The Hospitalised Care of Swine Influenza the HPA H1N1 ICU Network

1. 04 February 2012 The Hospitalised Care of Swine Influenza  & the HPA H1N1 ICU Network Dr Gail Thomson, Consultant Infectious Diseases, Medical Affairs, CEPR Photograph courtesy of CDC, USA Will mention the HPA H1N1 ICU Network Not going to be discussing high risk groups or vaccination. Focussing in on the treatment of ADULT, severe cases of pandemic (H1N1) 2009 in ICU setting. Will mention the HPA H1N1 ICU Network Not going to be discussing high risk groups or vaccination. Focussing in on the treatment of ADULT, severe cases of pandemic (H1N1) 2009 in ICU setting.

2. 04 February 2012 Spend more time on some issues than others.Spend more time on some issues than others.

3. 3 HPA H1N1 ICU network.Why and how was it set up? HPA NECC: June 4th 2009 � meeting with Fred Hayden � influenza guru At this time: three H1N1 cases in Intensive Care in Royal Alexandra, Paisley, Scotland Health Protection Scotland (HPS) � go ahead to HPA to set up a teleconference call with disease experts to help the Scots That evening � GT called members of the WHO clinical network and others to take part in call June 5th Mirrored what I had done for WHO during SARS and H5 Turkey event. Never thought I would have to do this to support my own country. Mirrored what I had done for WHO during SARS and H5 Turkey event. Never thought I would have to do this to support my own country.

4. 4 June 5th 2009The first teleconference call: WHO Geneva WHO Euro Fred Hayden Tim Uyeki & Scott Harper, CDC Edgar Bautista, Mexico City Karl Nicholson Jonathan Van Tam Barbara Bannister, DH Kevin Rooney, Intensivist, Paisley Alistair MacConnachie, Gartnavel Nick Sherwood, Birmingham City Bruce Taylor, Intensive Care Society Nick Phin Nick Gent Rachel Kandt Discussed the clinical management of the three cases Agreed to organise another call as the clinicians found it useful Particular lessons learned from Mexico: -Sudden deterioration -Run dry -Role of NIV -Concern over steroids.

5. 5 Weekly calls begunGradually added more and more people: CLINICAL, LAB & EPI all on the same call� Intensivists Virologists RMN Microbiologists Infection Control Nurses Pharmacists Infectious diseases Accident & Emergency NHS support: 2 senior registrars LaRS, CEPR, CFI, Chiltern, Holborn DH Royal Colleges Relevant professional bodies: PICS, ICS, BPAIIG, APAGBI International experts Clinicians from outside the U K World Health Organization

6. 04 February 2012

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8. 8 Epidemiology Update Influenza indicators show limited influenza activity across the UK. Rates of influenza-like illness (ILI) remain low and well within baseline levels across the UK. ILI rates have remained stable in England (12.8/100,000 in week 03 and 12.5/100,000 in Week 04). ILI rates have decreased in Wales and Northern Ireland and slightly increased in Scotland. NPFS assessments, authorisations and collections continue to decrease. Very few seasonal influenza viruses have been detected in recent weeks. Most other respiratory viruses have decreased with the exception of parainfluenza virus which has slightly increased. The weekly consultation rates for bronchitis have almost doubled in children aged less than 5 years. Up to week 03, there is an observed excess in the number of death registrations expected for this time of year for the third week in a row. Pandemic influenza infections are unlikely to have played any role in this excess. During the winter RSV, h metapneumovirus & adenovirus were picked up. Source HPA sitrep one week ago Very few regions globally are reporting increasing influenza activity, although influenza remains active in parts of North Africa, limited areas of eastern and south eastern Europe, and in parts of South and East Asia. Influenza B viruses accounted for 35.6% (1,083/3,044) of all influenza detections worldwide, an increase from 18.2% (505/2,771) last week. Almost half of all positive influenza specimens in China are Influenza B. During the winter RSV, h metapneumovirus & adenovirus were picked up. Source HPA sitrep one week ago Very few regions globally are reporting increasing influenza activity, although influenza remains active in parts of North Africa, limited areas of eastern and south eastern Europe, and in parts of South and East Asia. Influenza B viruses accounted for 35.6% (1,083/3,044) of all influenza detections worldwide, an increase from 18.2% (505/2,771) last week. Almost half of all positive influenza specimens in China are Influenza B.

9. 9 Weekly number of hospitalised cases of confirmed pandemic (H1N1) 2009 influenza and RCGP ILI consultation rates to 17 January 2010, England In England, a total of 2,643 laboratory confirmed cases have been reported as hospitalised to 03 February 2010. The true number of hospitalised cases may be higher due to under-ascertainment of confirmed cases. The majority (60%) of cases were aged 5 to 44 years and 52% of cases were female. In Scotland there have been 1,534 cumulative hospitalisations (to 01/02/10), 446 in Wales (to 04/02/10), and 574 in Northern Ireland (to 03/02/10).

10. 10 Cumulative number of deaths in the United Kingdom up to 3rd February 2010 (source: DH and Devolved Administrations). Patients continue to be hospitalised and admitted to critical care facilities, although these numbers are falling off. Deaths attributable to pandemic H1N1 (2009) are also still occurring. Falls in serious illness and death figures tend to lag behind overall incidence of flu. (CMO update). The worst recent daily estimate was at the height of the second wave (4 November 2009) with 172 patients hospitalised in critical care and 848 patients hospitalised overall. This week has seen a further decline from last week (13 January 2010) when there were 268 patients in hospital and 79 patients in critical care. CMO update, DH web. Over 70 per cent of people in England who died from pandemic H1N1 (2009) influenza had a moderate or severe underlying health condition, but almost 30 per cent had no (or only mild) prior illness. The pattern of attack of the pandemic H1N1(2009) influenza virus is now clear from studies of its transmission in different countries during the second half of 2009. For most people infected, their illness is less severe than in previous influenza pandemics of the 20th century. It predominantly attacks children and younger adults. The majority of serious complications are amongst people with underlying health problems, though about a fifth have been previously healthy. Many of the deaths are due to viral pneumonia. This profile is completely different to seasonal influenza. WHO continues to assess the impact of the influenza pandemic as moderate. Accurate assessments of mortality and mortality rates will likely be possible only one to two years after the pandemic has peaked, and will rely on methods similar to those used to calculate excess mortality during seasonal influenza epidemics. Source WHO assessment of severity. Paediatric papers: Lister et al, Lancet 2009 & MMWR in September. Patients continue to be hospitalised and admitted to critical care facilities, although these numbers are falling off. Deaths attributable to pandemic H1N1 (2009) are also still occurring. Falls in serious illness and death figures tend to lag behind overall incidence of flu. (CMO update). The worst recent daily estimate was at the height of the second wave (4 November 2009) with 172 patients hospitalised in critical care and 848 patients hospitalised overall. This week has seen a further decline from last week (13 January 2010) when there were 268 patients in hospital and 79 patients in critical care. CMO update, DH web. Over 70 per cent of people in England who died from pandemic H1N1 (2009) influenza had a moderate or severe underlying health condition, but almost 30 per cent had no (or only mild) prior illness. The pattern of attack of the pandemic H1N1(2009) influenza virus is now clear from studies of its transmission in different countries during the second half of 2009. For most people infected, their illness is less severe than in previous influenza pandemics of the 20th century. It predominantly attacks children and younger adults. The majority of serious complications are amongst people with underlying health problems, though about a fifth have been previously healthy. Many of the deaths are due to viral pneumonia. This profile is completely different to seasonal influenza. WHO continues to assess the impact of the influenza pandemic as moderate. Accurate assessments of mortality and mortality rates will likely be possible only one to two years after the pandemic has peaked, and will rely on methods similar to those used to calculate excess mortality during seasonal influenza epidemics. Source WHO assessment of severity. Paediatric papers: Lister et al, Lancet 2009 & MMWR in September.

11. 11 Patient Presentation - adult A wide range of flu-like symptoms may be experienced (pyrexia, sore throat, coughing, dyspnoea, myalgia, nausea and vomiting) but these may be mild. Some may deteriorate rapidly or present in extremis. The speed of onset of symptoms can be rapid. Although the majority of hospitalised patients have respiratory symptoms (productive cough, dyspnoea,hypoxaemia) some have signs of dysfunction in other systems (e.g. nausea & vomiting, diarrhoea, abdominal pain, encephalopathy). Pregnancy notes, source HPA FAQs: Evidence from N America, Australia and Europe shows that pregnant women are at an increased risk of severe disease and admission to hospital with swf. Studies from the US have shown that pregnant women are four times as likely to develop serious illness and they are four to five times more likely to be admitted to hospital with swf than the general population. The WHO has reported that 7-10% of all hosp patients with swf are pregnant women and they are more likely to need ICU when compared with the general population. The risk incr in the third trimester of pregnancy. Pregnancy notes, source HPA FAQs: Evidence from N America, Australia and Europe shows that pregnant women are at an increased risk of severe disease and admission to hospital with swf. Studies from the US have shown that pregnant women are four times as likely to develop serious illness and they are four to five times more likely to be admitted to hospital with swf than the general population. The WHO has reported that 7-10% of all hosp patients with swf are pregnant women and they are more likely to need ICU when compared with the general population. The risk incr in the third trimester of pregnancy.

12. 12 AssessmentDH Guidance for clinical management of adults & children

13. 13 Diagnosis - Laboratory The results of testing are dependent on the quality of the sample: site, skill, storage and time to testing. In those with an illness consistent with pandemic flu but where there is a negative nose or throat swab, then a sample from the lower airways should be sent for testing. Treatment should continue until the result of this sample is known. A negative result may also indicate the absence of infection and multiplex PCRs for respiratory viruses should be considered in all cases. Serial testing should only be undertaken with the agreement of the local virologist/microbiologist and against agreed treatment/management objectives. Oseltamvir resistance testing should be considered in patients with confirmed H1N1 who deteriorate or fail to respond clinically to treatment with oseltamivir. HPA web PCR testing is currently regarded as the �gold standard� for the laboratory detection of pandemic H1N1 (2009) influenza virusHPA web PCR testing is currently regarded as the �gold standard� for the laboratory detection of pandemic H1N1 (2009) influenza virus

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15. 15 Antivirals � first line First line therapy for suspected or confirmed pandemic influenza is oseltamivir, unless there is a strong suspicion of infection with an oseltamivir resistant strain. For treatment of pregnant women see RCOG & DH guidance. The conventional oseltamivir dose for treatment of pandemic influenza in ADULTS is 75mg bd. Although absorption may be effective in critically ill patients, clinicians may wish to ensure adequate plasma levels by increasing the dose to 150mg bd. [d/w pharmacist if renal impairment]. Paediatric guidance on RCPCH website and HPA There is evidence that viral shedding may be prolonged in critically ill patients, and in critical care settings treatment with oseltamivir may be increased to a minimum of 10 days. This is an unlicensed use but there are no currently reported safety concerns. Where there is evidence that this route of treatment is not effective then the use of parenteral zanamivir should be considered. In the severe cases intensivists using oseltamivir via NG tube for obvious reasons. Remembering also that zanamivir or Relenza blisters should not be used in a ventilated patient via a nebuliser due to the risk of the components blocking the ventilator tubing. MHRA. Canadians about to publish on dosage in critical care patients � 75mg adequate blood levels. Alternatives for ventilated cases � iv zanamivir, GSK, named patient basis. Can be available to units within 24 hours. First line therapy for suspected or confirmed pandemic influenza is oseltamivir, unless there is a strong suspicion of infection with an oseltamivir resistant strain, even if the patient is pregnant. The conventional oseltamivir dose for treatment of pandemic influenza is 75mg bd. Although absorption may be effective in critically ill patients, clinicians may wish to ensure adequate plasma levels by increasing the dose to 150mg bd. There is evidence that viral shedding may be prolonged in critically ill patients, and in critical care settings treatment with oseltamivir should be increased to a minimum of 10 days. This is an unlicensed use but there are no currently reported safety concerns. Where there is evidence that this route of treatment is not effective then the use of parenteral zanamivir should be considered. Oseltamivir schedules exist for those with stable impaired renal function. If a second line drug is required IV zanamivir should be used, which is available on a compassionate-use basis from the manufacturers. Zanamivir powder for inhalation should not be used as a nebuliser solution for patients receiving mechanical ventilation. Dual therapy with naso-gastric oseltamivir and iv zanamivir should normally only be considered for the treatment of patients with known severe immunocompromise. Refer to HPA web http://www.hpa.org.uk/HPA/Topics/InfectiousDiseases/InfectionsAZ/1240812234677 Very good editorial from Tim Uyeki of the CDC summarising some of the published evidence supporting the early use of antivirals in pandemic influenza (H1N1) 2009. Ref in particular: Jain, Over 200 US patients � data suggests that the use of AV is beneficial, esp when initiated early, since patients who were admitted to an ICU or died were less likely to have received such therapy within 48 hrs after the onset of symptoms; Dominguez Mexico 58 ICU patients � surviviors were more likely to havce received treatment with NAIs. P=0.006, CMO�s BMJ article deaths in England � observed delayed AV use in most fatal cases. Value of the observation is ltd by the absence of a control group. Canadians � CMAJ just published � Zarychanski et al � severe H1N1 necess ICU was associated with a longer interval from onset of symptoms to treatment with AN and the presence of underlying comorbidity. Regarding pregnancy � guidance if in hospital � oseltamivir. Lee 2009: observed a high proportion (120% to 140%) of untreated patients with persistent virus isolation beyond day 4�5 of illness, which strengthened their conclusions. On the basis of their findings, they recommend areas of further research regarding the management of patients hospitalized with influenza should include clinical trials on delayed antiviral therapy in compromised and seriously ill patients [16, 39, 48], the use of a higher-dose regimen (eg, 150 mg oseltamivir twice daily), A more prolonged course of treatment (15 days). From 11 February 2010 onwards, antivirals will only be authorised via health care professionals using either antiviral authorisation vouchers or the right hand side of FP10s (endorsed �ACP�). This allows us to continue to provide antivirals from a central stockpile free of charge. It also provides a safety checklist of dosages. Antiviral collection points will continue to function until the end of the current �flu season. The Government�s main scientific advisory group (SAGE) has reviewed antiviral policy and advised that general practitioners can continue to make antivirals available to all patients with influenza like illness subject to their clinical discretion and that this policy should continue to the end of the current seasonal �flu period � the end of March 2010. In the severe cases intensivists using oseltamivir via NG tube for obvious reasons. Remembering also that zanamivir or Relenza blisters should not be used in a ventilated patient via a nebuliser due to the risk of the components blocking the ventilator tubing. MHRA. Canadians about to publish on dosage in critical care patients � 75mg adequate blood levels. Alternatives for ventilated cases � iv zanamivir, GSK, named patient basis. Can be available to units within 24 hours. First line therapy for suspected or confirmed pandemic influenza is oseltamivir, unless there is a strong suspicion of infection with an oseltamivir resistant strain, even if the patient is pregnant. The conventional oseltamivir dose for treatment of pandemic influenza is 75mg bd. Although absorption may be effective in critically ill patients, clinicians may wish to ensure adequate plasma levels by increasing the dose to 150mg bd. There is evidence that viral shedding may be prolonged in critically ill patients, and in critical care settings treatment with oseltamivir should be increased to a minimum of 10 days. This is an unlicensed use but there are no currently reported safety concerns. Where there is evidence that this route of treatment is not effective then the use of parenteral zanamivir should be considered. Oseltamivir schedules exist for those with stable impaired renal function. If a second line drug is required IV zanamivir should be used, which is available on a compassionate-use basis from the manufacturers. Zanamivir powder for inhalation should not be used as a nebuliser solution for patients receiving mechanical ventilation. Dual therapy with naso-gastric oseltamivir and iv zanamivir should normally only be considered for the treatment of patients with known severe immunocompromise. Refer to HPA web http://www.hpa.org.uk/HPA/Topics/InfectiousDiseases/InfectionsAZ/1240812234677 Very good editorial from Tim Uyeki of the CDC summarising some of the published evidence supporting the early use of antivirals in pandemic influenza (H1N1) 2009. Ref in particular: Jain, Over 200 US patients � data suggests that the use of AV is beneficial, esp when initiated early, since patients who were admitted to an ICU or died were less likely to have received such therapy within 48 hrs after the onset of symptoms; Dominguez Mexico 58 ICU patients � surviviors were more likely to havce received treatment with NAIs. P=0.006, CMO�s BMJ article deaths in England � observed delayed AV use in most fatal cases. Value of the observation is ltd by the absence of a control group. Canadians � CMAJ just published � Zarychanski et al � severe H1N1 necess ICU was associated with a longer interval from onset of symptoms to treatment with AN and the presence of underlying comorbidity. Regarding pregnancy � guidance if in hospital � oseltamivir. Lee 2009: observed a high proportion (120% to 140%) of untreated patients with persistent virus isolation beyond day 4�5 of illness, which strengthened their conclusions. On the basis of their findings, they recommend areas of further research regarding the management of patients hospitalized with influenza should include clinical trials on delayed antiviral therapy in compromised and seriously ill patients [16, 39, 48], the use of a higher-dose regimen (eg, 150 mg oseltamivir twice daily), A more prolonged course of treatment (15 days). From 11 February 2010 onwards, antivirals will only be authorised via health care professionals using either antiviral authorisation vouchers or the right hand side of FP10s (endorsed �ACP�). This allows us to continue to provide antivirals from a central stockpile free of charge. It also provides a safety checklist of dosages. Antiviral collection points will continue to function until the end of the current �flu season. The Government�s main scientific advisory group (SAGE) has reviewed antiviral policy and advised that general practitioners can continue to make antivirals available to all patients with influenza like illness subject to their clinical discretion and that this policy should continue to the end of the current seasonal �flu period � the end of March 2010.

16. 16 Antivirals � second line If a second line drug is required IV zanamivir should be used, which is available on a compassionate-use basis from the manufacturers. Zanamivir powder for inhalation should not be used as a nebuliser solution for patients receiving mechanical ventilation. See MHRA.

17. 17 Oseltamivir resistance 1 Promote pandemic influenza vaccination to priority groups, household contacts of immunocompromised patients & health staff looking after cases of resistance. Avoid breaks in antiviral treatment. Consider antiviral resistance in patients with H1N1 who fail to improve after five days of oseltamivir treatment or deteriorate on a reasonable period of treatment and seek antiviral resistance testing. Promote the use of good infection control and personal hygiene measures Since the beginning of the pandemic a total of 4,975 pandemic influenza viruses have been analysed for the marker commonly associated with resistance to oseltamivir in seasonal influenza (H275Y); a total of 36 samples have been found to carry this mutation in the UK. Of these 4,975 viruses, 293 have been fully tested for susceptibility. Information on medical history was available for 25 cases, 23 of whom had an underlying medical condition: 18 were immunosuppressed and the remaining five cases had other underlying illnesses. Probable person to person transmission occurred in an outbreak in a hospital ward in November 2009. SOURCE SITREPSince the beginning of the pandemic a total of 4,975 pandemic influenza viruses have been analysed for the marker commonly associated with resistance to oseltamivir in seasonal influenza (H275Y); a total of 36 samples have been found to carry this mutation in the UK. Of these 4,975 viruses, 293 have been fully tested for susceptibility. Information on medical history was available for 25 cases, 23 of whom had an underlying medical condition: 18 were immunosuppressed and the remaining five cases had other underlying illnesses. Probable person to person transmission occurred in an outbreak in a hospital ward in November 2009. SOURCE SITREP

18. 18 Oseltamivir resistance II Use zanamivir for the treatment of patients with confirmed or suspected oseltamivir resistance who are still symptomatic, otherwise stop treatment. Agree within local health economy the use of either zanamivir monotherapy or oseltamivir and zanamivir dual therapy for the treatment of suspected or confirmed pandemic influenza in immunocompromised patients. Use zanamivir for prophylaxis for: i) immunocompromised close contacts of cases of pandemic influenza, regardless of whether the virus is susceptible or resistant ii) people with severe underlying health conditions who are close contacts of confirmed cases of oseltamivir resistant influenza

19. 19 Adjunctive pharmacologic therapy High dose systemic corticosteroids and other adjunctive therapies for viral pneumonitis are not recommended for use outside of the context of clinical trials. Low doses of corticosteroids may be considered in patients with septic shock who require vasopressors. Prolonged use of systemic high-dose corticosteroids can result in serious adverse events in influenza virus-infected patients, including opportunistic infection and possibly prolonged viral replication. Consequently corticosteroids should be avoided unless indicated for another reason. Source: WHO Clinical management of human infection with pandemic (H1N1) 2009: revised guidance. November 2009

20. 20 Microbiology associated with H1N1 Pneumococcus and group A streptococcus have been isolated. Special consideration should be given to secondary staphylococcal infection as this is relatively common in seasonal influenza A virus infection. Concern over MRSA & PVL variants has been raised and clinicians should be alert to this possibility. Routine protocols for the investigation of conventional pneumonias should be followed. I am not going to go into this further as I am sure you know more. Very few seasonal influenza viruses have been detected in recent weeks. RSV and other respiratory viruses account for the majority of positive virus detections among those tested, though the numbers detected have decreased in the last week with the exception of adenovirus. I am not going to go into this further as I am sure you know more. Very few seasonal influenza viruses have been detected in recent weeks. RSV and other respiratory viruses account for the majority of positive virus detections among those tested, though the numbers detected have decreased in the last week with the exception of adenovirus.

21. 21 Infection control � updated DH & HPA guidance From the available literature and incorporating UK expert opinion, the following procedures are considered likely to generate aerosols capable of transmitting influenza when undertaken on patients with influenza, ie are considered to be potentially infectious aerosol-generating procedures: Intubation, extubation and related procedures e.g. manual ventilation and open suctioning CPR (Guidance available Resusc Council web site) Bronchoscopy Surgery and PM procedures in which high speed devices are used Dental procedures NIV High frequency oscillating ventilation Induction of sputum If the procedures are essential take appropriate control measures. Cleaning afterwards Nebulisers: may generate an aerosol from material other than patient secretions For nebs � gloves, apron and surgical mask If the procedures are essential take appropriate control measures. Cleaning afterwards Nebulisers: may generate an aerosol from material other than patient secretions For nebs � gloves, apron and surgical mask

22. 22 DH Guidance

23. 23 Respiratory Rapidly progressive acute respiratory failure is relatively common preceding ICU admission,so ward-based monitoring must include respiratory rate and SpO2. A hospital �Early Warning System� may help identify deteriorating patients and prompt timely referral to critical care. Early intubation may be required in those with rapidly deteriorating respiratory function. Watch out for problems with compliance. Consider earlier use of APRV and HFO in cases of deteriorating compliance. ECMO has been used as a rescue therapy. To discuss a referral call Glenfield, Leicester. NIV notes: Early intubation seems to improve outcomes, particularly in cases of rapidly deteriorating respiratory function. Non-invasive ventilation (NIV) may be appropriate in patients with mild to moderate pneumonitis who are not deteriorating and are monitored in an intensive care area. NIV may also have a role in patients with an exacerbation of chronic obstructive pulmonary disease, particularly where NIV is used as �ceiling therapy�. However, NIV is a potential infectious aerosol generating procedure. The potential risks can be minimised by the use of negative pressure rooms, closed circuit NIV systems and appropriate personal protective equipment . ECMO notes: In Canada, Australia and New Zealand, ECMO has been used as a rescue therapy in 4% and 12% of ventilated cases resp (though these rates may be influenced by the availability of alternate modes of rescue ventlation). While the mortality of those patiens receiving ECMO in Australia was only 21%, not every patient who died from H1N1 was offered ECMO. A recent publication has also suggested that patients who might be considered for ECMO often survive without it. NIV notes: Early intubation seems to improve outcomes, particularly in cases of rapidly deteriorating respiratory function. Non-invasive ventilation (NIV) may be appropriate in patients with mild to moderate pneumonitis who are not deteriorating and are monitored in an intensive care area. NIV may also have a role in patients with an exacerbation of chronic obstructive pulmonary disease, particularly where NIV is used as �ceiling therapy�. However, NIV is a potential infectious aerosol generating procedure. The potential risks can be minimised by the use of negative pressure rooms, closed circuit NIV systems and appropriate personal protective equipment . ECMO notes: In Canada, Australia and New Zealand, ECMO has been used as a rescue therapy in 4% and 12% of ventilated cases resp (though these rates may be influenced by the availability of alternate modes of rescue ventlation). While the mortality of those patiens receiving ECMO in Australia was only 21%, not every patient who died from H1N1 was offered ECMO. A recent publication has also suggested that patients who might be considered for ECMO often survive without it.

24. 24 Predictive risk factors for ICUadmission, DH Guidance Dyspnoea Requirement for supplemental oxygen Pneumonia on admission Heart rate in adults Altered conscious level

25. 25 An Early Warning Scoring System Explain the usefulness of a system such as MEWS. Aware of abnormal physiology. MEWS does not guarantee that appropriate early action will result. High score or one that is not improving is difficult to ignore. Explain the usefulness of a system such as MEWS. Aware of abnormal physiology. MEWS does not guarantee that appropriate early action will result. High score or one that is not improving is difficult to ignore.

26. 26 Fluids Critically ill H1N1 patients tend to benefit from a conservative fluid strategy and their acute hypoxaemic respiratory failure often improves with a negative fluid balance. Some patients require RRT.

27. 27 Guidance

28. 28 Acknowledgements H1N1 ICU network � in particular Kevin Rooney, Nick Sherwood, Bruce Taylor, Paula Lister, David Menon, Julian Bion, Jake Dunning & Dan Taylor. HPA Pandemic Flu office & Nick Gent, LaRS Sudhanva, Virologist, Kings & RMN RCOA & RCPCH Barbara Bannister & Calum Semple, DH WHO Geneva & EURO