Both propofol and benzodiazepines, such as midazolam, depress the central nervous system and cause sedation and amnesia via the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). These actions do not affect pain receptors, so a completely sedated patient may still require pain medication. Although effects are dose-dependent, propofol is preferred for anesthesia and has a quicker onset and recovery period. Midazolam does not decrease blood pressure, respiratory reflexes, or brain activity as much as propofol. Because of this added safety, nurses can "push" midazolam during conscious sedation procedures rather than just relying on an infusion. Individual variability requiring changes to the infusion rate is more pronounced in midazolam, as is also the case for opioids (NYSORA, 2023).
Opioids increase the anesthetic effect of sedation drugs but do not provide amnesia. Their primary action is analgesia due to mu receptor binding in the central nervous system. Sedation drugs combined with sufentanil or remifentanil infusions for the intubated and sedated patient may be encountered. However, the most common opioid for conscious sedation is fentanyl. Synergy is an important concept in pharmacology that healthcare professionals should be familiar with since multiple drugs acting on different receptors create various effects.
Table 1: Common Perioperative Opioids
|Medication||Route||Time to Effect||Duration||Routine Dosage|
|10 mg IV<|
10 mg IM
30-60 mg PO
|Oxycodone||PO||10-15 min||4-6 hours||10-20 mg PO|
|Hydrocodone||PO||30-60 min||4-6 hours||15-30 mg PO|
|Fentanyl||IV||Immediate||1-2 hours||50 mcg IV|
|Codeine||PO||30-60 min||4-6 hours||200 mg|
|Nalbuphine||IM||15 min||3-6 hours||10 mg|
|IV = intravenous, IM = intramuscular, PO = orally|
|NYSORA, 2023; Gadsden, 2017|
Midazolam and fentanyl are an adequate combination, while propofol and remifentanil may cause a decreased possibility of awareness. Except for remifentanil, opioids accumulate in the body to cause respiratory depression, constipation, and other side effects long after discontinuation. These side effects can complicate subsequent dosing, as can tolerance to initial infusion rates as liver enzymes process opioids more quickly. Traditionally, intravenous and inhaled medications are the gold standard for initially bypassing the liver, avoiding the variability dependent on the metabolizing ability of hepatic enzymes. Intranasal and buccal administration of fentanyl or dexmedetomidine is rising in popularity (NYSORA, 2023). Correct doses of oral non-steroidal anti-inflammatory drugs (NSAIDs) block cyclooxygenase (COX) and play an essential role in pain control. Antidepressants, gabapentin, and pregabalin, typically reserved for nerve disorders, are useful adjuncts. Multimodal and preemptive interventions decrease pain and the risk of respiratory depression, constipation, nausea, pruritus, and other unfavorable side effects associated with opioids that usually require reversal agents to attenuate. By using lesser amounts of multiple drugs, the risk of complications from any particular approach or class of medications will hopefully decrease.
Local anesthetics such as lidocaine prevent or relieve pain by binding to receptors on nerve sodium channels to stop nerve conduction. They pass through lipid-soluble nerve membranes but retain a partially ionic form to be active in the sodium channel. They are manufactured as water-soluble salts but do not work well in acidic environments like infected wounds. The influence of pH also means that adding sodium bicarbonate to a local anesthetic speeds onset while decreasing injection pain. Local anesthetists alter the function of all organs conducting or transmitting nerve impulses, so advanced cardiac life support (ACLS) may be needed if an overdose occurs. Plasma concentration depends on the dose, absorption, vascularization, and other properties of the site injected and metabolism by the body. Sensory disturbances such as tongue numbness and tinnitus typically precede life-threatening reactions. Large doses can be used with peripheral nerve blocks without the seizures, coma, and eventually, respiratory and cardiac failure that could follow the same dose in the bloodstream or spinal cord (Gadsden, 2017).
As opioid tolerance increases in the patient population, options are available to provide simultaneous sedation and analgesia. Ketamine targets the N-methyl-D-aspartate (NMDA) receptor to create a dissociative state, while dexmedetomidine stimulates alpha-2 receptors to provide sedation and suppress the release of pain-stimulating neurotransmitters. As in critically ill patients, parameters such as respiratory rate are no longer valid indicators of pain control. Epidural and regional nerve blocks can provide analgesia for the sedated and intubated patient. Intravenous acetaminophen and the non-steroidal anti-inflammatory ketorolac are useful adjuncts in select patients. The dysphoric effects of ketamine or the sedative and hypotensive side effects of alpha-2 agonists require adequate patient and healthcare professional education (NYSORA, 2023).
Table 2: Choice of Local Anesthetic for Peripheral Nerve Blockade
|Anesthetic||Onset (min)||Duration of Anesthesia (h)||Duration of Analgesia (h)|
|3% 2-Chloroprocaine (+ HCO3)||10-15||1||2|
|3% 2-Chloroprocaine (+ HCO3 + epinephrine)||10-15||1.5-2||2-3|
|1.5% Mepivacaine (+ HCO3)||10-20||2-3||3-5|
|1.5% Mepivacaine (+ HCO3 + epinephrine)||10-20||2-5||3-8|
|2% Lidocaine (+ HCO3 + epinephrine)||10-20||2-5||3-8|
|0.5% Bupivacaine or levobupivacaine (+ epinephrine)||15-30||5-15||6-30|
Even if these drugs are rarely used outside surgery or the emergency department in some hospitals, nurses in other specialties require a basic knowledge of their duration and effect. Just as volatile anesthesia agents' physiologic and pharmacologic effects extend into the postoperative period, even short-acting drugs can accumulate and cause side effects much later. Potent drugs for intubation may wear off before sedation infusions reach therapeutic levels. The healthcare professional is responsible for understanding and anticipating potential risks and complications.