Definitions for the strength of evidence (Class I-III) and strength of recommendations (Level A-C) are repeated at the end of the Major Recommendations.
- What are the indications for N-acetylcysteine (NAC) in the acetaminophen overdose patient with a known time of acute ingestion who can be risk stratified by the Rumack-Matthew nomogram?
Level A recommendations. None specified.
Level B recommendations.
- Administer NAC to acute acetaminophen overdose patients with either possible or probable risk for hepatotoxicity as determined by the Rumack-Matthew nomogram to reduce the incidence of severe hepatotoxicity and mortality, ideally within 8 to 10 hours postingestion.
- Do not administer NAC to acute acetaminophen overdose patients with no risk for hepatotoxicity as determined by the Rumack-Matthew nomogram.
Level C recommendations. None specified.
- What are the indications for NAC in the acetaminophen overdose patient who cannot be risk stratified by the Rumack-Matthew nomogram?
Level A recommendations. None specified.
Level B recommendations. Administer NAC to patients with hepatic failure thought to be due to acetaminophen.
Level C recommendations. Administer NAC to patients who have hepatotoxicity thought to be due to acetaminophen and have a suspected or known acetaminophen overdose, including repeated supratherapeutic ingestions.
Definitions:
Literature Classification Schema^
Design/Class |
Therapy* |
Diagnosis** |
Prognosis*** |
1 |
Randomized, controlled trial or meta-analyses of randomized trials |
Prospective cohort using a criterion standard |
Population prospective cohort |
2 |
Nonrandomized trial |
Retrospective observational |
Retrospective cohort
Case control
|
3 |
Case series
Case report
Other (e.g., consensus, review)
|
Case series
Case report
Other (e.g., consensus, review)
|
Case series
Case report
Other (e.g., consensus, review)
|
^Some designs (e.g., surveys) will not fit this schema and should be assessed individually.
*Objective is to measure therapeutic efficacy comparing >2 interventions.
**Objective is to determine the sensitivity and specificity of diagnostic tests.
***Objective is to predict outcome including mortality and morbidity.
Approach to Downgrading Strength of Evidence
Downgrading |
Design/Class |
1 |
2 |
3 |
None |
I |
II |
III |
1 level |
II |
III |
X |
2 levels |
III |
X |
X |
Fatally flawed |
X |
X |
X |
*See "Description of Methods Used to Analyze the Evidence" field for more information.
Strength of Recommendations
Level A recommendations. Generally accepted principles for patient management that reflect a high degree of clinical certainty (i.e., based on strength of evidence Class I or overwhelming evidence from strength of evidence Class II studies that directly address all of the issues)
Level B recommendations. Recommendations for patient management that may identify a particular strategy or range of management strategies that reflect moderate clinical certainty (i.e., based on strength of evidence Class II studies that directly address the issue, decision analysis that directly addresses the issue, or strong consensus of strength of evidence Class III studies)
Level C recommendations. Other strategies for patient management that are based on preliminary, inconclusive, or conflicting evidence, or, in the absence of any published literature, based on panel consensus
There are certain circumstances in which the recommendations stemming from a body of evidence should not be rated as highly as the individual studies on which they are based. Factors such as heterogeneity of results, uncertainty about effect magnitude and consequences, strength of prior beliefs, and publication bias, among others, might lead to such a downgrading of recommendations.