01Approach to the Critical Patient/attcp68

Immediate priorities

›Airway and breathing threats

›Respiratory failure indicators

›SpO2 < 90% on room air

›PaO2 < 60 mmHg on ABG

›Rapidly progressive dyspnea

›Escalating oxygen requirement

›Transition to HFNC or NIV for moderate hypoxemia

›Early intubation for worsening ARDS

›If unable to protect airway, proceed to definitive airway control

›Lung-protective ventilation strategy

›Tidal volume 6 ml/kg ideal body weight

›Hemodynamic and shock assessment

›Shock physiology triggers

›SBP < 90 mmHg

›MAP < 65 mmHg

›Multiorgan failure markers

›Rising creatinine

›Worsening transaminases

›Vasopressor initiation for refractory hypotension

›Norepinephrine first line

›ICU level care

›Isolation and infection control

›Airborne plus contact plus droplet precautions immediately

›N95 respirator for all HCW contacts

›Gown, gloves, eye protection

›Negative pressure room if available

›Single-patient room minimum

02History/hx80

Exposure history

›Animal contact within prior 2 to 8 days

›Sick or dead poultry

›Backyard flocks

›Live bird markets

›Poultry depopulation activities

›Dairy cattle exposure

›Farm work on affected premises

›Milking or handling infected cows

›Raw or unpasteurized dairy products

›Raw milk consumption

›Unpasteurized cheese

›Wild bird contact

›Direct handling of dead birds

›Swimming in potentially contaminated water

›PPE use during exposure

›Eye protection worn

›Only 36% of farm workers used both eye protection and respirator

›Inadequate PPE strongly associated with infection

›Respirator or mask type

›Gloves and gown use

Symptom characterization

›Ocular symptoms

›Conjunctival injection unilateral or bilateral

›Present in 89 to 93% of recent U.S. clade 2.3.4.4b cases

›Tearing, discharge, photophobia

›Onset relative to exposure

›Incubation period typically 2 to 5 days

03Physical Exam/exam71

Vitals and general

›Stability snapshot

›Temperature

›Fever greater than 38 C in 46 to 75% depending on clade severity

›Hypothermia as severe sepsis marker

›Respiratory rate

›Greater than 30 per minute as severity marker

›Rising trend as fatigue indicator

›Blood pressure

›SBP < 90 mmHg as shock threshold

›MAP < 65 mmHg target for resuscitation

›Oxygen saturation

›Room air SpO2 below 90% requires immediate intervention

›Ambulatory desaturation assessment

›General appearance

›Respiratory distress

›Accessory muscle use

›Inability to speak full sentences

›Mental status

›Agitation from hypoxemia

›Somnolence as deterioration sign

Ocular exam

›Conjunctival findings

›Injection and hyperemia

›Unilateral or bilateral

›Present in approximately 89% of recent U.S. cases

›Discharge character

›Watery vs purulent

04Differential Diagnosis/ddx48

Life threats and close mimics

›Influenza mimics requiring immediate differentiation

›Seasonal influenza A or B

›ICD-10 J10 or J11

›Cannot be distinguished clinically from H5N1

›Requires subtype-specific RT-PCR

›COVID-19

›Overlapping respiratory syndrome

›Multiplex PCR panel recommended

›ICD-10 U07.1

›Other novel influenza A subtypes

›H7N9 avian influenza

›H9N2 avian influenza

›Variant swine influenza

›Severe respiratory illness mimics

›Legionella pneumophila

›ICD-10 A48.1

›Rapidly progressive bilateral pneumonia

›Urinary antigen test

›Mycoplasma pneumoniae

›ICD-10 J15.7

›Atypical pattern

›Cold agglutinins

›MERS-CoV

›Travel to Arabian Peninsula

›ICD-10 U04.9 coding variant

›Bacterial pneumonia with sepsis

›ICD-10 J15.9

05Laboratory Tests/lt60

Core infectious workup

›Viral diagnostics

›RT-PCR gold standard

›CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel with Influenza A H5 Subtyping Kit

›Results available in 4 to 6 hours

›Collect conjunctival AND nasopharyngeal swabs

›Specimen collection strategy

›Conjunctival swabs positive in 88% of cases vs 21 to 58% for NP swabs

›Throat swabs may outperform nasal swabs unlike seasonal influenza

›Multiple specimens increase diagnostic yield

›Rapid antigen test limitations

›Sensitivity 0 to 36% for H5N1

›Negative result does not exclude H5N1

›If influenza A positive but H1/H3 negative, immediately notify public health for H5 subtyping

Severity and prognostic labs

›Hematologic markers

›Complete blood count

›Lymphopenia in 73% of severe cases

›Neutropenia associated with fatal outcome

›Thrombocytopenia as severity marker

›Coagulation panel

›Prolonged PT and aPTT in severe cases

›Elevated D-dimer for DIC concern

›Hepatic and metabolic markers

›Liver function tests

›Elevated AST in 69% of severe cases

›Elevated ALT in 61% of severe cases

›Combined neutropenia plus elevated ALT predicted 91% of deaths in Vietnamese cohort

06Diagnostic Tests/dt82

Scoring Systems

›Severity stratification tools

›CURB-65 for community-acquired pneumonia severity

›Confusion

›Urea greater than 7 mmol/l

›Respiratory rate >= 30 per minute

›Blood pressure SBP < 90 or DBP <= 60 mmHg

›Age >= 65 years

›Score >= 3 higher mortality and ICU admission

›SOFA score for organ dysfunction

›Respiratory PaO2/FiO2 component

›Coagulation component

›Hepatic and renal components

›Score >= 2 as organ dysfunction threshold

›PaO2/FiO2 ratio for ARDS staging

›Berlin definition ARDS criteria

›Mild 200 to 300 mmHg

›Moderate 100 to 200 mmHg

›Severe less than 100 mmHg

›H5N1 specific severity determinants

›Clade-based risk stratification

›Clade 2.3.4.4b predominantly mild

›D1.1 genotype associated with severe illness

›Historic clades with approximately 50% case fatality

›Predictors of fatal outcome

›Combined neutropenia plus elevated ALT at admission

›Delayed presentation greater than 3 days

›Diarrhea plus mucosal bleeding

MRI

›MRI role in H5N1

›Limited acute utility in primary H5N1 management

›CT and bedside ultrasound preferred for hemodynamically unstable patients

›Availability and time constraints

›Brain MRI for neurologic complications

›Encephalopathy evaluation

›Suspected viral encephalitis

›Hemorrhagic or ischemic complications

›Contraindications and limitations

›Unstable ventilated patients

›Incompatible implants

›Infection control challenges in MRI environment

CT

›CT chest indications

›Severe or worsening respiratory illness

›Diffuse ground-glass opacities consistent with ARDS

›Rapid progression from unilateral to bilateral infiltrates

›Consolidation pattern characterization

›Complication evaluation

›Secondary bacterial pneumonia superimposed on viral illness

›Pleural effusion characterization

›Pulmonary embolism if clinical concern

›CT findings in severe H5N1

›Bilateral ground-glass opacities

›Consolidation with air bronchograms

›Rapid radiographic progression within days as hallmark

›CT utility limitations

›Mild conjunctivitis-only presentations

›CT unnecessary without respiratory symptoms

›CXR adequate first line

›Radiation and transport considerations

›Infection control during transport

›Renal function for contrast

Ultrasound

›Lung ultrasound

›Consolidation pattern

›Tissue-like echotexture with air bronchograms

›Shred sign at consolidation-aeration border

›Pleural effusion assessment

›Free fluid vs complex loculations

›Guidance for thoracentesis if needed

›B-lines for interstitial pattern

›Bilateral B-lines consistent with ARDS

›Superior to CXR for early interstitial edema detection

›Cardiac POCUS

›LV function assessment

›Myocarditis screen given 50% cardiac failure rate in severe Chinese cases

›Global systolic function estimate

›RV strain

›Cor pulmonale in severe hypoxemia

›McConnell sign

›Pericardial effusion screen

›Hemodynamic POCUS

›IVC collapsibility for fluid responsiveness

›Integration with clinical context

›Limitations in ventilated patients

›Carotid VTI for cardiac output estimate

07Disposition/dispo53

Admission indications

›Inpatient admission criteria

›Respiratory involvement

›SpO2 < 92% on room air

›Any supplemental oxygen requirement

›Pneumonia on imaging

›Hemodynamic instability

›SBP < 90 mmHg

›Shock or vasopressor requirement

›Significant laboratory derangements

›Lymphopenia below normal range

›Elevated transaminases above 2x normal

›Thrombocytopenia below 100 x 10 to the 9th per L

›Elevated LDH above 2x normal

›Neurologic symptoms

›Altered mental status

›Seizures

›Inability to tolerate oral antivirals

›Persistent vomiting

›Swallowing difficulty

›ICU admission criteria

›ARDS

›PaO2/FiO2 < 300 mmHg

›Bilateral infiltrates

›Non-cardiac origin

›Multiorgan failure

›Vasopressor requirement

›Renal replacement therapy need

08Treatment/t90

Antiviral therapy

›Oseltamivir (neuraminidase inhibitor) first line

›Mild disease regimen

›75 mg PO twice daily for 5 days

›Weight-based adjustment for children

›Renal dose adjustment for CrCl < 30 ml/min

›Severe or pneumonic disease regimen

›150 mg PO twice daily for 7 to 10 days

›Initiate immediately on clinical suspicion

›Benefit persists up to 6 to 8 days after symptom onset

›Oseltamivir reduces mortality by approximately 49%

›Dosing in renal impairment

›CrCl 10 to 30 ml/min: 75 mg once daily

›Hemodialysis: 30 mg after each session

›Alternative antivirals for resistant strains

›Zanamivir inhaled

›Active against oseltamivir-resistant H5N1 variants with H274Y mutation

›10 mg inhaled twice daily for 5 to 10 days

›Suboptimal lung delivery in severe pneumonic disease

›Peramivir IV

›Alternative neuraminidase inhibitor for IV route

›600 mg IV single dose for uncomplicated illness

›May extend to multiple doses for severe disease

›Useful when oral route unavailable

›Baloxavir marboxil

›Cap-dependent endonuclease inhibitor

›FDA approved for seasonal influenza

›H5N1 susceptibility reported

›40 mg single dose for less than 80 kg

›80 mg single dose for 80 kg or more

Post-exposure prophylaxis

›Antiviral prophylaxis protocol

›Oseltamivir 75 mg once daily for 7 to 10 days

›Initiate within 48 hours of exposure

›For close contacts of confirmed H5N1 cases

›For workers with high-risk unprotected exposure

›Healthcare worker prophylaxis

›Unprotected exposure during aerosol-generating procedures

›N95 failure or breach during care

›Renal dose adjustment for prophylaxis same proportional reduction as treatment

Supportive care

›Oxygen therapy

›Nasal cannula titration to SpO2 92 to 96%

›Low flow 1 to 6 L/min

›Escalate based on requirement

›High flow nasal cannula for moderate hypoxemia

›Flow rates 30 to 60 L/min

›FiO2 titrated to target

›Non-invasive ventilation consideration

›CPAP or BiPAP for hypoxemic respiratory failure

›Close monitoring for deterioration requiring intubation

›Mechanical ventilation for ARDS

›Lung-protective strategy

›Tidal volume 6 ml/kg ideal body weight

›Plateau pressure < 30 cmH2O

›PEEP titration

›Higher PEEP strategy for moderate to severe ARDS

›PEEP-FiO2 table per ARDSnet protocol

›Prone positioning

›16 hours per day for PaO2/FiO2 < 150 mmHg

›Class I recommendation for severe ARDS

›Fluid and electrolyte management

›IV fluid resuscitation for shock

›30 ml/kg crystalloid bolus if septic shock

›Reassess after each bolus

›Conservative fluid strategy once resuscitated

›Avoid fluid overload in ARDS

›Daily fluid balance monitoring

Medications to avoid

›Corticosteroids contraindicated in most cases

›Associated with increased mortality in H5N1

›Immunosuppression prolongs viral replication

›Increased risk of secondary bacterial pneumonia

›Exception for comorbid conditions requiring steroids

›Refractory septic shock with adrenal insufficiency

›Concurrent severe asthma or COPD exacerbation

›ACEP Level C evidence against routine steroid use

›Aspirin avoidance in children

›Reye syndrome risk with influenza

›Acetaminophen or ibuprofen for antipyresis

Infection control measures

›PPE protocol for healthcare workers

›N95 or higher respirator

›Fit-tested before use

›Donning and doffing supervision

›Gown and gloves for all patient contact

›Eye protection for all encounters

›Full airborne precautions during aerosol-generating procedures

›Patient isolation

›Negative pressure room preferred

›Single-patient room minimum

›Dedicated equipment

›Limited personnel contact

›Cohort team if possible

›Visitor restriction

09Special Populations/sp69

Pregnancy

›Pregnancy-specific considerations

›Increased baseline influenza severity risk

›Physiologic immunomodulation

›Increased oxygen demand

›Antiviral safety

›Oseltamivir generally considered safe in pregnancy

›Benefits of treatment outweigh theoretical risks

›No dose adjustment needed in pregnancy

›Imaging approach

›CXR with abdominal shielding when clinically indicated

›CT only when benefits outweigh radiation risk

›Ultrasound first for pleural assessment

›Maternal and fetal monitoring

›SpO2 target >= 95% to optimize fetal oxygenation

›Higher than standard adult target

›Continuous monitoring in admitted patients

›Fetal monitoring when viable gestation

›Continuous CTG for term pregnancies

›Obstetric consultation for all hospitalized pregnant patients

›Neonatal exposure risk

›Isolate neonate until maternal status clarified

›Neonatology consultation

Geriatric

›Older adult considerations

›Atypical presentation risk

›Afebrile despite active infection

›Delirium as primary presentation

10Background/b84

Epidemiology

›Global burden and historical cases

›WHO confirmed human cases 1997 to 2015

›Predominantly Southeast Asia and Egypt

›Overall case fatality rate approximately 50% in historic clades

›Systematic review of global cases 1997 to 2015 confirmed high mortality

›U.S. outbreak 2024 to 2025

›70 confirmed human cases March 2024 to May 2025

›Predominantly dairy farm workers and poultry workers

›Clade 2.3.4.4b predominant circulating strain

›Estimated case fatality 0.7% after adjusting for underreporting

›Transmission dynamics

›Primary route zoonotic

›Direct animal to human transmission

›No sustained human-to-human transmission documented with clade 2.3.4.4b

›Exposure pathways

›Infected poultry and their secretions

›Infected dairy cattle and raw milk

›Wild birds as reservoir

›Occupational risk

›Only 36% of exposed farm workers used adequate PPE

›Poultry depopulation activities highest risk

›Population at risk

›Most U.S. clade 2.3.4.4b cases had no underlying conditions

›76% of cases without underlying medical conditions

›Historically healthy young adults and children at risk for severe disease

›Geographic distribution

›Cases across multiple U.S. states associated with dairy cattle movement

›International cases ongoing in Asia and Africa with historic clades

Pathophysiology

›Viral biology

›H5N1 influenza A structure

›Hemagglutinin H5 subtype with high receptor affinity for lower respiratory tract

›Neuraminidase N1 subtype

›Highly pathogenic designation based on polybasic cleavage site

›Receptor binding differences from seasonal influenza

›Preferential binding to alpha-2-3 sialic acid receptors

›Predominantly in lower respiratory tract and intestine

›Explains tropism for severe pneumonia and GI involvement

›Clade evolution

›Clade 2.3.4.4b emerged with expanded mammalian host range

›Dairy cattle infection unprecedented in H5N1 history

›D1.1 genotype reassortant with capability for severe human disease

›Disease mechanisms

›Cytokine storm

›Dysregulated innate immune response

›Elevated IL-6, TNF-alpha, interferons

›Contributes to multiorgan dysfunction

›Direct viral injury

›Alveolar epithelial cell destruction

›Bilateral pneumonia progressing to ARDS

›Rapid radiographic progression within 24 to 48 hours

›Systemic spread

›Viremia reported in severe cases

›CNS involvement via direct invasion or cytokine-mediated injury

›Cardiac involvement via direct myocarditis

Therapeutic Considerations

›Antiviral resistance landscape

›Oseltamivir resistance mutation H274Y

›Rare but reported in some H5N1 strains

›Zanamivir active against H274Y resistant strains

›Resistance testing recommended for treatment failures

›Combination antiviral strategy

›No definitive clinical trial evidence for combination superiority

›Considered for severe disease or suspected resistance

›Oseltamivir plus baloxavir under investigation

›Immune modulation considerations

›Corticosteroids harmful in H5N1

›Associated with increased mortality in observational data

›Prolonged viral shedding with steroid use

›Avoid unless secondary indication is compelling

›Convalescent plasma

›Limited data in H5N1

›Investigational use for severe refractory disease

›WHO guidance supports consideration under compassionate use

›Pandemic preparedness context

›Vaccine stockpile

›Audenz H5N1-specific vaccine FDA-approved for high-risk individuals

›Seasonal influenza vaccines do not protect against H5N1

›Strategic national stockpile considerations

›Antiviral stockpile

›Strategic national stockpile maintained for neuraminidase inhibitors

›WHO advises maintaining antiviral reserves

›Surveillance importance

›Every case requires full public health investigation

›Genomic sequencing to detect concerning mutations

›Human-to-human transmission monitoring

11Patient Discharge Instructions/pdi42

copy discharge instructions

›H5N1 avian influenza home care instructions

›Take oseltamivir exactly as prescribed

›Complete the full course even if feeling better

›Take with food to reduce stomach upset

›Rest and stay well hydrated

›Water and clear fluids

›Avoid alcohol

›Isolate from others while ill

›Stay home from work or school until fever-free for 24 hours without antipyretics

›Avoid contact with poultry and livestock until cleared by public health

›Monitoring requirements

›Daily symptom check-in with health department or clinician

›Temperature twice daily

›Breathing difficulty assessment

›All household contacts monitored for 10 days from last exposure

›Contact public health if any household member develops symptoms

›Do not wait for symptoms to worsen before calling

›Warning signs requiring immediate return to emergency department

›Difficulty breathing at rest or with minimal activity

›Persistent or worsening fever after starting antivirals

›Chest pain

›Blue or grey colour to lips, face, or fingertips

›Confusion, unusual sleepiness, or difficulty waking

›Worsening eye redness or visual changes

›Coughing up blood

›Inability to keep fluids or medications down

›A negative rapid flu test does NOT exclude H5N1

12References/r29

Guidelines and key sources

›Primary clinical references

›Rolfes MA et al. Human Infections With Highly Pathogenic Avian Influenza A H5N1 Viruses in the United States From March 2024 to May 2025. Nature Medicine 2025

›70 U.S. cases characterization

›Conjunctival swab diagnostic superiority data

›Garg S et al. Highly Pathogenic Avian Influenza A H5N1 Virus Infections in Humans. NEJM 2025

›Clinical management guidance

›Antiviral recommendations

›WHO Writing Committee. Update on Avian Influenza A H5N1 Virus Infection in Humans. NEJM 2008

›Mortality predictors including neutropenia plus elevated ALT

›LDH as prognostic marker

›Supporting literature

›Blais-Savoie J et al. Examining the Threat of H5N1 Highly Pathogenic Avian Influenza to Human Health. Chest 2026

›Comprehensive clinical review

›Severity markers and clade comparison

›Adisasmito W et al. Effectiveness of Antiviral Treatment in Human Influenza A H5N1 Infections. Journal of Infectious Diseases 2010

›49% mortality reduction with oseltamivir

›Benefit up to 6 to 8 days after symptom onset

›Lai S et al. Global Epidemiology of Avian Influenza A H5N1 Virus Infection in Humans 1997 to 2015. Lancet Infectious Diseases 2016

›Systematic review of global case fatality data

›Guidance documents

›CDC Yellow Book 2025 Influenza chapter

›Travel-associated influenza guidance

›PPE recommendations

›WHO Rapid Advice Guidelines for Pharmacological Management of Sporadic Human Infection With Avian Influenza A H5N1. Lancet Infectious Diseases 2007

›Original WHO antiviral guidance

›Oseltamivir dosing framework

›AAP Committee on Infectious Diseases. Recommendations for Prevention and Control of Influenza in Children 2025 to 2026. Pediatrics 2025

Evidence & Review