Approach

The mainstay of treatment is early recognition of infection coupled with effective isolation and best available supportive care in a hospital setting. com.bmj.content.model.Caption@95c9f99 [Figure caption and citation for the preceding image starts]: Multidisciplinary ward rounds at the Save The Children Ebola treatment centre in Kerrytown, Sierra Leone (Ministry of Health representative, Cuban Medical Brigade representative, and a UK clinician) From the collection of Tom E. Fletcher, MBE, MBChB, MRCP, DTM&H; used with permission [Citation ends].

High case fatality rates may be related to the supportive care available in resource-poor, rural settings where outbreaks have occurred, and reflect the difficulties patients in these settings have in accessing basic medical care in a healthcare structure that is overwhelmed. [30] [118] com.bmj.content.model.Caption@90c0367 [Figure caption and citation for the preceding image starts]: General conditions at an Ebola treatment centre in West Africa, 2014 From the personal collection of Catherine F. Houlihan, MSc, MB ChB, MRCP, DTMH; used with permission [Citation ends]. com.bmj.content.model.Caption@682607b0 [Figure caption and citation for the preceding image starts]: Ward area at an Ebola treatment centre in West Africa, 2014 From the personal collection of Chris Lane, MSc; used with permission [Citation ends].

Cases imported to developed countries such as Spain, Germany, France, Norway, Italy, Switzerland, the UK, and the US present a different scenario with comprehensive supportive care available in these settings, including organ support in intensive care units. [119] [120] Despite this, the lack of specific, proven therapies means that fatalities occur even in developed countries where best supportive care is available. [121] [122] [123]

There was previously an active debate about the suitability of moving patients with advanced disease and a poor prognosis to intensive care where the risk for nosocomial infection may be high. It was thought that failure to provide full supportive care to those who are suspected (but not confirmed) of being infected may result in substandard care for these patients, who may subsequently be shown to have a treatable disease such as malaria. It is now clear that full supportive care can reduce mortality, with a reported survival rate of 81.5% in patients managed outside the West African setting, and that it should be provided whenever possible. [124] [125] [126] Local hospital protocols should consider how this situation would be handled for patients with suspected infection before possible transfer to the intensive care unit, and for those who have already been transferred there. [127] [123] [125] [128] [129]

Children should be managed by teams of health care workers with paediatric expertise. Planning for the care of children in non-endemic settings is complex and early involvement of intensivists has been advocated whenever feasible. [130] [131] [132]

Increased clinician-to-patient ratios are likely to reduce mortality. A staffing ratio of at least one clinician (defined as nurses, clinical officers, or physicians) to four patients is recommended to allow patient assessment three times daily. [133]

Ebola virus infection is a notifiable disease.

Isolation and infection control

Patients who are identified as being at risk of infection as per the World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC) case definitions should immediately be isolated in a room with private bathroom facilities:

All healthcare personnel attending to the patient must wear appropriate personal protective equipment (PPE) that conforms to published protocols. All contaminated materials (e.g., clothes, bed linens) should be treated as potentially infectious. The WHO and CDC produce detailed guidance on PPE:

The WHO and CDC produce detailed guidance on infection control for healthcare workers in West Africa:

Specimens for laboratory investigations (e.g., Ebola RT-PCR, FBC, serum creatinine and urea, LFTs, ABG, coagulation studies, blood cultures, and investigations for other conditions such as malaria) should be collected and sent off according to local and national protocols. Judicious selection of investigations is important in order to reduce risk of transmission to laboratory workers and other healthcare personnel. Placement of a central line early in the patient stay (if possible) allows bloods to be taken and fluids to be given while minimising the risk of needlestick injuries. [134] The WHO and CDC produce detailed guidance on specimen collection:

Fluid and electrolyte replacement

The high frequency of vomiting and diarrhoea means that patients are often dehydrated and hypovolaemic, particularly if they present late. This is probably responsible for the high case fatality rates in outbreaks as basic clinical monitoring (i.e., temperature, respiratory rate, pulse rate, blood pressure, and fluid input/output) is essential, but often difficult in resource-poor settings.

Oral rehydration solutions can be used for patients who can tolerate oral administration and who are not severely dehydrated, but the majority of patients require intravenous fluid replacement with either normal saline or lactated Ringer's solution. [118] [135] com.bmj.content.model.Caption@7dc7fbda [Figure caption and citation for the preceding image starts]: Oral rehydration solution supplies at an Ebola treatment centre in West Africa, 2014 From the personal collection of Chris Lane, MSc; used with permission [Citation ends]. com.bmj.content.model.Caption@14b9c83e [Figure caption and citation for the preceding image starts]: Insertion of an intravenous line in an adult with Ebola virus disease (West Africa) From the collection of Tom E. Fletcher, MBE, MBChB, MRCP, DTM&H; used with permission [Citation ends].

Markers of poor perfusion may indicate poor or inadequate oral intake and patients should be promptly switched to intravenous administration. Options include the peripheral or central intravenous route, or the intraosseous route. [133]

The volume of intravenous fluids required should be assessed based on clinical examination (i.e., level of dehydration, signs of shock) and fluid losses (i.e., volume of diarrhoea and/or vomitus). Large volumes of fluid replacement (up to 10 L/day) may be required in febrile patients with diarrhoea. [119] [136] [137] Large amounts of potassium replacement (e.g., 5-10 mmol [5-10 mEq/L] potassium chloride per hour) may also be required. [138] [120] [139]

Close supervision and frequent monitoring are required as it is important to assess response and prevent fluid overload. Patients should be checked frequently for signs of shock, dehydration, or overhydration, and the fluid rate adjusted accordingly. Systematic monitoring of vital signs (e.g., heart rate, blood pressure, urine output, gastrointestinal fluid loss) and volume status at least three times daily is required to detect hypovolaemia. [133]

Oral loperamide may help reduce profuse diarrhoea, but further evidence is required to determine its role and it is not currently recommended by the WHO. [140] [141] [142] [143]

The availability of point-of-care tests within the isolation facility makes monitoring the patient's biochemical status more efficient and reduces the risks associated with specimen transport. [127] Electrolyte monitoring should be performed daily, and repletion given as necessary. [118] More frequent monitoring can be considered if large volumes of intravenous fluids are being administered or if there are severe biochemical abnormalities present. High blood lactate levels can be a reliable measure of hypoperfusion and can help guide fluid resuscitation. [127]

WHO guidelines should be consulted for specific recommendations on fluid and electrolyte management as well as on maintaining adequate nutrition during acute illness and the convalescent phase.

World Health Organization (WHO): manual for the care and management of patients in Ebola care units/community care centres - interim emergency guidance

World Health Organization (WHO): clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker

Symptomatic management

Fever and pain:

  • Should be treated with paracetamol first line. Opioid analgesics (e.g., morphine) are preferable for more severe pain. Non-steroidal anti-inflammatory drugs (including aspirin) should be avoided due to their associated increased risk of bleeding and potential for nephrotoxicity. [143]

Gastrointestinal symptoms:

  • Fluid replacement is required for vomiting and diarrhoea as per the recommendations above.

  • Oral or intravenous anti-emetics (e.g., ondansetron, metoclopramide) are recommended for nausea/vomiting. [143]

  • Zinc is recommended in children with diarrhoea. [143]

  • Patients should be evaluated for gastrointestinal infections and managed accordingly. [143]

  • Faecal management systems were used successfully in the 2014 outbreak in West Africa in patients with severe diarrhoea. They were well tolerated and provided infection prevention and control benefits for healthcare workers. [144]

Heartburn/dysphagia/abdominal pain:

  • Patients may benefit from administration of a suitable antacid or a proton-pump inhibitor (e.g., omeprazole). [143]

Seizures:

  • Although uncommon, seizures are a feature of advanced disease and pose a risk to healthcare workers because they increase the risk of contact with the patient's body fluids. Recognition and correction of contributing factors (e.g., high temperature, hypoperfusion, electrolyte disturbances, hypoglycaemia) is essential. A benzodiazepine can be used to abort the seizure while an anticonvulsant (e.g., phenobarbital) can be given for repeated seizures. [143] If there is no intravenous access, it can be given intramuscularly or rectally.

Agitation:

  • Although uncommon, agitation may be associated with encephalopathy, or possibly a direct effect of the virus on the brain, and can occur in advanced disease. Judicious use of a sedative (e.g., haloperidol or a benzodiazepine) is imperative for keeping the patient calm and preventing needlestick injuries in healthcare workers. [143]

Respiratory distress:

  • Oxygen should be titrated to maintain SpO2 ≥90%. It should also be given if SpO2 <94%. Patients should be evaluated for pneumonia, fluid overload, wheezing, and congestive heart failure and managed accordingly. [143]

Intraosseous access may be required in some patients. com.bmj.content.model.Caption@4c7a469e [Figure caption and citation for the preceding image starts]: Insertion of an intraosseous line in a critically-ill adult with Ebola virus disease (West Africa) From the collection of Tom E. Fletcher, MBE, MBChB, MRCP, DTM&H; used with permission [Citation ends].

Sepsis/septic shock

Identification of sepsis or septic shock should be done rapidly using established criteria.

Management follows the same principles as for bacterial sepsis. Local guidance should be followed, but should include: [145]

  • Broad-spectrum antibiotics in the first hour after sending blood cultures

  • Rapid intravenous fluid resuscitation with assessment of response (within 30 minutes or faster if possible)

  • Appropriate airway management and oxygen administration

  • Monitoring of urine output preferably by urethral catheterisation, as well as vital signs and clinical features.

Broad-spectrum antibiotics are used in patients with infection to target the presumed translocation of gut organisms. This is not backed by any evidence, and blood cultures are difficult to do safely in infected patients. In some settings, especially in endemic areas where there is poor access to diagnostic tests, patients are routinely given broad-spectrum antibiotics as part of the management protocol.

Blood lactate levels are a useful tool to help assess perfusion and response to resuscitation.

In the absence of a response to initial management, inotropic support should be considered, preferably via a central venous catheter in an intensive care unit where invasive monitoring enables more aggressive fluid, electrolyte, and acid-base balance correction. [127] [129]

The possibility of haemorrhage should be considered, particularly in patients with skin or mucosal bleeding.

WHO guidelines should be consulted for specific recommendations on the management of sepsis/septic shock.

World Health Organization (WHO): manual for the care and management of patients in Ebola care units/community care centres - interim emergency guidance

World Health Organization (WHO): clinical management of patients with viral haemorrhagic fever: a pocket guide for the front-line health worker

Significant bleeding/haemorrhage

Major bleeding occurs infrequently, but is a manifestation of advanced infection that is usually, but not always, fatal.

When available, fresh whole blood or platelet and plasma transfusions should be given according to local protocols and guided by clinical and laboratory (if available) indicators (e.g., haemoglobin, haematocrit, INR). [143] [146]

Vitamin K and tranexamic acid are reasonable treatment options in patients who are bleeding. [143]

Organ dysfunction

Multi-organ dysfunction is a common feature of advanced infection and includes acute kidney injury, pancreatitis, adrenal failure, and liver damage. Liver damage (e.g., hepatitis) is common; however, jaundice is not a common feature. [147] Renal dysfunction is common, but can be reversed with adequate fluid resuscitation in the initial stages. [147] In patients with anuria who do not respond to fluid resuscitation, renal replacement therapy has been used, although there are no trial data to support the efficacy of this intervention. Of the 5 critically ill patients in Europe and North America with multi-organ failure who were managed with both invasive mechanical ventilation and renal replacement therapy, 3 died. [119] [121] [120] [123] [148]

Convalescent whole blood or plasma

There is limited evidence from past outbreaks that transfusion of blood from convalescent patients could be beneficial in the acute phase of infection, and may reduce mortality. [33] [149] Use of convalescent plasma is likely to be more achievable and effective than use of whole blood. [150] [151] The WHO has issued interim guidelines on the use of convalescent blood/plasma. Trials carried out in Guinea failed to show a survival benefit in patients treated with convalescent plasma, although the treatment appeared to be safe with no severe complications documented. [152] [153]

World Health Organization (WHO): use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks

World Health Organization (WHO): ethics of using convalescent whole blood and convalescent plasma during the Ebola epidemic

Malaria co-infection

Malaria should be tested for and treated with appropriate antimalarial therapy if present while keeping in mind the patient's risk for Ebola virus infection and the possibility of a dual infection. In endemic settings, malaria treatment is usually given as part of the routine management protocol, with or without confirmation of the infection.

Pregnant women

The reported case fatality rate has been higher (up to 96%) in pregnant women compared with non-pregnant women in previous outbreaks. [154]

The general medical management of pregnant women is the same as for any other person who is infected. Intrapartum haemorrhage and spontaneous abortion appear to be common in infected women; therefore, obstetric management should focus on monitoring for, and early treatment of, haemorrhagic complications. [155] [154] [156] [157] [158] Experience during the 2014 outbreak suggests that good outcomes can occasionally be achieved. [159]

Amniotic fluid has been shown to contain the virus, including when the level was found to be undetectable in blood. Therefore recommendations for delivery include avoiding the induction of labour, particularly rupturing of membranes. [159]

Recommendations for PPE use by healthcare workers caring for pregnant women are the same as for healthcare workers caring for non-pregnant adults. There are no data available to recommend one delivery method over another. Infected women or women with suspected infection are advised not to breastfeed unless breast milk has been shown to be PCR negative for Ebola virus. The WHO, CDC, and Public Health England have produced specific guidance for caring for pregnant women and neonates.

World Health Organization (WHO): Ebola virus disease in pregnancy: screening and management of Ebola cases, contacts and survivors

Centers for Disease Control and Prevention (CDC): guidance for screening and caring for pregnant women with Ebola virus disease for healthcare providers in US hospitals

Public Health England (PHE): Ebola in pregnancy - information for healthcare workers

Centers for Disease Control and Prevention (CDC): care of a neonate born to a mother who is confirmed to have Ebola, is a person under investigation, or has been exposed to Ebola

Communication with family

Isolation in hospital affects the psychological wellbeing of patients, including increased rates of depression, anxiety, anger, fear, and loneliness. Healthcare workers should facilitate communication with family and friends (e.g., use of mobile phones or the internet) in order to reduce psychological distress without increasing the risk of infection. [133]

Experimental therapies

An ethics committee convened by WHO approved the use of five investigational therapies under the framework of compassionate use/expanded access during the 2018 outbreaks in the Democratic Republic of the Congo: ZMapp, remdesivir, REGN3470-3471-3479 (a monoclonal antibody cocktail), favipirivir, and mAb114. [160] The rVSV-ZEBOV vaccine was also used. See Emerging section for more detail on experimental therapies.

Centers for Disease Control and Prevention (CDC): Ebola treatment

Public Health England: Ebola virus disease - clinical management and guidance

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