
• Do not let a negative Gram stain, an early neutrophilic pattern, or a negative tuberculosis polymerase chain reaction result override a high-risk clinical syndrome.
• Treat suspected bacterial meningitis promptly while diagnostic testing proceeds.

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Confirm treatment decisions against current local protocols.

Anticoagulated Minor Head Injury

Anticoagulated Minor Head Injury: CT, Disposition, and Safety Netting

Core principle

• Anticoagulation lowers the threshold for initial imaging after minor head trauma.
• It does not automatically require admission, observation, or serial CT after a reassuring evaluation.

Initial evaluation

• In adults taking anticoagulants or non-aspirin antiplatelet therapy, commonly used head-injury decision rules were not derived to safely exclude intracranial hemorrhage in this group.
• Do not rely on those decision tools alone to omit the initial noncontrast head CT.
• Assess neurologic status, including whether the examination and mental status are at baseline.

After a negative initial CT

• If the initial CT is negative and the neurologic examination is at baseline:
  • Routine repeat CT is generally not recommended.
  • Routine admission or observation solely for head injury is generally not recommended when there is no other indication for monitoring.
• A normal CT reduces risk but does not replace reassessment, clinical judgment, or discharge planning.

Residual risk and evidence limits

• Delayed hemorrhage is uncommon in local evidence summaries, with heterogeneous observational estimates around 1% to 2%.
• Most delayed bleeds identified on repeat imaging did not require intervention.
• Direct prospective comparisons of repeat CT, observation, and discharge remain limited.

Discharge requirements

Before discharge, confirm:

• Baseline mental status.
• No new focal neurologic deficit.
• Reliable supervision and the ability to return if symptoms evolve.

Provide explicit return precautions for:

• Worsening headache.
• Vomiting.
• Confusion or increasing drowsiness.
• New weakness.
• Speech or gait change.
• Seizure.
• Any neurologic deterioration.

When to observe or admit

• Clinical deterioration.
• Abnormal initial CT findings.
• Another medical reason for monitoring.
• Inability to arrange reliable follow-up or observation.

Important cautions

• Aspirin monotherapy is outside the principal recommendation scope because available evidence is limited.
• Older patients taking antiplatelet therapy who have loss of consciousness, amnesia, or GCS below 15 may need individualized observation.
• Institutional pathways and patient-specific factors remain decisive.
• Consider fall-risk assessment and review of the anticoagulation indication after the acute visit.

Summary takeaway

• Obtain an initial noncontrast head CT when appropriate for anticoagulated adults with minor head injury.
• After a negative CT and baseline neurologic examination, avoid routine serial CT, admission, or observation solely because of anticoagulant exposure.
• Use reassessment, reliable supervision, and clear safety-netting to individualize disposition.

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Apply local protocols and patient-specific clinical judgment.

Acute Aortic Syndromes

Acute Aortic Syndromes: Diagnose the Catastrophe

Scope

• Acute aortic syndromes include:
  • Aortic dissection
  • Intramural hematoma
  • Penetrating aortic ulcer

When to Suspect Acute Aortic Syndrome

• Consider acute aortic syndrome in patients with chest, back, or abdominal pain that is:
  • Abrupt and severe
  • Maximal at onset
  • Migrating
  • Tearing, ripping, sharp, or otherwise described as different from prior pain
• Pair the pain history with high-risk findings:
  • Pulse deficits
  • New diastolic murmur
  • Syncope
  • Neurologic deficits
  • ECG changes
• Normal blood pressure does not exclude type A dissection.

Diagnostic Approach

• CT angiography is the diagnostic test of choice.
• Use bedside transesophageal echocardiography when instability makes CT impractical.
• D-dimer-based decision rules are an adjunct only for selected low-risk patients.
  • The literature does not support routine rule-out use.
• When suspicion is high:
  • Do not delay transfer solely to obtain every imaging plane.
  • A noncontrast CT demonstrating aortic enlargement with a convincing clinical presentation should accelerate transfer to an aortic surgery center.

Initial Anti-Impulse Treatment

• Begin anti-impulse treatment while arranging definitive care.
• Target systolic blood pressure: 100 to 120 mmHg.
• Use intravenous beta blockade first:
  • Labetalol
  • Esmolol
• Add nicardipine if further blood pressure reduction is required.
• Give nitroprusside only after beta blockade because reflex tachycardia can increase aortic stress.
• Provide analgesia to reduce sympathetic drive.
• Establish large-bore intravenous access and monitor the patient.

Definitive Management

• Type A disease:
  • Involves the ascending aorta.
  • Requires emergency surgical management.
• Type B disease:
  • Involves the descending aorta.
  • Is managed medically unless complications develop.
  • Complications include malperfusion, rupture, or rapid expansion.

High-Risk Errors to Avoid

• Do not treat suspected acute coronary syndrome with anticoagulation or thrombolysis before excluding dissection.
• Do not be reassured by stable vital signs.
• Do not route a likely type A patient through a nonsurgical hospital.

Summary Takeaway

The essential sequence is early recognition, controlled impulse reduction, and rapid specialist transfer.

Pediatric Small-Bowel Obstruction

Pediatric Small-Bowel Obstruction: When to Operate

Core Clinical Principle

• The operative decision in pediatric small-bowel obstruction (SBO) is driven by two questions:
  • Is the bowel wall viable?
  • Is the obstruction likely to resolve without surgery?
• Suspected intestinal ischemia is time-critical.
• Perforation reflects ischemic necrosis rather than simple mechanical overdistension.

Why Children Require a Different Threshold

• Children are not small adults:
  • They have a thinner bowel wall and limited mucosal reserve.
  • In newborns, even a 180-degree volvulus may cause necrosis. Older children may require more than 360 degrees.
  • Neonatal bilious vomiting should be treated as midgut volvulus until proven otherwise.
• The threshold for concern about pediatric abdominal compartment syndrome is lower:
  • The overall mortality is around 48.87%, rising to 58.61% in neonates aged 0 to 30 days.

Three-Axis Serial Assessment

Reassess every 2 to 4 hours, using clinical findings, laboratory data, and imaging.

Clinical Assessment

• Monitor mental status, respiratory pattern, heart rate, blood pressure, urine output, abdominal distension, abdominal-wall color, bowel sounds, tenderness, rebound, and skin perfusion.
• Red flags: peritonitis, new tachypnea, signs of shock, and sudden abdominal-wall discoloration.

Laboratory Assessment

• Obtain complete blood count, electrolytes, C-reactive protein, lactate, and an arterial blood gas when the child is tachypneic.
• Red flags: metabolic acidosis with respiratory compensation, lactate greater than 2 mmol/L after resuscitation, and rising C-reactive protein.

Imaging Assessment

• Use serial abdominal radiographs every 4 to 6 hours, point-of-care ultrasound, and computed tomography when necessary.
• Red flags: a fixed loop with an unchanged pattern on two serial radiographs, worsening bowel-wall edema, increasing free fluid, and a clear transition point.

Time-Critical Presentations

Neonate With Bilious Vomiting

• Treat as possible midgut volvulus.
• Immediate actions:
  • Keep the patient NPO.
  • Decompress with a nasogastric tube.
  • Start intravenous fluids.
  • Obtain abdominal ultrasound for a whirlpool sign or an upper gastrointestinal series within 1 hour.
• A 6-hour delay can result in total midgut necrosis, short-bowel syndrome, or death.

Infant Aged 1 Month to 2 Years With Intermittent Crying and Bloody Stool

• Treat as possible intussusception.
• Use ultrasound first. The sensitivity is 89% to 95%. A point-of-care ultrasound can equal radiology accuracy.
• Pursue early contrast-enema reduction. The success rates is above 90% with early diagnosis.
• Refer for surgery after failed reduction or symptom duration beyond 48 hours.

High-Yield Decision Pearls

Fixed-Loop Sign

• A stable proximal gas pattern on two abdominal radiographs taken 4 to 6 hours apart suggests mechanical obstruction.
• This provides a practical serial marker when advanced imaging is unavailable.

Tachypnea Requires an Arterial Blood Gas

• New tachypnea in a child with SBO requires immediate arterial blood gas testing.
• Metabolic acidosis with respiratory compensation is a red flag for bowel ischemia and urgent surgical assessment.

Referral Criteria

Immediate Emergency Referral

• Neonatal bilious vomiting
• Suspected midgut volvulus
• Signs of intestinal ischemia
• Peritonitis
• Hemodynamic instability
• Failed intussusception reduction

Recommended Referral

• School-age adhesive SBO with no improvement after more than 24 hours of conservative treatment
• Recurrent distension after prior neonatal surgery
• No local pediatric ultrasound capability
• Family request

Pre-Referral Preparation

• Establish two intravenous lines.
• Place a nasogastric tube and document output.
• Send or obtain complete blood count, serum chemistries, arterial blood gas, lactate, abdominal radiograph, and point-of-care ultrasound files.
• Communicate age and symptoms, vital signs and arterial blood gas status, and the interventions already performed with their timeline.

Imaging and Documentation Considerations

Abdominal radiography, point-of-care ultrasound, and CT scan are standard.

Gastrografin use for a gastrointestinal-series also predicts conservative-treatment success:

• Dose: 5 to 10 mL/kg orally or by nasogastric tube
• Use caution in infants younger than 1 year

Documentation

• Record serial evaluations with timestamps and results.
• When changing from conservative management to surgery, document objective deterioration:
  • Lactate trend
  • Imaging comparison
  • Peritonitis findings
• Clear documentation supports medicolegal defensibility.

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Bottom Line

• The key tool is repeated bedside reassessment every 2 to 4 hours.
• Early recognition of ischemic red flags and disciplined three-axis reassessment should shorten time to surgical decision-making.

Tension Pneumothorax

Tension Pneumothorax: Decompress the Physiology, Not the Image

Core Principle

• Tension pneumothorax is a time-critical obstructive-shock syndrome.
• A one-way pleural air leak progressively raises intrapleural pressure, compresses the affected lung, shifts the mediastinum, and impairs venous return.
• Diagnose it clinically when deterioration occurs.
• In an unstable patient, imaging must not delay decompression.

Clinical Recognition

• Consider the diagnosis with:
  • Unilateral absent breath sounds.
  • Hypoxia, tachycardia, and hypotension.
  • Hyperresonance on the affected side.
• Do not require the classic triad before acting:
  • Tracheal deviation is late and unreliable.
  • Distended neck veins may be absent with hypovolemia.
  • Bilateral tension pneumothoraces may not produce an obvious mediastinal shift.

Positive-Pressure Ventilation Warning

• Maintain a high index of suspicion after positive-pressure ventilation.
• In a ventilated patient, abrupt falling oxygen saturation, rising airway pressures, and hypotension require immediate assessment.
• Assess the circuit and endotracheal tube while considering tension pneumothorax.
• Brief ventilator disconnection can transiently improve hemodynamics but is not definitive treatment.

Immediate Needle Decompression

• Use either site:
  • Second intercostal space at the midclavicular line.
  • Fourth or fifth intercostal space at the anterior axillary line.
• The lateral approach is preferred in obesity.
• Insert a 14-gauge angiocatheter that is at least 5 cm long:
  • Advance perpendicular to the chest wall.
  • Insert over the rib.
• An audible rush of air supports the diagnosis.

Definitive Management and Reassessment

• Needle decompression is a bridge, not definitive care.
• Place tube thoracostomy promptly and connect drainage.
• Monitor for reaccumulation because a catheter can kink or dislodge.
• In pulseless electrical activity, bilateral finger thoracostomy is the listed rescue maneuver.

Role of POCUS and Imaging

• Use POCUS only when it does not interrupt immediate treatment.
• Supportive POCUS findings include:
  • Absent lung sliding, suggesting pneumothorax.
  • A fixed, dilated IVC and hyperdynamic right ventricle, supporting tension physiology.
• In a stable patient, radiography or ultrasound can define findings.
• Negative or delayed imaging cannot overrule clinical deterioration.

Practical Takeaway

• Practice the sequence: recognize, decompress, definitively drain, and reassess.
• Follow local trauma and equipment protocols.

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Follow local trauma and equipment protocols.

Epiglottitis

Adult and Pediatric Epiglottitis: Airway Before Imaging

Core Principle

• Epiglottitis is an acute bacterial infection of the epiglottis and adjacent supraglottic structures.
• Airway obstruction can develop within hours.
• The immediate priority is to recognize a threatened airway, minimize agitation, mobilize an airway-capable team early, and preserve the patient's position of comfort.
• Do not prioritize routine throat examination or diagnostic imaging over airway safety.

Pediatric Recognition and Immediate Management

• High-risk clinical pattern:
  • Sudden fever and toxic appearance.
  • Drooling, dysphagia, or dysphonia.
  • Respiratory distress or tripod positioning.
  • Absent cough.
  • Stridor is a late and ominous sign.
• Avoid precipitating obstruction:
  • Do not use a tongue blade.
  • Do not otherwise manipulate the oropharynx when epiglottitis is suspected.
  • Keep the child upright and avoid forced supine positioning.
• Escalate early:
  • Involve ENT and anesthesiology.
  • Obtain a lateral neck radiograph only when the child is calm and clinically stable.
  • Imaging must never delay airway management.

Adult Recognition and Diagnostic Approach

• Adults may appear less acutely ill than children.
• Suspect epiglottitis when severe sore throat, odynophagia, dysphagia, saliva spitting, or voice change occurs despite a relatively benign oral examination.
• For a stable adult:
  • Flexible nasopharyngoscopy with airway-capable support can directly identify an erythematous, edematous epiglottis and supraglottic swelling.
  • CT or radiography are adjuncts for stable patients.
  • Imaging is not a substitute for airway planning or direct visualization.

Antimicrobial Therapy

• Assess and plan for the airway before initiating routine treatment.
• Source-based treatment options include:
  • Ceftriaxone or cefotaxime.
  • Add vancomycin for severe disease or relevant risk factors.
  • Ampicillin-sulbactam is an adult alternative without severe features.
• Modify antibiotic therapy according to culture results and local resistance patterns.

Adjuncts, Airway Preparation, and Monitoring

• Steroids have limited and controversial evidence.
• Nebulized epinephrine may temporarily reduce edema but cannot secure an airway.
• Anticipate difficult intubation:
  • Prepare smaller endotracheal tubes.
  • Ensure surgical-airway backup.
• Escalate monitoring for severe disease.
• Airway edema may peak 12 to 24 hours after presentation.
• Clinical improvement commonly begins by day 3 after appropriate treatment.

Practical Takeaways

• Suspected epiglottitis is an airway emergency until proven otherwise.
• Minimize agitation and avoid unnecessary oropharyngeal manipulation.
• Use imaging only in clinically stable patients and never allow it to delay airway management.
• Individual airway decisions require local difficult-airway pathways and specialist judgment.

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Individual airway decisions require local difficult-airway pathways and specialist judgment.

Catecholamine-Sparing Strategies in Septic Shock

Source and Scope

• Primary source: Dubech A, Picod A, Pierre A, Preau S, Favory R, Garcia B. Current and Future Strategies Aiming at Reducing Catecholamine Exposure in Septic Shock. Critical Care. 2026;30:427.[1]
• The source is a narrative review, not a treatment guideline or a systematic review.
• The review integrates physiology, randomized trials, observational studies, post hoc analyses, preclinical work, and emerging biomarker-guided strategies. These evidence types should not be treated as equivalent.
• Current bedside recommendations in these notes are reconciled with the 2026 Surviving Sepsis Campaign (SSC) adult guideline.[2,3]
• Disclosure context: the corresponding author reported honoraria for presentations and meetings related to DPP3, angiotensin II, and vasopressin outside this work. Emerging interventions should be interpreted with the same evidentiary caution applied to all narrative reviews.

Core Clinical Takeaway

• Norepinephrine remains the first-line vasopressor for septic shock because it restores perfusion pressure rapidly and has a more favorable safety profile than dopamine or epinephrine.
• Catecholamine sparing does not mean withholding norepinephrine from a hypotensive, hypoperfused patient.
• The practical goal is to:
  • Start norepinephrine early when vasoplegia persists.
  • Avoid prolonged severe hypotension.
  • Use the lowest dose that achieves an individualized perfusion goal.
  • Stop unnecessary fluid loading.
  • Reassess cardiac function, venous congestion, fluid responsiveness, and tissue perfusion.
  • Add nonadrenergic or adjunctive treatment when supported by the clinical phenotype and evidence.
• Higher norepinephrine doses are strongly associated with higher mortality, but this relationship is confounded by shock severity. It does not prove that norepinephrine itself is the cause of death.
• Many proposed catecholamine-sparing interventions shorten vasopressor exposure without demonstrating a survival benefit. A reduction in dose or duration is not automatically a patient-centered benefit.

Why Norepinephrine Remains Central

Arterial Tone and Perfusion Pressure

• Septic shock is characterized by profound vasodilation and loss of arterial vascular tone.
• Norepinephrine activates alpha-1 adrenergic receptors and produces dose-dependent increases in systemic vascular resistance and mean arterial pressure (MAP).
• Systemic vascular resistance is a derived global variable. It does not fully describe regional or microcirculatory flow.
• The major pressure drop in the circulation occurs across small arteries and arterioles, not uniformly across the entire vascular system.

The Vascular Waterfall Concept

• Critical closing pressure (Pcrit) is the arterial pressure below which a vessel collapses and flow stops, even if a nominal pressure gradient remains.
• Tissue perfusion pressure can be conceptualized as the gradient between arterial pressure and Pcrit.
• Microcirculatory flow also depends on the vascular waterfall gradient between Pcrit and mean systemic filling pressure (Pmsf).
• In septic vasoplegia:
  • Pcrit may fall toward Pmsf.
  • The vascular waterfall gradient narrows or disappears.
  • Cardiac output may remain normal or high while tissue perfusion remains inadequate.
• Norepinephrine can restore effective flow when it raises Pcrit above Pmsf and raises arterial pressure above the new Pcrit.
• Venous congestion raises Pmsf and can compress the Pcrit-to-Pmsf gradient. A normal MAP therefore does not guarantee adequate tissue perfusion.
• Bedside implication: reassess venous congestion, cardiac function, capillary refill, skin perfusion, urine output, mental status, and lactate kinetics rather than treating MAP as the only target.

Venous Return and Preload

• Alpha-mediated venoconstriction increases stressed venous volume and Pmsf.
• In preload-responsive patients, this may increase venous return and cardiac output.
• In a physiologic study of 25 preload-responsive patients with septic shock and diastolic arterial pressure of 40 mm Hg or lower, increasing norepinephrine raised preload indices and reduced the cardiac index response to a repeat passive leg raise from 19% to 13%.[1]
• Norepinephrine may therefore recruit preload reserve, but this does not replace direct assessment of fluid responsiveness.

Inotropic Effect

• Norepinephrine also stimulates beta-1 receptors.
• In 38 patients with early septic shock and MAP below 65 mm Hg, norepinephrine increased MAP from 56 to 80 mm Hg while left ventricular ejection fraction and Doppler systolic velocities increased.[1]
• This supports a clinically relevant inotropic effect during early shock despite the simultaneous increase in afterload.
• A fall in ejection fraction after restoring vascular tone may unmask previously hidden septic myocardial dysfunction rather than prove that norepinephrine newly injured the heart.

Macro-Microcirculatory Uncoupling

• Septic shock reduces functional capillary density and increases heterogeneity of microvascular flow.
• These abnormalities may persist after MAP and cardiac output normalize.
• Raising MAP from a critically low level can recruit pressure-dependent microvascular beds.
• Beyond that range, the microcirculatory response is heterogeneous because norepinephrine simultaneously restores perfusion pressure and constricts alpha-1 receptor-bearing arterioles.
• This loss of coherence between the macrocirculation and microcirculation explains why a higher MAP does not reliably improve lactate, mottling, or organ function.

Comparative Vasopressor Evidence

Dopamine

• SOAP II found no significant difference in 28-day mortality between dopamine and norepinephrine in patients with shock.
• Arrhythmias were substantially more frequent with dopamine: 24.1% versus 12.4%.
• This safety difference is a major reason dopamine no longer has a routine role in septic shock.

Epinephrine

• Epinephrine can achieve MAP targets but causes more tachyarrhythmia and beta-2 mediated lactate production.
• CAT and CATS did not demonstrate superior clinical outcomes with epinephrine-based treatment.
• An epinephrine-associated lactate increase may be pharmacologic rather than a direct marker of worsening tissue hypoxia, but it complicates interpretation of resuscitation.
• SSC 2026 suggests adding epinephrine when MAP remains inadequate despite norepinephrine and vasopressin, or when vasopressin is unavailable.[2,3]

Norepinephrine Shortage as a Natural Experiment

• During the 2011 United States norepinephrine shortage, substitution with other agents, mainly phenylephrine, was associated with a 3.7% absolute increase in hospital mortality.
• This was an observational natural experiment, not a randomized comparison, but it reinforces the clinical importance of ready access to norepinephrine.

Start Earlier to Use Less

CENSER

• CENSER randomized patients with sepsis and MAP below 65 mm Hg to early low-dose norepinephrine plus fluids or usual care with vasopressors after at least 30 mL/kg of crystalloid.[4]
• Shock control at 6 hours occurred in 76% of the early norepinephrine group and 48% of the usual-care group.
• Cardiogenic pulmonary edema occurred in 14.4% versus 27.7%.
• New-onset arrhythmia occurred in 11% versus 20%.
• Twenty-eight-day mortality did not differ significantly: 15.5% versus 21.9%.
• Interpretation: early norepinephrine improved early shock control and reduced complications, but CENSER did not establish a mortality benefit.

CLOVERS

• CLOVERS randomized 1,563 patients with sepsis-induced hypotension after at least 1 L of crystalloid to a restrictive fluid, vasopressor-prioritized strategy or a liberal fluid strategy.[5]
• Ninety-day mortality was 14.0% versus 14.9%, with no significant difference.
• The restrictive group received a median 2,134 mL less intravenous fluid during the protocol period.
• CLOVERS did not directly randomize immediate versus delayed norepinephrine. It supports the safety of a vasopressor-prioritized, fluid-restrictive strategy after initial fluid administration.
• A post hoc subgroup with advanced chronic kidney disease had lower 90-day death before discharge home with the restrictive strategy, but this exploratory result is not definitive and should not be generalized to all patients with kidney disease.

Bedside Markers of Vasoplegia

• A low diastolic arterial pressure may indicate loss of arterial tone.
• The diastolic shock index is heart rate divided by diastolic arterial pressure.
• A high diastolic shock index in a tachycardic patient may identify a vasoplegic phenotype likely to need early vasopressor support.
• These markers supplement, rather than replace, assessment of infection, preload, cardiac function, obstruction, and tissue perfusion.

Peripheral Norepinephrine

• SSC 2026 suggests starting vasopressors through a peripheral intravenous catheter rather than delaying therapy until central access is secured. Certainty of evidence is very low.[2,3]
• A protocolized prospective cohort of 635 patients used peripheral norepinephrine for a median of 5.8 hours and avoided central venous catheter placement for vasopressor delivery in 51.6% of patients.[1]
• The cohort used a strict protocol and a maximum norepinephrine dose of 15 micrograms/min. Extravasation occurred, but no patient developed tissue necrosis or required surgery.
• In a CLOVERS secondary analysis, peripheral vasopressors were common, with 3 peripheral infusion complications among 490 patients and no tissue necrosis. Central catheter complications occurred in 12 of 322 patients.[6]
• The 15 micrograms/min ceiling from one protocol should not be treated as a universal safety threshold.
• The SSC states that evidence is insufficient to define an optimal catheter size, anatomic site, dose limit, or duration.
• Safe use requires an institutional protocol that addresses:
  • A well-functioning peripheral line.
  • Frequent site assessment.
  • A dedicated infusion line when possible.
  • Prompt recognition of pain, swelling, blanching, leakage, or loss of blood return.
  • Immediate extravasation management.
  • Transition to central access when dose, duration, access quality, or the overall resuscitation plan makes it appropriate.

The Burden of Sustained Adrenergic Exposure

Cardiac Effects

• Early norepinephrine can improve preload, contractility, and perfusion pressure.
• Prolonged or high-dose adrenergic stimulation increases myocardial oxygen demand and wall stress.
• Catecholamine-associated myocardial injury is biologically plausible, with histologic, animal, biomarker, and Takotsubo-like evidence.
• Direct human evidence that norepinephrine independently causes clinically important myocardial injury remains limited.
• Sepsis-induced cardiomyopathy, altered loading conditions, ischemia, inflammation, and treatment exposure often coexist.

Arrhythmias

• Beta-1 stimulation contributes to atrial and ventricular arrhythmias.
• New-onset atrial fibrillation becomes more common as sepsis severity increases and is associated with longer ICU stay and higher mortality.
• A meta-analysis of vasopressin plus catecholamines versus catecholamines alone found a lower atrial fibrillation risk with vasopressin (relative risk 0.77) but no clear survival benefit.
• SEPSISPAM found more atrial fibrillation with a MAP target of 80 to 85 mm Hg than with 65 to 70 mm Hg: 6.7% versus 2.8%.

Metabolic Effects

• Catecholamines increase glycogenolysis, gluconeogenesis, lipolysis, insulin resistance, and substrate turnover.
• Beta-adrenergic stimulation can increase aerobic glycolysis and lactate production without tissue hypoxia, particularly with epinephrine.
• Severe acidosis can reduce myocardial contractility and vasopressor responsiveness.
• Observational data associate vasopressor exposure with ICU-acquired weakness, but residual confounding by severity, immobility, inflammation, corticosteroids, and mechanical ventilation is likely.

Immune Effects

• Catecholamines can suppress tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 while increasing interleukin-10 through beta-2 signaling.
• Experimental studies also suggest impaired neutrophil and macrophage phagocytosis, reduced oxidative burst, altered lymphocyte function, and enhanced bacterial growth or virulence.
• Most mechanistic immune evidence is in vitro or preclinical.
• Higher catecholamine exposure is associated with immunoparalysis, secondary infection, and mortality, but clinical causality remains unproven.

Strategy 1: Do Not Chase an Unnecessarily High MAP

Standard Initial Target

• SSC 2026 recommends an initial MAP target of 65 mm Hg rather than a higher target. This is a strong recommendation with moderate-certainty evidence.[2,3]
• For adults 65 years or older, SSC 2026 suggests an initial MAP range of 60 to 65 mm Hg rather than a higher range. This is a conditional recommendation with low-certainty evidence.
• The target should be treated as a range, not an exact single number.
• MAP should be individualized after considering tissue perfusion, chronic hypertension, neurologic disease, renal perfusion, arterial measurement reliability, and adverse effects of vasopressor escalation.

Evidence Against Routine High Targets

• SEPSISPAM found no mortality benefit from targeting 80 to 85 mm Hg instead of 65 to 70 mm Hg.
• A chronic-hypertension subgroup required less renal replacement therapy at the higher target, but this did not establish a universal survival benefit.
• OPTPRESS randomized 518 patients 65 years or older with septic shock in Japan to MAP 80 to 85 mm Hg or 65 to 70 mm Hg.[7]
• The trial stopped early for a signal of harm.
• Ninety-day mortality was 39.3% with the high target and 28.6% with the standard target, an absolute risk difference of 10.7%.
• The standard-target group also had more catecholamine-free days.
• The mechanism of harm remains uncertain because arrhythmias were not significantly increased.

Lower Targets

• Lower MAP targets may reduce vasopressor exposure in selected patients without active signs of tissue hypoperfusion.
• This does not mean that persistent MAP below 60 mm Hg is routinely safe.
• The risk from hypotension depends on depth, duration, baseline pressure, autoregulation, and organ-specific vulnerability.
• If a higher MAP is considered for chronic hypertension, a time-limited MAP test with simultaneous reassessment of capillary refill, urine output, cognition, lactate, cardiac function, and adverse effects is more defensible than automatically maintaining a high target.

Strategy 2: Resuscitate Perfusion, Not the Monitor Alone

ANDROMEDA-SHOCK

• ANDROMEDA-SHOCK randomized 424 patients to capillary refill time (CRT)-guided or lactate-targeted resuscitation after initial MAP stabilization.[8]
• Twenty-eight-day mortality was 34.9% versus 43.4%, but the difference did not reach conventional statistical significance.
• CRT-guided treatment used 408 mL less fluid during the first 8 hours and produced a 1-point lower Sequential Organ Failure Assessment score at 72 hours.
• A Bayesian reanalysis suggested a high probability of benefit, but it remained exploratory.

ANDROMEDA-SHOCK-2

• ANDROMEDA-SHOCK-2 randomized 1,501 patients with early septic shock, with 1,467 included in the primary analysis across 86 ICUs in 19 countries.[9]
• The intervention used CRT as the perfusion target and integrated pulse pressure, diastolic arterial pressure, fluid responsiveness, and bedside echocardiography to guide fluids, vasopressors, and inotropes.
• The hierarchical composite of mortality, duration of vital support, and hospital stay favored personalized resuscitation (win ratio 1.16; 95% confidence interval 1.02 to 1.33).
• The benefit was driven mainly by shorter duration of vital support, not mortality.
• Ninety-day mortality did not differ significantly: 32.1% versus 33.2%.
• Vasopressor support was approximately 0.95 day shorter with the personalized strategy.
• Interpretation: CRT-centered personalized resuscitation can reduce treatment intensity and organ-support duration, but it has not demonstrated a survival advantage.

Practical Perfusion Reassessment

• After achieving a minimum perfusion pressure, reassess:
  • CRT and mottling.
  • Mental status.
  • Urine output and renal trajectory.
  • Lactate trend and plausible nonhypoxic causes of hyperlactatemia.
  • Pulse pressure and diastolic arterial pressure.
  • Fluid responsiveness before additional boluses.
  • Left and right ventricular function.
  • Venous congestion.
• SSC 2026 suggests using CRT as an adjunct to other perfusion measures, not as a stand-alone target.

Strategy 3: Add Vasopressin to an Escalating Norepinephrine Requirement

Rationale and Evidence

• Relative vasopressin deficiency occurs in a subset of patients with septic shock.
• Vasopressin restores vascular tone through a nonadrenergic pathway and can reduce norepinephrine exposure.
• VASST did not improve its primary mortality outcome overall.[10]
• A prespecified subgroup receiving less than 15 micrograms/min of norepinephrine at randomization had a possible survival benefit, but subgroup results do not prove that earlier vasopressin improves survival.
• VANISH and VANCS II did not establish a mortality benefit. VANISH suggested less renal replacement therapy.
• Vasopressin-containing strategies reduce atrial fibrillation compared with catecholamines alone, but a mortality benefit remains uncertain.

2026 SSC Position

• SSC 2026 conditionally suggests adding vasopressin when norepinephrine doses are escalating, with moderate-certainty evidence.[2,3]
• The review describes a common approach of fixed-dose vasopressin at 0.03 units/min when norepinephrine approaches 0.25 micrograms/kg/min.[1]
• The publicly listed SSC recommendation does not establish 0.25 micrograms/kg/min as a mandatory threshold. Timing should follow the trajectory of shock, local protocols, and the patient's hemodynamic phenotype.
• Vasopressin is usually administered at a fixed low dose rather than titrated as the primary vasopressor.

Phenotype and Cautions

• Vasopressin may be particularly attractive in marked vasoplegia, preserved cardiac output, escalating norepinephrine exposure, or tachyarrhythmia.
• The hypothesis that patients with left ventricular systolic dysfunction may respond less favorably comes from physiologic reasoning and post hoc data. Left ventricular dysfunction is not an established absolute contraindication.
• Monitor for excessive vasoconstriction, digital or mesenteric ischemia, reduced cardiac output, and hyponatremia.
• A reinforcement-learning analysis associated closer agreement with model-recommended vasopressin timing with lower mortality. This was observational model-concordance evidence and requires prospective validation before clinical use.

Strategy 4: Angiotensin II and the Renin-Angiotensin System

Rationale

• Some patients with vasodilatory shock have low angiotensinogen, high renin, reduced angiotensin-converting enzyme activity, increased angiotensin II degradation, or impaired angiotensin II receptor signaling.
• This creates a plausible phenotype of functional angiotensin II deficiency.

ATHOS-3

• ATHOS-3 showed that angiotensin II increased MAP at 3 hours and reduced norepinephrine-equivalent dose in catecholamine-resistant vasodilatory shock.[11]
• Post hoc analyses suggested possible benefit in patients with acute kidney injury requiring renal replacement therapy and in patients with high baseline renin.
• These analyses are hypothesis-generating and have not prospectively validated renin-guided or kidney phenotype-guided treatment.

2026 SSC Position

• SSC 2026 suggests norepinephrine rather than angiotensin II as the first-line vasopressor.
• Angiotensin II is not part of the standard SSC escalation sequence, which moves from norepinephrine to vasopressin and then epinephrine when MAP remains inadequate.
• Angiotensin II may be considered as a rescue option in selected catecholamine-resistant vasodilatory shock according to availability, regulatory status, thrombosis risk, local expertise, and patient phenotype.

DPP3: Biomarker and Experimental Target

• Circulating dipeptidyl peptidase 3 (cDPP3) is released during cellular injury and degrades angiotensin peptides.
• In a multinational cohort of 585 patients with severe sepsis or septic shock, higher cDPP3 was associated with acute kidney injury, renal replacement therapy, and higher 28-day and 90-day mortality.
• Association does not establish that cDPP3 is the cause of organ failure.
• Procizumab, also called invobenitug, is a humanized monoclonal antibody that inhibits cDPP3.
• In a porcine septic shock model, cDPP3 inhibition reduced catecholamine requirements and improved fluid balance.
• A small human pilot study of STC3141 in 26 critically ill patients with sepsis provided early safety, tolerability, and pharmacokinetic information for histone neutralization, not efficacy evidence for cDPP3 inhibition. Human efficacy data for cDPP3 inhibition remain pending.
• SSC 2026 does not address cDPP3 inhibition.

Strategy 5: Corticosteroids

• Corticosteroids improve vascular responsiveness and generally accelerate shock reversal.
• APROCCHSS randomized 1,241 patients with septic shock to hydrocortisone plus fludrocortisone or placebo.[12]
• Ninety-day mortality was 43.0% versus 49.1% (relative risk 0.88).
• Vasopressor-free days through day 28 were 17 versus 15.
• Other major trials, including ADRENAL, did not demonstrate the same mortality effect with hydrocortisone alone but did show faster resolution of shock.
• The survival effect therefore should not be generalized across all steroid regimens and shock severities.
• SSC 2026 conditionally suggests intravenous corticosteroids for septic shock, with low-certainty evidence.
• Steroids should be viewed as an evidence-supported adjunct for ongoing vasopressor-dependent shock, not as a replacement for antibiotics, source control, fluids when indicated, or vasopressors.

Strategy 6: Short-Acting Beta-1 Blockade

Why It Was Studied

• Persistent adrenergic tachycardia increases myocardial oxygen demand and may impair diastolic filling and ventricular-arterial efficiency.
• Esmolol and landiolol can reduce heart rate quickly and can be stopped rapidly if hemodynamics deteriorate.

Conflicting Trial Results

• A single-center trial of 154 patients found lower norepinephrine requirements and lower 28-day mortality with esmolol, but the control mortality of 80.5% and unusually large fluid volumes limit generalizability.
• STRESS-L enrolled patients with established septic shock, tachycardia, and norepinephrine of at least 0.1 micrograms/kg/min for more than 24 hours.
• The trial stopped early for a possible harm signal. Landiolol did not improve the mean 14-day Sequential Organ Failure Assessment score, and 28-day mortality was numerically higher.
• LANDI-SEP improved a hemodynamic composite of heart-rate control without increased vasopressor support, but it did not reduce 28-day mortality.
• A post hoc analysis suggested different responses in sinus tachycardia and atrial fibrillation. This finding is exploratory and should not be used as proof that landiolol benefits atrial fibrillation or harms every patient with sinus tachycardia.
• Meta-analyses remain inconsistent and have low to moderate certainty.

Clinical Position

• SSC 2026 suggests against using beta-blockers as treatment for septic shock. This is a conditional recommendation with very-low-certainty evidence.[2,3]
• Routine beta-blockade for septic sinus tachycardia is not recommended.
• Before considering heart-rate reduction, correct pain, agitation, fever, hypovolemia, hypoxemia, anemia, withdrawal, and excessive beta-agonist exposure, and confirm adequate cardiac output and perfusion.
• Use outside a trial or specialized protocol requires extreme caution and real-time hemodynamic monitoring.

Strategy 7: Methylene Blue

• Excess nitric oxide activates soluble guanylate cyclase and cyclic guanosine monophosphate, contributing to vasoplegia.
• Earlier nonselective nitric oxide synthase inhibition with L-NMMA increased mortality, demonstrating that broad suppression of nitric oxide can be harmful.
• A single-center randomized trial of 91 patients tested methylene blue 100 mg in 500 mL saline over 6 hours daily for 3 days.[13]
• Time to vasopressor discontinuation was 69 hours versus 94 hours.
• Cumulative fluid balance and ICU length of stay were lower.
• Mortality was 33% versus 46%, but the difference was not significant.
• The trial was small and single center, and green urine could have compromised blinding.
• SSC 2026 concludes that evidence is insufficient to recommend intravenous methylene blue for refractory septic shock.
• Clinically important risks include serotonin toxicity with serotonergic drugs, hemolysis in glucose-6-phosphate dehydrogenase deficiency, pulse oximetry interference, and dose-related vascular effects. Safety cannot be inferred from the absence of major events in one small trial.

Emerging Immunomodulation and Blood Purification

Extracellular Histone Neutralization

• Extracellular histones released during cellular injury or NETosis can promote inflammation, endothelial injury, coagulation, and organ dysfunction.
• The histone-neutralizing compound mCBS reduced vasopressor requirement, lactate, interleukin-6, and kidney injury in a sheep model.
• STC3141 was evaluated in a 26-patient human pilot study for safety, tolerability, and pharmacokinetics.
• These findings establish feasibility, not clinical efficacy.
• SSC 2026 does not address extracellular histone neutralization.

Polymyxin B Hemoperfusion

• Unselected randomized trials of polymyxin B hemoperfusion did not improve survival or organ failure.
• A post hoc EUPHRATES analysis restricted to endotoxin activity assay values of 0.60 to 0.89 suggested lower mortality. Because it was post hoc, the result is vulnerable to subgroup-selection bias.
• TIGRIS prospectively enrolled 157 patients with septic shock and endotoxin activity assay values of 0.60 to 0.89.[14]
• Twenty-eight-day mortality was 39% with polymyxin B hemoperfusion and 45% with control.
• The Bayesian posterior probability of benefit was 95.3%, but the 95% credible interval for the adjusted odds ratio crossed 1.
• MAP, vasopressor dose, and vasopressor duration did not differ significantly.
• TIGRIS therefore generated an efficacy signal in a biomarker-selected population but did not demonstrate catecholamine sparing.
• SSC 2026 suggests against blood purification techniques and specifically suggests against polymyxin B hemoperfusion.

2026 SSC: Practical Summary

• Initial MAP:
  • Target approximately 65 mm Hg rather than a higher MAP.
  • For adults 65 years or older, consider an initial range of 60 to 65 mm Hg.
• Perfusion:
  • Use serial lactate in context.
  • Use CRT as an adjunct to other perfusion measures.
  • Use dynamic measures to guide additional fluid.
• Vasopressor access:
  • Start peripherally rather than delaying for central access when immediate support is needed.
• Vasopressor sequence:
  • Norepinephrine first.
  • Add vasopressin when norepinephrine is escalating.
  • Add epinephrine if MAP remains inadequate despite norepinephrine and vasopressin.
• Adjuncts:
  • Intravenous corticosteroids are conditionally suggested.
  • Beta-blockers are conditionally discouraged as treatment for septic shock.
  • Evidence is insufficient for intravenous methylene blue.
  • Blood purification and polymyxin B hemoperfusion are discouraged.
  • Angiotensin II is not preferred as first-line treatment and is not in the standard escalation sequence.
  • cDPP3 inhibition and extracellular histone neutralization remain investigational.

Bedside Catecholamine-Sparing Checklist

First Hour

• Recognize septic shock and begin infection treatment, source-control planning, and hemodynamic resuscitation immediately.
• Evaluate whether hypotension reflects vasoplegia, hypovolemia, myocardial dysfunction, obstruction, or a mixed state.
• Start norepinephrine promptly for persistent hypotension or severe vasoplegia, including through a monitored peripheral line when appropriate.
• Use fluid responsiveness rather than a fixed-volume reflex to guide additional boluses after initial resuscitation.
• Set an initial MAP target near 65 mm Hg, or 60 to 65 mm Hg in many adults 65 years or older, unless a clear patient-specific reason supports another target.

During Escalation

• Confirm that the blood pressure measurement is reliable.
• Reassess CRT, skin temperature, mottling, urine output, mental status, lactate trajectory, and acid-base status.
• Perform bedside echocardiography to assess left ventricular, right ventricular, valvular, and pericardial causes of persistent shock.
• Check for venous congestion and fluid intolerance.
• Add vasopressin when norepinephrine is escalating rather than waiting for extreme catecholamine doses.
• Consider corticosteroids for ongoing vasopressor-dependent septic shock.
• Treat persistent hypoperfusion with cardiac dysfunction using an individualized inotropic strategy rather than simply raising MAP.

Before Calling Shock Refractory

• Reassess source control and adequacy of antimicrobial therapy.
• Exclude occult bleeding, abdominal compartment syndrome, tamponade, tension pneumothorax, massive pulmonary embolism, adrenal crisis, and medication error.
• Confirm adequate but not excessive preload.
• Review arterial and central access, infusion concentration, pump function, and dose calculations.
• Reconsider whether the target MAP is unnecessarily high.
• Reserve angiotensin II, methylene blue, or other rescue therapies for selected cases with clear rationale, awareness of uncertain outcome evidence, and appropriate expertise.

Final Take-Home Points

• Norepinephrine is not the enemy. Untreated hypotension and hypoperfusion are immediately dangerous.
• The correct objective is the lowest effective catecholamine exposure that maintains individualized tissue perfusion.
• Early norepinephrine and monitored peripheral initiation can reduce hypotension and fluid loading without waiting for central access.
• A MAP of approximately 65 mm Hg is the usual starting point. Routine pursuit of 80 to 85 mm Hg adds catecholamine exposure and may harm older patients.
• CRT-centered, phenotype-based resuscitation reduces fluid and vasopressor exposure and shortens organ support, but has not shown a mortality benefit.
• Vasopressin is the best-established nonadrenergic catecholamine-sparing adjunct, although its survival benefit is uncertain and no single norepinephrine threshold fits every patient.
• Corticosteroids accelerate shock reversal. Survival effects vary by regimen and trial.
• Angiotensin II may be useful in selected catecholamine-resistant vasodilatory shock, but high-renin and renal-replacement subgroups remain post hoc hypotheses.
• Beta-blockers should not be used routinely for septic shock. Sinus tachycardia may be compensatory.
• Methylene blue shortens vasopressor duration in one small trial, but survival and safety remain uncertain.
• cDPP3 inhibition, histone neutralization, reinforcement-learning-guided vasopressin, and endotoxin-selected hemoperfusion are research strategies, not routine standards.
• Every apparent catecholamine-sparing intervention should be judged by patient-centered outcomes, not by a lower norepinephrine dose alone.

Selected References

1. Dubech A, Picod A, Pierre A, et al. Current and Future Strategies Aiming at Reducing Catecholamine Exposure in Septic Shock. Crit Care. 2026;30:427. https://doi.org/10.1186/s13054-026-06109-3
2. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Crit Care Med. 2026. https://doi.org/10.1097/CCM.0000000000007075
3. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2026. Intensive Care Med. 2026;52:863-936. https://doi.org/10.1007/s00134-026-08361-1
4. Permpikul C, Tongyoo S, Viarasilpa T, et al. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). Am J Respir Crit Care Med. 2019;199:1097-1105. https://doi.org/10.1164/rccm.201806-1034OC
5. National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N Engl J Med. 2023;388:499-510. https://doi.org/10.1056/NEJMoa2212663
6. Fernando SM, et al. Peripheral Vasopressor Use in Early Sepsis-Induced Hypotension. JAMA Netw Open. 2025;8:e2529148. https://doi.org/10.1001/jamanetworkopen.2025.29148
7. Endo A, Yamakawa K, Tagami T, et al. Efficacy of Targeting High Mean Arterial Pressure for Older Patients With Septic Shock (OPTPRESS). Intensive Care Med. 2025;51:883-892. https://doi.org/10.1007/s00134-025-07910-4
8. Hernandez G, Ospina-Tascon GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock. JAMA. 2019;321:654-664. https://doi.org/10.1001/jama.2019.0071
9. Hernandez G, et al. Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock. JAMA. 2025. https://doi.org/10.1001/jama.2025.20402
10. Russell JA, Walley KR, Singer J, et al. Vasopressin Versus Norepinephrine Infusion in Patients With Septic Shock. N Engl J Med. 2008;358:877-887. https://doi.org/10.1056/NEJMoa067373
11. Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017;377:419-430. https://doi.org/10.1056/NEJMoa1704154
12. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone Plus Fludrocortisone for Adults With Septic Shock. N Engl J Med. 2018;378:809-818. https://doi.org/10.1056/NEJMoa1705716
13. Ibarra-Estrada M, Kattan E, Aguilera-Gonzalez P, et al. Early Adjunctive Methylene Blue in Patients With Septic Shock. Crit Care. 2023;27:110. https://doi.org/10.1186/s13054-023-04397-7
14. Neyra JA, Legrand M, Tidswell MA, et al. Polymyxin B Haemoadsorption in Endotoxic Septic Shock (TIGRIS). Lancet Respir Med. 2026. https://doi.org/10.1016/S2213-2600(26)00047-0

Apply patient-specific hemodynamic assessment before clinical use.

Chikungunya Virus Infection

Chikungunya Virus Infection: Rheumatological Manifestations

Clinical Overview

• Chikungunya virus infection can cause acute polyarthralgia or polyarthritis and, in some patients, prolonged inflammatory rheumatic disease.
• Rheumatological manifestations may resemble viral arthritis, rheumatoid arthritis, or spondyloarthritis.

Clinical Phases

Acute Phase: 1 to 2 Weeks

• Polyarthralgia and polyarthritis
  • Sudden onset of severe joint pain and stiffness.
  • Usually symmetric and polyarticular.
  • Commonly affects peripheral joints, including the hands, wrists, ankles, and feet.
  • Joint swelling and inflammation may resemble viral arthritis or acute rheumatoid arthritis.
• Periarticular manifestations
  • Tenosynovitis.
  • Tendinitis.
  • Myalgia.

Post-Acute and Chronic Phase: Weeks to Years

• Chronic inflammatory rheumatism
  • Persistent inflammatory polyarthritis or relapsing and remitting arthralgia and arthritis.
  • May be associated with prolonged morning stiffness, bursitis, and tenosynovitis.
  • The phenotype may resemble seronegative rheumatoid arthritis or spondyloarthritis.
  • Structural damage or deforming erosive arthritis is rare.
• Risk of chronic symptoms
  • Chronic progression occurs in 30% to 60% of infected individuals.
  • Older adults and patients with pre-existing comorbidities have increased risk.

Laboratory Findings

• Acute-phase reactants
  • Erythrocyte sedimentation rate and C-reactive protein may be elevated.
• Autoantibodies
  • Rheumatoid factor and anti-cyclic citrullinated peptide antibodies are typically negative.
  • Low-titer or incidental positivity may occasionally occur.
• Virological and serological testing
  • Chikungunya virus RT-PCR: Use for early diagnostic confirmation during the initial viremic stage.
  • Chikungunya virus IgM and IgG serology: Useful after the acute viremic period to assess post-acute exposure and convalescence.

Management

Acute Phase Management

• Prioritize rest and adequate oral hydration.
• Use paracetamol (acetaminophen) as first-line symptomatic therapy.
• Rule out dengue fever before administering nonsteroidal anti-inflammatory drugs (NSAIDs) because of bleeding risk.
• Start NSAIDs only after dengue infection has been excluded and contraindications are absent.

Persistent or Chronic Phase Management

• Continue NSAIDs when clinically indicated and tolerated.
• Consider short courses of systemic corticosteroids for severe active inflammatory flares.
• Refer patients with persistent objective inflammatory arthritis to rheumatology.
• Disease-modifying antirheumatic drugs (DMARDs)
  • Consider DMARDs for unresolved inflammatory arthritis.
  • Methotrexate has the strongest supporting clinical evidence among the options named in the source note.
  • Hydroxychloroquine may be used as an alternative or adjunct, although supporting evidence is less consistent.

Differential Diagnosis

• Rheumatoid arthritis.
• Reactive arthritis.
• Spondyloarthritis.
• Parvovirus B19 arthritis.
• Hepatitis B viral arthritis.
• Hepatitis C viral arthritis.
• Other viral arthritides, including dengue, Zika, and Ross River virus.

Practical Takeaways

• Consider chikungunya virus infection in patients with abrupt, severe, symmetric peripheral polyarthralgia or polyarthritis.
• Distinguish acute chikungunya virus infection from dengue fever before NSAID treatment.
• Persistent inflammatory arthritis warrants reassessment and possible rheumatology referral.

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Ketamine vs Etomidate

Induction Agents: Ketamine vs Etomidate

Core Clinical Message

• Neither ketamine nor etomidate is universally hemodynamically stable.
• The induction dose, shock physiology, and preparation for peri-intubation hypotension may matter more than the drug label alone.

Etomidate

Mechanism and Hemodynamic Profile

• Etomidate is a gamma-aminobutyric acid type A (GABA-A) receptor agonist.
• It is generally considered the most cardiovascularly neutral commonly used induction agent.
• Heart rate, blood pressure, and myocardial contractility usually change little after an appropriate induction dose.
• It lowers intracranial pressure and cerebral oxygen demand.

Dose

• Typical induction dose: 0.2 to 0.3 mg/kg intravenously.

Limitations and Adverse Effects

• Etomidate inhibits 11-beta-hydroxylase and can suppress cortisol synthesis for up to 24 hours after a single dose.
  • The clinical importance of this effect, particularly in sepsis, remains debated.
• It may cause myoclonus, injection-site pain, and more nausea than some alternatives.
• It does not provide analgesia.

Ketamine

Mechanism and Hemodynamic Profile

• Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist and dissociative anesthetic.
• It usually increases heart rate and blood pressure through catecholamine release.
• Ketamine is also a direct myocardial depressant.
  • In patients with prolonged shock and depleted catecholamine reserves, direct myocardial depression may predominate and blood pressure can fall after induction.

Clinical Advantages

• Bronchodilation.
• Better preservation of respiratory drive and airway reflexes than many other induction agents.
• Analgesia.

Dose

• Typical induction dose: 1 to 2 mg/kg intravenously.
• Consider a lower dose in shock.

Intracranial Pressure

• The supplied note states that the older concern that ketamine raises intracranial pressure has largely been disproven.

Evidence Summary

• The supplied note describes a 2025 randomized trial of approximately 3,300 critically ill adults.
  • It reported no difference in 28-day mortality between ketamine and etomidate.
  • Cardiovascular collapse during intubation was reportedly more common with ketamine.
• This source summary does not provide a full citation. Verify the original study before using the result for protocol development or clinical decision-making.

Practical Selection

• Bronchospasm, asthma, or a need for analgesia: ketamine is often a useful option.
• Tenuous hemodynamics or head injury: etomidate is a reasonable option.
• Profound shock: either drug can precipitate collapse.
  • Reduce the induction dose.
  • Prepare vasopressors and resuscitation measures before induction.

Summary Takeaway

• Neither ketamine nor etomidate is reliably hemodynamically stable in every critically ill patient.
• Select the agent and dose according to the patient's physiology, airway indication, and readiness to treat peri-intubation hypotension.

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Follow local protocols and specialist guidance for clinical decisions.

Bicarbonate in Acute Kidney Injury

Bicarbonate in Acute Kidney Injury: Clinical Lecture Notes

1. Core Principle

• Improving serum pH is a biochemical reaction, not proof that the underlying etiology is resolved.
• Raising pH does not stop acid generation, eliminate accumulated acid anions, or guarantee improved clinical outcomes.
• Avoid reflexively prescribing sodium bicarbonate simply because serum bicarbonate or pH is low.

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2. Acidosis Etiology and Mechanisms

• Differentiate the underlying mechanism before intervention:
  • Hyperchloremic metabolic acidosis: Caused by relative chloride excess and a narrowed strong ion difference (SID). Stopping chloride-heavy fluids, switching to balanced solutions, or selectively giving bicarbonate aligns with underlying pathophysiology.
  • Lactic acidosis and ketoacidosis: Caused by organic acid overproduction. Bicarbonate fails to clear circulating lactate or ketoacid anions; restoring organ perfusion and resolving the primary trigger remain primary.
  • Uremic acidosis in AKI: Caused by impaired excretion of fixed acids (sulfates, phosphates, organic anions). Adding bicarbonate loads sodium without removing unmeasured anions.
  • Gastrointestinal or renal base loss: True bicarbonate depletion (such as severe diarrhea or proximal renal tubular acidosis) where replacement is physiologically rational.
  • Mixed acid-base disorders: Frequently coexist in critical illness and require separate diagnostic evaluation.

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3. Physicochemical Framework (Stewart Approach)

• Traditional Henderson-Hasselbalch model:
  • Interprets pH through the balance between PaCO2 and serum HCO3-.
• Stewart approach:
  • Blood pH is governed by three independent variables:
    • PaCO2.
    • Strong Ion Difference (SID = strong cations minus strong anions, primarily Na+ minus Cl-).
    • Total nonvolatile weak acids (primarily albumin and phosphate).
  • Serum HCO3- is a dependent variable, not an independent driver.
  • Sodium bicarbonate acts by adding Na+ without a corresponding Cl-, thereby widening the SID and shifting the water dissociation equilibrium toward higher pH.
  • Practical implication: Bicarbonate therapy modifies the strong ion balance rather than merely replacing a missing buffer.

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4. Respiratory Mechanics and Carbon Dioxide Generation

• Chemical reaction: HCO3- + H+ -> CO2 + H2O.
• Each dose of bicarbonate generates an obligatory CO2 load that requires adequate alveolar ventilation to eliminate.
• Risks in hypoventilating, exhausted, or poorly perfused patients:
  • Systemic CO2 retention.
  • Paradoxical intracellular and central nervous system acidification (lipophilic CO2 crosses cell membranes faster than charged HCO3-).
  • Serum pH may improve while intracellular and organ tissue acidosis worsens.
  • Correcting systemic acidemia blunts central respiratory drive, further aggravating hypoventilation.
• Bedside rule: Always assess whether the patient has sufficient ventilatory reserve to clear the newly generated CO2.

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5. Clinical Benefits vs Potential Adverse Effects

• Potential benefits:
  • Temporarily mitigates severe acidemia-induced myocardial depression and vascular hyporesponsiveness.
  • Promotes intracellular potassium shift in life-threatening hyperkalemia.
  • Partially restores coagulation factor and platelet enzymatic function impaired by profound acidemia.
  • Serves as a short-term bridge while arranging definitive etiology treatment or kidney replacement therapy.
• Known adverse effects and risks:
  • Hypernatremia and hyperosmolality from high-solute load.
  • Volume overload and worsening pulmonary edema in oliguric AKI or heart failure.
  • Acute drop in ionized calcium leading to myocardial dysfunction and tetany.
  • Hypokalemia and associated cardiac arrhythmias.
  • Metabolic alkalemia from overcorrection.
  • Left shift of the oxyhemoglobin dissociation curve, impairing tissue oxygen release.
  • Intracellular paradoxical acidosis from CO2 buildup.
  • Blunted ventilatory drive.

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6. Clinical Evidence: The BICAR-ICU Trial

• Trial design: Multicenter randomized controlled trial of 389 critically ill ICU patients with severe metabolic acidemia (pH <= 7.20), comparing 4.2% sodium bicarbonate infusion (target pH >= 7.30) against control.
• Primary outcome: No statistically significant difference in the overall composite endpoint of 28-day all-cause mortality and at least one organ failure by day 7.
• Pre-specified AKI subgroup (AKIN Stage 2-3, n = 182):
  • 28-day mortality was significantly lower in the bicarbonate arm (46% vs 63%).
  • Requirement for kidney replacement therapy was significantly reduced (51% vs 73%).
• Critical appraisal:
  • Subgroup analyses are hypothesis-generating and carry risk of false-positive findings.
  • Open-label design introduced potential clinician bias regarding triggers for initiating kidney replacement therapy.
  • Do not interpret as a universal indication to give bicarbonate to every patient with AKI and acidemia.

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7. Appropriate Indications vs Common Misuses

• Rational indications:
  • Severe metabolic acidemia (pH < 7.15 to 7.20) in AKI with hemodynamic instability.
  • Severe hyperchloremic metabolic acidosis alongside reduction of exogenous chloride intake.
  • Critical hyperkalemia with concomitant metabolic acidosis as part of multimodal temporization.
  • Documented severe bicarbonate-wasting states (severe diarrhea, RTA).
  • Short-term bridging while preparing for emergent kidney replacement therapy.
• Frequent misuses:
  • Infusing bicarbonate instead of restoring volume, perfusion, and microcirculation in circulatory shock.
  • Repeated sodium loading in patients with heavy unmeasured anion accumulation.
  • Administering bicarbonate to patients with ventilatory failure without airway or mechanical ventilatory support.
  • Overlooking cumulative sodium load in hypervolemic or severely oliguric patients.
  • Chasing normal laboratory numbers rather than modest physiological stabilization.
  • Relying on bicarbonate infusions to delay needed kidney replacement therapy.

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8. Bedside 5-Step Clinical Algorithm

• Step 1: Assess severity. Review pH, PaCO2, HCO3-, hemodynamic parameters, rhythm, and potassium level.
• Step 2: Determine mechanism. Calculate anion gap; evaluate chloride, lactate, ketones, albumin, and renal function.
• Step 3: Check ventilatory capacity. Verify whether spontaneous minute ventilation or mechanical ventilation can clear the extra CO2 burden.
• Step 4: Consider definitive alternatives. Restore tissue perfusion, stop chloride loading, manage sepsis or diabetic ketoacidosis, or initiate kidney replacement therapy.
• Step 5: Administer fractionated doses with discrete endpoints. Use small, incremental infusions; target a pH of roughly 7.20 to 7.25 rather than normal values; serial re-evaluation of blood gases, electrolytes, and ionized calcium is mandatory.

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9. Summary Takeaways

• Serum HCO3- is a dependent variable; sodium bicarbonate functions by expanding the strong ion difference.
• Bicarbonate infusion produces CO2; adequate alveolar ventilation is required.
• Improving pH is not equivalent to treating the underlying cause.
• Clearing accumulated unmeasured anions in severe AKI requires kidney replacement therapy, not additional sodium load.

Wellens Syndrome: ECG

Wellens Syndrome: ECG Recognition and Immediate Management

Clinical significance

• Wellens syndrome is a high-risk electrocardiographic pattern that occurs during a pain-free interval and indicates critical proximal left anterior descending (LAD) coronary stenosis.[1-3]
• It identifies patients at risk of an impending, extensive anterior myocardial infarction (MI).[1-3]
• The pattern is associated with transient ischemia from plaque rupture and spontaneous reperfusion rather than ongoing complete LAD occlusion.[1,3]

Required clinical context

• Recent angina or chest pain.
• ECG obtained while the patient is pain-free.[1,3,5]
• Cardiac biomarkers that are normal or only mildly elevated.[1,5]

Core ECG criteria

• Precordial T-wave abnormalities, most often in V2-V3, with possible extension from V1 through V6.[1,2,5]
• Isoelectric or minimally elevated ST segments.[1,5]
• No pathologic precordial Q waves or loss of R-wave progression.[1,5]
• No anterior ST-segment elevation greater than 1 mm suggesting acute anterior MI.[5]

T-wave patterns

• Type A: Biphasic T waves, with an initial positive deflection followed by a negative deflection.
  • Usually occurs in V2-V3.
  • May extend from V1 through V6.
  • Reported in approximately 24% to 30% of cases.[1,4,5]
• Type B: Deep, symmetric T-wave inversions.
  • Usually occurs in V2-V3.
  • May extend to V1 and V4-V6.
  • Reported in approximately 70% to 76% of cases.[1,4]

Relationship to de Winter pattern

• A Wellens pattern may evolve directly from a de Winter ECG pattern.[6]
• This evolution may reflect partial LAD recanalization.[6]

Emergency management

• Treat the pattern as a high-risk acute coronary syndrome, even if the patient is currently pain-free and troponin is normal.[2,3,6]
• Obtain urgent cardiology involvement.
• Pursue early coronary angiography.
• Avoid stress testing because it can be unsafe in the setting of critical proximal LAD disease.[2,3,6]

Summary takeaway

• Recognize Wellens syndrome from its characteristic pain-free precordial T-wave abnormalities in a patient with recent ischemic chest pain.
• Do not be reassured by symptom resolution, absence of ST elevation, or minimally elevated biomarkers.
• Escalate promptly for cardiology evaluation and early angiography rather than stress testing.

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References

1. Plappert C, Sherif M, Oeing C. Intermittent Chest Pain in a 46-Year-Old Patient. JAMA. 2022;328(20):2058-2059. doi:10.1001/jama.2022.19443.
2. Kontos MC, de Lemos JA, Deitelzweig SB, et al. 2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department. Journal of the American College of Cardiology. 2022;80(20):1925-1960. doi:10.1016/j.jacc.2022.08.750.
3. Honda S, Kawasaki T. Wellens' Syndrome. New England Journal of Medicine. 2022;387(12):e25. doi:10.1056/NEJMicm2201699.
4. Xenogiannis I, Vemmou E, Sharkey SW. Serial T-Wave Changes in a Patient With Chest Pain. JAMA Internal Medicine. 2022;182(8):874-875. doi:10.1001/jamainternmed.2022.2389.
5. Yazdi D, Sharim J. A Nearly Stressful Situation: A Case of Wellens Syndrome. JAMA Internal Medicine. 2019;179(5):704-706. doi:10.1001/jamainternmed.2019.0216.
6. Zhu Y, Luo S, Huang B. Evolution of de Winter Into Wellens on Electrocardiogram: What Happened? JAMA Internal Medicine. 2021;181(12):1647-1649. doi:10.1001/jamainternmed.2021.5734.

Clinical decisions should use local protocols and specialist consultation.