Article, Emergency Medicine

Intranasal sufentanil for the treatment of acute pain in a winter resort clinic

Unlabelled imageAmerican Journal of Emergency Medicine (2012) 30, 1817-1821

Original Contribution

Intranasal sufentanil for the treatment of acute pain in a winter resort clinic?

Jacob Steenblik BS, Mark Goodman MD, Virgil Davis MD, Christopher Gee MD, Christy L. Hopkins MD?, Robert Stephen MD, Troy Madsen MD

Department of Surgery, Division of Emergency Medicine, University of Utah School of Medicine, Salt Lake City, Utah

Received 8 December 2011; revised 29 February 2012; accepted 29 February 2012


Introduction: Painful extremity injuries are common patient complaints in resort clinics, urgent care clinics, and emergency departments. We hypothesized that intranasal (IN) sufentanil could provide rapid, noninvasive, effective pain relief to patients presenting with acute extremity injuries.

Methods: This was an unblinded, nonrandomized, observational study that enrolled a convenience sample of patients presenting to a university-affiliated ski clinic with acute moderate to severe pain associated with a traumatic injury between the months of January and March 2011. Patients were excluded if they reported an allergy to sufentanil or had hypoxia, significant head injury, or hypotension. Nurses administered IN sufentanil using an IN atomizer device. The nurse recorded patient-reported pain scores (0-10 scale) on arrival and at 10, 20, and 30 minutes after administration of sufentanil.

Results: During the study period, 40 patients were enrolled; 75% were men. The average age was 32 years (range, 16-60 years). The average dose of sufentanil was 37.7 ug. Five patients (12.5%) were given additional IN analgesia. Average pain on arrival was 9 (on a 10-point scale), and the mean reduction in pain scores was 4.7 (95% confidence interval [CI], 3.67-5.57) at 10 minutes, 5.79 (95% CI, 4.81-6.77) at 20 minutes, and 5.74 (95% CI, 4.72-6.76) at 30 minutes.

Conclusion: In this limited observational trial, IN sufentanil provided rapid, safe, and noninvasive pain relief to patients presenting with acute traumatic extremity injuries. Given the ease of administration, this may serve as a viable option for use in other settings, such as urgent care clinics and emergency departments.

(C) 2012


Painful extremity injuries, such as closed fractures, severe sprains, and Joint dislocations, comprise a large number of visits to winter resort clinics, urgent care centers, and

? Study support: There was no source of support, including grant support for this study.

* Corresponding author. University of Utah, Division of Emergency

Medicine, 30 North 1900 East, Room 1C026, Salt Lake City, UT 84132.

E-mail address: [email protected] (C.L. Hopkins).

emergency departments (EDs). Intranasal (IN) opiate administration may provide an alternative option for the administration of pain relief that is rapid, painless, and noninvasive [1].

Although patients with acute injuries may have moderate or severe pain, they often do not need an intravenous (IV) line placed for anything except Acute pain control. Placement of IV line is painful for patients and delays the Administration of analgesia. The delayed onset and difficult titration of oral and Intramuscular injections makes these routes suboptimal for rapid pain control. In addition, IV placement in more

0735-6757/$ – see front matter (C) 2012

austere conditions may not be performed because of limitations in both staff and supplies. The end result is that such patients often do not receive adequate pain control in a timely fashion.

Numerous studies exist confirming the efficiency and safety of IN opiates in postoperative patients [2-6]. In the ED and emergency medical system settings, the IN and intramuscular delivery of opiates for the treatment of painful extremity fractures has been shown to be clinically comparable in terms of both efficacy and safety [7-10]. This has been best studied in the pediatric population, where IN opiates have been recommended to rapidly control pain associated with isolated orthopedic injuries [7,8,10].

One drawback to the use of IN opiates in adults is the excessive volume of medication required to achieve adequate analgesia. The nasal cavity has limitED capacity for drug delivery and absorption. The ideal volume for absorption, with limited run off, is 0.5 mL or less in each nare [1,11]. Standard concentrations of fentanyl (50 ug/mL) when used in an adult weighing 70 kg would require a volume of almost 3 mL, which precludes adequate delivery of this drug. In the study by Saunders et al [10], the authors noted that fentanyl, at the standard concentration of 50 ug/mL, was less effective in teenagers because of the larger volumes of medication required to achieve pain relief. This was attributed to, in part, the increased oral run off from the high volumes of medication needed. Previous authors have reconcentrated the standard fentanyl concentration of 50 ug/mL to a concentrated dose of 150 ug/mL [7,9]. Unfortunately, the highly concentrated dose of fentanyl is not readily available and requires pharmacy compounding, which greatly adds to the cost of the drug.

Sufentanil is a synthetic opiate that is similar to fentanyl. It is better suited for optimal IN analgesia in adults because of its increased potency, low cost, and high therapeutic index. Sufentanil has 5 to 8 times the potency and twice the lipophilicity of fentanyl [12]. In addition, sufentanil has been found to have near 100% bioavailability at 30 minutes with a lower rate of cardiac and respiratory side effects than an equivalent dose given intravenously [12]. The generic formulation of sufentanil is inexpensive and readily available in the United States at a cost of less than $3.00 for 50 ug/mL. In addition, sufentanil has a high therapeutic index and a short half-life of 15 to 20 minutes. These characteristics suggest that it may be an ideal pain medication for transmucosal delivery to adult patients having acute pain.

We hypothesized that IN sufentanil could provide rapid, safe, and effective pain relief to patients presenting with extremity injuries and moderate to severe pain.


This was an unblinded, nonrandomized, observational study that was performed at an affiliate ski clinic of the University of Utah. Patients were enrolled between January 1 and April 17, 2011. Investigators enrolled a convenience

sample of patients between the ages of 16 and 60 years who presented with moderate to severe pain associated with an acute traumatic injury sustained at the nearby winter resort. The study was approved by the University of Utah’s Institutional Review Board.

Patients were included if they were able to consent to participation and did not display signs of impaired cognition. Patients were excluded if they had any clinical contraindi- cation to narcotic analgesia, a history of allergies to sufentanil or its components, preexisting hypoxia (oxygen saturation b88%), significant head injury requiring mental status monitoring, hypotension (systolic blood pressure [SBP] b90 mm Hg), nasal trauma or congestion precluding administration of IN medication, significant additional injuries that precluded the use of a narcotic analgesia, or clinically significant drug or alcohol intoxication.

Before the initiation of the study, clinic nurses were instructed on how to administer the IN sufentanil and trained on the treatment of potential complications. The staff used a standardized weight-based dosing medical record to aid in appropriate dosing and administration of the drug and recorded basic patient demographic information on a study sheet (see Appendix). Study authors were excluded from participating in the Satisfaction survey.

Nurses administered IN sufentanil at a dose of 0.5 ug/kg using an IN atomizer device while under physician supervision. All pain medications, dosages, and complica- tions were recorded. Patients were monitored for adverse events (sedation, respiratory depression, and hypotension) during the 30 minutes after medication administration.

Nursing staff used the 0 to 10 Numeric rating scale to document the initial and subsequent pain scores. Patients were verbally asked to self-report their pain intensity, with a score of “0” representing no pain and a score of “10” representing the worst pain the patient has experienced. We evaluated the efficacy of the therapy using both changes in pain scores as well as patient report of overall satisfaction with the treatment of their pain. The nursing staff was not blinded to the intent of the study.

Descriptive statistics were used to characterize the study population. The mean difference between the patient’s initial and subsequent pains scores were calculated after medication administration (STATA v. 7.0), StataCorp LP College Station, TX).


A total of 40 patients were enrolled during the 3.5-month study period. Seventy-five percent of the patients were men, and the average age for the study group was 32 years (range, 16-60 years). The most frequent injuries reported were upper extremity dislocations (55%) (see Table).

The average dose of IN sufentanil was 37.7 ug (95% confidence interval [CI], 35.3-40.1 ug). Five patients (12.5%) were given additional IN sufentanil at an average dose of 27.5

Injury a No. of patients (%)

Upper extremity dislocations

22 (55)

Upper extremity fractures

10 (25)

Lower extremity fractures

9 (23)

Lower extremity dislocations

1 (2.5)

Not recorded

a Some patients had multiple injuries.

1 (2.5)

ug (95% CI, 12.8-42.2 ug). Average pain scores were lower at the 10-, 20-, and 30-minute intervals when compared with the initial pain scores (see Fig.). The average self-reported initial pain score was 9. The mean reduction in pain scores (compared with initial scores) was 4.7 (95% CI, 3.67-5.57)

Table Specific injuries

at 10 minutes, 5.79 (95% CI, 4.81-6.77) at 20 minutes, and

5.74 (95% CI, 4.72-6.76) at 30 minutes.

The most common complication was dizziness, which occurred in 3 patients (7.5%). Two patients (5%) reported inadequate pain control. Vomiting was recorded in 1 patient (2.5%). In addition, hypoxia (oxygen saturation of 88%) occurred in 1 patient (2.5%) who had received a second dose of sufentanil. There were no episodes of hypotension or apnea recorded. Three patients received other forms of analgesia (2 received oral hydrocodone, and 1 received 50 ug of fentanyl).

Patient and provider satisfaction were recorded using a 5- point scale. Seventy-eight percent of patients, 83% of nurses, and 87% of physicians reported that they were “very satisfied” with treatment.


In this limited observational trial, sufentanil provided safe and effective pain relief of Isolated extremity injuries. Sufentanil, which is more concentrated than fentanyl, overcomes one of the major obstacles to delivery of IN opioid in adults, the large volume of solution required to achieve adequate analgesia. In addition, sufentanil’s rapid onset of action, low cost, and noninvasive delivery are

Mean Numeric rating scale -Pain Scale








Mean NRS pain score









Initial Score 10 Minutes 20 Minutes 30 Minutes

Fig. Mean numeric rating scale–pain scale.

attractive qualities for providers caring for patients who require rapid pain relief in environments that limit other forms of drug administration.

Intranasal sufentanil was effective in rapidly controlling acute pain in children and adults. The mean reduction in pain scores was 4.7 at 10 minutes, which was attributed to the drug’s rapid onset of action. The mean difference in pain scores increased to 5.7 at both 20- and 30-minute marks, exhibiting the lasting effect of analgesia.

Of the 40 patients, 35 (87.5%) achieved adequate pain control after 1 dose of medication, and 5 patients (12.5%) required an additional dose of IN sufentanil. Two patients (5%) reported inadequate pain control with the IN sufentanil. Redosage of medication may be more common in patients at the upper limits of weight range, in patients who take chronic pain medications, or in patients undergoing painful pro- cedures. Factors contributing to suboptimal pain control with this medication will require further study.

High patient, nurse, and provider satisfaction not only demonstrates effective pain control but also speaks of the ease of administration and minimal patient discomfort associated with IN use. Intranasal sufentanil may also be useful in procedural sedation for common procedures such as fracture care, Joint reductions, and laceration repairs. This was not specifically evaluated for in this case series and would require further study.

The delivery of IN sufentanil in our study resulted in minimal side effects. The most common side effect observed was dizziness (7.5%), followed by inadequate pain control (5%). Notably, hypoxia was observed in only

1 patient (2.5%) who had received a second dose of medication. There were no reported episodes of apnea. Our results are consistent with prior studies showing minimal side effects of IN sufentanil when administered at doses of less than 1.5 ug/kg [12,13]. The substantial decrease in pain scores and the high rate of patient and provider satisfaction, coupled with the minimal observed side effects, suggest that low-dose sufentanil (0.5 ug/kg) may be an optimal starting dose for control of acute pain in less monitored settings.

This study has several important limitations. Foremost, this study was an exploratory, unblinded, nonrandomized, observational study performed at a single site. In addition, this study was performed exclusively on patients presenting with extremity injuries. This population, in general, is composed of younger active individuals; thus, extrapolation of our results to other types of ambulatory patients or ED patients cannot be made. Adverse side effects were not adequately studied because of the study’s small sample size as well as the limited observation time after administration of the medication (30 minutes). Given the limited monitoring capabilities at the study site, further study in the adult population to evaluate for clinically significant side affects of this medication is warranted.

The medication dose was based on a weight-based dosage medical record; however, patient weight was not recorded on

study Quality assurance forms (only total dose adminis- tered). Thus, dose discrepancies were not evaluated in this study. Lastly, the clinic staff was not blinded to the study intent. This may have introduced bias in both the recorded pain scores and the recorded clinic staff and

patient satisfaction.

(Continued) Quality measures

Pain control (using pain scores before/after medication administration)

Complications: hypotension,

hypoxia, dysphoria, and nausea/vomiting


Intranasal sufentanil provided rapid adequate pain control in patients presenting with acute traumatic extremity injuries at a winter resort clinic. Given the ease of administration, this may serve as a viable option for the treatment of extremity

injuries in other ambulatory settings such as ED triage and

QA forms To be filled out by provider, registered nurse, and patient

Pt stamp or MRN

Gender (circle): male female Age:

Injury (circle all that apply):

urgent care settings. Additional experience with the use of IN sufentanil in this setting may further aid in appropriate patient selection and medication dosing.

upper extremity injury without fx or d/l

Lower ext injury without fx or d/l

Upper extfx Lower extfx

Appendix. Intranasal sufentanil guidelines

Upper extd/l Lower extd/l

Chest injury Abd/Pelvic injury

CHI (minor) Spine injury-suspected Other: (please specify)

Procedures performed (Circle all that apply):

None Hematoma


Age Monitoring



Delivery device

Pain relief for moderate to severe pain associated with traumatic injuries

16-60 y

Pulse oximetry checks every 10 min for 30 min

0.5 ug/kg; max dose 50 ug. Use medical record for doses per weight range.

Half of the total volume is administered up each nare

May repeat dose x1 after 30 min Any clinical contraindication to narcotic analgesia

Any history of allergy to sufentanil or sufentanil Preexisting hypoxia (oxygen saturation b90%)

Hypotension (SBP b90 mm Hg) Confusion or significant closed head injury requiring monitoring of Mental status changes

Nasal trauma precluding administration of medication Active upper respiratory tract infection with significant nasal congestion

Significant additional injuries that

preclude the use of narcotic analgesia

Clinically significant drug or alcohol intoxication Mucosal atomization device Products/MAD/


Bier Block

Upper extfx reduction Shoulder d/l reduction

Elbow d/l reduction Lower extfx reduction

Hip d/l reduction Knee d/l


Other (specify):

Pain medication given (Circle all that apply):

IN Sufentanil Dose: # Doses: PO pain medicine:

IM Pain Medication:

IV Pain Medication:

Initial Pain Score on arrival: (1-10) Time: 10 min Repeat Pain Score: (0-10) Time: 20 min Repeat Pain Score: (0-10) Time: 30 min Repeat Pain Score: (0-10) Time: Complications (circle all that apply):

Hypotension (sBPb90) Hypoxia (pulse

ox b88%)


Nausea Vomiting Inadequate Pain Control


Patient Satisfaction 1-5:

On a scale from 0-10, with 0 being very dissatisfied and 10 being very satisfied, how satisfied were you with the pain control you

received from the Nasal pain medication RN satisfaction 1-5:

How satisfied were you with the IN sufentanil given to your patient?

MD satisfaction 1-5:

How satisfied were you with the IN sufentanil given to your patient?

Treatment intervention for “>Protocol for treatment intervention for Abnormal vital signs


86-95 kg (188-209 lb) 45 uga

Draw up 1 mL and atomize half into each nare

96-105 kg (210-231 lb) 50 ug a

Draw up 1.1 mL and atomize half into each nare

a In this chart, each dose volume listed already has an extra 0.1 mL added to the dose to compensate for the amount of drug caught in the atomizer.



For any hypoxia (saturation b88%) or oversedation, hold all further respiratory depressant medications

The primary intervention is verbal and/or light physical stimulation

If hypoxia persists, nasal cannula oxygen is administered at a rate of 2-4 L/min

If the patient remains overly sedated or hypoxic at this point, assisted ventilation with BVM is provided,

and IV access is established

Naloxone (Narcan) is administered via IV in 0.2-mg dose increments every 3 min until sedation and/or hypoxia are resolved

If IV access is unable to be established, Narcan may be administered intranasally as well, dosed at 0.4-mg increments every 3 min until sedation and/or hypoxia are resolved


For any sustained (N2 consecutive BP measurements) hypotension (SBP b90 mm Hg), hold any additional sedative or analgesic medications

Start IV access and give a 500-1000 mL bolus of normal saline (0.9% normal saline) and notify the physician. Monitor BP every 3-5 min until hypotension resolves and no further episodes occur

If hypotension persists, repeat bolus to a total of 20-30 mL/kg of 0.9% NS.

BVM indicates bag-valve mask; BP, blood pressure.

Sufentanil Dosing Protocol (1 mL = 50 ug) Intranasal sufentanil dose: 0.5 ug/kg

35-44 kg (75-99 lb)

45-55 kg (100-121 lb)

56-65 kg (122-143 lb)

66-75 kg (144-165 lb)

76-85 kg (166-187 lb)

20 uga

Draw up 0.5 mL and atomize half into each nare

25 uga

Draw up 0.6 mL and atomize half into each nare

30 uga

Draw up 0.7 mL and atomize half into each nare

35 uga

Draw up 0.8 mL and atomize half into each nare

40 uga

Draw up 0.9 mL and atomize half into each nare

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