- Email: [email protected]
Amantadine and pneumonia in elderly stroke patients
metabolism and an increased rate of aspiration pneumonia.2 However, they omitted to comment on whether the swallowing reflex was assessed in their patients, and some patients might have developed community-acquired pneumonia rather than aspiration pneumonia. Hence, the recorded short-term beneficial effect of amantadine in the prevention of pneumonia may be attributable to its antiviral effect rather than the dopamine-release mechanism. As an antiviral drug, amantadine has been used in prophylaxis and treatment of influenza A virus, 3 a virus that is often implicated in the pathogenesis of pneumonia, especially in the elderly population. 4 T h e recognition of this virus infection is important since nursing home outbreaks of amantadine-resistant influenza A are becoming increasingly c o m m o n .4,5 The routine use of amantadine in elderly stroke patients to prevent pneumonia should not be encouraged before more is known about viral resistance to this agent. N N Chan EURODIAB, Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK (e-mail: [email protected]) 1
2
3
4
5
Nakagawa T, Wada H, Sekizawa K, Arai H, Sasaki H. Amantadine and pneumonia. Lancet 1999; 353: 1157. Nakagawa T, Sekizawa K, Arai H, Kikuchi R, Manabe K, Sasaki H. High incidence of pneumonia in elderly patients with basal ganglia infarction. Arch Intern Med 1997; 157: 321–24. Zimmerman RK, Ruben FL, Ahwesh ER. Influenza, influenza vaccine, and amantadine/rimantadine. J Fam Pract 1997; 45: 107–22. Mast EE, Harmon MW, Gravenstein S, et al. Emergence and possible transmission of amantadine-resistant virus during nursing home outbreaks of influenza A IH3N2. Am J Epidemiol 1991; 134: 988–97. Houck P, Hemhill M, LaCroix S, Hirsh D, Cox N. Amantadine-resistant influenza A in nursing homes. Identification of a resistant virus prior to drug use. Arch Intern Med 1995; 155: 533–37.
independence and provides a score ranging from 0 for total disability/dependence to 100 for full function/independence. The Barthel index of daily living activity was 73 (SE 5) in the patients who received amantadine and 76 (8) in those who received no active treatment. Daily living activities of the patients were high and none had depressed or altered consciousness. Furthermore, none of our patients had clinical symptoms of gastro-oesophageal reflux, although 16% (31) of 195 patients were reported to have cough without heartburn or other typical symptoms of gastro-oesophageal reflux.2 Therefore, improvement of consciousness and lower-oesophageal sphincter function might not be the most likely mechanism for beneficial effects induced by amantadine. N N Chan suggests that the beneficial effects of amantadine in the prevention of pneumonia are attributable to antiviral effects. During 3 years’ follow-up, two outbreaks of influenza A virus infection took place in the winter in the area we studied. Although 70% of total pneumonia occurred out of the winter season, our results could have been affected by the antiviral effects of amantadine. Therefore, the possible mechanism of amantadine-induced effects on prevention of pneumonia remains to be proven. We agree that more patients and longer follow-up are needed to establish amantadine therapy in the prevention of pneumonia in stroke patients. Kiyohisa Sekizawa, Masaru Yanai, Mutsuo Yamaya, Hiroyuki Arai, *Hidetada Sasaki Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai 980, Japan 1
Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Maryland State Med J 1965; 14: 61–65. 2 Allen CJ, Anvari M. Gastro-oesophageal reflux related cough and its response to laparoscopic fundoplication. Thorax 1998: 53: 963–68.
Authors’ reply Sir—We agree that the role of amantadine in the prevention of pneumonia in stroke patients is complex. As Shinji Teramoto and colleagues state, amantadine may improve either conscious state or lower-oesophageal sphincter function. Their comments, however, give us the opportunity to expand on the clinical details of our patients. We assessed overall neurological disability of the patients with the Barthel index,1 which consists of ten items for evaluating functional
THE LANCET • Vol 353 • June 19, 1999
Sir—In Takuma Nakagawa and c o l l e a g u e s 1 randomised study of amantadine (100 mg daily), the risk of pneumonia was lowered by about 20% in non-bedridden patients with a history of stroke. Their hypothesis is that amantadine improves the swallowing reflex. However, the investigators did not discuss the risk of influenza infection in their elderly patients (mean age 75–77 years in both groups). Influenza infection can cause significant morbidity and mortality in the elderly (with or without stroke),
and predisposes patients to bacterial pneumonia, especially due to Streptococcus pneumonia, Staphylococcus aureus, or gram-negative enteric pathogens.2 Three manifestations of pneumonia are associated with influenza: primary viral pneumonia, secondary bacterial pneumonia, and mixed viral and bacterial pneumonias. Influenza vaccination is associated with an overall reduction of 39% for pneumonia hospital admissions.3 In their earlier study, Nakagawa and c o w o r k e r s 4 showed that elderly bedridden patients with multiple cerebral infarctions can be effectively immunised against influenza. Since amantadine is an available antiinfluenza medication,5 it is important to know the immunisation status of the patients, and whether influenza A outbreaks occurred during the 3 years of the study. Although amantadine prevents outbreaks of influenza A, side-effects are common (gastrointestinal and central nervous system), especially in elderly people. In addition, because amantadine clearance is dependent on renal function, the dose of 100 mg daily may need to be reduced according to estimates of renal function. New antiviral agents to inhibit influenza neuraminidase are under development for use in prophylaxis and treatment of influenza A and B infections, with excellent tolerability profiles.5 A m a n t a d i n e lowers the rate of pneumonia in patients with cerebral infarctions because this drug lowers the incidence of influenza infection in this high-risk population, rather than by improving the swallowing reflex, as Nakagawa and colleagues suggest. Should our explanation be the case, influenza vaccination is probably more effective. Christophe Trivalle, Renée Sebag-Lanoe Service de Gérontologie et de Soins Palliatifs, Hôpital Paul Brousse, F-94804 Villejuif Cedex, France (e-mail: [email protected]) 1
Nakagawa T, Wada H, Sekizawa K, Arai H, Sasaki H. Amantadine and pneumonia. Lancet 1999; 353: 1157. 2 Muder RR. Pneumonia in residents of long-term care facilities: epidemiology, etiology, management, and prevention. Am J Med 1998; 105: 319–30. 3 Nichol KL, Wuorenma J, Von Sternberg T. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens. Arch Intern Med 1998; 1 5 8 : 1769–76. 4 Fukushima T, Nakayama K, Monma M, Sekizawa K, Sasaki H. Influenza vaccination in bedridden patients. Arch Intern Med 1999; 159: 316–17. 5 Calfee DP, Hayden FG. New approaches to influenza chemotherapy. Neuraminidase inhibitors. Drugs 1998; 5 6 : 537–53.
2157
2
3
4
5
Nakagawa T, Wada H, Sekizawa K, Arai H, Sasaki H. Amantadine and pneumonia. Lancet 1999; 353: 1157. Nakagawa T, Sekizawa K, Arai H, Kikuchi R, Manabe K, Sasaki H. High incidence of pneumonia in elderly patients with basal ganglia infarction. Arch Intern Med 1997; 157: 321–24. Zimmerman RK, Ruben FL, Ahwesh ER. Influenza, influenza vaccine, and amantadine/rimantadine. J Fam Pract 1997; 45: 107–22. Mast EE, Harmon MW, Gravenstein S, et al. Emergence and possible transmission of amantadine-resistant virus during nursing home outbreaks of influenza A IH3N2. Am J Epidemiol 1991; 134: 988–97. Houck P, Hemhill M, LaCroix S, Hirsh D, Cox N. Amantadine-resistant influenza A in nursing homes. Identification of a resistant virus prior to drug use. Arch Intern Med 1995; 155: 533–37.
independence and provides a score ranging from 0 for total disability/dependence to 100 for full function/independence. The Barthel index of daily living activity was 73 (SE 5) in the patients who received amantadine and 76 (8) in those who received no active treatment. Daily living activities of the patients were high and none had depressed or altered consciousness. Furthermore, none of our patients had clinical symptoms of gastro-oesophageal reflux, although 16% (31) of 195 patients were reported to have cough without heartburn or other typical symptoms of gastro-oesophageal reflux.2 Therefore, improvement of consciousness and lower-oesophageal sphincter function might not be the most likely mechanism for beneficial effects induced by amantadine. N N Chan suggests that the beneficial effects of amantadine in the prevention of pneumonia are attributable to antiviral effects. During 3 years’ follow-up, two outbreaks of influenza A virus infection took place in the winter in the area we studied. Although 70% of total pneumonia occurred out of the winter season, our results could have been affected by the antiviral effects of amantadine. Therefore, the possible mechanism of amantadine-induced effects on prevention of pneumonia remains to be proven. We agree that more patients and longer follow-up are needed to establish amantadine therapy in the prevention of pneumonia in stroke patients. Kiyohisa Sekizawa, Masaru Yanai, Mutsuo Yamaya, Hiroyuki Arai, *Hidetada Sasaki Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai 980, Japan 1
Mahoney FI, Barthel DW. Functional evaluation: the Barthel index. Maryland State Med J 1965; 14: 61–65. 2 Allen CJ, Anvari M. Gastro-oesophageal reflux related cough and its response to laparoscopic fundoplication. Thorax 1998: 53: 963–68.
Authors’ reply Sir—We agree that the role of amantadine in the prevention of pneumonia in stroke patients is complex. As Shinji Teramoto and colleagues state, amantadine may improve either conscious state or lower-oesophageal sphincter function. Their comments, however, give us the opportunity to expand on the clinical details of our patients. We assessed overall neurological disability of the patients with the Barthel index,1 which consists of ten items for evaluating functional
THE LANCET • Vol 353 • June 19, 1999
Sir—In Takuma Nakagawa and c o l l e a g u e s 1 randomised study of amantadine (100 mg daily), the risk of pneumonia was lowered by about 20% in non-bedridden patients with a history of stroke. Their hypothesis is that amantadine improves the swallowing reflex. However, the investigators did not discuss the risk of influenza infection in their elderly patients (mean age 75–77 years in both groups). Influenza infection can cause significant morbidity and mortality in the elderly (with or without stroke),
and predisposes patients to bacterial pneumonia, especially due to Streptococcus pneumonia, Staphylococcus aureus, or gram-negative enteric pathogens.2 Three manifestations of pneumonia are associated with influenza: primary viral pneumonia, secondary bacterial pneumonia, and mixed viral and bacterial pneumonias. Influenza vaccination is associated with an overall reduction of 39% for pneumonia hospital admissions.3 In their earlier study, Nakagawa and c o w o r k e r s 4 showed that elderly bedridden patients with multiple cerebral infarctions can be effectively immunised against influenza. Since amantadine is an available antiinfluenza medication,5 it is important to know the immunisation status of the patients, and whether influenza A outbreaks occurred during the 3 years of the study. Although amantadine prevents outbreaks of influenza A, side-effects are common (gastrointestinal and central nervous system), especially in elderly people. In addition, because amantadine clearance is dependent on renal function, the dose of 100 mg daily may need to be reduced according to estimates of renal function. New antiviral agents to inhibit influenza neuraminidase are under development for use in prophylaxis and treatment of influenza A and B infections, with excellent tolerability profiles.5 A m a n t a d i n e lowers the rate of pneumonia in patients with cerebral infarctions because this drug lowers the incidence of influenza infection in this high-risk population, rather than by improving the swallowing reflex, as Nakagawa and colleagues suggest. Should our explanation be the case, influenza vaccination is probably more effective. Christophe Trivalle, Renée Sebag-Lanoe Service de Gérontologie et de Soins Palliatifs, Hôpital Paul Brousse, F-94804 Villejuif Cedex, France (e-mail: [email protected]) 1
Nakagawa T, Wada H, Sekizawa K, Arai H, Sasaki H. Amantadine and pneumonia. Lancet 1999; 353: 1157. 2 Muder RR. Pneumonia in residents of long-term care facilities: epidemiology, etiology, management, and prevention. Am J Med 1998; 105: 319–30. 3 Nichol KL, Wuorenma J, Von Sternberg T. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens. Arch Intern Med 1998; 1 5 8 : 1769–76. 4 Fukushima T, Nakayama K, Monma M, Sekizawa K, Sasaki H. Influenza vaccination in bedridden patients. Arch Intern Med 1999; 159: 316–17. 5 Calfee DP, Hayden FG. New approaches to influenza chemotherapy. Neuraminidase inhibitors. Drugs 1998; 5 6 : 537–53.
2157