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L'ob?sit? peut ?tre facteur de risque pour la maladie H1N1 grave
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R?dacteur de nouvelles
de Robert Roos
Le 10 juillet 2009 (nouvelles de CIDRAP) - dans une s?rie de 10 cas de maladie grave avec le virus de la pand?mie H1N1 au Michigan, neuf patients ?taient ob?ses, proposant que les personnes tr?s de poids excessif puissent ?tre particuli?rement vuln?rables aux infections H1N1 repr?sentant un danger pour la vie, le centres pour le contr?le et la pr?vention des maladies (CDC) rapport? aujourd'hui.
Sept des neuf patients ob?ses ont ?t? consid?r?s extr?mement ob?ses, et trois des neuf patients sont morts, selon le rapport, ?dit? comme exp?dition de MMWR.
Les ? cliniciens devraient se rendre compte du potentiel pour des complications graves de l'infection originale de virus de la grippe (H1N1), en particulier dans les patients extr?mement ob?ses, ? le rapport de CDC indique.
Le rapport n'est pas la premi?re fois que l'ob?sit? a ?t? cit?e en tant que conclusion inopin?ment commune dans les patients pr?sentant la maladie H1N1 grave, mais les bonnes donn?es sur la mati?re sont rares, ont indiqu? Dr. Anthony Fiore, un ?pid?miologue m?dical dans la Division de grippe de CDC et un co-auteur du rapport.
? On l'a not? dans certaines des donn?es qui sont re?ues par l'OMS [l'organisation mondiale de la sant?], ? Fiore a dit des nouvelles de CIDRAP. ? C'a ?t? un ph?nom?ne que d'autres personnes ont not?, mais je ne pense pas dans une sorte quantitative de mani?re. ?
Profil de s?rie
Les 10 patients d?crits dans le rapport ont ?t? mentionn?s l'unit? chirurgicale de soins intensifs (SICU) au syst?me de sant? d'Universit? du Michigan entre les 26 mai et 18 juin. L'unit? se sp?cialise en soignant des patients avec le syndrome de d?tresse respiratoire aigu (ARD).
Les patients se sont ?tendus de 21 ? 53 ann?es, avec un ?ge m?dian de 46, et tout sauf un ?taient des hommes. Neuf ont ?t? classifi?s comme ob?ses sur la base d'un index de masse de corps plus de 30, et sept d'entre eux ont eu un index de 40 ou plus de, classifi? comme extr?mement ob?se. Deux des patients-un ob?ses de eux un asthme fumeur-eu, et un tiers ont eu l'affection pulmonaire chronique.
Chacun des 10 patients a eu besoin de la ventilation m?canique avanc?e, et deux ont ?t? trait?s avec l'oxyg?nation extracorporeal de membrane (ECMO). Six d'entre eux ont ?galement eu besoin du traitement pour l'?chec r?nal aigu. Neuf ont eu le syndrome multiorgan de dysfonctionnement une fois admis au SICU, et neuf soufferts du choc septique. Cinq patients se sont av?r?s pour avoir les emboles pulmonaires ? l'heure d'admission ou de plus tard.
Tous les patients ont re?u le traitement antiviral, mais les auteurs ont estim? que c'a ?t? commenc? une m?diane de 8 jours apr?s d?but-bien de sympt?me au del? de la fen?tre de deux jours recommand?e pour la plus grande efficacit?.
Au 8 juillet, deux patients recevaient toujours ECMO ou ventilation m?canique, cinq avaient ?t? transf?r?s de nouveau aux h?pitaux de r?f?rence en ?tat stable, et trois ?taient morts, le rapport indique.
Aucune ?vidence de l'infection bact?rienne n'a ?t? trouv?e dans les patients l'uns des, tous de qui a re?u le traitement antibiotique avant et apr?s qu'elles aient ?t? admises au SICU. Mais les auteurs disent qu'ils ne pourraient pas exclure la possibilit? d'infection bact?rienne non d?tect?e
Le rapport indique que les r?sultats globaux sugg?rent que les dommages de poumon des patients aient ?t? provoqu?s par la pneumonie virale primaire, mais leurs propres immuno-r?actions intenses pourraient avoir contribu? aussi bien.
Pr?dominance d'ob?sit? appel?e frappe
? La forte pr?sence de la s?rie d'ob?sit? dans ce cas-ci frappe, ? les ?tats de rapport.
Elle indique qu'elle est inconnue si l'ob?sit? est un facteur de risque ind?pendant pour des complications graves de l'infection H1N1. L'ob?sit? n'a pas ?t? ?tiquet?e comme facteur de risque pour la grippe saisonni?re grave. Cependant, une ?tude a prouv? que les souris avec l'ob?sit? suivre un r?gime-induite ?taient pour mourir des infections saisonni?res de grippe que les souris maigres ?taient, les ?tats de rapport.
En outre, elle note que les patients extr?mement ob?ses de grippe, compar?s aux patients normaux de poids, ont une plus forte pr?sence d'autres ?tats de sant? qui augmentent le risque de complications de grippe, y compris le coeur, le poumon, le foie, et les maladies m?taboliques.
? Ce pourrait r?ellement ?tre une issue que ce [ob?sit?] est un marqueur d'autres maladies chroniques ?tant ? la base, ? plut?t qu'un facteur de risque ind?pendant pour les complications H1N1, a indiqu? Fiore.
Il a dit qu'il est possible que l'ob?sit? conf?re ?galement un risque pour des complications graves dans la grippe saisonni?re, mais elle juste n'a pas ?t? identifi?e avant.
Fiore a indiqu? que la CDC ?tudie l'issue plus loin. ? Nous allons certainement regarder l'information dans nos donn?es de hosptalization d'une perspective nationale. Elle est provocante parce que ce n'est pas la sorte habituelle de facteur de risque m?dical que les gens cochent. Elle n'appara?t pas dans les codes habituels comme l'asthme ou l'arr?t du coeur congestif. ?
? Il y a une grande pr?dominance de l'ob?sit? dans le pays en ce moment, et de l'ob?sit? grave, ainsi nous nous attendrions ? ce que quelques patients de grippe aient ces conditions, mais nous n'avons pas une figure nationale, ? il avons comment?. Sur la base des enqu?tes de t?l?phone, la CDC a rapport? cette semaine que 26.1% d'Am?ricains ?taient ob?ses en 2008, ? partir de 25.6% de 2007.
Les fonctionnaires de CDC ont pr?c?demment mentionn? l'ob?sit? en tant que conclusion dans quelques patients pr?sentant les infections H1N1 graves. Dans une conf?rence de presse du 19 mai, Dr. Anne Schuchat a comment?, ? nous ont ?t? ?tonn?s par la fr?quence de l'ob?sit? parmi les cas graves ces nous le ′ VE d?pistant. Je pense que c' est un r?sultat important. La question de si les gens avec l'ob?sit? doivent ?tre trait?s diff?remment en termes de traitement antiviral ou vaccinations saisonni?res de grippe est une nous ′ au sujet du regard dans. ?
Le rapport d'aujourd'hui note que les 10 patients ont re?u le traitement d'oseltamivir dans des doses plus ?lev?es et sur une plus longue p?riode que la normale. Il indique que jusqu'? ce que plus soit connu, des r?gimes accrus d'oseltamivir peuvent ?tre consid?r?s pour les patients s?v?rement malades H1N1.
CDC. patients d'Intensif-soin avec le virus original grave infection-Michigan, juin 2009 de la grippe A (H1N1). Exp?dition de MMWR le 10 juillet 2009 ; 58 : 1-4 [texte int?gral]
Voyez ?galement :
Transcription de conf?rence de presse de CDC du 19 mai
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
* 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 class="data-table"> <tbody> <tr> <th class="header-row" scope="col" colspan="13"> TABLE. Selected characteristics of intensive-care patients with severe novel influenza A (H1N1) virus infection --- Michigan, June 2009
</th> </tr> <tr> <th class="column-head" scope="col" rowspan="6"> Patient
</th> <th class="column-head" scope="col" rowspan="6"> Age (yrs)
<!-- p class="table-data-8pt-bold">(yrs)</p --> </th> <th class="column-head" scope="col" rowspan="6"> Sex
</th> <th class="column-head" scope="col" rowspan="6"> Underlying conditions
</th> <th class="column-head" scope="col" rowspan="6"> Initial signs or symptoms
</th> <th class="column-head" scope="col" rowspan="6"> BMI*
</th> <th class="column-head" scope="col" rowspan="6"> No. days between onset and first hospitalization
</th> <th class="column-head" scope="col" rowspan="6"> No. days between illness onset and SICU? admission
</th> <th class="column-head" scope="col" rowspan="6"> Advanced mechanical ventilation
</th> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col" rowspan="6"> Vaso-pressors
</th> <th class="column-head" scope="col" rowspan="6"> Outcome**
</th> </tr> <tr> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> </tr> <tr> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> </tr> <tr> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> </tr> <tr> <th class="column-head" scope="col" colspan="2"> Diagnosis
</th> </tr> <tr> <th class="column-head" scope="col"> PE?
</th> <th class="column-head" scope="col"> MODS?
</th> </tr> <tr> <td scope="row" class="data-row"> 1
</td> <td class="data-row"> 28
</td> <td class="data-row"> M
</td> <td class="data-row"> Asthma
</td> <td class="data-row"> High fever, cough, sore throat that progressed to blood-tinged sputum, decreasing mental status
</td> <td class="data-row"> 34.2
</td> <td class="data-row"> 7
</td> <td class="data-row"> 8
</td> <td class="data-row"> HFOV??
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Death
</td> </tr> <tr> <td scope="row" class="data-row"> 2
</td> <td class="data-row"> 21
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, sore throat, dry cough, sneezing; progressed to tachypnea and dyspnea
</td> <td class="data-row"> 50.5
</td> <td class="data-row"> 7
</td> <td class="data-row"> 8
</td> <td class="data-row"> Bilevel
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 3
</td> <td class="data-row"> 48
</td> <td class="data-row"> F
</td> <td class="data-row"> Asthma, smoker
</td> <td class="data-row"> Shortness of breath, rhinorrhea, non-productive cough
</td> <td class="data-row"> 58.9
</td> <td class="data-row"> 5
</td> <td class="data-row"> 9
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 4
</td> <td class="data-row"> 35
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Upper respiratory tract illness symptoms
</td> <td class="data-row"> 51.7
</td> <td class="data-row"> 6
</td> <td class="data-row"> 8
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> Yes
</td> <td class="data-row"> No
</td> <td class="data-row"> No
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 5
</td> <td class="data-row"> 43
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, cough, malaise, chills, sweats
</td> <td class="data-row"> 48.7
</td> <td class="data-row"> 4
</td> <td class="data-row"> 5
</td> <td class="data-row"> HFOV to ECMO??
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Death
</td> </tr> <tr> <td scope="row" class="data-row"> 6
</td> <td class="data-row"> 52
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Sinus drainage, cough with clear sputum production, decreased appetite
</td> <td class="data-row"> NA??
</td> <td class="data-row"> 6
</td> <td class="data-row"> 13
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 7
</td> <td class="data-row"> 44
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, productive cough with black/red sputum, nausea, vomiting, diarrhea
</td> <td class="data-row"> 50.2
</td> <td class="data-row"> 5
</td> <td class="data-row"> 7
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Death
</td> </tr> <tr> <td scope="row" class="data-row"> 8
</td> <td class="data-row"> 51
</td> <td class="data-row"> M
</td> <td class="data-row"> Granulomatous chronic lung disease
</td> <td class="data-row"> Fever, worsening dyspnea, rigors, nausea, vomiting, malaise
</td> <td class="data-row"> 39.7
</td> <td class="data-row"> 1
</td> <td class="data-row"> 9
</td> <td class="data-row"> HFOV to ECMO
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> ECMO plus ventilator
</td> </tr> <tr> <td scope="row" class="data-row"> 9
</td> <td class="data-row"> 53
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, chills, cough, shortness of breath
</td> <td class="data-row"> 38.5
</td> <td class="data-row"> 7
</td> <td class="data-row"> 16
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 10
</td> <td class="data-row"> 53
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, cough
</td> <td class="data-row"> 47.8
</td> <td class="data-row"> 6
</td> <td class="data-row"> 6
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> HFOV
</td> </tr> <tr> <td scope="row" class="footnote-row" colspan="13"> * 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.
</td> </tr> </tbody> </table>
<!-- end MAIN CONTENT CELL --> <!-- FOOTER -->
Traduction machine
R?dacteur de nouvelles
de Robert RoosLe 10 juillet 2009 (nouvelles de CIDRAP) - dans une s?rie de 10 cas de maladie grave avec le virus de la pand?mie H1N1 au Michigan, neuf patients ?taient ob?ses, proposant que les personnes tr?s de poids excessif puissent ?tre particuli?rement vuln?rables aux infections H1N1 repr?sentant un danger pour la vie, le centres pour le contr?le et la pr?vention des maladies (CDC) rapport? aujourd'hui.
Sept des neuf patients ob?ses ont ?t? consid?r?s extr?mement ob?ses, et trois des neuf patients sont morts, selon le rapport, ?dit? comme exp?dition de MMWR.
Les ? cliniciens devraient se rendre compte du potentiel pour des complications graves de l'infection originale de virus de la grippe (H1N1), en particulier dans les patients extr?mement ob?ses, ? le rapport de CDC indique.
Le rapport n'est pas la premi?re fois que l'ob?sit? a ?t? cit?e en tant que conclusion inopin?ment commune dans les patients pr?sentant la maladie H1N1 grave, mais les bonnes donn?es sur la mati?re sont rares, ont indiqu? Dr. Anthony Fiore, un ?pid?miologue m?dical dans la Division de grippe de CDC et un co-auteur du rapport.
? On l'a not? dans certaines des donn?es qui sont re?ues par l'OMS [l'organisation mondiale de la sant?], ? Fiore a dit des nouvelles de CIDRAP. ? C'a ?t? un ph?nom?ne que d'autres personnes ont not?, mais je ne pense pas dans une sorte quantitative de mani?re. ?
Profil de s?rie
Les 10 patients d?crits dans le rapport ont ?t? mentionn?s l'unit? chirurgicale de soins intensifs (SICU) au syst?me de sant? d'Universit? du Michigan entre les 26 mai et 18 juin. L'unit? se sp?cialise en soignant des patients avec le syndrome de d?tresse respiratoire aigu (ARD).
Les patients se sont ?tendus de 21 ? 53 ann?es, avec un ?ge m?dian de 46, et tout sauf un ?taient des hommes. Neuf ont ?t? classifi?s comme ob?ses sur la base d'un index de masse de corps plus de 30, et sept d'entre eux ont eu un index de 40 ou plus de, classifi? comme extr?mement ob?se. Deux des patients-un ob?ses de eux un asthme fumeur-eu, et un tiers ont eu l'affection pulmonaire chronique.
Chacun des 10 patients a eu besoin de la ventilation m?canique avanc?e, et deux ont ?t? trait?s avec l'oxyg?nation extracorporeal de membrane (ECMO). Six d'entre eux ont ?galement eu besoin du traitement pour l'?chec r?nal aigu. Neuf ont eu le syndrome multiorgan de dysfonctionnement une fois admis au SICU, et neuf soufferts du choc septique. Cinq patients se sont av?r?s pour avoir les emboles pulmonaires ? l'heure d'admission ou de plus tard.
Tous les patients ont re?u le traitement antiviral, mais les auteurs ont estim? que c'a ?t? commenc? une m?diane de 8 jours apr?s d?but-bien de sympt?me au del? de la fen?tre de deux jours recommand?e pour la plus grande efficacit?.
Au 8 juillet, deux patients recevaient toujours ECMO ou ventilation m?canique, cinq avaient ?t? transf?r?s de nouveau aux h?pitaux de r?f?rence en ?tat stable, et trois ?taient morts, le rapport indique.
Aucune ?vidence de l'infection bact?rienne n'a ?t? trouv?e dans les patients l'uns des, tous de qui a re?u le traitement antibiotique avant et apr?s qu'elles aient ?t? admises au SICU. Mais les auteurs disent qu'ils ne pourraient pas exclure la possibilit? d'infection bact?rienne non d?tect?e
Le rapport indique que les r?sultats globaux sugg?rent que les dommages de poumon des patients aient ?t? provoqu?s par la pneumonie virale primaire, mais leurs propres immuno-r?actions intenses pourraient avoir contribu? aussi bien.
Pr?dominance d'ob?sit? appel?e frappe
? La forte pr?sence de la s?rie d'ob?sit? dans ce cas-ci frappe, ? les ?tats de rapport.
Elle indique qu'elle est inconnue si l'ob?sit? est un facteur de risque ind?pendant pour des complications graves de l'infection H1N1. L'ob?sit? n'a pas ?t? ?tiquet?e comme facteur de risque pour la grippe saisonni?re grave. Cependant, une ?tude a prouv? que les souris avec l'ob?sit? suivre un r?gime-induite ?taient pour mourir des infections saisonni?res de grippe que les souris maigres ?taient, les ?tats de rapport.
En outre, elle note que les patients extr?mement ob?ses de grippe, compar?s aux patients normaux de poids, ont une plus forte pr?sence d'autres ?tats de sant? qui augmentent le risque de complications de grippe, y compris le coeur, le poumon, le foie, et les maladies m?taboliques.
? Ce pourrait r?ellement ?tre une issue que ce [ob?sit?] est un marqueur d'autres maladies chroniques ?tant ? la base, ? plut?t qu'un facteur de risque ind?pendant pour les complications H1N1, a indiqu? Fiore.
Il a dit qu'il est possible que l'ob?sit? conf?re ?galement un risque pour des complications graves dans la grippe saisonni?re, mais elle juste n'a pas ?t? identifi?e avant.
Fiore a indiqu? que la CDC ?tudie l'issue plus loin. ? Nous allons certainement regarder l'information dans nos donn?es de hosptalization d'une perspective nationale. Elle est provocante parce que ce n'est pas la sorte habituelle de facteur de risque m?dical que les gens cochent. Elle n'appara?t pas dans les codes habituels comme l'asthme ou l'arr?t du coeur congestif. ?
? Il y a une grande pr?dominance de l'ob?sit? dans le pays en ce moment, et de l'ob?sit? grave, ainsi nous nous attendrions ? ce que quelques patients de grippe aient ces conditions, mais nous n'avons pas une figure nationale, ? il avons comment?. Sur la base des enqu?tes de t?l?phone, la CDC a rapport? cette semaine que 26.1% d'Am?ricains ?taient ob?ses en 2008, ? partir de 25.6% de 2007.
Les fonctionnaires de CDC ont pr?c?demment mentionn? l'ob?sit? en tant que conclusion dans quelques patients pr?sentant les infections H1N1 graves. Dans une conf?rence de presse du 19 mai, Dr. Anne Schuchat a comment?, ? nous ont ?t? ?tonn?s par la fr?quence de l'ob?sit? parmi les cas graves ces nous le ′ VE d?pistant. Je pense que c' est un r?sultat important. La question de si les gens avec l'ob?sit? doivent ?tre trait?s diff?remment en termes de traitement antiviral ou vaccinations saisonni?res de grippe est une nous ′ au sujet du regard dans. ?
Le rapport d'aujourd'hui note que les 10 patients ont re?u le traitement d'oseltamivir dans des doses plus ?lev?es et sur une plus longue p?riode que la normale. Il indique que jusqu'? ce que plus soit connu, des r?gimes accrus d'oseltamivir peuvent ?tre consid?r?s pour les patients s?v?rement malades H1N1.
CDC. patients d'Intensif-soin avec le virus original grave infection-Michigan, juin 2009 de la grippe A (H1N1). Exp?dition de MMWR le 10 juillet 2009 ; 58 : 1-4 [texte int?gral]
Voyez ?galement :
Transcription de conf?rence de presse de CDC du 19 mai
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
- CDC. Swine influenza A (H1N1) infection in two children---Southern California, March--April 2009. MMWR 2009;58:400--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.
- CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR 2008;57(No. RR-7).
- 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.
- 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.
- 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.
- 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.
- 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.
- van Wissen M, Keller TT, Ronkes B, et al. Influenza infection and risk of acute pulmonary embolism. Thromb J 2007;5:16.
- Ohrui T, Takahashi H, Ebihara S, et al. Influenza A virus infection and pulmonary microthromboembolism. Tohoku J Exp Med 2000;192:81--6.
- 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.
- 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.
- 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.
- 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.
- 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 class="data-table"> <tbody> <tr> <th class="header-row" scope="col" colspan="13"> TABLE. Selected characteristics of intensive-care patients with severe novel influenza A (H1N1) virus infection --- Michigan, June 2009
</th> </tr> <tr> <th class="column-head" scope="col" rowspan="6"> Patient
</th> <th class="column-head" scope="col" rowspan="6"> Age (yrs)
<!-- p class="table-data-8pt-bold">(yrs)</p --> </th> <th class="column-head" scope="col" rowspan="6"> Sex
</th> <th class="column-head" scope="col" rowspan="6"> Underlying conditions
</th> <th class="column-head" scope="col" rowspan="6"> Initial signs or symptoms
</th> <th class="column-head" scope="col" rowspan="6"> BMI*
</th> <th class="column-head" scope="col" rowspan="6"> No. days between onset and first hospitalization
</th> <th class="column-head" scope="col" rowspan="6"> No. days between illness onset and SICU? admission
</th> <th class="column-head" scope="col" rowspan="6"> Advanced mechanical ventilation
</th> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col" rowspan="6"> Vaso-pressors
</th> <th class="column-head" scope="col" rowspan="6"> Outcome**
</th> </tr> <tr> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> </tr> <tr> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> </tr> <tr> <th class="column-head" scope="col">
</th> <th class="column-head" scope="col">
</th> </tr> <tr> <th class="column-head" scope="col" colspan="2"> Diagnosis
</th> </tr> <tr> <th class="column-head" scope="col"> PE?
</th> <th class="column-head" scope="col"> MODS?
</th> </tr> <tr> <td scope="row" class="data-row"> 1
</td> <td class="data-row"> 28
</td> <td class="data-row"> M
</td> <td class="data-row"> Asthma
</td> <td class="data-row"> High fever, cough, sore throat that progressed to blood-tinged sputum, decreasing mental status
</td> <td class="data-row"> 34.2
</td> <td class="data-row"> 7
</td> <td class="data-row"> 8
</td> <td class="data-row"> HFOV??
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Death
</td> </tr> <tr> <td scope="row" class="data-row"> 2
</td> <td class="data-row"> 21
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, sore throat, dry cough, sneezing; progressed to tachypnea and dyspnea
</td> <td class="data-row"> 50.5
</td> <td class="data-row"> 7
</td> <td class="data-row"> 8
</td> <td class="data-row"> Bilevel
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 3
</td> <td class="data-row"> 48
</td> <td class="data-row"> F
</td> <td class="data-row"> Asthma, smoker
</td> <td class="data-row"> Shortness of breath, rhinorrhea, non-productive cough
</td> <td class="data-row"> 58.9
</td> <td class="data-row"> 5
</td> <td class="data-row"> 9
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 4
</td> <td class="data-row"> 35
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Upper respiratory tract illness symptoms
</td> <td class="data-row"> 51.7
</td> <td class="data-row"> 6
</td> <td class="data-row"> 8
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> Yes
</td> <td class="data-row"> No
</td> <td class="data-row"> No
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 5
</td> <td class="data-row"> 43
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, cough, malaise, chills, sweats
</td> <td class="data-row"> 48.7
</td> <td class="data-row"> 4
</td> <td class="data-row"> 5
</td> <td class="data-row"> HFOV to ECMO??
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Death
</td> </tr> <tr> <td scope="row" class="data-row"> 6
</td> <td class="data-row"> 52
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Sinus drainage, cough with clear sputum production, decreased appetite
</td> <td class="data-row"> NA??
</td> <td class="data-row"> 6
</td> <td class="data-row"> 13
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 7
</td> <td class="data-row"> 44
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, productive cough with black/red sputum, nausea, vomiting, diarrhea
</td> <td class="data-row"> 50.2
</td> <td class="data-row"> 5
</td> <td class="data-row"> 7
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Death
</td> </tr> <tr> <td scope="row" class="data-row"> 8
</td> <td class="data-row"> 51
</td> <td class="data-row"> M
</td> <td class="data-row"> Granulomatous chronic lung disease
</td> <td class="data-row"> Fever, worsening dyspnea, rigors, nausea, vomiting, malaise
</td> <td class="data-row"> 39.7
</td> <td class="data-row"> 1
</td> <td class="data-row"> 9
</td> <td class="data-row"> HFOV to ECMO
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> ECMO plus ventilator
</td> </tr> <tr> <td scope="row" class="data-row"> 9
</td> <td class="data-row"> 53
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, chills, cough, shortness of breath
</td> <td class="data-row"> 38.5
</td> <td class="data-row"> 7
</td> <td class="data-row"> 16
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Improved, transferred
</td> </tr> <tr> <td scope="row" class="data-row"> 10
</td> <td class="data-row"> 53
</td> <td class="data-row"> M
</td> <td class="data-row"> None
</td> <td class="data-row"> Fever, cough
</td> <td class="data-row"> 47.8
</td> <td class="data-row"> 6
</td> <td class="data-row"> 6
</td> <td class="data-row"> HFOV
</td> <td class="data-row"> No
</td> <td class="data-row"> Yes
</td> <td class="data-row"> Yes
</td> <td class="data-row"> HFOV
</td> </tr> <tr> <td scope="row" class="footnote-row" colspan="13"> * 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.
</td> </tr> </tbody> </table>
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