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MEDICAL GRANDROUNDS. October 22, 2009 Ledesma Hall Leonid Zamora MD. OBJECTIVES. To present a case of a young female who developed complicated pneumonia secondary to Influenza A(H1N1) Virus Infection To discuss the latest updates on the Virus. General Data. AMG 23 years old Female

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medical grandrounds

October 22, 2009

Ledesma Hall

Leonid Zamora MD

  • To present a case of a young female who developed complicated pneumonia secondary to Influenza A(H1N1) Virus Infection
  • To discuss the latest updates on the Virus.
general data
General Data
  • AMG
  • 23 years old
  • Female
  • Single
  • Filipino
  • a student from DLSU
  • Lives in Paranaque
  • Known Diabetic
history of present illness
  • 5 DAYS PTA
  • non-productive cough
  • body malaise
  • high grade fever (Tmax 40.5C)
  • Consult at RITM
    • throat swab done
    • voluntary isolation at home
history of present illness1
  • 2 DAYS PTA
  • persistence of the above symptoms
  • self-medicated with Cefuroxime 500mg 2x a day
  • No consult
history of present illness2
  • Few hours PTA
  • increasing frequency and severity of cough
  • Dyspnea
  • No chest pains, orthopnea, paroxysmal nocturnal dyspnea
  • Throat swab done in RITM  POSITIVE
  • ER consult


review of systems
Review of Systems
  • No headache
  • No loss of consciousness
  • No blurring of vision
  • No nausea, vomiting
  • No dysuria, hematuria
  • No diarrhea/constipation
  • No bleeding
  • No polyuria, polydipsia, polyphagia
past medical history
Past Medical History
  • Diabetes since 2007 – on Metformin 500mg TID and Rosiglitazone 4mg OD
  • Hypertensive since 2008 - no maintenance medications (HBP 150/90 – UBP 130/80)
  • (+) PCOS x 5 months on Norethisterone (Primolut) and Medroxyprogesterone acetate (Provera)
  • No previous hospitalizations or surgeries
  • No known allergies.
family history
Family History
  • Diabetes and Hypertension  both parents
  • (+) Asthma  maternal side (cousins)
  • No Asthma
  • No Cancer
personal and social history
Personal and Social History
  • Non smoker
  • Occasional alcoholic beverage drinker
  • No recent Travel outside Metro Manila
  • Student of DLSU – was recently closed due to reported cases of positive Inluenza A(H1N1)
physical examination
Physical Examination
  • Conscious, coherent, in respiratory distress
  • BP 110/70 HR 115 reg RR 30 Temp 39 C Ht 162.5cm Wt 109kg BMI 41.3
  • Warm moist skin. No active dermatosis.
  • Pink palpebral conjunctivae, anicteric sclerae, moist buccal mucosa, nonhyperemic posterior pharyngeal wall, tonsils not enlarged, (+) alar flaring.
  • Supple neck, no cervical lymphadenopathies, (+) neck vein distention, no carotid bruit.
physical examination1
Physical Examination
  • Symmetrical chest expansion, no lagging, (+) tight air entry, (+) wheezes, bilateral.
  • Adynamic precordium, AB at 5th Left intercostal space, Mid clavicular line, tachycardic, regular rhythm, no murmurs, no gallop rhythm.
  • Flabby abdomen, normoactive bowel sounds, non-tender, no masses, no organomegaly. No abdominal bruit.
  • Full and equal pulses. No cyanosis. No edema.
salient features
Salient Features
  • 23 years old, Female
  • a student from DLSU
  • Diabetic
  • Obese
  • Dyspnea
  • Increasing severity of cough
  • Fever
  • POSITIVE for A(H1N1)
  • in respiratory distress.
  • BP 110/70 HR 115 reg RR 30 Temp 39C
  • (+) alar flaring
  • (+) neck vein distention
  • (+) tight air entry
  • (+) wheezes, bilateral.
admitting impression


Severe Sepsis secondary to

Community Acquired Pneumonia

secondary to Influenza A(H1N1)

Diabetes Mellitus, Type 2, Non-insulin requiring

Obese Class III

Hypertension Stage 1

Polycystic Ovarian Syndrome

course in the ward
  • At the ER
    • In respiratory distress
    • VS
      • BP 110/70
      • HR 115 reg
      • RR 30
      • Temp 39 C
      • O2 sat 82% at room air
  • NPO
  • Hooked to Pulse Oximeter
  • MVM 0.5
  • PNSS 1L x 100ml/hr
  • Rx:
      • Fenoterol + Ipratropium (Berodual) nebulization q4h,
      • Oseltamivir 75mg tab q12h,
      • Budesonide 500mcg BID nebulization,
      • Hydrocortisone 100mg q8h
      • Paracetamol 300mg q4h
CXR (July 6, 2009)

hazy infiltrates in the upper lobe likely due to pneumonia, infiltrates in the right paracardiac and left lower lobe

course in the ward1
  • At the ER
    • In respiratory distress
    • VS
      • BP 110/70
      • HR 115 reg
      • RR 30
      • Temp 39 C
      • O2 sat 82%
  • Imp: Acute Respiratory Distress Syndrome
  • Infectious Disease Referral
    • Sputum GS/CS
    • Spec 16
    • Started with
      • Piperacillin-Tazobactam 4.5g IV q8h
      • Levofloxacin 500mg IV q24h
  • Pulmonology and Endocrinology Referral
acute respiratory distress syndrome
  • Acute onset of Respiratory Failure
  • Diffuse Bilateral infiltrates on Chest radiograph
  • Absence of left atrial hypertension (PCWP < 18 mmHg or no clinical evidence of increased left atrial pressure)
  • Hypoxemia, PaO2/FiO2 < 200
course in the ward2
  • At the ER
    • In respiratory distress
    • VS
      • BP 110/70
      • HR 115 reg
      • RR 30
      • Temp 39 C
      • O2 sat 84% at MVM 0.5
      • BIPAP not available
  • Pulmonology
    • DDIMER
    • Start
      • Enoxaparin 60mg SQ BID
    • Do ABGs q1h
    • Standby intubation
course in the ward3
  • At the ER
    • In respiratory distress
    • VS
      • BP 110/70
      • HR 115 reg
      • RR 32-34
      • O2 sats 83-84% on MVM
  • Shift MVM to inline neb at 0.6 FiO2
course in the ward4
  • 1st Hospital Day
  • At the ER
    • In respiratory distress
      • O2 sat 75% on in line neb at 0.6 FiO2
  • Intubate
    • MV settings
      • AC
      • FiO2 100
      • Vt 330
      • RR 20
      • PEEP 10
    • CXR post intubation
    • ABGs 30 min post
  • Transfer to MICU
    • Reintubated

Increase infiltrates in the right lung. ET tube in place

course in the ward5
  • 1st Hospital Day
  • MICU
    • Fever Tmax 39C
    • O2 sat 83% at FiO2 1.0
  • Infectious Disease
    • Discontinue Levofloxacin
    • Start
      • Moxifloxacin 400mg IV q24h
    • Blood CS x 2 sites
    • SPEC M
    • Refer to Nephrology for co management
    • Increase Vt to 500
course in the ward6
  • 1st Hospital Day
  • MICU
    • Fever Tmax 39.8C
    • BP 95/47
    • HR 114
  • Nephrology
    • Start IV Ig 50g + 500 ml sterile H2O
      • 1st Hour – 63.5 ml/hr
      • 2nd Hour – 127 ml/hr
      • 3rd Hour – 190 ml/hr
      • 4th Hour – 254 ml/hr until consumed
    • Pentoxifylline drip 300mg x 8h x 6 doses
pentoxifylline in severe sepsis a double blind randomized placebo controlled study

Pentoxifylline in severe sepsis: a double-blind, randomized placebo-controlled study

KH Staubach, J Schröder, P Zabel and F StüberDept. of Surgery, Medical University of Lübeck and Kiel, ForschungszentrumBorstel

Critical Care 1998, 2(Suppl 1):P017doi:10.1186/cc147


51 patients

  • MOF-score  lower in POF treated patients
  • PaO2/FioO2-ratio was significantly improved in POF treated patients
  • Pressure-adjusted heart rate (HR×CVP/MAP) was significantly improved from day 6 to day 10 (P < 0.05)

Polyclonal Intravenous Immunoglobulin for the Treatment of Severe Sepsis and Septic Shock in Critically Ill Adults: A Systematic Review and Meta-analysis

Conclusion: Demonstrates an overall reduction in mortality with the use of IVIg for the adjunctive treatment of severe sepsis and septic shock in adults

Critical Care Medicine: Kevin B. Laupland, MD, MSc; Andrew W. Kirkpatrick, MD; Anthony Delaney, MBBS, MSc. Published: 01/14/2008

course in the ward7
  • 1st Hospital Day
  • MICU
    • Fever Tmax 39.8C
    • BP 95/47
    • HR 114
    • CVP 20
  • Nephrology
    • Start
      • Dopamine 400mg/100ml PNSS at 3mcg/kg/min
      • Dobutamine 500mg/1ooml PNSS at 10mcg/kg/min
      • Voluven 6% 500ml x 25oml/hr
      • Hydrocortisone 50mg IV q8h
      • Furosemide 120mg IV now
course in the ward8
  • 1st Hospital Day
  • MICU
    • Albumin 3
  • Nephrology
    • Plasma Cortisol
    • CBC, CXR portable , DDIMER, CRP, Spec 16, Urinalysis, ABGs, Urine CS
    • Foley Catheter inserted
    • Start
      • Esomeprazole 40mg IVOD
      • Human Albumin 25% 100ml x 1 hr
course in the ward9
  • 1st Hospital Day
  • MICU
    • VS
      • O2 sats 83%
      • BP 123/64
    • Mech Vent Settings
      • AC
      • FiO2 1.0
      • Vt 400
      • RR 34
      • PEEP 20
  • Pulmonology
    • Shift Berodual to Terbutaline nebulization q8h
    • Acetylcysteine neb 600mg
course in the ward10
  • 2nd Hospital Day
    • Febrile Tmax 38.2
    • BP 114/60
      • Dobu 5mcg, Dopa 3mcg
    • HR 139
    • O2 sats 92%
    • Impression:
      • r/o Pneumocystis Carinii Pneumonia
    • CVP 22.5
  • Infectious Disease
    • Start
      • Cotrimoxazole 400/80mg IV q8h
    • Sputum for PCP – IF
  • Nephrology
      • Furosemide 20mg IV q6h
      • Mannitol 50mg IV drip 30min after furosemide dose
course in the ward11
  • 2ND Hospital Day
      • As treatment for fibroproliferative phase of ARDS
  • Pulmonology
    • Start
      • Methylprednisolone 4mg/kg q8h
      • Decrease FiO2 to 0.85  0.75
methylprednisolone infusion in early severe ards results of a randomized controlled trial

Methylprednisolone Infusion in Early Severe ARDS*Results of a Randomized Controlled Trial

CONCLUSIONS: Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay

AU Meduri GU; Golden E; Freire AX; Taylor E; Zaman M; Carson SJ; Gibson M; Umberger R SO Chest. 2007 Apr;131(4):954-63

course in the ward12
  • 3RD Hospital Day
    • HR 120s, RR 30s, dyspnea
    • O2sats 95% at FiO2 0.75
      • Na 151
  • ECG  sinus tachycardia
  • Hold Terbutaline
  • Increase FiO2 to 1.0
  • Nephrology
      • Shift IVF to 1/2NSS x 40ml/hr
      • Dec Furosemide 20mg q8h
      • Dec Mannitol 50mg to q8h
      • Give 2nd dose of IV Ig
course in the ward13
  • 4th Hospital Day
  • 7th Hospital Day
  • 8th Hospital day
    • VS
      • BP 120/70
      • Afebrile
      • O2sats 96%
  • Keep decreasing FiO2 below 1.0 to keep O2 sats above 90%
    • Weaning from Mech vent started
  • Patient was transferred out of MICU
    • Pip-Tazo Discontinued
    • Methylprednisolone tapering started
course in the ward14
  • 14TH Hospital Day
    • VS
      • BP 120/70
      • O2 sats 92%
      • On T-piece FiO2 0.35
      • RSB 18.87
  • 15th Hospital Day
      • ABGs pO2 – 75.7 (115)
      • At MVM 0.5
  • Patient was extubated
  • Shifted to MVM 0.5
  • Hooked to BIPAP
      • IPAP 15
      • EPAP 5
      • SIDEFLOW 70
course in the ward15
  • 17TH Hospital Day
      • ABGs pO2 – 85.6 on BIPAP
  • 21st Hospital Day
    • CBC (07/27/09)
      • WBC – 23.65 (14.4)
    • Urine CS E.Coli
      • Sensitive to Cefuroxime
    • Imp: Hospital Acquired UTI
  • BIPAP shifted to O2 at 3LPM
  • Start Cefuroxime 500mg BID
  • Foley cath removed
course in the ward16
  • 28TH Hospital Day
  • 31st Hospital Day
  • HRCT done
  • MGH
clinical course of ards
Clinical Course of ARDS
  • Exudative Phase (Day 1-7)
  • Proliferative Phase (Day 7-21)
  • Fibrotic Phase
final diagnosis
  • Severe Complicated Pneumonia H1N1 infection with Acute Respiratory Distress Syndrome
  • Diabetes Mellitus, Type 2, Non insulin Requiring
  • Obese Class III
  • Hypertension Stage I
  • Polycystic Ovarian Syndrome
Influenza is usually a respiratory infection


Regular person-to-person transmission

Primarily throughcontact with respiratory droplets

Transmission from objects (fomites) possible

National Center for Disease Prevention and Control, DOH

key characteristics
Key Characteristics


Viral shedding can begin 1 day before symptom onset

Peak shedding first 3 days of illness

Correlates with temperature

Subsides usually by 5-7th day in adults

Infants, children and the immuno-compromised may shed the virus longer

National Center for Disease Prevention and Control, DOH

Incubation period

Time from exposure to onset of symptoms

1 to 4 days (average = 2 days)


In temperate zones, sharp peaks in winter months

In tropical zones, circulates year-round with seasonal increases.

National Center for Disease Prevention and Control, DOH

individuals at increased risk for hospitalizations and death
Individuals at Increased Risk for Hospitalizations and Death

Elderly >65 years

Children less than two years

Certain chronic diseases

Heart or lung disease, including asthma

Metabolic disease, including diabetes

HIV/AIDs, other immuno-suppression

Conditions that can compromise respiratory function or the handling of respiratory secretions

Pregnant women

National Center for Disease Prevention and Control, DOH

intensive care patients with severe novel influenza a h1n1 virus infection michigan june 2009
Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

10 patients wiith Influenza A(H1N1) and ARDS admitted at ICU. Of the 10 patients 9 were obese (BMI>30) including 7 who are extremely obese (BMI>40). Five had pulmonary emboli; Nine had MODS. 3 patients died. Clinicians should be aware of the potential for severe complications of H1N1 virus infection in extremely obese patients.

  • Predominance of males
  • High prevalence of obesity
  • Frequency of clinically significant pulmonary emboli and MODS
influenza a viruses
Influenza A Viruses

Influenza A viruses categorized by subtype

Classified according to two surface proteins

Hemagglutinin (H) – 16 known

Neuraminidase (N) – 9 known



National Center for Disease Prevention and Control, DOH

A / Sydney / 05 / 97 (H3N2)


Strain number

Virus subtype

Virus type

Place virus


Year isolated

National Center for Disease Prevention and Control, DOH

influenza a h1n1 is a novel virus
Influenza A (H1N1) is a novel virus
  • Unusual combination of genetic material from pigs, birds & humans which have re-assorted
  • Affects all age groups
  • Vaccines for human seasonal flu can not protect humans against the novel virus

National Center for Disease Prevention and Control, DOH

swine influenza viruses
Swine Influenza Viruses
  • RNA viruses
  • Pigs can be infected by avian influenza and human influenza viruses as well as swine influenza viruses.
  • Re-assort and new viruses that are a mix of swine, human and avian influenza viruses can EMERGE

National Center for Disease Prevention and Control, DOH


Genetic Re-assortment


National Center for Disease Prevention and Control, DOH

signs symptoms of influenza a h1n1
Signs & Symptoms of Influenza A (H1N1)
  • Fever
  • Lethargy
  • Lack of appetite
  • Coughing
  • Runny Nose
  • Sore throat
  • Nausea / Vomiting
  • Diarrhea

National Center for Disease Prevention and Control, DOH

swine h1n1 vs human h1n1
Swine H1N1 vs. Human H1N1
  • swine H1N1 flu virus NOT the same as human H1N1 virus
  • antigenically very different from human H1N1 viruses
  • vaccines for human seasonal flu can not protect humans from swine H1N1

National Center for Disease Prevention and Control, DOH

transmission food borne
Transmission: Food-Borne?
  • NO
  • Influenza A (H1N1) viruses are not transmitted through food
  • Safe to eat properly handled and cooked pork and pork products
  • Cook pork at an internal temperature of 70°C (160°F)

National Center for Disease Prevention and Control, DOH

diagnosis and laboratory confirmation
Diagnosis and Laboratory Confirmation
  • Clinically diagnosed
  • Respiratory Specimen
    • first 4 to 5 days of illness
    • can shed for 10 days or longer
  • Specimens sent to US CDC
    • ONLY laboratory that can isolate and identify swine influenza type A virus

National Center for Disease Prevention and Control, DOH

  • Upper respiratory tract specimens as recommended are the most appropriate.
  • taken from the deep nostrils (nasal swab), nasopharynx (nasopharyngeal swab), Nasopharyngeal aspirate, throat or bronchial aspirate.
laboratory diagnosis
Laboratory Diagnosis

Rapid Influenza Diagnostic Test

  • Antigen detection test that detect influenza viral nucleoprotein antigen
  • Can provide results within

30 minutes

  • Sensitivity 40-69%
CDC rRT-PCR Swine Flu Assay
  • Sensitivity : 99.8%
  • Specificity: 92%
  • Influenza A (H1N1) is sensitive to:
    • Oseltamivir (tamiflu)
    • Zanamivir
  • Self medication is discouraged, may induce drug resistance
  • Chemoprophylaxis
    • Oseltamivir

National Center for Disease Prevention and Control, DOH

CDC Health Advisory
  • Distributed via Health Alert Network

July 09, 2009

Three Reports of Oseltamivir Resistant Novel Influenza A (H1N1) Viruses

  • Post-exposure prophylaxis for health care workers, first responders and workers who did not have adequate PPE when in contact.
  • Anti-viral prophylaxis is not recommended

to close contacts except when they belong

to high risk group.

  • Process of production is underway, but may take 5 – 6 months
  • Seasonal influenza vaccine provides protection against the seasonal human influenza strains only

National Center for Disease Prevention and Control, DOH


0.5 mL doses contain 15 µg hemagglutinin of the vaccine strain A/California/7/2009 (H1N1)Two doses separated by 4 weeks for children 2-9 years(CDC. Update on influenza A (H1N1) monovalent vaccines. MMWR Morb Mortal Wkly Rep. 2009;58:1100-1101.)

interim guidelines no 2 infection control and use of personal protective equipment in influenza a


  • Standard and droplet precautions when working in direct contact
  • If there is risk of splashes: particulate respirator; eye protection;clean, non-sterile, long sleeved gown; sterile gloves
  • Frequent and proper handwashing
Isolate patient in a single room.

Reinforce standard precautions with droplet and contact precaution

Use appropriate Personal Protective Equipment for all those entering patients rooms.

Restrict number of visitors.

Healthcare workers on direct contact should monitor their own temperature 2X a day and report any febrile event.


Influenza vaccine is the best prevention for seasonal influenza.

Inactivated viruses in the vaccine developed from three circulating strains (generally 2 Type A and 1 Type B strain)

Therefore, seasonal “flu shot” only works for 3 influenza subtypes and will not work on pandemic strains.

Live, intranasal spray vaccine for healthy non-pregnant persons 5-49 years

Inactivated, injectable vaccine for persons 6 months and older

National Center for Disease Prevention and Control, DOH

influenza viruses
Influenza Viruses

Classified into types A, B, and C

Only Types A and B cause significant disease

Types B and C limited to humans

Type A viruses

More virulent

Affect many species

C Goldsmith, CDC

National Center for Disease Prevention and Control, DOH

american journal of kidney diseases

American Journal of Kidney Diseases

Prehypertension, Obesity, and Risk of Kidney Disease: 20 year follow up The HUNT 1 Study in Norway (June 11, 2009)

Participants with prehypertension are not at increased risk of serious kidney outcomes if BMI is less than 30kg/m2. However, the risk of Kidney disease increases substantially if prehypertension is present in obese participants.


CORTISOL 1659.731 nmol/L 7/13/09

ESR 70 mm/hr

HbA1c – 8.1%


HRCT: Predominantly interstitial infiltrates in both lungs with associated ground glass opacities in both upper lobes. The interstitial infiltrates may represent interstitial fibrosis with superimposed acute alveolar inflammatory or infectious process.

Minimal pneumomediastinum and subcutaneous emphysema.


CXR: Jul 6 – Hazy infiltrates in the right upper lobe likely due to pneumonia. There are also infiltrates in the right paracardiac and left lower lobe. Heart is magnified. Bones and soft tissues are normal.

Jul 7 – Increase infiltrates in the right lung. ET tube in place.

Jul 8 – right suprahilar and paracardiac infiltrates appear confluent, however there is partial clearing of the infiltrates seen in the peripheral chest. Infiltrates in the left are unchanged.

Jul 13 – Complete resorption of the right side pneumothorax. Slight clearing of Pulmonary congestion. ET tube in place.

Jul 17 – No significant change in the opacities in both lungs. Minimal subcutaneous emphysema.

Jul 19 – Moderate resorption of subcutaneous emphysema. No significant change in infiltrates.


The FDA has approved 4 vaccine preparations. The following data highlight relevant issues:

All influenza vaccine preparations in the United States for the 2009-2010 season contain residual egg protein and none contain adjuvant;

Children 6 months to 9 years of age who are given influenza A (H1N1) monovalent vaccine should receive 2 doses separated by about 4 weeks; persons ≥ 10 years of age should receive 1 dose;

The influenza A (H1N1) monovalent vaccines were made according to standards used for seasonal and influenza vaccines and have the same age group indications, precautions, and contraindications as vaccines that are FDA-approved for seasonal flu; preliminary data indicate that the safety and efficacy of the 2009 Influenza A (H1N1) monoclonal vaccine is the same as winter;

There is minimal evidence of significant antigenic change since the first characterization of the virus in April 2009, indicating that the virus continues to be well matched with the vaccine strain; and

The vaccines of the 4 suppliers have some differences that are important to recognize:for seasonal flu vaccines;

Side effects, including local pain at the injection site, were reported in 46% of recipients, and systemic reactions (headache, malaise or myalgias) were reported in 45%; the safety profile is consistent with the experience with seasonal flu vaccine;

Influenza activity due to influenza A (H1N1) increased in September 2009 and is expected to continue through fall and


Children 6 months to 9 years of age should receive 2 doses separated by 3 weeks. Children 10 years and older and adults should receive 1 dose.

  • The following groups should receive the vaccine as soon as it becomes available:
  • Pregnant women;
  • People who live with or care for infants younger than 6 months of age;
  • Healthcare workers (HCWs) and emergency medical personnel;
  • Persons 6 months to 24 years of age;
  • Persons 25-64 years of age who have chronic diseases (including immunodeficiency states) that pose risk for influenza.
  • When more vaccine becomes available, the following persons should be vaccinated:
  • Healthy persons ages 25-64 years; and
  • Adults 65 years of age and older.