The Effect of Intranasal Administration of Remifentanil on Intubating Conditions and Airway Response

1
The Effect of Intranasal Administration of
Remifentanil on Intubating Conditions and Airway
Response After Sevoflurane Induction of
Anesthesia in Children (Anesth Analg
20081071176 81)Department of Anesthesiology,
ChildrensNational Medical Center, Washington
Journal Meeting 2008.09.23 R4??? Albert Wai
Cheung, LAU
????????????? China Medical University Hospital,
Anesthesia Department
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Background

• Intubation without the use of muscle relaxants in
  children is frequently done before IV access is
  secured.
• In this randomized controlled trial, we compared
  intubating conditions and airway response to
  intubation (coughing and/or movement) after
  sevoflurane induction in children at 2 and 3 min
  after the administration of intranasal
  remifentanil (4 mcg/kg) or saline.

3

• Sevoflurane is now the standard inhaled induction
  drug for children.
• It has a pleasant smell, does not irritate the
  airways, and has a low blood gas solubility
  coefficient.
• These properties result in fast and pleasant
  induction of anesthesia.

4

• High concentrations (8) of sevoflurane were
  reported to induce epileptiform
  electroencephalogram activity in children.1012
• The effects of these high concentrations in
  children who may be hypovolemic because of
  prolonged fasting are not known.

5

• Several authors recommend 5 sevoflurane as a
  safe inspired concentration after loss of eyelash
  reflex in children.12
• The ability to perform laryngoscopy and tracheal
  intubation under light sevoflurane anesthesia
  is often facilitated by the use of IV adjuncts,
  such as opioids and propofol, or neuromuscular
  blocking drugs.

6

• Remifentanil hydrochloride is a potent
  ultrashort-acting opioid analgesic that undergoes
  rapid metabolism by tissue and plasma esterases.
• The mean half-life in children has been found to
  be similar across age groups, with means of 3.4
  5.7 min.13

7

• In children, it has been shown to provide
  acceptable tracheal intubating conditions without
  neuromuscular blocking drugs when combined with
  IV propofol induction.15,16

8

• Fentanyl has been used nasally to control pain
  and/or irritability after bilateral myringotomy
  tube surgery in children with good results. 17,18

9

• Our hypothesis was that remifentanil,
  administered intranasally at a dose of 4 mcg/kg,
  2 3 min before laryngoscopy, would increase the
  percentage of patients with acceptable intubation
  conditions after a 5 sevoflurane induction when
  compared to patients who received no remifentanil.

10
Methods

• 188 children, 17-yr old, were studied. Nasal
  remifentanil
• (4 mcg/kg) or saline was administered 1 min after
  an 8 sevoflurane N2O induction. The sevoflurane
  concentration was then reduced to 5 in oxygen,
  and ventilation assisted/controlled.
• An anesthesiologist blinded to treatment
  assignment used a validated score to evaluate the
  conditions for laryngoscopy response to
  intubation.
• Blood samples for determination of remifentanil
  blood concentrations were collected from 17
  children at baseline, 2, 3, 4, and 10 min after
  nasal administration of remifentanil.

11

• We conducted a double-blind, randomized,
  controlled trial to compare
• intubating conditions and airway response to
  intubation as primary outcomes, and
• hemodynamic response, chest wall compliance and
  oxygen saturation as secondary outcomes.

12

• Included were 188 ASA physical Status I or II
  pediatric patients, aged 17 yr, undergoing
  elective surgical procedures that require
  tracheal intubation.
• Excluded were children with a history of upper
  respiratory tract infection in the previous week,
  reactive airway disease requiring daily
  treatment, or in whom a difficult intubation was
  anticipated.

13

• At level 1, participants were randomly allocated
  to receive nasally either remifentanil (4 mcg/kg)
  or placebo (equal volume of saline).
• At level 2, each level 1 group was randomly
  allocated to have either 2 or 3 min intubating
  times.
• In addition, blood samples were obtained from 17
  patients to determine the pharmacokinetics of
  nasally administered remifentanil in children.
• The IRB approval, and parental consent were
  obtained in all cases.

14

• An investigator, blinded to the duration of time
  from nasal drug administration (being outside the
  room during induction), attempted laryngoscopy
  and intubation, and scored the response19 (Table
  1).

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Results

• Good or excellent intubating conditions were
  achieved at 2 min (after the remifentanil bolus)
  in 68.2 and at 3 min in 91.7 of the children
  who received intranasal remifentanil versus 37
  and 23 in children who received placebo (Plt
  0.01).
• The mean remifentanil plasma concentrations (
  ?SD) at 2, 3, 4, and 10 min were 1.0
  (0.60), 1.47 (0.52), 1.70 (0.46), 1.16 (0.36)
  ng/mL, respectively.
• Peak plasma concentration was observed at 3.47
  min. There were no complications associated with
  the use of nasal remifentanil.

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Discussion

• Use of nasal remifentanil in this study resulted
  in better intubating conditions in children
  during light sevoflurane anesthesia than placebo.
• This approach, therefore, can allow for earlier
  laryngoscopy and intubation under light
  sevoflurane anesthesia.

24

• A survey of members of the Society for Pediatric
  Anesthesia found that tracheal intubation using
  an inhaled anesthetic without muscle relaxation
  (IAWMR) was used in children by 44 of the
  respondents.23
• Anesth Analg 19998873741
• In that study, the most commonly stated reason
  for using IAWMR was the lack of need for a muscle
  relaxant during intubation or maintenance of
  anesthesia.

25

• Difficulty with pediatric venous access, because
  of either technical challenge or lack of an
  assistant able to place an IV, were other reasons
  many survey responders used IAWMR.
• Anesthesiologists who most often used IAWMR had
  three times the odds of working most cases alone
  without an assistant to start an IV line.

26

• Inomata and Nishikawa25 suggested an ED95 (95
  effective dose) end-tidal sevoflurane conc. of
  4.68 for tracheal intubation be obtained by
  inspired conc. of 5 sevoflurane in oxygen for an
  average of 3.5 min.
• Can J Anaesth 19964380611

27

• The average induction time required for smooth
  tracheal intubation in 95 of children breathing
  sevoflurane 5 in oxygen has been found 3 min 14
  s. 26
• Anaesthesia 1998534405

28

• IAWMR technique is sometimes facilitated by the
  use of adjuvants, such as topical lidocaine,28
• Anesth Analg 1999891328
• or IV administration of an opioid, to blunt the
  airway response to laryngoscopy and intubation.

29

• Crawford et al.16 showed that, after propofol
  induction in infants, an IV dose of 3 mcg/kg of
  remifentanil (90s) was effective in achieving
  adequate intubation conditions 90 s after
  remifentanil administration, and that the dose
  response of remifentanil for tracheal intubation
  was similar in infants and children.
• Anesth Analg 20051001599604

30

• Crawford et al.16 calculated the ED50 and ED95
  doses of IV remifentanil, that are required to
  achieve acceptable intubating conditions after 4
  mg/kg IV propofol induction, to be
• 1.7 ? 0.1 mcg/kg (ED50)
• 2. 88 ? 0.5 mcg/kg (ED95), respectively.

31

• The choice of a 4 mcg/kg dose of nasal
  remifentanil was based on an assumption that
  blood levels of nasally administered drugs are
  about half that obtained after IV dosing. 32
• Can J Anaesth 1989364947
• The optimal dose of IV remifentanil for tracheal
  intubation under sevoflurane anesthesia in adults
  was found by Joo et al. 14 to be 2 mcg/kg,
• hence our 4 mcg/kg dosing.

32

• intubation conditions with IV remifentanil in
  children used 3 mcg/kg, which is a higher dose
  than we used in our study.15
• Other authors reported that an IV dose of 45
  mcg/kg of remifentanil may be even more reliable
  in achieving good intubating conditions after
  2mg/kg of IV propofol in adults.34

33

• Remifentanil at 3.3 ng/mL combined with
  sevoflurane at 1-minimum alveolar anesthetic
  concentration provided excellent conditions for
  intubation without muscle relaxants in 50 of
  adult patients.35

34

• Propofol anesthesia, a target remifentanil blood
  concentration of 515 ng/mL provided good
  intubating conditions and absence of cough about
  75 of the time.36

35

• Future studies should examine the intubating
  conditions and the possible side effects of using
  a higher remifentanil dose nasally.

36
Conclusions

• Nasal administration of remifentanil produces
  good-to-excellent intubating conditions in 23
  min after sevoflurane induction of anesthesia.

37
Thank you for your attention.

• Thank you for your attention.

38

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39

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40

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41

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42

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43

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44

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45

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46

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47

• Electrical seizures during sevoflurane anesthesia
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48

• Sevoflurane mask induction of anaesthesia is
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