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Research Letters |

Rhabdomyolysis Associated With 2009 Influenza A(H1N1) FREE

Estela Ayala, MD; Frank T. Kagawa, MD; John H. Wehner, MD; James Tam, MD; Daya Upadhyay, MD
JAMA. 2009;302(17):1863-1864. doi:10.1001/jama.2009.1582.
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To the Editor: Rhabdomyolysis, which has been associated with infections from various strains of influenza,1 requires prompt clinical suspicion and targeted clinical management to prevent renal failure. We are not aware of prior reports of rhabdomyolysis in patients with 2009 influenza A(H1N1)–induced respiratory failure.

A 28-year-old woman presented in June 2009 with 1 week of shortness of breath, muscle aches, and fevers. Two days before presentation, she had been prescribed moxifloxacin and hydrocodone/acetaminophen for presumed pneumonia without any significant improvement. She denied any significant medical history or regular medication use prior to her illness, had a family history of sickle cell trait, and smoked 2 to 3 cigarettes daily for 1 year. On examination, she was obese (body mass index, 40; calculated as weight in kilograms divided by height in meters squared), febrile (body temperature, 38.3°C), tachycardic, and tachypneic, with a digital pulse oximetry saturation of 80% on room air.

Her admission laboratory tests included white blood cell count, 2800/μL (normal, 3500-11 000/μL); hematocrit, 45% (normal, 36%-46%); platelet count, 128 × 103/μL (normal, 140-450 × 103/μL); potassium, 3.6 mEq/L (normal, 3.5-5.0 mEq/L); ionized calcium, 4.16 mg/dL (normal, 4.64-5.28 mg/dL; to convert to mmol/L, multiply by 0.25); phosphorus, 2.0 mg/dL (normal, 2.5-4.8 mg/dL); serum creatinine, 0.9 mg/dL (normal, 0.5-1.2 mg/dL); lactic dehydrogenase, 1875 U/L (normal, 112-220 U/L); and creatine kinase level, 27 820 U/L (normal, 13-156 U/L). The urinalysis revealed 3+ hemoglobin and 7 red blood cells per high-power field; myoglobin was not assayed. A chest radiograph revealed diffuse bilateral alveolar infiltrates.

Within a few hours of her presentation, the patient was intubated and mechanically ventilated for hypoxemic respiratory failure. She received broad-spectrum antimicrobial agents, including 5 days of oseltamivir, 75 mg twice daily, for suspected 2009 influenza A(H1N1) pneumonia. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal smear performed at the Santa Clara County Public Health Department was negative for influenza A. Fiberoptic bronchoscopy revealed extremely erythematous and friable mucosa with bloody bronchoalveolar lavage (BAL) fluid that grew influenza A, identified as 2009 H1N1 by the California Department of Public Health laboratory. Treatment with intense hydration (22 L over 96 hours) and intravenous sodium bicarbonate was initiated for suspected rhabdomyolysis, following which there was a progressive reduction in creatine kinase levels (Figure). Her creatinine level remained normal. A search for other etiologies of rhabdomyolysis was unrevealing. The patient was extubated on hospital day 15 and discharged home 3 days later. She provided consent for publishing this case report, which was approved by the Santa Clara Valley Medical Center human subjects review committee.

Place holder to copy figure label and caption
Figure. Creatine Kinase in Patient With 2009 Influenza A(H1N1)
Graphic Jump Location

Normal range for creatine kinase is 13 to 156 U/L.

Rhabdomyolysis may occur because of genetic defects, trauma, exertion, muscle hypoxia, body-temperature changes, metabolic and electrolyte disorders, drugs and toxins, and bacterial or viral infections.1 Although the incidence of rhabdomyolysis associated with viral pneumonia is not clearly defined, a case series of 63 patients with influenza pneumonia showed 9.5% had rhabdomyolysis.2

Although the disease spectrum of 2009 H1N1 is unclear, it may have a greater propensity for muscular inflammation than other viral infections or seasonal influenza serotypes. A recent report3 showed mild to moderate elevation of creatine kinase levels in 62% of patients with 2009 H1N1 pneumonia and respiratory failure. However, the true incidence of rhabdomyolysis in 2009 H1N1 and the mechanisms underlying its pathogenesis remain unknown. It has been presumed that viral invasion, viral toxin, or cytokine may induce myonecrosis causing rhabdomyolysis.4

Although real-time RT-PCR has advanced the ability to diagnose 2009 H1N1,5 a negative nasopharyngeal specimen may not rule out a lower respiratory tract infection, as was seen in this patient. In patients with pulmonary involvement, samples such as BAL may improve the diagnostic yield.

In the setting of a worldwide pandemic, physicians should be aware that rhabdomyolysis may present as a complication in a critically ill patient with 2009 influenza A(H1N1)–induced respiratory failure.

Author Contributions: Dr Kagawa had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Ayala, Kagawa, Wehner.

Acquisition of data: Ayala, Wehner, Tam.

Analysis and interpretation of data: Ayala, Wehner, Upadhyay.

Drafting of the manuscript: Ayala, Kagawa, Upadhyay.

Critical revision of the manuscript for important intellectual content: Ayala, Kagawa, Wehner, Tam, Upadhyay.

Study supervision: Kagawa, Wehner, Upadhyay.

Financial Disclosures: None reported.

Additional Contributions: Vibha Mohindra, MD, Santa Clara Valley Medical Center, had the insight to suggest checking a creatine kinase level on this patient. She received no compensation for her contribution.

Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury.  N Engl J Med. 2009;361(1):62-72
PubMed   |  Link to Article
Takayanagi N, Tokunaga D, Kubota M,  et al.  Community-acquired pneumonia with rhabdomyolysis.  Nihon Kokyuki Gakkai Zasshi. 2005;43(12):731-735
PubMed
Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S,  et al; INER Working Group on Influenza.  Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico.  N Engl J Med. 2009;361(7):680-689
PubMed   |  Link to Article
Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis: three case reports and review.  Clin Infect Dis. 1996;22(4):642-649
PubMed   |  Link to Article
 CDC protocol of realtime RTPCR for influenza A(H1N1) [April 30, 2009]. World Health Organization Web site. http://www.who.int/csr/resources/publications/swineflu/realtimeptpcr/en/index.html. Accessed September 21, 2009

Figures

Place holder to copy figure label and caption
Figure. Creatine Kinase in Patient With 2009 Influenza A(H1N1)
Graphic Jump Location

Normal range for creatine kinase is 13 to 156 U/L.

Tables

References

Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury.  N Engl J Med. 2009;361(1):62-72
PubMed   |  Link to Article
Takayanagi N, Tokunaga D, Kubota M,  et al.  Community-acquired pneumonia with rhabdomyolysis.  Nihon Kokyuki Gakkai Zasshi. 2005;43(12):731-735
PubMed
Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S,  et al; INER Working Group on Influenza.  Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico.  N Engl J Med. 2009;361(7):680-689
PubMed   |  Link to Article
Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis: three case reports and review.  Clin Infect Dis. 1996;22(4):642-649
PubMed   |  Link to Article
 CDC protocol of realtime RTPCR for influenza A(H1N1) [April 30, 2009]. World Health Organization Web site. http://www.who.int/csr/resources/publications/swineflu/realtimeptpcr/en/index.html. Accessed September 21, 2009

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