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Clinical guidelines are used increasingly to set practice standards
and quality measures. NEJM Journal Watch not only publishes
summaries of the latest clinical research, but also helps you to keep
up with the guidelines most important to general medical practice.
Our physician-editors regularly survey a broad range of medical
journals to identify practice guidelines from a variety of disciplines.
They choose clinically impactful recommendations and highlight
key points, pointing out what’s new and what remains unchanged.
This collection of Guideline Watches is of broad relevance to
clinical practice, spanning outpatient and inpatient medicine and
addressing both primary care and subspecialty perspectives.
We hope you enjoy this compilation and find it useful for providing
the best and most responsible patient care.
New Surviving Sepsis Guidelines
In this update, recommendations include using balanced crystalloid for resuscitation and steroids for persistent
shock.
Patricia Kritek, MD, reviewing Crit Care Med 2021 Nov.
Sponsoring Organizations: Society of Critical Care Medicine (SCCM); European Society of Intensive Care
Medicine (ESICM)
Background
This is the fourth update to these guidelines; the third update was published in 2017 (NEJM JW Gen Med
Mar 1 2017 and Intensive Care Med 2017; 43:304).
Key Points
• The recommendation for an initial fluid bolus of 30 mL/kg was downgraded from a strong
recommendation to a weak recommendation, based on the low quality of evidence. However,
resuscitation should start immediately.
• Balanced crystalloid solution (e.g., lactated Ringer’s solution) should be used (rather than normal
saline) for resuscitation.
• Administration of vasopressors should be initiated via peripheral access, as opposed to waiting for
placement of central venous access.
• Patients with ongoing vasopressor requirements should receive intravenous corticosteroids (this
recommendation was strengthened); however, administration of intravenous vitamin C is explicitly
not recommended.
• Adult patients who survive to discharge should have follow-up for physical, cognitive, and emotional
problems associated with their admission.
COMMENT
These new guidelines highlight what has evolved in the care of patients with sepsis or septic shock
in the past 5 years, while also maintaining emphasis on key principles, such as early, appropriate
antibiotic administration. Many intensivists have balked at a uniform first fluid bolus for all patients
because of potential deleterious effects on frail patients, including those with heart failure or kidney
disease; this update reflects that concern. This change likely will be reflected in the Centers for
Medicare & Medicaid Services (CMS) sepsis bundle measures in 2022. Use of steroids is associated
with faster resolution of shock and shorter length of stay. Many providers have adopted the default
use of balanced crystalloid solutions, as reflected in this document. Finally, the emphasis on long-
term effects of critical illness is important and an area of growing focus.
Key Recommendations
• Patients with isolated subsegmental pulmonary embolism (PE): Rule out proximal deep venous
thrombosis (e.g., with ultrasonography). If risk for recurrent VTE is low, surveillance is recommended
over anticoagulation. If risk for recurrent VTE is high, anticoagulation is recommended. (Weak recom-
mendation, low-certainty evidence)
• Patients with incidentally discovered asymptomatic PE (other than isolated subsegmental PE): Same
initial and long-term anticoagulation that patients with symptomatic PE receive should be used. (Weak
recommendation, moderate-certainty evidence)
• Patients with cancer-associated VTE: Direct-acting oral anticoagulants (DOACs; i.e., apixaban, edoxaban,
or rivaroxaban) should be used for the treatment phase of therapy (strong recommendation, moderate-
certainty evidence). Caveat: for patients with luminal gastrointestinal malignancies, apixaban or low-
molecular-weight heparin is preferred to reduce bleeding risk.
• Patients with antiphospholipid syndrome: Warfarin (target international normalized ratio, 2.5) is
recommended over DOAC therapy during the treatment phase for VTE. (Weak recommendation, low-
certainty evidence)
• Catheter-assisted mechanical thrombectomy: Recommended for patients with PE and hypotension
who also have high bleeding risk, failed systemic thrombolysis, or shock that is likely to lead to death
before systemic thrombolysis can take effect. (Weak recommendation, low-certainty evidence)
• Initial anticoagulation setting: Outpatient treatment is recommended over hospitalization in patients
with low-risk PE, if access to medications and outpatient care is available. (Strong recommendation,
low-certainty evidence)
• Treatment-phase anticoagulants: DOACs are recommended over warfarin. (Strong recommendation,
moderate-certainty evidence)
Extended-phase therapy (beyond 3 months) for VTE: Extended anticoagulation should be offered to
patients with unprovoked VTE — i.e., with no major or minor transient risk factors. Risk for recurrent
VTE, risk for bleeding, and patients’ values and preferences should be considered in decisions about
extended anticoagulation therapy. (Strong recommendation, moderate-certainty evidence)
– Low-dose apixaban or rivaroxaban is recommended over full doses of these agents. (Weak recom-
mendation, very low-certainty evidence)
– Aspirin is recommended for patients who are stopping anticoagulation. (Weak recommendation,
low-certainty evidence)
COMMENT
Although much of the guidance in this update already is prevalent in clinical practice, some of the
updated recommendations might help forge greater consistency among providers who care for
patients with VTE.
