According to the 2015 South African Society of Anaesthesiologists (SASA) pain guideline, intravenous (IV) remifentanil offers equivalent analgesia to morphine and is associated with less nausea and vomiting.³

Furthermore, state the authors of the guideline, remifentanil is safe to use during caesarean sections, and is a ‘very useful agent in the critical care environment’.³

According to the authors of the 2020-2025 SASA guidelines for the safe use of procedural sedation and analgesia for diagnostic and therapeutic procedures in adults, remifentanil is a valuable supplemental sedative for short painful, as well as longer, procedures.⁴

The guidelines describe remifentanil as ‘an extremely potent, ultrashort-acting opiate that can be used in combination with hypnotic sedatives to provide sedation and analgesia’.⁴

How to use remifentanil

The authors stress that remifentanil should not be used outside the hospital environment and must not be administered by any person other than anaesthetists or highly trained sedation practitioners with anaesthetic experience.⁴

For procedural sedation and analgesia (PSA), small bolus doses can be titrated, but with extreme care. The dose administered by continuous infusion must not exceed 0.05μg/kg/minute.⁴

Remifentanil when used with propofol for PSA should be administered in a separate syringe. Precise titration of remifentanil when used in combination with propofol should be achieved by using target-controlled infusions.⁴

Advantages of remifentanil

The main advantage of remifentanil, developed in 1987, is its extremely brief half-life. The elimination half-life is three to six minutes and is independent of dose and duration. The drug is cleared by nonspecific blood and tissue esterases, without the involvement of the liver. Other short-acting opiates require hepatic clearance.⁴

Furthermore, remifentanil’s analgesic effect occurs within 60 seconds to 1.6 minutes compared to fentanyl, which takes around 6.6 minutes. Remifentanil’s effect peaks at two minutes and its duration of action is 20 minutes.^4,5,6,7

Compared to other short acting opioids (fentanyl, alfentanil and sufentanil), remifentanil is associated with deeper anaesthesia and analgesia intra-operatively.⁸

A large trial involving more than 2 500 in- and outpatients treated with fentanyl or remifentanil found that patients treated with the latter, responded to verbal commands faster (after both inpatient and outpatient surgery), and, after day surgery, recovered faster and were discharged from hospital sooner.⁸

Another study showed that patients treated with remifentanil regained post-operative functional abilities earlier compared to those who received fentanyl.⁸

Patients treated with remifentanil experienced effective analgesia and attenuation of intraoperative responses irrespective of their age (including paediatric and elderly patients), body weight, the degree of renal or hepatic impairment, type (eg major abdominal, coronary artery bypass graft, neuro-, ear, nose, and throat, or ophthalmic surgeries) and duration of surgery being undertaken, whether the drug was combined with IV or volatile hypnotic agents, or whether the drug was used in the in- or outpatient setting.⁸

Data also suggested that IV remifentanil is an effective opioid analgesic during caesarean section, with generally no significant difference in Apgar or Neurologic and Adaptive Capacity Scores at most time points in neonates born to mothers receiving a remifentanil-versus a fentanyl-based anaesthetic regimen.⁸

Furthermore, remifentanil’s rapid offset allows for earlier neurological assessment during sedation holds, and there is no need for dose adjustments in patients with chronic or acute kidney injury (offset times are about twice as long in moderate-severe renal impairment, however, as the difference is only 16.5 minutes this is not usually significant).⁹

Remifentanil’s predictable offset times makes it particularly suitable for use in patients with multi-organ dysfunction.⁹

 Importance of patient selection

Safe use of remifentanil relies on appropriate patient selection. Remifentanil is not suitable for any patient that has a potentially difficult airway, is morbidly obese, is not starved, or is for a potentially prolonged procedure.⁸

It also needs to be carried out in a location that is equipped to deal with any complications and has full monitoring and a resuscitation kit available.⁸

Key messages⁸

• Remifentanil is a versatile drug that can be used in various anaesthetic and critical care situations
• It has an ultrafast offset and short half-life, making it an ideal agent for analgosedation in the ICU
• It can be used effectively for awake fibre-optic intubation and conscious sedation
• When epidural is not possible, remifentanil patient-controlled analgesia can be used in obstetric units that are set up for its use
• Using target controlled infusions and avoiding boluses will help to avoid significant cardiovascular and respiratory side effects of remifentanil.

REFERENCES

1. Schumacher M and Fukuda K. Opioids. Miller’s Anesthesia, 24, 680-741.e15.
2. Mobi Mims. Parenteral anaesthetics. https://www.mobimims.co.za/Product/Index?id=dd70f701-49c0-4b91-96f6-23cdc335fee8&classificationid=2e023cf7-9984-49dd-9e7f-d797f1c6c51b
3. South African Society of Anaesthesiologists (SASA). South African Acute Pain Guidelines. https://painsa.org.za/wp-content/uploads/2016/07/SASA-Acute-Pain-Guidelines_2015.pdf
4. South African Society of Anaesthesiologists (SASA). Guidelines for the safe use of procedural sedation and analgesia for diagnostic and therapeutic procedures in adults: 2020–2025. file:///C:/Users/rene.bosman/Downloads/robyn,+Journal+editor,+SAJAA(V26)+2392+SASA+Adult+Guidelines+for+Procedural+Sedation+and+Analgesia.pdf
5. Vutskits L and Davidson A. Pediatric Anesthesia. Miller’s Anesthesia, 77, 2420-2458.e6.
6. Shafi A, Berry AJ, Sumnall H, et al.Synthetic opioids: A review and clinical update. Therapeutic Advances in Psychopharmacology, 2022.
7. Scott LJ, Perry CM. Remifentanil: a review of its use during the induction and maintenance of general anaesthesia. Drugs, 2005.
8. Atterton B, Lobaz S. Remifentanil use in Anaesthesia and Critical Care. World Federation of Societies of Anaesthesiologists. Online activity. https://resources.wfsahq.org/atotw/remifentanil-use-in-anaesthesia-and-critical-care/