1. Critical Care Management of Human Swine Influenza Infection
Dr Grace SM LAM
Department of Intensive Care
PYNEH

2. Situation Report in Hong Kong
As of 14:30 30 July 2009
Confirmed cases: 3459
Serious cases: 11
Intensive care treatment : 6
H1N1 mortality : 2
As the number of cases increases, we will be seeing more serious H1N1 infection and mortality

3. Case illustration (1) 37/F Filipino Good past health
Given birth to a baby boy 6 months ago
Just arrived in HK to work as a domestic helper
Noticed to have fever on routine body check
CXR: normal
Given antibiotic by private clinic

4. Case illustration (2) 10 days later
Attended AED for persistent RN, sorethroat, diarrhoea
SaO2 78% on RA
Repeated CXR…

5. Case illustration (3) Direct admission to ICU Imipenem + Azithromycin
Failed non-invasive ventilation
Intubated on D2

6. Case illustration (4) Initial NPA influenza A & B rapid test –ve
D4: Tracheal aspirate x M protein +ve
Started on tamiflu and amantadine
D5: NPA x HSI +ve
Tamiflu dose doubled 150mg BD
Amantadine stopped
N-acetylcysteine & statin started
Nebulized zanamivir not tolerated

7. Case illustration (5) D7: ECMO
(Extra-Corporeal Membrane Oxygenation) started
Condition complicated by:
Acute renal failure
Tension pneumothorax
Hemolysis
Succumbed on D21

8. Increased risk of influenza-related complications
Pregnancy
Immunocompromised
Chronic illness
Adults ≥65
Children <6

9. In serious condition at initial presentation Rapid deterioration 37
Common features:
Young & fit adults
In serious condition at initial presentation
Rapid deterioration
Single organ failure 48 34 39
PWH 23

10. Case series of first 18 patients with severe HSI infection in Mexico
29 June 2009
Case series of first 18 patients with severe HSI infection in Mexico
Similar picture:
Previously healthy young to middle-age adults
Rapid progression: 5-7 days from ILI to pneumonia
Fulfilled criteria of ALI /ARDS on presentation
Mortality among those ventilated was 58%

11. Investigations
Initial NPA rapid influenza test & RT-PCR can be negative:
For intubated patients,
Send ETA or bronchial aspirate x RT-PCR
Repeat HSI investigation if
Clinically deteriorating CAP + a cause

12. Treatment of serious HSI infection
General supportive treatment
Anti-virals
Treatment of coexisting or secondary bacterial infection
Adjunctive treatment
Treatment of refractory hypoxemia

13. Anti-viral agents Current strain of HSI
Susceptible to neuraminidase inhibitors (oseltamivir & zanamivir)
Resistant to adamantanes (amantadine & rimantidine)
Beneficial effect of antivirals maximized if started <48hrs after onset of disease
∴Empirical anti-viral for severe pneumonia admitted to ICU

14. Oseltamivir (Tamiflu®)
75mg BD
Up to 150mg BD in obese patients?
Side effects
Rash, Nausea, Diarrhoea, Hallucination in children
Mutation at the neuraminidase gene can confer resistance to oseltamivir
Global monitoring of HSI mutations
WHO reference labs (UK, US, Australia, Japan) carry out sequencing on samples of viruses sent in on a regular basis

15. Zanamivir (Relenza®)
Mutation at the neuraminidase gene has no impact on zanamivir susceptibility
Oral inhalation ∵ poor systemic absorption
Dose: 2x5mg inhalations BD

16. Nebulized Zanamivir Premature study termination – Underpowered
2003
Premature study termination – Underpowered
More patients in Zanamivir group had no/mild cough on D3
Well tolerated

17. Nebulized Zanamivir Consider use in: Oseltamivir resistance
Clinical efficacy
Drug preparation
iv preparation supplied by drug company used by study
Homemade preparation 15mg in 3-5ml NS Q6h
Dosage
Loss of PEEP in intubated patients
Consider use in:
Oseltamivir resistance
Contraindications to oseltamivir or oral medications
Deterioration despite treatment with oseltamivir

18. Antibiotic Empirical antibiotic for community-acquired pneumonia
Mortality increases 10x in HSI infection + bacterial co-infection
30-80% co-infection ∵ Streptococcus pneumoniae & Haemophilus influenzae
Increased risk of secondary Staphylococcus aureus infection

19. Antibiotic Consider empirical coverage x CA-MRSA in:
Non-Chinese ethnicity (e.g. Filipinos, Caucasian)
Presented with hemoptysis
Concurrent skin infection (e.g. abscess)
Known exposure to CA-MRSA (self or contacts)
Positive rapid test for influenza
CXR suggestive of staphylococcal infection (e.g. cavitatory, pneumatoceles)
Pleural fluid or BAL show clusters of GPC

20. Acetylcysteine Synergism with oseltamivir High dose
Improved survival against lethal influenza infection in mice
High dose
Similar to dose used for treatment of paracetamol overdose

21. Extra-Corporeal Membrane Oxygenation (ECMO)体外膜肺氧合
Veno-venous ECMO
Blood passes through an oxygenator
Oxygenation & ventilation by diffusion
“Adding another lung”
Patient’s lungs can be rested
Protective lung ventilation strategy
又称体外维生系统
ECMO in pediatric patient

23. CESAR study
Conventional ventilation or ECMO for Severe Adult Respiratory failure
Survival without severe disability (confined to bed, or unable to dress/wash oneself) by 6 months
ECMO: 57 in 90 patients (63%)
Conventional ventilation: 41 in 87 patients (47%)
Relative risk reduction in favour of ECMO group
0.69 (95% confidence interval, 0.05–0.97; P = 0.03)

24. ECMO
Established treatment modality internationally for selected adult respiratory failure
As of January 2008, an international
registry recorded 1416 cases with
a survival of 51%
Used in selected H1N1 infected patients
“Guidelines for the provision of critical care in response to influenza pandemic”
Issued by Australian NSW Intensive care taskforce
Section on case selection and treatment protocol for ECMO

25. Indication & Contraindications of ECMO
Severe reversible respiratory failure despite maximum conventional therapies
Contraindications

26. Take home messages (1)
As the number of cases increases, we will be seeing more serious H1N1 infections & fatalities
Patients with serious H1N1 infection are often young and previously fit, with rapid clinical deterioration
NPA x RT-PCR does not have 100% sensitivity
Tracheal aspirate & BAL might have a higher sensitivity in those with lower respiratory tract infection
Repeat RT-PCR if in doubt

27. Take home messages (2)
There is no randomized controlled trials on treatment of H1N1
Treatment modalities in addition to general supportive treatment include:
Oseltamivir, zanamivir (?nebulized)
Antibiotic
Adjunctive treatment
ECMO as a last resort in selected cases

28. H1N1 forum @ www.hksccm.org

29. The End
Thank you