Patients with confirmed influenza A (H1N1)
From 15 July to 30 of November 2009 a total of 182 cases of suspected pandemic H1N1 were hospitalised, of which 64 (35%) were confirmed pandemic H1N1 with RT-PCR (Fig1). The Department of Gastroenterology and Infectious Diseases had 498 admissions in this given time-period in 2008 and 495 admissions in 2009.
The median age of patients with a positive influenza-test was 42 years (19 - 69 years), and there were 26 men (41%) and 38 women (59%). The median time from onset of illness to hospital admission was three days (range 0 - 20) and the median length of stay in hospital was three days (0.3 - 47).
Fifty five (86%) of the 64 patients who tested positive, had one or more underlying medical conditions. Patient characteristics are shown in Additional file 1. Chronic pulmonary disease was the most common predisposing risk factor seen in 34% of the patients with Influenza A (Additional file 1). Three patients (5%) were pregnant, of whom one had a chronic pulmonary disease.
Demographics and vital signs at admission
The patients with positive H1N1 tests were significantly younger, had a higher heart rate on admission, and were more often non-ethnic Norwegians and healthcare workers, compared to the H1N1 negative patients. Established hypertension was more common in the H1N1 negative group (Additional file 1).
Fever
Only 31 (48%) of the patients with confirmed pandemic Influenza A had fever on admission (temperature measurement available for 63 of 64 patients). Information on the pre-admission use of antipyretic drugs (paracetamol, ibuprofen and various immunosuppressants) was scarcely available (N = 25 patients).
Bacteriology and antibiotics
Blood cultures were obtained in 51 patients (80%). There was growth of Streptococcus pneumonia in two cultures and of Streptococcus viridans in one, altogether in 6%. All strains were susceptible to penicillin. Six patients received antibiotics before admission. During the hospital stay 33 patients (52%) received 47 treatment-courses of antibiotics. Median duration of antibiotic treatment was six days The most common antibiotics used were penicillin and cefotaxime. Eight patiens received penicillin, where four of these changed to cefotaxime. Similarly, six patients received cefotaxime monotherapy, and 4 patients changed from cefotaxime to penicillin.
Radiology
Chest radiography was performed in 59 (92%) of the patients with influenza A and revealed pneumonia in 24 patients (41%). The comparative figures for H1N1 negative patients were 101 x-rays performed (86%) and 45 diagnosed with pneumonia (45%).
Antiviral treatment
One pregnant patient was offered treatment but refused. Seven patients (11%) started oseltamivir before admission to hospital, 44 (69%) started on the same day they were admitted, the remaining eight started oseltamivir one to four days after admission. No patients received zanamivir. Four patients died - of these one did not receive antiviral treatment, one started oseltamivir two days prior to hospital admission and two patients started at admission. Six patients needed mechanical ventilation - two of these had started oseltamivir before admission, the remaining four started at admission.
Vaccination
Six of the 64 patients with confirmed H1N1 Influenza A had been vaccinated with 2009 H1N1-specific vaccines. Two of these received their vaccine the same day as they were admitted; the remaining four were vaccinated one, two, 11 and 21 days prior to admission. One of the six vaccinated patients died. This patient received the vaccine 21 days prior to admission. He had an aggressive chronic lymphatic leukaemia.
Number of admitted patients and length of stay
Figure 1 shows the total number of admissions (both patients with positive and negative tests) according to week. There was a marked increase in the number of admissions between week 41-47 and especially between weeks 43-45. There was no recorded wave of 2009 pandemic Influenza A before this but there were some sporadic cases.
The length of stay for the patients with a positive H1N1 test was relatively short (Figure 2) with a median stay of 3 days.
ICU admissions and outcome
Of the patients with confirmed Influenza A, 27% were admitted to the ICU compared to 15% of H1N1 negative patients (ns). Clinical findings including fever, tachycardia, tachypnea, and hypoxia was more prevalent in the ICU admitted H1N1 positive patients compared to the H1N1 positive patients admitted to the Infectious Disease (ID) ward consistent with the selection criteria for ICU admission.
Putative associations between underlying medical conditions and demographics were explored by univariate analyses using admission to the ICU as the dependent variable, and are described in Additional file 2. The H1N1 positive patients admitted to the ICU tended to be younger, have a higher heart rate, and had a higher Body Mass Index (BMI) than the H1N1 negative ICU admitted patients.
Hypertension was the only medical condition that was significantly associated with a more serious outcome defined by ICU admission or death, with a univariate oddsratio of the composite endpoint in H1N1 positive and negative patients of 6.1 (95% CI 1.3 - 29.3) and 3.2 (95% CI 1.2 - 8.7), respectively (Additional file 2).
Possible associations were further explored in a multiple regression analysis with ICU admission as the dependant variable. In the H1N1 negative patients, hypertension did not remain significant in a stepwise model, nor did any of the other variables (diabetes, chronic heart failure and excessive alcohol consumption). However, in the H1N1 positive patients, hypertension remained significant with an OR of approximately 7 and p < 0,03 in all models.
Ten patients improved rapidly and left the ICU within one (six patients) or two days (four patients). Most of them were dehydrated and had moderate respiratory problems. One had Addisons disease and was admitted to the ICU because of an Addison crisis. Among the seven patients with three or more days in the ICU, two patients had severe pneumococcal sepsis. Both survived after 26 and 14 days in the ICU and they both needed mechanical ventilation. In total four patients (6%) died. All had at least one risk factor (one patient had one risk factor, two had two risk factors and one had three risk factors). One was multi-handicapped and ventilator was not indicated of ethical reasons. Another young patient with severe obesity (BMI 37) had severe respiratory problems on admission and died after six days of mechanical ventilation and four days with extracorporeal membrane oxygenation (ECMO). The patient's mother, who had rheumatoid arthritis treated with hydroxychloroquine sulphate, was admitted to our hospital after seven days with influenza symptoms. After two weeks in the ICU she died of a viral pneumonia. The last patient who died had an underlying aggressive malignant haematological disease.
Secondary cases and absence from work
We had no secondary H1N1 Influenza A among the staff and no increase in employers being absent from work at the Departments of Infectious Diseases and Intensive Care. One nurse on another ward who had been in contact with one of the patients with influenza, tested positive for H1N1 Influenza A, but recovered within seven days.
Patients with negative tests for Influenza A
The most common discharge-diagnoses for these patients were pneumonia, septicaemia and other infections (e.g. urinary tract, upper respiratory tract) (Figure 3). The remaining patients had non-infection diagnoses like myocardial infarction, trauma with fever and gastrointestinal symptoms. Eight of the influenza negative patients (7%) died. The characteristics of the patients with negative tests for Influenza A are given in Additional file 1. Signs and symptoms on admission could not help us determine who would have a positive test for Influenza A.