01Approach to the Critical Patient/attcp40

Immediate recognition and stabilization

›Critical presentation triggers

›Febrile prodrome (fever, myalgias, headache) followed by sudden-onset dyspnea

›Transition from prodrome to cardiopulmonary phase can occur within hours

›Most deaths occur within 24 hours of hospital admission

›Hypotension plus thrombocytopenia plus bilateral infiltrates on CXR

›High specificity cluster for HPS in endemic area

›Rapidly worsening hypoxia despite supplemental oxygen

›Anticipate intubation requirement

Airway and breathing

›Oxygenation failure management

›SpO2 target 92-96% on supplemental oxygen

›High-flow nasal cannula for moderate hypoxia

›Prepare for rapid sequence intubation if deteriorating

›Delay intubation until VA-ECMO access secured if feasible

›Post-intubation hemodynamic collapse risk is high

›Pre-place femoral vascular sheaths early based on clinical suspicion

›Lung-protective ventilation if intubated

›Tidal volume 6 mL/kg ideal body weight

›Plateau pressure target <30 cmH2O

Hemodynamic support priorities

›Cardiogenic-distributive shock pattern

›Avoid aggressive IV fluid resuscitation

›Exacerbates pulmonary capillary leak and non-cardiogenic pulmonary edema

›Increases mortality with excess volume loading

›Inotrope initiation for low cardiac output

›Dobutamine or epinephrine as first-line for cardiac index <2.5 L/min/m2

›Norepinephrine for vasopressor support of refractory hypotension

02History/hx37

Exposure history

›Rodent contact within past 5-50 days

›Incubation period median 18 days (range 5-50 days)

›Cleaning rodent-infested enclosed spaces (cabins, sheds, barns, garages)

›Disturbing rodent nests or droppings without respiratory protection

›Geographic and activity context

›Western US states carry highest risk; cases reported in 39 US states

›Rural wilderness travel, camping, hiking in endemic areas

›Occupational exposures: farming, forestry, military field training, construction

›Seasonal pattern: peak incidence spring and summer

Prodromal symptoms

›Classic febrile prodrome (2-7 days duration)

›Fever: present in 100% of cases

›Myalgias: present in 100%; severe and universal

›Headache: present in 71%

›Chills and malaise

›Notable absence of rhinorrhea and sore throat (distinguishes from influenza)

›Gastrointestinal symptoms

›Abdominal pain, nausea, vomiting, diarrhea in 76%

›GI-predominant prodrome can lead to misdiagnosis of acute abdomen

›Unnecessary surgical exploration risk if HPS not considered

Cardiopulmonary phase symptoms

›Transition alarm features

›Sudden onset cough (initially dry) after febrile prodrome

›Progressive dyspnea evolving over hours

›Chest tightness

›Cardiovascular symptoms

›Palpitations and lightheadedness

03Physical Exam/exam37

Vital signs

›Hemodynamic assessment

›Fever: present in essentially all cases

›Tachypnea: present in 100%; early and prominent

›Tachycardia: present in 94%

›Hypotension: present in 50% on admission

›SBP <90 mmHg

›MAP <65 mmHg

Respiratory exam

›Pulmonary findings

›Bilateral crackles developing in cardiopulmonary phase

›May be initially absent in prodromal phase

›Rapid progression to diffuse crackles with pulmonary edema

›Signs of increased work of breathing

›Accessory muscle use

›Inability to speak full sentences

›Absence of pharyngeal erythema and rhinorrhea

›Key feature distinguishing HPS from influenza or typical URI

Cardiovascular and perfusion exam

›Shock physiology signs

›Mottled skin indicating low cardiac output

›Prolonged capillary refill time

›Diaphoresis

›Volume status assessment

›Jugular venous pressure (elevated in right heart failure)

›Peripheral edema (late finding)

Skin and extremity exam

›Cutaneous findings

04Differential Diagnosis/ddx38

Life-threatening mimics

›Influenza and viral pneumonia

›Most common initial misdiagnosis

›ICD-10: J09-J11

›HPS distinguished by thrombocytopenia, hemoconcentration, and immunoblasts on smear

›Absence of rhinorrhea and sore throat favors HPS

›Sepsis with ARDS

›ICD-10: A41.9 / J80

›HPS has unique hemodynamic pattern: hypovolemia plus systolic dysfunction plus increased permeability

›Classic septic shock typically shows vasodilatory pattern

›Pneumonic plague

›ICD-10: A20.2

›Must consider in western US geographic overlap

›Rapid progression with hemoptysis and gram-negative coccobacilli distinguish

›Community-acquired pneumonia (atypical)

›ICD-10: J18.9

›Bilateral infiltrates overlap with HPS

›HPS lacks purulent sputum and toxic granulation on smear

Other infectious mimics

›Leptospirosis

›ICD-10: A27.9

›Similar rodent exposure history

›Differentiated by jaundice, conjunctival suffusion, and renal predominance

›Dengue and other arboviral infections

›ICD-10: A90

›Fever plus thrombocytopenia overlap

›Travel history and geographic exposure guide differentiation

›Q fever (Coxiella burnetii)

05Laboratory Tests/lt44

Complete blood count

›CBC with differential

›Thrombocytopenia: median nadir 64,000/microL

›Platelet count <40,000/microL associated with increased mortality

›Rapid decline in serial counts indicates progression

›Leukocytosis with left shift: median peak WBC 26,000/microL

›Hemoconcentration: elevated hematocrit

›Rising hematocrit is independent predictor of death

›Peripheral blood smear

›Immunoblasts >10% of total leukocytes: highly characteristic of HPS

›Absence of toxic granulation in myeloid series

›Presumptive diagnostic criteria: >=4 of 5 features

›Thrombocytopenia

›Left shift

›No toxic granulation

›Hemoconcentration

›Immunoblasts >10%

›Sensitivity 96%, specificity 99% when >=4 criteria met

Metabolic panel and organ function

›Basic metabolic panel

›Creatinine: mild elevation common

›Sodium: hyponatremia present in some cases

›Lactate: >4.0 mmol/L is ominous prognostic marker

›Associated with 100% mortality without ECMO support

›Liver function tests

›Transaminase elevation: mild, non-specific

›LDH: elevated, correlates with tissue injury

›Coagulation studies

06Diagnostic Tests/dt46

Scoring Systems

›Presumptive diagnostic criteria (laboratory-based)

›Five-feature score: thrombocytopenia, left shift, no toxic granulation, hemoconcentration, immunoblasts >10%

›>=4 of 5 features: sensitivity 96%, specificity 99%

›Single most accessible rapid bedside tool for presumptive diagnosis

›Severity stratification

›Mild: prodromal symptoms only, no hypoxia, platelets >115,000/microL

›Moderate: hypoxia requiring supplemental O2, bilateral infiltrates, thrombocytopenia

›Severe: refractory shock, cardiac index <2.5 L/min/m2, lactate >4.0 mmol/L, need for ECMO

›Hemodynamic severity markers

›Cardiac index <2.5 L/min/m2 combined with lactate >4.0 mmol/L

›Associated with 100% mortality without mechanical circulatory support

›ECMO decision threshold in experienced centers

›Pulse pressure <20 mmHg indicating severe cardiac dysfunction

MRI

›MRI role in HPS

›No established role in acute HPS management

›Chest CT and echocardiography are more practical in critically ill patients

›Not recommended as primary diagnostic modality

›Brain MRI if neurologic complications suspected

›Hantavirus encephalitis is rare but reported

›Indicated for altered mental status not explained by hemodynamic cause

CT

›Chest CT findings

›Bilateral septal thickening: characteristic pattern in cardiopulmonary phase

›Ground-glass opacities: bilateral and diffuse

›Pleural effusions: bilateral; highly prevalent in severe cases

›Kerley B lines on CT correlating with interstitial edema

07Disposition/dispo16

ICU admission criteria

›All suspected HPS cases require ICU admission

›No patient with suspected HPS should be discharged from the ED

›Transition from prodrome to cardiopulmonary phase can occur within hours

›Ideally admitted to center with VA-ECMO capability

Transfer criteria

›Transfer indications

›Transfer early to ECMO-capable center

›Do not wait for serologic confirmation

›Clinical suspicion plus abnormal routine labs sufficient to trigger transfer

›Pre-transfer stabilization

›Establish inotropic support before transfer

›Anticipate need for emergent vascular access during transfer

›Consult critical care, infectious disease, and ECMO team before transfer

Discharge criteria

›No discharge criteria in acute presentation

›Discharge from ED is not appropriate for any suspected acute HPS

›Prodromal-phase patients identified early require hospital admission for monitoring

›Return-to-ED instructions warranted only for patients seen with very low suspicion and minimal symptoms

08Treatment/t65

Initial resuscitation

›Fluid management strategy

›Restrict IV fluid resuscitation

›Avoid aggressive volume loading: exacerbates capillary leak and pulmonary edema

›Prefer inotropes and vasopressors over volume

›Supplemental oxygen

›Initiate immediately for any hypoxia

›High-flow nasal cannula for moderate hypoxia

›Prepare for emergent intubation if SpO2 declining despite HFNC

Hemodynamic support

›Inotropic therapy

›Dobutamine IV

›Indication: cardiac index <2.5 L/min/m2

›Starting dose: 2-5 mcg/kg/min continuous infusion

›Titration: increase by 2.5 mcg/kg/min every 10-15 minutes to hemodynamic target

›Maximum: 20 mcg/kg/min

›Epinephrine IV

›Alternative first-line inotrope

›Starting dose: 0.05-0.1 mcg/kg/min continuous infusion

›Titration: increase by 0.05 mcg/kg/min every 5-10 minutes

›Maximum: 1.0 mcg/kg/min

›Vasopressor therapy

›Norepinephrine IV

›Indication: refractory hypotension despite inotropic support

›Starting dose: 0.05-0.1 mcg/kg/min continuous infusion

›Titration: increase by 0.05 mcg/kg/min every 5 minutes to MAP target 65 mmHg

›Maximum: 1.0 mcg/kg/min

Mechanical circulatory support

›Venoarterial ECMO

›Indication: refractory cardiogenic shock or respiratory failure

›Cardiac index <2.5 L/min/m2 despite maximal medical therapy

›Lactate >4.0 mmol/L not improving

›PEA, VF, or VT not responding to conventional resuscitation

›Outcomes: 80% survival reported in case series with early ECMO

›Strategy: pre-place femoral vascular sheaths early based on presumptive diagnosis

›Consider delaying intubation until ECMO access secured to avoid post-intubation collapse

›High-volume hemofiltration

›May serve as bridge or alternative to ECMO in select patients

›Removes cytokines contributing to capillary leak and hemodynamic instability

›Evidence limited to case series

Ventilator management

›Lung-protective ventilation strategy

›Tidal volume: 6 mL/kg ideal body weight

›Plateau pressure target <30 cmH2O

›PEEP titrated to oxygenation and hemodynamics

›FiO2 reduction target

›SpO2 92-96% to minimize oxygen toxicity

›Prone positioning consideration for refractory hypoxia

›P/F ratio <150 mmHg as threshold per standard ARDS protocols

Hemodynamic monitoring

›Invasive monitoring

›Arterial line: continuous blood pressure and serial ABG monitoring

›Central venous catheter: vasopressor and inotrope delivery

›Transpulmonary thermodilution or PA catheter for cardiac index trending

›Guide inotrope titration and ECMO decision-making

Therapies without proven benefit

›Ribavirin

›No survival benefit in placebo-controlled trial for HCPS

›Not recommended

›Corticosteroids

›High-dose methylprednisolone: no proven benefit

›Not recommended as routine therapy

›Convalescent plasma

›Possible benefit observed with Andes virus in open study

›Not standard of care; SNV data lacking

Infection control and public health

›Notification requirements

›Report all suspected cases to state/local health department and CDC

›Sin Nombre virus: standard precautions only (no person-to-person transmission)

›Andes virus: contact/droplet precautions

›Only hantavirus with documented person-to-person transmission

›Monitor household contacts for 40 days

09Special Populations/sp48

Pregnancy

›HPS in pregnancy

›High maternal and fetal mortality

›No large prospective series; case reports document fulminant maternal collapse

›Fetal hypoxia parallels maternal hypoxic respiratory failure

›Management approach

›Immediate ICU admission with maternal-fetal medicine consultation

›Hemodynamic support with inotropes permissible in pregnancy

›Norepinephrine: limited human safety data; use if benefit outweighs risk

›ECMO has been used in pregnant patients with life-threatening respiratory failure

›Differential considerations

›HELLP syndrome: overlapping thrombocytopenia and abdominal pain

›Peripartum cardiomyopathy: bilateral infiltrates can mimic

›Fetal monitoring throughout acute illness

›Multidisciplinary team: obstetrics, critical care, neonatology

Geriatric

›Older adult considerations

›Atypical presentation risk

›Fever may be blunted or absent

›Myalgias may be attributed to baseline musculoskeletal conditions

›GI symptoms may be attributed to other causes

›Hemodynamic vulnerability

›Reduced cardiac reserve limits tolerance of cardiogenic shock

›Pre-existing diastolic dysfunction worsens pulmonary edema

›Lower BP thresholds may represent significant deterioration

›Polypharmacy interactions

›Beta-blockers may blunt tachycardia as early warning sign

›Diuretics may compound hypovolemia

10Background/b50

Epidemiology

›Global and US burden

›Sin Nombre virus (SNV): primary cause in North America

›Cases reported in 39 US states; western states carry highest risk

›Approximately 850 cases confirmed in the US since 1993 (historical data)

›Case fatality rate: approximately 35-40%

›Seasonal peak: spring and summer

›Rodent populations peak with vegetation abundance

›Human outdoor activity increases concurrently

›Environmental and geographic drivers

›Reservoir: deer mice (Peromyscus maniculatus) for SNV

›Drought followed by heavy rainfall increases rodent populations

›Open developed areas and arid climates associated with higher risk

›Peridomestic rodent infestation as major urban exposure pathway

›Demographic patterns

›Age >18 years and female sex identified as independent mortality prognostic factors

›Rural residence associated with increased case fatality

›Certain HLA haplotypes may influence disease severity

Pathophysiology

›Viral entry and tropism

›Transmission: inhalation of aerosolized rodent urine, feces, and saliva

›No person-to-person transmission for SNV

›Andes virus: documented person-to-person transmission (sexual contact, close household contact)

›Viral tropism for endothelial cells of pulmonary vasculature

›Immunopathogenesis

›T-cell-mediated immunopathology drives capillary leak (not direct viral cytopathic effect)

›Massive endothelial permeability increase leads to non-cardiogenic pulmonary edema

›Concomitant myocarditis contributes to depressed systolic function

11Patient Discharge Instructions/pdi30

copy discharge instructions

›Discharge instructions for Hantavirus Pulmonary Syndrome

›What you were diagnosed with

›You were evaluated for possible hantavirus infection, a rare but serious illness spread from rodents

›This infection can cause severe lung and heart problems that worsen rapidly

›Medications

›There is no specific antiviral medication proven to treat this infection

›Take all prescribed medications as directed

›Activity restrictions

›Rest at home and avoid strenuous activity

›Do not return to areas with known rodent exposure until fully recovered

›Rodent exposure prevention

›Seal all entry points in your home to prevent rodent access

›Use wet cleaning methods (damp mop/wipe) in rodent-contaminated areas; do not sweep or vacuum dry droppings

›Wear an N95 respirator during any cleanup in rodent-contaminated spaces

›Ventilate enclosed spaces (cabins, sheds) for at least 30 minutes before entering

›Return to emergency department immediately for

›Any new cough or shortness of breath

›Worsening difficulty breathing

›Chest tightness or pressure

›Feeling faint, dizzy, or lightheaded

›High fever (>38.5 degrees C) that is not improving

›Inability to keep fluids down

›Decreased urine output

›Household contacts

›If you were potentially exposed to Andes virus, notify household contacts to monitor for symptoms for 40 days

›Contact your local health department for guidance on exposure management

›Follow-up

12References/r18

Guidelines and key sources

›Primary references

›Abdoler EA, Malani PN. What Is Hantavirus? JAMA. 2025. https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2025.5014

›Vial PA, Ferres M, Vial C, et al. Hantavirus in Humans: A Review of Clinical Aspects and Management. Lancet Infect Dis. 2023. https://pubmed.ncbi.nlm.nih.gov/37105214

›Riquelme R. Hantavirus. Semin Respir Crit Care Med. 2021. https://pubmed.ncbi.nlm.nih.gov/34918323

›Ulloa-Morrison R, Pavez N, Parra E, et al. Critical Care Management of Hantavirus Cardiopulmonary Syndrome. J Crit Care. 2024. https://pubmed.ncbi.nlm.nih.gov/39024823

›Epidemiology and natural history

›Duchin JS, Koster FT, Peters CJ, et al. Hantavirus Pulmonary Syndrome: A Clinical Description of 17 Patients. NEJM. 1994. https://www.nejm.org/doi/full/10.1056/NEJM199404073301401

›Watson DC, Sargianou M, Papa A, et al. Epidemiology of Hantavirus Infections in Humans. Crit Rev Microbiol. 2014. https://pubmed.ncbi.nlm.nih.gov/23607444

›Hartline J, Mierek C, Knutson T, Kang C. Hantavirus Infection in North America: A Clinical Review. Am J Emerg Med. 2013. https://pubmed.ncbi.nlm.nih.gov/23680331

›Graziano KL, Tempest B. Hantavirus Pulmonary Syndrome: A Zebra Worth Knowing. Am Fam Physician. 2002. https://pubmed.ncbi.nlm.nih.gov/12358213

›ECMO and advanced therapy

›Crowley MR, Katz RW, Kessler R, et al. Successful Treatment of Adults With Severe HPS With ECMO. Crit Care Med. 1998. https://pubmed.ncbi.nlm.nih.gov/9468181

›Lopez R, Perez-Araos R, Salazar A, et al. Targeted high volume hemofiltration in severe HCPS. J Med Virol. 2021. https://onlinelibrary.wiley.com/doi/10.1002/jmv.26930

›Special populations and prognostic factors

›Tortosa F, Ragusa MA, Neumann I, et al. Prognostic Factors for Mortality in New World Hantaviruses. BMJ Open. 2026. https://pubmed.ncbi.nlm.nih.gov/41592833

›Thorp L, Fullerton L, Whitesell A, Dehority W. Hantavirus Pulmonary Syndrome 1993-2018. Pediatrics. 2023. https://pubmed.ncbi.nlm.nih.gov/36855865

›Martinez VP, Di Paola N, Alonso DO, et al. Super-Spreaders and Person-to-Person Transmission of Andes Virus. NEJM. 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2009040

›Gorris ME, Whitesell A, Telford C, Shoemaker T, Bartlow AW. Hantavirus Associated With Open Developed Areas and Arid Climates. Transbound Emerg Dis. 2025. https://pubmed.ncbi.nlm.nih.gov/41141578

Evidence & Review

Evidence & Review