Medic 27 and Engine 227 respond to a report of a traffic collision involving a pedestrian. While en route, they’re advised that the incident involves a skateboarder who shot out into traffic near a local skate park and was hit by a car. On arrival, the crew finds an 8-year-old male patient who’s in extreme pain and presenting with an obvious fracture dislocation of the ankle. As the engine crew works to stabilize and splint the child’s ankle in place, he screams out in pain with every touch or movement of the ankle.
The lead paramedic prepares to establish an IV line to administer morphine to his young patient but can’t see or palpate any peripheral veins. He initially asks for the intraosseous (IO) needle placement gun his service uses on other difficult IV access cases, but his partner reminds him of the child’s pain and the additional pressure and pain the patient will have to endure during the IO procedure. So he changes to the intranasal (IN) delivery of fentanyl to reduce the child’s pain.
Although morphine can produce a better quality of analgesia in many instances, it isn’t as strong or fast-acting as fentanyl and produces a higher incident rate of nausea and vomiting. Fentanyl is lipophilic, allowing rapid penetration through the blood-brain barrier. Consequently, it’s 75–100 times stronger than morphine.
Fentanyl citrate (sublimaze) is a synthetic opioid agonist, which primarily interacts with the mu-opioid receptor of the brain. Activation of the mu-opioid receptor results in analgesia and euphoria. Mostly, the mu-receptors exist presynaptically in the periaqueductal gray region, and in the superficial dorsal horn of the spinal cord.
The periaqueductal gray (PAG), which is also called the “central gray,” is the gray matter around the cerebral aqueduct within the tegmentum of the midbrain. It plays a role in the descending modulation of pain and in defensive behavior.
The ascending pain and temperature fibers of the spinothalamic tract also send information to the PAG via the spinomesencephalic tract (so-named because the fibers originate in the spine and terminate in the PAG, in the mesencephalon or midbrain).
As with morphine, fentanyl can cause some respiratory depression, but to a lesser extent than morphine.1 Mu-receptor activation can also cause nausea and vomiting, and tolerance and dependence with chronic activation. However, fentanyl has less emetic activity than either morphine or meperidine. Histamine assays in test subjects indicate that clinically significant histamine release rarely occurs with fentanyl.2
In a controlled study conducted by Hospira Inc., doses of fentanyl up to 50 mcg/kg showed no clinically significant histamine release. Therefore, fentanyl also presents less hypotensive effects than morphine or meperidine—a fact that should be considered if the patient has lost a significant amount of blood or has the potential to go into shock.
Fentanyl can be given via IV, across mucous membranes or through the skin, intramuscularly (IM) and intrathecally, or through the theca of the spinal cord into the subarachnoid space. However, IN administration of fentanyl can be especially useful in the prehospital emergent care of pediatric patients because it decreases the need for immediate IV access, which can cause pain and stress to young patients already in pain and stressed by the incident or their injury. In fact, IN administration of fentanyl will cause an almost immediate reduction, around 60 seconds, of pain and anxiety and serve to facilitate easier IV access in the pediatric patient.
The safety and effectiveness of fentanyl administration for prehospital pain management has been confirmed in a retrospective chart review of patients who were administered fentanyl and transported by ambulance during 2002–2003.3 Pre- and post-management data were abstracted, including vital signs, verbal numeric pain scale scores, medications administered and recovery interventions. In addition, the emergency department (ED) charts of a sub-group of these patients were reviewed for similar data elements.
The results were that 2,129 patients received fentanyl for prehospital analgesia, and only 12 (0.6%) had a vital sign abnormality that could’ve been caused by the use of fentanyl alone. Only one of the 611 patients who had field and ED charts reviewed had a vital sign abnormality that necessitated a recovery intervention. There were no hospital admissions or patient deaths attributed to the use of fentanyl. There was a statistically significant improvement in subjective pain scores (8.4–3.7).
Clinically, this correlates with improvement from severe to mild pain. This study showed that fentanyl was effective in decreasing pain without causing significant hypotension, respiratory depression, hypoxemia or sedation. Fentanyl citrate can be safely and effectively used for pain management in the prehospital setting.
Fentanyl Dosage Cautions
Fentanyl is mainly metabolized by cytochrome P450 (cyp)3A4 (CYP3A4). The major metabolite is nor-fentanyl, and minor metabolites include despropionylfentanyl, hydroxyfentanyl and hydroxynorfentanyl. These metabolites show negligible pharmacological activity. Unlike other opioid medications, the metabolism of fentanyl is unaffected by liver disease, and because fentanyl doesn’t have active metabolites, its actions are also unaffected by renal failure.4
Co-administration of drugs that inhibit CYP3A4 may impair fentanyl clearance and result in increased or prolonged effects. CYP3A4-inhibiting drugs are macrolide antibiotics, (e.g., azithromycin and clarithromycin) azole antifungal agents (e.g., ketoconazole and fluconazole) and protease inhibitors.
CYP3A4-inducers, such as phenytoin and carbamazepine, will accelerate the metabolism of fentanyl and decrease its half-life. Therefore, patients receiving any of these drugs in combination with fentanyl should be carefully monitored.4
Severe and unpredictable potentiation by the MAO inhibitors, selegiline, procarbazine and phenelzine have been reported for morphine and other narcotic analgesics. This includes serotonin syndrome and hypertension. Although this hasn’t been reported for fentanyl, there is insufficient data to establish that this doesn’t occur with its use. Therefore, when EMS providers administer fentanyl to patients who have received MAO inhibitors in the past 14 days, they should also closely monitor these patients and be ready to administer vasodilators and beta-blockers for the treatment of hypertension if indicated.
As with other potent narcotics, the respiratory depressant effect of fentanyl may persist longer than the measured analgesic effect. After administering fentanyl, providers should monitor their patients for O2 saturation, side stream and/or mainline end-tidal carbon dioxide, blood pressure and respiratory rate, as well as their 12-leads via an ECG machine.
Fentanyl may cause muscle rigidity, particularly involving the muscles of respiration. This effect is related to the dose and speed of injection. If providers encounter stiff chest syndrome, they can manage it by using Narcan or paralyzing the patient and intubating them. Fentanyl may also produce other signs and symptoms that are characteristic of narcotic analgesics including euphoria, miosis, bradycardia and bronchoconstriction.
Because fentanyl is an opioid antagonist, resuscitative and intubation equipment, as well as oxygen, should be readily available when the drug is administered. Peak respiratory depressant effect is between five and 15 minutes after administration. Oxygen should be titrated in conjunction with the patient’s pulse oximetry (SpO2) readings via pulse oximetry to maintain the patient at the 94% level. Fentanyl should also be used with caution in the following patient populations:
- Head injury or suspected head injury;
- Increased intracranial pressure;
- Chronic obstructive pulmonary disorder; or
- Any other condition that can potentially compromise respiration.
Other patient populations for which providers should use caution include pregnant patients, patients in labor and pediatric patients who are younger than 2 years old.
Pregnant patients: Fentanyl citrate has been shown to have teratogenic effects. Providers should use fentanyl on pregnant patients only if the potential benefit justifies the potential risk to the fetus.
Patients in labor: Because there’s insufficient data to support fentanyl use in labor and delivery, such use isn’t recommended.
Pediatric patients younger than 2 years old: The safety and efficacy of fentanyl citrate in children under 2 years of age has not been established.
Providing the appropriate analgesia is both prudent and humane on the part of prehospital providers. Fentanyl is a high-potency opiate with minimal hemodynamic effects. Because of its lipophilic nature and rapid biphasic redistribution, onset of analgesia occurs rapidly, but for a short duration.
Its most significant adverse reaction is dose and administration rate-dependent respiratory depression, which can be managed by the same ALS personnel administering the drug. Its actions can be rapidly reversed with naloxone.
Fentanyl has been shown to be safe and effective in the prehospital setting. As with the administration of any medication to a patient, prehospital personnel must be ever vigilant for any adverse reactions, monitor medicated patients closely and be prepared to reverse or manage their effects via medications or airway management techniques and devices. JEMS
1. Claxton A, McGuire G, Chung F, et al. Evaluation of morphine versus fentanyl for postoperative analgesia after ambulatory surgical procedures. Anesth Analg. 1997;84(3):509–514.
2. Hospira Inc. Fentanyl full prescribing information. (U.S.) 2007.
3. Kanowitz A, Dunn TM, Kanowitz EM, et al. Safety and effectiveness of fentanyl administration for prehospital pain management. Prehosp Emerg Care. 2006;10(1):1–7.
4. Janssen Pharmaceutica. Fentanyl full prescribing information. (U.S.) 2001.
This article originally appeared in August 2011 JEMS as “Fewer Tears & Fears: Intranasal fentanyl administration can relieve pediatric patient pain & anxiety.”
Hanks GW, Conno F, Cherny N, et al. Morphine and alternative opoids in cancer pain: The EAPC recommendations. Br J Cancer. 2001;84(5):587–593.