Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emergesupdated 10 February 2004



# Introduction
During 2003 Severe Acute Respiratory Syndrome caused by a novel coronavirus (SARS-CoV) emerged as an infectious disease with a significant inhospital mortality and posed a considerable occupational risk for healthcare workers. The initial SARS outbreak ended in July 2003 when the World Health Organisation (WHO) announced that all known person-to-person transmission of SARS-CoV had ceased. At the time of preparation of these guidelines, there have been a further two laboratory-acquired cases of SARS and further community-acquired cases. These cases emphasise the potential for SARS to re-emerge and spread unpredictably. These guidelines document the hospital management of adults with probable or confirmed SARS. They are meant only as a brief summary for clinicians. These guidelines do not cover the management in the community of a person under investigation (PUI) (see Case Definitions).
Guidelines for the management of paediatrics cases have not yet been developed.
As more information about SARS becomes available, guidance will be appropriately updated. Please consult the latest guidance available on the websites of the British Thoracic Society (http:// www.brit-thoracic.org.uk/) and Health Protection Agency (http://www.hpa.org.uk/infections/ topics_az/SARS/menu.htm).

## Uk sars case definitions if sars re-emerges
The following case definitions (see [fig_ref] Table 1: Case definition for a probable case of SARS An individual with a... [/fig_ref] are designed for use during an outbreak of SARS, once the re-emergence of SARS has been verified by the World Health Organisation (WHO).
It is anticipated that patients with SARS will have a respiratory illness severe enough to warrant hospital admission. Management of such cases is covered in Sections 2 -4. A person with a mild respiratory illness and a potential epidemiological link to SARS should be defined as a PUI (see [fig_ref] Table 4: Case definition for a person under investigation http [/fig_ref] and should be assessed in primary care and reviewed within 72 h.
A PUI does not require routine hospitalisation nor do they require a chest radiograph (CXR) or laboratory investigation for SARS CoV as part of their assessment. A PUI should only be hospitalised if his or her condition deteriorates. The management of such patients is covered in Section 5. If these patients are subsequently found to have radiographic evidence consistent with SARS, they should be reclassified as a 'probable SARS' case unless an alternative diagnosis is made.
A PUI should be reported to local Health Protection Units but does not need to be reported to CDSC Colindale.
Please discuss the classification of SARS patients with the Health Protection Agency's Communicable Disease Surveillance Centre (CDSC) Duty doctor (Tel.: 0208-200-6868) and complete a standard SARS report form and fax to your local Consultant in Communicable Disease Control (CCDC) and CDSC (details at: http://www.hpa.org.uk/infections/ topics_az/SARS/forms.htm).  Negative antibody test on acute serum followed by positive antibody test on convalescent phase serum tested in parallel OR  Four-fold or greater rise in antibody titre between the acute and convalescent phase sera tested in parallel (c) Virus isolation  Isolation in cell culture of SARS-CoV from any specimen; plus PCR confirmation using a validated method

## Adult presenting to hospital with probable sars
Patients are likely to present initially with a clinical picture of pneumonia which may be consistent with SARS. Therefore, other causes of pneumonia should be considered. Confirmation that a patient has SARS may occur following further investigation.

## Infection control issues
Detailed guidance regarding the infection control issues during hospital management of a patient, or patients, presenting with SARS can be found at the HPA website: http://www.hpa.org.uk/infections/ topics_az/SARS/hops_infect_cont.htm.
Briefly, the key recommendations are:
(a) Give the patient a surgical mask to wear continuously (unless requiring face mask for oxygen

## Recommendation
Confirm the travel history and/or history of contact with a patient with SARS. Explore other possible causes of pneumonia. Assess pneumonia disease severity according to the BTS guidelines on the management of community acquired pneumonia (CAP) in adults (http:// www.brit-thoracic.org.uk/guide/guidelines.html).In addition, determine whether the patient has any medical history of illness associated with a more severe outcome of SARS, i.e. diabetes and cardiopulmonary disease. [bib_ref] Clinical features and short-term outcomes of 144 patients with SARS in the..., Booth [/bib_ref] Obtain investigations as listed below (observe high risk infection control measures for all samples).

## Laboratory testing for sars
For full details, please see the HPA website at http://www.hpa.org.uk/infections/topics_az/ SARS/micro.htm. Only send specimens once CDSC have been informed of a case via their standard report form. Please observe strict infection control procedures. All specimens should be double bagged and labelled as a biohazard. Do not obtain a nasopharyngeal aspirate as this is likely to generate aerosols.

## Microbiology

## Specific management of a patient with probable or confirmed sars
Admit the patient to a designated isolation unit (see Section 2.1). Manage as for severe CAP according to BTS guidelines.Administer fluids and oxygen as required. Commence intravenous co-amoxiclav 1.2 g tds or cefuroxime 1.5 g tds plus erythromycin 500 mg qds or clarithromycin 500 mg bd. Please refer to the BTS guidelines for alternative recommended regimens.

## Oxygen therapy
Oxygen supplementation should be administered according to standard/local guidelines. However, in order to reduce the risk of aerosol generation and hence spread of infection, high flow oxygen is not recommended, i.e. avoid oxygen flow rates of . 6 l/min. It should be possible to provide 30 -40% oxygen supplementation using a standard low flow oxygen system and an air-entrainer together with a Ventimask.

## Respiratory support and procedures
Procedures and practices that promote the generation of aerosols [fig_ref] Table 5: Procedures that might promote the generation of aerosols [/fig_ref] should be avoided wherever possible to reduce the risk of infection to healthcare workers. [bib_ref] Severe acute respiratory syndrome (SARS): infection control, Li [/bib_ref] [bib_ref] SARS: experience at Prince of Wales Hospital, Hong Kong, Tomlinson [/bib_ref] If such procedures need to be performed, e.g. tracheal intubation, it is advised that experienced operators only should undertake these procedures. These should, where possible, be planned and controlled. These procedures should ideally be undertaken in a negative pressure room. Only a minimum number of staff should be present and all must wear gowns, gloves, goggles/visors and respirators as described under infection control issues (see Section 2.1). Entry and exit from the room should be minimised during the procedure. The use of powered air purifying respirators (PAPRs) during aerosol generating procedures is not recommended. This is because there are concerns over the removal, disposal, cleaning and decontamination of this equipment, which may increase the potential risk of self-contamination and at this time there is inadequate evidence to determine whether PAPRs further reduce the transmission of SARS. If PAPRs are used, staff must be properly trained in their safe use.

## Critical care
In studies from Canada and Singapore, approximately 20% of patients with suspected or probable SARS, according to the prevailing WHO case definition from March to June 2003, required ICU admission. [bib_ref] Acute respiratory distress syndrome in critically ill patients with severe acute respiratory..., Lew [/bib_ref] [bib_ref] Critically ill patients with severe acute respiratory syndrome, Fowler [/bib_ref] Of these patients, 66 -76% required mechanical ventilation. Average length of ICU stay was 10 days.

## Recommendation
Preplanning and early consultation with local critical care providers is recommended. [bib_ref] Anaesthesia and SARS, Kamming [/bib_ref] Patients who are likely to require intubation, should be identified early and the procedure should be undertaken electively. In order to avoid the use of CPAP or NIV, early intubation and invasive positive pressure ventilation (IPPV) may be required in some patients with impending respiratory failure.
The following issues need to be carefully considered: Further guidance for the management of critically ill patients is being developed.

## Potential additional treatments for sars steroids
The use of high-dose steroids has been anecdotally reported to contribute to decrease in fever and need for oxygen supplementation. 14 A study from Guangzhou, China has suggested that the early administration of high-dose steroids together with CPAP ventilation is associated with a lower mortality. [bib_ref] Description and clinical treatment of an early outbreak of severe acute respiratory..., Zhao [/bib_ref] However, these findings are not based on adequately controlled data and there remain concerns regarding the use of high-dose steroids. The use of CPAP is certainly no longer recommended (see Section 2.5.2). In a retrospective analysis of Hong Kong patients who had received ribavirin in combination with different steroid regimens, patients who received initial high dose pulsed methylprednisolone intravenously had less oxygen requirement, better radiological improvement and less likelihood to require rescue pulse steroid use than patients who received non-pulse steroid therapy. However, the overall mortality rate, and requirement for mechanical ventilation or admission to the intensive care unit was the same for both regimens. [bib_ref] High dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome, Ho [/bib_ref] Recommendation The current recommendation is to consider moderate doses of steroid (prednisolone 30 -40 mg/day or iv equivalent) in severely ill patients with SARS with increasing oxygen requirements who have a PaO 2 , 10 kPa or O 2 sats , 90% on air.

## Ribavirin
Currently there is no convincing evidence that ribavirin alters clinical outcome. In laboratory studies, no in vitro activity against SARS-associated coronavirus (SARS-CoV) has been consistently demonstrated either. In addition, use of ribavirin is associated with significant toxicity including haemolysis (in , 76%) and decrease in haemoglobin of 2 g/dl or more (in , 49%). [bib_ref] Clinical features and short-term outcomes of 144 patients with SARS in the..., Booth [/bib_ref] 

## Recommendation
The routine use of ribavirin in patients with SARS is not recommended.

## Interferon
The antiviral activity of interferons against SARS coronavirus has been measured in vitro and interferon beta appears to be particularly active. [bib_ref] Treatment of SARS with human interferons, Cinatl [/bib_ref] The World Health Organisation is currently coordinating plans for clinical trials of interferons in the event of re-emergence of the disease. Recommendation None can be given at this time.

## Management of the close contacts of a probable or confirmed sars case
Generate a list of all close contacts. This should be initiated by the attending physician at the time of first contact with the patient. The local hospital infection control and Occupational Health teams may need to be involved if any healthcare workers are identified as close contacts. Record the date on which all close contacts last had contact with the case and inform them about SARS. Inform the local CCDC/Health Protection team of any contacts and their details to ensure follow-up.

## Contacts of a probable sars case
These contacts may continue with everyday activities, as long as they remain well. The local Health Protection Team will contact them on a regular basis to review their health.

## Contacts of a confirmed sars case
These contacts should be isolated at home. Please refer to the Health Protection Agency's guidelines on voluntary home isolation at http://www.hpa. org.uk/infections/topics_az/SARS/homeiso.htm.
If a contact becomes unwell within 10 days of their contact with a probable or confirmed SARS case they should phone a doctor urgently. For more information please refer to: http://www.hpa.org. uk/infections/topics_az/SARS/Guidelines.htm.

## Discharge from hospital and follow up of a probable or confirmed sars case
Guidelines for the safe discharge of patients recovering from SARS have been published by WHO. Please refer to the WHO website at http:// www.who.int/csr/sars/discharge/en/.
Briefly, the following criteria should be considered before discharge:
(a) Afebrile for 48 h (b) Resolving cough (c) Laboratory tests, if previously abnormal, returning to normal (d) Chest X-ray improved.

## On discharge from hospital
Patients should monitor and record their temperature twice daily. If they have an elevated temperature of 38 8C or above on two consecutive occasions they should inform (by telephone) the healthcare facility from which they were discharged.
Patients should remain at home for 7 days after discharge, keeping contact with others at a minimum. This is to reduce the risk of transmission until more is known regarding the potential for continued carriage in convalescent cases.
Additional home confinement may need to be considered, particularly in patients who are immunosuppressed. Inform the local Health Protection Team/CCDC regarding the hospital discharge of patients to ensure follow-up in the community.

## Surveillance follow-up
A standard follow-up form should be completed and faxed to the local CCDC and CDSC on day 2, day 10, and/or once the patient is asymptomatic. Forms are available from http://www.hpa.org.uk/infections/ topics_az/SARS/forms.htm. Follow-up post-discharge will be the responsibility of the local infection control team.
Convalescent serology should be obtained at 21 days after the date of disease onset.

## Management of a person under investigation (pui) who requires hospital admission but has a normal chest radiograph
PUIs who have symptoms and signs consistent with a lower respiratory tract infection (LRTI) but have a normal CXR do not fulfil the SARS case definition (see [fig_ref] Table 1: Case definition for a probable case of SARS An individual with a... [/fig_ref]. Patients should be discharged and followed up in primary care unless their symptoms or social circumstances warrant continued hospital care.
Up to 30% of patients with probable SARS may initially present with normal chest radiographs. Therefore, PUIs who need ongoing hospitalisation require careful medical review in the first 48 h following admission.

## Recommendation
Infection control measures as for patients with probable SARS should apply (see Section 2.1) until it is clinically clear that the PUI does not have probable SARS. Such patients should be treated as for non-pneumonic LRTI.
If the patient improves with treatment in the first 48 h following admission, the likelihood of SARS is small. Infection control measures may be relaxed and the patient discharged if this is clinically appropriate.
If the patient does not improve with initial treatment (either no change or deteriorates), a repeat CXR should be obtained. An abnormal CXR with changes consistent with SARS would require the patient to be re-classified as having Probable SARS and be managed accordingly (see Section 2). If the repeat CXR remains normal, the patient remains a PUI. Further repeat CXRs may be required at 1 -2 days intervals depending on clinical circumstances.
A PUI should be reported to the local Health Protection Unit but does not need to be reported to CDSC Colindale.

# Appendix a
These guidelines were produced as a joint initiative between the British Thoracic Society, the British Infection Society and the Health Protection Agency.
Membership of the Guideline Development Group:
Lead
[table] Table 1: Case definition for a probable case of SARS An individual with a respiratory illness requiring hospitalisation on clinical grounds and characterised by:AND a potential epidemiological link-i.e.: In the 10 days before the onset of illness: a history of travel to an area classified by WHO as having recent local transmission (http://www.who.int/csr/sars/ areas/en/) OR a history of exposure to laboratories or institutes which have retained SARS virus isolates and/or diagnostic specimens from SARS patients OR Close contact a with a probable or confirmed SARS case AND No alternate diagnosis to fully explain their illness [/table]
[table] Table 2: Case definition for a confirmed case of SARS [/table]
[table] Table 3: Case definition for a discarded case [/table]
[table] Table 4: Case definition for a person under investigation http://www.who.int/csr/sars/ areas/en/) OR a history of exposure to laboratories or institutes which have retained SARS virus isolates and/or diagnostic specimens from SARS patients a As per footnote toTable 1. [/table]
[table] Table 5: Procedures that might promote the generation of aerosols (non-exhaustive list) [/table]