Page 209 Acute Pain Management

Opioids
Single‐dose pharmacokinetic data in healthy volunteers for a number of opioids administered
by the IN route have been summarised by Dale et al (Dale et al, 2002). The mean
bioavailabilities and T max reported were fentanyl 71% and 5 minutes; sufentanil 78% and
10 minutes; alfentanil 65% and 9 minutes; butorphanol 71% and 49 minutes; oxycodone 46%
and 25 minutes; and buprenorphine 48% and 30 minutes. A later comparison of IN and IV
fentanyl showed mean T max values of 12.8 and 6.0 minutes and times to onset of analgesia
of 7 and 2 minutes respectively; the bioavailabilty of IN fentanyl was 89% (Foster et al, 2008
Level II).
Hydromorphone, when given to volunteers in doses of 1 mg or 2 mg IN and compared with
2 mg IV, had median times to peak blood concentration after the 1 mg and 2 mg IN doses
of 20 minutes and 25 minutes respectively and an overall bioavailability of only 55% (Coda
et al, 2003).
Clinical data also exist for the effectiveness of several opioids administered via the IN route,
including fentanyl (Toussaint et al, 2000 Level II; Manjushree et al, 2002 Level II; Paech et al, 2003
Level II; Christrup et al, 2008 Level II; Foster et al, 2008 Level II), butorphanol (Abboud et al, 1991
Level II; Wermeling et al, 2005), pethidine (Striebel et al, 1993 Level II; Striebel et al, 1995 Level II)
and morphine (Stoker et al, 2008 Level II).
Fentanyl had similar analgesic efficacy when given by the IN or IV routes (Toussaint et al, 2000
Level II; Manjushree et al, 2002 Level II; Paech et al, 2003 Level II) as did butorphanol (Abboud et al,
1991 Level II) and morphine (Christensen et al, 2008 Level II). IN pethidine was more effective than
SC injections of pethidine (Striebel et al, 1995 Level II).
In patients undergoing third molar extraction, mean T max values were 12.8 and 6.0 minutes
(P<0.001), times to onset of analgesia were 7 and 2 minutes (P<0.001), and durations of effect
were 56 and 59 minutes (P = NS) after IN and IV fentanyl administration respectively (Christrup
et al, 2008 Level II). Also after third molar extraction, mean times to onset of analgesia were CHAPTER 6
11 minutes for both 15 mg IN and 7.5 mg IV morphine and efficacy profiles were similar
(Christensen et al, 2008 Level II).
When fentanyl was used in the prehospital setting, there was no difference in effectiveness
between IN fentanyl (180 mcg +/‐ 2 doses of 60 mcg at > or =5 minute intervals) and IV
morphine (2.5 to 5 mg +/‐ 2 doses of 2.5 to 5 mg at > or =5‐minute intervals) (Rickard et al,
2007 Level II).
Patient‐controlled intranasal analgesia (PCINA) using diamorphine (bolus doses of 0.5mg)
was less effective than PCA IV morphine (1 mg bolus doses) after joint replacement surgery
(Ward et al, 2002 Level II) but provided better pain relief in doses of 0.1 mg/kg compared with
0.2 mg/kg IM morphine in children with fractures (Kendall et al, 2001 Level II). In children,
IN fentanyl at a dose of 1.7 mcg/kg was shown to be as effective as IV morphine 0.1 mg/kg
in children presenting to an emergency department with an acute fracture (Borland et al, 2007
Level II) and equivalent to oral morphine for pain relief during burn wound dressing changes
(Borland et al, 2005 Level II) (see Sections 9.3 and 10.4.2).
A comparison of two different doses of IN sufentanil (0.025 and 0.05 mcg/mL), given as
often as every 5 minutes in order to obtain a verbal pain score of less than 4 after inguinal
hernia repair or haemorrhoidectomy, confirmed the effectiveness of the nasal route for
postoperative analgesia, although the larger doses enabled effective pain relief to be achieved
more rapidly (Mathieu et al, 2006 Level II).
Adverse effects can be related to the drug itself or to the route of administration. Systemic
effects appear to be no higher for IN administration than for other routes with equivalent

Acute pain management: scientific evidence 161