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

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

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

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

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

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

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

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

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

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%

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

H1N1 forum @ www.hksccm.org

The End Thank you