Sufentanil
Highly potent μ opioid agonist in anaesthesia and pain therapy
Sufentanil is a synthetic opioid of the fentanyl family and one of the strongest clinically used analgesics overall. Its analgesic potency is about 500 to 1000 times that of morphine and 5 to 10 times that of fentanyl. Janssen developed the substance in the 1970s, and European authorisation followed in 1983. In Germany intravenous preparations (Sufenta) and sublingual tablets (Dzuveo, Zalviso) are available. Sufentanil is a controlled substance under the German Narcotics Act.
It is the standard solution in cardiothoracic anaesthesia, in neurosurgery and in many complex operations. Because of its rapid onset, favourable haemodynamic stability and high lipophilicity, sufentanil is particularly widespread in critically ill patients and in obstetric epidural anaesthesia. The sublingual dosage form offers an option for postoperative pain in selected settings.
Mechanism of Action
Sufentanil is a highly selective μ opioid receptor agonist. After receptor binding, Gi proteins inhibit adenylate cyclase, voltage gated calcium channels close and potassium channels open. Presynaptically, release of excitatory neurotransmitters such as glutamate and substance P is suppressed; postsynaptically hyperpolarisation occurs. Signal transmission in nociceptive fibres is dampened and pain perception is reduced.
High lipophilicity leads to very rapid passage across the blood brain barrier. Intravenous onset of analgesia is 1 to 3 minutes, peak effect at 3 to 5 minutes, with dose dependent duration between 30 minutes and several hours. The context sensitive half life during continuous infusion is more favourable than that of fentanyl.
In contrast to morphine, sufentanil releases practically no histamine, which improves cardiovascular stability. Negative inotropic effects are small and mean arterial pressure remains stable at typical anaesthetic doses. Typical opioid effects such as bradycardia, respiratory depression, constipation and miosis are markedly dose dependent.
Indications
- General anaesthesia: as analgesic in balanced or TIVA based anaesthesia, particularly in cardiothoracic, neurosurgical and major abdominal procedures
- Cardiac anaesthesia: high doses in coronary bypass surgery or valve replacement because of cardiovascular stability
- Epidural and obstetric analgesia: frequently combined with ropivacaine or bupivacaine, small doses act rapidly and selectively analgesic
- Intensive care: analgesic during mechanical ventilation, administered continuously intravenously
- Postoperative pain therapy: sublingual tablets (Zalviso) via a patient controlled dosing system in selected clinics
- Acute analgesia: sublingual single dose (Dzuveo) for moderate to severe acute pain in medically supervised settings
Dosage and Administration
Intravenous anaesthesia: induction 0.25 to 30 µg per kg body weight depending on the procedure and co medication, maintenance as bolus or infusion until the end of surgery. Dose is titrated individually to blood pressure, heart rate and autonomic parameters. Obstetric epidural anaesthesia: often 10 to 20 µg sufentanil together with a local anaesthetic as epidural test dose, followed by continuous infusion.
Sublingual tablets (Dzuveo 30 µg): single dose in medically supervised setting, earliest repeat after one hour. Patient controlled sublingual analgesia (Zalviso 15 µg): dosing controlled by the device, 20 minute lockout between doses, use for a maximum of 72 hours. Duration and indication are determined by the clinician.
Renal impairment: no mandatory dose adjustment, but caution is advised because of potential metabolite accumulation in severe impairment. Hepatic impairment: consider dose reduction because hepatic metabolism via CYP3A4 applies. Use only with continuous monitoring of breathing, circulation and consciousness.
Side Effects
Very common and common: respiratory depression (the most important dose limiting risk), bradycardia, hypotension, sedation, nausea, vomiting, constipation, pruritus (particularly after epidural dosing), muscle rigidity (thoracic rigidity with rapid high dose administration).
Uncommon to rare: laryngospasm, bronchospasm, urinary retention, allergic reactions, postoperative myoclonus, hyperalgesia with prolonged infusion, neurotoxic effects at very high single doses.
Tolerance and dependence: with repeated use, tolerance, physical dependence and withdrawal syndrome are possible. In intensive care with prolonged sedation, stepwise weaning is standard.
Important: the narrow therapeutic window requires administration only by practitioners trained in anaesthesia and resuscitation. Access to a ventilator, oxygen and naloxone must be immediately available.
Interactions
- Other opioids, benzodiazepines, alcohol, sedatives: additive respiratory depression and sedation, combinations raise the risk of fatal respiratory arrest
- CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): sufentanil plasma levels rise, respiratory depression is prolonged
- CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John's wort): plasma levels fall, loss of efficacy
- Monoamine oxidase inhibitors: risk of serotonin syndrome, avoid combination within 14 days of stopping an MAO inhibitor
- Muscle relaxants: sufentanil induced thoracic rigidity complicates ventilation, relaxation facilitates control
- Serotonergic substances (SSRIs, SNRIs, tramadol): risk of serotonin syndrome with concurrent use
Special Notes
Anaesthesia practice: sufentanil may only be given by clinicians experienced in emergency medicine and anaesthesia. Equipment for airway management, ventilation and resuscitation must be available. Postoperative monitoring continues at least until spontaneous breathing returns and pain control is normalised.
High risk patients: advanced age, obesity, sleep apnoea syndrome, severe pulmonary dysfunction, severe hepatic impairment, hypothyroidism, adrenal insufficiency, shock. Dose reduction and intensified monitoring are required in all these groups.
Pregnancy: established and acceptable in obstetric epidural analgesia. With systemic use at higher doses there is a risk of neonatal respiratory depression; readiness with naloxone at the neonate is standard. Breastfeeding: short single doses are usually compatible, with higher doses a pause of several hours is advised.
Driving: after sufentanil administration do not drive or operate machinery for at least 24 hours; individual clearance with the treating physician is required.
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Frequently Asked Questions
How strong is sufentanil compared to morphine?
Depending on the model and receptor binding, sufentanil is about 500 to 1000 times stronger than morphine. Ampoules therefore contain only microgram amounts of active substance, while morphine is dosed in milligrams. This potency makes sufentanil ideal for anaesthesia but demands meticulous care in dosing and monitoring.
Why sufentanil rather than fentanyl?
The reasons are pharmacodynamic. Sufentanil has even higher receptor affinity, a more favourable context sensitive half life with continuous infusion and better cardiovascular stability, which is valued in cardiac surgery. For short procedures and rescue analgesia fentanyl remains equivalent.
Can I drive after a sufentanil anaesthesia?
No, not on the day of the procedure and usually not on the following day either. Even after apparently normal wakefulness has returned, reaction time and judgement can be impaired. Clear the return to driving with your anaesthetist; a minimum of 24 hours usually applies.
Is sufentanil safe in obstetrics?
Yes, at low doses in the epidural setting sufentanil is an established option, mentioned in the S1 guidelines on obstetric epidural analgesia. The onset is rapid and the effect on the neonate is small. Administration is performed by experienced anaesthetists under continuous monitoring.
Sources
- EMA, European Medicines Agency
- AWMF, Guidelines on Anaesthesia and Postoperative Pain Therapy
- Gelbe Liste, Sufentanil active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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