Related Experiment Video
Updated: Dec 14, 2025

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex
Published on: July 4, 2018
Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis
Kathleen E Wheeler1, Ryan Grilli2, John E Centofanti1,2
1Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
Abstract:
This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU.
Data Sources:
We searched PubMed, Embase, the Cochrane Library, CINAHL Plus, and Web of Science.
Study Selection:
Two independent reviewers screened citations. Eligible studies included randomized controlled trials comparing efficacy and safety of an adjuvant-plus-opioid regimen to opioids alone in adult ICU patients.
Data Extraction:
We conducted duplicate screening of citations and data abstraction.
Data Synthesis:
Of 10,949 initial citations, we identified 34 eligible trials. These trials examined acetaminophen, carbamazepine, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium sulfate, nefopam, nonsteroidal anti-inflammatory drugs (including diclofenac, indomethacin, and ketoprofen), pregabalin, and tramadol as adjunctive analgesics. Use of any adjuvant in addition to an opioid as compared to an opioid alone led to reductions in patient-reported pain scores at 24 hours (standard mean difference, -0.88; 95% CI, -1.29 to -0.47; low certainty) and decreased opioid consumption (in oral morphine equivalents over 24 hr; mean difference, 25.89 mg less; 95% CI, 19.97-31.81 mg less; low certainty). In terms of individual medications, reductions in opioid use were demonstrated with acetaminophen (mean difference, 36.17 mg less; 95% CI, 7.86-64.47 mg less; low certainty), carbamazepine (mean difference, 54.69 mg less; 95% CI, 40.39-to 68.99 mg less; moderate certainty), dexmedetomidine (mean difference, 10.21 mg less; 95% CI, 1.06-19.37 mg less; low certainty), ketamine (mean difference, 36.81 mg less; 95% CI, 27.32-46.30 mg less; low certainty), nefopam (mean difference, 70.89 mg less; 95% CI, 64.46-77.32 mg less; low certainty), nonsteroidal anti-inflammatory drugs (mean difference, 11.07 mg less; 95% CI, 2.7-19.44 mg less; low certainty), and tramadol (mean difference, 22.14 mg less; 95% CI, 6.67-37.61 mg less; moderate certainty).
Conclusions:
Clinicians should consider using adjunct agents to limit opioid exposure and improve pain scores in critically ill patients.
Related Concept Videos
Analgesia and Pain Management
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Local Anesthetics: Clinical Application as Epidural Anesthesia
Since epidural anesthetics can be infused through an epidural catheter, all types of drugs, including short-acting ones, can be administered. Chloroprocaine and lidocaine are examples of short and long-duration anesthetics, respectively. Bupivacaine...
Opioid Analgesics: Morphine and Other Natural Cogeners
Adrenergic Agonists: Therapeutic Uses
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
Parenteral Anesthetics: Overview

