Assisted ventilation 151

As superimposing infections add to the morbidity and mortality and offset the beneficial effects of corticosteroids in SARS, it is of vital importance that strict control of hyperglycemia during corticosteroid administration is implemented to reduce the chance of septic complications (Van den Berghe et al 2001) and measures are taken to prevent ventilator-associated pneumonia (Collard et al 2003). Successful control of superimposing infections also demands a judicious use of empirical and culture-directed antimicrobials.

In summary, corticosteroids must not be indiscriminately prescribed for SARS, but should only be used according to the above principles and by exercising good clinical judgment.

Other immunomodulators

Thymosin alpha 1 (Zadaxin®, SciClone Pharmaceuticals Inc., USA) is used in the treatment of chronic viral hepatitis B and C, and has also been administered to SARS patients in some Chinese hospitals (Zhao Z et al 2003; Gao et al 2003). It is a relatively safe product and may augment T-cell function. The role and effectiveness of this agent in SARS has not yet been determined.

Other immunomodulatory agents in anecdotal use included tumor necrosis factor blocking agents, namely etanercept (Enbrel®, Immunex Corporation, USA) and infliximab (Remicade®, Centocor Inc., USA), and some other compounds like cyclophosphamide, azathioprine, cyclosporin and thalidomide.

Assisted ventilation

Despite treatment efforts, some SARS patients still develop acute hypoxemic respiratory failure. According to the current literature, 2030% of SARS warranted admission into intensive care units, and 1020% eventually required intubation and mechanical ventilation.

The initial management of SARS-related respiratory failure is oxygen supplementation. If the oxygen saturation remains low or dyspnea persists, assisted ventilation, either through non-invasive or invasive means, has to be considered.

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152 SARS Treatment

Non-invasive ventilation

Non-invasive ventilation (NIV) is instituted via a face or nasal mask, as distinguished from invasive ventilation which necessitates endotracheal intubation. It is a valuable treatment for acute respiratory failure of various causes, and can avoid complications associated with intubation and invasive ventilation (Baudouin et al 2002; Peter et al 2002). Its application in SARS may be of particular benefit since SARS patients are frequently treated with high dose corticosteroids, which predispose them to infections including ventilator-associated pneumonia.

NIV, as either continuous positive airway pressure (CPAP) or bi-level pressure support, was commonly employed in many Chinese hospitals (Zhong & Zeng 2003; Luo & Qian 2003; Liu et al 2003; Xiao et al 2003; Zhao Z et al 2003; Wu et al 2003; Li H et al 2003) and in one hospital in Hong Kong (So et al 2003). Its use can improve oxygenation and tachypnea within an hour, and this may help to prevent adding further corticosteroids for respiratory failure (Liu et al 2003). In general, NIV was found to be able to avoid intubation and invasive ventilation in up to two-thirds of SARS patients with deterioration (Xiao et al 2003; Zhao Z et al 2003; Unpublished data from Hong Kong).

NIV can be given using a CPAP of 4-10 cm H2O or bi-level pressure support with an inspiratory positive airway pressure (IPAP) of <10 cm H2O and an expiratory positive airway pressure (EPAP) of 4-6 cm H2O. Contrary to the scenarios for non-SARS-related acute respiratory distress syndrome, higher pressures were generally not necessary and should be avoided whenever possible, because not only was there usually no additional clinical improvement observed, but it can also add to the risk of pneumothorax and pneumomediastinum. The latter conditions are known complications of SARS, even without assisted positive pressure ventilation (Peiris et al 2003b).

Although NIV can improve patient outcome, the infective risks associated with aerosol generation have hampered its use in many hospitals. Nevertheless, centers with experience have reported the use of NIV to be safe, if the necessary precautions are taken (Li H et al 2003; Zhao Z et al 2003; Unpublished data from Hong Kong). In addition to the recommended standard infection control measures for aerosol-

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