Current issues of ACP Journal Club are published in Annals of Internal Medicine


Prognosis

34% mortality rate from SARS in critically ill patients at 28 days in Toronto

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ACP J Club. 2004 Jan-Feb;140:20. doi:10.7326/ACPJC-2004-140-1-020


Clinical Impact Ratings

Hospitalists: 6 stars

Infectious Disease: 6 stars

Critical Care: 5 stars

Pulmonology: 5 stars


Source Citation

Fowler RA, Lapinsky SE, Hallett D, et al. Critically ill patients with severe acute respiratory syndrome. JAMA. 2003;290:367-73. [PubMed ID: 12865378]


Abstract

Question

What is the clinical course and mortality rate of critically ill patients with the severe acute respiratory syndrome (SARS)?

Design

Inception cohort followed for 8 weeks.

Setting

Intensive care units (ICUs) of 13 hospitals (5 university and 8 community) in Toronto, Ontario, Canada.

Patients

38 critically ill patients (mean age 57 y, 61% men) of 196 patients with probable or suspected SARS, defined according to World Health Organization criteria. Suspected SARS was defined by the presence of fever > 38°C, respiratory symptoms, and history of travel to a location associated with SARS transmission or close contact with a known SARS patient. Probable SARS included the addition of lung infiltrates evident on chest radiograph. Patients were defined as critically ill if they were admitted to the ICU and required mechanical ventilation, inspired oxygen concentration ≥ 60%, or inotropic medication.

Assessment of prognostic factors

Age, sex, occupation (health care worker [HCW] or non-HCW), duration of fever or respiratory symptoms, comorbid conditions, Acute Physiology and Chronic Health Evaluation II scores, and sepsis-related organ failure assessment scores.

Main outcome measures

Mortality at 28 days after ICU admission. Secondary outcomes were proportion of SARS-related critical illness, location and ventilation requirements at day 28, number of tertiary-care ICUs placed under quarantine, and number of HCWs contracting SARS secondary to ICU SARS transmission.

Main results

Among the 38 patients admitted to the ICU, 31 (82%) met criteria for the acute respiratory distress syndrome. 29 patients (76%) required mechanical ventilation. 13 patients (34%) died by day 28. The mortality rate for those on mechanical ventilation was 45%. At day 28, 16% of patients were still in the ICU, 5% were in a hospital ward, and 45% had been discharged. At 8 weeks, 15 patients (39%) had died. Factors associated with a poor outcome were older age, history of diabetes mellitus, admission tachycardia, and elevated creatine kinase level. 2 episodes of SARS transmission by ICU patients to HCWs occurred in 2 of the 5 university hospitals causing 164 HCWs to be quarantined, 35 critical care beds to be closed for 10 days, and 16 HCWs to develop SARS. In 4 of 8 community hospitals, 38 beds were closed because of ICU SARS transmission.

Conclusions

In critically ill patients with the severe acute respiratory syndrome (SARS), 28-day mortality was 34%. Intensive care unit transmission of SARS to health care workers led to substantial bed closures and health care worker quarantine.

Source of funding: No external funding.

For correspondence: Dr. S.E. Lapinsky, Mount Sinai Hospital, Toronto, Ontario, Canada. E-mail stephen.lapinsky@utoronto.ca.


Commentary

Providing critical care to patients with SARS has many challenges. The optimal therapy and specific type of supportive care needed for the best outcomes are unknown. The close interaction with patients and the increased potential for exposure to respiratory secretions place HCWs who work in critical care units at high risk for nosocomial acquisition of the SARS coronavirus (1).

The studies by Fowler and colleagues and Lew and colleagues of patients critically ill with SARS in Toronto and Singapore, respectively, offer important information about prognosis. Strengths of the study by Fowler and colleagues include a clearly defined inception cohort of critically ill patients and standardized assessment of severity of illness, sepsis-related organ failure, and radiologic progression. The key finding—that one third of patients admitted to the ICU died by 28 days, with a 45% mortality rate in those on mechanical ventilation—is a sobering reminder of why it is important to contain the spread of this virus. Not unexpectedly, older patients were at highest risk for death. Although many other potentially relevant prognostic factors were examined, including duration of fever and respiratory illness before admission to the critical care unit, the small data set limits the number of factors that can be examined in a multivariable model.

Similarly, Lew and colleagues describe a carefully defined cohort of patients with SARS. Follow-up time was longer in this study and again the prognosis was poor—half of critically ill patients died at 13 weeks. There were too few outcome events in this series to clearly define key independent prognostic factors. Given these limitations, a good argument can be made for pooling data from these and other SARS critical care cohort studies in a meta-analysis.

Our understanding of therapy for SARS is limited to small observational studies and anecdotal experience. It is clear that randomized, placebo-controlled trials are needed to establish effective therapy for SARS in case it reappears and that to achieve sufficient power, international clinical trials will be required. The World Health Organization can play a key role in coordinating such efforts. Priority should be given to establishing trials of early therapy. More data about predictors for early disease are needed for these planning efforts. Although reports on the features of SARS were quickly published (2, 3), these data were compiled before the end of the outbreak and therefore are limited by incomplete case ascertainment and follow-up. Additional information about the influence of viral load in prognosis is needed. Unlike other respiratory viral illnesses where the viral load is high initially and then diminishes, viral load tends to increase over the first several days of illness in SARS (4). It would be valuable to assess whether the rate of increase in viral load or whether a high baseline viral load is independently associated with poor prognosis.

SARS has had devastating effects on hospitalized patients and HCWs. We need to be prepared for a recurrence, which means bolstering surveillance and infection control measures. The poor outcomes described in the studies by Fowler and colleagues and Lew and colleagues dramatically illustrate why this is so important.

Mark Loeb, MD
McMaster University
Hamilton, Ontario, Canada


References

1. Cluster of severe acute respiratory syndrome cases among protected health-care workers—Toronto, Canada, April 2003. MMWR Morb Mortal Wkly Rep. 2003;52:433-6. [PubMed ID: 12807083]

2. Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003;289:2801-9. [PubMed ID: 12734147]

3. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348:1986-94. [PubMed ID: 12682352]

4. Peiris JS, Chu CM, Cheng VC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361:1767-72. [PubMed ID: 12781535]