PURPOSE
- Recognize that large volumes of patients with ARDS from COVID-19 will strain drug supply for many sedative, opiate and paralytic drugs typically used in critical care
- Shortages are expected and as a result the following strategies are recommended:
- conservation strategies
- appropriate substitutions
- purchase strategies
- situational awareness of at-risk medications
- This requires a concerted effort coordinated between government, drug companies, hospital purchasing, pharmacists, nurses and physicians.
- This could impact both COVID-19 and non-COVID-19 critical care patients
- Recognize that choices may deviate from usual practice to preserve optimal supply for the greatest number of patients
GENERAL
- Not all patients require sedatives, opiates or paralytics
- Recommend patient specific ordering, dosing and titration
- Utilize enteral or IV intermittent dosing of drugs to minimize infusions where possible
- Daily assessment of individual patient need for sedatives, opiates, and paralytics
- Daily awakening trials or dose reduction strategies (non-paralysed patient), if appropriate based on ventilator settings
- If delirium identified, initiate appropriate, evidence-based therapies
- These recommendations are for ventilated patients in the critical care environment only
- Patient allergy or intolerance may be a contraindication to these recommendations
- Drug supply and usage is expected to be fluid, and constant re-assessments of priority of use will be required
- decision making will be supported by twice-weekly drug dashboard status reports
OPIATE INFUSIONS
1st line – Hydromorphone (equivalent to 2nd line)
This should be based on local supply considerations.
- Rationale
- Evolving fentanyl shortage
- Prolonged expected duration of infusion
- Easier conversion calculation to enteral formulation vs. fentanyl
- Initiate enteral hydromorphone or morphine at the time of infusion to reduce IV dose requirement
- Suggested initial order
- Hydromorphone infusion 0.5 – 3 mg/hr
- Hydromorphone 2mg NG/OG q6h standing
- Hydromorphone 1-2mg IV q1h PRN
- Monitor for ileus and feeding intolerance as this could be more significant with hydromorphone compared to fentanyl
- If hydromorphone supplies become limited,
2nd line – Fentanyl (equivalent to 1st line)
This should be based on local supply considerations.
- Initiate enteral hydromorphone or morphine at time of infusion to reduce infusion dose requirement and conserve IV supply
- Suggested initial order
- Fentanyl 0-200mcg/hr infusion
- Hydromorphone 2mg NG/OG q6h standing
- Hydromorphone 1-2mg IV q1h PRN
- Consider fentanyl patch in discussion with Critical Care Pharmacist
3rd line – Morphine
- Contraindicated with renal dysfunction
- Acute kidney injury is common in COVID-19 and is often rapid onset and severe, therefore morphine not recommended as primary opiate given above alternatives provided supply is maintained.
4th line – Remifentanil
- Plan
- Review dosage, dispensing, availability
- RN education on use and titration prior to use
- Prioritize use in non-COVID-19 critical care patients requiring opiate infusions
SEDATIVE INFUSIONS
Initial sedation
- Recommend propofol as first-line sedative in patients expected to be ventilated for at least 5 days
- Add lower dose midazolam (intermittent) as required
1st line – Propofol
- If the patient is expected to improve within 1-4 days, consider propofol as 1st line sedative without supplemental benzodiazepines
- In patients requiring additional sedation despite hydromorphone (or fentanyl) and midazolam at 10mg/hr in a steady-state, add propofol at a lower dose (e.g. 0-200mg/hr)
- No specific enteral substitute is available for propofol
2nd line – Midazolam
- Suggested initial order
- Midazolam 2-4mg IV bolus
- Midazolam 3mg/hr infusion (range 0-10 mg/hr)
- Limit of 10mg/hr to prevent accumulation and reduce drug usage
- If sedation inadequate, add lower-dose propofol to midazolam
- Midazolam 2-4mg IV q1h PRN given prior to adjusting infusion dose
- If midazolam shortages pending – change to PRN Lorazepam
- Clonazepam 1mg NG/OG q8h standing
- Midazolam is poorly titratable as an infusion
- Recommend giving bolus dose of the amount to be increased on the infusion rate (e.g. if increasing infusion from 3mg/hr to 5mg/hr, give 2mg bolus then increase).
- Midazolam may accumulate leading to long-term sedation even after the infusion has been stopped – deposition in fat tissue, delayed clearance in acute kidney injury
- Reduce dose by half every morning unless on paralytic infusion
- As ventilator settings improve (e.g PSV, FiO2 < 50%), and/or the patient is approaching liberation from mechanical ventilation, stop midazolam
- start alternate short-acting sedative infusion only if required (e.g. propofol, ketamine, dexmedetomidine).
Additional sedative considerations
Ketamine infusion
- Consider in patients who are challenging to wake up due to coughing fits and associated desaturations or ventilator dyssynchrony
- Ketamine has antitussive properties
- Ketamine infusion can continue during extubation at physician discretion
- Ketamine is in relatively short supply and is not recommended as first line sedative
Dexmedetomidine infusion
- Consider in patients who are challenging to wake up due to delirium or agitation
- Dexmedetomidine infusion can continue during extubation at physician discretion
- Dexmedetomidine is in relatively short supply and is not recommended as first line sedative
Anesthetic gases
- Inhalational sedation can be considered where anesthetic ventilators are being used in a pandemic situation
- Recommend anesthesiology consultation
PARALYTIC INFUSIONS
General
- Paralysis based solely on P/F ratio is NOT recommended as an evidenced based strategy to reduce mortality in all ARDS patients
- All paralyzed patients should be under appropriate deep sedation
- Paralysis infusion is not required for all patients undergoing prone positioning
- Consider bolus dosing PRN if appropriate
- Recommend dose titration based on clinical assessment rather than high fixed-dose infusions
- When paralysis infusion is required it should be used for the shortest possible duration with daily assessment for ongoing need and frequent trials off paralysis (e.g. q24h)
- Recommend rocuronium infusions as first line, unless contraindicated
1st line – Rocuronium
- Rationale
- expected greater supply versus cisatracurium
- Contraindications
- Absolute – allergy
- Relative – severe renal failure (prolonged duration of action)
- Bolus 1mg/kg IV followed by titration of infusion to desired effect.
- Titration range 0.3-0.6 mg/kg/hr
2nd line – Cisatracurium (Nimbex)
- Shortages are expected
- Reserve for patients who have contraindications to rocuronium infusion
- Bolus 0.2 mg/kg IV once, followed by titration of infusion to desired effect
- Titration range 0.06-0.18 mg/kg/hr
Other
- Consider sourcing other paralytic agents if shortage of rocuronium develops
INHALED PULMONARY VASODILATORS
General
- Pulmonary vasodilators may improve oxygenation in ARDS patients, but do not have an evidence based recommendation.
- Inhaled nitric oxide and inhaled flolan are examples of frequently available inhaled pulmonary vasodilators
Inhaled Flolan (epoprostanol)
- See considerations and use in mechanical ventilation document
- Currently on backorder with highly limited supply expected
- Recommend careful patient selection
- If no evidence of significant improvement in oxygenation, it should be discontinued
ANTIBIOTICS
General
- Twice weekly antimicrobial stewardship program (ASP) review is recommended
- Early switch to enteral antibiotics where appropriate to preserve IV supply
Ceftriaxone
- Bacterial co-infection in early COVID-19 disease is very uncommon. Consider stopping.
- Consider early switch to Amoxicillin-clavulanic acid (enteral) based on clinical stability, absorption and ASP review
COVID-19 SPECIFIC THERAPIES
- We recommend enrollment in clinical trials rather than empiric use of non-evidenced based therapies.