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Clinical Meetings at RH Year 2009

2009 Jul - Pandemic H1N1 2009/ Human Swine Influenza: Sharing of the Serious Cases

Hospitals responsible: CMC, QEH, TMH, PWH; Chairman: Dr CY Tam, Dr ML Wong; Moderator: Dr WC Yu


Case 1
(Presented by Prof. David Hui, Department of Medicine & Therapeutics, Prince of Wales Hospital) A 23 year-old university student with good past health was admitted on 15 July 2009 with fever, cough with blood-stained sputum and sore throat for 1 week. She enjoyed good past health and lived with her parents, siblings and domestic helper. She returned to Hong Kong from the United Kingdom on 14 June 2009 and had no known contact with patients with respiratory symptoms. Her family members were all asymptomatic.

She attended a general practitioner’s clinic on 9 July 2009 and was prescribed oral clarithromycin 500mg twice daily for 4 days. Her symptoms did not improve and she attended the same general practitioner on 13 July 2009 and was given a dose of intramuscular Rocephin and she was referred to hospital for further management. She stayed in a private hospital for 2 days and the first nasal swab for influenza A and B antigen detection (rapid test) was negative. Repeated nasal swab for swine flu RT-PCR was positive. As she was also noted to have abnormal liver function tests, abdomen ultrasonography was performed, which revealed fatty liver disease. Tamiflu 75mg twice daily was started in the private hospital. She was transferred to PWH for further treatment on 15 July 2009.

On arrival, her blood pressure was 115/85mmHg and her pulse was 110/min. She had fever with temperature 38.2oC. Her body mass index was 30 kg/m2. Her respiratory rate was 20/min with SaO2 95% on 3L/min oxygen administered via nasal cannula. Bilateral basal crepitations were heard during physical examination. Her JVP was not elevated and cardiovascular examination showed normal heart sounds with no murmurs. Abdominal examination was unremarkable. CXR showed bronchopneumonic changes over bilateral lower zones.

Her blood results upon admission to PWH were as follows:
Hb 13.4 g/dL, platelet 173, white cell count 5.8 X 109/L, lymphocyte count 0.7 X109/L
PT 10.1 sec, INR 1.01, APTT 50.5 sec
Sodium 130 mmol/L, potassium 3.1 mmol/L, urea 2.0 mmol/L, creatinine 49 μmol/L
Total protein 70 g/L, albumin 36 g/L, total bilirubin 4 umol/L, ALP 70 IU/L, ALT 39 IU/L, LDH 313 U/L
Arterial blood gas: pH 7.39, pCO2 5.5 kPa, PO2 11.2 kPa, HCO3 24 mmol/L, base excess -1 mmol/L, O2 saturation 0.94 (on 3 L/min O2)

She was started on oral Tamiflu 150mg twice daily, oral linezolid 600mg twice daily and oral levofloxacin 750mg daily on admission. She developed desaturation and was admitted to the intensive care unit (ICU) for close monitoring on the same day of admission. She deteriorated further and was intubated on 18 July 2009. She was given low dose inotropic support with noradrenaline. Relenza nebulization, simvastatin and IVIG were also prescribed to her during her stay in ICU.

She responded to the treatment with gradual improvement and was extubated on 24 July 2009. She was transferred to the general medical ward for further treatment on 16 July 2009. Oxygen supplement was gradually weaned off. She was discharged home on 30 July 2009.

Case 2 (Presented by Dr. Johnny Chan, Department of Medicine, Queen Elizabeth Hospital) A 48 year-old previously healthy saleslady, developed fever, cough with yellowish sputum, sore throat, chills and rigors on 8 July 2009. Being a chronic smoker of 1 packet per day for 20 years, she had no recent history of travel or contact with patients with known Human Swine Influenza (HSI). Despite medications offered by 3 different general practitioners in the following week, which included paracetamol, non-steroidal anti-inflammatory agents and cough mixtures, she felt increasingly unwell with progressive dyspnoea and eventually attended emergency room one week after symptom onset. Upon admission, her SaO2 was only 85% in room air and she was running a fever of 38.5C. Blood tests revealed lymphopenia, thrombocytopenia and mildly deranged liver function tests. She was promptly transferred to the Intensive Care Unit (ICU) on the same day of hospital admission. Initial CXR revealed consolidations over right upper, right middle, and left lingular lobes. (Fig. 1) The tests for HSI subsequently turned out to be positive. Apart from profound type I respiratory failure that required mechanical ventilation with high PEEP, high PiO2 and NO therapy, she also developed shock with the requirement of high dose inotropes. Apart from administration of antibiotics like Tazocin, Klacid and Vancomycin (subsequently Linezolid), she was given Tamiflu 150mg twice daily, acetylcysteine, anti-oxidant therapy and corticosteroid of a physiological dose in ICU. Nebulized Zanamivir (Relenza) had also been administered. Bronchoscopic findings were essentially normal, while CT thorax (Fig. 2) revealed extensive consolidations in both lungs, predominantly in the lower lobes. She was eventually able to be weaned off from mechanical ventilation and discharged back to the general ward after almost 3 weeks’ stay in ICU. She was subsequently transferred to Kowloon Hospital for a short period of rehabilitation.


Case 3 (An initial false-negative HSI test)
(Prepared/presented by Dr Chow Chee Wung/Dr Wong Mo Lin, Department of Medicine, Caritas Medical Centre)
Madam K is a 39-year-old clerk, married but with no children. Being a non- smoker and non-drinker, she had a history of thyroid cyst only. She had no relevant travel or contact history with HSI infection. She developed fever, chills, cough and sore throat on 9/7/09 and had been managed by her general practitioner for 2 consecutive days before she attended our AED on 12/7/09. She was only admitted to the hospital on her second attendance to AED on13/7/09 when her CXR showed haziness over both lower zones. She ran a high fever of 39.4 C at that time but she did not complain of any shortness of breath.

In the EM ward: BP 144/85, P 127/min, SaO2 96% on room air, WBC 5.3 x 109/L, lymphocytes 0.5 x 109/L, and she was given intravenous Amoxycillin-Clavulanate. NPA RT-PCR for swine flu was sent on 14/7/09 and the result returned to be negative the next day. However, since the follow-up CXR on 15/7/09 showed increased haziness over both lower zones, Clarithromycin was also added to cover any possible atypical pneumonia.

With her persistent high fever, she was transferred to our medical ward on 15/7/09 at around 9 pm. Her SaO2 was only 85% upon the transfer. Intravenous Amoxycillin- Clavulanate was switched to Cefepime empirically but her condition did not improve, and she was transferred to ICU subsequently on 16/7/09. Her SaO2 dropped to 90% while she was on 4 L/min of oxygen. ABG showed type I respiratory failure. Repeated WBC was normal with persistent lymphopenia while the liver and renal function tests were normal. CK and LDH levels were mildly elevated to 261 and 341 IU/L respectively and the first CRP was 202mg/L. Blood for HIV was negative. Repeated CXR showed marked increase of consolidative changes over both lower zones and HRCT confirmed wide spread airspace shadowing over corresponding areas. (Fig.1)

Her condition continued to deteriorate and eventually required intubation and mechanical ventilation with PEEP. Bronchoscopy was performed with bronchial lavage on 17/7/09. RT PCR for swine flu was positive for both tracheal and bronchial aspirates. Tamiflu at 75mg BD was initiated and continued for 10 days.



During her ICU stay, she required a long period of high PEEP of up to 28cmH2O for around 12 days while she was on mechanical ventilation. She had MRSA and Acinetobacter infections, with Vancomycin and Ciprofloxacin being prescribed. There was also the development of acute coronary syndrome, as evidenced by new T wave inversion over anterior leads and raised troponin I. Echocardiogram showed impaired left ventricular contraction with an ejection fraction (EF) of 40% only, together with hypokinesia over anteroseptal and apical segments of left ventricle. Aspirin was started. Improvement of left ventricular function (EF 71%) was observed in the follow-up echocardiogram on 24/8/09. Enoxaparin had been given for 10 days for prophylaxis of thromboembolism. Fortunately, her condition improved and she was able to come off ventilator support. The total duration of mechanical ventilation and ICU stay were 23 and 33 days respectively. She received further rehabilitation in general ward with much improvement. On Day 45 of admission, she was discharged home. She was able to walk unaided with no shortness of breath. CXR before discharge showed residual fibrosis mainly over both lower zone and HRCT thorax on Day 49 showed ground glass attenuation, streaky shadows and small cystic areas in both lung fields compatible with residual fibrosis & bronchiectasis due to previous inflammation. (Fig.2)

Lung function test on Day 52 showed evidence of restrictive lung disease, with the post bronchodilator FEV1 being 1.95L (82% predicted) and FVC 2.0L (71% predicted). The ratio of FEV1/FVC was 97.3%. Her vital capacity(VC) read 1.95L (69% predicted) while the residual volume (RV) and total lung capacity registered 0.96L (60% predicted) and 2.91L (59% predicted) respectively.

The arterial blood gas (RA) on Day 52 showed no evidence of hypoxia with pH 7.40, pCO2 39mmHg, pO2 79mmHg, HCO3 23mmol/L, tCO2 24mmol/L, BE -0.9mmol/L.

Case 4 (A critically ill pregnant patient)
(Presented by Dr. Sin Kit Man, Department of Medicine, Tuen Mun Hospital)
A young pregnant lady at 36th week of gestation attended Emergency Department on 20th Aug because of fever, sore throat and cough for 2 days, which did not resolve after treatment received in Mainland. There was no relevant contact history. As the NPA test turned out to be positive for HSI, she was admitted to isolation ward for further observation. Upon admission, there was high fever at 39 degrees C, and she was noted to have a SaO2 of only 91% in room air. There were no clinical signs of deep vein thrombosis. She was given oxygen supplement of 2L/min. CXR taken with abdominal shield revealed left lower lobe consolidation. (fig.1) She was given Relenza and Augmentin upon admission. However, in view of progressive increase in dyspnoea, persistent fetal tachycardia, as well as the observed vulnerability with HSI infections in pregnant women, emergency Caesarean section was offered on Day 2 admission. Post-operatively she required mechanical ventilation and inotropic support in ICU. CXR revealed bilateral consolidations. (fig.2) Tamiflu (150mg twice daily) and nebulised Relenza were offered on top of intravenous broad spectrum antibiotics. Fortunately her clinical course gradually stabilized and with steady improvements afterwards. Since mechanical ventilation was successfully weaned off on Day 3 and that the fever was also subsiding, she was discharged back to isolation ward on the subsequent day. Her baby was healthy with no evidence of infection.

From 17 July to 11 Aug. 2009, 8 confirmed swine flu H1N1 pregnant women had been admitted to our hospital. Most of them were in their 1st or 2nd trimesters and all had recovered uneventfully. Although pregnancy has been noted to be a recognized risk for complications in HSI, our patients appeared not to be that alarming (table 1) until our 8th case (presented above). To our knowledge, she would be the first critical case of pregnant woman with HSI infection in Hong Kong.


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