MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

[Giuseppe]

Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009 (MMWR, edited)

July 10, 2009 / 58(Dispatch);1-4

Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009


In April 2009, CDC reported the first two cases in the United States of human infection with a novel influenza A (H1N1) virus (1). As of July 6, a total of 122 countries had reported 94,512 cases of novel influenza A (H1N1) virus infection, 429 of which were fatal; in the United States, a total of 33,902 cases were reported, 170 of which were fatal.*

Cases of novel influenza A (H1N1) virus infection have included rapidly progressive lower respiratory tract disease resulting in respiratory failure, development of acute respiratory distress syndrome (ARDS), and prolonged intensive care unit (ICU) admission (2).

Since April 26, communitywide transmission of novel influenza A (H1N1) virus has occurred in Michigan, with 655 probable and confirmed cases reported as of June 18 (Michigan Department of Community Health [MDCH], unpublished data, 2009).

This report summarizes the clinical characteristics of a series of 10 patients with novel influenza A (H1N1) virus infection and ARDS at a tertiary-care ICU in Michigan.

Of the 10 patients, nine were obese (body mass index [BMI] ≥30), including seven who were extremely obese (BMI ≥40); five had pulmonary emboli; and nine had multiorgan dysfunction syndrome (MODS).

Three patients died.

Clinicians should be aware of the potential for severe complications of novel influenza A (H1N1) virus infection, particularly in extremely obese patients.

The surgical intensive care unit (SICU) at the University of Michigan Health System (UMHS) specializes in the evaluation of adult patients with severe ARDS for advanced mechanical ventilation and possible extracorporeal membrane oxygenation (ECMO).

During May 26--June 18, the unit received 13 patients for evaluation from outlying hospitals, 10 of whom were confirmed to have novel influenza A (H1N1) virus infection by testing of respiratory specimens with real-time reverse transcription--polymerase chain reaction (rRT-PCR) at MDCH and CDC.

Direct immunofluorescent antibody staining at UMHS was negative for influenza A in all 10 patients. Viral culture at UMHS was positive for influenza A in two patients.

All 10 patients were referred to the SICU because of severe hypoxemia, ARDS, and an inability to achieve adequate oxygenation with conventional ventilation modalities. Medical records of all 10 patients were reviewed for demographics, case characteristics, clinical findings, and clinical course.

Illness onset of the 10 patients occurred during May 22--June 13.

The median age was 46 years (range: 21--53 years); nine patients were obese, including seven who were extremely obese (Table). In the three fatal cases, the time from illness onset to death ranged from 17 to 30 days. Four patients received steroids during their illness before transfer to the SICU; two with asthma received oral steroids as outpatients during the initial evaluation and treatment of their acute respiratory illness (one was on chronic oral steroids for underlying lung disease, and one without chronic pulmonary disease was prescribed oral steroids and oral antimicrobials).

Five patients received intravenous corticosteroids during their SICU hospitalization: four for treatment of severe vasopressor-dependent refractory septic shock, and one for continuation of therapy for chronic pulmonary disease.

All 10 patients required initial advanced mechanical ventilation (high-frequency oscillatory or bilevel ventilation with high mean airway pressures [32--55 cm H20]). Two patients required veno-venous ECMO support. Six required continuous renal replacement therapy (CRRT) for acute renal failure.

Upon transfer to the SICU, five had elevated white blood cell counts, and one had a decreased white blood cell count. The median white blood cell count (WBC) was 9,500 cells/mm3 (range: 3,700--19,700 cells/mm3; normal: 4,000--10,000 cells/mm3). All ten patients had elevated aspartate transaminase (AST) levels. The median AST level was 83.5 IU/L (range: 41--109 IU/L; normal: 8--30 IU/L). Six of the nine patients who were tested had elevated creatine phosphokinase (CPK) levels. The median CPK level was 999 IU/L (range: 51-- 6,572 IU/L; normal: 38--240 IU/L).

Nine patients were admitted to the SICU with MODS, and nine manifested septic shock requiring vasopressor support. All 10 patients required tracheostomy.

Chest radiograph findings in all 10 patients were abnormal, with bilateral infiltrates consistent with severe multilobar pneumonia or ARDS. Computed tomography (CT) of the chest confirmed pulmonary emboli in four patients at admission to the SICU and in one additional patient who deteriorated 6 days after admission to the SICU.

A hypercoagulable state was evident in two additional patients. One of these patients had frequent clotting of the CRRT circuit despite regional citrate anticoagulation. Another patient had bilateral iliofemoral deep venous thromboses, necessitating systemic heparin anticoagulation. None of the 10 patients had evidence of concomitant disseminated intravascular coagulation by laboratory studies.

As of July 8, none of the 10 patients had evidence of bacterial infection after admission to the SICU or in subsequent blood, bronchoalveolar lavage, or urine cultures. All patients received antibiotic therapy upon admission to the initial hospitals, and broad spectrum antibiotics were continued upon transfer to the SICU.

The timing of antiviral treatment initiation was difficult to determine because patients were transferred from other hospitals; however, the estimated median number of days from illness onset to initiation of antiviral treatment was 8 days (range: 5--12 days). During their care at the SICU, all 10 patients were administered oseltamivir and amantadine beyond the standard 5-day course, including higher-dose oseltamivir (up to 150 mg orally twice a day), with dose adjustment for decreased renal function.

As of July 8, one patient remained in the SICU requiring ECMO, one remained on advanced mechanical ventilation, five were transferred back to the referring facility in stable condition, and three had died.

Autopsies were performed on two patients; results in both patients confirmed bilateral severe hemorrhagic viral pneumonitis with interstitial inflammation and diffuse alveolar damage and concurrent bilateral pulmonary emboli.


Reported by:

LM Napolitano, MD, PK Park, MD, KC Sihler, MD, T Papadimos, MD, Div of Acute Care Surgery, Univ of Michigan Health System; C Chenoweth, MD, S Cinti, MD, C Zalewski, MPH, Div of Infectious Diseases and Infection Control, Univ of Michigan Health System; R Sharangpani, MD, Univ of Michigan School of Public Health; P Somsel, DrPH, E Wells, MD, Michigan Dept of Community Health. AM Fry, MD, AE Fiore, MD, MPH, JM Villanueva, PhD, S Lindstrom, PhD, TM Uyeki, MD, Influenza Div, National Center for Immunization and Respiratory Diseases, CDC.


Editorial Note:

This report describes the clinical findings of a limited series of patients with novel influenza A (H1N1) virus infection and refractory ARDS admitted to a tertiary-care ICU for advanced mechanical ventilation. This patient group represents the most severely ill subset of persons with novel influenza A (H1N1) virus infection and is notable for the predominance of males, the high prevalence of obesity (especially extreme obesity), and the frequency of clinically significant pulmonary emboli and MODS.

All required advanced mechanical ventilator support, reflecting severe pulmonary damage.

The pulmonary compromise described in this report suggests that severe pulmonary damage occurred as a result of primary viral pneumonia. Although data are not available, this damage also might be attributable to secondary host immune responses (e.g., through cytokine dysregulation triggered by high viral replication).

However, bacterial coinfection in the lung not identified by blood culture or bronchoalveolar lavage cannot be excluded.

Only three of the patients in this series had underlying conditions associated with a higher risk for seasonal influenza complications. Conditions associated with an increased risk for complications from seasonal influenza include extremes of age, pregnancy, chronic underlying medical conditions (e.g., pulmonary, cardiovascular, hepatic, hematologic, neurologic, and neuromuscular conditions and metabolic disorders or immunosuppression), long-term aspirin therapy in persons aged ≤18 years, and being a resident of a nursing home or other chronic-care facility (3).

However, fatal disease associated with novel influenza A (H1N1) virus infection has occurred among persons without these conditions who previously were healthy (2).

The high prevalence of obesity in this case series is striking. Whether obesity is an independent risk factor for severe complications of novel influenza A (H1N1) virus infection is unknown. Obesity has not been identified previously as a risk factor for severe complications of seasonal influenza. In a mouse model, diet-induced obese mice had significantly higher mortality when infected with seasonal influenza virus compared with their leaner counterparts (4). In addition, extremely obese patients have a higher prevalence of comorbid conditions that confer higher risk for influenza complications, including chronic heart, lung, liver, and metabolic diseases.

One study of patients admitted to critical-care units indicated that obesity was an independent risk factor for mortality (5). A meta-analysis concluded that prolonged duration of mechanical ventilation and longer SICU length of stay, but not mortality, are associated with obesity (6). Another study reported that extremely obese ICU patients had higher rates of mortality, nursing home admission, and ICU complications compared with moderately obese patients (BMI 30--39) (7). Further investigations of the role of extreme obesity and accompanying comorbidities in severely ill patients with novel influenza A (H1N1) virus infection are needed.

Pulmonary emboli are not known to be a common complication of ARDS or of sepsis syndrome, but both ARDS and sepsis represent hypercoagulable states (8). Pulmonary emboli were not noted in patients hospitalized with novel influenza A (H1N1) virus infection in Mexico (3). One clinical study did not identify any increased risk for pulmonary embolism with seasonal influenza virus infection (9). However, a report of two patients with rapidly progressive hypoxemia associated with influenza A (H3N2) virus infection noted that they received a diagnosis of acute pulmonary embolism (10). Clinicians providing care to patients with novel influenza A (H1N1) virus infection should be aware of the potential for patients with ARDS to develop a hypercoagulable state and for pulmonary emboli to cause severe complications, including fatal outcomes.

Two observational studies have demonstrated a reduction in mortality with oseltamivir treatment among hospitalized patients with seasonal influenza compared with untreated patients (11,12). Although early antiviral treatment (<48 hours from illness onset) is optimal to reduce illness among outpatients with seasonal influenza (13), a reduction in mortality of hospitalized persons with seasonal influenza or avian influenza A (H5N1) virus infection was reported even when oseltamivir treatment was initiated later (11,14). Early antiviral treatment of hospitalized patients with suspected influenza is recommended, including for patients admitted ≥48 hours after illness onset (13).

The patients in this series received higher oseltamivir dosing and longer duration of treatment than standard therapy. Data to inform clinical guidance are needed on viral shedding, pharmacokinetics, and clinical effectiveness of standard versus higher-dose oseltamivir treatment and on optimal duration of therapy for patients, including obese persons, with severe or progressive novel influenza A (H1N1) virus infection. Limited data for seasonal influenza treatment suggest that doubling the oseltamivir dose is well-tolerated with a comparable adverse event profile as the standard adult dose (75 mg orally twice a day) (15). Higher oseltamivir dosing and longer duration of treatment has been suggested for H5N1 (avian influenza) patients with severe pulmonary disease (14).

Until additional data are available, higher oseltamivir dosage (e.g., 150 mg orally twice a day for adults) or extending the duration of treatment can be considered for severely ill hospitalized patients with novel influenza A (H1N1) virus infection.

Further characterization of severe cases of novel influenza A (H1N1) virus infection in the United States and worldwide is needed to determine the frequency of the findings from this limited case-series. Clinicians caring for patients with suspected novel influenza A (H1N1) virus infection should monitor them closely for rapid clinical deterioration, especially with regard to increasing oxygenation requirements and potential for development of complications (e.g., respiratory failure, ARDS, multiorgan failure, septic shock, and pulmonary emboli).

Empiric antiviral treatment is recommended for all hospitalized patients at admission with suspected novel influenza A (H1N1) virus infection,? including persons who have received a diagnosis of community-acquired pneumonia. Empiric antibiotic agents also should be used as appropriate for suspected bacterial infection. Depending on the antiviral susceptibilities of circulating influenza A virus strains, either zanamivir monotherapy or combination therapy with oseltamivir (for treatment of novel influenza A [H1N1] virus infection) and rimantadine (for treatment of oseltamivir-resistant seasonal influenza A [H1N1]) might be indicated in hospitalized patients until final virus identification is available. In communities in which novel influenza A (H1N1) virus is the predominant circulating influenza virus, oseltamivir or zanamivir should be administered as early as possible to hospitalized patients with suspected novel influenza A (H1N1) virus infection, even before diagnostic testing results are available.

Clinicians should be aware that negative results of rapid influenza diagnostic tests, immunoflouresence, or viral culture do not exclude the possibility of novel influenza A (H1N1) virus infection.

Although five patients in this case-series received corticosteroids, their role in the management of severely ill patients with novel influenza A (H1N1) virus infection is unclear, and routine corticosteroid use is not recommended.?

Many hospitalized patients with novel influenza A (H1N1) virus infection have had underlying comorbidities recognized to be high-risk conditions for complications of seasonal influenza. However, clinicians should be aware that severe illness and fatal outcomes also can occur in patients without known risk factors for complications of seasonal influenza, including persons with extreme obesity.


Acknowledgment

This report is based, in part, on contributions from C Miller, PhD, Michigan Department of Community Health.


References

1. CDC. Swine influenza A (H1N1) infection in two children---Southern California, March--April 2009. MMWR 2009;58:400--2.
2. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009. Available at: http://content.nejm.org/cgi/reprint/NEJMoa0904252.pdf.
3. CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR 2008;57(No. RR-7).
4. Smith AG, Sheridan PA, Harp JB, Beck MA. Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J Nutr 2007;137:1236--43.
5. Bercault N, Boulain R, Kuteifan K, et al. Obesity-related excess mortality rate in an adult intensive care unit: a risk-adjusted matched cohort study. Crit Care Med 2004;32:998--1003.
6. Akinnusi ME, Pineda LA, El Solh AA. Effect of obesity on intensive care morbidity and mortality: a meta analysis. Crit Care Med 2008;36:151--8.
7. Yaegashi M, Jean R, Zuriqat M, Noack S, Homel P. Outcome of morbid obesity in the intensive care unit. J Intensive Care Med 2005;20:147--54.
8. Schultz MJ, Haitsma JJ, Zhang H, Slutsky AS. Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia---a review. Crit Care Med 2006;34:871--7.
9. van Wissen M, Keller TT, Ronkes B, et al. Influenza infection and risk of acute pulmonary embolism. Thromb J 2007;5:16.
10. Ohrui T, Takahashi H, Ebihara S, et al. Influenza A virus infection and pulmonary microthromboembolism. Tohoku J Exp Med 2000;192:81--6.
11. McGeer A, Green KA, Plevneshi A. Shigayeva A, et al Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007;45:1568--75.
12. Hanshaoworakul W, Simmerman JM, Narueponjirakul U, et al. Severe human influenza infections in Thailand: oseltamivir treatment and risk factors for fatal outcome. PlosMed 2009;4:e6051.
13. Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children-diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003--32.
14. Abdel-Ghafar AN, Chotpitayasunohdh T, Gao Z, et al. Update on avian influenza A (H5N1) virus infection in humans. N Engl J Med 2008;358:261--73.
15. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza. JAMA 2000;282:1016--24.

(*) Information on the number of cases of novel influenza A (H1N1) virus infection worldwide is available from the World Health Organization at http://www.who.int/csr/don/2009_07_06/en/index.html. Information on the number of cases of novel influenza A (H1N1) virus infection in the United States is available from CDC at http://www.cdc.gov/h1n1flu/update.htm.
(?) Interim guidance on antiviral recommendations for patients with novel influenza A (H1N1) virus infection and their close contacts is available from CDC at http://www.cdc.gov/h1n1flu/recommendations.htm.
(?) Initial guidance on the clinical management of patients with novel influenza A (H1N1) virus infection is available from the World Heallth Organization at http://www.who.int/csr/resources/pub...1_May_2009.pdf.


[TABLE. Selected characteristics of intensive-care patients with severe novel influenza A (H1N1) virus infection --- Michigan, June 2009]

[Patient - Age (yrs) - Sex - Underlying conditions - Initial signs or symptoms - BMI* - No. days between onset and first hospitalization - No. days between illness onset and SICU? admission - Advanced mechanical ventilation - Diagnosis: PE? - MODS? - Vaso-pressors - Outcome** ]

1. 28 - M - Asthma - High fever, cough, sore throat that progressed to blood-tinged sputum, decreasing mental status - 34.2 - 7 - 8 - HFOV?? - Yes - Yes - Yes - Death
2. 21 - M - None - Fever, sore throat, dry cough, sneezing; progressed to tachypnea and dyspnea - 50.5 - 7 - 8 - Bilevel - Yes - Yes - Yes - Improved, transferred
3. 48 - F - Asthma, smoker - Shortness of breath, rhinorrhea, non-productive cough - 58.9 - 5 - 9 - HFOV - No - Yes - Yes - Improved, transferred
4. 35 - M - None - Upper respiratory tract illness symptoms - 51.7 - 6 - 8 - HFOV - Yes - No - No - Improved, transferred
5. 43 - M - None - Fever, cough, malaise, chills, sweats - 48.7 - 4 - 5 - HFOV to ECMO?? - Yes - Yes - Yes - Death
6. 52 - M - None - Sinus drainage, cough with clear sputum production, decreased appetite - NA?? - 6 - 13 - HFOV - Yes - Yes - Yes - Improved, transferred
7. 44 - M - None - Fever, productive cough with black/red sputum, nausea, vomiting, diarrhea - 50.2 - 5 - 7 - HFOV - No - Yes - Yes - Death
8. 51 - M - Granulomatous chronic lung disease - Fever, worsening dyspnea, rigors, nausea, vomiting, malaise - 39.7 - 1 - 9 - HFOV to ECMO - No - Yes - Yes - ECMO plus ventilator
9. 53 - M - None - Fever, chills, cough, shortness of breath - 38.5 - 7 - 16 - HFOV - No - Yes - Yes - Improved, transferred
10. 53 - M - None - Fever, cough - 47.8 - 6 - 6 - HFOV - No - Yes - Yes - HFOV

(*) Body mass index. Based on admitting weight at University of Michigan Health System surgical intensive care unit.
(?) Surgical intensive care unit.
(?) Pulmonary emboli.
(?) Multiorgan dysfunction syndrome.
(**) As of July 8, 2009.
(??) High-frequency oscillatory ventilation.
(??) Extracorporeal membrane oxygenation.
(??) Not available. Height unknown; weight = 72 kg.

Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the U.S. Department of Health and Human Services. CDC is not responsible for the content of pages found at these sites. URL addresses listed in MMWR were current as of the date of publication.
All MMWR HTML versions of articles are electronic conversions from typeset documents. This conversion might result in character translation or format errors in the HTML version. Users are referred to the electronic PDF version (http://www.cdc.gov/mmwr) and/or the original MMWR paper copy for printable versions of official text, figures, and tables. An original paper copy of this issue can be obtained from the Superintendent of Documents, U.S. Government Printing Office (GPO), Washington, DC 20402-9371; telephone: (202) 512-1800. Contact GPO for current prices.
**Questions or messages regarding errors in formatting should be addressed to mmwrq@cdc.gov.
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<cite cite="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0710a1.htm?s_cid=mm58d0710a1_e">Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009</cite>

[wotan]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

One thing I found interesting was that, even though they discussed obesity in the article, they didn't actually list it as an underlying conditions, leading to 7/10 having no underlying conditions.

[AlaskaDenise]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

It's unfortunate that they went so long without antiviral treatment.

...the estimated median number of days from illness onset to initiation of antiviral treatment was 8 days (range: 5--12 days). During their care at the SICU, all 10 patients were administered oseltamivir and amantadine beyond the standard 5-day course, including higher-dose oseltamivir (up to 150 mg orally twice a day), with dose adjustment for decreased renal function.

I presume they didn't get earlier treatment because their cases were considered mild. It's beginning to look as if they guidelines should say anyone with certain underlying conditions should receive antivirals, even when the case is still mild.

.

[german-docter]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

It's unfortunate that they went so long without antiviral treatment.

I presume they didn't get earlier treatment because their cases were considered mild. It's beginning to look as if they guidelines should say anyone with certain underlying conditions should receive antivirals, even when the case is still mild.

.

AlaskaDenise,
exactly ! IMO the time delay in starting antivirals is one of the main reasons for fatal courses in novel Influenza everywhere in the world.

Related posts:

http://www.flutrackers.com/forum/showthread.php?t=113191

post#3
Re: N Engl J Med. Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico
________________________________________
Comment: This report of 18 cases of pneumonia and confirmed S-OIV infection in Mexico, recently published in the New England Journal of Medicine, shows some illustrative aspects. Those who died already were in an advanced state of sepsis and SIRS at the time of admission with respiratory failure, ARDS, hypoxemia, acidosis, DIC and renal failure as well. In both groups (those who resolved the disease and the fatal cases) the time between onset of illness and time of admission was 6 days (median). Nobody of them had been given antivirals until they were hospitalized, although 12 of 18 patients (67 percent) had been seeking medical advice at other institutions as outpatients before hospitalisation. That obviously might have contributed to the high cfr in the early days of novel influenza in Mexico.

Quote:

http://content.nejm.org/cgi/reprint/NEJMoa0904252v1.pdf

Pneumonia and Respiratory Failure from Swine-Origin Influenza A (H1N1) in Mexico
Rogelio Perez-Padilla et al.
published on June 29, 2009, at NEJM.org. N Engl J Med 2009;361.
(?)
The time between onset of symptoms and admission to the hospital ranged from 4 to 25 days (median, 6) (Fig. 2). All patients had fever, with temperatures higher than 38?C, cough, and dyspnea or respiratory distress. Four of the five children (all under 14 years of age) had diarrhea, and only two patients (11%) reported wheezing. The median Acute Physiology and Chronic Health Evaluation II score was 14 (range, 4 to 32), and the median Sequential Organ Failure Assessment score was 6 (range, 1 to 13); both were higher, indicating more severe abnormalities among the patients who died than among those who lived (Table 2). Twelve patients sought medical care at other institutions as outpatients before hospitalization at INER and were treated with one or more antibiotics: ceftriaxone (five patients), amikacin (three), azithromycin (one), amoxicillin?clavulanate (two) or other macrolides (three), or another agent (two). (?)

Treatment
None of the patients had received oseltamivir before admission; 14 received it in the hospital, at a dose of 75 mg twice a day for a minimum of 5 days; 11 began receiving it at admission (a mean of 8 days after the onset of symptoms) and 3 between 2 and 10 days after admission. (?)

Some of these pathogenetic mechanisms have been discussed in the following thread in conjunction with the fatal Argentina-cases.

I give a warning that IMO any politically influenced strategy of restrictions in early antiviral treatment in supposed ?mild? cases (or prophylaxis) as is done in the UK now, might increase the number of fatal cases in novel Influenza.
Antivirals save lifes !

http://www.flutrackers.com/forum/sho...=112758&page=2

related post:

http://www.flutrackers.com/forum/showthread.php?t=112758

credits to: FrenchieGirl post # 28
June 27th, 2009, 05:28 PM

Re: Argentina: unusual serious cases in young people
________________________________________
It looks like the policy is changing towards more aggressive treatment, viz:

Lungs to be "burned" in hours
There is a seriousness of patients' unusual '

"We're seeing the placement of young patients, between 15 and 50 years with pneumonia, some rapidly evolving towards a gravity which for many is unusual, in which the lung is' fire 'in a matter of hours," said Dr. Jorge San Juan, head of the Department of Intensive Care Hospital Mu?iz.

This has led to patients with these characteristics begin to be treated in an increasingly aggressive. THE NATION As reported yesterday, doctors from the Ministry of Health received the directive to take, from now on, all cases of influenza and potential influenza A (H1N1), with the recommendation to perform chest radiographs for patients with symptoms of fever and fatigue and internal quickly to all suffering from pneumonia.
"Today, it is known that the virus is circulating mass, the attitude we have with patients depends on clinical assessment made by the doctor not to become a serious case. It is not necessary to diagnose laboratory [confirming the new virus infection] to begin treatment, "said Dr. Vilma Savy, Chief of the Respiratory Virus Malbr?n institute.
(?)

[AlaskaDenise]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

I give a warning that IMO any politically influenced strategy of restrictions in early antiviral treatment in supposed ?mild? cases (or prophylaxis) as is done in the UK now, might increase the number of fatal cases in novel Influenza.Antivirals save lifes !

If supplies of anti-virals are expected to be limited, would you advise anyone with "underlying conditions" to seek anti-viral treatment ASAP when they suspect they have novel H1N1?

.

[tropical]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

I see #5 as a retorical question ended with ,
because the right treatment suggestion was supported by #3.

If the systems caught short on antivirals, that must not afects the actual existant illnessed - they must be treated adequately, no matter if the antivirals finished prior the new mutation, legal claims onto doctors aren't filled because of stranded guideliness probably.

At least they could give a chance to private antiviral somministration if the serious/death risk growed - not stimulating free roamings without early preventive treatments of suspected cases.

The actual serious victims treatment rights are failured if the doctors early appearance decisions are biased by an non-early somministration because of antiviral depots shortness, or delaying Tamiflu resistance insurgence.
Such above behaviour is pure triaging without highlight it to the patients.


Stated by post #1 news,
early treatment, and dose doubling for serious hospitalized patients:

"Two observational studies have demonstrated a reduction in mortality with oseltamivir treatment among hospitalized patients with seasonal influenza compared with untreated patients (11,12). Although early antiviral treatment (<48 hours from illness onset) is optimal to reduce illness among outpatients with seasonal influenza (13), a reduction in mortality of hospitalized persons with seasonal influenza or avian influenza A (H5N1) virus infection was reported even when oseltamivir treatment was initiated later (11,14). Early antiviral treatment of hospitalized patients with suspected influenza is recommended, including for patients admitted ≥48 hours after illness onset (13).

The patients in this series received higher oseltamivir dosing and longer duration of treatment than standard therapy. Data to inform clinical guidance are needed on viral shedding, pharmacokinetics, and clinical effectiveness of standard versus higher-dose oseltamivir treatment and on optimal duration of therapy for patients, including obese persons, with severe or progressive novel influenza A (H1N1) virus infection. Limited data for seasonal influenza treatment suggest that doubling the oseltamivir dose is well-tolerated with a comparable adverse event profile as the standard adult dose (75 mg orally twice a day) (15). Higher oseltamivir dosing and longer duration of treatment has been suggested for H5N1 (avian influenza) patients with severe pulmonary disease (14).

Until additional data are available, higher oseltamivir dosage (e.g., 150 mg orally twice a day for adults) or extending the duration of treatment can be considered for severely ill hospitalized patients with novel influenza A (H1N1) virus infection."

[AlaskaDenise]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

I see #5 as a retorical question ended with ,
because the right treatment suggestion was supported by #3.

The question in #5 was directed to a presumed professional (german-docter), while the "answer" in #3 was only a layperson's comment. My comments should never be taken as medical advice, unless I quote another qualified source. Also the question was about all underlying conditions, while the article was about only one - obesity.

.

[AlaskaDenise]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

...a reduction in mortality of hospitalized persons with seasonal influenza or avian influenza A (H5N1) virus infection was reported even when oseltamivir treatment was initiated later (11,14). Early antiviral treatment of hospitalized patients with suspected influenza is recommended, including for patients admitted ≥48 hours after illness onset (13).

It appears we need to clarify our terms. I was using the term "early" to mean measured from symptom onset & I believe that was German-docter's meaning also, while the article was using the term "early" to mean relative to admission date (which could be several days from symptom onset).

Thanks for bringing up the subject so we can clarify those differences.

.

[german-docter]

Re: MMWR Morb Mortal Wkly Rep. Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

If supplies of anti-virals are expected to be limited, would you advise anyone with "underlying conditions" to seek anti-viral treatment ASAP when they suspect they have novel H1N1?

.

It appears we need to clarify our terms. I was using the term "early" to mean measured from symptom onset & I believe that was German-docter's meaning also, while the article was using the term "early" to mean relative to admission date (which could be several days from symptom onset).
Thanks for bringing up the subject so we can clarify those differences.

.

Clarified: Yes, "early" to mean measured from symptom onset !

Stockpile of antivirals vary from country to country. Governments will decide whether restrictions or open access to antivirals may be the best option for the country which would be dependent on the capability of the national Health Services and the true amount of antiviral stockpile. The risk of a run-off in antivirals in the later course of a pandemic (then not being available for serious cases) would be a problem for political leaders. In most of the countries the decisions on how to deal with antivirals obviously have already been made (behind closed doors without information of the public) and the strategies are included in the national pandemic plans (e.g. UK and Germany).

Given the high effectiveness of antiviral therapy in novel influenza so far and the relatively low impact of adverse effects IMO for medical reasons it would be adequate to keep the barrier for antiviral therapy low. Since the results of influenza-tests are not available immediately the decision has to be made on clinical aspects (fever, ILI etc.) alone. Whether Tamiflu could be free as an ?over the counter?- drug or whether it should always be prescribed by a doctor could be another decision. In case of doubt, I guess, most people would make an individual decision in favor of taking Tamiflu. Note that Oseltamivir (Tamiflu) is approved for treatment and prophylaxis of influenza (novel influenza and seasonal influenza as well).

Summary: Antivirals are effective in the treatment and prophylaxis of (novel) influenza and should be given as early as possible after the start of symptoms. The reasons for national restrictions in the use of antivirals are (at least at the moment) not due to medical but primarily to political considerations (especially due to limited national stockpile of antivirals).
Again: Antivirals save lifes !

Quote:

http://www.ecdc.europa.eu/en/files/pdf/Publications/0907_GUI_Public_Health_use_of_Influenza_Antivirals_during_Influenza_Pandemic.pdf

ECDC INTERIM GUIDANCE
Public health use of influenza antivirals during influenza pandemics

Stockholm, June 2009 [release July 1, 2009]

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This evidence indicates that certain antiviral drugs, particularly the neuraminidase inhibitors (oseltamivir and zanamivir), offer some treatment benefits by reducing the duration of illness from influenza usually by 1?2 days and also reducing complications and the need for antibiotics in infected individuals. This effect is limited by the need for the drugs to be given early (within 48 hours of the start of symptoms). There is also some weak evidence from observational studies that the drugs might reduce morbidity and even mortality in sicker patients even if given later than the 48 hours.
Trials in healthy adults suggest infection can be prevented with prophylaxis treatment with a 70% to 90% effectiveness rate provided the drug is taken as prescribed.

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Currently the antiviral stockpiles in European countries seem to vary from coverage of a few per cent of the population to more than 50% of the population. However, even with stockpiles in place it is almost inevitable that demand for antiviral drugs will outweigh supply in a pandemic. Because of this, it is important that advanced strategic and logistical planning is carried out to optimise the usefulness of existing stockpiles. An important general principle is that having stockpiles is of limited use without the agreed objectives, protocols, administration and delivery systems to go with them.

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Based on the available evidence ECDC suggests the following prioritisation strategy for antiviral use:

1 People with more severe disease. The first priority is to treat people with more severe influenza illness even if they are beyond the 48 hour ?window? following the start of symptoms when it is considered that antivirals are effective. However, for these patients it is even more important that there are adequate supplies of appropriate antibiotics available to treat secondary infections, and other essential drugs.

2 People most at risk of severe disease. Among these, priority could be given to those most at risk of developing severe disease. For seasonal influenza these are those for whom seasonal influenza vaccination is recommended: older people, those with pre-existing chronic conditions, and healthcare workers with direct patient contact. However, this may need to be modified during a pandemic to reflect those most at risk from the pandemic strain*. When both pandemic and seasonal viruses are circulating the seasonal and pandemic higher-risk groups will need to be combined.
Some countries may want to consider giving prophylaxis in households containing people at higher risk though this would be a complicated policy to implement.

3 All people just starting an illness. After the more severe cases antivirals could be prioritised for people just starting their illness (within 48 hours of the first symptoms) because that is when these drugs are most effective.

4 Use for prophylaxis. Countries with larger stocks of antivirals can consider giving them also for prophylaxis. Candidate groups are: close contacts of cases, family contacts, and key workers for business continuity purposes. Home stockpiles are not recommended as supplies are limited though inevitably some people can be expected to request these from their doctors as they did with bird flu.

5 Healthcare workers with direct patient contact are a special case. They need to have reasonable protection with personal protective equipment. Should they become sick they need to receive antivirals promptly and to stay home from work. Countries with larger stocks may consider prophylaxis for certain groups of these workers.

Even greater challenges are posed by the organisational aspects of antiviral delivery. Namely the evidence indicating that antiviral treatment may only deliver its limited benefits if it is given within the first 48 hours following the start of symptoms. This will be particularly critical during a pandemic. Hence, for antivirals to be effective in treating infection, resources should also be put in place to develop protocols and systems to ensure their rapid delivery and administration. (...)