Analgesics used during surgery: From Fentanyl and Remifentanil to PCA and NSAIDs

Introduction

Analgesic management during surgery is one of the core components of anesthesia management. If surgery proceeds with insufficient analgesia, the patient may experience intraoperative awareness, or hemodynamic instability due to increased blood pressure and heart rate. Conversely, overdose of analgesics can lead to respiratory depression, hypotension, and delayed emergence.
To maintain this balance appropriately, anesthesiologists use multiple analgesics according to their characteristics. This article organizes the main analgesics used during and after surgery by their pharmacology, clinical application, and route of administration.

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1. Fentanyl

Basic Information

Fentanyl is a synthetic opioid that acts on μ-opioid receptors. Compared to morphine, it is highly lipophilic and rapidly crosses the blood-brain barrier, resulting in a fast onset of action (1-2 minutes after intravenous injection).
Metabolic pathway: Primarily metabolized to norfentanyl by hepatic CYP3A4 and excreted in urine. It has no active metabolites and is considered less affected by renal impairment.
Duration of action: During continuous infusion, CSDT (context-sensitive decrement time) is prolonged due to accumulation in adipose tissue, which may lead to delayed emergence after long-term administration.

Main side effects
・Respiratory depression (most important; antagonist is naloxone)
・Nausea and vomiting
・Pruritus (especially with neuraxial/epidural administration)
・Constipation and urinary retention
・Chest wall rigidity (with large, rapid doses)

Clinical Usage

Administer 1.5-8 μg/kg intravenously before surgery or during induction, and add 25-50 μg as needed during surgery. The duration of action is about 30-60 minutes, making it suitable for short- to medium-term analgesic supplementation. As the number of doses increases, the duration of action extends, so it is also used for postoperative analgesia.
Use in ICU: Used as continuous analgesia in combination with sedation (dexmedetomidine, propofol). However, caution is required regarding accumulation during long-term administration, and dose adjustment based on regular pain assessment (e.g., NRS, BPS scores) is important.

2. Remifentanil

Basic Information

Remifentanil is a μ-opioid receptor agonist like fentanyl, but it differs decisively in that it has an ester bond in its structure.
Metabolic pathway: Hydrolyzed by non-specific esterases in plasma and tissues.Hardly affected by hepatic or renal function. The metabolite (GR90291) has almost no activity and is excreted renally.
Half-life: The effect-site half-life is extremely short, at about 3-5 minutes.Effects disappear 3-10 minutes after stopping administration is its greatest feature. CSDT is also almost constant, and it does not cause delayed emergence even after long-term administration.

Main side effects
・Respiratory depression (pronounced with rapid administration, stronger than fentanyl)
・Bradycardia and hypotension (vagal stimulation and vasodilation)
・Chest wall rigidity (with large, rapid doses)
・Opioid-Induced Hyperalgesia (OIH: A phenomenon where postoperative pain is exacerbated after long-term, high-dose administration. Early establishment of postoperative analgesia is important)

Clinical Usage

Continuous intravenous infusion is the standard. During surgery, adjust between ~2 μg/kg/min depending on the intensity of surgical stress. Bolus doses may be given during light anesthesia. It has recently become available for use in the ICU.

Distinction from fentanyl:

Precautions when using remifentanil:
Because the analgesic effect disappears immediately upon stopping administration, it is necessary to establish postoperative analgesia before the end of surgery using acetaminophen, NSAIDs, additional fentanyl, or nerve blocks.

3. IV-PCA (Intravenous Patient-Controlled Analgesia)

Concept

PCA (Patient-Controlled Analgesia) is an analgesic management method that allows patients to self-administer additional analgesics by pressing a button when they feel pain. IV-PCA is via intravenous administration. Fentanyl or morphine is used.

Basic elements of settings

Benefits and Precautions

Benefits: Because patients can autonomously adjust analgesia according to their pain, it is less likely to result in excess or deficiency. Good analgesia can be obtained while reducing the frequency of nursing intervention.
Precautions: Proxy operation (family members pressing the button) is strictly prohibited due to the risk of overdose. Monitoring for respiratory depression and over-sedation is necessary. In patients with renal impairment or the elderly, be aware of the accumulation of active metabolites of morphine (fentanyl is often more suitable).

4. Application of fentanyl to regional anesthesia

Subarachnoid administration (intrathecal)

As detailed in the previous article "Spinal Anesthesia," intrathecal administration of fentanyl (10–25 μg) is useful for supplementing early analgesia before the onset of local anesthetics and for reducing visceral traction pain during surgery.
Because of its high lipid solubility, it is rapidly absorbed into spinal tissue, and its duration of action is relatively short, at 2–4 hours. Although the risk of delayed respiratory depression is lower compared to morphine, monitoring for a certain period postoperatively is still necessary.

Epidural administration and PCEA (Patient-Controlled Epidural Analgesia)

Fentanyl is also used for continuous or single-dose administration into the epidural space. A portion of the fentanyl administered epidurally acts directly on the spinal cord, while a portion is absorbed into the systemic circulation.
PCEA (Patient-Controlled Epidural Analgesia) is a form of PCA using an epidural catheter. Typically, a mixture of a local anesthetic (such as 0.1–0.2% ropivacaine) and fentanyl is used.

Typical PCEA setting example

• Ropivacaine 0.1–0.2% + Fentanyl 2–4 μg/mL

• Background infusion: 3–8 mL/h

• Bolus: 2–4 mL

• Lockout: 15–30 minutes

Epidural analgesia has been shown tosignificantly reduce opioid consumptioncompared to systemic administration, and it also contributes to the recovery of bowel motility, reduction of postoperative pulmonary complications, and early mobilization.

5. Acetaminophen and NSAIDs: Non-opioid analgesics

To reduce dependence on opioids and mitigate side effects in postoperative pain management, "multimodal analgesia," which combinesnon-opioid analgesics, is the standard approach. The central drugs for this are acetaminophen and NSAIDs.

Acetaminophen (Acetaminophen / Paracetamol)

Mechanism of action: It acts on both the periphery and the central nervous system, but the details have not been fully elucidated. It is thought to involve the serotonin system, the endocannabinoid system, and COX inhibition (weak). It has almost no anti-inflammatory effect, with antipyretic and analgesic effects being its primary actions.

Characteristics
・Almost no side effects on the gastrointestinal tract or kidneys
・No antiplatelet effect → Does not affect the risk of postoperative bleeding
・Intravenous formulations (Acelio®) are widely used during and after surgery
・Caution regarding hepatotoxicity (dose-dependent; 1g per dose, 4g or less per day)

Standard for postoperative administration: Scheduled administration of 1g per dose every 6 hours is recommended. Scheduled administration stabilizes the blood concentration of the analgesic and can significantly reduce opioid consumption.

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

Mechanism of action: They inhibit COX (cyclooxygenase) and suppress prostaglandin synthesis, thereby exerting anti-inflammatory, analgesic, and antipyretic effects.
Representative drugs: Flurbiprofen (Ropion®), Celecoxib (COX-2 selective)
Characteristics
・Differs from acetaminophen in that it has anti-inflammatory effects
・Can reduce opioid consumption by 30–50%
・Possibility of gastrointestinal ulcers, renal dysfunction, and antiplatelet effects (increased risk of postoperative bleeding)

Key points for selective use

Clinical approach: If there are no issues with gastrointestinal, renal, or bleeding risks, a strategy of combining NSAIDs and acetaminophen on a scheduled basis (such as alternating administration) and using opioids as rescue medication is recommended. For patients with renal impairment or high gastrointestinal risk, avoid NSAIDs and focus on acetaminophen.

Summary

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