ACEP COVID-19 Field Guide

Authors: Jamie Allen, DO, Chief Resident, Emergency Medicine Residency, Lehigh Valley Health Network; Susan R. Wilcox, MD, FACEP, Division Chief, Critical Care, Department of Emergency Medicine, Associate Professor of Emergency Medicine, Harvard Medical School, Associate Chief Medical Officer, Boston MedFlight; and Nicholas Johnson, MD, FACEP, Assistant Professor Emergency Medicine, Adjunct Assistant Professor Division of Pulmonary, Critical Care, & Sleep Medicine, Associate Program Director, Critical Care Medicine Fellowship.

• Admission or transfer to the ICU should be based on your facility’s criteria for patients meeting “ICU-level care.”
• The average number of days of symptoms for patients requiring hospitalization is 3 to 11 days.
• The average number of days of ICU admission is 9 to 10 days of illness.
• The primary causes of ICU admission include hypoxic respiratory failure and ARDS.

Additional resources

• NIH COVID-19 Treatment Guidelines. 
• Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19) [published online ahead of print, 2020 Mar 28]. Intensive Care Med. 2020;1-34. doi:10.1007/s00134-020-06022-5
• Disclaimer: The information contained herein is subject to change. The final version of the article will be published as soon as approved on ccmjournal.org.
• American Society of Anesthesiologists’ COVID-19: information for health care professionals. ASA website.
• Additional guidance from the American Association for Respiratory Care on SARS CoV-2.

Treatment of hypoxemia

1. NIPPV: Use of BiPAP/CPAP is not routinely recommended due to the risk of aerosolization and an increased 90-day mortality rate, as compared to patients receiving high-flow oxygen.
   1. FLORALI study: There was no significant difference in the overall intubation rates between NIPPV, a nonrebreather mask, and high-flow oxygen, but there was a decreased 90-day mortality rate for patients receiving high-flow nasal cannula (HFNC).
   2. In absence of indication for endotracheal intubation, a closely monitored trial of NIPPV for adults can be used when HFNC is unavailable.
   3. NIPPV should be used in a negative-pressure room, as able. The expiratory limb should be fitted with a viral filter and a tight mask seal should be ensured. Providers caring for patients receiving NIPPV should use airborne precautions.
2. HFNC: HFNC is the preferred noninvasive method of oxygenation in the ICU-level patient.
3. Mechanical ventilation: Low tidal volume ventilation (≤6 ml/kg of predicted body weight) should be used. Plateau pressure should be <30 cmH20. PEEP should be titrated using PEEP ladder or to minimize driving pressure (Plateau-PEEP). Respiratory rate should be set to maintain pH >7.15, if possible. FiO2 and PEEP should be titrated to maintain SpO2 88%-92% or PaO2 >55 mmHg. Additional information can be found in the ARDSnet protocol.

Rapid sequence intubation recommendations

• Perform intubation in a negative-pressure room whenever possible.
• Perform preoxygenation with nasal cannula, a nonrebreather mask, or high-flow nasal cannula, as indicated by the degree of hypoxia.
• Avoid bag-valve-mask (BVM) ventilation whenever possible.
• Rapid sequence intubation is the preferred method.
• Ketamine or etomidate is a reasonable induction agent.
• Succinylcholine or rocuronium 1.5 mg/kg should be used to minimize the time to onset.
• Wait until the neuromuscular block (NMB) has taken full effect to start laryngoscopy to reduce the risk of coughing.
• Propofol may be used for induction, but caution should be taken with dose-dependent hypotension and QTc prolongation if the patient is also receiving azithromycin/hydroxychloroquine.
• Post-induction vasopressor support may be required.
• Use of video laryngoscopy is preferred. Maximize first-pass success, and maintain clinician distance from the airway.
• Intubation should be performed by the most experienced airway manager.
• If BVM is required post intubation, fully inflate the cuff, and use a viral filter prior to bagging or connecting the ventilator.
• Use of a viral filter on BVM and in the ventilatory circuit is strongly recommended.
• Use of EtCO₂ monitoring and visualization of the tube passing the cords are preferred for tube placement confirmation. (Avoid excess exposure to x-ray technicians; avoid close-contact auscultation.) 

Sedation of the ventilated Covid-19 patient

1. Propofol
   1. A national shortage of available propofol may be looming.
   2. QTc prolongation: Caution should be used in patients also receiving azithromycin/hydroxychloroquine.
   3. Hypertriglyceridemia has been noted in critically ill COVID-19 patients.
   4. Caution should be used with prolonged propofol infusions to avoid propofol infusion syndrome.
1. Acts on GABA receptors; sedative/hypnotic
2. Considerations:
2. Benzodiazepines
   1. Benzodiazepines may be preferred over propofol due to a lack of QTc prolongation.
   2. There is less dose-dependent hypotension at therapeutic levels (see “Hemodynamic Characteristics of Midazolam, Propofol, and Dexmedetomidine in Healthy Volunteers”).
   3. Caution should be used with lorazepam and diazepam infusions for propylene-glycol toxicity (eg, unexplained metabolic acidosis, elevated anion gap, hyperosmolality, and then clinical deterioration). 
1. Act on GABA receptors
2. Considerations:
3. Dexmedetomidine
1. Central acting alpha-2 agonist
2. Dexmedetomidine is not recommended as the initial sedative of choice, or at all (preferred in vent weaning, sedation <24 hours).
3. May be suitable for patients undergoing ventilator weaning and breathing trials.

Analgesia of the ventilated COVID-19 patient

• Multiple options include fentanyl, morphine, and dilaudid.
• Considerations: National fentanyl shortages may occur; consider other opioid infusions. 
• NSAIDs: According to the WHO on March 19, there is no scientific evidence to suggest NSAIDs worsen COVID; use NSAIDs cautiously in all critically ill patients.

Vasopressor therapy in the COVID-19 patient

• Agents:
• Norepinephrine
• Vasopressin
• Epinephrine
• Phenylephrine

• Considerations:
• Choice of agents and goals of therapy should still be consistent with the Surviving Sepsis Campaign guidelines.
• Norepinephrine remains the first-line agent of choice for shock.
• Second-line therapy: vasopressin (to raise MAP or decrease norepinephrine dose) or epinephrine added to norepinephrine to maintain MAP >65 mm Hg
• Epinephrine is recommended as the first-line agent for decreased cardiac output or a bradycardic patient.
• Inotropic agents (dobutamine, milrinone) can be considered in patients who demonstrate myocardial dysfunction.

• Bhatraju PK, Ghassemieh BJ, Nichols M, et al. COVID-19 in critically ill patients in the Seattle region - case series [published online ahead of print, 2020 Mar 30]. N Engl J Med. 2020;10.1056/NEJMoa2004500. doi:10.1056/NEJMoa2004500 
• This case series of patients from Seattle describes no new myocardial dysfunction on echocardiogram, although it is a small sample size (N = 9).

Use of paralytics in the mechanically ventilated COVID-19 ARDS patient

• Agents: 
• Rocuronium

• Nondepolarizing agent
• Onset 1 minute
• Recovery time 30 to 40 minutes

• Vecuronium

• Nondepolarizing agent
• Onset 2 to 3 minutes
• Recovery time 30 to 45 minutes

• Cisatracurium

• Onset 5 to 7 minutes
• Recovery 40 seconds to 5 minutes
• Metabolized via Hofmann degradation
• Use in the setting of liver or renal dysfunction.

• Considerations:
• The original ACURASYS study by Papazian et al in 2010 showed 9.1% absolute difference in the 90-day mortality rate in the paralyzed group, although this is not statistically significant.
• Results met significance after being controlled for baseline PaO₂:FiO₂, SAPS II, and plateau pressure.
• The ROSE trial from 2019 showed no difference in the primary outcome or 90-day mortality rate.
• For patients who are sedated but remain dyssynchronous with a ventilator, a NMB is appropriate to facilitate lung-protective ventilation.
• Adequate deep sedation must be given to all paralyzed patients.

Use of prone positioning in ARDS

• A benefit was demonstrated in the PROSEVA trial by Guérin et al in mechanically ventilated patients with severe ARDS (inclusion: ARDS <36 hours; PaO2:FIO2  <150; FIO2 of at least 60%; PEEP >5; Tv: ≤6 ml/kg)
• Benefits: improved oxygenation via improved V/Q matching; keeps alveoli open and evenly distributed at end-expiration to avoid ventilator-induced lung injury 
• Prone positioning for mechanically ventilated patients is recommended for 12 to 16 hours per day.
• Prone positioning can be considered in patients on nasal cannula and high-flow oxygen (ie, non-mechanically ventilated patients). It appears safe and may improve oxygenation, but its impact on mortality, ventilator-free days, or longer-term outcomes is unclear.
  • Prone positioning for non-intubated patients can be done in cycles of 2-4 hours (as tolerated) with brief periods in the supine position for comfort.

• Beneficial in patients with moderate-to-severe ARDS PaO2:FIO2  <150
• The decision to prone a patient should generally be made in conjunction with and after discussion with a critical care attending.
• Multiple complications (eg, device dislodgement, , difficult to perform procedures, facial edema, skin breakdown,; labor intensive)
• Patients should be transitioned back to the supine position at least every 16 hours per the PROSEVA protocol. If patients meet the following criteria >4 hours after returning to the supine position, proning cycles should be stopped. If they do not meet the criteria below, proning cycles should continue.
• PROSEVA criteria for stopping proning improvement in oxygenation: Supine; PaO2:FIO2  ≥150 with PEEP <10 and  FiO2 ≤60%, a decrease in the PaO2:FIO2  of more than 20%  relative to the ratio in the supine position, before two consecutive prone sessions; or complications occurring during a prone session and leading to its immediate interruption

Contraindications:

• Untrained staff
• Increased intracranial pressure; increased abdominal pressure
• Abdominal and/or chest wounds
• Cervical spine injury
• Extreme obesity
• Hemodynamic instability

Use of ECMO for COVID-19 patients

• Veno-venous ECMO is most commonly used.
• 551 suspected or confirmed cases of COVID-19 are on ECMO (worldwide) (as of April 24, 2020).
  • 52/122 (42%) of patients taken off ECMO thus far have been discharged alive.
• Current indications (as of April 1, 2020):
  • pH <7.25 with PaCO₂ >60 for more than 6 hours and no contraindications → use ECMO
  • Try adjunctive measures first:
  • Prone positioning (unless contraindicated), NMB, high PEEP ventilation, inhaled pulmonary vasodilators, or recruitment maneuvers
  • If adjunctive measures fail and any of the following are present and no contraindication to ECMO → use ECMO:
  • P/f <80 for more than 6 hours
  • P/f <50 for more than 3 hours
  • pH <7.25 with PaCO₂ >60 for more than 6 hours
• If P/f ratio >150:
• If P/f ratio <150: 
• Contraindications:
• Terminal disease, severe CNS damage, DNR status, and advanced directives refusing such therapy 
• More information is available via the Extracorporeal Life Support Organization (ELSO):
  • This PDF is available in other languages.
• Extracorporeal Life Support Organization. ELSO guidance document: ECMO for COVID-19 patients with severe cardiopulmonary failure. 2020 Mar 24.
• Extracorporeal Life Support Organization. ECMO for COVID-19. ELSO website.

Additional references

1. Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med. 2006;354(17):1775-1786. doi:10.1056/NEJMoa052052
2. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically ill patients in the Seattle region - case series [published online ahead of print, 2020 Mar 30]. N Engl J Med. 2020;10.1056/NEJMoa2004500. doi:10.1056/NEJMoa2004500
3. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1334-1349. doi:10.1056/NEJM200005043421806
4. Barrot L, Asfar P, Mauny F, et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Engl J Med. 2020;382(11):999-1008. doi:10.1056/NEJMoa1916431
5. Caputo ND, Strayer RJ, Levitan R. Early self-proning in awake, non-intubated patients in the emergency department: a single ED's experience during the COVID-19 pandemic [published online ahead of print, 2020 Apr 22]. Acad Emerg Med. 2020;10.1111/acem.13994. doi:10.1111/acem.13994
6. Guérin C, Reignier J, Richard JC, et al. PROSEVA Study Group. Prone Positioning in Severe Acute Respiratory Distress Syndrome. N Engl J Med (2013);368: 2159–2168. 
7. Sud S, Friedrich J, Adhikari N, et al. Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis. CMAJ (2014);186 (10): 381-390.