This document discusses the management of the 2009 H1N1 influenza pandemic. It summarizes experiences from the Southern Hemisphere, published case studies, and local cases. Key points include: most severe cases are in younger populations; prolonged mechanical ventilation is often required; antiviral treatment should begin within 48 hours for best effect. The document also covers infection control, triage protocols if resources are overwhelmed, and the need for pandemic preparedness and palliative care.

1. Pandemic 2009 H1N1 Influenza PeteyLaohaburanakit, MD, FCCP Intensive Care Unit Rogue Valley Medical Center October 8, 2009

2. Outline Introduction Global experiences with 2009 H1N1 Southern hemisphere Published cohorts Hospital management Case identification Infection control and prevention Treatment Disaster preparedness, triage, and allocation of scarce resources

3. 2009 H1N1 Influenza A Quadruple re-assortment of RNAs from two swine strains, one human strain and one avian strain First recognized in March-April 2009 in Mexico Phase 6 pandemic status by June 2009 Currently named 2009 H1N1 Influenza by CDC

4. 2009 H1N1 Influenza A 1976 – present 2009 H1N1

5. The Big Deal Novel virus to humans Sustained human-to-human transmission Causes severe, fatal illnesses in unusual populations May re-assort with seasonal flu (H3N2) or avian flu (H5N1) Unknown interactions with seasonal flu

6. Risk Groups for Seasonal Flu Chronic lung disease Cardiac disease Immunosuppression Diabetes mellitus Chronic kidney disease

7. Risk Groups for 2009 H1N1 Same as seasonal flu risk groups PLUS Pregnancy* Obesity* Age 6 months to 24 years old* Highest illness rates Second highest mortality rates Age 25 to 64 years old* Highest mortality rates

8. Is the mortality rate higher than seasonal flu? Study from Australia and New Zealand NEJM 2009 October

10. Experiences with 2009 H1N1 Data from Southern hemisphere Published cohorts Mexico city Spain Michigan Local experience at RVMC

11. 2009 H1N1 in Southern Hemisphere Reports from Argentina, Australia, Chile, New Zealand, and Uruguay Viral strain similar to the U.S. strain Similar at-risk groups Highest mortality in adults 25-64 years of age 47-60% with known risk factors for severe disease Increased risks of complications in pregnant women Assessment of 2009 Influenza A (H1N1) Pandemic on Selected Countries in the Southern Hemisphere. Department of Health and Human Services. August 26, 2009.

12. 2009 H1N1 in Southern Hemisphere About 6-7 week ascent to peak followed by rapid decline Community mitigation measures School closures Cancellation of mass gatherings Isolation, quarantine, other social distancing Healthcare systems experienced stress Geographically isolated Relatively short-lived

13. Good news or Bad news? During Spring/Summer, hospitalization rates in the U.S. is 2.6 per 100,000 population (as opposed to 7.8 to 21.7 for the Southern hemisphere). Schools open in the fall. Our flu season officially starts October 4th 2009.

14. Second Waves Miller MA et al. New England J Med 2009 ; 360:2595-2598. USUAL INFLUENZA SEASON DEATHS

15. Mexico City 488 with influenza-like illness (ILI) 114 confirmed by PCR 22 observed in ER 33 hospitalized for more than 24 hours. 13 (39.3%) required non-invasive ventilation. 9 (27%) required mechanical ventilation; average time on MV was 7 days (range 1-25 days). Data courtesy of Dr. Guillermo Dominguez-Cherit

16. Mexico City

17. Mexico City

18. Mexico City

19. Mexico City

20. Mexico City

21. Mexico City * Some patients required both non-invasive and invasive ventilation.

22. Mexico City

23. Mexico City

24. Spain Rello J, et al. Crit Care 2009;13:R148.

25. Spain

26. Spain

27. Spain

28. Spain

29. Michigan Intensive Care Patients With Severe Novel Influenza (H1N1) Virus Infection – Michigan MMWR. June 2009

30. Michigan

31. RVMC – All cases Fourteen cases of confirmed H1N1 (as of October 6) Average age 17 years (range 35 days-42 years) Male : Female = 1.2:1 Average hospital length of stay 6.5 days Excluding ICU patients, hospital LOS 2 days Two patients expired.

32. RVMC – ICU cases 4 admitted to ICU Age 25-34 years old 3/4 developed severe ARDS. All ARDS patients required high-frequency oscillator. Two deaths, one transferred to a long-term acute care facility on mechanical ventilation, one discharged from hospital after 3 days Average hospital/ICU LOS is 16 days (range 3-52 days)

33. RVMC – ICU Cases

34. Common Themes Severe disease found in younger patients (pooled mean is 40 years old). The majority of ICU admits required prolonged invasive mechanical ventilation. Non-invasive ventilation not effective. Significant portion required HFOV or ECMO.

35. Common Themes Spain and Michigan reported range of 4-8 days from onset to first antiviral dose. ICU mortality rates varied from 28 to 45% (Mexico City, Spain, and Michigan).

37. Hospital Management Case identification Clinical diagnosis Laboratory confirmation Infection control and Prevention Treatment of suspected cases Disaster preparedness, triage, and allocation of scarce resources

38. Case Identification Symptoms and signs Fever Cough Malaise Myalgias Diarrhea and vomiting* Laboratory findings Leucopenia or lymphopenia Elevated serum lactate dehydrogenase (LD)

39. Case Identification Laboratory confirmation Priority groups Those require hospitalization Those at risk of developing complications Samples Nasopharyngeal swabs or aspirate Nasal swab plus throat swab Nasal wash Tracheal aspirate

40. Sampling Use personal protective equipment while swabbing. Swab horizontally, away from nasal septum. Samples need to be placed in viral transport media and placed on ice or cold packs or at 4 ºC for transport.

41. Diagnostic Tests Rapid antigen detection Immunofluorescence Nucleic acid testing : rRT-PCR Viral culture Antibody testing Acute sample Convalescent sample

42. Diagnostic Tests Beigel JH. Crit Care Med 2008;36:2660-2666.

43. Diagnostic Tests Recommendation Send two swabs in one viral transport media for both rapid antigen detection and rRT-PCR for 2009 H1N1 If 2009 H1N1 continues to predominate Positive rapid antigen leads to treatment with Oseltamivir or Zanamivir If seasonal flu becomes co-dominant with 2009 H1N1 Positive rapid antigen may indicate combination treatment with Oseltamivir and Amantadine OR Zanamivir as single agent Negative rapid antigen test does not exclude influenza infection!

45. Infection Control and Prevention Droplet and standard precautions Surgical mask Eye protection Gloves Close contact is < 6 feet CDC recommends isolation until symptoms resolved or > 7 days after onset, whichever is longer. RVMC recommends isolation until hospital discharge.

46. Infection Control and Prevention Fit-tested N95 masks for aerosol generating procedureslisted in the WHO infection control recommendations Aspiration of respiratory tract Intubation Resuscitation Bronchoscopy Autopsy

47. Infection Control and Prevention Hand hygiene Cough etiquette Self-quarantine and social distancing Vaccination

48. Why personal hygiene is important

49. Infection Control and Prevention N95 masks? - Pros McIntyre R et al. (unpublished data) 1936 healthcare workers in China Randomized to surgical masks or N95 N95 group had 75% reduction in influenza-like illness, 75% reduction in confirmed influenza Surgical mask had no efficacy Other details unavailable What’s the control group? Usage and compliance? Other preventive measures?

50. Infection Control and Prevention N95 masks? - Cons Loeb M et al. JAMA 2009;302(17):e-pub ahead of print Oct 1, 2009. 446 nurses in 8 Ontario hospitals Randomized to either surgical masks or fit-tested N-95 masks 23.6% of surgical masks group and 22.9% of N-95 group developed laboratory confirmed influenza

51. Infection Control and Prevention Problems with N95 Evidence to support the use is not very strong. Inadequate supply, especially in outpatient settings Requires fit testing Not practical for prolonged, day-to-day use Uncomfortable Costly Difficult to maintain compliance

52. What should we do? CDC, AMA, and IOM recommend the use of fit-tested N95. IDSA, APIC and SHEA recommend surgical masks. RVMC Infection Control recommends Droplet/contact precautions plus eye protection N95 for aerosol-generating procedures

54. Treatment Supportive care Isolation Oxygen therapy Intravenous hydration Symptomatic relief Critical care needs : ventilator, hemodynamic support, etc. Antiviral therapy Adjunct therapies – Not generally recommended Prophylactic antibiotics Steroid

55. Antiviral Therapy 2009 H1N1 is resistant to Amantadine and Rimantadine. Susceptible to neuraminidase inhibitors Oseltamivir Zanamivir

56. Antiviral Therapy Benefits of antiviral therapy Shortens the duration of symptoms Decreases the risks of complicated disease Decreases viral shedding Timing Best results if initiated < 48 hours after onset May still help after 48 hours if symptoms are severe or in pregnant patients

57. Oseltamivir Oral formulation Dosage 75 mg po bid for 5 days 150 mg po bid for 10 days for the critically ill Side effects/practical issues Neuropsychiatric side effects Oseltamivir resistance Poor GI absorption

58. Zanamivir Inhalation via Diskhaler® Report of intravenous use (unlabeled) Kidd IM et al. Lancet 2009;374;1036. Dosage Two inhalations (10 mg total) twice a day for 5 days Side effects/practical issues Headache Cough and bronchospasm Not appropriate in children < 7 years old Not administrable via ventilator circuit

59. Oseltamivir resistance Risk factors Prior exposure to Oseltamivir (prophylaxis or treatment) Immunocompromised patients Treatment options in suspected resistance Zanamivir when appropriate Oseltamivir plus Rimantadine or Amantadine Oseltamivir, Rimantadine plus Ribavirin

60. Antiviral Prophylaxis CDC guidance – September 22, 2009 Close contact in high risks of complications Close unprotected contact in healthcare workers, first responders An alternative is to treat early if symptoms occur after a suspected exposure.

61. Secondary Bacterial Infection Retrospective pathologic review suggested secondary bacterial infection was a common cause of death in Pandemic H1N1 in 1918. Occurs several days after onset. Staphylococcus aureusincluding MRSA Necrotizing pneumonia Pneumatocele Gram negative bacteria

63. Send samples for rRT-PCR ± Rapid antigen

64. Start empiric antiviral treatmentSupportive care ± follow up

66. Send samples for rRT-PCR ± Rapid antigen

67. Start empiric antiviral treatmentHigh risks for disease acquisition/spread Consider antiviral treatment Supportive care ± follow up

69. Disaster Preparedness, Triage and Allocation of Resources At a given time, most hospitals operate at over 90% capacity. Does not take much to overwhelm healthcare resources. Hospitals, practitioners, hospital staff need to prepare for a surge in patient load.

70. What NOT to do

71. Disaster Preparedness Be prepared “Know your enemies and know yourself, you will be victorious a hundred times in a hundred battles…” Sun Tzu’s The Art of War

72. Disaster Preparedness Educate yourself CDC guidance Flu.gov or Flu.oregon.gov American Medical Association Society of Critical Care Medicine New England Journal of Medicine H1N1 Center

73. Disaster Preparedness Protect yourself Personal hygiene Vaccination Protective equipments Self quarantine Social distancing if needed

74. Disaster Preparedness Maximize staffing Tiered staffing model Physicians, mid-level practitioners, RNs, RTs, and pharmacists Maximize hospital facility Outpatient surgery, short stay unit Cafeteria Auditorium Alternate care site (ACS)

75. Tiered Staffing

76. Definition of Triage “Scarce resources are used to provide the maximum benefit to the population at large, even if it means that other victims who might have been saved under usual circumstances cannot be treated optimally…” Christian M et al. Critical care during a pandemic: report from Ontario Health Plan for an influenza pandemic (OHPIP) working group on admission/discharge triage. 2006

77. Triage Every practitioner performs triage every single day, knowingly or unknowingly. Prioritization of patients with semi-objective risk calculation or eyeballing When resources are available, trials of treatment are reasonable. When resources are limited, trial of treatment may exhaust extensive resources and cause others to die.

78. The Scenario One ventilator Three H1N1 patients 34-year-old single mother of 2 82-year-old man who is a big donor to hospital foundation with severe emphysema and depends on home oxygen 18-year-old male with drug abuse history How do we decide who gets the ventilator?

79. Ethical Principles in Triage Responsibility toward the common good Individual needs Available resources

80. Response Thresholds Christian M et al. Critical care during a pandemic: report from OHPIP working group on admission/discharge triage. 2006

81. Opportunities for Triage

82. Mortality Prediction for Triage Objective Reliable Valid Sequential organ failure assessment (SOFA) score Christian MD et al. Development of a triage protocol for critical care during an influenza pandemic. CMAJ 2006; 175:1377-1381.

83. SOFA Score

84. Modified SOFA Score

85. Utah Hospitals and Health Systems Association. Utah Pandemic Influenza Hospital and ICU Triage Guidelines. January 10, 2009.

86. Exclusion Criteria for Admission Utah Hospitals and Health Systems Association. Utah Pandemic Influenza Hospital and ICU Triage Guidelines. January 10, 2009.

87. The Scenario One ventilator Three H1N1 patients 34-year-old single mother of 2 82-year-old man who is a big donor to hospital foundation with severe emphysema and depends on home oxygen 18-year-old male with drug abuse history How do we decide who gets the ventilator?

88. Who Gets the ICU Bed and Ventilator?

89. Multi-modality Model White DB et al. Ann Intern Med 2009;150:132-138.

90. Palliative Care Services Those triaged to non-critical care must be treated nonetheless. Simple treatment measures may be provided if resources are available (e.g. oxygen, medications). Patients should be ensured adequate symptom relief and palliative care expertise.

91. Take Home Messages Recognize high-risk groups for severe 2009 H1N1 disease Most hospitalized patients are younger and could become critically ill quickly. High index of suspicion Isolate early and sufficiently. Protect yourself and your patients.

92. Take Home Messages Treat early and adequately Treatment most effective within 48 hours Treatment beyond 48 hours warranted in pregnancy and those with persistent, severe symptoms Double dose, double duration for severe cases Be informed, educated and prepared.