Summary of COVID-19 medicines guidance: Critical care

David Erskine, Director, London Medicines Information Services, Specialist Pharmacy ServicePublished

This page summarises and signposts to medicine related guidance we’re aware of from professional and government bodies relating to coronavirus and critical care.

Our advice is constantly reviewed as the pandemic situation evolves.

Whilst we have tried to ensure that the information on this page is complete, please report a concern if you feel anything is omitted or inaccurate.

To see our professional guidance summaries for other clinical areas, click here

Advice in this area includes:

DHSC: Publication of an interim position statement: Interleukin-6 inhibitors (tocilizumab or sarilumab) for patients admitted to ICU with COVID-19 pneumonia (adults)

Published 8 January 2021

As emergent (not yet peer-reviewed) data from the immune modulation arm of the REMAP-CAP trial indicate positive benefits with the use of tocilizumab and sarilumab in patients admitted to an intensive care unit (ICU) the DHSC has issued interim guidance on which patients should receive this treatment.

  • Eligible patients include those admitted to ICU with severe pneumonia requiring respiratory support, such as high-flow nasal oxygen, continuous positive airway pressure (CPAP) or non-invasive ventilation, or invasive mechanical ventilation; and whose COVID-19 infection is confirmed by microbiological testing or where a multidisciplinary team has a high level of confidence that the clinical and radiological features suggest that COVID-19 is the most likely diagnosis.
  • Ineligiblity criteria include being in ICU or requiring respiratory support for more than 24 hours, previous hypersensitivity reaction to tocilizumab or sarilumab, having an infection that might be made worse by tocilizumab or sarilumab, having raised transaminase levels (> 5 times upper limit of normal), baseline platelet count < 50×109/L, baseline absolute neutrophil count < 2×109/L, a pre-exisitng treatment or condition that results in ongoing immunosuppression.
  • The recommended dose of tocilizumab is 8mg/kg (up to a maximum of 800mg) to be administered as an intravenous infusion.  A single dose is to be administered, with the option to repeat a dose in 12-24 hours after the initial dose if there has not been sufficient clinical improvement.
  • The recommended dose of sarilumab is 400mg to be given as a once-only intravenous infusion.
  • No adverse interactions with corticosteroids or remdesivir are expected.
  • The interim statement states that tolizumab or sarilumab should not be used during pregnancy unless clinically necessary.

MHRA. CAS Alert:  Corticosteroids in the treatment of suspected or confirmed COVID-19

Issued 3 Sept 2020

Based on the results of the REMAP-CAP trial for hydrocortisone and a meta-analysis of corticosteroids (that included results from 7 RCTs including REMAP-CAP and the RECOVERY study of dexamethasone). The MHRA has advised that corticosteroids have been demonstrated to have a clear place in the management of patients with severe or critical COVID-19 disease (as defined by WHO – definitions provided within CAS) but should not be used in patients with non-severe disease. It is stated the guidance applies primarily to patients who are hospitalised and receiving supplemental oxygen but may apply to some non-hospitalised patients.

The following dose regimens for adults are recommended

  • The recommended regimen in adults is dexamethasone 6mg (orally or by injection) once daily for 7-10 days or hydrocortisone 50mg (by injection) three times daily for 7 -10 days. Treatment should stop if discharged from hospital within 10 days.
  • A longer low-dose hydrocortisone regimen (lasting up to 28 days) may be considered for use in patients with septic shock.
  • Prescribers are referred to relevant SPC for use in children, pregnancy or breastfeeding women.
  • Co- prescription of a PPI should be considered for gastroprotection according to local policies
  • Interaction advice wrt to remdesivir updated to state: “Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely”

 

NICE: COVID-19 prescribing briefing: corticosteroid

Issued 03 Sep 2020

A summary of the evidence to support implementation of the CAS Alert above. Provides a visual representation of the results of the RECOVERY study of dexamethasone in hospitalised patients with COVID-19 who were on oxygen but not mechanical ventilation and patients who were on mechanical ventilation at the start of the study.

 

NHS England/ NHS Improvement. Clinical guide for the management of surge during the Coronavirus pandemic: critical care rapid learning

Last updated 16 May 2020

  • Recommends consideration of mixing anaesthetic medications into a single syringe and using alternative administration routes (e.g. nasogastric delivery of electrolytes and intradermal insulin) to help meet increased demand and prevent shortages of pumps and syringe drivers.

NICE: COVID-19 rapid guideline: critical care in adults

Last updated 3 Sept 2020

  • Provides information on general principles of clinical decision making (including recommendations on appropriate use of the Clinical Frailty Scale) but no specific treatment recommendations except to highlight CAS Alert on use of corticosteroids as discussed above

NHSE/I: Clinical guide for the optimal use of Oxygen therapy during the coronavirus pandemic

November 2020 Version 1

To support prioritisation of oxygen flow for the most severely ill adults, the target saturation levels have been reduced from 94-98% to 92-96%. A lower threshold of 90% may be acceptable in some circumstances.

Royal College of Anaesthetists/ Association of anaesthetistsCovid-19 potential anaesthetic drug list

Published 17 April 2020

Provides a brief overview of key facts for:

  • anaesthetics (thiopental, isoflurance, etomidate and hyperbaric 2% prilocaine)
  • neuromuscular blocking drugs (vecuronium, suxamethonium and pancuronium)
  • analgesics (clonidine, oxycodone, tramadol, pethidine, diclofenac, ketorolac and parecoxib)
  • phenylephrine

Royal College of Anaesthetists/ Association of anaesthetists

Guidance on potential changes to anaesthetic drug usage and administration during pandemic emergency pressures 

Published 2 April 2020 (but now archived)

Advice on potential mitigating actions to reduce impact of increase in demand for medicines used in anaesthesia and critical care. Recommendations include:

  • Work with pharmacy to develop safe ways to use all the contents of drug vials/ ampoules eg through sharing vials
  • Use inhalational anaesthesia for maintenance and restrict use of propofol for maintenance where possible
  • Provides list of alternative medicines/ techniques which could be considered if there are insufficient supplies of first line drugs for induction, neuromuscular blockade (RSI and routine), maintenance, analgesia (short and long-acting), non-opioid analgesia, sedation and transfer, vasopressor (bolus and infusion).

Royal College of Anaesthetists/ Association of anaesthetists

Guidance on adaptations to standard UK critical care medication prescribing and administration practices during pandemic emergency pressures

Published 2 April 2020 (but now archived)

Advice on potential mitigating actions to reduce impact of increase in demand for medicines used in anaesthesia and critical care. Recommendations include:

  • Critical Care and Departments of Anaesthesia should work together to review and reallocate medicine stock supplies from areas where clinical demand has reduced
  • Prepare to adapt and guide local practice, where demand for certain products is high.
  • Consider combining sedatives (eg midazolam and morphine, propofol and alfentanil) following discussion with pharmacists.
  • Regularly review whether intravenous medicines can be changed to an alternative route, particularly enteral
  • Consider bolus dosing/administration of medicines where possible (eg magnesium, certain antibiotics).
  • Provides alternative drug options and clinical advice when first line drug supplies are insufficient to meet demand for sedation, neuromuscular blockade/ paralysis, vasopressors/ vasoactive drugs, non-opioid analgesia/ anti-pyretic, hypoglycaemics, antibiotics, stress ulcer prophylaxis.

The Faculty of Intensive Care Medicine, Intensive Care Society, Association of Anaesthetists and Royal College of Anaesthetists: Joint COVID-19 Guidance Website

  • Provides links to a series of national resources but no specific recommendations

NHS England/ NHS Improvement: Clinical guides for the management of critical care adults in hospital

Last updated November 2020 (just hyperlinks updated from original version published April 2020)

  • Antibiotics should only be considered if there is suspected bacterial superinfection. Consider empirical influenza treatment with oseltamivir until respiratory PCR result is available and be aware that aspergillus co-infections have been reported in patients with COVID-19.
  • Where patients are already taking NSAIDs or ACEIs/ARBs for other conditions, continued treatment is supported by national and international bodies.
  • Routine corticosteroids are not recommended due to risk of prolonged viral shedding, bacterial superinfection and worse outcomes. However, when required for other indications they should not be withheld. Selected use of corticosteroids may be of benefit in hypotension resistant to high dose vasopressor therapy. (but see more recent advice on corticosteroids above)
  • Medical management of renal failure, including diuretics to maintain urine output, may be useful to delay the requirement for renal replacement therapy.
  • Pay close attention to thromboprophylaxis including non-pharmacological (intermittent pneumatic compression stockings, TEDS).
  • Use of pharmacological agents to control delirium may be associated with an increased risk of mortality, especially where long Q-T interval can occur (beware use with other medicines which share this effect).
  • To support prioritisation of oxygen flow for the most severely ill adults, the target saturation levels for all in-patients has been reduced from 94-98% to 92-96%. A lower threshold of 90% may be acceptable in some circumstances.

Administration update (12th January 2021): new material added