Clinical Practice Guidelines and Consensus Statements About Pain Management in Critically Ill End-of-life Patients

A Systematic Review

Alejandro Durán-Crane, MD; Andrés Laserna, MD; María A. López-Olivo, MD, PhD, MSC; John A. Cuenca, MD; Diana Paola Díaz, MD; Yenny Rocío Cardenas, MD, MSC; Catherine Urso, BS; Keara O'Connell, BMBS; Kian Azimpoor, BS; Clara Fowler, MSLS; Kristen J. Price, MD; Charles L. Sprung, MD, JD, MCCM; Joseph L. Nates, MD, MBA, CMQ, MCCM


Crit Care Med. 2019;47(11):1619-1626. 

In This Article

Materials and Methods

Protocol and Registration

We conducted our systematic review using the Cochrane method. The protocol was published elsewhere.[12] Our report adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Eligibility Criteria

We included clinical practice guidelines, consensus statements, and benchmarks for quality from global societies and professional organizations that provide recommendations for pain management at the end-of-life in the ICU. We excluded previous versions of guidelines that were updated by the same society or organization.

Information Sources

The databases searched were PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Biblioteca Virtual en Salud from their date of inception to March 28, 2019. No restrictions on language or publication date were used. In addition, two reviewers manually searched the bibliography list of each relevant citation to identify additional eligible articles.


A professional librarian built a specific and sensitive search strategy based on terms defined by an anesthesiologist who specializes in pain management and two ICU anesthesiologists (see the protocol for the complete list of search terms and Boolean operators [12]).

Study Selection

Two investigators independently screened citations from the initial search using a two-step approach in which first the title and then the abstracts were screened for eligibility. For citations that were considered potentially relevant, the full text was retrieved and further screened for eligibility. In cases of disagreement, a third investigator was consulted to determine eligibility.

Data Collection Process

Two investigators independently collected data from eligible publications. Any disagreements were resolved through consensus among three investigators.

Data Items

We collected information on study characteristics, pain assessment recommendations, and suggested interventions for pain management, including recommendations in the following categories: 1) initial drug dosing, titration, maximum dose, and route of administration; 2) side effect management; 3) the principle of "double effect"; 4) neuromuscular blockade use; and 5) palliative care consultation. The authors determined these categories as a way to summarize the literature.

Risk of Bias in Individual Studies

All documents included were assessed independently by four reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE)–II instrument.[13] A final decision by the evaluator was to recommend the document, recommend it with modifications, or not recommend it.

Synthesis of Results

Descriptive statistics were performed for individual AGREE-II domain scores (median and maximum–minimum). The recommendations were examined using a narrative synthesis (tabular and thematic analysis), and the results were presented in categories.