One of the things I have observed over the years is that the distinction between sedation, analgesia and paralysis is commonly misunderstood. This is not unique to paramedicine; it is something I have experienced with healthcare providers at all levels and in many different areas of practice. [Fill out the form on this page to download a set of sedation terminology flashcards to guide your study.]
The goal of this article is to provide some tools to select the appropriate sedative agent, an approach to safely provide sedation and give prehospital providers a common language to use when communicating with other healthcare providers.
What is sedation?
Analgesia and sedation are often referred to together. Clinically, they tend to overlap, but they have different objectives. The goal of analgesia is the relief of pain. Sedation causes a sense of calm by depressing the central nervous system [1]. Several sedatives are referred to as “sedative-hypnotics,” where hypnotic refers to their ability to induce drowsiness or encourage sleep [2].
Intubation and ventilation frequently involve a third class of drugs known as neuromuscular blockers (NMBs) or skeletal muscle relaxants (often referred to as paralytics). There are depolarizing blockers (like succinylcholine) and non-depolarizing blockers (like rocuronium), but both exert their effects by blocking the effects of acetylcholine moving from the nerve to the muscle [2]. Importantly, these drugs have no impact on pain or consciousness; NMBs only block outgoing nerve signals, not incoming sensory nerves.
Practically speaking, this means a patient who receives sedation may be asleep and still experiencing pain. A patient who receives analgesia can have the perception of pain removed and still be awake. Importantly, a patient who receives an NMB can be completely unable to move or even breathe, but still be conscious, awake and experiencing pain.
Sedatives and the brain
One of the most important concepts in understanding how sedatives work is understanding the neurotransmitters glutamate and GABA. Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS), and GABA is the major inhibitory neurotransmitter. They work together; glutamate acts as the brain’s gas pedal, and GABA acts as the brakes. Most sedatives work by pushing harder on the brakes (stimulating GABA) or taking the foot off the gas pedal (blocking glutamate). While several receptors in the excitatory system stimulate glutamate, the most common one manipulated by sedatives is NDMA [2].
Major neurotransmitters involved with sedation
Appreciating the role of glutamate and GABA provides a much deeper understanding of how sedatives are used. A great example of this is the relationship between alcohol and benzodiazepines. Drugs like diazepam (a benzodiazepine) work by stimulating GABA. Alcohol (ethanol), also works by stimulating GABA [2]. This is the pharmacological rationale for why diazepam works to help avoid alcohol withdrawal. With alcohol dependence, the body adapts to the constant GABA stimulation (foot on the brake) by increasing glutamate (stepping on the gas) to maintain balance. If the alcohol is suddenly withdrawn (the foot comes off the brake), but the glutamate is still upregulated (the foot is still on the gas), it is this imbalance, high levels of excitatory neurotransmitters, that leads to seizures in alcohol withdrawal. Treatment of these seizures aims to restore the balance between excitatory and inhibitory neurotransmitters – hence, the role of benzodiazepines such as lorazepam, midazolam or diazepam as first-line anticonvulsants.
Not all sedation is the same!
Sedating a patient can produce a wide range of clinical outcomes, ranging from anxiolysis (you should not operate any heavy machinery) to anesthesia (after you are asleep we will start your surgery). There are four levels of non-dissociative sedation (ketamine falls under the separate category of dissociative). They are based on the patient’s responsiveness, ability to maintain a spontaneous airway, and normal vitals (ASA 2019). The term continuum reflects the fact that a patient can show qualities of more than one category.
Continuum of depth of sedation [7]
Applying standardized terminology allows healthcare providers at all levels to speak a common language. This, combined with an understanding of the fundamental difference between the role of sedation, analgesia and neuromuscular blockers, is necessary for anyone providing sedation.
Table 1: Sedation-related terminology
References
1. Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018: A Report by the American Society of Anesthesiologists Task Force on Moderate Procedural Sedation and Analgesia, the American Association of Oral and Maxillofacial Surgeons, American College of Radiology, American Dental Association, American Society of Dentist Anesthesiologists, and Society of Interventional Radiology. Anesthesiology. 2018 Mar;128(3):437-479. doi: 10.1097/ALN.0000000000002043. PMID: 29334501
2. Katzung BG, Trevor AJ, editors. Basic & clinical pharmacology. 14th edition. McGraw-Hill 2018.
3. Sanders RD, Weimann J, Maze M, Warner DS, Warner MA. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. The Journal of the American Society of Anesthesiologists. 2008 Oct 1;109(4):707-22.
4. Forman SA. Clinical and molecular pharmacology of etomidate. Anesthesiology. 2011 Mar;114(3):695-707. doi: 10.1097/ALN.0b013e3181ff72b5. PMID: 21263301; PMCID: PMC3108152.
5. Kotani Y, Shimazawa M, Yoshimura S, Iwama T, Hara H. The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. CNS Neurosci Ther. 2008 Summer;14(2):95-106. doi: 10.1111/j.1527-3458.2008.00043.x. PMID: 18482023; PMCID: PMC6494023
6. American Society of Anesthesiologists. (Oct 23, 2019). Continuum of depth of sedation: Definition of general anesthesia and level of sedation/Analgesia. Retrieved from https://www.asahq.org/standards-and-guidelines/continuum-of-depth-of-sedation-definition-of-general-anesthesia-and-levels-of-sedationanalgesia
7. Green SM, Krauss B. Procedural sedation terminology: moving beyond “conscious sedation”. Annals of emergency medicine. 2002 Apr 1;39(4):433-5.
