01Approach to the Critical Patient/attcp62

Immediate priorities

›Airway and breathing threats

›Rapidly progressive hypoxemia

›SpO2 often below 93% on room air at presentation

›Mean onset-to-respiratory failure approximately 9 days

›ARDS development

›Occurs in 83 to 90% of hospitalized patients

›Bilateral ground-glass opacities with rapid multilobar progression

›Intubation indications

›Inability to maintain SpO2 despite HFNC

›Refractory hypoxemia not responding to NIV

›If intubated, lung-protective ventilation immediately

›Tidal volume 6 mL per kg IBW

›Plateau pressure target below 30 cmH2O

›Circulation and sepsis threats

›Septic shock pattern

›SBP below 90 mmHg

›MAP below 65 mmHg

›Multiorgan dysfunction

›Acute kidney injury monitoring

›Rhabdomyolysis with elevated creatine kinase

›DIC with coagulation derangement

›If septic shock, vasopressors and ICU escalation

›Norepinephrine first-line vasopressor

›Broad-spectrum antibiotics for bacterial co-infection

›Isolation and public health

›Airborne plus contact plus standard precautions immediately

›Negative pressure room if available

02History/hx74

Exposure history

›Poultry contact

›Live poultry market visit within prior 10 days

›Adjusted OR 3.4 for live market exposure

›Direct poultry handling

›Matched OR 7.8 for direct poultry contact

›Occupational poultry work

›Market vendor or farm worker

›Travel history

›Travel to mainland China within prior 10 days

›All five epidemics confined to China 2013 to 2017

›Endemic area residence

›Urban live bird markets as primary exposure site

›Human contact

›Ill household members with similar illness

›Four family clusters with possible limited human-to-human transmission

›Healthcare exposure to confirmed H7N9 patients

Symptom onset and progression

›Classic presentation

›High fever onset

›Often above 39 degrees Celsius

›Universal in hospitalized cases

›Cough initially dry then productive

›Sputum production with progression

›Hemoptysis in approximately 24%

›Dyspnea with rapid deterioration

›Median onset-to-hospitalization 4 days

›Median onset-to-ARDS 7 days

03Physical Exam/exam54

Vital signs

›Stability assessment

›Temperature

›High fever above 39 degrees Celsius typical

›Hypothermia as severe sepsis marker

›Respiratory rate

›Tachypnea common at presentation

›Rising trend as marker of fatigue

›Blood pressure

›Hypotension in septic shock

›MAP below 65 mmHg as resuscitation trigger

›Oxygen saturation

›SpO2 often below 93% on room air

›Ambulatory desaturation assessment

Respiratory exam

›Lung findings

›Bilateral crackles and rales

›Diffuse rather than focal distribution

›Correlates with bilateral ground-glass opacities

›Decreased breath sounds

›Consolidation pattern

›Pleural effusion in approximately 50%

›Respiratory distress signs

›Accessory muscle use

›Nasal flaring

›Inability to speak full sentences

›Upper airway exam

›Notably absent upper airway findings

04Differential Diagnosis/ddx45

Life-threatening diagnoses

›Pandemic and avian influenza

›Avian influenza A H5N1

›Similar severity but younger median age 29 years versus 61

›ICD-10 J09.X2

›Longer onset-to-hospitalization than H7N9

›H7N9 avian influenza

›ICD-10 J09.X2

›Poultry exposure in China within prior 10 days

›Other severe respiratory infections

›SARS-CoV-2 and COVID-19

›ICD-10 U07.1

›Overlapping bilateral GGO pattern

›Distinguish by exposure history and PCR

›MERS-CoV

›ICD-10 J06.9

›Travel to Middle East and camel exposure

›Hantavirus pulmonary syndrome

›Rodent exposure history

›North American distribution

Common mimics

›Community-acquired pneumonia

›Bacterial CAP

›ICD-10 J18.9

›Responds to antibiotics

›Lobar rather than bilateral multilobar pattern

›Legionella pneumonia

›Hyponatremia and diarrhea overlap

05Laboratory Tests/lt70

Core infection labs

›Complete blood count

›Lymphocytopenia

›Present in 88.3% of confirmed cases

›Characteristic finding

›Thrombocytopenia

›Present in 73.0% of confirmed cases

›Leukopenia or normal white cell count

›High WBC unusual and suggests bacterial co-infection

›Inflammatory markers

›C-reactive protein

›Markedly elevated in most cases

›Limited specificity

›Procalcitonin

›Elevated

›May help identify bacterial co-infection

Organ function and injury markers

›Hepatic panel

›AST elevation

›Nearly universal

›Marker of multiorgan involvement

›LDH elevation

›Nearly universal

›Correlates with disease severity

›Creatine kinase

›Elevated CK

›Myositis and rhabdomyolysis

›Monitor for acute kidney injury consequence

06Diagnostic Tests/dt72

Scoring Systems

›Severity scoring tools

›APACHE II

›Used in published H7N9 case series

›Higher scores predict ICU need and mortality

›qSOFA

›RR above 22 per minute

›SBP at or below 100 mmHg

›Altered mental status

›Screening tool for sepsis identification

›SOFA score

›Full organ dysfunction assessment

›Tracks multiorgan failure progression

›Score limitations

›No H7N9-specific validated severity score exists

›Clinical trajectory and imaging progression guide decisions

›All confirmed cases with pneumonia require hospitalization

›Scoring used for ICU triage not admission decision

MRI

›MRI chest role

›Limited utility in acute H7N9

›CT preferred given superior resolution and speed

›Availability and patient stability constraints

›Problem-solving indications

›Suspected cardiac involvement

›Myocarditis characterization

›Contraindications

›Unstable ventilated patients

07Disposition/dispo45

Admission criteria

›Hospitalization required for virtually all confirmed cases

›99% of published case series required hospitalization

›Any suspected H7N9 with pneumonia or hypoxemia warrants admission

›Observation warranted even in mild cases

›Rapid deterioration typical course

›Serial imaging and repeat testing during observation

›ICU indications

›Respiratory failure

›Requirement for HFNC

›Intubation and mechanical ventilation

›ECMO consideration for refractory hypoxemia

›Hemodynamic instability

›Vasopressor requirement

›Septic shock pattern

›Multiorgan dysfunction

›Acute kidney injury requiring renal replacement

›DIC with active bleeding

›ICU required in approximately 76.6% of confirmed cases

Transfer and consultation

›Mandatory specialist consultation

›Infectious disease

›Mandatory for all suspected cases

›Antiviral management guidance

›Pulmonary and critical care

›Ventilatory management

›ECMO candidacy assessment

›Public health authorities

08Treatment/t101

Infection control measures

›Isolation precautions

›Airborne plus contact plus standard precautions

›Negative pressure room if available

›N95 respirator for all healthcare workers entering room

›Duration of isolation

›Until clinical improvement and confirmed cessation of viral shedding

›Negative RT-PCR confirmation preferred

Antiviral therapy

›Oseltamivir

›Standard dose

›75 mg PO twice daily for 5 days minimum

›Extend in critically ill or immunocompromised until viral clearance

›High-dose for critically ill

›150 mg PO twice daily

›Used in published case series with severe disease

›Renal dose adjustment

›Dose reduce for CrCl below 30 mL per minute

›Resistance concern

›R292K neuraminidase mutation may emerge during treatment

›Switch to alternative agent if clinical deterioration on therapy

›Peramivir

›Indication

›Oral route unavailable

›Clinical deterioration on oseltamivir

›Dosing

›600 mg IV daily

›Single dose for uncomplicated; extend in critically ill

›Renal adjustment required

›Dose reduce for CrCl below 50 mL per minute

›Zanamivir

›Inhaled or IV formulation

›Alternative when oseltamivir resistance confirmed

›IV formulation available through emergency access

›Inhaled dosing

›10 mg inhaled twice daily for 5 days

›Avoid in patients with underlying airway disease

›Timing principle

›Initiate antivirals empirically on clinical suspicion

›Do not wait for confirmatory RT-PCR

›Early treatment within 48 hours associated with lower mortality

›Benefit may extend up to 5 days post-onset

Drugs to avoid

›Adamantanes contraindicated

›Amantadine and rimantadine

›H7N9 viruses universally resistant

›No role in treatment or prophylaxis

›Corticosteroids

›Avoid in H7N9 management

›Associated with prolonged viral shedding

›Associated with worse clinical outcomes

›No mortality benefit demonstrated

›Salicylates

›Avoid in influenza illness

›Reye syndrome risk

Respiratory support

›Supplemental oxygen

›Titrate to SpO2 target 92 to 96%

›Nasal cannula initial approach

›HFNC for moderate to severe hypoxemia

›NIV consideration

›Limited evidence in H7N9 specifically

›High conversion to intubation expected

›Mechanical ventilation

›Lung-protective ventilation strategy

›Tidal volume 6 mL per kg IBW

›Plateau pressure below 30 cmH2O

›PEEP titration for oxygenation

›Prone positioning for severe ARDS

›PaO2 to FiO2 ratio below 150 mmHg

›Minimum 16 hours per session

›ECMO

›Consideration for refractory hypoxemia

›Failed conventional ventilation

›PaO2 to FiO2 ratio persistently below 80 mmHg

›Refer to ECMO-capable center early

›Before clinical deterioration precludes transport

Antibiotics for bacterial co-infection

›Empiric broad-spectrum antibiotics

›Secondary bacterial infection in 66.7% of ICU cases

›Klebsiella pneumoniae

›MRSA

›Acinetobacter

›Initial regimens used in published series

›Fluoroquinolones

›Piperacillin-tazobactam

›Carbapenems for resistant organisms

›De-escalation strategy

›Review cultures and sensitivities at 48 to 72 hours

›Narrow spectrum when possible

›Minimize resistance pressure

Supportive care

›Fluid management

›Aggressive resuscitation for septic shock

›30 mL per kg crystalloid initial bolus

›Reassess response with lactate and clinical exam

›Conservative fluid strategy once stabilized

›ARDS fluid balance targets negative to even

›Renal replacement therapy

›Continuous RRT for severe acute kidney injury

›Volume overload complicating ventilation

›Uremia or electrolyte derangement

›Public health management

›Close contact prophylaxis

›Oseltamivir twice-daily dosing for exposed contacts

›Monitor close contacts for 7 days

›Contact tracing coordination with health authorities

09Special Populations/sp65

Pregnancy

›Maternal risk

›H7N9 in pregnancy

›Limited published data

›Physiologic changes increase respiratory compromise risk

›Decreased FRC and increased oxygen consumption

›Fetal monitoring

›Viable gestation continuous fetal monitoring

›Obstetrician involvement mandatory

›Antiviral safety

›Oseltamivir generally considered safe in pregnancy

›Benefits outweigh risks in severe H7N9

›Standard or high dose based on severity

›Avoid amantadine in pregnancy

›Teratogenicity concerns

›Also ineffective for H7N9

›Oxygenation targets

›Maintain SpO2 above 95% when feasible

›Fetal oxygenation depends on maternal saturation

›Prone positioning considerations

›Limited in later pregnancy

›Alternative positioning strategies required

›Delivery considerations

›Early delivery only for fetal distress or maternal deterioration

›Airborne precautions in delivery suite

›Neonatal team isolation readiness

Geriatric

›Age-related risk

10Background/b73

Epidemiology

›Emergence and burden

›Novel reassortant avian-origin influenza A virus

›Emerged in China in 2013

›1,568 confirmed human infections by 2019

›Case-fatality ratio approximately 40%

›Five epidemic waves

›2013 to 2017 in mainland China

›No new human cases detected since 2019

›Pandemic risk designation

›CDC ranks H7N9 highest potential pandemic risk of all influenza viruses

›Case characteristics

›Median age 61 years

›Male-to-female ratio 2.4 to 1

›ICU admission in 76.6% of confirmed cases

›Overall case-fatality ratio 28 to 40%

›Underlying conditions in 61 to 73% of cases

›Transmission epidemiology

›Poultry exposure primary route

›Live bird markets dominant exposure site

›No sustained human-to-human transmission documented

›Four family clusters identified

›Limited human-to-human transmission could not be excluded

›Environmental source

›H7N9 detected in poultry, migratory birds, and live market environments

Pathophysiology

›Viral characteristics

›Reassortant virus composition

›Hemagglutinin from wild aquatic bird H7 viruses

›Neuraminidase from Yangtze River Delta lineage H7N9 viruses

›Internal genes from H9N2 viruses

›Receptor binding

›Dual binding to human alpha-2,6 and avian alpha-2,3 sialic acid receptors

›Enables lower respiratory tract tropism in humans

›Disease mechanism

›Predominant lower respiratory tract infection

›Upper respiratory tract involvement minimal

›Direct viral injury to alveolar epithelium

›Cytokine dysregulation

›Markedly elevated IL-6 and IL-10

›Cytokine storm contributing to ARDS and multiorgan failure

›Multiorgan failure pathway

›ARDS most common cause of death

›Secondary bacterial infection in 66.7%

›Acute kidney injury from viral and hypoperfusion injury

›Rhabdomyolysis and myositis

›Left ventricular failure in up to 33%

›Genetic susceptibility

›IFITM3 rs12252-C/C genotype

›May predict severe illness

›Interferon-induced transmembrane protein 3 polymorphism

Therapeutic Considerations

›Neuraminidase inhibitor evidence

›Oseltamivir cornerstone of treatment

›Early treatment within 48 hours associated with lower mortality

›High-dose 150 mg twice daily used in critically ill without clear mortality benefit

›Resistance emergence

›R292K mutation conferring NAI resistance reported during treatment

›Higher oseltamivir MIC in some isolates

›Switch strategy required if clinical deterioration on oseltamivir

›Peramivir IV alternative

›Useful when enteral route unavailable

›Single daily dosing simpler than oral BID

›Steroid avoidance rationale

›Prolonged viral shedding documented

›Worse clinical outcomes in observational data

›No proven benefit for ARDS in H7N9 specifically

›Contrast with other ARDS contexts

›General ARDS steroid evidence does not apply given viral replication concerns

›Pandemic preparedness implications

›Pre-pandemic H7N9 vaccines developed

›Current H7N9 vaccines not widely distributed

›Antiviral stockpiling rationale

›Oseltamivir and peramivir in national stockpiles

›Global surveillance importance

›Live bird market closures in China reduced case counts

11Patient Discharge Instructions/pdi34

copy discharge instructions

›H7N9 avian influenza recovery instructions

›Complete the full course of antiviral medication exactly as prescribed

›Oseltamivir typically 5 days minimum

›Do not stop early even if feeling better

›Strict respiratory hygiene

›Cover coughs and sneezes with elbow or tissue

›Wash hands frequently with soap and water

›Wear a surgical mask around household members until cleared

›Avoid contact with live poultry or bird markets until fully recovered and cleared by your doctor

›Do not share utensils towels or bedding with household members during recovery

›Monitoring close contacts

›Household members and close contacts

›Monitor for fever or respiratory symptoms for 7 days after last exposure

›Contact doctor immediately if symptoms develop

›Post-exposure preventive treatment may have been prescribed

›Warning signs to return to the emergency room immediately

›Worsening shortness of breath or difficulty breathing at rest

›SpO2 below home oximeter target if provided

›Coughing up blood or blood-tinged sputum

›New confusion or unusual sleepiness

›High fever not improving after 48 hours of antivirals

›Chest pain or pressure

›Decreased urination or dark urine suggesting kidney problems

›Signs of severe illness including blue lips or fingertips

›Expected recovery course

›Recovery is prolonged

›Weeks to months for full respiratory recovery

12References/r39

Guidelines and key sources

›CDC and public health guidance

›CDC Yellow Book 2025 Influenza chapter

›Exposure risk and post-exposure prophylaxis guidance

›Oseltamivir twice-daily dosing for close contact prophylaxis

›MMWR 2017 H7N9 Fifth Epidemic Update

›Risk factor analysis for severe disease

›Age-stratified fatality risk data

›Landmark clinical studies

›Li Q et al. NEJM 2014

›Epidemiology of Human Infections with Avian Influenza A H7N9 in China

›Key epidemiologic and clinical characterization

›Gao HN et al. NEJM 2013

›Clinical Findings in 111 Cases of Influenza A H7N9

›Lymphocytopenia 88.3% and thrombocytopenia 73.0% data

›Gao R et al. NEJM 2013

›Human Infection with Novel Avian-Origin Influenza A H7N9 Virus

›Initial characterization of outbreak

›Wang X et al. Lancet Infectious Diseases 2017

›Epidemiology across five epidemics 2013 to 2017

›Peramivir and antiviral management data

›Imaging and diagnostic references

›Wang Q et al. Radiology 2013

›Emerging H7N9 Pneumonia Radiologic Findings

›Ground-glass opacity and consolidation patterns

›Yu WQ et al. Internal Medicine Journal 2020

›H7N9 Avian Influenza Pneumonia Retrospective Analysis

›Pleural effusion approximately 50% and residual fibrotic changes

Evidence & Review