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generating procedures (Centers for Disease Prevention and Control [CDC] May 6, September 23, 2003; World Health Organization [WHO] April 24, 2003), the use of exhalation ports which generate round-the-tube laminar airflow (e.g. Whisper Swivel II, Respironics Inc., USA) and viral-bacterial filters interposed between the mask and exhalation port may further reduce the infective risk.

Invasive mechanical ventilation

Patients with SARS-related respiratory failure who continue to deteriorate while on NIV, or in whom NIV is contraindicated, should be promptly intubated and mechanically ventilated. The actual endotracheal intubation procedure bears a high infective risk and healthcare workers must strictly adhere to all infection control measures. To minimize the risk, the procedure is best performed by highly skilled personnel (Lapinsky & Hawryluck 2003) using rapid sequence induction. Other approaches like a “modified awake” intubation technique and elective intubation upon recognizing signs of imminent need for airway management have been recommended (Cooper et al 2003).

Most centers (Lew et al 2003; Gomersall & Joynt 2003) used ventilation method and settings with reference to the strategies for acute respiratory distress syndrome (ARDS) (The ARDS network 2000). Both pressure and volume control ventilation can be employed. The tidal volume should be kept low at 5-6 ml per Kg of the predicted body weight, and plateau pressures be kept less than 30 cm H2O. Positive end-expiratory pressure (PEEP) should also be titrated to as low as possible to maintain the oxygenation, since a high rate (34%) of barotraumas have been reported (Fowler et al 2003). Mechanically ventilated patients should be adequately sedated and a short-term neuromuscular blockade may be required for permissive hypercapnia.

Clinical outcomes

In this SARS epidemic, which eventually involved 8098 probable cases worldwide, the overall case-fatality ratio has been updated to 9.6%. Significant regional differences were seen. China had the greatest number (5327) of cases, but its case-fatality ratio was reported as being only 7%. Hong Kong came second with 1755 cases, of whom

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17% died. Taiwan, Canada and Singapore followed, and their ratios were 11%, 17%, and 14% respectively (WHO September 23, 2003). Age-stratified ratios were estimated to be <1% in patients ≤24 years old, 6% in 25-44 years old, 15% in 45-64 years old, and >50% in elderly ≥65 years old (WHO May 7, 2003). The estimates in Hong Kong were 13% in patients <60 years old, and 43% in those ≥60 (Donnelly et al 2003).

In addition to age, death rates may be affected by other patient factors such as genetic predispositions, the immune status, pre-existing comorbidities and cardiopulmonary reserve, and by the disease severity which depends theoretically on the viral strain’s virulence, viral load and magnitude of the host’s immune response. The rates may also be related to other factors such as case selection and volume, facilities and manpower, treatment strategies and regimens.

A multi-center study comparing four treatment regimens in Guangzhou, China, found that a regimen (Appendix 2) of early use of higher dose corticosteroids, coupled with nasal continuous positive airway pressure (CPAP) ventilation, produced the least mortality. All 60 clinically-defined SARS patients (mean age 30.5 years) treated with this regimen survived, 40% of them used CPAP and none required mechanical ventilation. Only a small number of deaths were recorded out of a further 160 cases treated with the same regimen (Zhao Z et al 2003).

Favorable protocol-driven treatment outcomes were also reported from a center in Hong Kong. The protocol (Appendix 1) was applied to 88 consecutively admitted SARS patients (mean age 42), of whom 97% were laboratory-proven cases. The overall mortality was 3.4% (3/88) occurring in patients aged ≥65 only, out of which two died from co-morbidities instead. 24% required intensive care unit admission, 14% received non-invasive ventilation (bi-level pressure support) and 10% invasive mechanical ventilation. High-resolution computed tomography performed 50 days after the commencement of treatment showed that most survivors did not have clinically significant lung scarring, and none required any form of pulmonary rehabilitation (Lau & So 2003).

Based on the treatment experiences of the above and other centers with similar outcomes, suffice it to say that SARS may not be a dis

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ease of high mortality, at least in non-elderly patients. Even though a substantial portion may require a period of assisted ventilation, the mortality rate could be kept down to just a few percent by using appropriate management and therapeutic strategies.

Outlook

We have gained much experience in the treatment of SARS. Without being complacent, scientists and clinicians alike are striving for more effective treatment aiming to lower mortality and transmission rates as much as possible. This can only be achieved together with an increased understanding of the viral structure and processes (Holmes 2003; Thiel et al 2003) and by defining the potential targets for drug and vaccine development.

The development of vaccines and new drugs for human use usually take many years. To expedite the development, the collaborative efforts around the world that unraveled the etiologic agent of SARS will be continued. Previous knowledge obtained from the HIV may give us a lead (Ho D 2003; Kliger & Levanon 2003; De Groot 2003), as well as the information known about the existing vaccines for animal coronaviruses (Clarke 2003). Three-dimensional computer modeling of key viral proteins may also facilitate the search and design of antivirals (Anand et al 2003). On the other hand, massive random screening and targeted searching of potential compounds by various institutions have already tested hundreds of thousands of compounds in vitro, and have had several hits which could be targets for further research (Abbott 2003).

In addition to the antiviral studies, research on the gene expression profiles (Cameron et al 2003; Lin M et al 2003) and the disease immune profiles (Li Z et al 2003; Beijing Group of National Research Project for SARS 2003) are in progress. In the future, they may facilitate the diagnosis, monitoring and tailoring of specific immunotherapies.

While awaiting research breakthroughs, we have to rely on the existing treatment modalities, which have been overviewed in this chapter. It is envisaged that with the early use of efficacious antiviral agents singly or in combination, the necessity for high dose immunomodula

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