Last Updated: July 8, 2021
Most of the hemodynamic recommendations below are similar to those previously published in the Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Ultimately, adult patients with COVID-19 who require fluid resuscitation or hemodynamic management of shock should be treated and managed identically to adult patients with septic shock.1
- For adults with COVID-19 and shock, the COVID-19 Treatment Guidelines Panel (the Panel) recommends using dynamic parameters, skin temperature, capillary refilling time, and/or lactate levels over static parameters to assess fluid responsiveness (BIIa).
In a systematic review and meta-analysis of 13 randomized clinical trials in intensive care unit (ICU) patients without COVID-19 (n = 1,652),2 dynamic assessment to guide fluid therapy reduced mortality (risk ratio 0.59; 95% CI, 0.42–0.83), ICU length of stay (weighted mean difference -1.16 days; 95% CI, -1.97 to -0.36), and duration of mechanical ventilation (weighted mean difference -2.98 hours; 95% CI, -5.08 to -0.89). Dynamic parameters used in these trials included stroke volume variation (SVV), pulse pressure variation (PPV), and stroke volume change with passive leg raise or fluid challenge. Passive leg raising, followed by PPV and SVV, appears to predict fluid responsiveness with the greatest accuracy.3 The static parameters included components of early goal-directed therapy (e.g., central venous pressure, mean arterial pressure [MAP]).
Resuscitation of patients with shock who do not have COVID-19 based on serum lactate levels has been summarized in a systematic review and meta-analysis of seven randomized clinical trials (n = 1,301). Compared with central venous oxygen saturation-guided therapy, early lactate clearance-directed therapy was associated with a reduction in mortality (relative ratio 0.68; 95% CI, 0.56–0.82), shorter ICU stay (mean difference -1.64 days; 95% CI, -3.23 to -0.05), and shorter duration of mechanical ventilation (mean difference -10.22 hours; 95% CI, -15.94 to -4.50).4
- For the acute resuscitation of adults with COVID-19 and shock, the Panel recommends using buffered/balanced crystalloids over unbalanced crystalloids (BIIa).
A pragmatic randomized trial compared the use of balanced and unbalanced crystalloids for intravenous (IV) fluid administration in critically ill adults without COVID-19 (n = 15,802). The rate of the composite outcome of death, new renal-replacement therapy, or persistent renal dysfunction was lower in the balanced crystalloids group than in the unbalanced crystalloids group (OR 0.90; 95% CI, 0.82–0.99; P = 0.04).5 A secondary analysis compared outcomes in a subset of patients with sepsis (n = 1,641). Compared to treatment with unbalanced crystalloids, treatment with balanced crystalloids resulted in fewer deaths (aOR 0.74; 95% CI, 0.59–0.93; P = 0.01) and more vasopressor-free and renal replacement-free days.6 A subsequent meta-analysis of 21 non-COVID-19 randomized controlled trials (n = 20,213) that included the pragmatic trial cited above compared balanced crystalloids to 0.9% saline for resuscitation of critically ill adults and children. The trial reported nonsignificant differences between the treatment groups in hospital mortality (OR 0.91; 95% CI, 0.83–1.01) and acute kidney injury (OR 0.92; 95% CI, 0.84–1.00).7
- For the acute resuscitation of adults with COVID-19 and shock, the Panel recommends against the initial use of albumin for resuscitation (BI).
A meta-analysis of 20 non-COVID-19 randomized controlled trials (n = 13,047) that compared the use of albumin or fresh-frozen plasma to crystalloids in critically ill patients found no difference in all-cause mortality between the treatment groups.8 In contrast, a meta-analysis of 17 non-COVID-19 randomized controlled trials (n = 1,977) that compared the use of albumin to crystalloids specifically in patients with sepsis observed a reduction in mortality among the patients who received albumin (OR 0.82; 95% CI, 0.67–1.0; P = 0.047).9 Given the higher cost of albumin and the lack of a definitive clinical benefit, the Panel recommends against the routine use of albumin for initial acute resuscitation of patients with COVID-19 and shock (BI).
- For adults with COVID-19 and shock, the Panel recommends norepinephrine as the first-choice vasopressor (AI).
Norepinephrine increases MAP due to its vasoconstrictive effects, with little change in heart rate and less increase in stroke volume compared to dopamine. Dopamine increases MAP and cardiac output, primarily due to an increase in stroke volume and heart rate. Norepinephrine is more potent than dopamine and may be more effective at reversing hypotension in patients with septic shock. Dopamine may be particularly useful in patients with compromised systolic function, but it causes more tachycardia and may be more arrhythmogenic than norepinephrine.10 It may also influence the endocrine response via the hypothalamic pituitary axis and have immunosuppressive effects.11 A systematic review and meta-analysis of 11, non-COVID-19 randomized controlled trials that compared vasopressors used to treat patients with septic shock found that norepinephrine use resulted in lower all-cause mortality (RR 0.89; 95% CI, 0.81–0.98) and a lower risk of arrhythmias (RR 0.48; 95% CI, 0.40–0.58) than dopamine use.12 Although the beta-1 activity of dopamine would be useful in patients with myocardial dysfunction, the greater risk of arrhythmias limits its use.13,14
- For adults with COVID-19 and shock, the Panel recommends titrating vasoactive agents to target a MAP of 60 to 65 mm Hg, over higher MAP targets (BI).
A recent individual patient-data meta-analysis of two, non-COVID-19 randomized controlled trials (n = 894) comparing higher versus lower blood pressure targets for vasopressor therapy in adult patients with shock reported no significant difference between the patients in the higher and lower target groups in 28-day mortality (OR 1.15; 95% CI, 0.87–1.52), 90-day mortality (OR 1.08; 95% CI, 0.84–1.44), myocardial injury (OR 1.47; 95% CI, 0.64–3.56), or limb ischemia (OR 0.92; 95% CI, 0.36–2.10).15 The risk of arrhythmias was increased in patients allocated to the higher target group (OR 2.50; 95% CI, 1.35–4.77). Similarly, the recently published “65 Trial,” a randomized clinical trial in patients without COVID-19 (n = 2,463), reported no significant difference in mortality between patients with vasopressor therapy guided by a MAP target of 60 to 65 mm Hg and those with treatment guided by a higher, standard of care MAP target (41% vs. 43.8%; RR 0.93; 95% CI, 0.85–1.03).16 With an indication of improved outcome with lower MAP targets (and no firm indication of harm), the Panel recommends titrating vasoactive agents to a MAP target of 60 to 65 mm Hg (BI).
Additional Recommendations for Adults With COVID-19 and Shock Based on General Principles of Critical Care
- The Panel recommends against using hydroxyethyl starches for intravascular volume replacement in adult patients with COVID-19 and sepsis or septic shock (AI).
- When norepinephrine is available, the Panel recommends against using dopamine for adult patients with COVID-19 and shock (AI).
- As a second line vasopressor, the Panel recommends adding either vasopressin (up to 0.03 units/min) (BIIa) or epinephrine (BIIb) to norepinephrine to raise MAP to target or adding vasopressin (up to 0.03 units/min) (BIIa) to decrease norepinephrine dosage.
- The Panel recommends against using low-dose dopamine for renal protection (AI).
- The Panel recommends using dobutamine in adult patients with COVID-19 who show evidence of cardiac dysfunction and persistent hypoperfusion despite adequate fluid loading and the use of vasopressor agents (BIII).
- The Panel recommends that all adult patients with COVID-19 who require vasopressors have an arterial catheter placed as soon as practical, if resources are available (BIII).
- For adult patients with refractory septic shock who have completed a course of corticosteroids to treat COVID-19, the Panel recommends using low-dose corticosteroid therapy (“shock-reversal”) over no corticosteroid therapy (BIIa).
- A typical corticosteroid regimen in septic shock is hydrocortisone 200 mg IV per day administered either as an infusion or in intermittent doses. The duration of hydrocortisone therapy is usually a clinical decision.
- Adult patients who are receiving corticosteroids for COVID-19 are receiving sufficient replacement therapy such that they do not require additional hydrocortisone.
- Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486-552. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28098591.
- Bednarczyk JM, Fridfinnson JA, Kumar A, et al. Incorporating dynamic assessment of fluid responsiveness into goal-directed therapy: a systematic review and meta-analysis. Crit Care Med. 2017;45(9):1538-1545. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28817481.
- Bentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT. Will this hemodynamically unstable patient respond to a bolus of intravenous fluids? JAMA. 2016;316(12):1298-1309. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27673307.
- Pan J, Peng M, Liao C, Hu X, Wang A, Li X. Relative efficacy and safety of early lactate clearance-guided therapy resuscitation in patients with sepsis: a meta-analysis. Medicine (Baltimore). 2019;98(8):e14453. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30813144.
- Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378(9):829-839. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29485925.
- Brown RM, Wang L, Coston TD, et al. Balanced crystalloids versus saline in sepsis. a secondary analysis of the SMART clinical trial. Am J Respir Crit Care Med. 2019;200(12):1487-1495. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31454263.
- Antequera Martin AM, Barea Mendoza JA, Muriel A, et al. Buffered solutions versus 0.9% saline for resuscitation in critically ill adults and children. Cochrane Database Syst Rev. 2019;7:CD012247. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31334842.
- Lewis SR, Pritchard MW, Evans DJ, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018;8:CD000567. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30073665.
- Delaney AP, Dan A, McCaffrey J,Finfer S. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis. Crit Care Med. 2011;39(2):386-391. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21248514.
- Regnier B, Rapin M, Gory G, Lemaire F, Teisseire B, Harari A. Haemodynamic effects of dopamine in septic shock. Intensive Care Med. 1977;3(2):47-53. Available at: https://www.ncbi.nlm.nih.gov/pubmed/893773.
- Beck G, Brinkkoetter P, Hanusch C, et al. Clinical review: immunomodulatory effects of dopamine in general inflammation. Crit Care. 2004;8(6):485-491. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15566620.
- Avni T, Lador A, Lev S, Leibovici L, Paul M, Grossman A. Vasopressors for the treatment of septic shock: systematic review and meta-analysis. PLoS One. 2015;10(8):e0129305. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26237037.
- Regnier B, Safran D, Carlet J, Teisseire B. Comparative haemodynamic effects of dopamine and dobutamine in septic shock. Intensive Care Med. 1979;5(3):115-120. Available at: https://www.ncbi.nlm.nih.gov/pubmed/500939.
- De Backer D, Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Crit Care Med. 2003;31(6):1659-1667. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12794401.
- Lamontagne F, Day AG, Meade MO, et al. Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med. 2018;44(1):12-21. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29260272.
- Lamontagne F, Richards-Belle A, Thomas K, et al. Effect of reduced exposure to vasopressors on 90-day mortality in older critically ill patients with vasodilatory hypotension: a randomized clinical trial. JAMA. 2020;323(10):938-949. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32049269.